@article {pmid39845577, year = {2025}, author = {Ludolph, A and Wiesenfarth, M}, title = {Tofersen and other antisense oligonucleotides in ALS.}, journal = {Therapeutic advances in neurological disorders}, volume = {18}, number = {}, pages = {17562864251313915}, pmid = {39845577}, issn = {1756-2856}, abstract = {The advent of antisense oligonucleotide (ASO) therapies in neurodegenerative disorders is associated with enormous hope. Nusinersen treatment was a breakthrough intervention in the recessive disease spinal muscular atrophy, and superoxide dismutase 1 (SOD1) amyotrophic lateral sclerosis (ALS) seems to be the paradigm disease in dominant degenerative diseases. The results of treatment with the ASO tofersen in SOD1-ALS show that the drug has a convincing beneficial effect on ALS caused by SOD1 mutations, that preclinical studies in rodents predicted the therapeutic effect in the human disease, and that clinical efficacy is associated with a specific sequence of effects of the drug on mechanistic and degenerative biomarkers and, subsequently, functional outcomes such as weight stabilization and ALSFRS-R. Therefore, the enthusiasm seems to be justified; but this should be followed by an attempt to obtain further insights with the goal to improve this therapy. In particular, the following issues are only partially resolved: Which mechanisms are responsible for the clinical effect following the downregulation of SOD1 protein by ASOs? Is long-term downregulation of SOD1 function associated with side effects? Is there an autoimmune response caused by this and other ASO? Is prevention of SOD1-associated ALS possible?}, }
@article {pmid39840019, year = {2024}, author = {De Cleene, N and Schwarzová, K and Labrecque, S and Cerejo, C and Djamshidian, A and Seppi, K and Heim, B}, title = {Olfactory dysfunction as potential biomarker in neurodegenerative diseases: a narrative review.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1505029}, pmid = {39840019}, issn = {1662-4548}, abstract = {Neurodegenerative diseases represent a group of disorders characterized by progressive degeneration of neurons in the central nervous system, leading to a range of cognitive, motor, and sensory impairments. In recent years, there has been growing interest in the association between neurodegenerative diseases and olfactory dysfunction (OD). Characterized by a decline in the ability to detect or identify odors, OD has been observed in various conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS). This phenomenon often precedes the onset of other clinical symptoms, suggesting its potential utility as an early marker or prodromal symptom of neurodegenerative diseases. This review provides a vast literature overview on the current knowledge of OD in PD, AD, ALS, and HD in order to evaluate its potential as a biomarker, particularly in the early and prodromal stages of these diseases. We summarize the most common methods used to measure olfactory function and delve into neuropathological correlations and the alterations in neurotransmitter systems associated with OD in those neurodegenerative diseases, including differences in genetic variants if applicable, and cater to current pitfalls and shortcomings in the research.}, }
@article {pmid39838446, year = {2025}, author = {Ou, K and Jia, Q and Li, D and Li, S and Li, XJ and Yin, P}, title = {Application of antisense oligonucleotide drugs in amyotrophic lateral sclerosis and Huntington's disease.}, journal = {Translational neurodegeneration}, volume = {14}, number = {1}, pages = {4}, pmid = {39838446}, issn = {2047-9158}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/drug therapy/therapy ; Humans ; *Huntington Disease/genetics/drug therapy/therapy ; *Oligonucleotides, Antisense/therapeutic use ; Animals ; Genetic Therapy/methods/trends ; }, abstract = {Amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD) are diverse in clinical presentation and are caused by complex and multiple factors, including genetic mutations and environmental factors. Numerous therapeutic approaches have been developed based on the genetic causes and potential mechanisms of ALS and HD. Currently, available treatments for various neurodegenerative diseases can alleviate symptoms but do not provide a definitive cure. Gene therapy, which aims to modify or express specific proteins for neuroprotection or correction, is considered a powerful tool in managing neurodegenerative conditions. To date, antisense oligonucleotide (ASO) drugs targeting the pathological genes associated with ALS and HD have shown promising results in numerous animal studies and several clinical trials. This review provides a comprehensive overview of the development, mechanisms of action, limitations, and clinical applications of ASO drugs in neurodegenerative diseases, with a specific focus on ALS and HD therapeutic strategies.}, }
@article {pmid39838017, year = {2025}, author = {McCaig, CD}, title = {Neurological Diseases can be Regulated by Phase Separation.}, journal = {Reviews of physiology, biochemistry and pharmacology}, volume = {187}, number = {}, pages = {273-338}, pmid = {39838017}, issn = {0303-4240}, mesh = {Humans ; *Nervous System Diseases ; Animals ; Superoxide Dismutase/metabolism ; Motor Neuron Disease ; Neurons/metabolism ; Phase Separation ; }, abstract = {Several neurological diseases arise from abnormal protein aggregation within neurones and this is closely regulated by phase separation. One such is motor neurone disease and aberrant aggregation of superoxide dismutase. Again these events are regulated by electrical forces that are examined.}, }
@article {pmid39834554, year = {2025}, author = {Sarallah, R and Jahani, S and Soltani Khaboushan, A and Moaveni, AK and Amiri, M and Majidi Zolbin, M}, title = {The role of CXCL12/CXCR4/CXCR7 axis in cognitive impairment associated with neurodegenerative diseases.}, journal = {Brain, behavior, & immunity - health}, volume = {43}, number = {}, pages = {100932}, pmid = {39834554}, issn = {2666-3546}, abstract = {Neurodegenerative diseases, including Alzheimer's Disease (AD), Parkinson's Disease (PD), Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS), are characterized by progressive neuronal loss and cognitive impairment (CI). The: Cysteine-X-cysteine chemokine ligand 12(CXCL12)/CXC chemokine receptor type 4 (CXCR4)/CXC chemokine receptor type 7 (CXCR7) axis has emerged as a critical molecular pathway in the development of CI in these disorders. This review explores the role of this axis in the pathogenesis of CI across these neurodegenerative diseases, synthesizing current evidence and its implications for targeted therapies. In AD, dysregulation of this axis contributes to amyloid-β accumulation and tau hyperphosphorylation, leading to synaptic dysfunction and cognitive decline. PD studies reveal that CXCL12/CXCR4 signaling influences dopaminergic neuron survival and microglial activation, affecting cognitive function. In MS, the axis modulates neuroinflammation and demyelination processes, impacting cognitive performance. ALS research indicates that the CXCL12/CXCR4/CXCR7 pathway is involved in motor neuron degeneration and associated cognitive deficits. Across these diseases, the axis influences neuroinflammation, synaptic plasticity, and neuronal survival through various signaling cascades, including PI3K/AKT, MAPK, and JAK/STAT pathways. Emerging evidence suggests that modulating this axis could provide neuroprotective effects and potentially alleviate cognitive symptoms. This review highlights the potential of the CXCL12/CXCR4/CXCR7 axis as a therapeutic target for addressing CI in neurodegenerative diseases. It also underscores the need for further research to fully elucidate its role and develop effective interventions, potentially leading to improved clinical management strategies for these devastating disorders.}, }
@article {pmid39834320, year = {2025}, author = {Lero, CM and Park, S and Mroz, EL}, title = {Mapping the evidence of self-compassion in caregiver wellbeing for caregivers of persons with neurodegenerative disease: A scoping review.}, journal = {Palliative & supportive care}, volume = {23}, number = {}, pages = {e38}, doi = {10.1017/S1478951524001639}, pmid = {39834320}, issn = {1478-9523}, mesh = {Humans ; *Caregivers/psychology ; *Neurodegenerative Diseases/psychology/complications ; *Empathy ; }, abstract = {OBJECTIVES: Caregivers of those with neurodegenerative disease (ND) manage complex symptoms which impact their wellbeing. Self-compassion can promote maintenance of wellbeing during challenging experiences, including caregiving. Little guidance exists for observationally studying self-compassion or targeted interventions for this population. Our objective was to complete a scoping review of research describing self-compassion in the context of caregiver wellbeing of caregivers of those living with ND.
METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-analysis extension for Scoping Reviews (PRISMA-ScR) guidelines, 3 online databases identified 350 peer-reviewed articles, 18 of which were included in this study. Eligibility included being written in English, targeting caregivers of those living with ND, and examination of self-compassion. Articles were organized by the incorporation or characterization of self-compassion in the study design.
RESULTS: Alzheimer's disease predominated study samples of care recipients. Across study types self-compassion appeared as a theoretical concept, emerging theme, variable associated with other outcomes, and main outcome variable. Self-compassion is frequently measured using the Self-Compassion Scale, full or short form .
SIGNIFICANCE OF RESULTS: The study of self-compassion with caregivers of individuals living with ND is growing. Current literature is somewhat unfocussed, leading to gaps in understanding conceptualization to achieve maximum intervention benefits. Clarifying the role of self-compassion in caregiver wellbeing will provide a lens through which non-pharmacologic, psychotherapeutic, and behavioral intervention development may be framed to reduce negative psychological outcomes. The most frequently represented ND is Alzheimer's disease or other dementia, obscuring other NDs like amyotrophic lateral sclerosis, Parkinson's disease, and others.}, }
@article {pmid39831374, year = {2025}, author = {Risi, B and Imarisio, A and Cuconato, G and Padovani, A and Valente, EM and Filosto, M}, title = {Mitochondrial DNA (mtDNA) as fluid biomarker in neurodegenerative disorders: A systematic review.}, journal = {European journal of neurology}, volume = {32}, number = {1}, pages = {e70014}, doi = {10.1111/ene.70014}, pmid = {39831374}, issn = {1468-1331}, mesh = {Humans ; *DNA, Mitochondrial/cerebrospinal fluid/genetics ; *Biomarkers/cerebrospinal fluid/blood ; *Neurodegenerative Diseases/cerebrospinal fluid/genetics/diagnosis/blood ; Amyotrophic Lateral Sclerosis/genetics/cerebrospinal fluid/blood/diagnosis ; }, abstract = {BACKGROUND: Several studies evaluated peripheral and cerebrospinal fluid (CSF) mtDNA as a putative biomarker in neurodegenerative diseases, often yielding inconsistent findings. We systematically reviewed the current evidence assessing blood and CSF mtDNA levels and variant burden in Parkinson's disease (PD), Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). Multiple sclerosis (MS) was also included as a paradigm of chronic neuroinflammation-driven neurodegeneration.
METHODS: Medline, Embase, Scopus and Web of Science were searched for articles published from inception until October 2023. Studies focused on mtDNA haplogroups or hereditary pathogenic variants were excluded. Critical appraisal was performed using the Quality Assessment for Diagnostic Accuracy Studies criteria.
RESULTS: Fifty-nine original studies met our a priori-defined inclusion criteria. The majority of CSF-focused studies showed (i) decreased mtDNA levels in PD and AD; (ii) increased levels in MS compared to controls. No studies evaluated CSF mtDNA in ALS. Results focused on blood cell-free and intracellular mtDNA were contradictory, even within studies evaluating the same disease. This poor reproducibility is likely due to the lack of consideration of the many factors known to affect mtDNA levels. mtDNA damage and methylation levels were increased and reduced in patients compared to controls, respectively. A few studies investigated the correlation between mtDNA and disease severity, with conflicting results.
CONCLUSIONS: Additional well-designed studies are needed to evaluate CSF and blood mtDNA profiles as putative biomarkers in neurodegenerative diseases. The identification of "mitochondrial subtypes" of disease may enable novel precision medicine strategies to counteract neurodegeneration.}, }
@article {pmid39828029, year = {2025}, author = {Fantini, J and Azzaz, F and Di Scala, C and Aulas, A and Chahinian, H and Yahi, N}, title = {Conformationally adaptive therapeutic peptides for diseases caused by intrinsically disordered proteins (IDPs). New paradigm for drug discovery: Target the target, not the arrow.}, journal = {Pharmacology & therapeutics}, volume = {}, number = {}, pages = {108797}, doi = {10.1016/j.pharmthera.2025.108797}, pmid = {39828029}, issn = {1879-016X}, abstract = {The traditional model of protein structure determined by the amino acid sequence is today seriously challenged by the fact that approximately half of the human proteome is made up of proteins that do not have a stable 3D structure, either partially or in totality. These proteins, called intrinsically disordered proteins (IDPs), are involved in numerous physiological functions and are associated with severe pathologies, e.g. Alzheimer, Parkinson, Creutzfeldt-Jakob, amyotrophic lateral sclerosis (ALS), and type 2 diabetes. Targeting these proteins is challenging for two reasons: i) we need to preserve their physiological functions, and ii) drug design by molecular docking is not possible due to the lack of reliable starting conditions. Faced with this challenge, the solutions proposed by artificial intelligence (AI) such as AlphaFold are clearly unsuitable. Instead, we suggest an innovative approach consisting of mimicking, in short synthetic peptides, the conformational flexibility of IDPs. These peptides, which we call adaptive peptides, are derived from the domains of IDPs that become structured after interacting with a ligand. Adaptive peptides are designed with the aim of selectively antagonizing the harmful effects of IDPs, without targeting them directly but through selected ligands, without affecting their physiological properties. This"target the target, not the arrow" strategy is promised to open a new route to drug discovery for currently undruggable proteins.}, }
@article {pmid39828018, year = {2025}, author = {Sharma, D and Singh, V and Kumar, A and Singh, TG}, title = {Genistein: A Promising Ally in Combating Neurodegenerative Disorders.}, journal = {European journal of pharmacology}, volume = {}, number = {}, pages = {177273}, doi = {10.1016/j.ejphar.2025.177273}, pmid = {39828018}, issn = {1879-0712}, abstract = {Neurodegenerative disorders arise when nerve cells in the brain or peripheral nervous system gradually lose functions and eventually die. Although certain therapies may alleviate some of the physical and mental symptoms associated with neurodegenerative disorders, hence slowing their progression, but no sure-shot treatment is currently available. It was shown that the rise in life expectancy and the number of elderly people in the community led to an increasing trend in the incidence and prevalence of neurodegenerative disease. Phytomolecules are demonstrating their effectiveness in combating, regression, and delaying various diseases. Genistein is one of soy isoflavone with antioxidant, anti-inflammatory, and estrogenic effects. Researchers demonstrated that Genistein treatment significantly reduced hyperglycemia, improved cognitive performance by modulating acetylcholinesterase activity and oxidative stress, and alleviated neuroinflammatory conditions in mice. This paper evaluates (in vivo and in vitro) various molecular targets of isoflavones and their ability to effectively counter several neurodegenerative disorders such as Parkinson's, Alzheimer's, and Huntington's diseases and amyotrophic lateral sclerosis. In this review, we aim to provide an overview of the role that genistein plays in delaying the development of neurodegenerative disorders.}, }
@article {pmid39827337, year = {2025}, author = {Mwale, PF and Hsieh, CT and Yen, TL and Jan, JS and Taliyan, R and Yang, CH and Yang, WB}, title = {Chitinase-3-like-1: a multifaceted player in neuroinflammation and degenerative pathologies with therapeutic implications.}, journal = {Molecular neurodegeneration}, volume = {20}, number = {1}, pages = {7}, pmid = {39827337}, issn = {1750-1326}, support = {NSTC 112-2320-B-038 -018 -MY3//National Science and Technology Council/ ; CGH-MR-A11315//Cathay General Hospital/ ; CGH-MR-A11314//Cathay General Hospital/ ; }, mesh = {Humans ; *Chitinase-3-Like Protein 1/metabolism ; *Neurodegenerative Diseases/metabolism/pathology ; *Neuroinflammatory Diseases/metabolism ; Animals ; }, abstract = {Chitinase-3-like-1 (CHI3L1) is an evolutionarily conserved protein involved in key biological processes, including tissue remodeling, angiogenesis, and neuroinflammation. It has emerged as a significant player in various neurodegenerative diseases and brain disorders. Elevated CHI3L1 levels have been observed in neurological conditions such as traumatic brain injury (TBI), Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Creutzfeldt-Jakob disease (CJD), multiple sclerosis (MS), Neuromyelitis optica (NMO), HIV-associated dementia (HAD), Cerebral ischemic stroke (CIS), and brain tumors. This review explores the role of CHI3L1 in the pathogenesis of these disorders, with a focus on its contributions to neuroinflammation, immune cell infiltration, and neuronal degeneration. As a key regulator of neuroinflammation, CHI3L1 modulates microglia and astrocyte activity, driving the release of proinflammatory cytokines that exacerbate disease progression. In addition to its role in disease pathology, CHI3L1 has emerged as a promising biomarker for the diagnosis and monitoring of brain disorders. Elevated cerebrospinal fluid (CSF) levels of CHI3L1 have been linked to disease severity and cognitive decline, particularly in AD and MS, highlighting its potential for clinical diagnostics. Furthermore, therapeutic strategies targeting CHI3L1, such as small-molecule inhibitors and neutralizing antibodies, have shown promise in preclinical studies, demonstrating reduced neuroinflammation, amyloid plaque accumulation, and improved neuronal survival. Despite its therapeutic potential, challenges remain in developing selective and safe CHI3L1-targeted therapies, particularly in ensuring effective delivery across the blood-brain barrier and mitigating off-target effects. This review addresses the complexities of targeting CHI3L1, highlights its potential in precision medicine, and outlines future research directions aimed at unlocking its full therapeutic potential in treating neurodegenerative diseases and brain pathologies.}, }
@article {pmid39822067, year = {2025}, author = {Zhu, Y and Verkhratsky, A and Chen, H and Yi, C}, title = {Understanding glucose metabolism and insulin action at the blood-brain barrier: Implications for brain health and neurodegenerative diseases.}, journal = {Acta physiologica (Oxford, England)}, volume = {241}, number = {2}, pages = {e14283}, pmid = {39822067}, issn = {1748-1716}, support = {RCJC20231211090018040//Shenzhen Fundamental Research Program/ ; ZDSYS20220606100801003//Shenzhen Fundamental Research Program/ ; 2022B1515020012//Basic and Applied Basic Research Foundation of Guangdong Province/ ; 32170980//National Natural Science Foundation of China/ ; }, mesh = {*Blood-Brain Barrier/metabolism ; Humans ; *Neurodegenerative Diseases/metabolism ; Animals ; *Insulin/metabolism ; *Glucose/metabolism ; Brain/metabolism ; }, abstract = {The blood-brain barrier (BBB) is a highly selective, semipermeable barrier critical for maintaining brain homeostasis. The BBB regulates the transport of essential nutrients, hormones, and signaling molecules between the bloodstream and the central nervous system (CNS), while simultaneously protecting the brain from potentially harmful substances and pathogens. This selective permeability ensures that the brain is nourished and shielded from toxins. An exception to this are brain regions, such as the hypothalamus and circumventricular organs, which are irrigated by fenestrated capillaries, allowing rapid and direct response to various blood components. We overview the metabolic functions of the BBB, with an emphasis on the impact of altered glucose metabolism and insulin signaling on BBB in the pathogenesis of neurodegenerative diseases. Notably, endothelial cells constituting the BBB exhibit distinct metabolic characteristics, primarily generating ATP through aerobic glycolysis. This occurs despite their direct exposure to the abundant oxygen in the bloodstream, which typically supports oxidative phosphorylation. The effects of insulin on astrocytes, which form the glial limitans component of the BBB, show a marked sexual dimorphism. BBB nutrient sensing in the hypothalamus, along with insulin signaling, regulates systemic metabolism. Insulin modifies BBB permeability by regulating the expression of tight junction proteins, angiogenesis, and vascular remodeling, as well as modulating blood flow in the brain. The disruptions in glucose and insulin signaling are particularly evident in neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, where BBB breakdown accelerates cognitive decline. This review highlights the critical role of normal glucose metabolism and insulin signaling in maintaining BBB functionality and investigates how disruptions in these pathways contribute to the onset and progression of neurodegenerative diseases.}, }
@article {pmid39821843, year = {2025}, author = {Zhang, J and Guo, R and Zhou, Z and Fu, Z and Akogo, HY and Li, Y and Zhang, X and Wang, N and Liu, Y and Li, H and Feng, B and Cui, H and Ma, J}, title = {Neural Stem/Progenitor Cell Therapy in Patients and Animals with Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-analysis.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {39821843}, issn = {1559-1182}, support = {81801278//National Natural Science Foundation of China/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative malady that causes progressive degeneration and loss of motor neuron function in the brain and spinal cord, eventually resulting in muscular atrophy, paralysis, and death. Neural stem/progenitor cell (NSPC) transplantation can improve bodily function in animals and delay disease progression in patients with ALS. This paper summarizes and analyzes the efficacy and safety of neural stem/progenitor cell (NSPC) transplantation as a treatment for ALS, aiming to improve function and delay disease progression in patients. We present a summary of the pathogenic mechanism and causative genes associated with ALS and describe the mechanism and efficacy of NSPC treatment for ALS. We comprehensively searched for relevant English-language articles published between January 1, 2000 and October 1, 2023, across the following five medical databases: PubMed, EMBASE, OVID, Web of Science, and the Cochrane Library. We examined experimental indices of physical function in animals and patients who underwent stem cell transplantation. All statistical analyses were performed via Review Manager 5.4. The study comprised a total of 16 investigations, including 5 clinical studies and 11 animal studies and involving 66 patients and 203 animals. The meta-analysis revealed that the administration of NSPCs appeared to yield positive outcomes in clinical patients, as assessed by the ALS functional rating scale and forced vital capacity. Furthermore, improvements following cell injection were observed in the rotarod test results, the Basso-Beattie-Bresnahan Locomotor Rating Scale score, weight, and survival time. Our meta-analysis, which was grounded in randomized controlled trials, revealed that the transplantation of neural stem/progenitor cells (NSPCs), has potential effects on ALS patients, enhancing the physical function of animals and mitigating degenerative effects in individuals. These underscored the promise of NSPC therapy as a viable treatment option. We report that the transplantation of neural stem/progenitor cells (NSPCs) is promising for enhancing bodily function and slowing the progression of ALS in affected patients. In this review, we summarize the treatment of ALS with NSPCs, evaluating both its efficacy and safety. Through database searches, we identified 16 studies involving 66 patients and 203 animals and analyzed the experimental indices of physical function following stem cell transplantation. The meta-analysis results indicated a positive impact of NSPCs on the clinical conditions of patients and the behavior of animals. A meta-analysis of randomized controlled trials further supported the conclusion that NSPC transplantation has a beneficial effect on improving physical function and mitigating degeneration in ALS patients.}, }
@article {pmid39820998, year = {2025}, author = {Hamad, AA and Alkhawaldeh, IM and Nashwan, AJ and Meshref, M and Imam, Y}, title = {Tofersen for SOD1 amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {}, number = {}, pages = {}, pmid = {39820998}, issn = {1590-3478}, abstract = {OBJECTIVE: Tofersen, an antisense oligonucleotide, has recently received FDA and EMA approval for treating amyotrophic lateral sclerosis (ALS) in adults with SOD1 gene mutations. This systematic review and meta-analysis synthesized evidence on tofersen's safety and efficacy in patients with SOD1-related ALS.
METHODS: A comprehensive search of three databases was conducted from inception through October 2024. Eligible studies included clinical trials, observational studies, and case studies. Meta-analyses were conducted using a random-effects model in RevMan.
RESULTS: Twelve studies involving 195 patients treated with tofersen met the inclusion criteria, comprising two randomized controlled trials (RCTs), five cohort studies, one case series, and four case reports. Tofersen demonstrated promising effects, notably reducing SOD1 levels in cerebrospinal fluid and neurofilament light chain (NfL) in plasma, a biomarker strongly correlated with ALS progression and survival. Meta-analysis of RCTs showed a significantly lower rate of decline in ALS Functional Rating Scale-Revised (ALSFRS-R) scores from baseline in the tofersen group compared to placebo (SMD = 0.44, 95% CI [0.05 to 0.83], P = 0.03) and a significant reduction in the decline of predicted Slow Vital Capacity (P = 0.005). In a pre-post meta-analysis of five studies, a significant decrease in ALS progression rate (ALSFRS-R decline rate) was observed (MD = -0.28, 95% CI [-0.40 to -0.15], P < 0.0001). Reported adverse events were consistent with ALS progression or procedural effects.
CONCLUSION: Current evidence suggests that tofersen effectively reduces SOD1 and NfL levels and slow disease progression in SOD1 ALS, showing promise as a targeted therapeutic option.}, }
@article {pmid39736981, year = {2024}, author = {Zhang, Y and Li, N and Ge, Z and Li, F}, title = {Blood component therapy for dry eye disease: a systematic review and network meta-analysis.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1500160}, pmid = {39736981}, issn = {2296-858X}, abstract = {OBJECTIVE: Blood component therapy has shown promising potential as an emerging treatment for dry eye disease; however, it remains unclear which specific blood component is the most effective. This study aims to compare the efficacy of different blood components in the treatment of dry eye disease through a network meta-analysis, with the goal of providing the latest and most reliable evidence for clinical practice.
METHODS: We conducted a systematic search of the PubMed, Web of Science, Cochrane, Embase, and Scopus databases, with the search concluding on June 1, 2024. Two independent researchers performed literature screening, data extraction, and quality assessment.
RESULTS: A total of 16 randomized controlled trials (RCTs) involving 898 patients with dry eye disease were included. Six different blood components were utilized in treating dry eye disease, with platelet-rich plasma (PRP) being the most widely used. The results of the network meta-analysis indicated that platelet-rich plasma eye drops (PRPD) significantly outperformed artificial tears (AT) in improving the corneal fluorescein staining score (CFSS), while autologous serum (ALS) and umbilical cord serum (UCS) also demonstrated significantly better effects than AT in enhancing tear break-up time (TBUT). Additionally, ALS, PRP injection (PRPI), and PRPD showed significantly superior outcomes compared to AT in improving the ocular surface disease index (OSDI). However, no statistically significant differences were found among the various treatment modalities regarding their effects on Schirmer's I value, CFSS, TBUT, and OSDI. SUCRA analysis predicted that UCS was the most effective in improving Schirmer's I value and TBUT, while PRP excelled in enhancing CFSS and OSDI. Limitations such as publication bias and issues related to randomization, allocation concealment, and blinding may affect the reliability of the current findings.
CONCLUSION: Blood component therapy can significantly improve the pathological damage and ocular surface health in patients with dry eye disease. For those with aqueous-deficient dry eye, UCS may represent the optimal treatment option. In contrast, for patients with more severe corneal epithelial damage, PRP may offer a more effective therapeutic approach.
https://www.crd.york.ac.uk/PROSPERO/, CRD42024534091.}, }
@article {pmid39577115, year = {2024}, author = {Abdian, S and Fakhri, S and Moradi, SZ and Khirehgesh, MR and Echeverría, J}, title = {Saffron and its major constituents against neurodegenerative diseases: A mechanistic review.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156097}, doi = {10.1016/j.phymed.2024.156097}, pmid = {39577115}, issn = {1618-095X}, mesh = {Animals ; Humans ; *Carotenoids/pharmacology/therapeutic use ; *Crocus/chemistry ; Cyclohexenes/pharmacology ; Glucosides/pharmacology ; *Neurodegenerative Diseases/drug therapy ; Neuroprotective Agents/chemistry/pharmacology ; Phytochemicals/pharmacology ; *Plant Extracts/chemistry/pharmacology/therapeutic use ; Signal Transduction/drug effects ; Terpenes/pharmacology ; Vitamin A/analogs & derivatives ; }, abstract = {BACKGROUND: Neurodegeneration has been recognized as the main pathophysiological alteration in the majority of brain-related diseases. Despite contemporary attempts to provide acceptable medicinal therapies, the conclusion has not been much beneficial. Besides, the complex pathophysiological mechanisms behind neurodegenerative diseases (NDDs) urge the needs for finding novel multi-target agents. Accordingly, saffron with major active constituents and as multi-targeting agents have shown beneficial effects in modulating NDDs with higher efficacy and lower side effects.
PURPOSE: The present study provides a systematic and comprehensive review of the existing in vitro, in vivo, and clinical data on the effectiveness, and signaling pathways of saffron and its key phytochemical components in the management of NDDs. The need to develop novel saffron delivery systems is also considered.
METHODS: Studies were identified through a systematic and comprehensive search in Science Direct, PubMed, and Scopus databases through April 30, 2024. The whole saffron major constituents (e.g., saffron, crocin, crocetin, picrocrocin, and safranal) and NDDs (e.g., neuro*, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, Huntington*, Parkinson*, Alzheimer*, and brain) were selected as keywords to find related studies. In the systematic analysis, 64 articles were directly included in the current study. Additional reports were added within the comprehensive studies in the review.
RESULTS: Saffron and its active metabolites crocin, crocetin, safranal, and picrocrocin have shown acceptable efficacy in managing NDDs like Alzheimer's disease, Parkinson's disease, Attention deficit hyperactivity disorder, depression, and other NDDs via modulating apoptotic (e.g., caspases, Bax/Bcl-2, cytochrome c, and death receptors), inflammatory (e.g., NF-κB, IL-1β, IL-6, TNF-α, and COX-2), and oxidative strass (e.g., Nrf2, GSH, GPx, CAT, SOD, MDA, ROS, and nitrite) signaling pathways. The presented in vitro, in vivo, and clinical evidences showed us a better future of controlling NDDs with higher efficacy, while decreasing associated side effects with no significant toxicity. Additionally, employing novel delivery systems could increase the efficacy of saffron phytoconstituents to resolve the issues pharmacokinetic limitations.
CONCLUSION: Saffron and its major constituents employ anti-inflammatory, anti-apoptotic and antioxidant mechanisms in modulating several dysregulated-signaling pathways in NDDs. However, further research is necessary to elucidate the precise underlying mechanisms in exploring the feasibility of using saffron active compounds against NDDs. More studies should focus on dose-response relationships, long-term effects, highlighting key mechanisms, and designing more well-controlled clinical trials. Additionally, developing stable and cost-benefit novel delivery systems in future works helps to remove the pharmacokinetic limitations of saffron major constituents.}, }
@article {pmid39574800, year = {2024}, author = {Bouajila, N and Domenighetti, C and Aubin, HJ and Naassila, M}, title = {Alcohol consumption and its association with cancer, cardiovascular, liver and brain diseases: a systematic review of Mendelian randomization studies.}, journal = {Frontiers in epidemiology}, volume = {4}, number = {}, pages = {1385064}, pmid = {39574800}, issn = {2674-1199}, abstract = {BACKGROUND: The health effects of alcohol consumption, particularly regarding potential protective benefits of light to moderate intake compared to abstinence, remain a subject of ongoing debate. However, epidemiological studies face limitations due to imprecise exposure measurements and the potential for bias through residual confounding and reverse causation. To address these limitations, we conducted a systematic review of Mendelian Randomization (MR) studies examining the causal relationship between alcohol consumption and cancers, cardiovascular, liver, and neurological diseases.
METHODOLOGY: We searched PubMed, ScienceDirect and Embase and Europe PMC up to 05/2024 for MR studies investigating the association of genetically predicted alcohol consumption with cancers, cardiovascular, liver and neurological diseases. We assessed methodological quality based on key elements of the MR design a genetic association studies tool.
RESULTS: We included 70 MR studies that matched our inclusion criteria. Our review showed a significant association of alcohol consumption with multiple cancers such as oral and oropharyngeal, esophageal, colorectal cancers, hepatocellular carcinoma and cutaneous melanoma. While the available studies did not consistently confirm the adverse or protective effects of alcohol on other cancers, such as lung cancer, as suggested by observational studies. Additionally, MR studies confirmed a likely causal effect of alcohol on the risk of hypertension, atrial fibrillation, myocardial infraction and vessels disease. However, there was no evidence to support the protective effects of light to moderate alcohol consumption on cognitive function, Alzheimer's disease, and amyotrophic lateral sclerosis, as reported in observational studies while our review revealed an increased risk of epilepsy and multiple sclerosis. The available studies provided limited results on the link between alcohol consumption and liver disease.
CONCLUSIONS: Despite the valuable insights into the causal relationship between alcohol consumption and various health outcomes that MR studies provided, it is worth noting that the inconsistent ability of genetic instrumental variables to distinguish between abstainers, light and moderate drinkers makes it difficult to differentiate between U or J-shaped vs. linear relationships between exposure and outcome. Additional research is necessary to establish formal quality assessment tools for MR studies and to conduct more studies in diverse populations, including non-European ancestries.
www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021246154, Identifier: PROSPERO (CRD42021246154).}, }
@article {pmid39441150, year = {2024}, author = {Hamad, AA and Alkhawaldeh, IM and Abbas, A and Elaraby, A and Meshref, M}, title = {Incidence and risk factors of venous thromboembolism in patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {La Tunisie medicale}, volume = {102}, number = {10}, pages = {610-515}, pmid = {39441150}, issn = {2724-7031}, mesh = {*Amyotrophic Lateral Sclerosis/epidemiology/complications ; Humans ; *Venous Thromboembolism/epidemiology/etiology ; Incidence ; Risk Factors ; Male ; Female ; }, abstract = {AIMS: This systematic review and meta-analysis aimed to determine the annual incidence rate of venous thromboembolism (VTE) and identify risk factors of VTE in amyotrophic lateral sclerosis (ALS) patients.
METHODS: A comprehensive search of three databases was conducted up to April 8, 2024, to identify longitudinal studies reporting VTE incidence in ALS patients. The included studies were either prospective or retrospective, following up with ALS patients. Quality assessment was performed using the NIH tool for observational cohort studies. Meta-analysis was conducted using Open Meta Analyst, employing a random-effect model. Subgroup, Meta-regression, and sensitivity analyses were also carried out.
RESULTS: Our analysis included eight studies comprising a total of 26,758 ALS patients that met the inclusion criteria. The pooled annual incidence of VTE across all studies was found to be 22 cases per 1,000 person-year (95% CI = 18 to 27). Subgroup analysis revealed that the annual incidence of VTE in males was 19 cases per 1,000 person-year (95% CI = 15 to 22), while in females, it was 20 cases per 1,000 person-year (95% CI = 16 to 25). Leave-one-out analysis demonstrated that the incidence ranged from 21 to 28 cases per 1,000 person-year when excluding each study individually. Meta-regression analysis did not find a significant association between age and the risk of VTE (P = 0.079). Based on the included studies, risk factors of VTE in ALS patients included a history of VTE, non-invasive ventilation, immobility, and decreased functional status.
CONCLUSION: Patients with ALS face a higher risk of developing VTE compared to individuals of the same age. These findings underscore the importance of implementing preventive measures and closely monitoring VTE in ALS patients.}, }
@article {pmid39434139, year = {2024}, author = {Agah, E and Mojtabavi, H and Behkar, A and Heidari, A and Ajdari, A and Shaka, Z and Mousavi, SV and Firoozeh, N and Tafakhori, A and Rezaei, N}, title = {CSF and blood levels of Neurofilaments, T-Tau, P-Tau, and Abeta-42 in amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {953}, pmid = {39434139}, issn = {1479-5876}, mesh = {Humans ; *Amyloid beta-Peptides/cerebrospinal fluid/blood ; *Amyotrophic Lateral Sclerosis/blood/cerebrospinal fluid/diagnosis ; Biomarkers/blood/cerebrospinal fluid ; Neurofilament Proteins/blood/cerebrospinal fluid ; Peptide Fragments/cerebrospinal fluid/blood ; Phosphorylation ; Publication Bias ; *tau Proteins/cerebrospinal fluid/blood ; }, abstract = {Recent literature suggests that markers of neuroaxonal damage, such as neurofilaments and tau protein, might serve as potential biomarkers for ALS. We conducted this systematic review and meta-analysis study to compare cerebrospinal fluid (CSF) and blood levels of total tau (t-tau), phosphorylated tau (p-tau), amyloid beta peptide 42 (Abeta-42), and neurofilaments in ALS patients and controls. A systematic search of Cochrane Library, PubMed, Embase, and ISI Web of Science was conducted on March 18, 2022, and updated on January 26, 2023. Observational studies that compared the concentrations of neurofilament light chain (NfL), neurofilament heavy chain (NFH), t-tau, p-tau, or Abeta-42 in CSF or peripheral blood of ALS patients and controls were included. Data from relevant studies were independently extracted and screened for quality using a standard tool, by at least two authors. Meta-analysis was conducted when a minimum of 3 studies reported the same biomarker within the same biofluid. A total of 100 studies were eligible for at least one meta-analysis. CSF and blood levels of NfL (standardized mean difference (SMD) [95% CI]; CSF: 1.46 [1.25-1.68]; blood: 1.35 [1.09-1.60]) and NFH (CSF: 1.32 [1.13-1.50], blood: 0.90 [0.58-1.22]) were significantly higher in ALS patients compared with controls. The pooled differences between ALS patients and controls were not significant for CSF t-tau, blood t-tau, and CSF Abeta-42, but CSF p-tau was lower in ALS patients (-0.27 [-0.47- -0.07]). Significantly decreased p-tau/t-tau ratios were found in ALS patients compared with controls (-0.84 [-1.16- -0.53]). Heterogeneity was considerable in most of our meta-analyses. CSF and blood neurofilament levels, as well as the CSF p-tau/t-tau ratio, might be potential candidates for improving ALS diagnosis. Further research is warranted to better understand the underlying mechanisms and the clinical implications of these biomarker alterations.}, }
@article {pmid39395475, year = {2024}, author = {Kim, SY and Kim, M and Park, K and Hong, S}, title = {A systematic review on analytical methods of the neurotoxin β-N-methylamino-L-alanine (BMAA), and its causative microalgae and distribution in the environment.}, journal = {Chemosphere}, volume = {366}, number = {}, pages = {143487}, doi = {10.1016/j.chemosphere.2024.143487}, pmid = {39395475}, issn = {1879-1298}, mesh = {*Amino Acids, Diamino/analysis ; *Microalgae/metabolism ; *Cyanobacteria Toxins ; *Neurotoxins/analysis ; *Cyanobacteria/metabolism ; *Tandem Mass Spectrometry ; *Environmental Monitoring/methods ; Ecosystem ; Chromatography, Liquid ; Diatoms/metabolism ; Water Pollutants, Chemical/analysis/metabolism ; }, abstract = {β-N-Methylamino-L-alanine (BMAA), a neurotoxin produced by various microalgal groups, is associated with neurodegenerative diseases and is considered a major environmental factor potentially linked to sporadic amyotrophic lateral sclerosis. This study systematically reviews the analytical methods used to study BMAA in publications from 2019 to the present. It also investigates the causative microalgae of BMAA and its geographical distributions in aquatic ecosystems based on studies conducted since 2003. A comprehensive search using the Web of Science database revealed that hydrolysis for extraction (67%), followed by quantification using LC-MS/MS (LC: 84%; MS/MS: 88%), is the most commonly employed method in BMAA analysis. Among analytical methods, RPLC-MS/MS had the highest percentage (88%) of BMAA-positive results and included a high number of quality control (QC) assessments. Various genera of cyanobacteria and diatoms have been reported to produce BMAA. The widespread geographical distribution of BMAA across diverse ecosystems highlights significant environmental and public health concerns. Notably, BMAA accumulation and biomagnification are likely more potent in marine or brackish water ecosystems than in freshwater ecosystems, potentially amplifying its ecological impacts. Future research should prioritize advanced, sensitive methods, particularly LC-MS/MS with as many QC assessments as possible, and should expand investigations to identify novel microalgal producers and previously uncharted geographical areas, with a special focus on marine or brackish water ecosystems. This effort will enhance our understanding of the environmental distribution and impacts of BMAA.}, }
@article {pmid39355247, year = {2024}, author = {Yang, JL and Wu, JY and Liu, JJ and Zheng, GQ}, title = {Herbal medicines for SOD1[G93A] mice of amyotrophic lateral sclerosis: preclinical evidence and possible immunologic mechanism.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1433929}, pmid = {39355247}, issn = {1664-3224}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/immunology/genetics ; Animals ; Mice ; *Disease Models, Animal ; Mice, Transgenic ; Humans ; Superoxide Dismutase-1/genetics ; Herbal Medicine ; }, abstract = {Currently, there is no cure or effective treatment for Amyotrophic Lateral Sclerosis (ALS). The mechanisms underlying ALS remain unclear, with immunological factors potentially playing a significant role. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), a systematic review of preclinical studies was conducted, searching seven databases including PubMed, covering literature from the inception of the databases to April 10, 2024. Methodological quality of the included literature was assessed using CAMARADES, while the risk of bias in the included studies was evaluated using SYRCLE's ROB tool. Review Manager 5.4.1 statistical software was used for meta-analysis of the outcomes. The scoping review followed the Joanna Briggs Institute Methodological Guidelines and reporting of this review followed the PRISMA-extension for Scoping Reviews (PRISMA -ScR) checklist to explore the immunological mechanisms of Herbal Medicine (HM) in treating ALS. This systematic review and meta-analysis involved 18 studies with a total of 443 animals. The studies scored between 4 to 8 for methodological quality and 3 to 7 for risk of bias, both summing up to 10.A remarkable effects of HM in ALS mice, including onset time(Standardized Mean Difference(SMD): 1.75, 95% Confidence Interval(CI) (1.14 ~ 2.36), Z = 5.60, P < 0.01), survival time(SMD = 1.42, 95% CI (0.79 ~ 2.04), Z = 4.44, P < 0.01), stride length(SMD=1.90, 95% CI (1.21 to 2.59), Z = 5.39, P < 0.01) and duration time (Mean Difference(MD)=6.79, 95% CI [-0.28, 13.87], Z=1.88, P =0.06), showing HM's certain efficiency in treating ALS mice. The scoping review ultimately included 35 articles for review. HMs may treat ALS through mechanisms such as combating oxidative stress, excitatory amino acid toxicity, and calcium cytotoxicity, understanding and exploring the mechanisms will bring hope to patients. Individual herbs and their formulations within HM address ALS through a variety of immune pathways, including safeguarding the blood-brain barrier, countering neuroinflammation, impeding complement system activation, mitigating natural killer cell toxicity, and regulating T cell-mediated immune pathways. The preclinical evidence supports the utilization of HM as a conventional treatment for ALS mice. Growing evidence indicates that HM may potentially delay neurological degeneration in ALS by activating diverse signaling pathways, especially immune pathways.}, }
@article {pmid39292414, year = {2024}, author = {Ataman, R and Alhasani, R and Auneau-Enjalbert, L and Quigley, A and Michael, HU and Ahmed, S}, title = {The psychometric properties of the Quality of Life in Neurological Disorders (Neuro-QoL) measurement system in neurorehabilitation populations: a systematic review.}, journal = {Journal of patient-reported outcomes}, volume = {8}, number = {1}, pages = {106}, pmid = {39292414}, issn = {2509-8020}, support = {36053//Canadian Foundation of Innovation and the Ministry of Health of Quebec/ ; }, mesh = {Humans ; *Nervous System Diseases/rehabilitation/psychology/diagnosis ; *Neurological Rehabilitation/methods ; *Psychometrics/methods ; *Quality of Life/psychology ; Reproducibility of Results ; }, abstract = {OBJECTIVE: To systematically review the literature of existing evidence on the measurement properties of the Quality of Life in Neurological Disorders (Neuro-QoL) measurement system among neurorehabilitation populations.
DATA SOURCES: The Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guided this systematic review in which we searched nine electronic databases and registries, and hand-searched reference lists of included articles.
STUDY SELECTION: Two independent reviewers screened selected articles and extracted data from 28 included studies.
DATA EXTRACTION: COSMIN's approach guided extraction and synthesizing measurement properties evidence (insufficient, sufficient), and the modified GRADE approach guided synthesizing evidence quality (very-low, low, moderate, high) by diagnosis.
DATA SYNTHESIS: Neuro-QoL has sufficient measurement properties when used by individuals with Huntington's disease, Multiple Sclerosis, Parkinson's disease, stroke, lupus, cognitive decline, and amyotrophic lateral sclerosis. The strongest evidence is for the first four conditions, where test-retest reliability, construct validity, and responsiveness are nearly always sufficient (GRADE: moderate-high). Structural validity is assessed only in multiple sclerosis and stroke but is often insufficient (GRADE: moderate-high). Criterion validity is sufficient in some stroke and Huntington's disease domains (GRADE: high). Item response theory analyses were reported for some stroke domains only. There is limited, mixed evidence for responsiveness and measurement error (GRADE: moderate-high), and no cross-cultural validity evidence CONCLUSIONS: Neuro-QoL domains can describe and evaluate patients with Huntington's disease, multiple sclerosis, Parkinson's disease, and stroke, but predictive validity evidence would be beneficial. In the other conditions captured in this review, a limited number of Neuro-QoL domains have evidence for descriptive use only. For these conditions, further evidence of structural validity, measurement error, cross-cultural validity and predictive validity would enhance the use and interpretation of Neuro-QoL.}, }
@article {pmid39230722, year = {2024}, author = {Chalitsios, CV and Ley, H and Gao, J and Turner, MR and Thompson, AG}, title = {Apolipoproteins, lipids, lipid-lowering drugs and risk of amyotrophic lateral sclerosis and frontotemporal dementia: a meta-analysis and Mendelian randomisation study.}, journal = {Journal of neurology}, volume = {271}, number = {10}, pages = {6956-6969}, pmid = {39230722}, issn = {1432-1459}, support = {Thompson/Apr23/896-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/genetics/epidemiology ; *Apolipoproteins/antagonists & inhibitors/blood/genetics ; *Frontotemporal Dementia/blood/genetics/epidemiology ; Hypolipidemic Agents/pharmacology/therapeutic use ; Lipids/blood ; Mendelian Randomization Analysis ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have clinical, pathological and genetic overlapping. Lipid pathways are implicated in ALS. This study examined the effect of blood lipid levels on ALS, FTD risk, and survival in ALS.
METHODS: A systematic review and meta-analysis of high and low-density lipoprotein cholesterol (HDL-c and LDL-c), total cholesterol, triglycerides, apolipoproteins B and A1 levels with ALS was performed. Two-sample Mendelian randomisation (MR) analysis sought the causal effects of these exposures on ALS, FTD, and survival in ALS. The effect of lipid-lowering drugs was also examined using genetic proxies for targets of lipid-lowering medications.
RESULTS: Three cohort studies met the inclusion criteria for meta-analysis. Meta-analysis indicated an association between higher LDL-c (HRper mmol/L = 1.07, 95%CI:1.02-1.12; I 2 =18%) and lower HDL-c (HRper mmol/L = 0.83, 95%CI:0.74-0.94; I 2 =0%) with an increased risk of ALS. MR suggested causal effects of higher LDL-c (ORIVW = 1.085, 95%:CI 1.008-1.168, pFDR = 0.0406), total cholesterol (ORIVW = 1.081, 95%:CI 1.013-1.154, pFDR = 0.0458) and apolipoprotein B (ORIVW = 1.104, 95%:CI 1.041-1.171, pFDR = 0.0061) increasing ALS risk, and higher apolipoprotein B level increasing FTD risk (ORIVW = 1.424, 95%CI 1.072-1.829, pFDR = 0.0382). Reducing LDL-c through APOB inhibition was associated with lower ALS (ORIVW = 0.84, 95%CI 0.759-0.929, pFDR = 0.00275) and FTD risk (ORIVW = 0.581, 95%CI 0.387-0.874, pFDR = 0.0362).
CONCLUSION: These data support the influence of LDL-c and total cholesterol on ALS risk and apolipoprotein B on the risk of ALS and FTD. Potential APOB inhibition might decrease the risk of sporadic ALS and FTD. Further work in monogenic forms of ALS and FTD is necessary to determine whether blood lipids influence penetrance and phenotype.}, }
@article {pmid39182937, year = {2024}, author = {Silva, ST and Costa, IM and Souza, AA and Pondofe, K and Melo, LP and Resqueti, VR and Valentim, R and Gonçalves, F and Ribeiro, TS}, title = {Physical therapy for the management of global function, fatigue and quality of life in amyotrophic lateral sclerosis: systematic review and meta-analyses.}, journal = {BMJ open}, volume = {14}, number = {8}, pages = {e076541}, pmid = {39182937}, issn = {2044-6055}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/therapy ; *Quality of Life ; *Physical Therapy Modalities ; *Fatigue/therapy/etiology ; Randomized Controlled Trials as Topic ; }, abstract = {OBJECTIVES: To critically evaluate the effectiveness of physical therapy interventions in improving global function, quality of life and fatigue in individuals with amyotrophic lateral sclerosis (ALS).
DESIGN: Systematic review and meta-analyses.
DATA SOURCES: MEDLINE, EMBASE, Cochrane Library (CENTRAL) and Physiotherapy Evidence Database (PEDro) were searched through 31 January 2023.
ELIGIBILITY CRITERIA: We included randomised clinical trials (RCTs) that compared physical therapy interventions that act on global function, fatigue and quality of life in individuals with ALS with any other non-physiotherapeutic methods and techniques, placebo or non-intervention. The primary outcome measure was the evaluation of global function. Secondary outcomes were quality of life, fatigue and adverse events.
DATA EXTRACTION AND SYNTHESIS: Two independent authors used a researcher-developed extraction form and the Rayyan software to search, screen and code included studies. The risk of bias was assessed using the PEDro scale. Meta-analyses were conducted employing random effects. Outcomes were succinctly presented in Grading of Recommendations, Assessment, Development and Evaluation evidence profiles.
RESULTS: Our searches identified 39 415 references. After study selection, three studies were included in the review. Such studies involved 62 participants with a mean age of 54.6 years. In the evaluated trials, 40 were male, while 22 participants were female. Regarding the type of onset of the disease, 58 participants had spinal onset of ALS, and four had bulbar.
CONCLUSIONS: Physical therapy intervention may improve the global function of individuals with ALS in the short term; however, clinically, it was inconclusive. In terms of quality of life and fatigue, physical therapy intervention is not more effective than control in the short term. Adverse events are not increased by physical therapy intervention in the short term. Due to significant methodological flaws, small sample sizes, wide CIs and clinical interpretation, our confidence in the effect estimate is limited.
PROSPERO REGISTRATION NUMBER: CRD42021251350.}, }
@article {pmid39168358, year = {2024}, author = {Ueno, Y and Morishima, Y and Hata, T and Shindo, A and Murata, H and Saito, T and Nakamura, Y and Shindo, K}, title = {Current progress in microRNA profiling of circulating extracellular vesicles in amyotrophic lateral sclerosis: A systematic review.}, journal = {Neurobiology of disease}, volume = {200}, number = {}, pages = {106639}, doi = {10.1016/j.nbd.2024.106639}, pmid = {39168358}, issn = {1095-953X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/genetics/diagnosis ; Biomarkers/blood ; *Extracellular Vesicles/metabolism/genetics ; *MicroRNAs/blood/genetics ; }, abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease affecting upper and lower motor neurons, leading to death resulting mainly from respiratory failure, for which there is currently no curative treatment. Underlying pathological mechanisms for the development of ALS are diverse and have yet to be elucidated. Non-invasive testing to isolate circulating molecules including microRNA to diagnose ALS has been reported, but circulating extracellular vesicle (EV)-derived microRNA has not been fully studied in the ALS population.
METHODS: A systematic literature review to explore studies investigating the profile of microRNAs in EVs from blood samples of ALS patients was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline.
RESULTS: Eleven studies including a total of 263 patients with ALS were included in the present systematic review. The majority of patients had sporadic ALS, though a small number of patients with ALS having genetic mutations were included. Seven studies used plasma-derived EVs, and the remaining four studies used serum-derived EVs. RNA sequencing or microarrays were used in eight studies, and quantitative PCR was used in eight studies, of which five studies used RNA sequencing or microarrays for screening and quantitative PCR for validation. There was overlap of miR-199a-3p and miR-199a-5p in three studies.
CONCLUSIONS: Overall, the systematic review addressed the current advances in the profiling of microRNAs in circulating EVs of ALS patients. Blood samples, isolation of EVs, and microRNA analysis were diverse. Although there was an overlap of miR-199a-3p and miR-199a-5p, collection of further evidence is warranted.}, }
@article {pmid39075493, year = {2024}, author = {Mangal, AL and Mücke, M and Rolke, R and Appelmann, I}, title = {Advance directives in amyotrophic lateral sclerosis - a systematic review and meta-analysis.}, journal = {BMC palliative care}, volume = {23}, number = {1}, pages = {191}, pmid = {39075493}, issn = {1472-684X}, mesh = {*Amyotrophic Lateral Sclerosis/psychology/therapy/complications ; Humans ; *Advance Directives/statistics & numerical data/psychology ; Advance Care Planning/statistics & numerical data/standards ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the upper and lower motoneuron. It is associated with a life expectancy of 2-4 years after diagnosis. Individuals experience paralysis, dysphagia, respiratory failure and loss of communicative function, rendering advance care planning (ACP) critically important. This systematic review primarily aimed to internationally compare the application of advance directives (AD) and ACP in ALS. Its secondary aim was to identify ACP preferences, identify fields for future research and to generate recommendations for improving patient care through ACP.
METHODS: We conducted a systematic literature review and meta-analysis. Five electronic databases (Embase, Medline, Scopus, PsycInfo and CENTRAL) were searched for qualitative and quantitative primary literature from 1999 to 2024. Cross-references were used to identify additional publications. Study selection was performed based on inclusion criteria. Number and content of AD were extracted systematically. After statistical analysis consecutive meta-analysis was performed for international differences and changes over time. Quality assessment of studies was performed using the MMAT (Mixed Methods Appraisal Tool). PROSPERO Registration (June 07, 2021) : CRD42021248040.
RESULTS: A total of 998 records was screened of which 26 were included in the synthesis. An increase in publication numbers of 88.9% was observed from 1999 to 2024. Results regarding use and content of AD were heterogeneous and international differences were detected. AD were signed in 60.4% of records (1,629 / 2,696 patients). The number of AD decreased over time when separating the review period in two decades (1st 1999-2011: 78% vs. 2nd 2012-2024: 42%). Study quality was superior in qualitative and mixed method designs compared to quantitative studies.
CONCLUSION: Further prospective studies should include detailed analyses on preferences regarding ventilation and artificial nutrition in ALS and should encompass countries of the global south. Despite the complexity of ACP with regard to individual patient needs, ACP should be part of each individual support plan for ALS patients and should specifically comprise a discussion on the preferred place of death. The available disease-specific AD documents should be preferred.}, }
@article {pmid39030740, year = {2024}, author = {Jonson, C and Levine, KS and Lake, J and Hertslet, L and Jones, L and Patel, D and Kim, J and Bandres-Ciga, S and Terry, N and Mata, IF and Blauwendraat, C and Singleton, AB and Nalls, MA and Yokoyama, JS and Leonard, HL}, title = {Assessing the lack of diversity in genetics research across neurodegenerative diseases: A systematic review of the GWAS Catalog and literature.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {20}, number = {8}, pages = {5740-5756}, pmid = {39030740}, issn = {1552-5279}, support = {U19AG079774/NS/NINDS NIH HHS/United States ; R01 AG062588/AG/NIA NIH HHS/United States ; ZO1AG000534/HH/HHS/United States ; U19 AG079774/AG/NIA NIH HHS/United States ; P30 AG062422/AG/NIA NIH HHS/United States ; P01 AG019724/AG/NIA NIH HHS/United States ; R01 AG057234/AG/NIA NIH HHS/United States ; 75N95022C00031/NS/NINDS NIH HHS/United States ; //Intramural Research Program/ ; P01AG019724/NS/NINDS NIH HHS/United States ; P30AG062422/NS/NINDS NIH HHS/United States ; /ALZ/Alzheimer's Association/United States ; U54NS123985/NS/NINDS NIH HHS/United States ; 75N95022C00031/DA/NIDA NIH HHS/United States ; U54 NS123985/NS/NINDS NIH HHS/United States ; R01AG057234/NS/NINDS NIH HHS/United States ; R01AG062588/NS/NINDS NIH HHS/United States ; //Global Brain Health Institute; and the Mary Oakley Foundation/ ; //Rainwater Charitable Foundation/ ; }, mesh = {Humans ; Genetic Predisposition to Disease/genetics ; *Genome-Wide Association Study ; *Neurodegenerative Diseases/genetics ; White People/genetics ; }, abstract = {The under-representation of non-European cohorts in neurodegenerative disease genome-wide association studies (GWAS) hampers precision medicine efforts. Despite the inherent genetic and phenotypic diversity in these diseases, GWAS research consistently exhibits a disproportionate emphasis on participants of European ancestry. This study reviews GWAS up to 2022, focusing on non-European or multi-ancestry neurodegeneration studies. We conducted a systematic review of GWAS results and publications up to 2022, focusing on non-European or multi-ancestry neurodegeneration studies. Rigorous article inclusion and quality assessment methods were employed. Of 123 neurodegenerative disease (NDD) GWAS reviewed, 82% predominantly featured European ancestry participants. A single European study identified over 90 risk loci, compared to a total of 50 novel loci in identified in all non-European or multi-ancestry studies. Notably, only six of the loci have been replicated. The significant under-representation of non-European ancestries in NDD GWAS hinders comprehensive genetic understanding. Prioritizing genomic diversity in future research is crucial for advancing NDD therapies and understanding. HIGHLIGHTS: Eighty-two percent of neurodegenerative genome-wide association studies (GWAS) focus on Europeans. Only 6 of 50 novel neurodegenerative disease (NDD) genetic loci have been replicated. Lack of diversity significantly hampers understanding of NDDs. Increasing diversity in NDD genetic research is urgently required. New initiatives are aiming to enhance diversity in NDD research.}, }
@article {pmid39025824, year = {2024}, author = {Lorenc, T and Khouja, C and Harden, M and Fulbright, H and Thomas, J}, title = {Defensive healthcare practice: systematic review of qualitative evidence.}, journal = {BMJ open}, volume = {14}, number = {7}, pages = {e085673}, pmid = {39025824}, issn = {2044-6055}, mesh = {Humans ; *Qualitative Research ; *Defensive Medicine ; Attitude of Health Personnel ; }, abstract = {OBJECTIVE: To synthesise qualitative evidence on clinicians' views and experiences of defensive practice.
DESIGN: Systematic review of qualitative data.
DATA SOURCES: MEDLINE, Embase, PsycINFO, AMED, Maternity and Infant Care, CINAHL, ASSIA, Sociological Abstracts, Proquest Dissertations & Theses and PROSPERO were searched from 2000 to October 2023.
ELIGIBILITY CRITERIA: We included English-language studies of clinicians which reported qualitative data on the impact of litigation or complaints on clinical practice.
DATA EXTRACTION AND SYNTHESIS: We coded findings data line by line using a grounded theory approach. We assessed quality using Hawker et al's tool and synthesised data thematically.
RESULTS: 17 studies were included. Participants identify a range of clinical decisions which may be defensively motivated, relating to diagnosis and documentation as well as to treatment. Defensive practice often relates to a diffuse sense of risk rather than the direct threat of litigation and may overlap with other motivations, such as perceived pressure from patients or the desire to avoid harm. Defensive practice is seen to be harmful in many ways, but again, these perceptions may gain force from broader narratives of mistrust and disempowerment, as much as from the risk of litigation.
CONCLUSIONS: The idea of defensive practice, as enacted, is more complex than some theoretical accounts suggest and may often function to express broader concerns about the work of clinical care. The qualitative evidence calls into question the view of defensive practice as a key mediator linking litigation risk to inappropriate treatment and excess costs.}, }
@article {pmid38988765, year = {2024}, author = {Readman, MR and Polden, M and Gibbs, MC and Donohue, A and Chhetri, SK and Crawford, TJ}, title = {Oculomotor atypicalities in motor neurone disease: a systematic review.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1399923}, pmid = {38988765}, issn = {1662-4548}, abstract = {INTRODUCTION: Cognitive dysfunction is commonplace in Motor Neurone Disease (MND). However, due to the prominent motor symptoms in MND, assessing patients' cognitive function through traditional cognitive assessments, which oftentimes require motoric responses, may become increasingly challenging as the disease progresses. Oculomotor pathways are apparently resistant to pathological degeneration in MND. As such, abnormalities in oculomotor functions, largely driven by cognitive processes such as saccades and smooth pursuit eye movement, may be reflective of frontotemporal cognitive deficits in MND. Thus, saccadic and smooth pursuit eye movements may prove to be ideal mechanistic markers of cognitive function in MND.
METHODS: To ascertain the utility of saccadic and smooth pursuit eye movements as markers of cognitive function in MND, this review summarizes the literature concerning saccadic and smooth pursuit eye movement task performance in people with MND.
RESULTS AND DISCUSSION: Of the 22 studies identified, noticeable patterns suggest that people with MND can be differentiated from controls based on antisaccade and smooth pursuit task performance, and thus the antisaccade task and smooth pursuit task may be potential candidates for markers of cognition in MND. However, further studies which ascertain the concordance between eye tracking measures and traditional measures of cognition are required before this assumption is extrapolated, and clinical recommendations are made.
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=376620, identifier CRD42023376620.}, }
@article {pmid38978024, year = {2024}, author = {Endalamaw, A and Gilks, CF and Ambaw, F and Shiferaw, WS and Assefa, Y}, title = {Explaining inequity in knowledge, attitude, and services related to HIV/AIDS: a systematic review.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {1815}, pmid = {38978024}, issn = {1471-2458}, mesh = {Humans ; *HIV Infections/psychology ; *Health Knowledge, Attitudes, Practice ; Healthcare Disparities ; }, abstract = {BACKGROUND: Equitable service provision and coverage are important responses to end the threat of the HIV/AIDS pandemic. Understanding inequity supports policies and programmes to deliver tailored interventions. There is continuous evidence generation on inequity in HIV/AIDS services. However, there was a lack of evidence on the global picture of inequity in behavioural and biomedical services related to HIV/AIDS. This systematic review assessed inequities in knowledge, attitude, HIV testing, and ART coverage across individual-level social groups and multiple (dis)advantage categories.
METHODS: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline, with a PROSPERO registration number CRD42024521247. The risk of bias was assessed by using Hoy et al's and Joanna Brigg's quality appraisal checklists for cross-sectional quantitative and qualitative studies, respectively. The search date was from inception to the final database search date (May 29, 2023). The included articles were either quantitative or qualitative studies. We used mixed-methods approach to analyse the data from the review articles. Quantitative descriptive analysis was conducted to estimate frequency of articles published from different countries around the world. Qualitative content analysis of the findings from the original studies was conducted using the PROGRESS plus framework which stands for: place of residence, occupation or employment status, gender, religion, education status, socioeconomic status, and social capital.
RESULTS: Out of 6,029 articles that were accessed and screened, only 72 articles met the inclusion criteria. More articles on HIV-related equity in knowledge, attitude, testing, and ART were published in developed countries than in developing countries. Individuals from higher-income households had better knowledge about HIV/AIDS. Unfavourable attitudes towards people living with HIV and HIV/AIDS-associated stigma were common among women. HIV/AIDS service coverage (HIV testing or ART coverage) was higher among richer and urban residents. HIV/AIDS-associated stigma and lower levels of knowledge about HIV/AIDS were observed among multiple disadvantageous groups due to the intersection of two or more identities.
CONCLUSIONS: The current review revealed that there have been disparities in HIV/AIDS services between social classes. Ending service disparity towards the global threat of HIV/AIDS demands tailored interventions based on socially disadvantaged groups (e.g., poor, rural dwellers, and women) and intersectional determinants. There is a need to understand the deep-rooted causes of inequity and the challenges that an equity-oriented system faces over time. More studies on inequity are needed, including intersectional inequity, which has been rarely studied in developing countries.}, }
@article {pmid38968328, year = {2024}, author = {Gowrishankar, S and Smith, ME and Creber, N and Muzaffar, J and Borsetto, D}, title = {Immunosuppression in stem cell clinical trials of neural and retinal cell types: A systematic review.}, journal = {PloS one}, volume = {19}, number = {7}, pages = {e0304073}, pmid = {38968328}, issn = {1932-6203}, mesh = {Humans ; *Stem Cell Transplantation/methods ; *Immunosuppression Therapy/methods ; Retina/immunology ; Immunosuppressive Agents/therapeutic use ; Clinical Trials as Topic ; }, abstract = {BACKGROUND: Pharmacologic immunosuppression regimes are commonly employed in stem cell clinical trials to mitigate host immune rejection and promote survival and viability of transplanted cells. Immunosuppression and cell survival has been extensively studied in retinal and spinal tissues. The applicability of stem cell therapy is rapidly expanding to other sensory organs such as the ear and hearing. As regenerative therapy is directed to new areas, a greater understanding of immunosuppression strategies and their efficacy is required to facilitate translation to organ-specific biologic microenvironments.
OBJECTIVE: This systematic review appraises the current literature regarding immunosuppression strategies employed in stem cell trials of retinal and neural cells.
METHODS: This systematic review was performed in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria included studies presenting data on neural or retinal cells as part of an in-human clinical trial that detailed the immunosuppression regime used. Exclusion criteria included non-English language studies, animal studies, review articles, case reports, editorials, and letters. The databases Medline, Embase, Scopus, Web of Science, and the Cochrane Library were searched from inception to February 2024. Risk of bias was evaluated using the ROBINS-I tool.
RESULTS: Eighteen articles fit the inclusion criteria. Nine articles concerned retinal cells, 5 concerned spinal cord injury, and 4 concerned amyotrophic lateral sclerosis. A multi-drug and short-term immunosuppression regime were commonly employed in the identified studies. Detected immune responses in treated patients were rare. Common immunosuppression paradigms included tacrolimus, mycophenolate mofetil and tapering doses of steroids. Local immunosuppression with steroids was employed in some studies concerning retinal diseases.
DISCUSSION: A short-term course of systemic immunosuppression seemed efficacious for most included studies, with some showing grafted cells viable months to years after immunosuppression had stopped. Longer-term follow-up is required to see if this remains the case. Side effects related to immunosuppression were uncommon.}, }
@article {pmid38870470, year = {2024}, author = {McDool, E and Carlton, J and Powell, PA and Coates, E and Knox, L and Mayberry, E and Appleby, N and Griffiths, AW and Hobson, E and McDermott, CJ}, title = {Measuring Health-Related Quality of Life in Amyotrophic Lateral Sclerosis: A Systematic Review and Conceptual Framework.}, journal = {Neurology}, volume = {103}, number = {2}, pages = {e209549}, pmid = {38870470}, issn = {1526-632X}, mesh = {*Amyotrophic Lateral Sclerosis/psychology/physiopathology ; Humans ; *Quality of Life/psychology ; Patient Reported Outcome Measures ; }, abstract = {BACKGROUND AND OBJECTIVES: The assessment of health-related quality of life (HRQoL) in patients with amyotrophic lateral sclerosis (ALS) is heterogeneous and inconsistent. The objectives of this study were (1) to develop a comprehensive conceptual framework of HRQoL in ALS and (2) map the content of existing patient-reported outcome measures (PROMs) used in ALS to this novel framework.
METHODS: Our model of HRQoL in ALS (Health-related Quality of life in Amyotrophic Lateral Sclerosis, QuALS) was developed from a systematic literature review and consultative input from key stakeholders (patients, carers, and health care professionals). Five electronic databases were searched in April 2022. Primary studies of any design that assessed HRQoL in ALS by using a multi-item PROM and/or qualitative methods were identified. Using an a priori framework, HRQoL themes were extracted and iteratively modified from the content of each PROM and qualitative study quotations identified in the literature. The conceptual framework was ratified by stakeholders with lived experience and clinical experts. The QuALS framework was used to map the content of identified PROMs and qualitative studies based on thematic coverage.
RESULTS: QuALS covers 3 high-level domains of HRQoL (physical, psychological, and social functioning) and consists of 7 themes (Activities; Physical Health; Autonomy; Cognition; Feelings and Emotions; Self-identity; Relationships), characterized by 42 subthemes. Of 8,220 studies identified, 274 were included in the review that informed QuALS. In these studies, 111 PROMs were used to assess at least 1 aspect of HRQoL, and 11 studies used qualitative methods. Of the 3 high-level domains, physical functioning was the most commonly assessed, particularly within ALS-specific PROMs where almost one-quarter of PROMs exclusively assessed physical functioning. None of the PROMs or qualitative studies identified assessed all aspects of HRQoL in the QuALS framework.
DISCUSSION: This study presents a new comprehensive conceptual framework of HRQoL in ALS (QuALS), informed by a robust systematic review of existing literature and stakeholder input, incorporating lived experience. QuALS provides a valuable resource for researchers and clinicians interested in taking a holistic approach to assessing and understanding the full impact of ALS on HRQoL and how this may be affected by treatments.}, }
@article {pmid38830181, year = {2024}, author = {Weemering, DN and Beelen, A and Kliest, T and van Leeuwen, LAG and van den Berg, LH and van Eijk, RPA}, title = {Trial Participation in Neurodegenerative Diseases: Barriers and Facilitators: A Systematic Review and Meta-Analysis.}, journal = {Neurology}, volume = {103}, number = {1}, pages = {e209503}, pmid = {38830181}, issn = {1526-632X}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; *Clinical Trials as Topic ; *Patient Participation ; Patient Selection ; }, abstract = {BACKGROUND AND OBJECTIVES: Clinical trials in neurodegenerative diseases often encounter selective enrollment and under-representation of certain patient populations. This delays drug development and substantially limits the generalizability of clinical trial results. To inform recruitment and retention strategies, and to better understand the generalizability of clinical trial populations, we investigated which factors drive participation.
METHODS: We reviewed the literature systematically to identify barriers to and facilitators of trial participation in 4 major neurodegenerative disease areas: Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, and Huntington disease. Inclusion criteria included original research articles published in a peer-reviewed journal and evaluating barriers to and/or facilitators of participation in a clinical trial with a drug therapy (either symptomatic or disease-modifying). The Critical Appraisal Skills Program checklist for qualitative studies was used to assess and ensure the quality of the studies. Qualitative thematic analyses were employed to identify key enablers of trial participation. Subsequently, we pooled quantitative data of each enabler using meta-analytical models.
RESULTS: Overall, we identified 36 studies, enrolling a cumulative sample size of 5,269 patients, caregivers, and health care professionals. In total, the thematic analysis resulted in 31 unique enablers of trial participation; the key factors were patient-related (own health benefit and altruism), study-related (treatment and study burden), and health care professional-related (information availability and patient-physician relationship). When meta-analyzed across studies, responders reported that the reason to participate was mainly driven by (1) the relationship with clinical staff (70% of the respondents; 95% CI 53%-83%), (2) the availability of study information (67%, 95% CI 38%-87%), and (3) the use or absence of a placebo or sham-control arm (53% 95% CI 32%-72%). There was, however, significant heterogeneity between studies (all p < 0.001).
DISCUSSION: We have provided a comprehensive list of reasons why patients participate in clinical trials for neurodegenerative diseases. These results may help to increase participation rates, better inform patients, and facilitate patient-centric approaches, thereby potentially reducing selection mechanisms and improving generalizability of trial results.}, }
@article {pmid38820331, year = {2025}, author = {Dessie, G and Li, J and Nghiem, S and Doan, T}, title = {Prevalence and Determinants of Stunting-Anemia and Wasting-Anemia Comorbidities and Micronutrient Deficiencies in Children Under 5 in the Least-Developed Countries: A Systematic Review and Meta-analysis.}, journal = {Nutrition reviews}, volume = {83}, number = {2}, pages = {e178-e194}, pmid = {38820331}, issn = {1753-4887}, support = {//Australia National University/ ; }, mesh = {Child, Preschool ; Female ; Humans ; Infant ; *Anemia/epidemiology ; Comorbidity ; *Developing Countries/statistics & numerical data ; *Growth Disorders/epidemiology ; *Micronutrients/deficiency ; Prevalence ; *Wasting Syndrome/epidemiology ; }, abstract = {CONTEXT: Despite shifting from addressing isolated forms of malnutrition to recognizing its multifaceted nature, evidence on the prevalence and determinants of micronutrient deficiencies, and their coexistence with undernutrition in children under 5, remains insufficient, unsystematic, and incohesive.
OBJECTIVE: The aim of this systematic review and meta-analysis was to assess the prevalence and determinants of stunting-anemia and wasting-anemia comorbidities and micronutrient deficiencies in children under 5 in the least-developed countries (LDCs).
DATA SOURCES: Electronic searches took place from January 15, 2023, to February 14, 2024, across multiple databases, including PubMed, Embase, Web of Science, SCOPUS, African Index Medicus (AIM), World Health Organization's Institutional Repository for Information Sharing (IRIS), and African Journals Online. The search spanned the years 2000 to 2024, yet it yielded eligible full-text English research articles from only 2005 to 2021 conducted in LDCs. Studies lacking quantitative data on malnutrition types and their determinants were excluded.
DATA EXTRACTION: Two independent authors assessed articles for bias and quality using Hoy et al's 10-item scale and Newcastle-Ottawa Scale (NOS) criteria. Prevalence and other details were extracted using a Joanna Briggs Institute Excel template. Authors extracted adjusted odds ratios (aORs) for determinant factors such as sex and vitamin A and iron supplementation.
DATA ANALYSIS: The search yielded 6248 articles from 46 LDCs. Sixty-nine articles, with a total sample size of 181 605, met inclusion criteria for the final meta-analysis. Vitamin A deficiency affected 16.32% of children, and iodine deficiency affected 43.41% of children. The pooled prevalence of wasting-anemia and stunting-anemia comorbidity was 5.44% and 19.47%, respectively. Stunting was associated with vitamin A deficiency (aOR: 1.54; 95% CI: 1.01-2.37), and not taking vitamin A supplementation was associated with iron-deficiency anemia (aOR: 1.37; 95% CI: 1.21-1.55).
CONCLUSION: A significant proportion of children under 5 in LDCs experienced stunting-anemia and wasting-anemia comorbidities and micronutrient deficiencies. This study underscores the urgent need to address factors driving these burdens.
PROSPERO registration no. CRD42023409483.}, }
@article {pmid38775181, year = {2024}, author = {Marriott, H and Spargo, TP and Al Khleifat, A and Andersen, PM and Başak, NA and Cooper-Knock, J and Corcia, P and Couratier, P and de Carvalho, M and Drory, V and Gotkine, M and Landers, JE and McLaughlin, R and Pardina, JSM and Morrison, KE and Pinto, S and Shaw, CE and Shaw, PJ and Silani, V and Ticozzi, N and van Damme, P and van den Berg, LH and Vourc'h, P and Weber, M and Veldink, JH and , and Dobson, RJ and Schwab, P and Al-Chalabi, A and Iacoangeli, A}, title = {Mutations in the tail and rod domains of the neurofilament heavy-chain gene increase the risk of ALS.}, journal = {Annals of clinical and translational neurology}, volume = {11}, number = {7}, pages = {1775-1786}, pmid = {38775181}, issn = {2328-9503}, support = {//Maudsley NHS Foundation Trust/ ; 22-PDF-609//ALS Association Milton Safenowitz Research/ ; MR/R024804/1/MRC_/Medical Research Council/United Kingdom ; //BHF British Heart Foundation/ ; //Darby Rimmer MND Foundation/ ; NIHR202421//National Institute for Health Research/ ; Al Khleifat/Oct21/975-799/MNDA_/Motor Neurone Disease Association/United Kingdom ; //MND Scotland/ ; ES/L008238/1//Economic and Social Research Council/ ; //Alan Davidson Foundation/ ; /WT_/Wellcome Trust/United Kingdom ; //Alzheimer's Research UK/ ; //Rosetrees Trust/ ; MR/L501529/1/MRC_/Medical Research Council/United Kingdom ; //My Name'5 Doddie Foundation/ ; //GlaxoSmithKline/ ; //MRC Medical Research Council/ ; //The NIHR Maudsley Biomedical Research Centre/ ; //Spastic Paraplegia Foundation/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/epidemiology ; Genetic Predisposition to Disease/genetics ; Mutation ; Mutation, Missense ; *Neurofilament Proteins/genetics ; Protein Domains/genetics ; }, abstract = {OBJECTIVE: Neurofilament heavy-chain gene (NEFH) variants are associated with multiple neurodegenerative diseases, however, their relationship with ALS has not been robustly explored. Still, NEFH is commonly included in genetic screening panels worldwide. We therefore aimed to determine if NEFH variants modify ALS risk.
METHODS: Genetic data of 11,130 people with ALS and 7,416 controls from the literature and Project MinE were analysed. We performed meta-analyses of published case-control studies reporting NEFH variants, and variant analysis of NEFH in Project MinE whole-genome sequencing data.
RESULTS: Fixed-effects meta-analysis found that rare (MAF <1%) missense variants in the tail domain of NEFH increase ALS risk (OR 4.55, 95% CI 2.13-9.71, p < 0.0001). In Project MinE, ultrarare NEFH variants increased ALS risk (OR 1.37 95% CI 1.14-1.63, p = 0.0007), with rod domain variants (mostly intronic) appearing to drive the association (OR 1.45 95% CI 1.18-1.77, pMadsen-Browning = 0.0007, pSKAT-O = 0.003). While in the tail domain, ultrarare (MAF <0.1%) pathogenic missense variants were also associated with higher risk of ALS (OR 1.94, 95% CI 0.86-4.37, pMadsen-Browning = 0.039), supporting the meta-analysis results. Finally, several tail in-frame deletions were also found to affect disease risk, however, both protective and pathogenic deletions were found in this domain, highlighting an intricate architecture that requires further investigation.
INTERPRETATION: We showed that NEFH tail missense and in-frame deletion variants, and intronic rod variants are risk factors for ALS. However, they are not variants of large effect, and their functional impact needs to be clarified in further studies. Therefore, their inclusion in routine genetic screening panels should be reconsidered.}, }
@article {pmid38762656, year = {2024}, author = {Li, Z and Kang, H}, title = {Efficacy of non-pharmacological interventions for individuals with amyotrophic lateral sclerosis: systematic review and network meta-analysis of randomized control trials.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {11365}, pmid = {38762656}, issn = {2045-2322}, mesh = {*Amyotrophic Lateral Sclerosis/therapy/physiopathology ; Humans ; *Randomized Controlled Trials as Topic ; *Quality of Life ; *Network Meta-Analysis ; Exercise Therapy/methods ; Treatment Outcome ; Muscle Strength ; }, abstract = {This network meta-analysis (NMA) aimed to compare the efficacy of five non-pharmacological interventions, including exercise intervention (EI), nutritional intervention (NI), respiratory intervention (RI), psychological intervention (PSI), and integrated physical intervention (IPI), on functional status, quality of life, muscle strength, pulmonary function, and safety in patients with amyotrophic lateral sclerosis (ALS). We searched nine databases, PubMed, Cochrane, Embase, Scopus, Web of Science, CNKI, CBM, WFPD, and CSTJ, for randomized controlled trials of ALS patients. The primary outcome was the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score. Secondary outcomes were the McGill Quality of Life Questionnaire (McGill-QoL), Medical Research Council (MRC)-sum score, Forced Vital Capacity (FVC), and Fatigue Severity Scale (FSS) score. This NMA was conducted using random-effect models to calculate the standard mean difference (SMD) and 95% confidence interval (CI). All types of supplemental interventions had some benefit for patients with ALS. EI had a beneficial effect on the ALSFRS-R score (SMD: 1.01; 95% CI 0.50-1.51), FVC (SMD: 0.78; 95% CI 0.02-1.55), McGill-QoL (SMD: 0.71 95% CI 0.33-1.08), and MRC (SMD: 1.11; 95% CI 0.08-2.14). RI had a beneficial effect on the ALSFRS-R score (SMD: 0.83 95% CI 0.12-1.55). IPI had a beneficial effect on the ALSFRS-R score (SMD: 0.65 95% CI 0.06-1.24). NI had a beneficial effect on the McGill-QoL (SMD: 0.63 95% CI 0.02-1.23). The current study findings support a multimodal intervention strategy with an emphasis on EI for slowing disease progression in patients with ALS.}, }
@article {pmid38759021, year = {2024}, author = {Pupillo, E and Al-Chalabi, A and Sassi, S and Arippol, E and Tinti, L and Vitelli, E and Copetti, M and Leone, MA and Bianchi, E}, title = {Methodological Quality of Clinical Trials in Amyotrophic Lateral Sclerosis: A Systematic Review.}, journal = {Journal of neuromuscular diseases}, volume = {11}, number = {4}, pages = {749-765}, pmid = {38759021}, issn = {2214-3602}, mesh = {*Amyotrophic Lateral Sclerosis/therapy ; Humans ; *Clinical Trials as Topic/standards ; *Research Design ; }, abstract = {BACKGROUND: More than 200 clinical trials have been performed worldwide in ALS so far, but no agents with substantial efficacy on disease progression have been found.
OBJECTIVE: To describe the methodological quality of all clinical trials performed in ALS and published before December 31, 2022.
METHODS: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta Analyses.
RESULTS: 213 trials were included. 47.4% manuscripts described preclinical study evaluation, with a positive effect in all. 67.6% of trials were conducted with a parallel-arm design, while 12.7% were cross-over studies; 77% were randomized, while in 5.6% historical-controls were used for comparison. 70% of trials were double blind. Participant inclusion allowed forced vital capacity (or corresponding slow vital capacity)<50% in 15% cases, between 55-65% in 21.6%, between 70-80% in 14.1% reports, and 49.3% of the evaluated manuscripts did not provide a minimum value for respiratory capacity at inclusion. Disease duration was < 6-months in 6 studies, 7-36 months in 68, 37-60 months in 24, 8 trials requested more than 1-month of disease duration, while in 107 reports a disease duration was not described. Dropout rate was ≥20% in 30.5% trials, while it was not reported for 8.5%.
CONCLUSION: The methodological quality of the included studies was highly variable. Major issues to be addressed in future ALS clinical trials include: the requirement for standard animal toxicology and phase I studies, the resource-intensive nature of phase II-III studies, adequate study methodology and design, a good results reporting.}, }
@article {pmid38720896, year = {2024}, author = {Zong, J and Yang, Y and Wang, H and Zhang, H and Yang, X and Yang, X}, title = {The two-directional prospective association between inflammatory bowel disease and neurodegenerative disorders: a systematic review and meta-analysis based on longitudinal studies.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1325908}, pmid = {38720896}, issn = {1664-3224}, mesh = {Humans ; *Inflammatory Bowel Diseases/complications ; *Neurodegenerative Diseases/epidemiology/etiology ; Longitudinal Studies ; Risk Factors ; Prospective Studies ; }, abstract = {OBJECTIVE: Previous studies reported possible connections between inflammatory bowel disease (IBD) and several neurodegenerative disorders. However, the comprehensive relationships between IBD and various neurodegenerative disorders were not summarized. We executed a meta-analysis of longitudinal studies to provide an estimate of the strength of the two-directional prospective association between IBD and neurodegenerative disorders.
METHODS: We accomplished a thorough bibliographic search of PubMed, Web of Science, Embase, PsycINFO, and Cochrane Library databases until June 2023 to locate relevant longitudinal studies. The extracted data were then analyzed via meta-analysis using either a fixed or random effects model.
RESULTS: The final analysis encompassed 27 studies. Individuals with IBD faced an increased risk of developing four neurodegenerative disorders than the general public, namely, Alzheimer's disease (hazard ratio[HR] = 1.35, 95% confidence interval [CI]: 1.03-1.77, P=0.031), dementia (HR =1.24, 95% CI: 1.13-1.36, P<0.001), multiple sclerosis (HR =2.07, 95% CI:1.42-3.02, P<0.001) and Parkinson's disease (HR =1.23, 95% CI:1.10-1.38, P<0.001). Two articles reported an increased incidence of amyotrophic lateral sclerosis or multiple system atrophy in IBD patients. Three studies investigated the prospective association between multiple sclerosis and IBD, revealing an elevated risk of the latter in patients with the former. (HR=1.87, 95% CI:1.66-2.10, P<0.001).
INTERPRETATION: These findings verified the two-directional relationship between the brain-gut axis, specifically demonstrating a heightened risk of various neurodegenerative diseases among IBD patients. It may be profitable to prepare screening strategies for IBD patients to find neurodegenerative diseases during the long-term course of treatment for IBD with a view to potential earlier diagnosis and treatment of neurodegenerative diseases, reducing public health and social burden.
PROSPERO (CRD42023437553).}, }
@article {pmid38682227, year = {2024}, author = {Mohammadi, S and Ghaderi, S and Mohammadi, M and Najafi Asli Pashaki, Z and Khatyal, R and Mohammadian, F and Mohammadjani, S}, title = {Thalamic Alterations in Motor Neuron Diseases: A Systematic Review of MRI Findings.}, journal = {Journal of integrative neuroscience}, volume = {23}, number = {4}, pages = {77}, doi = {10.31083/j.jin2304077}, pmid = {38682227}, issn = {0219-6352}, mesh = {Humans ; *Thalamus/diagnostic imaging/pathology/physiopathology ; *Motor Neuron Disease/diagnostic imaging/pathology/physiopathology ; *Magnetic Resonance Imaging ; Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology/physiopathology ; }, abstract = {BACKGROUND: Motor neuron diseases (MNDs) are progressive neurodegenerative disorders characterized by motor impairment and non-motor symptoms. The involvement of the thalamus in MNDs, especially in conditions such as amyotrophic lateral sclerosis (ALS), and its interaction with frontotemporal dementia (FTD), has garnered increasing research interest. This systematic review analyzed magnetic resonance imaging (MRI) studies that focused on thalamic alterations in MNDs to understand the significance of these changes and their correlation with clinical outcomes.
METHODS: Following PRISMA 2020 guidelines, the PubMed and Scopus databases were searched from inception to June 2023 for studies related to MRI findings in the thalamus of patients with MNDs. Eligible studies included adult patients diagnosed with ALS or other forms of MND who underwent brain MRI, with outcomes related to thalamic alterations. Studies were evaluated for risk of bias using the Newcastle-Ottawa scale.
RESULTS: A total of 52 studies (including 3009 MND patients and 2181 healthy controls) used various MRI techniques, including volumetric analysis, diffusion tensor imaging, and functional MRI, to measure thalamic volume, connectivity, and other alterations. This review confirmed significant thalamic changes in MNDs, such as atrophy and microstructural degradation, which are associated with disease severity, progression, and functional disability. Thalamic involvement varies across different MND subtypes and is influenced by the presence of cognitive impairment and mutations in genes including chromosome 9 open reading frame 72 (C9orf72). The synthesis of findings across studies indicates that thalamic pathology is a prevalent early biomarker of MNDs that contributes to motor and cognitive deficits. The thalamus is a promising target for monitoring as its dysfunction underpins a variety of clinical symptoms in MNDs.
CONCLUSIONS: Thalamic alterations provide valuable insights into the pathophysiology and progression of MNDs. Multimodal MRI techniques are potent tools for detecting dynamic thalamic changes, indicating structural integrity, connectivity disruption, and metabolic activity.}, }
@article {pmid38674921, year = {2024}, author = {Wang, W and Pan, D and Liu, Q and Chen, X and Wang, S}, title = {L-Carnitine in the Treatment of Psychiatric and Neurological Manifestations: A Systematic Review.}, journal = {Nutrients}, volume = {16}, number = {8}, pages = {}, pmid = {38674921}, issn = {2072-6643}, mesh = {Humans ; *Carnitine/therapeutic use ; Dietary Supplements ; *Mental Disorders/drug therapy ; *Nervous System Diseases/drug therapy ; }, abstract = {OBJECTIVE: L-carnitine (LC), a vital nutritional supplement, plays a crucial role in myocardial health and exhibits significant cardioprotective effects. LC, being the principal constituent of clinical-grade supplements, finds extensive application in the recovery and treatment of diverse cardiovascular and cerebrovascular disorders. However, controversies persist regarding the utilization of LC in nervous system diseases, with varying effects observed across numerous mental and neurological disorders. This article primarily aims to gather and analyze database information to comprehensively summarize the therapeutic potential of LC in patients suffering from nervous system diseases while providing valuable references for further research.
METHODS: A comprehensive search was conducted in PubMed, Web Of Science, Embase, Ovid Medline, Cochrane Library and Clinicaltrials.gov databases. The literature pertaining to the impact of LC supplementation on neurological or psychiatric disorders in patients was reviewed up until November 2023. No language or temporal restrictions were imposed on the search.
RESULTS: A total of 1479 articles were retrieved, and after the removal of duplicates through both automated and manual exclusion processes, 962 articles remained. Subsequently, a meticulous re-screening led to the identification of 60 relevant articles. Among these, there were 12 publications focusing on hepatic encephalopathy (HE), while neurodegenerative diseases (NDs) and peripheral nervous system diseases (PNSDs) were represented by 9 and 6 articles, respectively. Additionally, stroke was addressed in five publications, whereas Raynaud's syndrome (RS) and cognitive disorder (CD) each had three dedicated studies. Furthermore, migraine, depression, and amyotrophic lateral sclerosis (ALS) each accounted for two publications. Lastly, one article was found for other symptoms under investigation.
CONCLUSION: In summary, LC has demonstrated favorable therapeutic effects in the management of HE, Alzheimer's disease (AD), carpal tunnel syndrome (CTS), CD, migraine, neurofibromatosis (NF), PNSDs, RS, and stroke. However, its efficacy appears to be relatively limited in conditions such as ALS, ataxia, attention deficit hyperactivity disorder (ADHD), depression, chronic fatigue syndrome (CFS), Down syndrome (DS), and sciatica.}, }
@article {pmid38622643, year = {2024}, author = {Filipe, CB and Carreira, NR and Reis-Pina, P}, title = {Optimizing breathlessness management in amyotrophic lateral sclerosis: insights from a comprehensive systematic review.}, journal = {BMC palliative care}, volume = {23}, number = {1}, pages = {100}, pmid = {38622643}, issn = {1472-684X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/therapy ; *Dyspnea/etiology/therapy ; Palliative Care/methods/standards ; Noninvasive Ventilation/methods/standards ; Quality of Life ; Analgesics, Opioid/therapeutic use ; }, abstract = {BACKGROUND: Breathlessness is a prevalent symptom affecting the quality of life (QOL) of Amyotrophic Lateral Sclerosis (ALS) patients. This systematic review explored the interventions for controlling breathlessness in ALS patients, emphasizing palliative care (PALC), non-invasive ventilation (NIV), opioids, and non-pharmacological strategies.
METHODS: A comprehensive search of PubMed, Cochrane Library, and Web of Science databases was conducted. Eligibility criteria encompassed adults with ALS or motor neuron disease experiencing breathlessness. Outcomes included QOL and symptom control. Study designs comprised qualitative studies, cohort studies, and randomized controlled trials.
RESULTS: Eight studies were included, most exhibiting low bias risk, comprising one randomized controlled trial, three cohort studies, two comparative retrospective studies, and two qualitative studies (interviews). Most studies originated from Europe, with one from the United States of America. The participants totaled 3423, with ALS patients constituting 95.6%. PALC consultations significantly improved symptom assessment, advance care planning, and discussions about goals of care. NIV demonstrated efficacy in managing breathlessness, with considerations for device limitations. Opioids were effective, though predominantly studied in non-ALS patients. Non-pharmacological strategies varied in efficacy among patients.
CONCLUSION: The findings underscore the need for individualized approaches in managing breathlessness in ALS. PALC, NIV, opioids, and non-pharmacological strategies each play a role, with unique considerations. Further research, especially ALS-specific self-management studies, is warranted.}, }
@article {pmid38601118, year = {2024}, author = {Patel, GD and Liu, L and Li, A and Yang, YH and Shen, CC and Brand-Saberi, B and Yang, X}, title = {Mesenchymal stem cell-based therapies for treating well-studied neurological disorders: a systematic review.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1361723}, pmid = {38601118}, issn = {2296-858X}, abstract = {BACKGROUND: Millions of people across the globe are affected by conditions like Amyotrophic Lateral Sclerosis (ALS), Parkinson's Disease (PD), Multiple Sclerosis (MS), Spinal Cord Injury (SCI), and Traumatic Brain Injury (TBI), although most occurrences are common in the elderly population. This systematic review aims to highlight the safety of the procedures, their tolerability, and efficacy of the available therapies conducted over the years using mesenchymal stem cells (MSCs) in treating the neurological conditions mentioned above.
METHODS: PubMed was used to search for published data from clinical trials performed using mesenchymal stem cells. Studies that provided the necessary information that mentioned the efficacy and adverse effects of the treatment in patients were considered for this review.
RESULTS: In total, 43 manuscripts were selected after a strategic search, and these studies have been included in this systematic review. Most included studies reported the safety of the procedures used and the treatment's good tolerability, with mild adverse events such as fever, headache, mild pain at the injection site, or nausea being common. A few studies also reported death of some patients, attributed to the progression of the disease to severe stages before the treatment. Other severe events, such as respiratory or urinary infections reported in some studies, were not related to the treatment. Different parameters were used to evaluate the efficacy of the treatment based on the clinical condition of the patient.
CONCLUSION: Mesenchymal stem cells transplantation has so far proven to be safe and tolerable in select studies and patient types. This systematic review includes the results from the 43 selected studies in terms of safety and tolerability of the procedures, and several adverse events and therapeutic benefits during the follow-up period after administration of MSCs.}, }
@article {pmid38560980, year = {2024}, author = {Xiang, SR and Ma, Q and Dong, J and Ren, YF and Lin, JZ and Zheng, C and Xiao, P and You, FM}, title = {Contrasting Effects of Music Therapy and Aromatherapy on Perioperative Anxiety: A Systematic Review and Meta-Analysis.}, journal = {Complementary medicine research}, volume = {31}, number = {3}, pages = {278-291}, doi = {10.1159/000538425}, pmid = {38560980}, issn = {2504-2106}, mesh = {*Aromatherapy ; *Music Therapy ; Humans ; *Anxiety/therapy ; Heart Rate ; }, abstract = {INTRODUCTION: Music therapy and aromatherapy have been demonstrated effective for perioperative anxiety. However, the available studies have indicated discordant results about which adjunct treatment is better for perioperative anxiety. Therefore, we conducted this meta-analysis to explore the contrasting effects between them.
METHODS: Six electronic databases were searched for clinical trials evaluating the efficacy of music therapy compared with aromatherapy in alleviating perioperative anxiety. The primary outcome was the postintervention anxiety level. Secondary outcomes included differences in blood pressure and heart rate before and after the intervention as well as pain scores at intraoperative and postoperative time points. The study protocol was registered on PROSPERO (CRD42021249737).
RESULTS: Twelve studies (894 patients) were included. The anxiety level showed no statistically significant difference (SMD, 0.28; 95% CI: -0.12, 0.68; p = 0.17). The analysis of blood pressure and heart rate also did not identify statistically significant differences. Notably, the pain scores at the intraoperative time point suggested that aromatherapy was superior to music therapy (WMD, 0.29 cm; 95% CI: 0.05, 0.52; p = 0.02), while those at 4 h after surgery indicated the opposite results (WMD, -0.48 cm; 95% CI: -0.60, -0.36; p < 0.001).
CONCLUSION: Low-to-moderate quality evidence suggests that music therapy and aromatherapy have similar potential to relieve perioperative anxiety. The potential data indicate that the two therapies have different benefits in intervention duration and age distribution. More direct high-quality comparisons are encouraged in the future to verify this point.
UNLABELLED: EinleitungMusik- und Aromatherapie haben sich bei perioperativen Angstzuständen als wirksam erwiesen. Die verfügbaren Studien zeigten jedoch widersprüchliche Ergebnisse zur Frage, welche adjuvante Therapie bei perioperativen Angstzuständen besser ist. Daher führten wir die vorliegende Metaanalyse durch, um die unterschiedlichen Effekte der beiden Therapien zu untersuchen.MethodenSechs (6) elektronische Datenbanken wurden nach klinischen Studien zur Wirksamkeit von Musiktherapie im Vergleich zur Aromatherapie bei der Linderung perioperativer Angstzustände durchsucht. Primäres Zielkriterium war das Angstniveau nach der Intervention. Die sekundären Zielkriterien umfassten die Unterschiede bei Blutdruck und Herzfrequenz vor und nach der Intervention sowie die Schmerz-Scores zu intra- und postoperativen Zeitpunkten. Das Studienprotokoll wurde auf PROSPERO (CRD42021249737) registriert.ErgebnisseZwölf (12) Studien (894 Patienten) wurden eingeschlossen. Das Angstniveau zeigte keinen statistisch signifikanten Unterschied (SMD, 0,28; 95%-KI: −0,12, 0,68, p = 0,17) und auch die Analyse von Blutdruck und Herzfrequenz ergab keine statistisch signifikanten Unterschiede. Insbesondere die Schmerz-Scores zum intraoperativen Zeitpunkt sprachen dafür, dass die Aromatherapie gegenüber der Musiktherapie überlegen war (WMD, 0,29 cm; 95%-KI: 0,05, 0,52; p = 0,02), während die Werte 4 Stunden nach der Operation gegenteilige Ergebnisse zeigten (WMD, −0,48 cm; 95%-KI: −0,60, −0,36, p < 0,001).SchlussfolgerungEvidenzen von geringer bis mässiger Qualität deuten darauf hin, dass Musik- und Aromatherapie ein vergleichbares Potenzial bei der Linderung perioperativer Ängste besitzen. Die potenziellen Daten zeigen, dass die beiden Therapien unterschiedliche Vorteile hinsichtlich Interventionsdauer und Altersverteilung haben. Künftig sollten mehr direkte und qualitativ hochwertige Vergleiche durchgeführt werden, um diesen Aspekt zu überprüfen.}, }
@article {pmid38551974, year = {2024}, author = {Jiménez-García, AM and Bonnel, G and Álvarez-Mota, A and Arias, N}, title = {Current perspectives on neuromodulation in ALS patients: A systematic review and meta-analysis.}, journal = {PloS one}, volume = {19}, number = {3}, pages = {e0300671}, pmid = {38551974}, issn = {1932-6203}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Quality of Life ; *Neurodegenerative Diseases ; Exercise Therapy/methods ; Muscle Spasticity ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, resulting in muscle weakness, paralysis, and eventually patient mortality. In recent years, neuromodulation techniques have emerged as promising potential therapeutic approaches to slow disease progression and improve the quality of life of ALS patients. A systematic review was conducted until August 8, 2023, to evaluate the neuromodulation methods used and their potential in the treatment of ALS. The search strategy was applied in the Cochrane Central database, incorporating results from other databases such as PubMed, Embase, CTgov, CINAHL, and ICTRP. Following the exclusion of papers that did not fulfil the inclusion criteria, a total of 2090 records were found, leaving a total of 10 studies. R software was used to conduct meta-analyses based on the effect sizes between the experimental and control groups. This revealed differences in muscle stretch measures with manual muscle testing (p = 0.012) and resting motor threshold (p = 0.0457), but not with voluntary isometric contraction (p = 0.1883). The functionality of ALS was also different (p = 0.007), but not the quality of life. Although intracortical facilitation was not seen in motor cortex 1 (M1) (p = 0.1338), short-interval intracortical inhibition of M1 was significant (p = 0.0001). BDNF showed no differences that were statistically significant (p = 0.2297). Neuromodulation-based treatments are proposed as a promising therapeutic approach for ALS that can produce effects on muscle function, spasticity, and intracortical connections through electrical, magnetic, and photonic stimulation. Photobiomodulation stands out as an innovative approach that uses specific wavelengths to influence mitochondria, with the aim of improving mitochondrial function and reducing excitotoxicity. The lack of reliable placebo controls and the variation in stimulation frequency are some of the drawbacks of neuromodulation.}, }
@article {pmid38504632, year = {2024}, author = {Higashihara, M and Pavey, N and Menon, P and van den Bos, M and Shibuya, K and Kuwabara, S and Kiernan, MC and Koinuma, M and Vucic, S}, title = {Reduction in short interval intracortical inhibition from the early stage reflects the pathophysiology in amyotrophic lateral sclerosis: A meta-analysis study.}, journal = {European journal of neurology}, volume = {31}, number = {7}, pages = {e16281}, pmid = {38504632}, issn = {1468-1331}, mesh = {*Amyotrophic Lateral Sclerosis/physiopathology ; Humans ; *Transcranial Magnetic Stimulation ; *Neural Inhibition/physiology ; *Motor Cortex/physiopathology ; Evoked Potentials, Motor/physiology ; }, abstract = {BACKGROUND AND PURPOSE: Cortical hyperexcitability has been identified as a diagnostic and pathogenic biomarker of amyotrophic lateral sclerosis (ALS). Cortical excitability is assessed by transcranial magnetic stimulation (TMS), a non-invasive neurophysiological technique. The TMS biomarkers exhibiting highest sensitivity for cortical hyperexcitability in ALS remain to be elucidated. A meta-analysis was performed to determine the TMS biomarkers exhibiting the highest sensitivity for cortical hyperexcitability in ALS.
METHODS: A systematic literature review was conducted of all relevant studies published in the English language by searching PubMed, MEDLINE, Embase and Scopus electronic databases from 1 January 2006 to 28 February 2023. Inclusion criteria included studies reporting the utility of threshold tracking TMS (serial ascending method) in ALS and controls.
RESULTS: In total, more than 2500 participants, incorporating 1530 ALS patients and 1102 controls (healthy, 907; neuromuscular, 195) were assessed with threshold tracking TMS across 25 studies. Significant reduction of mean short interval intracortical inhibition (interstimulus interval 1-7 ms) exhibited the highest standardized mean difference with moderate heterogeneity (-0.994, 95% confidence interval -1.12 to -0.873, p < 0.001; Q = 38.61, p < 0.05; I[2] = 40%). The reduction of cortical silent period duration along with an increase in motor evoked potential amplitude and intracortical facilitation also exhibited significant, albeit smaller, standardized mean differences.
CONCLUSION: This large meta-analysis study disclosed that mean short interval intracortical inhibition reduction exhibited the highest sensitivity for cortical hyperexcitability in ALS. Combined findings from this meta-analysis suggest that research strategies aimed at understanding the cause of inhibitory interneuronal circuit dysfunction could enhance understanding of ALS pathogenesis.}, }
@article {pmid38471489, year = {2024}, author = {D'Souza, A and Zink, K and Langhorst, J and Wildner, M and Stupp, C and Keil, T}, title = {How Effective Is Drinking Natural Mineral Water against Heartburn from Functional Dyspepsia, Gastroesophageal Reflux Disease, or Other Causes? A Systematic Review of Clinical Intervention Studies.}, journal = {Complementary medicine research}, volume = {31}, number = {3}, pages = {253-265}, pmid = {38471489}, issn = {2504-2106}, mesh = {Humans ; *Mineral Waters/therapeutic use ; *Gastroesophageal Reflux/therapy/drug therapy ; *Heartburn/drug therapy ; *Dyspepsia/drug therapy ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: For centuries, spring and other natural waters have been recommended as external or internal remedies for numerous diseases. For studies that examined the effects of drinking mineral waters against heartburn, gastroesophageal reflux disease (GERD), or functional dyspepsia, a systematic review is lacking.
OBJECTIVES: The main aim of this systematic review was to examine the effects of drinking natural mineral waters on heartburn from various causes by identifying all published intervention studies and critically appraising their methods as well as summarizing their results.
METHODS: We systematically searched the largest medical literature database MEDLINE, further relevant web sources, and gray literature for randomized and nonrandomized trials, with or without control groups, up to September 2021 and no language restrictions. Further inclusion criteria were adult patients with heartburn, drinking cure with natural mineral water as the intervention, compared to no or other interventions (care-as-usual, waiting list). We defined the reduction of heartburn symptoms and duration of disease episodes as primary and quality of life as secondary outcomes. Two reviewers independently carried out the study quality assessments (risk of bias) using the National Institutes of Health-Study Quality Assessment Tools.
RESULTS: Nine trials comprising 393 patients from Italy, Russia, Ukraine, and Germany fulfilled all inclusion criteria. We identified three randomized controlled trials (all with poor methodological quality), plus six before-after (pre/post) intervention studies without a control group. The intervention groups of the three comparative trials seemed to show a stronger reduction of self-reported heartburn symptoms, and duration of heartburn episodes than the respective control groups; however, they all had poor methodological quality.
CONCLUSION: Based on the best available evidence of clinical studies, we cannot recommend or advise against drinking natural mineral waters as a treatment for heartburn. The potential benefits of natural mineral waters that were reported in some studies with a lower evidence level (e.g., lacking a control group) should be verified by good quality randomized clinical trials with adequate comparison groups and longer follow-up periods.
UNLABELLED: HintergrundSeit Jahrhunderten werden Quell- und andere natürliche Wässer als äußerliche oder innerliche Heilmittel für zahlreiche Krankheiten empfohlen. Für Studien, die die Wirkung des Trinkens von Mineralwasser gegen Sodbrennen, gastroösophageale Refluxkrankheit (GERD) oder funktionelle Dyspepsie untersuchten, fehlt eine systematische Übersicht.ZielsetzungDas Hauptziel dieser systematischen Übersichtsarbeit war es, die Auswirkungen von Trinkkuren mit natürlichen Mineralwässern auf Sodbrennen verschiedener Ursachen zu untersuchen, indem alle veröffentlichten Interventionsstudien identifiziert und ihre Methoden kritisch bewertet sowie ihre Ergebnisse zusammengefasst wurden.MethodenWir durchsuchten systematisch die größte medizinische Literaturdatenbank MEDLINE, weitere relevante Internetquellen und graue Literatur nach randomisierten und nicht-randomisierten Studien, mit oder ohne Kontrollgruppen, bis September 2021 und ohne sprachliche Einschränkungen. Weitere Einschlusskriterien waren erwachsene Patienten mit Sodbrennen, Trinkkur mit natürlichem Mineralwasser als Intervention, im Vergleich zu keiner oder anderen Interventionen (care-as-usual, Warteliste). Wir definierten die Abnahme der Symptome des Sodbrennens und die Dauer der Krankheitsepisoden als primäre und die Lebensqualität als sekundäre Endpunkte. Zwei Gutachter bewerteten unabhängig voneinander die Qualität der Studien (Verzerrungsrisiko) anhand der National Institutes of Health-Study Quality Assessment Tools.ErgebnisseNeun Studien mit 393 Patienten aus Italien, Russland, der Ukraine und Deutschland erfüllten alle Einschlusskriterien. Wir identifizierten drei randomisierte kontrollierte Studien (alle mit schlechter methodischer Qualität) sowie sechs Vorher-Nachher-Studien (Prä-/Post-Studien) ohne Kontrollgruppe. Die Interventionsgruppen der drei randomisierten Vergleichsstudien schienen eine stärkere Verringerung der selbstberichteten Symptome und der Dauer der Episoden des Sodbrennens zu zeigen als die jeweiligen Kontrollgruppen, allerdings waren sie alle von schlechter methodischer Qualität.SchlussfolgerungAuf der Grundlage der besten verfügbaren Belege aus klinischen Studien können wir das Trinken natürlicher Mineralwässer zur Behandlung von Sodbrennen weder empfehlen noch davon abraten. Die potenziellen Vorteile natürlicher Mineralwässer, die in einigen Studien mit geringerer Evidenz (z. B. ohne Kontrollgruppe) berichtet wurden, sollten durch qualitativ hochwertige randomisierte klinische Studien mit angemessenen Vergleichsgruppen und längeren Nachbeobachtungszeiträumen überprüft werden.}, }
@article {pmid38417402, year = {2024}, author = {Hu, N and Soh, KL and Japar, S and Li, T}, title = {Ear-Marking Relief: A Meta-Analysis on the Efficacy of Auricular Acupressure in Alleviating Anxiety Disorders.}, journal = {Complementary medicine research}, volume = {31}, number = {3}, pages = {266-277}, doi = {10.1159/000537734}, pmid = {38417402}, issn = {2504-2106}, mesh = {Humans ; *Acupressure ; *Anxiety Disorders/therapy ; Randomized Controlled Trials as Topic ; Auriculotherapy/methods ; }, abstract = {BACKGROUND: The increasing worldwide mental health crisis, notably anxiety, emphasizes the urgency for available and effective interventions. Traditional therapies, although beneficial, pose limitations due to their considerable costs and possible adverse effects, thereby inviting alternative treatments such as auricular acupressure (AA). This non-pharmacological, integrative method, underpinned by Eastern and Western medical principles, presents a significant prospect for managing anxiety.
OBJECTIVE: This study aims to evaluate the existing evidence on the efficacy of AA in reducing anxiety, as elucidated through a systematic review.
METHODS: A comprehensive search of randomized controlled trials was conducted across various databases: the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, Chinese National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), Wan Fang, and Database for Chinese Technical Periodicals (VIP). Two reviewers retrieved the pertinent studies and assessed their methodological quality. A meta-analysis was then conducted, incorporating data from all relevant time points.
RESULTS: Upon examining 25 studies encompassing 1,909 participants, it was discerned that AA significantly diminished anxiety (SMD = -1.1074; 95% confidence interval, -1.348 to -0.801; z = 7.70, p < 0.01). Subgroup analyses indicated that neither an increased number of auricular points nor extended intervention augmented effects. Larger effect sizes were associated with probing and avoidance of sham acupressure. Notably, 23 of the 25 studies exhibited some bias, suggesting further research is necessary.
CONCLUSIONS: The extant evidence advocates for AA as an effective supplementary intervention that reduces patient anxiety. The results hint at a potential placebo effect elicited by sham acupressure, necessitating rigorous control group definitions in future inquiries. The study findings suggest that fewer acupressure points and shorter intervention durations could effectively alleviate anxiety symptoms. Nonetheless, the significant heterogeneity across the studies underscores the requirement for more stringent research methodologies to substantiate these conclusions.
UNLABELLED: HintergrundDie weltweit zunehmende Krise der psychischen Gesundheit, vor allem von Angstzuständen, zeigt, dass dringend verfügbare und wirksame Interventionen erforderlich sind. Herkömmliche Therapien sind zwar hilfreich, werden aber durch ihre hohen Kosten und möglichen unerwünschten Wirkungen eingeschränkt, so dass alternative Behandlungen wie die Ohrakupressur gefragt sind. Diese nicht-pharmakologische, integrative Methode, die sich auf östliche und westliche medizinische Prinzipien stützt, stellt eine bedeutsame Perspektive für die Behandlung von Angstzuständen dar.ZielZiel dieser Studie ist es, die vorhandenen Evidenzen für die Wirksamkeit der Ohrakupressur (auricular acupressure, AA) zur Verringerung von Angstzuständen, die in einer systematischen Übersichtsarbeit ermittelt wurden, zu bewerten.MethodenEs wurde eine umfassende Suche nach randomisierten kontrollierten Studien in verschiedenen Datenbanken durchgeführt: Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, Chinese National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), Wan Fang und Database for Chinese Technical Periodicals (VIP). Zwei Gutachter suchten die einschlägigen Studien heraus und bewerteten ihre methodische Qualität. Anschliessend erfolgte eine Metaanalyse, bei der Daten aller relevanten Zeitpunkte berücksichtigt wurden.Ergebnisse:Die Untersuchung von 25 Studien mit 1’909 Teilnehmern ergab, dass die Ohrakupressur (AA) Angstzustände signifikant verringerte (SMD = −1,1074; 95%-KI: −1,348 bis −0,801; z = 7,70, p < 0,01). Subgruppenanalysen zeigten, dass die Effekte weder durch eine höhere Anzahl von Ohrpunkten noch durch eine längere Intervention verstärkt wurden. Grössere Effektstärken waren mit Sondenverwendung und Vermeidung von Scheinakupressur assoziiert. Hervorzuheben ist, dass 23 der 25 Studien eine gewisse Verzerrung aufwiesen, weshalb weitere Untersuchungen erforderlich sind.SchlussfolgerungenDie vorhandene Evidenzlage stützt die Ohrakupressur (AA) als wirksame unterstützende Intervention, die die Angst der Patienten verringert. Die Ergebnisse deuten auf einen potenziellen Placeboeffekt durch Scheinakupressur hin, so dass in künftigen Untersuchungen strenge Kontrollgruppendefinitionen erforderlich sind. Die Studienergebnisse sprechen dafür, dass eine geringere Anzahl von Akupressurpunkten und kürzere Interventionszeiten die Angstsymptome wirksam lindern können. Die starke Heterogenität der Studien zeigt allerdings, dass strengere wissenschaftliche Methoden erforderlich sind, um diese Schlussfolgerungen zu untermauern.}, }
@article {pmid38381447, year = {2024}, author = {Bahr, T and Vu, TA and Tuttle, JJ and Iezzi, R}, title = {Deep Learning and Machine Learning Algorithms for Retinal Image Analysis in Neurodegenerative Disease: Systematic Review of Datasets and Models.}, journal = {Translational vision science & technology}, volume = {13}, number = {2}, pages = {16}, pmid = {38381447}, issn = {2164-2591}, mesh = {Humans ; Algorithms ; *Alzheimer Disease/diagnostic imaging ; *Deep Learning ; Machine Learning ; *Neurodegenerative Diseases/diagnostic imaging ; Datasets as Topic ; *Retina/diagnostic imaging ; }, abstract = {PURPOSE: Retinal images contain rich biomarker information for neurodegenerative disease. Recently, deep learning models have been used for automated neurodegenerative disease diagnosis and risk prediction using retinal images with good results.
METHODS: In this review, we systematically report studies with datasets of retinal images from patients with neurodegenerative diseases, including Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, and others. We also review and characterize the models in the current literature which have been used for classification, regression, or segmentation problems using retinal images in patients with neurodegenerative diseases.
RESULTS: Our review found several existing datasets and models with various imaging modalities primarily in patients with Alzheimer's disease, with most datasets on the order of tens to a few hundred images. We found limited data available for the other neurodegenerative diseases. Although cross-sectional imaging data for Alzheimer's disease is becoming more abundant, datasets with longitudinal imaging of any disease are lacking.
CONCLUSIONS: The use of bilateral and multimodal imaging together with metadata seems to improve model performance, thus multimodal bilateral image datasets with patient metadata are needed. We identified several deep learning tools that have been useful in this context including feature extraction algorithms specifically for retinal images, retinal image preprocessing techniques, transfer learning, feature fusion, and attention mapping. Importantly, we also consider the limitations common to these models in real-world clinical applications.
TRANSLATIONAL RELEVANCE: This systematic review evaluates the deep learning models and retinal features relevant in the evaluation of retinal images of patients with neurodegenerative disease.}, }
@article {pmid38347315, year = {2024}, author = {Huang, SL and Shen, YL and Peng, WY and Ye, K and Zheng, H}, title = {Edaravone for patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Acta neurologica Belgica}, volume = {124}, number = {3}, pages = {895-904}, pmid = {38347315}, issn = {2240-2993}, support = {no. 2021JDTD0007//Sichuan Province Science and Technology Support Program/ ; }, mesh = {*Edaravone/therapeutic use ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Free Radical Scavengers/therapeutic use ; Randomized Controlled Trials as Topic/methods ; Treatment Outcome ; }, abstract = {BACKGROUND AND OBJECTIVE: The effectiveness and long-term efficacy of edaravone, a recommended treatment for amyotrophic lateral sclerosis (ALS), has not been examined in real-world settings. This study aims to evaluate the effectiveness and long-term efficacy of edaravone.
METHODS: The OVID Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases were searched for articles published between January 1, 2000, and May 1, 2023. Two investigators independently screened the retrieved articles for randomized controlled trials (RCTs), cohort studies, or single-arm trials that evaluated the effect of edaravone on amyotrophic lateral sclerosis (ALS). The risk of bias was evaluated using the revised Cochrane Risk-of-Bias (RoB 2.0) tool for randomized controlled trials (RCTs) and the Risk-of-Bias In Non-randomized Studies of Interventions (ROBINS-I) tool for observational studies. The primary outcome was the ALSFRS-R score assessed at month 6, with secondary outcomes including the ALSFRS-R scores evaluated at months 9, 12, and 18, forced vital capacity (FVC), and adverse events. The certainty of evidence was assessed using the GRADE approach.
RESULTS: The analysis included 16 studies with a total of 4828 participants. Among these, four were randomized controlled trials (RCTs) and 12 were observational studies. Of the RCTs, four were rated as having a low risk of bias, while six of the observational studies were rated as having a low risk of bias. Edaravone was associated with slightly slower progression in the reduction of ALSFRS-R score at month 6 compared to placebo (mean difference 1.01, 95%CI -0.87 to 3.09, p = 0.293), as shown by evidence from RCTs. However, observational studies did not show any benefit of adding edaravone to routine practice (mean difference 1.85, 95%CI -2.05 to 5.75, p = 0.352). The change from baseline in ALSFRS-R score was -2.1, -4.04, -7.5, -6.82, and -7.9 at months 3, 6, 9, 12, and 18, respectively. The GRADE assessment indicated moderate certainty for evidence from RCTs, while evidence from observational studies had very low certainty.
CONCLUSION: Due to the limited number of studies and confounding issues in observational studies, further examination of the added benefits of edaravone to routine practice is necessary through RCTs, particularly regarding its long-term efficacy.}, }
@article {pmid38330934, year = {2024}, author = {Yang, L and Li, Y and Zhang, S and Qian, H and Xu, W and Yu, J}, title = {Efficacy of Acupuncture Combined with Traditional Chinese Medicine Fumigation Therapy in Sequelae of Pelvic Inflammatory Disease: A Systematic Review and Meta-Analysis.}, journal = {Complementary medicine research}, volume = {31}, number = {2}, pages = {175-186}, doi = {10.1159/000536101}, pmid = {38330934}, issn = {2504-2106}, abstract = {BACKGROUND AND OBJECTIVE: Acupuncture combined with traditional Chinese medicine fumigation is increasingly being used in treating sequelae of pelvic inflammatory disease (SPID). However, there is a lack of meta-analysis on the effectiveness of acupuncture combined with traditional Chinese medicine fumigation in treating SPID. The aim of this study was to assess the feasibility of combining acupuncture with traditional Chinese medicine fumigation in the treatment of SPID.
METHODS: We searched eight databases for studies on acupuncture combined with traditional Chinese medicine fumigation for the treatment of SPID from the date of establishment to October 29, 2022. We assessed the quality of included studies by using the Cochrane bias risk tool. Pooled results were expressed as risk ratios (RRs), with a 95% confidence interval (CI). In addition, we identified sources of heterogeneity by sensitivity analysis, assessed publication bias by Egger's test, and assessed the quality of the evidence by Grades of Recommendation, Assessment, Development, and Evaluation (GRADE). All statistical analyses were performed by Review Manager 5.3 and Stata 14.
RESULTS: Finally, seven studies with a total of 663 participants were included. We found a significant difference in the total effective rate in the acupuncture combined with the fumigation group compared with the acupuncture group in the treatment of SPID (RR = 1.17, 95% CI [1.09, 1.25], p = 0.0001 < 0.05; I2 = 0%; 6 trials), and a significant difference in the total effective rate in the acupuncture combined with fumigation group compared with the fumigation group in the treatment of SPID (RR = 1.42, 95% CI [1.21, 1.66], p = 0.0001 < 0.05; 5 trials).
CONCLUSION: The clinical efficacy of acupuncture combined with herbal fumigation in the treatment of SPID is relatively good. Larger scale studies are needed in the future.
UNLABELLED: Hintergrund und ZielAkupunktur in Kombination mit Fumigation, einem Verfahren der Traditionellen Chinesischen Medizin, wird zunehmend in der Behandlung von Folgeerscheinungen von Beckenentzündungen (SPID; sequelae of pelvic inflammatory disease) eingesetzt. Es mangelt jedoch an Metaanalysen zur Wirksamkeit der Akupunktur in Kombination mit Fumigation gemäß der Traditionellen Chinesischen Medizin in der Behandlung von SPID. Das Ziel dieser Studie ist die Beurteilung der Machbarkeit der Kombination aus Akupunktur und Fumigation gemäß der Traditionellen Chinesischen Medizin in der Behandlung von SPID.MethodenWir durchsuchten acht Datenbanken nach Studien zur Akupunktur in Kombination mit Fumigation gemäß der Traditionellen Chinesischen Medizin in der Behandlung von Folgeerscheinungen von SPID von der Einrichtung bis zum 29. Oktober 2022. Wir beurteilten die Qualität der eingeschlossenen Studien mit dem Cochrane-Tool zur Bewertung des Bias-Risikos. Die gepoolten Ergebnisse wurden als Risikoquotient (RR; risk ratio) mit 95%-Konfidenzintervall (KI) ausgedrückt. Zusätzlich identifizierten wir Quellen für Heterogenität mittels Sensitivitätsanalyse, beurteilten den Publikations-Bias mittels Egger-Test und bewerteten die Qualität der Evidenz nach Grad der Empfehlungsstärke, Beurteilung, Entwicklung und Evaluierung (GRADE). Alle statistischen Analysen erfolgten mit Review Manager 5.3 und Stata 14.ErgebnisseIm Endeffekt wurden 7 Studien mit insgesamt 663 Teilnehmern eingeschlossen. Wir fanden einen signifikanten Unterschied in der Gesamt-Effektivitätsrate bei der Gruppe, die zur Behandlung von SPID Akupunktur in Kombination mit Fumigation erhielt, im Vergleich zur reinen Akupunkturgruppe (RR = 1,17; 95%-KI [1,09; 1,25]; p = 0,0001 < 0,05; I2-Wert = 0%; 6 Studien), und einen signifikanten Unterschied in der Gesamt-Effektivitätsrate bei der Gruppe, die zur Behandlung von SPID Akupunktur in Kombination mit Fumigation erhielt, im Vergleich zur reinen Fumigationsgruppe (RR = 1,42; 95%-KI [1,21; 1,66]; p = 0,0001 < 0,05; 5 Studien).SchlussfolgerungDie klinische Wirksamkeit der Akupunktur in Kombination mit Kräuter-Fumigation zur Behandlung von SPID ist relativ gut. Zukünftig sind größere Studien erforderlich.}, }
@article {pmid38301596, year = {2024}, author = {Wang, H and Liu, YT and Ren, YL and Guo, XY and Wang, Y}, title = {Association of peripheral immune activation with amyotrophic lateral sclerosis and Parkinson's disease: A systematic review and meta-analysis.}, journal = {Journal of neuroimmunology}, volume = {388}, number = {}, pages = {578290}, doi = {10.1016/j.jneuroim.2024.578290}, pmid = {38301596}, issn = {1872-8421}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/immunology ; Biomarkers ; *Neurodegenerative Diseases/immunology ; *Parkinson Disease/immunology ; }, abstract = {BACKGROUND: Recent studies have revealed the link between immune activation and neurodegenerative diseases.
METHODS: By employing meta-analysis, we estimated the standardized mean difference (SMD) and their corresponding 95% confidence intervals (CIs) between the groups.
RESULTS: According to the pre-set criteria, a total of 21 published articles including 2377 ALS patients and 1244 HCs, as well as 60 articles including 5111 PD patients and 4237 HCs, were identified. This study provided evidence of peripheral immune activation in the pathogenesis of ALS and PD.
CONCLUSION: Our results suggested monitoring changes in peripheral blood immune cell populations, particularly lymphocyte subsets, will benefit understanding the developments and exploring reliable and specific biomarkers of these two diseases.}, }
@article {pmid38286111, year = {2024}, author = {Wang, M and Wang, T and Gu, F}, title = {Efficacy of Huanglian Jiedu Decoction for Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.}, journal = {Complementary medicine research}, volume = {31}, number = {2}, pages = {187-200}, doi = {10.1159/000536453}, pmid = {38286111}, issn = {2504-2106}, abstract = {OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder, and there is an increasing interest in the potential benefits of traditional Chinese medicine, such as Huanglian Jiedu decoction (HJD), for its management. This meta-analysis aimed to determine the efficacy and safety of HJD in the treatment of T2DM.
METHODS: A systematic review was conducted across six databases including PubMed, Embase, Cochrane, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang, from their inception to August 24, 2023. We focused on randomized controlled trials (RCTs) that evaluated HJD as both a monotherapy and in combination treatments for T2DM patients. Data analysis was performed using RevMan 5.3 and Stata 17.0, with evaluations for heterogeneity and publication bias. Additionally, subgroup analyses were stratified based on the duration of treatment.
RESULTS: A total of 40 studies involving 3,934 participants were included in the meta-analysis. Both HJD monotherapy and combined with other therapies significantly reduced hemoglobin A1C (HbA1c) fasting blood glucose (FBG) and 2-h postprandial glucose (2hPG) levels, as well as improved insulin resistance. Furthermore, combination therapy enhanced the efficacy rate and favorably altered lipid profiles, including increasing HDL-C and decreasing LDL-C, TC, and TG levels. It was worth noting that the results of the subgroup analysis indicated that, in terms of reducing HbA1c and 2hPG, the efficacy of HJD alone for a duration of less than 3 months was found to be potentially superior to that observed in treatments exceeding 3 months. Adverse event assessment suggested that HJD did not increase the incidence of side effects, including diarrhea, affirming its safety.
CONCLUSION: HJD appears to be an effective and safe alternative or adjunctive therapy for T2DM, showing significant improvements in glycemic control and lipid profiles without increasing adverse events. Further rigorous, multicenter RCTs outside China are warranted to validate these findings.
UNLABELLED: ZielDiabetes mellitus Typ 2 (DMT2) ist eine weit verbreitete Stoffwechselerkrankung, und es besteht ein steigendes Interesse an den potenziellen Vorteilen der traditionellen chinesischen Medizin, wie beispielsweise Huanglian Jiedu-Dekokt (HJD), zu seiner Behandlung. Mit dieser Metaanalyse sollten die Wirksamkeit und Sicherheit von HJD zur Behandlung von DMT2 ermittelt werden.MethodenEs wurde eine systematische Recherche in sechs Datenbanken durchgeführt, darunter PubMed, Embase, Cochrane, Web of Science, China National Knowledge Infrastructure (CNKI) und Wanfang, für die Zeit vom Beginn der Datenbank bis zum 24. August 2023. Dabei lag unser Hauptaugenmerk auf randomisierten kontrollierten Studien (RCTs), die HJD sowohl als Monotherapie als auch in Kombinationstherapien bei Patienten mit DMT2 untersuchten. Die Datenanalyse erfolgte mithilfe von RevMan 5.3 und Stata 17.0 mit Untersuchungen auf Heterogenität und Publikationsverzerrungen. Darüber hinaus wurden Subgruppenanalysen stratifiziert nach Behandlungsdauer durchgeführt.ErgebnisseInsgesamt wurden 40 Studien mit 3.934 Teilnehmern in die Metaanalyse eingeschlossen. HJD führte sowohl als Monotherapie als auch in Kombination mit anderen Therapien zu einer signifikanten Senkung des HbA1c-Nüchternblutzuckerspiegels (fasting blood glucose, FBG) und der postprandialen Blutzuckerwerte 2 Stunden nach dem Essen (2-h postprandial glucose, 2hPG) sowie zu einer Verbesserung der Insulinresistenz. Darüber hinaus verbesserte die Kombinationstherapie die Wirksamkeitsrate und führte zu einer positiven Veränderung der Lipidprofile, die eine Erhöhung der HDL-Cholesterinwerte und eine Senkung der LDL-, Gesamtcholesterin- und Trigylceridwerte einschloss. Erwähnenswert ist, dass nach den Ergebnissen der Subgruppenanalyse die Wirksamkeit von HJD als Monotherapie in Hinblick auf die Senkung der HbA1c- und 2hPG-Werte bei einer Behandlungsdauer von weniger als drei Monaten gegenüber derjenigen von Behandlungen, die länger als drei Monate dauerten, potenziell überlegen war. Die Bewertung der unerwünschten Ereignisse zeigte, dass HJD nicht zu einem Anstieg der Nebenwirkungen wie Durchfall führte, was seine Sicherheit bestätigte.SchlussfolgerungHJD scheint eine wirksame und sichere Alternative oder Zusatztherapie bei DMT2 zu sein, die signifikante Verbesserungen der Blutzuckerkontrolle und der Lipidprofile ohne Zunahme der unerwünschten Ereignisse bewirkt. Weitere rigorose, multizentrische RCTs außerhalb Chinas sind erforderlich, um diese Ergebnisse zu validieren.}, }
@article {pmid38254647, year = {2023}, author = {Lauria, G and Curcio, R and Tucci, P}, title = {A Machine Learning Approach for Highlighting microRNAs as Biomarkers Linked to Amyotrophic Lateral Sclerosis Diagnosis and Progression.}, journal = {Biomolecules}, volume = {14}, number = {1}, pages = {}, pmid = {38254647}, issn = {2218-273X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; Biomarkers ; Machine Learning ; *MicroRNAs/genetics ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons in the brain and spinal cord. The early diagnosis of ALS can be challenging, as it usually depends on clinical examination and the exclusion of other possible causes. In this regard, the analysis of miRNA expression profiles in biofluids makes miRNAs promising non-invasive clinical biomarkers. Due to the increasing amount of scientific literature that often provides controversial results, this work aims to deepen the understanding of the current state of the art on this topic using a machine-learning-based approach. A systematic literature search was conducted to analyze a set of 308 scientific articles using the MySLR digital platform and the Latent Dirichlet Allocation (LDA) algorithm. Two relevant topics were identified, and the articles clustered in each of them were analyzed and discussed in terms of biomolecular mechanisms, as well as in translational and clinical settings. Several miRNAs detected in the tissues and biofluids of ALS patients, including blood and cerebrospinal fluid (CSF), have been linked to ALS diagnosis and progression. Some of them may represent promising non-invasive clinical biomarkers. In this context, future scientific priorities and goals have been proposed.}, }
@article {pmid38030693, year = {2023}, author = {Vanbilsen, N and Kotz, SA and Rosso, M and Leman, M and Triccas, LT and Feys, P and Moumdjian, L}, title = {Auditory attention measured by EEG in neurological populations: systematic review of literature and meta-analysis.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {21064}, pmid = {38030693}, issn = {2045-2322}, support = {G082021N//Fonds Wetenschappelijk Onderzoek/ ; 1295923N//Fonds Wetenschappelijk Onderzoek/ ; }, mesh = {Humans ; Cross-Sectional Studies ; *Attention ; *Parkinson Disease ; Gait ; Electroencephalography ; }, abstract = {Sensorimotor synchronization strategies have been frequently used for gait rehabilitation in different neurological populations. Despite these positive effects on gait, attentional processes required to dynamically attend to the auditory stimuli needs elaboration. Here, we investigate auditory attention in neurological populations compared to healthy controls quantified by EEG recordings. Literature was systematically searched in databases PubMed and Web of Science. Inclusion criteria were investigation of auditory attention quantified by EEG recordings in neurological populations in cross-sectional studies. In total, 35 studies were included, including participants with Parkinson's disease (PD), stroke, Traumatic Brain Injury (TBI), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS). A meta-analysis was performed on P3 amplitude and latency separately to look at the differences between neurological populations and healthy controls in terms of P3 amplitude and latency. Overall, neurological populations showed impairments in auditory processing in terms of magnitude and delay compared to healthy controls. Consideration of individual auditory processes and thereafter selecting and/or designing the auditory structure during sensorimotor synchronization paradigms in neurological physical rehabilitation is recommended.}, }
@article {pmid38008065, year = {2024}, author = {Maier, GS and Rosar, G and Dietz, G and Hemken, N and Kafchitsas, K and Seeger, JB and Horas, K}, title = {Effectiveness of Mud-Pack Therapy and Mud-Bath Therapy in Osteoarthritis: A Systematic Review.}, journal = {Complementary medicine research}, volume = {31}, number = {1}, pages = {30-39}, doi = {10.1159/000535437}, pmid = {38008065}, issn = {2504-2106}, mesh = {Humans ; *Mud Therapy ; *Osteoarthritis, Knee ; *Osteoarthritis, Hip ; Quality of Life ; *Low Back Pain ; }, abstract = {OBJECTIVES: Osteoarthritis has a tremendous socioeconomic impact in terms of drug spending, hospital admissions, work productivity, and temporary or permanent incapacity. Mud therapy has been discussed as potential conservative treatment options for osteoarthritis. However, findings from several trials still remain controversial. For this reason, we aimed to systematically review the highest evidence provided by published trials to estimate the clinical effect of mud-pack and mud-bath therapy for the treatment of osteoarthritis.
METHODS: We searched PubMed, PEDro, and the Cochrane CENTRAL Register for Controlled Trials for articles published between 2000 and 2020 using the terms "orthopedics," "orthopaedics," "musculoskeletal," "osteoarthritis," and "mud bath," "mud pack."
RESULTS: Of the 19 studies included, 15 examined the effects of mud-bath therapy in knee osteoarthritis treatment. One study focused on the treatment effect of mud bath on hand osteoarthritis, another study examined treatment effects in hip and knee osteoarthritis, and two studies enrolled patients with chronic low back pain caused by lumbar spine osteoarthritis. We systematically reviewed the data obtained from the literature and summarized the results on the basis of the main outcomes. The results show significant improvements in function, quality of life, and perceived pain for patients with osteoarthritis.
CONCLUSION: Results of randomized controlled trials suggest that mud therapy is part of a promising integrated and synergistic multidisciplinary approach in combination with other treatment forms like pharmacotherapy or physiotherapy.
UNLABELLED: ZieleDie sozio-ökonomischen Auswirkungen der Arthrose sind immens. Heiltorfbehandlungen sind seit einiger Zeit als mögliche Ergänzung der konservativen Therapieoptionen dieser Erkrankung Gegenstand wissenschaftlicher Untersuchungen. Ziel dieser Studie war es, die aktuellen Erkenntnisse zur Heiltorftherapie bei Arthrose zusammenzufassen.MethodenWir führten eine systematische Literaturrecherche der Datenbanken Pubmed, PEDro und Cochrane CENTRAL Register of Controlled Trials durch. Hierbei wurden Artikel, die zwischen 2000 und 2020 publiziert wurden und mit den Schlagwörtern “orthopedics”, “orthopaedics”, “musculoskeletal”, “osteoarthritis” und “mud-bath”, “mud-pack” assoziiert waren, erfasst.ErgebnisseVon den 19 näher untersuchten Studien beschäftigten sich 15 mit den Effekten der Heiltorftherapie bei Patienten mit Kniearthrose, eine Studie untersuchte Patienten mit Arthrose der Hand, eine weitere Studie untersuchte die Auswirkung der Therapie bei Arthrose der Hüfte. 2 Studien untersuchten den Effekt der Moorbäder bei Patienten mit chronischen Rückenschmerzen. Insgesamt zeigten sich signifikante Verbesserungen der Funktion, Lebensqualität und Schmerzlinderung bei den Patienten unter Heiltorftherapie.ZusammenfassungDie Ergebnisse der randomisierten, kontrollierten Studien zeigen, dass die Heiltorftherapie eine vielversprechende Ergänzung in einem multidisziplinären Ansatz der Arthrosetherapie ist.}, }
@article {pmid37968433, year = {2024}, author = {Quattrocchi, S and Bonan, L and Cirillo, L and Avoni, P and Di Stasi, V and Rizzo, G and Liguori, R and Vacchiano, V}, title = {Bibrachial amyotrophy as a rare manifestation of intraspinal fluid collection: a case report and systematic review.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {5}, pages = {2279-2288}, pmid = {37968433}, issn = {1590-3478}, mesh = {Humans ; Male ; Middle Aged ; *Magnetic Resonance Imaging ; Electromyography ; Motor Neuron Disease/diagnosis/complications ; }, abstract = {INTRODUCTION: Intraspinal cerebrospinal fluid (CSF) collection has been reported as a rare cause of lower motor neuron (LMN) disorder. We report a case of bibrachial diplegia associated with intraspinal CSF collection and perform a systematic literature review.
PATIENT AND METHODS: A 52-year-old man developed a bibrachial amyotrophy over 6 years, confirmed by the presence of cervical subacute neurogenic changes at electromyography (EMG). Brain magnetic resonance imaging (MRI) revealed cerebral siderosis, while spine MRI showed a ventral longitudinal intraspinal fluid collection (VLISFC) from C2 to L2. No CSF leakage was localized at myelography; a conservative treatment was chosen. We searched for all published cases until 30th April 2023 and extrapolated data of 44 patients reported in 27 publications.
RESULTS: We observed a male predominance, a younger disease onset compared to amyotrophic lateral sclerosis, and a quite long disease duration, highlighting a slow disease progression. LMN signs were more frequently bilateral, mostly involving C5-C6 myotomes. Around 61% of patients presented additional symptoms, but only three referred to a history of headache. Accordingly, CSF opening pressure was mostly normal. Spinal MRI revealed the presence of VLISFC and in some cases myelomalacia. EMG patterns displayed both chronic and subacute neurogenic change in the cervical region. The disease course mainly depended on the treatment choice, which was mostly represented by a surgical approach when a specific dural defect was detected by imaging.
CONCLUSION: Bibrachial diplegia due to VLISFC can be a treatable cause of focal amyotrophy and presents some clinical and radiological "red flags" which cannot be missed by a clinical neurologist.}, }
@article {pmid37952511, year = {2023}, author = {Zhang, X and Qu, X and Zou, Y}, title = {The Effect of Astragalus on Humoral and Cellular Immune Response: A Systematic Review and Meta-Analysis of Human Studies.}, journal = {Complementary medicine research}, volume = {30}, number = {6}, pages = {535-543}, doi = {10.1159/000534826}, pmid = {37952511}, issn = {2504-2106}, mesh = {Humans ; *Interleukin-10 ; *Interleukin-2 ; Interleukin-4 ; Interleukin-6 ; Tumor Necrosis Factor-alpha ; Biomarkers ; }, abstract = {INTRODUCTION: Astragalus is used in traditional Chinese medicine for immune system disorders. Its effect on immune system function is evaluated in multiple studies. The objective of this systematic review and meta-analysis was to evaluate the effect of Astragalus on humoral and cellular immune response in human studies.
METHODS: A comprehensive search of electronic databases was conducted to identify relevant studies published up to April 2023. Studies that assessed the impact of Astragalus on humoral and cellular immune markers were included. The data were extracted, and a random-effects meta-analysis was performed to determine the overall effect size. Subgroup analyses were conducted based on outcome measures.
RESULTS: A total of 19 studies, including 1,094 human participants, were included in the meta-analysis. The analysis of humoral immune markers revealed a significant reduction in proinflammatory cytokines, including IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ, following Astragalus intervention (SMD -2.8765, 95% CI: -3.2385 to -2.5145, p < 0.0001). In the cellular immunity domain, Astragalus was found to significantly increase CD3 levels and the CD4/CD8 ratio (SMD 2.4629, 95% CI: 1.9598; 2.9661). Subgroup analyses based on outcome measures supported these findings. However, substantial heterogeneity was observed among the included studies.
CONCLUSION: This systematic review and meta-analysis provide evidence supporting the immunomodulatory effects of Astragalus on humoral and cellular response. Astragalus demonstrated a significant reduction in proinflammatory cytokines and an enhancement of cellular immune markers, suggesting its potential as a therapeutic agent for immune-related disorders.
UNLABELLED: EinleitungAstragalus wird in der traditionellen chinesischen Medizin bei Erkrankungen des Immunsystems eingesetzt. Seine Wirkung auf das Immunsystem ist in mehreren Studien untersucht worden. Das Ziel dieser systematischen Übersichtsarbeit und Metaanalyse ist es, die Wirkung von Astragalus auf die humorale und zelluläre Immunantwort in Studien am Menschen zu untersuchen.MethodenEine umfassende Suche in elektronischen Datenbanken wurde durchgeführt, um einschlägige Studien zu finden, die bis April 2023 veröffentlicht wurden. Eingeschlossen wurden Studien, die die Auswirkung von Astragalus auf Marker der humoralen und zellulären Immunantwort untersuchten. Die Daten wurden extrahiert und eine Random-Effects-Metaanalyse durchgeführt, um die Gesamt-Effektstärke zu ermitteln. Subgruppenanalysen wurden basierend auf Zielgrößen durchgeführt.ErgebnisseInsgesamt 19 Studien mit 1’094 menschlichen Teilnehmern wurden in die Metaanalyse eingeschlossen. Die Analyse der humoralen Immunmarker ergab eine signifikante Abnahme proinflammatorischer Zytokine, darunter IL-2, IL-4, IL-6, IL-10, TNF-α und IFN-γ, nach Anwendung von Astragalus (SMD –2.8765; 95%-KI: −3.2385, −2.5145; p < 0.0001). Bei der zellulären Immunität zeigte Astralagus eine signifikante Erhöhung der CD3-Konzentration und des CD4/CD8-Quotienten (SMD 2.4629; 95%-KI: 1.9598, 2.9661). Die Subgruppenanalysen nach Zielgrößen bestätigten diese Ergebnisse. Zwischen den eingeschlossenen Studien bestand jedoch erhebliche Heterogenität.SchlussfolgerungDiese systematische Übersichtsarbeit und Metaanalyse liefert Belege für die immunmodulatorischen Effekte von Astragalus auf die humorale und zelluläre Immunantwort. Astragalus zeigte eine signifikante Abnahme proinflammatorischer Zytokine und eine Verbesserung von Markern der zellulären Immunität, was auf sein Potenzial als Therapeutikum bei immunvermittelten Störungen hindeutet.}, }
@article {pmid37910562, year = {2023}, author = {Lugg, A and Schindle, M and Sivak, A and Tankisi, H and Jones, KE}, title = {Nerve excitability measured with the TROND protocol in amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Journal of neurophysiology}, volume = {130}, number = {6}, pages = {1480-1491}, doi = {10.1152/jn.00174.2023}, pmid = {37910562}, issn = {1522-1598}, support = {RGPIN-2017-05624//Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (NSERC)/ ; }, mesh = {Humans ; Action Potentials/physiology ; *Amyotrophic Lateral Sclerosis ; Axons/physiology ; Biomarkers ; Prospective Studies ; Clinical Protocols ; }, abstract = {This meta-analysis assessed the 30+ nerve excitability indices generated by the TROND protocol to identify potential biomarkers for amyotrophic lateral sclerosis (ALS). A comprehensive search was conducted in multiple databases to identify human studies that tested median motor axons. Forest plot analyses were performed using a random-effects model to determine the pooled effect (Z-score), heterogeneity (I[2]), and Cohen's d for potential biomarker identification. Out of 2,866 studies, 23 studies met the inclusion criteria, incorporating data from 719 controls and 942 patients with ALS. Seven indices emerged as potential biomarkers: depolarizing threshold electrotonus (TEd) 90-100 ms, strength-duration time constant (SDTC), superexcitability, TEd 40-60 ms, resting I/V slope, 50% depolarizing I/V, and subexcitability (ranked by the magnitude of the difference between patients and controls from largest to smallest). In a sensitivity analysis focusing on patients with larger compound muscle action potentials (CMAPs), only four indices were potential biomarkers: TEd 10-20 ms, TEd 90-100 ms, superexcitability, and SDTC. Among the extensive range of 30+ excitability indices generated by the TROND protocol, we have identified seven indices that effectively differentiate patients with ALS from healthy controls. Furthermore, a smaller subset of four indices shows promise as potential biomarkers when the CMAP remains relatively large. However, most studies were considered to be at moderate risk of bias due to case-control designs and absence of sensitivity and specificity calculations, underscoring the need for more prospective diagnostic test-accuracy studies with appropriate disease controls.NEW & NOTEWORTHY This meta-analysis uncovers seven potential axonal excitability biomarkers for lower motor neuron pathology in ALS, shedding light on ion channel dysfunction. The identified dysfunction aligns with the primary pathology-protein homeostasis disruption. These biomarkers could fill a gap to detect presymptomatic spread of the disease in the spinal cord and monitor treatments targeting protein homeostasis and limiting spread, toward enhancing patient care.}, }
@article {pmid37906991, year = {2023}, author = {Prohaska, S and Matthias, K}, title = {Effectiveness of Mindfulness-Based Stress Reduction as a Nondrug Preventive Intervention in Patients with Migraine: A Systematic Review with Meta-Analyses.}, journal = {Complementary medicine research}, volume = {30}, number = {6}, pages = {525-534}, doi = {10.1159/000534653}, pmid = {37906991}, issn = {2504-2106}, mesh = {Adult ; Humans ; *Mindfulness ; Treatment Outcome ; *Migraine Disorders/prevention & control ; Headache ; Stress, Psychological ; }, abstract = {INTRODUCTION: Migraine is a neurological disorder characterized by recurrent, severe headaches that are often accompanied by other symptoms. There are various factors that can trigger a migraine in sufferers. Stress can be such a trigger. Drug and nondrug treatments are available for the preventive treatment of migraine. According to a German guideline, mindfulness can be recommended for the prophylaxis of migraine. Therefore, the aim was to investigate the effectiveness of mindfulness-based stress reduction (MBSR) in relation to patient-relevant outcomes in adult patients with migraine. Patient-relevant outcomes in this context are migraine frequency, headache intensity during a migraine attack, depressive symptoms, and quality of life.
MATERIAL AND METHODS: The conduct of this study was guided by the PRISMA 2020 statement. A systematic literature search for randomized controlled trials (RCTs) of the effectiveness of MBSR in adult migraine patients was conducted in December 2021 in three databases: MEDLINE via PubMed, the Cochrane Library, and Web of Science. In addition, a review of reference lists and a search of study registries were performed. The last search was conducted on October 7, 2022. In a two-step process, studies were selected based on predefined inclusion and exclusion criteria. The potential for bias was assessed using the Cochrane Risk of Bias Tool 2. The results were summarized descriptively and by means of quantitative synthesis.
RESULTS: Four RCTs with a total of 275 patients and the follow-up publication of one of these studies were included. The risk of bias in one study each was judged to be low or of some concern and high in two studies. Four studies were included in the quantitative analysis. For the endpoint migraine frequency, the meta-analytic summary of three studies failed to show a statistically significant benefit for MBSR (SMD: -0.23; 95% CI: -0.79 to 0.32). For the endpoint depressive symptoms, a meta-analytic summary of three studies showed a statistically significant benefit for MBSR (SMD: -0.59; 95% CI: -0.93 to -0.25). No study had examined the severity of headaches during a migraine episode.
CONCLUSION: Some results suggest that migraine patients may benefit from MBSR. However, the evidence base is currently insufficient for recommendations on the use of MBSR as a nondrug treatment option. Further adequately powered, high-quality RCTs are needed.
UNLABELLED: EinleitungMigräne ist eine neurologische Erkrankung, die durch wiederkehrende, starke Kopfschmerzen gekennzeichnet ist, die häufig von anderen Symptomen einhergehen. Es gibt verschiedene Faktoren, die bei den Betroffenen eine Migräne auslösen können. Ein solcher Auslöser kann Stress sein. Für die präventive Behandlung der Migräne stehen medikamentöse und nichtmedikamentöse Verfahren zur Verfügung. Laut einer deutschen Leitlinie kann Achtsamkeit zur Prophylaxe von Migräne empfohlen werden. Ziel der Studie war es daher, die Wirksamkeit von achtsamkeitsbasierter Stressreduktion (MBSR) in Bezug auf patientenrelevante Outcomes bei erwachsenen Migränepatienten zu untersuchen. Patientenrelevante Outcomes in diesem Zusammenhang sind Migränehäufigkeit, Kopfschmerzintensität während einer Migräneattacke, depressive Symptome und Lebensqualität.MethodenDie Durchführung dieser Studie orientierte sich am PRISMA-Statement. Eine systematische Literatursuche nach randomisierten kontrollierten Studien zur Wirksamkeit von MBSR bei erwachsenen Migränepatienten wurde im Dezember 2021 in drei Datenbanken durchgeführt: MEDLINE über PubMed, die Cochrane Library und Web of Science. Darüber hinaus wurden Referenzlisten und Studienregister durchsucht. Die letzte Suche erfolgte am 7. Oktober 2022. In einem zweistufigen Verfahren wurden die Studien anhand von vordefinierten Ein- und Ausschlusskriterien ausgewählt. Das Verzerrungspotential der Studien wurde mit dem Cochrane Risk of Bias Tool 2 bewertet. Die Ergebnisse wurden deskriptiv und mit Hilfe einer quantitativen Synthese zusammengefasst.ErgebnisseEs wurden vier randomisiert-kontrollierte Studien mit insgesamt 275 Patienten und die Nachfolgepublikation einer dieser Studien eingeschlossen. Das Verzerrungspotential wurde bei je einer Studie als gering oder bedenklich und bei zwei Studien als hoch eingestuft. Vier Studien wurden in die quantitative Analyse einbezogen. Für den Endpunkt Migränehäufigkeit ergab die metaanalytische Zusammenfassung von drei Studien keinen statistisch signifikanten Vorteil für MBSR (SMD −0.23; 95% CI −0.79 bis 0.32). Für den Endpunkt depressive Symptome zeigte eine metaanalytische Zusammenfassung von drei Studien einen statistisch signifikanten Vorteil für MBSR (SMD −0.59; 95% CI −0.93 bis −0.25). Keine Studie hatte die Schwere der Kopfschmerzen während einer Migräneepisode untersucht.SchlussfolgerungEinige Ergebnisse deuten darauf hin, dass Migränepatienten von MBSR profitieren können. Allerdings ist die Evidenzbasis derzeit nicht ausreichend, um Empfehlungen für den Einsatz von MBSR als nichtmedikamentöse Behandlungsoption abzuleiten. Es werden daher weitere qualitativ hochwertige randomisiert-kontrollierte Studien mit ausreichender statistischer Power benötigt.}, }
@article {pmid37838979, year = {2024}, author = {Jagadish, A and Shankaranarayana, AM and Natarajan, M and Solomon, JM}, title = {Transcranial direct current stimulation for fatigue in neurological conditions: A systematic scoping review.}, journal = {Physiotherapy research international : the journal for researchers and clinicians in physical therapy}, volume = {29}, number = {1}, pages = {e2054}, doi = {10.1002/pri.2054}, pmid = {37838979}, issn = {1471-2865}, mesh = {Humans ; *Brain Injuries, Traumatic ; Fatigue/therapy/etiology ; *Multiple Sclerosis/complications/therapy ; *Parkinson Disease ; Quality of Life ; *Stroke ; *Transcranial Direct Current Stimulation/adverse effects ; }, abstract = {BACKGROUND AND PURPOSE: Fatigue following neurological conditions negatively impacts daily activities, reducing overall quality of life. Transcranial direct current stimulation (tDCS) for fatigue management is still underexplored. This scoping review explores its use in managing fatigue among various neurological conditions.
METHODS: A thorough literature search was carried out using PubMed, Scopus, CINAHL, Web of Science, Embase, ProQuest, and the Cochrane Library. Google Scholar and clinicaltrials.gov were manually searched for gray literature and ongoing trials, respectively. Regardless of the study design, all studies utilizing tDCS for the management of fatigue in various neurological conditions were considered. Two reviewers independently screened all the studies, following which the data were retrieved.
RESULTS: Studies employing tDCS for fatigue management across neurological conditions is as follows: Multiple sclerosis (MS) (n = 28, 66%), stroke (n = 5, 12%), Parkinson's disease (PD) (n = 4, 10%), post-polio syndrome (PPS) (n = 2, 5%), traumatic brain injury (TBI) (n = 2, 5%), and amyotrophic lateral sclerosis (n = 1, 2%). All the studies used anodal stimulation, with the common stimulation site being the left dorsolateral prefrontal cortex for MS, stroke, and PD. A stimulation intensity of 1.0-4.0 mA with a duration ranging from 15 to 30 min in 1 to 24 sessions were commonly reported. The Fatigue Severity Scale (n = 21) and Modified Fatigue Impact Scale (n = 17) were frequently implemented outcome measures. Regardless of the study design, 36/42 (85.7%) studies reported an improvement in fatigue scores in the tDCS group. The common adverse events noted were tingling (n = 8, 35%), headache (n = 6, 26%), and itching (n = 6, 26%).
DISCUSSION: Application of tDCS for fatigue was explored in individuals with stroke, PD, PPS, and TBI after MS. Even though a wide range of treatment parameters and outcome measures were adopted to assess and target fatigue, tDCS proves to have a promising role in alleviating this symptom.}, }
@article {pmid37838538, year = {2024}, author = {Wang, SA and Lee, HW and Ko, YC and Sun, JT and Matsuyama, T and Lin, CH and Hsieh, MJ and Chiang, WC and Ma, MH}, title = {Effect of crew ratio of advanced life support-trained personnel on patients with out-of-hospital cardiac arrest: A systematic review and meta-analysis.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {123}, number = {5}, pages = {561-570}, doi = {10.1016/j.jfma.2023.10.008}, pmid = {37838538}, issn = {0929-6646}, mesh = {Humans ; *Out-of-Hospital Cardiac Arrest/therapy/mortality ; *Emergency Medical Services ; *Advanced Cardiac Life Support ; Cardiopulmonary Resuscitation ; Taiwan ; Return of Spontaneous Circulation ; Japan ; }, abstract = {BACKGROUND/PURPOSE: This review aimed to investigate the effect of crew ratios of on-scene advanced life support (ALS)-trained personnel on patients with out-of-hospital cardiac arrest (OHCA).
METHODS: We systematically searched PubMed, Ovid EMBASE, and the Cochrane Central Register of Controlled Trials databases from the inception date until September 30, 2022, for eligible studies. Two reviewers independently screened the studies for relevance, extracted data, and quality. We compared the effect of the ratio of on-scene ALS-trained personnel >50 % to those with a ratio ≤50 % among prehospital personnel on the clinical outcomes of OHCA patients. The primary outcome was survival-to-discharge and secondary outcomes were any return of spontaneous circulation (ROSC), sustained ROSC (≥2 h), and favourable neurological outcome at discharge (cerebral performance category scores: 1 or 2). Pooled odds ratios (ORs) were calculated, and the certainty of evidence was assessed.
RESULTS: From 10,864 references, we identified four non-randomised studies, including 16,475 patients. Two studies were performed in Japan and two in Taiwan. There were significant differences in survival-to-discharge (OR: 1.24, 95 % confidence interval [CI]: 1.07-1.44, I[2]: 7 %), any ROSC (OR:1.22, 95 % CI: 1.04-1.43, I[2]: 74 %) and sustained ROSC (OR: 1.39, 95 % CI: 1.16-1.65, I[2]: 40 %), but insignificant differences in favourable neurological outcome at discharge. The overall certainty of evidence was rated as very low for all outcomes.
CONCLUSION: Prehospital ALS care with a ratio of on-scene ALS-trained personnel >50 % could improve OHCA patient outcomes than crew ratios ≤50 %. Further studies are required to reach a robust conclusion.}, }
@article {pmid37710261, year = {2023}, author = {Zeng, Q and Wang, K and Liu, WX and Zeng, JZ and Li, XL and Zhang, QF and Ren, SQ and Xu, WM}, title = {Efficacy of high-fidelity simulation in advanced life support training: a systematic review and meta-analysis of randomized controlled trials.}, journal = {BMC medical education}, volume = {23}, number = {1}, pages = {664}, pmid = {37710261}, issn = {1472-6920}, support = {2023NSFSC1475//Sichuan Province Science and Technology Support Program/ ; 2023-207//Health Commission of Sichuan Province/ ; 2021ZX01//Sichuan Provincial People's Hospital/ ; KLET-202104//Ministry of Education Hainan Medical University/ ; R2021012//Peking Union Medical Foundation/ ; }, mesh = {Humans ; Computer Simulation ; Educational Status ; *High Fidelity Simulation Training ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: Simulation is an increasingly used novel method for the education of medical professionals. This study aimed to systematically review the efficacy of high-fidelity (HF) simulation compared with low-fidelity (LF) simulation or no simulation in advanced life support (ALS) training.
METHODS: A comprehensive search of the PubMed, Chinese Biomedicine Database, Embase, CENTRAL, ISI, and China Knowledge Resource Integrated Database was performed to identify randomized controlled trials (RCTs) that evaluated the use of HF simulation in ALS training. Quality assessment was based on the Cochrane Handbook for Systematic Reviews of Interventions version 5.0.1. The primary outcome was the improvement of knowledge and skill performance. The secondary outcomes included the participants' confidence and satisfaction at the course conclusion, skill performance at one year, skill performance in actual resuscitation, and patient outcomes. Data were synthesized using the RevMan 5.4 software.
RESULTS: Altogether, 25 RCTs with a total of 1,987 trainees were included in the meta-analysis. In the intervention group, 998 participants used HF manikins, whereas 989 participants received LF simulation-based or traditional training (classical training without simulation). Pooled data from the RCTs demonstrated a benefit in improvement of knowledge [standardized mean difference (SMD) = 0.38; 95% confidence interval (CI): 0.18-0.59, P = 0.0003, I[2] = 70%] and skill performance (SMD = 0.63; 95% CI: 0.21-1.04, P = 0.003, I[2] = 92%) for HF simulation when compared with LF simulation and traditional training. The subgroup analysis revealed a greater benefit in knowledge with HF simulation compared with traditional training at the course conclusion (SMD = 0.51; 95% CI: 0.20-0.83, P = 0.003, I[2] = 61%). Studies measuring knowledge at three months, skill performance at one year, teamwork behaviors, participants' satisfaction and confidence demonstrated no significant benefit for HF simulation.
CONCLUSIONS: Learners using HF simulation more significantly benefited from the ALS training in terms of knowledge and skill performance at the course conclusion. However, further research is necessary to enhance long-term retention of knowledge and skill in actual resuscitation and patient's outcomes.}, }
@article {pmid37575992, year = {2023}, author = {Mohammadi, M and Yarmohammadi, A and Salehi-Abargouei, A and Ghasemirad, H and Shirvani, M and Ghoshouni, H}, title = {Uric acid and glaucoma: a systematic review and meta-analysis.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1159316}, pmid = {37575992}, issn = {2296-858X}, abstract = {BACKGROUND: Glaucoma, the leading cause of irreversible blindness, is a common disorder that contributes to gradual optic nerve degeneration. The beneficial impacts of uric acid (UA) have been reported in some neurodegenerative conditions such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. But the results of current studies about the association between serum UA level and glaucoma are conflicting. The present meta-analysis was conducted to provide a better understanding of the association between serum UA level and glaucoma.
METHODS: We searched the databases of PubMed, Scopus, Web of Science, and Google Scholar systematically until November 20, 2022 to identify case-control studies, comparing the serum UA concentrations of the patients with glaucoma and controls. The mean ± standard division difference was used to assess the difference in serum UA concentrations between the glaucoma patients and controls.
RESULTS: Six studies involving 1,221 glaucoma patients and 1,342 control group were included in the present meta-analysis. This meta-analysis using a random effect model indicated that the mean UA level in glaucoma patients was 0.13 (I[2] = 91.92%, 95% CI = -0.42 to 0.68) higher than the controls; however, it was not statistically significant.
CONCLUSIONS: Our findings provide evidence that glaucoma patients have a higher serum UA level compared to the controls, but this difference is not statistically significant. Prospective studies are needed to determine the possible association between increased UA and glaucoma pathogenesis.
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022364055, identifier: CRD42022364055.}, }
@article {pmid37573779, year = {2023}, author = {Zhang, Z and Zhu, Y and Zhu, C and Li, S and Zhao, Y and Yang, J and Qin, Y and Hou, J and Zhang, J and Han, C}, title = {Effects of Dihuang Yinzi Decoction on Alzheimer's Disease: A Systematic Review and Meta-Analysis.}, journal = {Complementary medicine research}, volume = {30}, number = {5}, pages = {440-452}, doi = {10.1159/000531931}, pmid = {37573779}, issn = {2504-2106}, mesh = {Humans ; *Alzheimer Disease/drug therapy ; Treatment Outcome ; *Medicine ; Medicine, Chinese Traditional ; China ; }, abstract = {OBJECTIVE: The aim of this study was to systematically evaluate the therapeutic effects of Dihuang Yinzi decoction on Alzheimer's disease (AD) and provide a medical evidence-based clinical application of traditional Chinese medicine (TCM).
METHODS: A comprehensive search was conducted across multiple databases, including PubMed, Embase, Cochrane Library, China National Journals Full-text Database, VIP Database for Chinese Technical Periodicals, Wan Fang database, and SinoMed database, to collect clinical randomized controlled trials of Dihuang Yinzi decoction in the treatment of AD. Strict literature screening was performed based on predefined inclusion and exclusion criteria. The Cochrane Collaboration risk of bias assessment tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system recommendation-level method was used to assess the quality of the included studies. Review Manager 5.4 and Stata 17 software were used for data synthesis and processing, while GRADE Profiler 3.6 software was used to evaluate the quality of evidence for outcome indicators (risk ratio, standardized mean difference, and weighted mean difference).
RESULTS: A total of 11 studies involving 798 patients met the inclusion criteria. Dihuang Yinzi decoction, whether used alone or in combination with conventional Western medicine, demonstrated superior efficacy compared to conventional Western medicine alone in improving the clinical effective rate, TCM syndrome score, activity of daily living score, Mini-Mental State Examination score, and Hasegawa Dementia Scale score in AD treatment. Furthermore, it exhibited a favorable safety profile. However, the GRADE evidence quality rating for the included studies was low.
CONCLUSIONS: Dihuang Yinzi decoction, either used alone or in combination with conventional Western medicine, shows promising results in enhancing cognitive and memory functions as well as the self-care ability of patients with AD. However, the low GRADE evidence quality rating highlights the need for focused advancements in the planning and execution of clinical randomized controlled trials during future research attempts.
UNLABELLED: ZIELZiel dieser Studie ist es, die therapeutischen Effekte von Dihuang Yinzi-Dekokt auf die Alzheimer-Krankheit systematisch zu bewerten und eine evidenzbasierte klinische Anwendung der traditionellen chinesischen Medizin (TCM) bereitzustellen.MethodenEs wurde eine umfassende Suche in mehreren Datenbanken, darunter PubMed, Embase, Cochrane Library, China National Journals Volltext-Datenbank, VIP Database for Chinese Technical Periodicals, Wan Fang Datenbank und SinoMed-Datenbank durchgeführt, um randomisierte, kontrollierte klinische Studien zu Dihuang Yinzi-Dekokt in der Behandlung der Alzheimer-Krankheit zu erfassen. Die strenge Literatursuche erfolgte auf Grundlage von vordefinierten Ein-und Ausschlusskriterien. Zur Bewertung der Qualität der eingeschlossenen Studien wurden das Risk-of-Bias-Tool von Cochrane und das GRADE (Grading of Recommendations Assessment, Development, and Evaluation)-System zur Beurteilung der Empfehlungsgrade herangezogen. Die Datensynthese und -verarbeitung erfolgten mithilfe der Review Manager 5.4- und der Stata 17-Software, während für die Bewertung der Evidenzqualität der Outcome-Indikatoren (Risikoverhältnis, standardisierte Mittelwertdifferenz und gewichtete Mittelwertdifferenz) die Software GRADE Profiler 3.6 verwendet wurde.ErgebnisseInsgesamt erfüllten 11 Studien, an denen 798 Patienten teilnahmen, die Einschlusskriterien. Dihuang Yinzi-Dekokt zeigte allein oder in Kombination mit konventioneller westlicher Medizin eine überlegene Wirksamkeit gegenüber der alleinigen Verwendung von konventioneller westlicher Medizin in Bezug auf die klinische Gesamtwirksamkeitsrate, den TCM-Syndrom-Score, den Score für die Alltagsaktivitäten, den Mini-Mental State Examination-Score und den Score der Hasegawa-Demenz-Skala in der Behandlung der Alzheimer-Krankheit. Darüber hinaus wies es ein günstiges Sicherheitsprofil auf. Die Evidenzqualität der eingeschlossenen Studien gemäß GRADE wurde jedoch als gering eingestuft.SchlussfolgerungenDihuang Yinzi-Dekokt zeigt allein oder in Kombination mit konventioneller westlicher Medizin vielversprechende Ergebnisse in Bezug auf die Verbesserung der kognitiven und Gedächtnisfunktionen sowie die Selbstversorgungsfähigkeit von Alzheimer-Patienten. Die niedrige Bewertung der Evidenzqualität gemäß GRADE unterstreicht jedoch die Notwendigkeit von zielgerichteten Weiterentwicklungen bei der Planung und Durchführung von randomisierten, kontrollierten klinischen Studien in zukünftigen Forschungsunternehmungen.}, }
@article {pmid37558576, year = {2023}, author = {Prado, MB and Pedro, KM and Adiao, KJB}, title = {Efficacy, safety and tolerability of high caloric diet in amyotrophic lateral sclerosis patients: A systematic review and meta-analysis.}, journal = {Revue neurologique}, volume = {179}, number = {9}, pages = {1008-1019}, doi = {10.1016/j.neurol.2023.01.731}, pmid = {37558576}, issn = {0035-3787}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Prospective Studies ; *Motor Neuron Disease ; Diet ; Carbohydrates/therapeutic use ; }, abstract = {BACKGROUND: Several randomized clinical trials were done to determine whether supplementation with a high caloric diet, either through carbohydrate or lipid supplementation, is safe, tolerable and improves survival. However, most of these trials are small and the results are conflicting.
METHODS: Randomized prospective trials utilizing high caloric supplementation among patients with amyotrophic lateral sclerosis (ALS) were searched using the terms [("amyotrophic lateral sclerosis" or "motor neuron disease" or "ALS" or "MND") and ("high calorie" or "high fat" or "high protein" or "high carbohydrate" or "supplementation")] in Medline, Cochrane, Embase, Scopus, Prospero and Herdin by two independent neurologists. Journal articles deemed relevant were assessed for eligibility.
MAIN RESULTS: There were 57 articles obtained from databases, 49 of which were excluded. Four articles were further excluded since all of them had different interventions. Overall, there were 311 ALS patients included in the study, 176 of them were from the intervention group while 135 were used as controls. Overall, high caloric supplementation in ALS was deemed safe and tolerable, and also when adverse events, tolerability and mortality are combined using meta-analysis. Although in most publications the efficacy of giving high caloric supplementation has been generally beneficial, some of the outcome parameters are not statistically different from controls when studies are combined using meta-analysis.
CONCLUSIONS: Current evidence suggests that high calorie supplementation is generally safe and tolerable for patients with ALS. However, it has not been shown to be efficacious in improving weight and functional disability.}, }
@article {pmid37451615, year = {2023}, author = {Yen, H and Yen, H and Huang, CH and Huang, IH and Hung, WK and Su, HJ and Tai, CC and Haw, WWY and Flohr, C and Yiu, ZZN and Chi, CC}, title = {Systematic Review and Critical Appraisal of Urticaria Clinical Practice Guidelines: A Global Guidelines in Dermatology Mapping Project (GUIDEMAP).}, journal = {The journal of allergy and clinical immunology. In practice}, volume = {11}, number = {10}, pages = {3213-3220.e11}, doi = {10.1016/j.jaip.2023.07.002}, pmid = {37451615}, issn = {2213-2201}, mesh = {Humans ; Australia ; Databases, Factual ; *Dermatology ; Stakeholder Participation ; *Urticaria/diagnosis/therapy ; Practice Guidelines as Topic ; }, abstract = {BACKGROUND: Management of urticaria can be optimized with clinical practice guidelines (CPGs). However, the quality of recent urticaria CPGs remains unclear.
OBJECTIVE: To identify and appraise urticaria CPGs worldwide published in the last 5 years.
METHODS: A search for relevant urticaria CPGs was conducted between January 1, 2017, and May 31, 2022, using the following databases: MEDLINE, Embase, National Institute for Health and Care Excellence (NICE) Evidence Search, Guidelines International Network, ECRI Guidelines Trust, Australian Clinical Practice Guidelines, Trip Medical Database, and DynaMed. The included CPGs were critically appraised using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, Lenzer et al's red flags, and the Institute of Medicine (IOM) criteria of trustworthiness.
RESULTS: We included 21 urticaria CPGs. Most guidelines reviewed treatment recommendations of chronic spontaneous urticaria. The majority of guidelines were from European and Asian countries with high and high-middle sociodemographic index, written in English, and openly accessible. Seventeen guidelines (81%) had at least 1 AGREE II domain rated poor quality. Applicability, rigor of development, and stakeholder involvement were the 3 AGREE II domains that scored the lowest across guidelines. Appraisal with Lenzer et al's red flags showed that 18 guidelines (86%) raised at least 1 red flag indicating potential bias. The top 3 domains raising red flags were: no inclusion of nonphysician experts/patient representative/community stakeholders, no or limited involvement of a methodologist in the evaluation of evidence, and lack of external review. Based on IOM's criteria of trustworthiness, 20 guidelines (95%) had 1 or more criteria that did not meet best practice standards. The 3 domains with the highest number of best practice standards not met were updating procedures, rating strength of recommendations, and external review. Guidelines scored highest for the AGREE II domains of defining scope and purpose and clarity of presentation, and had the most fully met IOM's best practice standard for articulation of recommendations. However, only 1 urticaria CPG by NICE was identified as rigorously developed across all 3 appraisal tools.
CONCLUSIONS: The quality of urticaria CPGs in the last 5 years varied widely. Only the NICE urticaria guideline consistently demonstrated excellent quality, high trustworthiness, and low risk of bias. Use of a rigorous framework to rate certainty of evidence and grade strength of recommendation, involvement of methodologists, stakeholder engagement with external review, and clear guidance for updating can help improve the quality of future CPGs.}, }
@article {pmid37436254, year = {2023}, author = {Cunha-Correia, CD and Gama, MDP and Fontana, PN and Fantini, FGMM and Prado, GF and Dourado Júnior, MET and Schwingel, PA}, title = {Noninvasive mechanical ventilation assistance in amyotrophic lateral sclerosis: a systematic review.}, journal = {Sao Paulo medical journal = Revista paulista de medicina}, volume = {142}, number = {1}, pages = {e2022470}, pmid = {37436254}, issn = {1806-9460}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/complications ; *Noninvasive Ventilation/methods ; Quality of Life ; Respiration, Artificial/adverse effects ; *Respiratory Insufficiency/therapy/complications ; }, abstract = {BACKGROUND: Respiratory failure is the most common cause of death in patients with amyotrophic lateral sclerosis (ALS), and morbidity is related to poor quality of life (QOL). Non-invasive ventilation (NIV) may be associated with prolonged survival and QOL in patients with ALS.
OBJECTIVES: To assess whether NIV is effective and safe for patients with ALS in terms of survival and QOL, alerting the health system.
DESIGN AND SETTING: Systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting standards using population, intervention, comparison, and outcome strategies.
METHODS: The Cochrane Library, CENTRAL, MEDLINE, LILACS, EMBASE, and CRD databases were searched based on the eligibility criteria for all types of studies on NIV use in patients with ALS published up to January 2022. Data were extracted from the included studies, and the findings were presented using a narrative synthesis.
RESULTS: Of the 120 papers identified, only 14 were related to systematic reviews. After thorough reading, only one meta-analysis was considered eligible. In the second stage, 248 studies were included; however, only one systematic review was included. The results demonstrated that NIV provided relief from the symptoms of chronic hypoventilation, increased survival, and improved QOL compared to standard care. These results varied according to clinical phenotype.
CONCLUSIONS: NIV in patients with ALS improves the outcome and can delay the indication for tracheostomy, reducing expenditure on hospitalization and occupancy of intensive care unit beds.
PROSPERO database: CRD42021279910 - https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=279910.}, }
@article {pmid37428208, year = {2023}, author = {Johnston, B and Dönmez, CF and Julião, M}, title = {Effectiveness of dignity therapy in the context of culturally competent care in people with palliative care needs: a systematic review of systematic reviews.}, journal = {Current opinion in supportive and palliative care}, volume = {17}, number = {3}, pages = {186-192}, pmid = {37428208}, issn = {1751-4266}, mesh = {Humans ; *Culturally Competent Care ; *Palliative Care/psychology ; Quality of Life/psychology ; Respect ; Systematic Reviews as Topic ; }, abstract = {PURPOSE OF REVIEW: This review aims to synthesise the evidence from systematic reviews and meta-analyses on the efficacy of dignity therapy (DT) in relation to psychosocial and spiritual outcomes in the context of person-centred and culturally competent care for people with supportive and palliative care needs.
RECENT FINDINGS: Thirteen reviews were found, including seven conducted by nurses. Most reviews were of high quality, including various study populations such as cancer, motor neurone disease and non-malignant conditions. Six psychosocial and spiritual outcomes were identified: quality of life, anxiety, depression, hopefulness, meaning and purpose in life, and suffering based on the cultural variations in the implementation of DT.
SUMMARY: DT has a positive impact on anxiety, depression, suffering, and meaning and purpose in life for people with palliative care needs, but the evidence is somewhat conflicted as to whether DT is effective in improving hope, quality of life and spiritual outcomes in the context of culturally competent care. Nurse-led DT seems desirable given its pivotal role when caring for people with palliative care needs. More randomised controlled trials should be conducted for people with different cultural backgrounds to provide person-centred, culturally competent supportive and palliative care.}, }
@article {pmid37316187, year = {2023}, author = {Iverson, GL and Castellani, RJ and Cassidy, JD and Schneider, GM and Schneider, KJ and Echemendia, RJ and Bailes, JE and Hayden, KA and Koerte, IK and Manley, GT and McNamee, M and Patricios, JS and Tator, CH and Cantu, RC and Dvorak, J}, title = {Examining later-in-life health risks associated with sport-related concussion and repetitive head impacts: a systematic review of case-control and cohort studies.}, journal = {British journal of sports medicine}, volume = {57}, number = {12}, pages = {810-821}, doi = {10.1136/bjsports-2023-106890}, pmid = {37316187}, issn = {1473-0480}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; *Sports ; *Brain Concussion/epidemiology/etiology ; Cohort Studies ; Case-Control Studies ; *Dementia ; }, abstract = {OBJECTIVE: Concern exists about possible problems with later-in-life brain health, such as cognitive impairment, mental health problems and neurological diseases, in former athletes. We examined the future risk for adverse health effects associated with sport-related concussion, or exposure to repetitive head impacts, in former athletes.
DESIGN: Systematic review.
DATA SOURCES: Search of MEDLINE, Embase, Cochrane, CINAHL Plus and SPORTDiscus in October 2019 and updated in March 2022.
ELIGIBILITY CRITERIA: Studies measuring future risk (cohort studies) or approximating that risk (case-control studies).
RESULTS: Ten studies of former amateur athletes and 18 studies of former professional athletes were included. No postmortem neuropathology studies or neuroimaging studies met criteria for inclusion. Depression was examined in five studies in former amateur athletes, none identifying an increased risk. Nine studies examined suicidality or suicide as a manner of death, and none found an association with increased risk. Some studies comparing professional athletes with the general population reported associations between sports participation and dementia or amyotrophic lateral sclerosis (ALS) as a cause of death. Most did not control for potential confounding factors (eg, genetic, demographic, health-related or environmental), were ecological in design and had high risk of bias.
CONCLUSION: Evidence does not support an increased risk of mental health or neurological diseases in former amateur athletes with exposure to repetitive head impacts. Some studies in former professional athletes suggest an increased risk of neurological disorders such as ALS and dementia; these findings need to be confirmed in higher quality studies with better control of confounding factors.
PROSPERO REGISTRATION NUMBER: CRD42022159486.}, }
@article {pmid37308302, year = {2023}, author = {Wolfson, C and Gauvin, DE and Ishola, F and Oskoui, M}, title = {Global Prevalence and Incidence of Amyotrophic Lateral Sclerosis: A Systematic Review.}, journal = {Neurology}, volume = {101}, number = {6}, pages = {e613-e623}, pmid = {37308302}, issn = {1526-632X}, mesh = {*Amyotrophic Lateral Sclerosis/epidemiology ; Incidence ; Prevalence ; Humans ; Africa/epidemiology ; Asia/epidemiology ; Europe/epidemiology ; North America/epidemiology ; South America/epidemiology ; Oceania/epidemiology ; }, abstract = {BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disorder affecting upper and lower motor neurons. Due to its rarity and rapidly progressive nature, studying the epidemiology of ALS is challenging, and a comprehensive picture of the global burden of this disease is lacking. The objective of this systematic review was to describe the global incidence and prevalence of ALS.
METHODS: We searched MEDLINE, Embase, Global Health, PsycInfo, Cochrane Library, and CINAHL to identify articles published between January 1, 2010, and May 6, 2021. Studies that were population based and reported estimates of prevalence, incidence, and/or mortality of ALS were eligible for inclusion. This study focuses on the incidence and prevalence. Quality assessment was performed using a tool developed to evaluate methodology relevant to prevalence and incidence studies. This review was registered with PROSPERO, CRD42021250559.
RESULTS: This search generated 6,238 articles, of which 140 were selected for data extraction and quality assessment. Of these, 85 articles reported on the incidence and 61 on the prevalence of ALS. Incidence ranged from 0.26 per 100,000 person-years in Ecuador to 23.46 per 100,000 person-years in Japan. Point prevalence ranged from 1.57 per 100,000 in Iran to 11.80 per 100,000 in the United States. Many articles identified cases with ALS from multiple data sources.
DISCUSSION: There is variation in reported incidence and prevalence estimates of ALS across the world. While registries are an important and powerful tool to quantify disease burden, such resources are not available everywhere. This results in gaps in reporting of the global epidemiology of ALS, as highlighted by the degree of variation (and quality) in estimates of incidence and prevalence reported in this review.}, }
@article {pmid37284659, year = {2023}, author = {Zhu, Q and Zhou, J and Zhang, Y and Huang, H and Han, J and Cao, B and Xu, D and Zhao, Y and Chen, G}, title = {Risk factors associated with amyotrophic lateral sclerosis based on the observational study: a systematic review and meta-analysis.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1196722}, pmid = {37284659}, issn = {1662-4548}, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting the upper and lower motor neurons. Though the pathogenesis of ALS is still unclear, exploring the associations between risk factors and ALS can provide reliable evidence to find the pathogenesis. This meta-analysis aims to synthesize all related risk factors of ALS to understand this disease comprehensively.
METHODS: We searched the following databases: PubMed, EMBASE, Cochrane library, Web of Science, and Scopus. Moreover, observational studies, including cohort studies, and case-control studies, were included in this meta-analysis.
RESULTS: A total of 36 eligible observational studies were included, and 10 of them were cohort studies and the rest were case-control studies. We found six factors exacerbated the progression of disease: head trauma (OR = 1.26, 95% CI = 1.13, 1.40), physical activity (OR = 1.06, 95% CI = 1.04, 1.09), electric shock (OR = 2.72, 95% CI = 1.62, 4.56), military service (OR = 1.34, 95% CI = 1.11, 1.61), pesticides (OR = 1.96, 95% CI = 1.7, 2.26), and lead exposure (OR = 2.31, 95% CI = 1.44, 3.71). Of note, type 2 diabetes mellitus was a protective factor for ALS. However, cerebrovascular disease (OR = 0.99, 95% CI = 0.75, 1.29), agriculture (OR = 1.22, 95% CI = 0.74, 1.99), industry (OR = 1.24, 95% CI = 0.81, 1.91), service (OR = 0.47, 95% CI = 0.19, 1.17), smoking (OR = 1.25, 95% CI = 0.5, 3.09), chemicals (OR = 2.45, 95% CI = 0.89, 6.77), and heavy metal (OR = 1.5, 95% CI = 0.47, 4.84) were not risk factors for ALS based on meta-analyses.
CONCLUSIONS: Head trauma, physical activity, electric shock, military service, pesticides, and lead were risk factors for ALS onset and progression. But DM was a protective factor. This finding provides a better understanding of ALS risk factors with strong evidence for clinicians to rationalize clinical intervention strategies.
INPLSY REGISTRATION NUMBER: https://inplasy.com/inplasy-2022-9-0118/, INPLASY202290118.}, }
@article {pmid37210484, year = {2023}, author = {Jandhyala, R}, title = {Neutral theory: applicability and neutrality of clinical study endpoints where a disease-specific instrument is available.}, journal = {BMC medical research methodology}, volume = {23}, number = {1}, pages = {121}, pmid = {37210484}, issn = {1471-2288}, mesh = {Humans ; *Rare Diseases/diagnosis/epidemiology ; *Endpoint Determination ; Clinical Studies as Topic ; }, abstract = {BACKGROUND: There is a pressing need to improve the accuracy of rare disease clinical study endpoints. Neutral theory, first described here, can be used to assess the accuracy of endpoints and improve their selection in rare disease clinical studies, reducing the risk of patient misclassification.
METHODS: Neutral theory was used to assess the accuracy of rare disease clinical study endpoints and the resulting probability of false positive and false negative classifications at different disease prevalence rates. Search strings were extracted from the Orphanet Register of Rare Diseases using a proprietary algorithm to conduct a systematic review of studies published until January 2021. Overall, 11 rare diseases with one disease-specific disease severity scale (133 studies) and 12 rare diseases with more than one disease-specific disease severity scale (483 studies) were included. All indicators from clinical studies were extracted, and Neutral theory was used to calculate their match to disease-specific disease severity scales, which were used as surrogates for the disease phenotype. For those with more than one disease-severity scale, endpoints were compared with the first disease-specific disease severity scale and a composite of all later scales. A Neutrality score of > 1.50 was considered acceptable.
RESULTS: Around half the clinical studies for half the rare diseases with one disease-specific disease severity score (palmoplantar psoriasis, achalasia, systemic lupus erythematosus, systemic sclerosis and Fournier's gangrene) met the threshold for an acceptable match to the disease phenotype, one rare disease (Guillain-Barré syndrome) had one study with an acceptable match, and four diseases (Behcet's syndrome, Creutzfeldt-Jakob disease, atypical hemolytic uremic syndrome and Prader-Willi syndrome) had no studies. Clinical study endpoints in almost half the rare diseases with more than one disease-specific DSS (acromegaly, amyotrophic lateral sclerosis, cystic fibrosis, Fabry disease and juvenile rheumatoid arthritis) were a better match to the composite, while endpoints in the remaining rare diseases (Charcot Marie Tooth disease, Gaucher disease Type I, Huntington's disease, Sjogren's syndrome and Tourette syndrome) were a worse match. Misclassifications varied with increasing disease prevalence.
CONCLUSIONS: Neutral theory confirmed that disease-severity measurement needs improvement in rare disease clinical studies, especially for some diseases, and suggested that the potential for accuracy increases as the body of knowledge on a disease increases. Using Neutral theory to benchmark disease-severity measurement in rare disease clinical studies may reduce the risk of misclassification, ensuring that recruitment and treatment effect assessment optimise medicine adoption and benefit patients.}, }
@article {pmid37205225, year = {2023}, author = {Cannon, AE and Zürrer, WE and Zejlon, C and Kulcsar, Z and Lewandowski, S and Piehl, F and Granberg, T and Ineichen, BV}, title = {Neuroimaging findings in preclinical amyotrophic lateral sclerosis models-How well do they mimic the clinical phenotype? A systematic review.}, journal = {Frontiers in veterinary science}, volume = {10}, number = {}, pages = {1135282}, pmid = {37205225}, issn = {2297-1769}, abstract = {BACKGROUND AND OBJECTIVES: Animal models for motor neuron diseases (MND) such as amyotrophic lateral sclerosis (ALS) are commonly used in preclinical research. However, it is insufficiently understood how much findings from these model systems can be translated to humans. Thus, we aimed at systematically assessing the translational value of MND animal models to probe their external validity with regards to magnetic resonance imaging (MRI) features.
METHODS: In a comprehensive literature search in PubMed and Embase, we retrieved 201 unique publications of which 34 were deemed eligible for qualitative synthesis including risk of bias assessment.
RESULTS: ALS animal models can indeed present with human ALS neuroimaging features: Similar to the human paradigm, (regional) brain and spinal cord atrophy as well as signal changes in motor systems are commonly observed in ALS animal models. Blood-brain barrier breakdown seems to be more specific to ALS models, at least in the imaging domain. It is noteworthy that the G93A-SOD1 model, mimicking a rare clinical genotype, was the most frequently used ALS proxy.
CONCLUSIONS: Our systematic review provides high-grade evidence that preclinical ALS models indeed show imaging features highly reminiscent of human ALS assigning them a high external validity in this domain. This opposes the high attrition of drugs during bench-to-bedside translation and thus raises concerns that phenotypic reproducibility does not necessarily render an animal model appropriate for drug development. These findings emphasize a careful application of these model systems for ALS therapy development thereby benefiting refinement of animal experiments.
https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022373146.}, }
@article {pmid37168926, year = {2023}, author = {Duan, QQ and Jiang, Z and Su, WM and Gu, XJ and Wang, H and Cheng, YF and Cao, B and Gao, X and Wang, Y and Chen, YP}, title = {Risk factors of amyotrophic lateral sclerosis: a global meta-summary.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1177431}, pmid = {37168926}, issn = {1662-4548}, abstract = {BACKGROUND: The etiology of amyotrophic lateral sclerosis (ALS) remains largely unknown. This study aimed to summarize the relationship between ALS and its genetic and non-genetic risk factors.
METHOD: A search of relevant literature from PubMed, Embase, and Cochrane Database from inception to December 2022 was performed. Random-effects or fixed-effects models were performed by Stata MP 15.0 to pool multivariate or adjusted ratios (OR). PROSPERO registration number: CRD42022301549.
RESULTS: 230 eligible studies were included, of which 67 involved 22 non-genetic factors, and 163 involved genetic factors. Four aspects of non-genetic factors, including lifestyle, environmental and occupational exposures, pre-existing diseases/comorbidity and medical exposures, and others, were analyzed. Exposure to heavy metals (OR = 1.79), pesticides (OR = 1.46), solvents (OR = 1.37), previous head trauma (OR = 1.37), military service (OR = 1.29), stroke (OR = 1.26), magnetic field (OR = 1.22) and hypertension (OR = 1.04) are significant risk factors, but use of antidiabetics (OR = 0.52), high BMI (OR = 0.60 for obese and overweight vs. normal and underweight), living in urban (OR = 0.70), diabetes mellitus (OR = 0.83), and kidney disease (OR = 0.84) decrease the risk for ALS. In addition, eight common ALS-related genes were evaluated, the mutation frequencies of these genes were ranked from highest to lowest as SOD1 (2.2%), C9orf72 (2.1%), ATXN2 (1.7%), FUS (1.7%), TARDBP (0.8%), VCP (0.6%), UBQLN2(0.6%) and SQSTM1 (0.6%) in all the ALS patients.
CONCLUSIONS: Our findings suggested that effective intervention for risk exposure and timely modification of lifestyle might prevent the occurrence of ALS. Genetic mutations are important risk factors for ALS and it is essential to detect genetic mutations correctly and scientifically.
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=301549, identifier: CRD42022301549.}, }
@article {pmid37163838, year = {2023}, author = {Zhang, Y and Ren, R and Yang, L and Nie, Y and Zhang, H and Shi, Y and Sanford, LD and Vitiello, MV and Tang, X}, title = {Sleep in amyotrophic lateral sclerosis: A systematic review and meta-analysis of polysomnographic findings.}, journal = {Sleep medicine}, volume = {107}, number = {}, pages = {116-125}, doi = {10.1016/j.sleep.2023.04.014}, pmid = {37163838}, issn = {1878-5506}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis ; Polysomnography ; Sleep ; Sleep, REM ; Sleep Latency ; }, abstract = {BACKGROUND: This study explores the polysomnographic differences between amyotrophic lateral sclerosis (ALS) patients and healthy controls.
METHODS: An electronic literature search was conducted in MEDLINE, EMBASE, All EBM databases, Web of Science, and CNKI from inception to Oct 2022.
RESULTS: Meta-analyses revealed significant reductions in sleep efficiency, total sleep time, N2%, slow wave sleep percentage, minimum SpO2, and mean SpO2, and increases in wake time after sleep onset and N1%, sleep latency, rapid eye movement sleep latency, time spent with SpO2 < 90%, oxygen desaturation index, and apnea hypopnea index in ALS patients compared with controls. Sensitivity analyses showed that some heterogeneity was explained by excluding patients taking medications impacting sleep, whether studies employed an adaptation night, and the use of different PSG scoring rules.
CONCLUSIONS: Significant polysomnographic abnormalities are present in ALS. Our findings underscore the need for a comprehensive PSG assessment of sleep changes in ALS patients. When performing PSG examinations in ALS, whether the patients are taking medication impacting sleep and the scoring system used should be considered.}, }
@article {pmid37037728, year = {2023}, author = {Shaw, AV and Verma, Y and Tucker, S and Jain, A and Furniss, D}, title = {Relative motion orthoses for early active motion after finger extensor and flexor tendon repairs: A systematic review.}, journal = {Journal of hand therapy : official journal of the American Society of Hand Therapists}, volume = {36}, number = {2}, pages = {332-346}, doi = {10.1016/j.jht.2023.02.011}, pmid = {37037728}, issn = {1545-004X}, mesh = {Humans ; Retrospective Studies ; Orthotic Devices ; *Tendon Injuries/surgery/rehabilitation ; Tendons ; Fingers ; *Finger Injuries/surgery/rehabilitation ; Range of Motion, Articular ; }, abstract = {BACKGROUND: The relative motion (RM) orthosis was introduced over 40 years ago for extensor tendon rehabilitation and more recently applied to flexor tendon repairs.
PURPOSE: We systematically reviewed the evidence for RM orthoses following surgical repair of finger extensor and flexor tendon injuries including indications for use, configuration and schedule of orthosis wear, and clinical outcomes.
STUDY DESIGN: Systematic review.
METHODS: A PRISMA-compliant systematic review searched eight databases and five trial registries, from database inception to January 7, 2022. The protocol was registered prospectively (CRD42020211579). We identified studies describing patients undergoing rehabilitation using RM orthoses after surgical repair of acute tendon injuries of the finger and hand.
RESULTS: For extensor tendon repairs, ten studies, one trial registry and five conference abstracts met inclusion criteria, reporting outcomes of 521 patients with injuries in zones IV-VII. Miller's criteria were predominantly used to report range of motion; with 89.6% and 86.9% reporting good or excellent outcomes for extension lag and flexion deficit, respectively. For flexor tendon repairs, one retrospective case series was included reporting outcomes in eight patients following zones I-II repairs. Mean total active motion was 86%. No tendon ruptures were reported due to the orthosis not protecting the repair for either the RME or RMF approaches.
DISCUSSION: Variation was seen in use of RME plus or only, use of night orthoses and orthotic wear schedules, which may be the result of evolution of the RM approach. Since Hirth et al's 2016 scoping review, there are five additional studies, including two RCTs reporting the use of the RM orthosis in extensor tendon rehabilitation.
CONCLUSIONS: There is now good evidence that the RM approach is safe in zones V-VI extensor tendon repairs. Limited evidence currently exists for zones IV and VII extensor and for flexor tendon repairs. Further high-quality clinical studies are needed to demonstrate its safety and efficacy.}, }
@article {pmid37018859, year = {2023}, author = {Kamalian, A and Foroughmand, I and Koski, L and Darvish, M and Saghazadeh, A and Kamalian, A and Razavi, SZE and Abdi, S and Dehgolan, SR and Fotouhi, A and Roos, PM}, title = {Metal concentrations in cerebrospinal fluid, blood, serum, plasma, hair, and nails in amyotrophic lateral sclerosis: A systematic review and meta-analysis.}, journal = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)}, volume = {78}, number = {}, pages = {127165}, doi = {10.1016/j.jtemb.2023.127165}, pmid = {37018859}, issn = {1878-3252}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/cerebrospinal fluid ; Lead ; *Selenium ; Serum ; *Neurodegenerative Diseases ; Nails ; Cross-Sectional Studies ; Plasma ; Hair ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with progressive muscle wasting, paralysis, and respiratory failure. Whereas approximately 10-15 % of ALS cases are familial, the etiology of the remaining, sporadic ALS cases remains largely unknown. Environmental exposures have been suggested as causative factors for decades, and previous studies have found elevated concentrations of metals in ALS patients.
PURPOSE: This meta-analysis aims to assess metal concentrations in body fluids and tissues of ALS patients.
METHODS: We searched the MEDLINE and EMBASE databases on December 7th, 2022 for cross-sectional, case-control, and cohort studies which measure metal concentrations in whole blood, blood plasma, blood serum, cerebrospinal fluid (CSF), urine, erythrocytes, nail, and hair samples of ALS patients. Meta-analysis was then performed when three or more articles existed for a comparison.
FINDINGS: Twenty-nine studies measuring 23 metals were included and 13 meta-analyses were performed from 4234 screened entries. The meta-analysis results showed elevated concentrations of lead and selenium. Lead, measured in whole blood in 6 studies, was significantly elevated by 2.88 µg/L (95 % CI: 0.83-4.93, p = 0.006) and lead, measured in CSF in 4 studies, was significantly elevated by 0.21 µg/L (95 % CI: 0.01 - 0.41, p = 0.04) in ALS patients when compared to controls. Selenium, measured in serum/plasma in 4 studies, was significantly elevated by 4.26 µg/L (95% CI: 0.73 - 7.79, p = 0.02) when compared to controls.Analyses of other metal concentrations showed no statistically significant difference between the groups.
CONCLUSION: Lead has been discussed as a possible causative agent in ALS since 1850. Lead has been found in the spinal cord of ALS patients, and occupational exposure to lead is more common in ALS patients than in controls. Selenium in the form of neurotoxic selenite has been shown to geochemically correlate to ALS occurrence in Italy. Although no causal relationship can be established from the results of this meta-analysis, the findings suggest an involvement of lead and selenium in the pathophysiology of ALS. After a thorough meta-analysis of published studies on metal concentrations in ALS it can only be concluded that lead and selenium are elevated in ALS.}, }
@article {pmid36998129, year = {2023}, author = {Khaafi, F and Javadi, B}, title = {Molecular Targets Underlying the Neuroprotective Effects of Boswellic Acid: A Systematic Review.}, journal = {Mini reviews in medicinal chemistry}, volume = {23}, number = {19}, pages = {1912-1925}, doi = {10.2174/1389557523666230330113611}, pmid = {36998129}, issn = {1875-5607}, mesh = {Humans ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Alzheimer Disease/drug therapy ; *Parkinson Disease/drug therapy ; }, abstract = {BACKGROUND: Neurodegenerative procedures include a large spectrum of disorders with diverse pathological features and clinical manifestations, such as Alzheimer's Disease (AD), Parkinson's disease (PD), Multiple sclerosis, and Amyotrophic lateral sclerosis (ALS). Neurodegenerative diseases (NDs) are indicated by progressive loss of neurons and cognitive function, which is associated with free radical formation, extra and intercellular accumulation of misfolded proteins, oxidative stress, mitochondrial and neurotrophins dysfunction, bioenergetic impairment, inflammation, and apoptotic cell death. Boswellic acid is a pentacyclic triterpene molecule of plant origin that has been applied for treating several inflammatory disorders. Numerous studies have also investigated its' therapeutic potential against multiple NDs.
OBJECTIVE: In this article, we aim to review the neuroprotective effects of boswellic acid on NDs and the related mechanisms of action.
METHODS: The databases of PubMed, Google Scholar, Web of Sciences, and Scopus were searched to find studies that reported the effects of boswellic acid on NDs without time limits. Review articles, letters, editorials, unpublished data, and articles not published in the English language were not included in the study.
RESULTS: Overall, 17 studies were included in the present study (8 NDs in general, 5 AD, 3 PD, and 1 ALS). According to the reports, boswellic acid exerts anti-inflammatory, antioxidant, antiapoptotic, and neuromodulatory effects against NDs. Boswellic acid decreases Tau phosphorylation and amyloid-β (Aβ) generation in AD. This substance also protects nigrostriatal dopaminergic neurons and improves motor impairments in PD and modulates neurotransmitters, decreases the demyelination region, and improves behavioral functions in ALS.
CONCLUSION: Due to the significant effects of boswellic acid in NDs, more clinical studies are necessary to evaluate the pharmacokinetics of this substance because it seems that boswellic acid can be used as a complementary or alternative treatment in patients with NDs.}, }
@article {pmid36970522, year = {2023}, author = {Saucier, D and Registe, PPW and Bélanger, M and O'Connell, C}, title = {Urbanization, air pollution, and water pollution: Identification of potential environmental risk factors associated with amyotrophic lateral sclerosis using systematic reviews.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1108383}, pmid = {36970522}, issn = {1664-2295}, abstract = {INTRODUCTION: Despite decades of research, causes of ALS remain unclear. To evaluate recent hypotheses of plausible environmental factors, the aim of this study was to synthesize and appraise literature on the potential associations between the surrounding environment, including urbanization, air pollution and water pollution, and ALS.
METHODS: We conducted a series (n = 3) of systematic reviews in PubMed and Scopus to identify epidemiological studies assessing relationships between urbanization, air pollution and water pollution with the development of ALS.
RESULTS: The combined search strategy led to the inclusion of 44 articles pertaining to at least one exposure of interest. Of the 25 included urbanization studies, four of nine studies on living in rural areas and three of seven studies on living in more highly urbanized/dense areas found positive associations to ALS. There were also three of five studies for exposure to electromagnetic fields and/or proximity to powerlines that found positive associations to ALS. Three case-control studies for each of diesel exhaust and nitrogen dioxide found positive associations with the development of ALS, with the latter showing a dose-response in one study. Three studies for each of high selenium content in drinking water and proximity to lakes prone to cyanobacterial blooms also found positive associations to ALS.
CONCLUSION: Whereas markers of air and water pollution appear as potential risk factors for ALS, results are mixed for the role of urbanization.}, }
@article {pmid36963821, year = {2023}, author = {Yang, T and Xiao, Y and Cheng, Y and Huang, J and Wei, Q and Li, C and Shang, H}, title = {Epigenetic clocks in neurodegenerative diseases: a systematic review.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {94}, number = {12}, pages = {1064-1070}, doi = {10.1136/jnnp-2022-330931}, pmid = {36963821}, issn = {1468-330X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Neurodegenerative Diseases/genetics/pathology ; *Alzheimer Disease/genetics ; *Parkinson Disease/genetics ; Epigenesis, Genetic/genetics ; }, abstract = {BACKGROUND: Biological ageing is one of the principal risk factors for neurodegenerative diseases. It is becoming increasingly clear that acceleration of DNA methylation age, as measured by the epigenetic clock, is closely associated with many age-related diseases.
METHODS: We searched the PubMed and Web of Science databases to identify eligible studies reporting epigenetic clocks in several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD).
RESULTS: Twenty-three studies (12 for AD, 4 for PD, 5 for ALS, and 2 for HD) were included. We systematically summarised the clinical utility of 11 epigenetic clocks (based on blood and brain tissues) in assessing the risk factors, age of onset, diagnosis, progression, prognosis and pathology of AD, PD, ALS and HD. We also critically described our current understandings to these evidences, and further discussed key challenges, potential mechanisms and future perspectives of epigenetic ageing in neurodegenerative diseases.
CONCLUSIONS: Epigenetic clocks hold great potential in neurodegenerative diseases. Further research is encouraged to evaluate the clinical utility and promote the application.
PROSPERO REGISTRATION NUMBER: CRD42022365233.}, }
@article {pmid36921894, year = {2023}, author = {Khan, A and Frazer-Green, L and Amin, R and Wolfe, L and Faulkner, G and Casey, K and Sharma, G and Selim, B and Zielinski, D and Aboussouan, LS and McKim, D and Gay, P}, title = {Respiratory Management of Patients With Neuromuscular Weakness: An American College of Chest Physicians Clinical Practice Guideline and Expert Panel Report.}, journal = {Chest}, volume = {164}, number = {2}, pages = {394-413}, doi = {10.1016/j.chest.2023.03.011}, pmid = {36921894}, issn = {1931-3543}, mesh = {Humans ; Quality of Life ; Respiration, Artificial ; *Noninvasive Ventilation ; *Respiratory Insufficiency/etiology/therapy ; *Physicians ; }, abstract = {BACKGROUND: Respiratory failure is a significant concern in neuromuscular diseases (NMDs). This CHEST guideline examines the literature on the respiratory management of patients with NMD to provide evidence-based recommendations.
STUDY DESIGN AND METHODS: An expert panel conducted a systematic review addressing the respiratory management of NMD and applied the Grading of Recommendations, Assessment, Development, and Evaluations approach for assessing the certainty of the evidence and formulating and grading recommendations. A modified Delphi technique was used to reach a consensus on the recommendations.
RESULTS: Based on 128 studies, the panel generated 15 graded recommendations, one good practice statement, and one consensus-based statement.
INTERPRETATION: Evidence of best practices for respiratory management in NMD is limited and is based primarily on observational data in amyotrophic lateral sclerosis. The panel found that pulmonary function testing every 6 months may be beneficial and may be used to initiate noninvasive ventilation (NIV) when clinically indicated. An individualized approach to NIV settings may benefit patients with chronic respiratory failure and sleep-disordered breathing related to NMD. When resources allow, polysomnography or overnight oximetry can help to guide the initiation of NIV. The panel provided guidelines for mouthpiece ventilation, transition to home mechanical ventilation, salivary secretion management, and airway clearance therapies. The guideline panel emphasizes that NMD pathologic characteristics represent a diverse group of disorders with differing rates of decline in lung function. The clinician's role is to add evaluation at the bedside to shared decision-making with patients and families, including respect for patient preferences and treatment goals, considerations of quality of life, and appropriate use of available resources in decision-making.}, }
@article {pmid36897461, year = {2023}, author = {Zhang, G and E, M and Zhou, X}, title = {Environmental and Occupational solvents exposure and amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {44}, number = {8}, pages = {2803-2809}, pmid = {36897461}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/chemically induced/epidemiology ; Solvents/toxicity ; *Occupational Exposure/adverse effects ; Case-Control Studies ; Odds Ratio ; Risk Factors ; Environmental Exposure ; }, abstract = {Studies focusing on the association between environmental and occupational solvent exposure and amyotrophic lateral sclerosis (ALS) have yielded inconsistent results. Herein we present the results of a meta-analysis on the correlation between solvent exposure and ALS. We searched for eligible studies that reported ALS with exposure to solvents in PubMed, Embase, and Web of Science up to December 2022. The Newcastle-Ottawa scale was used to evaluate the quality of the article and a meta-analysis was performed using a random effect model. Thirteen articles, including two cohort studies and 13 case-control studies with 6365 cases and 173,321 controls were selected. The odds ratio (OR) for the association between solvent exposure and ALS was 1.31 (95% confidence interval [CI], 1.11-1.54) with moderate heterogeneity (I[2] = 59.7%; p = 0.002). Subgroup and sensitivity analyses confirmed the results, and publication bias was not detected. These results indicated that environmental and occupational solvent exposure was associated with the risk of ALS.}, }
@article {pmid36881218, year = {2023}, author = {Zahir, F and Hanman, A and Yazdani, N and La Rosa, S and Sleik, G and Sullivan, B and Mehdipour, A and Malouka, S and Kuspinar, A}, title = {Assessing the psychometric properties of quality of life measures in individuals with amyotrophic lateral sclerosis: a systematic review.}, journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation}, volume = {32}, number = {9}, pages = {2447-2462}, pmid = {36881218}, issn = {1573-2649}, mesh = {Adult ; Humans ; *Amyotrophic Lateral Sclerosis ; Patient Reported Outcome Measures ; Psychometrics/methods ; *Quality of Life/psychology ; Reproducibility of Results ; }, abstract = {PURPOSE: Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in adults. There are many patient-reported outcome measures (PROMs) for measuring quality of life (QoL) and health-related QoL (HRQoL) within this population; however, there is limited consensus regarding which are most valid, reliable, responsive, and interpretable. This systematic review assesses the psychometric properties and interpretability of QoL and HRQoL PROMs for individuals with ALS.
METHODS: This review was conducted following the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) methodology for systematic reviews of PROMs. MEDLINE, EMBASE, and CINAHL databases were searched. Studies were included if their aim was to evaluate one or more psychometric properties or the interpretability of QoL or HRQoL PROMs in individuals with ALS.
RESULTS: We screened 2713 abstracts, reviewed 60 full-text articles, and included 37 articles. Fifteen PROMs were evaluated including generic HRQoL (e.g., SF-36), ALS-specific HRQoL (e.g., ALSAQ-40), and individualized QoL (e.g., SEIQoL) measures. Evidence for internal consistency and test-retest reliability were acceptable. For convergent validity, 84% of hypotheses were met. For known-groups validity, outcomes were able to distinguish between healthy cohorts and other conditions. Responsiveness results ranged from low to high correlations with other measures over 3-24 months. Evidence for content validity, structural validity, measurement error, and divergent validity was limited.
CONCLUSION: This review identified evidence in support of the ALSAQ-40 or ALSAQ-5 for individuals with ALS. These findings can guide healthcare practitioners when selecting evidence-based QoL and HRQoL PROMs for patients and provide researchers with insight into gaps in the literature.}, }
@article {pmid36842953, year = {2023}, author = {Vautier, A and Lebreton, AL and Codron, P and Awada, Z and Gohier, P and Cassereau, J}, title = {Retinal vessels as a window on amyotrophic lateral sclerosis pathophysiology: A systematic review.}, journal = {Revue neurologique}, volume = {179}, number = {6}, pages = {548-562}, doi = {10.1016/j.neurol.2022.11.010}, pmid = {36842953}, issn = {0035-3787}, mesh = {*Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology ; *Retinal Vessels/diagnostic imaging/physiopathology ; Humans ; *Microvessels/diagnostic imaging/physiopathology ; Angiography/methods ; *Tomography, Optical Coherence ; Saccades ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a rare fatal motor neuron disease. Although many potential mechanisms have been proposed, the pathophysiology of the disease remains unknown. Currently available treatments can only delay the progression of the disease and prolong life expectancy by a few months. There is still no definitive cure for ALS, and the development of new treatments is limited by a lack of understanding of the underlying biological processes that trigger and promote neurodegeneration. Several scientific results suggest a neurovascular impairment in ALS providing perspectives for the development of new biomarkers and treatments. In this article, we performed a systematic review using PRISMA guidelines including PubMed, EmBase, GoogleScholar, and Web of Science Core Collection to analyze the scientific literature published between 2000 and 2021 discussing the neurocardiovascular involvement and ophthalmologic abnormalities in ALS. In total, 122 articles were included to establish this systematic review. Indeed, microvascular pathology seems to be involved in ALS, affecting all the neurovascular unit components. Retinal changes have also been recently highlighted without significant alteration of the visual pathways. Despite the peripheral location of the retina, it is considered as an extension of the central nervous system (CNS) as it displays similarities to the brain, the inner blood-retinal barrier, and the blood-brain barrier. This suggests that the eye could be considered as a 'window' into the brain in many CNS disorders. Thus, studying ocular manifestations of brain pathologies seems very promising in understanding neurodegenerative disorders, mainly ALS. Optical coherence tomography angiography (OCT-A) could therefore be a powerful approach for exploration of retinal microvascularization allowing to obtain new diagnostic and prognostic biomarkers of ALS.}, }
@article {pmid36776068, year = {2023}, author = {Hui, BSM and Zhi, LR and Retinasamy, T and Arulsamy, A and Law, CSW and Shaikh, MF and Yeong, KY}, title = {The Role of Interferon-α in Neurodegenerative Diseases: A Systematic Review.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {94}, number = {s1}, pages = {S45-S66}, pmid = {36776068}, issn = {1875-8908}, mesh = {Humans ; *Neurodegenerative Diseases/pathology ; Interferon-alpha/therapeutic use ; Cytokines ; Databases, Factual ; }, abstract = {BACKGROUND: Neurodegenerative diseases (NDs) impose significant financial and healthcare burden on populations all over the world. The prevalence and incidence of NDs have been observed to increase dramatically with age. Hence, the number of reported cases is projected to increase in the future, as life spans continues to rise. Despite this, there is limited effective treatment against most NDs. Interferons (IFNs), a family of cytokines, have been suggested as a promising therapeutic target for NDs, particularly IFN-α, which governs various pathological pathways in different NDs.
OBJECTIVE: This systematic review aimed to critically appraise the currently available literature on the pathological role of IFN-α in neurodegeneration/NDs.
METHODS: Three databases, Scopus, PubMed, and Ovid Medline, were utilized for the literature search.
RESULTS: A total of 77 journal articles were selected for critical evaluation, based on the inclusion and exclusion criteria. The studies selected and elucidated in this current systematic review have showed that IFN-α may play a deleterious role in neurodegenerative diseases through its strong association with the inflammatory processes resulting in mainly neurocognitive impairments. IFN-α may be displaying its neurotoxic function via various mechanisms such as abnormal calcium mineralization, activation of STAT1-dependent mechanisms, and increased quinolinic acid production.
CONCLUSION: The exact role IFN-α in these neurodegenerative diseases have yet to be determine due to a lack in more recent evidence, thereby creating a variability in the role of IFN-α. Future investigations should thus be conducted, so that the role played by IFN-α in neurodegenerative diseases could be delineated.}, }
@article {pmid36763275, year = {2023}, author = {Gong, Y and Zhang, X and Zhao, X and Chang, H and Zhang, J and Gao, Z and Mi, Y and Chen, Y and Zhang, H and Huang, C and Yu, Z}, title = {Global ambient particulate matter pollution and neurodegenerative disorders: a systematic review of literature and meta-analysis.}, journal = {Environmental science and pollution research international}, volume = {30}, number = {14}, pages = {39418-39430}, pmid = {36763275}, issn = {1614-7499}, support = {2018YFA0606200//National Key R&D Program of China/ ; 42075178//National Natural Science Foundation of China/ ; 81602819//National Natural Science Foundation of China/ ; 214200510016//Zhongyuan Science and Technology Innovation Leadership Program/ ; 201300310800//Major Public Welfare Special Projects of Henan Province/ ; 222102310165//Key Project of Science and Technology of Henan Province/ ; ZD202203//Open Research Fund of National Health Commission Key Laboratory of Birth Defects Prevention & Henan Key Laboratory of Population Defects Prevention/ ; }, mesh = {Humans ; *Air Pollutants/analysis ; *Air Pollution/analysis ; *Alzheimer Disease/epidemiology ; *Dementia, Vascular ; Environmental Exposure/analysis ; *Parkinson Disease ; Particulate Matter/analysis ; }, abstract = {Previous studies on particulate matter (PM) exposure and neurodegenerative disorders showed inconsistent results, and few studies systematically examined the long-term effect of PM on neurodegenerative diseases, including all-cause dementia, Alzheimer's disease, Parkinson's disease, vascular dementia, amyotrophic lateral sclerosis, and cognitive function decline. We systematically searched for published studies in PubMed, Embase, Cochrane Library, and Web of Science up to October 31, 2022. To facilitate a comparison of effect sizes from different studies, we standardized units across studies to a 10 μg/m[3] increase for PM. Heterogeneity was assessed by Cochran's Q test and I[2] statistic. Publication bias was evaluated using funnel plots and Egger's tests. Subgroup analysis, meta-regression, and sensitivity analysis were performed. The protocol for this review was registered with PROSPERO (CRD42021277112). Of the 3403 originally identified studies, a meta-analysis was finally performed in 49 studies. The results showed that there was a significant positive association between long-term PM2.5 exposure and all-cause dementia, Alzheimer's disease as well as Parkinson's disease, with pooled OR of 1.30 (95%CI: 1.14, 1.47, I[2] = 99.3%), 1.65 (95%CI: 1.37, 1.94, I[2] = 98.2%), and 1.17 (95%CI: 1.00, 1.33, I[2] = 91.8%). A positive association between PM10 and vascular dementia was observed (OR = 1.12, 95%CI: 1.04, 1.21, I[2] = 0.0%). Association between PM exposure and decreased cognitive function score was found. Our results highlight the important role of PM pollution, particularly PM2.5, in the risk of age-related neurodegenerative diseases and cognitive function decline.}, }
@article {pmid36751865, year = {2024}, author = {Abrahao, A and Phung, L and Fam, D and Escorcio-Bezerra, ML and Robinson, LR and Jones, KE and Zinman, L}, title = {Motor Unit Number Index of the Upper Trapezius: A Meta-Analysis and Cross-sectional Study of Its Reliability.}, journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques}, volume = {51}, number = {1}, pages = {129-133}, doi = {10.1017/cjn.2023.20}, pmid = {36751865}, issn = {0317-1671}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Biomarkers ; Cross-Sectional Studies ; Muscle, Skeletal ; Reproducibility of Results ; *Superficial Back Muscles ; }, abstract = {Motor unit number index of the upper trapezius (MUNIX-Trapezius) is a candidate biomarker for bulbar lower motor neuron function; however, reliability data is incomplete. To assess MUNIX-Trapezius reliability in controls, we conducted a systematic review, a cross-sectional study (n = 20), and a meta-analysis. We demonstrated a high inter- and intra-rater intraclass correlation (0.86 and 0.94, respectively), indicating that MUNIX-Trapezius is reliable with between-study variability moderated by age and MUNIX technique. With further validation, this measure can serve as a disease monitoring and response biomarker of bulbar function in the therapeutic development for amyotrophic lateral sclerosis.}, }
@article {pmid36748473, year = {2023}, author = {Berry, JD and Blanchard, M and Bonar, K and Drane, E and Murton, M and Ploug, U and Ricchetti-Masterson, K and Savic, N and Worthington, E and Heiman-Patterson, T}, title = {Epidemiology and economic burden of amyotrophic lateral sclerosis in the United States: a literature review.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {24}, number = {5-6}, pages = {436-448}, doi = {10.1080/21678421.2023.2165947}, pmid = {36748473}, issn = {2167-9223}, mesh = {Humans ; United States/epidemiology ; *Amyotrophic Lateral Sclerosis/epidemiology ; Financial Stress ; Prevalence ; Registries ; Databases, Factual ; Cost of Illness ; Health Care Costs ; }, abstract = {Objective: This review sought to gain a comprehensive, up-to-date understanding of the epidemiology and cost and healthcare resource use (HCRU) burden of amyotrophic lateral sclerosis (ALS) in the US, at a patient and national level. Methods: A targeted literature review (TLR) to identify epidemiological evidence (prevalence, incidence, mortality, survival), and systematic literature review (SLR) to identify cost and HCRU data published since January 2016, were performed. MEDLINE databases and Embase searches were conducted in January 2021. Key congresses (2019-2020) and bibliographies of relevant SLRs were hand-searched. Two high-quality SLRs were reviewed for additional cost data published between January 2001-2015. Registry and database studies were prioritized for epidemiological evidence. To allow comparison between studies in this publication, only evidence from the US was considered, with costs inflated to the 2020/2021 cost-year and converted to US dollars. Results: Eight studies from the epidemiology TLR, and eighteen from the cost and HCRU SLR, were extracted. Reported ALS incidence in the US was ∼1.5 per 100,000 person-years, and point prevalence ranged from 3.84-5.56 per 100,000 population. Total US national costs spanned ∼$212 million-∼$1.4 billion USD/year, and variably consisted of direct costs associated with HCRU and indirect costs. Conclusions: The national cost of ∼$1.02 billion USD/year (estimated using a prevalence of 16,055 cases) best aligns with prevalence estimates found in the TLR (equating to ∼13,000-18,000 cases). However, large-scale, population-based studies are necessary to precisely assess US epidemiology of ALS and capture all costs needed to inform cost-effectiveness models and resource planning.}, }
@article {pmid36722043, year = {2023}, author = {Fakhri, S and Darvish, E and Narimani, F and Moradi, SZ and Abbaszadeh, F and Khan, H}, title = {The regulatory role of non-coding RNAs and their interactions with phytochemicals in neurodegenerative diseases: a systematic review.}, journal = {Briefings in functional genomics}, volume = {22}, number = {2}, pages = {143-160}, doi = {10.1093/bfgp/elac055}, pmid = {36722043}, issn = {2041-2657}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/genetics/metabolism ; *Alzheimer Disease/genetics/metabolism ; *Parkinson Disease/drug therapy/genetics/metabolism ; RNA, Untranslated/genetics ; Phytochemicals/pharmacology/therapeutic use ; }, abstract = {Neurodegenerative diseases (NDDs) are on the rise in the world. Therefore, it is a critical issue to reveal the precise pathophysiological mechanisms and novel therapeutic strategies to deal with such conditions. Passing through different mechanisms, non-coding RNAs (ncRNAs) play a pivotal role in NDDs through various mechanisms, by changing the expression of some genes, interference with protein translation and alterations in some signaling pathways. It urges the need to introduce novel strategies and therapeutic agents with multi-targeting potentials. Phytochemicals are hopeful antioxidants and anti-inflammatory agents with promising modulatory roles on dysregulated signaling pathways and protein translation during NDDs. In this study, the role of ncRNAs (e.g. lncRNAs, miRNA, siRNAs and piRNAs) was highlighted in NDDs. This study also aimed to investigate the role of phytochemicals (phenolic compounds, alkaloids, terpenoids and sulfur compounds) in the modulation of ncRNAs during NDDs such as Alzheimer's disease, Parkinson's disease, epilepsy, depression and amyotrophic lateral sclerosis.}, }
@article {pmid36619561, year = {2022}, author = {Alqarni, S and Alsebai, M}, title = {Could VGF and/or its derived peptide act as biomarkers for the diagnosis of neurodegenerative diseases: A systematic review.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {1032192}, pmid = {36619561}, issn = {1664-2392}, mesh = {Adult ; Animals ; Female ; Humans ; Male ; Rats ; *Alzheimer Disease ; Amyloid beta-Peptides ; *Amyotrophic Lateral Sclerosis/diagnosis ; Biomarkers ; Dopamine ; Nerve Growth Factors ; *Neurodegenerative Diseases/diagnosis ; Observational Studies as Topic ; }, abstract = {BACKGROUND: The increasing ageing population has led to an increase in the prevalence of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). However, as yet, there are no simple biomarkers to predict the onset of such diseases. Recently, VGF and its peptides have been highlighted in neurodegenerative diseases. VGF (non-acronymic) is a polypeptide induced in PC12 cells by neurotrophic factors.
OBJECTIVE: This systematic review aimed to determine whether VGF and/or its derived peptides can be used as biomarkers for the diagnosis of ALS, PD, and AD with specific attention to (1) the levels of VGF and/or its derived peptides, (2) amyloid-beta, (3) dopamine, and (4) cognitive score.
METHODOLOGY: A search was undertaken in the Ovid EMBASE, Cochrane Library, PubMed, Scopus, and Web of Science for observational studies. Publications that assessed the level of VGF and/or its derived peptides among people with neurodegenerative diseases and compared them with healthy people were included. The quality of the included studies was assessed using the National Heart, Lung, and Blood Institute Quality Assessment Tool.
RESULT: A search of the databases yielded 834 studies, of which, eight observational studies met the inclusion criteria with a total of 673 participants (51.7% males) aged >18 years. Seven studies showed significant decreases in VGF and its derived peptides in adults with AD, PD, and ALS compared to healthy controls (p<0.05). However, one study showed that there was no significant difference in VGF in AD compared to healthy control(p>0.05). Furthermore, only one study reported that VGF levels were positively correlated with those of tissue dopamine but not with Aβ1-42, and low levels of VGF were associated to cognitive deficits.
CONCLUSION: The use of VGF and its derivatives for the diagnosis of PD, ALS, AD remains unclear, so further investigation of the role of VGF in neurodegenerative diseases and pathophysiology is needed to provide new insights.}, }
@article {pmid36618399, year = {2022}, author = {Jiang, Z and Wang, Z and Wei, X and Yu, XF}, title = {Inflammatory checkpoints in amyotrophic lateral sclerosis: From biomarkers to therapeutic targets.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1059994}, pmid = {36618399}, issn = {1664-3224}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/diagnosis/drug therapy/etiology ; *Neurodegenerative Diseases ; Biomarkers ; Motor Neurons/metabolism ; Proteins/therapeutic use ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor neuron damage. Due to the complexity of the ALS, so far the etiology and underlying pathogenesis of sporadic ALS are not completely understood. Recently, many studies have emphasized the role of inflammatory networks, which are comprised of various inflammatory molecules and proteins in the pathogenesis of ALS. Inflammatory molecules and proteins may be used as independent predictors of patient survival and might be used in patient stratification and in evaluating the therapeutic response in clinical trials. This review article describes the latest advances in various inflammatory markers in ALS and its animal models. In particular, this review discusses the role of inflammatory molecule markers in the pathogenesis of the disease and their relationship with clinical parameters. We also highlight the advantages and disadvantages of applying inflammatory markers in clinical manifestations, animal studies, and drug clinical trials. Further, we summarize the potential application of some inflammatory biomarkers as new therapeutic targets and therapeutic strategies, which would perhaps expand the therapeutic interventions for ALS.}, }
@article {pmid36586129, year = {2022}, author = {Zhang, A and Xu, H and Huang, J and Guo, S and Tian, T and Lei, X and He, D}, title = {Amyotrophic lateral sclerosis with primary progressive aphasia: a case report and literature review.}, journal = {Neuro endocrinology letters}, volume = {43}, number = {6}, pages = {293-302}, pmid = {36586129}, issn = {2354-4716}, mesh = {Male ; Female ; Humans ; *Amyotrophic Lateral Sclerosis ; C9orf72 Protein/genetics ; *Frontotemporal Dementia/genetics/pathology/psychology ; Mutation ; *Aphasia, Primary Progressive ; }, abstract = {The association between amyotrophic lateral sclerosis (ALS) and primary progressive aphasia (PPA) is rarely seen in patients. A case of ALS-PPA with a possible reticulon 2 (RTN2) mutation was reported in this study. Moreover, we systematically reviewed the previous reports of 28 ALS cases with progressive non-fluent aphasia (PNFA) and semantic dementia (SD) to identified the unique pathologic features and strong heritability of ALS-PPA. There is a different heritability among the ALS-SD, ALS-PNFA, and the ALS-unclassified PPA groups (p=0.003). Males are more prone to have ALS-PPA than females in all the three groups (p=0.028). PPA-ALS usually starts with cognitive impairment, and the onset most often involves the bulbar. In addition, chromosome 9 open reading frame 72(C9ORF72) and TANK-binding kinase 1 (TBK1) are important pathogenic genes of PPA-ALS. Overall, heritability is of high certainty in ALS-SD, ALS-PNFA, and the ALS-unclassified PPA groups. TAR (Trans-Activator Regulatory) DNA-binding Protein 43 (TDP43) is a 100% predictive pathologic protein of ALS-PPA. C9ORF72 and TBK1 are important pathogenic genes of PPA-ALS.}, }
@article {pmid36462105, year = {2023}, author = {Gao, M and Zhu, L and Chang, J and Cao, T and Song, L and Wen, C and Chen, Y and Zhuo, Y and Chen, F}, title = {Safety and Efficacy of Edaravone in Patients with Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-analysis.}, journal = {Clinical drug investigation}, volume = {43}, number = {1}, pages = {1-11}, pmid = {36462105}, issn = {1179-1918}, support = {No. 2019-JYB-TD-003//Special Funds for Basic Scientific Research in Central Universities of China/ ; }, mesh = {Humans ; Edaravone/adverse effects ; *Amyotrophic Lateral Sclerosis/drug therapy ; Surveys and Questionnaires ; }, abstract = {BACKGROUND AND OBJECTIVE: The efficacy and safety of edaravone for the treatment of amyotrophic lateral sclerosis (ALS) remain unclear. The aim of this meta-analysis was to provide evidence-based medical guidance and advice for the clinical application of edaravone in the treatment of ALS.
METHODS: PubMed, Embase, Chinese Biomedical Literature Database (CBM), Cochrane Library and Web of Science were searched through 09 March 2022 for randomized controlled trials (RCTs) on the safety and efficacy of edaravone versus placebo during follow-up of patients with ALS. A summary of the outcome measures with GRADE was performed. This study was registered on PROSPERO (ID: CRD 42022319997).
RESULTS: Five RCTs with a total of 566 participants were included, and there was a significant difference (mean difference [MD] 1.33, 95% confidence interval [CI] 0.33-2.34; p = 0.009) in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score between the treatment and placebo groups. The edaravone group had an increased grip strength (MD 0.26, 95% CI 0.03-0.49; p = 0.03) and modified Norris Scale score (MD 2.81, 95% CI 1.18-4.43; p = 0.0007). However, there were no significant differences between groups for the change in forced vital capacity (FVC)% (MD 0.55, 95% CI - 3.15 to 4.24; p = 0.77), pinch strength (MD 0.05, 95% CI - 0.05 to 0.16; p = 0.33) or Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) score (MD - 4.76, 95% CI - 9.56 to 0.03; p = 0.05). The incidence of adverse events (AEs) (risk ratio [RR] 0.09, 95% CI 0.93-1.05; p = 0.65), serious adverse events (SAEs) (RR 0.72, 95% CI 0.52-1.00; p = 0.05) and the number of deaths (risk difference [RD] 0.00, 95% CI - 0.02 to 0.03; p = 0.83) were not statistically different from the placebo group. The quality of evidence was low only for SAEs, and the remaining outcome measures were of moderate quality.
CONCLUSIONS: Compared with placebo, edaravone may provide potential clinical benefits in the treatment of ALS and may not increase the number of AEs and deaths. However, due to the low-quality evidence of the included studies and the small sample size, more high-quality and high-standard research evidence is needed to confirm these results.
PROTOCOL REGISTRATION: This study was registered on PROSPERO (ID: CRD 42022319997).}, }
@article {pmid36411673, year = {2022}, author = {Das, T and Kaur, H and Gour, P and Prasad, K and Lynn, AM and Prakash, A and Kumar, V}, title = {Intersection of network medicine and machine learning towards investigating the key biomarkers and pathways underlying amyotrophic lateral sclerosis: a systematic review.}, journal = {Briefings in bioinformatics}, volume = {23}, number = {6}, pages = {}, doi = {10.1093/bib/bbac442}, pmid = {36411673}, issn = {1477-4054}, support = {BMI/11(63)/2020//Indian Council of Medical Research/ ; YSS/2015/000228/LS//Science and Engineering Research Board/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Biomarkers/metabolism ; Machine Learning ; }, abstract = {BACKGROUND: Network medicine is an emerging area of research that focuses on delving into the molecular complexity of the disease, leading to the discovery of network biomarkers and therapeutic target discovery. Amyotrophic lateral sclerosis (ALS) is a complicated rare disease with unknown pathogenesis and no available treatment. In ALS, network properties appear to be potential biomarkers that can be beneficial in disease-related applications when explored independently or in tandem with machine learning (ML) techniques.
OBJECTIVE: This systematic literature review explores recent trends in network medicine and implementations of network-based ML algorithms in ALS. We aim to provide an overview of the identified primary studies and gather details on identifying the potential biomarkers and delineated pathways.
METHODS: The current study consists of searching for and investigating primary studies from PubMed and Dimensions.ai, published between 2018 and 2022 that reported network medicine perspectives and the coupling of ML techniques. Each abstract and full-text study was individually evaluated, and the relevant studies were finally included in the review for discussion once they met the inclusion and exclusion criteria.
RESULTS: We identified 109 eligible publications from primary studies representing this systematic review. The data coalesced into two themes: application of network science to identify disease modules and promising biomarkers in ALS, along with network-based ML approaches. Conclusion This systematic review gives an overview of the network medicine approaches and implementations of network-based ML algorithms in ALS to determine new disease genes, and identify critical pathways and therapeutic target discovery for personalized treatment.}, }
@article {pmid36398461, year = {2022}, author = {Rufino, RA and Pereira-Rufino, LDS and Vissoto, TCS and Kerkis, I and Neves, ADC and da Silva, MCP}, title = {The Immunomodulatory Potential Role of Mesenchymal Stem Cells in Diseases of the Central Nervous System.}, journal = {Neuro-degenerative diseases}, volume = {22}, number = {2}, pages = {68-82}, doi = {10.1159/000528036}, pmid = {36398461}, issn = {1660-2862}, mesh = {Humans ; *Mesenchymal Stem Cells/metabolism ; *Neurodegenerative Diseases/therapy ; Central Nervous System ; *Multiple Sclerosis ; *Parkinson Disease/metabolism ; }, abstract = {INTRODUCTION: Several studies indicate the role of mesenchymal stem cells (MSCs) as an important tool in regenerative medicine associated with injuries that affect the central nervous system (CNS). The MSCs have the capacity to differentiate into cells of the embryonic tissue, such as the mesoderm. So, these cells can be found in a variety of tissues. Also, the MSCs can release immunomodulatory and neurotrophic factors performance as inflammation mediators operating in injured tissue regeneration. Furthermore, they can differentiate into neural-like cells in vitro. Thereby, because of the high immunomodulatory role of MSCs, this review sought to describe the main immunomodulatory mechanisms performed by MSCs in CNS recovery after tissue injury or neurodegenerative diseases.
METHODS: PubMed and ScienceDirect were searched between January 2011 to March 2021, and 43 articles met the criteria of the review.
RESULTS: This systematic review indicates that MSCs were used in vivo experimental multiple sclerosis, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, ischemic stroke, and traumatic brain injury. The treatment MSCs were usually from human origin, derived from bone marrow, and administered intravenously.
CONCLUSION: It was shown that MSCs, independent from origin or administration pathway, can reduce inflammation and help in the recovery and preservation of injured neural tissue. Thus, the use of MSCs represents a potential therapeutic option in the treatment of neurological disorders mediated by inflammatory processes.}, }
@article {pmid36341104, year = {2022}, author = {Zhou, B and Wei, J and Zhang, Y and Liu, Y and Shan, S and Ye, S and Li, B and Fan, D and Luo, Y}, title = {Different observation period of exercise training in amyotrophic lateral sclerosis patients: A meta-analysis.}, journal = {Frontiers in neurology}, volume = {13}, number = {}, pages = {986882}, pmid = {36341104}, issn = {1664-2295}, abstract = {OBJECTIVE: The purpose of this meta-analysis was to evaluate the effect of more intensive exercise training on the functional ability of patients with amyotrophic lateral sclerosis.
METHODS: Randomized controlled trials on exercise training in amyotrophic lateral sclerosis patients were retrieved from PubMed, Embase, Web of Science, Cochrane Library and other databases, and meta-analysis was conducted using a fixed effect model or random effect model. Sensitivity analysis was used as a means to study heterogeneity.
RESULTS: A total of 8 randomized controlled trials involving 330 patients with amyotrophic lateral sclerosis were included in this study. The results showed that there was statistical significance in the influence of more intensive exercise training on amyotrophic lateral sclerosis Functional Rating Scale in the short term (0-4 months) and the medium term (5-8 months) (P < 0.05). There was no significant difference in the effect of the amyotrophic lateral sclerosis Functional Rating Scale-Revised in the short term (0-4 months) or long term (9-12 months) (P ≥ 0.05). In the medium term (5-8 months), there was statistical significance (P < 0.05). There was no significant difference in Forced vital capacity (FVC%) in the short term (0-4 months) (P > 0.05).
CONCLUSION: More intensive exercise training may slow the decline in functional score of amyotrophic lateral sclerosis patients, and more studies should be carried out in the future to verify the effect of more intensive exercise training in patients with amyotrophic lateral sclerosis.}, }
@article {pmid36277914, year = {2022}, author = {Liao, Y and He, S and Liu, D and Gu, L and Chen, Q and Yang, S and Li, D}, title = {The efficacy and safety of Chinese herbal medicine as an add-on therapy for amyotrophic lateral sclerosis: An updated systematic review and meta-analysis of randomized controlled trials.}, journal = {Frontiers in neurology}, volume = {13}, number = {}, pages = {988034}, pmid = {36277914}, issn = {1664-2295}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) has attracted widespread attention because of its unknown pathogenesis, rapid progression, and life-threatening and incurable characteristics. A series of complementary therapies, including Chinese herbal medicine (CHM), is available for use in the clinic and has been the focus of much research. However, it is unclear as to whether supplementary CHM relieves disease symptoms or extends life span; thus, we conducted this updated meta-analysis to validate the efficacy and safety of this practice.
METHODS: We searched six electronic databases for randomized controlled trials involving CHM and patients with ALS that were published up to April 2022. Two researchers independently screened the literature, assessed the risk of bias for each trial, and then extracted data. The methodological quality of the included trials was assessed using the Cochrane risk of bias tool, and a pooled data analysis was performed using RevMan 5.3.
RESULTS: A total of 14 trials led to the publication of 15 articles featuring 1,141 participants during the study period; the articles were included in the systematic review. In terms of increasing ALS functional rating scale (ALSFRS) scores, CHM was superior to the placebo after 3 months of treatment [mean difference (MD):0.7; 95% CI:0.43 to 0.98; P < 0.01] and to riluzole after 4 weeks of treatment (MD: 2.87; 95% CI: 0.81 to 4.93; P < 0.05), and it was superior to conventional medicine (CM) alone when used as an add-on therapy after 8 weeks of treatment (MD: 3.5; 95% CI: 0.51 to 6.49; P < 0.05). The change in the modified Norris score (m-Norris) from baseline to the end of more than 3 months of treatment was significantly different when compared between the CHM plus CM group and the CM alone group (MD: 2.09; 95% CI: 0.62 to 3.55; P < 0.01). In addition, CHM had a significantly better effect on increase in clinical effective rate (RR: 1.54; 95% CI: 1.23 to 1.92; P < 0.01) and improvement in forced vital capacity (MD: 7.26; 95% CI: 2.92 to 11.6; P < 0.01). However, there was no significant difference between the CHM therapy and CM in terms of improving life quality (MD: 5.13; 95% CI: -7.04 to 17.31; P = 0.41) and decreasing mortality (RR: 0.41; 95% CI: 0.04 to 4.21; P = 0.46).
CONCLUSION: The analysis suggested that the short-term adjunct use of CHM could improve the ALSFRS score and clinical effect with a good safety profile when compared with the placebo or riluzole alone. However, future research should be centered on the long-term efficacy of patient-oriented outcomes.
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=323047, identifier: CRD42022323047.}, }
@article {pmid36120351, year = {2022}, author = {Song, Y and Jia, Q and Guan, X and Kazuo, S and Liu, J and Duan, W and Feng, L and Zhang, C and Gao, Y}, title = {Herbal medicine for amyotrophic lateral sclerosis: A systematic review and meta-analysis.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {946548}, pmid = {36120351}, issn = {1663-9812}, abstract = {Background: The effect of herbal medicine (HM) on amyotrophic lateral sclerosis (ALS) is controversial. Clinical trials investigating HMs continue; however, the use of HM is still questioned. We aimed to systematically review the literature pertaining to the effects and safety of HM in ALS. Methods: Randomised controlled trials (RCTs) that investigated the efficacy of HMs in ALS patients compared to any types of controls were identified. Nine databases and six registers were searched from their inception dates to 25 March 2022. Per the PRISMA guidelines, trials were identified and extracted. The risk of bias was evaluated using the Cochrane's tool. Certainty of evidence was assessed as per the GRADE criteria. Forest plots were constructed to assess the effect size and corresponding 95% CIs using fixed-effect models, and random-effect models were employed when required. The primary outcome was the activity limitation measured by validated tools, such as the revised ALS Functional Rating Scale. Results: Twenty studies (N = 1,218) were eligible. Of these, only five studies were double-blinded, and two were placebo-controlled. Fourteen HMs (fifty-one single botanicals) were involved; Astragalus mongholicus Bunge, Atractylodes macrocephala Koidz., and Glycyrrhiza glabra L. were commonly used in nine, eight, and six trials, respectively. For delaying activity limitation, Jiweiling injection (MD, 2.84; 95% CI, 1.21 to 4.46; p = 0.0006) and Shenmai injection (SMD, 1.07; 0.69 to 1.45; p < 0.00001) were significantly more efficacious than Riluzole, but the evidence was low quality. For ameliorating motor neuron loss, Jiweiling injection [right abductor pollicis brevis (APB): MD, 32.42; 7.91 to 56.93; p = 0.01 and left APB: MD, 34.44; 12.85 to 56.03; p = 0.002] was favoured, but the evidence was very low quality. Nine studies reported one hundred and twenty-three adverse events, twenty-six of which occurred in the treatment groups and ninety-seven in the control groups. Conclusion: Very low to low quality of evidence suggests that HMs seem to produce superior treatment responses for ALS without increased risk of adverse events. Additional studies with homogeneous participants, reduced methodological issues, and more efficient outcome measures are required to provide confirmatory evidence. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021277443.}, }
@article {pmid36110394, year = {2022}, author = {Zejlon, C and Nakhostin, D and Winklhofer, S and Pangalu, A and Kulcsar, Z and Lewandowski, S and Finnsson, J and Piehl, F and Ingre, C and Granberg, T and Ineichen, BV}, title = {Structural magnetic resonance imaging findings and histopathological correlations in motor neuron diseases-A systematic review and meta-analysis.}, journal = {Frontiers in neurology}, volume = {13}, number = {}, pages = {947347}, pmid = {36110394}, issn = {1664-2295}, abstract = {OBJECTIVES: The lack of systematic evidence on neuroimaging findings in motor neuron diseases (MND) hampers the diagnostic utility of magnetic resonance imaging (MRI). Thus, we aimed at performing a systematic review and meta-analysis of MRI features in MND including their histopathological correlation.
METHODS: In a comprehensive literature search, out of 5941 unique publications, 223 records assessing brain and spinal cord MRI findings in MND were eligible for a qualitative synthesis. 21 records were included in a random effect model meta-analysis.
RESULTS: Our meta-analysis shows that both T2-hyperintensities along the corticospinal tracts (CST) and motor cortex T2[*]-hypointensitites, also called "motor band sign", are more prevalent in ALS patients compared to controls [OR 2.21 (95%-CI: 1.40-3.49) and 10.85 (95%-CI: 3.74-31.44), respectively]. These two imaging findings correlate to focal axonal degeneration/myelin pallor or glial iron deposition on histopathology, respectively. Additionally, certain clinical MND phenotypes such as amyotrophic lateral sclerosis (ALS) seem to present with distinct CNS atrophy patterns.
CONCLUSIONS: Although CST T2-hyperintensities and the "motor band sign" are non-specific imaging features, they can be leveraged for diagnostic workup of suspected MND cases, together with certain brain atrophy patterns. Collectively, this study provides high-grade evidence for the usefulness of MRI in the diagnostic workup of suspected MND cases.
https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020182682.}, }
@article {pmid36067736, year = {2022}, author = {Gaitanidis, A and Kandilogiannakis, L and Filidou, E and Tsaroucha, A and Kolios, G and Pitiakoudis, M}, title = {Stem Cell Therapies for Gastrointestinal Anastomotic Healing: A Systematic Review and Meta-Analysis on Results from Animal Studies.}, journal = {European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes}, volume = {63}, number = {4}, pages = {173-181}, doi = {10.1159/000526603}, pmid = {36067736}, issn = {1421-9921}, mesh = {Animals ; Anastomosis, Surgical/adverse effects/methods ; *Anastomotic Leak/etiology/prevention & control ; Wound Healing ; *Digestive System Surgical Procedures/adverse effects ; Rectum/surgery ; }, abstract = {BACKGROUND: Despite considerable progress in surgical techniques, anastomotic leak (AL) is a common complication after gastrointestinal surgery. Stem cells are a promising therapy to improve healing and have been used in gastrointestinal anastomoses. In this study, we perform a systematic review and meta-analysis to evaluate the efficacy of stem cell therapies in preventing ALs among animal studies.
METHODS: A systematic review of the literature was performed by searching PubMed, Web of Science, and the Cochrane Library. We considered all anastomoses of the gastrointestinal tract (excl. biliary) from the esophagus to the rectum. Outcomes included AL rates on postoperative day (POD) 7 and the latest time point reported.
RESULTS: Fourteen studies were identified, evaluating stem cells in gastrointestinal anastomoses, of which 1 was on esophageal, 2 on gastric, 2 on small intestinal, and 9 on colorectal anastomoses. Meta-analysis did not show significant differences in AL rates on POD 7 (odds ratio [OR] 0.34, 95% confidence interval [CI]: 0.04-3.15, p = 0.248, I2 = 34.1%, 95% CI: 0-75.2%, Q = 6.07, df = 4, p = 0.194), but there was a nonsignificant trend for lower AL rates at the latest time point reported (OR 0.28, 95% CI: 0.08-1.01, p = 0.052, I2 = 34%, 95% CI: 0-70.8%, Q = 10.6, df = 7, p = 0.157).
CONCLUSION: Stem cell therapy may be associated with lower AL rates in gastrointestinal anastomoses, though meta-analysis is severely inhibited by heterogeneous study design. More studies are needed to determine the therapeutic potential of stem cells.}, }
@article {pmid36047007, year = {2023}, author = {Bekteshi, S and Konings, M and Karlsson, P and Criekinge, TV and Dan, B and Monbaliu, E}, title = {Teleintervention for users of augmentative and alternative communication devices: A systematic review.}, journal = {Developmental medicine and child neurology}, volume = {65}, number = {2}, pages = {171-184}, doi = {10.1111/dmcn.15387}, pmid = {36047007}, issn = {1469-8749}, mesh = {Humans ; Cohort Studies ; *Communication Disorders/etiology/therapy ; *Autistic Disorder ; Language Therapy/methods ; Communication ; }, abstract = {AIM: To synthesize existing evidence on the effectiveness of speech-language teleinterventions delivered via videoconferencing to users of augmentative and alternative communication (AAC) devices.
METHOD: A systematic literature search was conducted in 10 electronic databases, from inception until August 2021. Included were speech-language teleinterventions delivered by researchers and/or clinicians via videoconferencing to users of AAC devices, without restrictions on chronological age and clinical diagnosis. The quality of the studies included in the review was appraised using the Downs and Black checklist and the Single-Case Experimental Design Scale; risk of bias was assessed using the Risk Of Bias In Non-Randomized Studies - of Interventions and the single-case design risk of bias tools.
RESULTS: Six teleinterventions including 25 participants with a variety of conditions, such as Down syndrome, autism, Rett syndrome, and amyotrophic lateral sclerosis met the inclusion criteria. Five studies used a single-case experimental design and one was a cohort study. Teleinterventions included active consultation (n = 2), functional communication training (n = 2), brain-computer interface (n = 1), and both teleintervention and in-person intervention (n = 1). All teleinterventions reported an increase in participants' independent use of AAC devices during the training sessions compared to baseline, as well as an overall high satisfaction and treatment acceptability.
INTERPRETATION: Speech-language teleinterventions for users of AAC devices show great potential for a successful method of service delivery. Future telehealth studies with larger sample sizes and more robust methodology are strongly encouraged to allow the generalization of results across different populations.
WHAT THIS PAPER ADDS: Individuals can learn to use augmentative and alternative communication (AAC) devices independently during tele-AAC interventions. Service providers and recipients reported an overall high satisfaction and acceptability for AAC services delivered via teleinterventions. Speech-language teleinterventions may be an effective method of providing AAC intervention services.}, }
@article {pmid35976476, year = {2022}, author = {Bellomo, G and Piscopo, P and Corbo, M and Pupillo, E and Stipa, G and Beghi, E and Vanacore, N and Lacorte, E}, title = {A systematic review on the risk of neurodegenerative diseases and neurocognitive disorders in professional and varsity athletes.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {43}, number = {12}, pages = {6667-6691}, pmid = {35976476}, issn = {1590-3478}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/complications ; Athletes ; *Chronic Traumatic Encephalopathy/epidemiology/diagnosis ; *Cognitive Dysfunction/epidemiology/complications ; *Dementia/complications ; *Football ; *Neurodegenerative Diseases/epidemiology/complications ; *Parkinson Disease/complications ; *Soccer ; }, abstract = {OBJECTIVE: The aim of this systematic review (SR) was to gather all available epidemiological evidence on former participation in any type of sport, at a professional and varsity level, as a potential risk factor for neurodegenerative diseases (NDs) and neurocognitive disorders (NCDs).
DESIGN: Systematic searches were performed on PubMed, the Cochrane databases, and the ISI Web of Knowledge databases. Included studies were assessed using the NOS checklist.
All epidemiological studies reporting data on the possible association between a clinical diagnosis of amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND), dementia or mild cognitive impairment (MCI), Parkinson's disease (PD), chronic traumatic encephalopathy (CTE) at any stage and with any clinical pattern and the former participation in any types of sport at a varsity and professional level were included.
RESULTS: Data from the 17 included studies showed a higher frequency of NDs and NCDs in former soccer and American football players. Updating the previous SR confirmed a higher frequency of ALS/MND in former soccer players. Data reported a significantly higher risk of dementia/AD in former soccer players, and of MCI in former American football players. Results also showed a significantly higher risk of PD in former soccer and American football players, and a significantly higher risk of CTE in former boxers and American football players. This SR confirmed a higher risk of NDs and NCDs in former professional/varsity athletes. However, the pathological mechanisms underlying this association remain unclear, and further high-quality studies should be performed to clarify whether the association could be sport specific.}, }
@article {pmid35927763, year = {2022}, author = {Cui, C and Sun, J and McKay, KA and Ingre, C and Fang, F}, title = {Medication use and risk of amyotrophic lateral sclerosis-a systematic review.}, journal = {BMC medicine}, volume = {20}, number = {1}, pages = {251}, pmid = {35927763}, issn = {1741-7015}, support = {R01 TS000324/TS/ATSDR CDC HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/epidemiology ; Anti-Bacterial Agents ; Case-Control Studies ; Humans ; Hypoglycemic Agents ; Observational Studies as Topic ; Retrospective Studies ; }, abstract = {BACKGROUND: Studying whether medications act as potential risk factors for amyotrophic lateral sclerosis (ALS) can contribute to the understanding of disease etiology as well as the identification of novel therapeutic targets. Therefore, we conducted a systematic review to summarize the existing evidence on the association between medication use and the subsequent ALS risk.
METHODS: A systematic review was conducted in Medline, Embase, and Web of Science from the date of database establishment to December 10, 2021. References of identified articles were further searched for additional relevant articles. Studies were included if (1) published in English, (2) explored medication use as exposure and development of ALS as outcome, and (3) the design was a human observational study. Clinical trials, reviews, comments, editorials, and case reports were excluded. Quality assessment was performed using a pre-validated tool for non-randomized studies, the Newcastle-Ottawa Assessment Scale (NOS).
RESULTS: Of the 4760 studies identified, 25 articles, including 13 case-control studies, five nested case-control studies, six cohort studies, and one retrospective chart review, were included in the review. Among these studies, there were 22 distinct study populations that included 171,407 patients with ALS, seven classes of medication examined, and 23 studies with a NOS ≥ 5. There was a general lack of agreement between studies on the associations of cholesterol-lowering drugs, anti-inflammatory drugs, immunosuppressants, antibiotics, oral contraceptives (OCs) or hormone replacement therapy (HRT), antihypertensive drugs, antidiabetics, and drugs for psychiatric and neurological disorders with the subsequent risk of ALS. However, it appeared that statins, aspirin, OCs/HRT, antihypertensives, and antidiabetics were unlikely related to a higher risk of ALS. The positive associations noted for antibiotics, antidepressants, and skeletal muscle relaxants might be attributable to prodromal symptoms of ALS.
CONCLUSIONS: There is currently no strong evidence to link any medication use with ALS risk.}, }
@article {pmid35915574, year = {2023}, author = {Glennie, N and Harris, FM and France, EF}, title = {Perceptions and experiences of control among people living with motor neurone disease: a systematic review and thematic synthesis.}, journal = {Disability and rehabilitation}, volume = {45}, number = {16}, pages = {2554-2566}, doi = {10.1080/09638288.2022.2104942}, pmid = {35915574}, issn = {1464-5165}, mesh = {Humans ; Qualitative Research ; *Health Personnel ; }, abstract = {PURPOSE: Current research suggests that feeling a lack of control is common among people living with Motor Neurone Disease (plwMND). This systematic review explores and synthesises evidence about: (1) What factors contribute towards perceptions of control in plwMND (2) How do plwMND attempt to maintain control in their daily lives?
METHODS: A systematic search from inception to January 2022 for peer-reviewed journal articles in English reporting qualitative and mixed-method primary studies or reviews of plwMND's perceptions or experiences of control was conducted on CINAHL, MEDLINE, PsycINFO, ASSIA, Embase and AMED. Eligible articles underwent quality appraisal, data extraction and a thematic synthesis was carried out.
RESULTS: Twenty publications, 19 primary studies and one review, from nine countries, reporting the views of 578 participants aged from 20 to 90 years were included. Two key analytical themes were identified (1) diagnosis can lead to a disruption of previously held control beliefs (2) plwMND use a range of control strategies to attempt to retain control in their lives.
CONCLUSION: This is the first systematic review and qualitative evidence synthesis to reveal the strategies plwMND use to regain control and that control beliefs about health, fate, identity and bodily control are significantly altered by the diagnosis. Implications for rehabilitationOutcome measures for plwMND should consider personal values and preferences as well as objective clinical measurements.plwMND use a range of control strategies which may alter and change over time therefore healthcare professionals may also need to review and adapt treatment decisions over time.The differing viewpoints of healthcare professionals and plwMND should be considered in clinical situations to reduce the potential for conflict.}, }
@article {pmid35899034, year = {2022}, author = {Hecker, P and Steckhan, N and Eyben, F and Schuller, BW and Arnrich, B}, title = {Voice Analysis for Neurological Disorder Recognition-A Systematic Review and Perspective on Emerging Trends.}, journal = {Frontiers in digital health}, volume = {4}, number = {}, pages = {842301}, pmid = {35899034}, issn = {2673-253X}, abstract = {Quantifying neurological disorders from voice is a rapidly growing field of research and holds promise for unobtrusive and large-scale disorder monitoring. The data recording setup and data analysis pipelines are both crucial aspects to effectively obtain relevant information from participants. Therefore, we performed a systematic review to provide a high-level overview of practices across various neurological disorders and highlight emerging trends. PRISMA-based literature searches were conducted through PubMed, Web of Science, and IEEE Xplore to identify publications in which original (i.e., newly recorded) datasets were collected. Disorders of interest were psychiatric as well as neurodegenerative disorders, such as bipolar disorder, depression, and stress, as well as amyotrophic lateral sclerosis amyotrophic lateral sclerosis, Alzheimer's, and Parkinson's disease, and speech impairments (aphasia, dysarthria, and dysphonia). Of the 43 retrieved studies, Parkinson's disease is represented most prominently with 19 discovered datasets. Free speech and read speech tasks are most commonly used across disorders. Besides popular feature extraction toolkits, many studies utilise custom-built feature sets. Correlations of acoustic features with psychiatric and neurodegenerative disorders are presented. In terms of analysis, statistical analysis for significance of individual features is commonly used, as well as predictive modeling approaches, especially with support vector machines and a small number of artificial neural networks. An emerging trend and recommendation for future studies is to collect data in everyday life to facilitate longitudinal data collection and to capture the behavior of participants more naturally. Another emerging trend is to record additional modalities to voice, which can potentially increase analytical performance.}, }
@article {pmid35898325, year = {2022}, author = {Zhu, Y and Xu, Y and Xuan, R and Huang, J and István, B and Fekete, G and Gu, Y}, title = {Mixed Comparison of Different Exercise Interventions for Function, Respiratory, Fatigue, and Quality of Life in Adults With Amyotrophic Lateral Sclerosis: Systematic Review and Network Meta-Analysis.}, journal = {Frontiers in aging neuroscience}, volume = {14}, number = {}, pages = {919059}, pmid = {35898325}, issn = {1663-4365}, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease whose primary hallmark is the progressive degeneration of motor neurons in the brainstem, spinal cord, and cerebral cortex that leads to weakness, spasticity, fatigue, skeletal muscle atrophy, paralysis, and even death. Exercise, as a non-pharmacological tool, may generally improve muscle strength, cardiovascular function, and quality of life. However, there are conflicting reports about the effect of exercise training in adults with ALS.
AIMS: This systematic review and network meta-analysis aim to conduct a mixed comparison of different exercise interventions for function, respiratory, fatigue, and quality of life in adults with ALS.
METHODS: Randomized controlled trials with ALS participants were screened and included from the databases of PubMed, Medline, and Web of Science. Physical exercise interventions were reclassified into aerobic exercise, resistance training, passive exercise, expiratory muscle exercise, and standard rehabilitation. Patient-reported outcome measures would be reclassified from perspectives of function, respiratory, fatigue, and quality of life. The effect size would be transferred into the percentage change of the total score.
RESULT: There were 10 studies included, with the agreement between authors reaching a kappa-value of 0.73. The network meta-analysis, which was conducted under the consistency model, identified that a combined program of aerobic exercise, resistance exercise, and standard rehabilitation showed the highest potential to improve quality of life (0.64 to be the best) and reduce the fatigue (0.39 to be the best) for ALS patients, while exercise program of aerobic and resistance training showed the highest potential (0.51 to be the best) to improve ALS patients' physical function. The effect of exercise on the respiratory was still unclear.
CONCLUSION: A multi-modal exercise and rehabilitation program would be more beneficial to ALS patients. However, the safety and guide for practice remain unclear, and further high-quality randomized controlled trials (RCTs) with a larger sample are still needed.
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021253442, CRD42021253442.}, }
@article {pmid35861443, year = {2022}, author = {Chapman, C and Bayes, S and Sim, M}, title = {Communication surrounding initiation and withdrawal of non-invasive ventilation in adults with motor neurone disease.}, journal = {International journal of palliative nursing}, volume = {28}, number = {7}, pages = {298-306}, doi = {10.12968/ijpn.2022.28.7.298}, pmid = {35861443}, issn = {2052-286X}, mesh = {Adult ; Communication ; Humans ; *Motor Neuron Disease ; *Noninvasive Ventilation ; Palliative Care ; }, abstract = {BACKGROUND: Motor neurone disease causes respiratory weakness that can lead to death. While non-invasive ventilation relieves symptoms, there are complex issues to consider prior to commencement.
AIM: To identify what is known and understood about the clinician communication of non-invasive ventilation by people with motor neurone disease.
METHOD: The Joanna Briggs Institute approach to systematic reviews was followed for literature retrieval and selection.
DATA SOURCES: Research literature published between 1990-2019 in English from the Medline, CINAHL, ProQuest Research Library and the Cochrane Library of Systematic Reviews databases were used.
RESULTS: A total of two themes emerged: communication challenges doctors face when discussing non-invasive ventilation withdrawal, and the importance of well-timed, effective communication by clinicians-specifically the influence clinicians have on family decision-making.
CONCLUSIONS: Guidance on communications around palliative care, non-invasive ventilation introduction and withdrawal exist, however implementation is often not straightforward. Research into the communication surrounding non-invasive ventilation from those living with motor neuron disease, their families and clinicians is required to inform guideline implementation and practice.}, }
@article {pmid35754054, year = {2022}, author = {Su, WM and Gu, XJ and Duan, QQ and Jiang, Z and Gao, X and Shang, HF and Chen, YP}, title = {Genetic factors for survival in amyotrophic lateral sclerosis: an integrated approach combining a systematic review, pairwise and network meta-analysis.}, journal = {BMC medicine}, volume = {20}, number = {1}, pages = {209}, pmid = {35754054}, issn = {1741-7015}, mesh = {Adaptor Proteins, Signal Transducing/genetics ; Alleles ; *Amyotrophic Lateral Sclerosis/genetics ; Autophagy-Related Proteins/genetics ; Genotype ; Humans ; Network Meta-Analysis ; }, abstract = {BACKGROUND: The time of survival in patients with amyotrophic lateral sclerosis (ALS) varies greatly, and the genetic factors that contribute to the survival of ALS are not well studied. There is a lack of a comprehensive study to elucidate the role of genetic factors in the survival of ALS.
METHODS: The published studies were systematically searched and obtained from PubMed, EMBASE, and the Cochrane Library without any language restrictions from inception to Oct 27, 2021. A network meta-analysis for ALS causative/risk genes and a systematic review and pairwise meta-analysis for other genetic modifiers were conducted. The PROSPERO registration number: CRD42022311646.
RESULTS: A total of 29,764 potentially relevant references were identified, and 71 papers were eligible for analysis based on pre-decided criteria, including 35 articles in network meta-analysis for 9 ALS causative/risk genes, 17 articles in pairwise meta-analysis for four genetic modifiers, and 19 articles described in the systematic review. Variants in three genes, including ATXN2 (HR: 3.6), C9orf72 (HR: 1.6), and FUS (HR:1.8), were associated with short survival of ALS, but such association was not identified in SOD1, TARDBP, TBK1, NEK1, UBQLN2, and CCNF. In addition, UNC13A rs12608932 CC genotype and ZNF521B rs2275294 C allele also caused a shorter survival of ALS; however, APOE ε4 allele and KIFAP3 rs1541160 did not be found to have any effect on the survival of ALS.
CONCLUSIONS: Our study summarized and contrasted evidence for prognostic genetic factors in ALS and would help to understand ALS pathogenesis and guide clinical trials and drug development.}, }
@article {pmid35619278, year = {2023}, author = {Prieto-Oliveira, P}, title = {HERVs Role in the Pathogenesis, Diagnosis or Prognosis of Aging Diseases: A Systematic Review.}, journal = {Current molecular medicine}, volume = {23}, number = {7}, pages = {678-687}, doi = {10.2174/1566524022666220525144135}, pmid = {35619278}, issn = {1875-5666}, mesh = {Male ; Female ; Pregnancy ; Humans ; *Endogenous Retroviruses ; Biomarkers ; Placenta ; *Prostatic Neoplasms/genetics ; Aging/genetics ; }, abstract = {INTRODUCTION: HERVs are human endogenous retroviruses, which represent about 8% of the human genome, and have various physiological functions, especially in pregnancy, embryo development and placenta formation. However, their involvement in diseases is not well defined. Some studies have observed changes in HERV expression according to age.
OBJECTIVE: Therefore, the aim of this systematic review was to analyze their role in pathogenesis and usage as diagnosis or prognosis biomarkers in aging disorders.
METHODS: In this study, a search on the Pubmed interface was performed for papers published from January 1953 to June 1[st], 2021.
RESULTS: 45 articles have been included, which matched the eligibility criteria and evaluated the following diseases: breast cancer, prostate cancer, amyotrophic lateral sclerosis (ALS), osteoarthritis, Alzheimer's disease, immuno-senescence, cognitive impairment, cataract, glaucoma and hypertension.
CONCLUSION: In conclusion, the results suggested that HERVs play a role in the pathogenesis and can be used as biomarkers for the diagnosis or prognosis of aging disorders.}, }
@article {pmid35616250, year = {2023}, author = {Nona, RJ and Greer, JM and Henderson, RD and McCombe, PA}, title = {HLA and amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {24}, number = {1-2}, pages = {24-32}, doi = {10.1080/21678421.2022.2078665}, pmid = {35616250}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Genome-Wide Association Study ; *Neurodegenerative Diseases ; HLA Antigens ; Motor Neurons ; }, abstract = {Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with loss of upper and lower motor neurones. It leads to death by respiratory failure and has a typical prognosis of 2-3 years. The immune system has been shown to play a role in the pathophysiology of ALS. Some of the most important immune genes are within the human leukocyte antigen (HLA) region, and a recent genome-wide association study (GWAS) has identified a risk allele for ALS within the HLA region. Older studies have also suggested an HLA association with ALS, with certain HLA alleles showing differing expression between patients and controls. This systematic review and meta-analysis examines the previous studies performed in this field.Methods: We used established publication search engines. Findings were excluded if they did not meet the selection criteria. We then undertook statistical meta-analysis on the eligible papers, using a fixed effects model.Results: There were eight eligible papers. There were three statistically significant meta-analysis findings, although these would not be significant after correction for multiple comparisons. The frequencies of HLA-A9 and HLA-DR4 genotypes were lower in ALS subjects than controls, and HLA-B35 was higher in ALS subjects.Discussion: This systematic review and meta-analysis do not confirm all the previously reported associations of HLA with ALS, but shows three alleles of interest. However, there are limitations to the studies, which include the use of older serotyping methodology and the small numbers of subjects. Given the recent GWAS association with HLA, further modern HLA studies are warranted.}, }
@article {pmid35614165, year = {2022}, author = {Gao, J and Dharmadasa, T and Malaspina, A and Shaw, PJ and Talbot, K and Turner, MR and Thompson, AG}, title = {Creatine kinase and prognosis in amyotrophic lateral sclerosis: a literature review and multi-centre cohort analysis.}, journal = {Journal of neurology}, volume = {269}, number = {10}, pages = {5395-5404}, pmid = {35614165}, issn = {1432-1459}, support = {MR/T006927/1/MNDA_/Motor Neurone Disease Association/United Kingdom ; TURNER/OCT18/989-797/MNDA_/Motor Neurone Disease Association/United Kingdom ; TURNER/OCT15/972-797/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/S004920/1/MRC_/Medical Research Council/United Kingdom ; MALASPINA/APR13/817-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/T006927/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Amyotrophic Lateral Sclerosis/complications ; Cohort Studies ; Creatine Kinase ; Female ; Humans ; Male ; *Neurodegenerative Diseases/complications ; Prognosis ; Prospective Studies ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a prognostically heterogeneous neurodegenerative disease. Blood creatine kinase (CK) level has been inconsistently reported as a prognostic biomarker and raised levels in some ALS patients have been presumed to reflect muscle wasting, which is also variable.
METHODS: MEDLINE was systematically searched for papers related to CK in ALS and the relevant studies were reviewed. Using data from 222 ALS patients in a multi-centre, prospective, longitudinal cohort, survival analyses using Kaplan-Meier and Cox proportional hazards models were undertaken in relation to CK and other prognostic factors.
RESULTS: Twenty-five studies investigating CK in ALS were identified, of which 10 specifically studied the link between CK and survival. Five studies observed no association, four found that higher CK levels were associated with longer survival and one, the opposite. In our cohort (n = 222), 39% of patients had a CK level above the laboratory reference range. Levels were higher in males compared to females (p < 0.001), in patients with limb versus bulbar onset of symptoms (p < 0.001) and in patients with higher lower motor neuron burden (p < 0.001). There was no significant trend in longitudinal CK values. Although a higher standardised log (CK) at first visit was associated with longer survival in univariate analysis (hazard ratio 0.75, p = 0.003), there was no significant association after adjusting for other prognostic covariates.
CONCLUSION: While raised CK levels in ALS do reflect lower motor neuron denervation to a large extent, they are not independently associated with survival when measured in the symptomatic phase of the disease.}, }
@article {pmid35472653, year = {2022}, author = {Gerges, ANH and Hordacre, B and Pietro, FD and Moseley, GL and Berryman, C}, title = {Do Adults with Stroke have Altered Interhemispheric Inhibition? A Systematic Review with Meta-Analysis.}, journal = {Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association}, volume = {31}, number = {7}, pages = {106494}, doi = {10.1016/j.jstrokecerebrovasdis.2022.106494}, pmid = {35472653}, issn = {1532-8511}, mesh = {Adult ; *Cerebral Palsy ; Evoked Potentials, Motor/physiology ; Functional Laterality/physiology ; Humans ; *Motor Cortex ; *Stroke/diagnosis/therapy ; *Stroke Rehabilitation/methods ; Transcranial Magnetic Stimulation ; }, abstract = {OBJECTIVE: Interhemispheric inhibition is an important cortical mechanism to support motor control. Altered interhemispheric inhibition has been the target of neuromodulation interventions. This systematic review investigated the evidence for altered interhemispheric inhibition in adults with unilateral neurological conditions: stroke, amyotrophic lateral sclerosis, cerebral palsy, complex regional pain syndrome, traumatic brain injury, and cerebral palsy METHODS: We pre-registered the protocol and followed PRISMA guidelines. Five databases were systematically searched to identify studies reporting interhemispheric inhibition measures in unilateral neurological conditions and healthy controls. Data were grouped according to the measure (ipsilateral silent period and dual-coil), stimulated hemisphere, and stage of the condition (subacute and chronic).
RESULTS: 1372 studies were identified, of which 14 were included (n = 226 adults with stroke and 161 age-matched controls). Ipsilateral silent period-duration was longer in people with stroke than in controls (stimulation of dominant hemisphere) regardless of stroke stage. Motor evoked potential was less suppressed in people with sub-acute stroke (stimulation of the unaffected hemisphere) than controls (stimulation of dominant hemisphere) and this reversed in chronic stroke.
CONCLUSION: Detection of altered interhemispheric inhibition appears to be dependent on the measure of interhemispheric inhibition and the stage of recovery.
SIGNIFICANCE: Rebalancing interhemispheric inhibition using neuromodulation is considered a promising line of treatment for stroke rehabilitation. Our results did not find compelling evidence to support consistent alterations in interhemispheric inhibition in adults with stroke.}, }
@article {pmid35431812, year = {2022}, author = {Mirian, A and Moszczynski, A and Soleimani, S and Aubert, I and Zinman, L and Abrahao, A}, title = {Breached Barriers: A Scoping Review of Blood-Central Nervous System Barrier Pathology in Amyotrophic Lateral Sclerosis.}, journal = {Frontiers in cellular neuroscience}, volume = {16}, number = {}, pages = {851563}, pmid = {35431812}, issn = {1662-5102}, abstract = {INTRODUCTION: Recent studies have implicated changes in the blood-central nervous system barriers (BCNSB) in amyotrophic lateral sclerosis (ALS). The objective of this scoping review is to synthesize the current evidence for BCNSB structure and functional abnormalities in ALS studies and propose how BCNSB pathology may impact therapeutic development.
METHODS: A literature search was conducted using Ovid Medline, EMBASE, and Web of Science, from inception to November 2021 and limited to entries in English language. Simplified search strategy included the terms ALS/motor neuron disease and [BCNSB or blood-brain barrier (BBB) or blood-spinal cord barrier (BSCB)]. Henceforth, BCNSB is used as a term that is inclusive of the BBB and BSCB. Four independent reviewers conducted a title and abstract screening, hand-searched the reference lists of review papers, and performed a full text review of eligible studies. Included studies were original peer-reviewed full text publications, evaluating the structure and function of the BCNSB in preclinical models of ALS, clinical ALS, or postmortem human ALS tissue. There was no restriction on study design. The four reviewers independently extracted the data.
RESULTS: The search retrieved 2,221 non-duplicated articles and 48 original studies were included in the synthesis. There was evidence that the integrity of the BCNSB is disrupted throughout the course of the disease in rodent models, beginning prior to symptom onset and detectable neurodegeneration. Increased permeability, pharmacoresistance with upregulated efflux transporters, and morphological changes in the supporting cells of the BCNSB, including pericytes, astrocytes, and endothelial cells were observed in animal models. BCNSB abnormalities were also demonstrated in postmortem studies of ALS patients. Therapeutic interventions targeting BCNSB dysfunction were associated with improved motor neuron survival in animal models of ALS.
CONCLUSION: BCNSB structural and functional abnormalities are likely implicated in ALS pathophysiology and may occur upstream to neurodegeneration. Promising therapeutic strategies targeting BCNSB dysfunction have been tested in animals and can be translated into ALS clinical trials.}, }
@article {pmid35378353, year = {2022}, author = {Georges, M and Perez, T and Rabec, C and Jacquin, L and Finet-Monnier, A and Ramos, C and Patout, M and Attali, V and Amador, M and Gonzalez-Bermejo, J and Salachas, F and Morelot-Panzini, C}, title = {Proposals from a French expert panel for respiratory care in ALS patients.}, journal = {Respiratory medicine and research}, volume = {81}, number = {}, pages = {100901}, doi = {10.1016/j.resmer.2022.100901}, pmid = {35378353}, issn = {2590-0412}, mesh = {*Amyotrophic Lateral Sclerosis/complications/epidemiology/therapy ; Cough ; Humans ; *Neurodegenerative Diseases/complications ; Quality of Life ; *Respiratory Insufficiency/etiology/therapy ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive diaphragm weakness and deteriorating lung function. Bulbar involvement and cough weakness contribute to respiratory morbidity and mortality. ALS-related respiratory failure significantly affects quality of life and is the leading cause of death. Non-invasive ventilation (NIV), which is the main recognized treatment for alleviating the symptoms of respiratory failure, prolongs survival and improves quality of life. However, the optimal timing for the initiation of NIV is still a matter of debate. NIV is a complex intervention. Multiple factors influence the efficacy of NIV and patient adherence. The aim of this work was to develop practical evidence-based advices to standardize the respiratory care of ALS patients in French tertiary care centres.
METHODS: For each proposal, a French expert panel systematically searched an indexed bibliography and prepared a written literature review that was then shared and discussed. A combined draft was prepared by the chairman for further discussion. All of the proposals were unanimously approved by the expert panel.
RESULTS: The French expert panel updated the criteria for initiating NIV in ALS patients. The most recent criteria were established in 2005. Practical advice for NIV initiation were included and the value of each tool available for NIV monitoring was reviewed. A strategy to optimize NIV parameters was suggested. Revisions were also suggested for the use of mechanically assisted cough devices in ALS patients.
CONCLUSION: Our French expert panel proposes an evidence-based review to update the respiratory care recommendations for ALS patients in daily practice.}, }
@article {pmid35323084, year = {2023}, author = {Fitzgerald, S and Gracey, F and Trigg, E and Broomfield, N}, title = {Predictors and correlates of emotionalism across acquired and progressive neurological conditions: A systematic review.}, journal = {Neuropsychological rehabilitation}, volume = {33}, number = {5}, pages = {945-987}, doi = {10.1080/09602011.2022.2052326}, pmid = {35323084}, issn = {1464-0694}, mesh = {Female ; Humans ; Cross-Sectional Studies ; *Alzheimer Disease ; Emotions ; *Stroke/complications/psychology ; *Cognitive Dysfunction ; }, abstract = {Emotionalism can develop following a range of neurological disorders; however the aetiology of emotionalism is still unclear. To identify anatomical, neuropsychological and psychological predictors and correlates of emotionalism across neurological disorders: stroke, Parkinson's disease, multiple sclerosis, traumatic brain injury, Alzheimer's disease, vascular dementia and amyotrophic lateral sclerosis. To explore if these predictors and correlates of emotionalism differ across neurological disorders. A comprehensive systematic search was completed of four databases: MEDLINE, CINAHL Complete, PsycINFO and EMBASE. Methodological quality was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies and each study was graded according to the level of evidence using the Scottish Intercollegiate Guidelines Network. Fifty papers (participants N = 1922) were included. 25 studies were rated as "Fair," 21 "Good" and 4 "Poor." The review identified predictors and correlates found in several neurological disorder such as bulbar networks, serotonergic pathways, genetics and female gender. Multiple studies across diseases (stroke, MS, ALS) indicate emotionalism is associated with cognitive impairment, especially frontal deficits. Due to the disproportionate number of studies identified across neurological disorders, it is difficult to draw definitive answers. Further research is required across neurological disorders to explore similarities and differences in anatomical, neuropsychological and psychological predictors and correlates.}, }
@article {pmid35321093, year = {2022}, author = {Tessarollo, L and Yanpallewar, S}, title = {TrkB Truncated Isoform Receptors as Transducers and Determinants of BDNF Functions.}, journal = {Frontiers in neuroscience}, volume = {16}, number = {}, pages = {847572}, pmid = {35321093}, issn = {1662-4548}, abstract = {Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family of secreted growth factors and binds with high affinity to the TrkB tyrosine kinase receptors. BDNF is a critical player in the development of the central (CNS) and peripheral (PNS) nervous system of vertebrates and its strong pro-survival function on neurons has attracted great interest as a potential therapeutic target for the management of neurodegenerative disorders such as Amyotrophic Lateral Sclerosis (ALS), Huntington, Parkinson's and Alzheimer's disease. The TrkB gene, in addition to the full-length receptor, encodes a number of isoforms, including some lacking the catalytic tyrosine kinase domain. Importantly, one of these truncated isoforms, namely TrkB.T1, is the most widely expressed TrkB receptor in the adult suggesting an important role in the regulation of BDNF signaling. Although some progress has been made, the mechanism of TrkB.T1 function is still largely unknown. Here we critically review the current knowledge on TrkB.T1 distribution and functions that may be helpful to our understanding of how it regulates and participates in BDNF signaling in normal physiological and pathological conditions.}, }
@article {pmid35313253, year = {2022}, author = {Ahmed, N and Baker, MR and Bashford, J}, title = {The landscape of neurophysiological outcome measures in ALS interventional trials: A systematic review.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {137}, number = {}, pages = {132-141}, pmid = {35313253}, issn = {1872-8952}, support = {EP/V050419/1/MRC_/Medical Research Council/United Kingdom ; COV-LT-0022/DH_/Department of Health/United Kingdom ; MC/PC/13071/MRC_/Medical Research Council/United Kingdom ; BASHFORD/JUN16/947-795/MNDA_/Motor Neurone Disease Association/United Kingdom ; MC_PC_14101/MRC_/Medical Research Council/United Kingdom ; MC_PC_13071/MRC_/Medical Research Council/United Kingdom ; MC/PC/14101/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/therapy ; Electromyography ; Humans ; Neurophysiology/methods ; Outcome Assessment, Health Care ; Transcranial Magnetic Stimulation ; }, abstract = {OBJECTIVE: We collated all interventional clinical trials in amyotrophic lateral sclerosis (ALS), which utilised at least one neurophysiological technique as a primary or secondary outcome measure. By identifying the strengths and limitations of these studies, we aim to guide study design in future trials.
METHODS: We conducted and reported this systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eight databases were searched from inception. In total, 703 studies were retrieved for screening and eligibility assessment.
RESULTS: Dating back to 1986, 32 eligible interventional clinical trials were identified, recruiting a median of 30 patients per completed trial. The most widely employed neurophysiological techniques were electromyography, motor unit number estimation (including motor unit number index), neurophysiological index and transcranial magnetic stimulation (including resting motor threshold and short-interval intracortical inhibition). Almost 40% of trials reported a positive outcome with respect to at least one neurophysiological measure. The interventions targeted either ion channels, immune mechanisms or neuronal metabolic pathways.
CONCLUSIONS: Neurophysiology offers many promising biomarkers that can be utilised as outcome measures in interventional clinical trials in ALS. When selecting the most appropriate technique, key considerations include methodological standardisation, target engagement and logistical burden.
SIGNIFICANCE: Future trial design in ALS would benefit from a standardised, updated and easily accessible repository of neurophysiological outcome measures.}, }
@article {pmid35239007, year = {2022}, author = {Li, J and Liu, Q and Sun, X and Zhang, K and Liu, S and Wang, Z and Yang, X and Liu, M and Cui, L and Zhang, X}, title = {Genotype-phenotype association of TARDBP mutations in Chinese patients with amyotrophic lateral sclerosis: a single-center study and systematic review of published literature.}, journal = {Journal of neurology}, volume = {269}, number = {8}, pages = {4204-4212}, pmid = {35239007}, issn = {1432-1459}, support = {XDB39040100//the Strategic Priority Research Program of the Chinese Academy of Sciences/ ; 2021-1-I2M-034//the CAMS Innovation Fund for Medical Sciences (CIFMS) grant/ ; 2016-I2M-1-002//the CAMS Innovation Fund for Medical Sciences (CIFMS) grant/ ; 2021-1-I2M-018//the CAMS Innovation Fund for Medical Sciences (CIFMS) grant/ ; 81971293//the National Natural Science Foundation of China/ ; 81788101//the National Natural Science Foundation of China/ ; 2016YFC0905100//the National Key Research and Development Program of China/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/genetics ; Asian People/genetics ; *DNA-Binding Proteins/genetics ; Genetic Association Studies ; Humans ; Mutation ; }, abstract = {BACKGROUND: This study aims to determine the genetic and clinical features of TARDBP-mutated patients in our cohort of Chinese patients with amyotrophic lateral sclerosis (ALS) combined with data in the literature.
METHODS: We performed TARDBP mutation screening in 1258 Chinese ALS patients, including 1204 sporadic ALS (sALS) and 54 familial ALS (fALS) patients. A systematic literature review was conducted by searching TARDBP-mutated patients from China in the online databases.
RESULTS: In our cohort, the mutant frequency of TARDBP variants was 0.3% (4/1258), with two recurrent variants (p.G294V, p.G298V) and one novel variant (p.S332G) identified. Combining with data in the literature review, the TARDBP-mutant frequency in the Chinese population was 1.4% (83/5998), with 0.8% (46/5470) in sALS and 7.0% (37/528) in fALS. Most patients had limb onset (63.0%), with an average life expectancy of 4.3 years (range 0.5-13). Disease durations significantly differed (p = 0.002), with p.M337V showing the longest duration (80 months) and p.N378D showing the shortest duration (16.7 months).
CONCLUSION: Our study found that TARDBP mutation was not rare in Chinese fALS patients. Different TARDBP mutations were associated with specific features in phenotypes.}, }
@article {pmid35163214, year = {2022}, author = {Rasheed, M and Asghar, R and Firdoos, S and Ahmad, N and Nazir, A and Ullah, KM and Li, N and Zhuang, F and Chen, Z and Deng, Y}, title = {A Systematic Review of Circulatory microRNAs in Major Depressive Disorder: Potential Biomarkers for Disease Prognosis.}, journal = {International journal of molecular sciences}, volume = {23}, number = {3}, pages = {}, pmid = {35163214}, issn = {1422-0067}, support = {Grant # 81601114, U1532264, 81801073//National Natural Science Foundation of China/ ; }, mesh = {Biomarkers/blood ; Circulating MicroRNA/analysis/*genetics ; Depression/genetics ; Depressive Disorder, Major/*genetics/therapy ; Gene Expression/genetics ; Gene Expression Profiling/methods ; Gene Ontology ; Humans ; MicroRNAs/genetics/metabolism ; Prognosis ; Transcriptome/genetics ; }, abstract = {Major depressive disorder (MDD) is a neuropsychiatric disorder, which remains challenging to diagnose and manage due to its complex endophenotype. In this aspect, circulatory microRNAs (cimiRNAs) offer great potential as biomarkers and may provide new insights for MDD diagnosis. Therefore, we systemically reviewed the literature to explore various cimiRNAs contributing to MDD diagnosis and underlying molecular pathways. A comprehensive literature survey was conducted, employing four databases from 2012 to January 2021. Out of 1004 records, 157 reports were accessed for eligibility criteria, and 32 reports meeting our inclusion criteria were considered for in-silico analysis. This study identified 99 dysregulated cimiRNAs in MDD patients, out of which 20 cimiRNAs found in multiple reports were selected for in-silico analysis. KEGG pathway analysis indicated activation of ALS, MAPK, p53, and P13K-Akt signaling pathways, while gene ontology analysis demonstrated that most protein targets were associated with transcription. In addition, chromosomal location analysis showed clustering of dysregulated cimiRNAs at proximity 3p22-p21, 9q22.32, and 17q11.2, proposing their coregulation with specific transcription factors primarily involved in MDD physiology. Further analysis of transcription factor sites revealed the existence of HIF-1, REST, and TAL1 in most cimiRNAs. These transcription factors are proposed to target genes linked with MDD, hypothesizing that first-wave cimiRNA dysregulation may trigger the second wave of transcription-wide changes, altering the protein expressions of MDD-affected cells. Overall, this systematic review presented a list of dysregulated cimiRNAs in MDD, notably miR-24-3p, let 7a-5p, miR-26a-5p, miR135a, miR-425-3p, miR-132, miR-124 and miR-16-5p as the most prominent cimiRNAs. However, various constraints did not permit us to make firm conclusions on the clinical significance of these cimiRNAs, suggesting the need for more research on single blood compartment to identify the biomarker potential of consistently dysregulated cimiRNAs in MDD, as well as the therapeutic implications of these in-silico insights.}, }
@article {pmid35082326, year = {2022}, author = {Daneshafrooz, N and Joghataei, MT and Mehdizadeh, M and Alavi, A and Barati, M and Panahi, B and Teimourian, S and Zamani, B}, title = {Identification of let-7f and miR-338 as plasma-based biomarkers for sporadic amyotrophic lateral sclerosis using meta-analysis and empirical validation.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {1373}, pmid = {35082326}, issn = {2045-2322}, mesh = {Algorithms ; Amyotrophic Lateral Sclerosis/*blood/*genetics/metabolism ; Biomarkers/blood ; Circulating MicroRNA/*blood/*genetics ; Down-Regulation/genetics ; Empirical Research ; Gene Expression Profiling/methods ; High-Throughput Nucleotide Sequencing/methods ; Humans ; MicroRNAs/*blood/*genetics ; Protein Interaction Maps/genetics ; ROC Curve ; Real-Time Polymerase Chain Reaction/methods ; Reverse Transcriptase Polymerase Chain Reaction/methods ; Transcriptome/*genetics ; Up-Regulation/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease that in most cases occurs sporadic (sALS). The disease is not curable, and its pathogenesis mechanisms are not well understood yet. Given the intricacy of underlying molecular interactions and heterogeneity of ALS, the discovery of molecules contributing to disease onset and progression will open a new avenue for advancement in early diagnosis and therapeutic intervention. Here we conducted a meta-analysis of 12 circulating miRNA profiling studies using the robust rank aggregation (RRA) method, followed by enrichment analysis and experimental verification. We identified miR-451a and let-7f-5p as meta-signature miRNAs whose targets are involved in critical pathogenic pathways underlying ALS, including 'FoxO signaling pathway', 'MAPK signaling pathway', and 'apoptosis'. A systematic review of 7 circulating gene profiling studies elucidated that 241 genes up-regulated in sALS circulation with concomitant being targets of the meta-signature miRNAs. Protein-protein interaction (PPI) network analysis of the candidate targets using MCODE algorithm revealed the main subcluster is involved in multiple cascades eventually leads apoptosis, including 'positive regulation of neuron apoptosis. Besides, we validated the meta-analysis results using RT-qPCR. Indeed, relative expression analysis verified let-7f-5p and miR-338-3p as significantly down-regulated and up-regulated biomarkers in the plasma of sALS patients, respectively. Receiver operating characteristic (ROC) analysis also highlighted the let-7f-5p and miR-338-3p potential as robustness plasma biomarkers for diagnosis and potential therapeutic targets of sALS disease.}, }
@article {pmid34938264, year = {2021}, author = {Aljabri, A and Halawani, A and Bin Lajdam, G and Labban, S and Alshehri, S and Felemban, R}, title = {The Safety and Efficacy of Stem Cell Therapy as an Emerging Therapy for ALS: A Systematic Review of Controlled Clinical Trials.}, journal = {Frontiers in neurology}, volume = {12}, number = {}, pages = {783122}, pmid = {34938264}, issn = {1664-2295}, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a heterogeneous course that ultimately leads to death. Currently, there is no cure, and new treatments that can slow the progression of the disease are needed. Stem cell (SC) transplantation is an emerging therapy that has shown a lot of potential in recent clinical trials. This review is aimed to examine the results of various clinical trials on this topic, thus assessing the safety and efficacy of SC transplantation as a potential treatment for ALS. We identified 748 studies in our search, of which 134 full-text studies were assessed for eligibility. Six studies met the inclusion criteria and were included in this review. Although some of the included studies showed the positive effect of SC transplantation, other studies found that there was no significant difference compared to the control group. We observed more positive effects with bone marrow mesenchymal stem cells (BM-MSC) treatments than Granulocyte colony-stimulating factor (G-CSF) ones. However, other factors, such as route of administration, number of doses, and number of cells per dose, could also play a role in this discrepancy. Based on this information, we conclude that more properly conducted clinical trials are needed to appreciate the benefit of this treatment.}, }
@article {pmid34912191, year = {2021}, author = {Poulin-Brière, A and Rezaei, E and Pozzi, S}, title = {Antibody-Based Therapeutic Interventions for Amyotrophic Lateral Sclerosis: A Systematic Literature Review.}, journal = {Frontiers in neuroscience}, volume = {15}, number = {}, pages = {790114}, pmid = {34912191}, issn = {1662-4548}, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a mid-life onset neurodegenerative disease that manifests its symptomatology with motor impairments and cognitive deficits overlapping with Frontotemporal Lobar Degeneration (FTLD). The etiology of ALS remains elusive, with various mechanisms and cellular targets implicated, and no treatment can reverse or stop the progression of the pathology. Therapeutic interventions based on passive immunization are gaining attention for neurodegenerative diseases, and FDA recently approved the first antibody-based approach for Alzheimer's disease. The present systematic review of the literature aims to highlight the efforts made over the past years at developing antibody-based strategies to cure ALS. Thirty-one original research papers have been selected where the therapeutic efficacy of antibodies were investigated and described in patients and animal models of ALS. Antibody-based interventions analyzed, target both extracellular molecules implicated in the pathology and intracellular pathogenic proteins known to drive the disease, such as SOD1, TDP-43 or C9ORF72 repeats expansions. The potentials and limitations of these therapeutic interventions have been described and discussed in the present review.}, }
@article {pmid34906131, year = {2021}, author = {Larsson, SC and Burgess, S}, title = {Causal role of high body mass index in multiple chronic diseases: a systematic review and meta-analysis of Mendelian randomization studies.}, journal = {BMC medicine}, volume = {19}, number = {1}, pages = {320}, pmid = {34906131}, issn = {1741-7015}, support = {204623/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; RG/13/13/30194/BHF_/British Heart Foundation/United Kingdom ; MC_UU_00002/7/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; RG/18/13/33946/BHF_/British Heart Foundation/United Kingdom ; CH/12/2/29428/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {Adiposity ; Adult ; Body Mass Index ; *Diabetes Mellitus, Type 2/epidemiology/genetics ; Female ; Genome-Wide Association Study ; Humans ; Male ; Mendelian Randomization Analysis ; *Multiple Chronic Conditions ; Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: Obesity is a worldwide epidemic that has been associated with a plurality of diseases in observational studies. The aim of this study was to summarize the evidence from Mendelian randomization (MR) studies of the association between body mass index (BMI) and chronic diseases.
METHODS: PubMed and Embase were searched for MR studies on adult BMI in relation to major chronic diseases, including diabetes mellitus; diseases of the circulatory, respiratory, digestive, musculoskeletal, and nervous systems; and neoplasms. A meta-analysis was performed for each disease by using results from published MR studies and corresponding de novo analyses based on summary-level genetic data from the FinnGen consortium (n = 218,792 individuals).
RESULTS: In a meta-analysis of results from published MR studies and de novo analyses of the FinnGen consortium, genetically predicted higher BMI was associated with increased risk of type 2 diabetes mellitus, 14 circulatory disease outcomes, asthma, chronic obstructive pulmonary disease, five digestive system diseases, three musculoskeletal system diseases, and multiple sclerosis as well as cancers of the digestive system (six cancer sites), uterus, kidney, and bladder. In contrast, genetically predicted higher adult BMI was associated with a decreased risk of Dupuytren's disease, osteoporosis, and breast, prostate, and non-melanoma cancer, and not associated with Alzheimer's disease, amyotrophic lateral sclerosis, or Parkinson's disease.
CONCLUSIONS: The totality of the evidence from MR studies supports a causal role of excess adiposity in a plurality of chronic diseases. Hence, continued efforts to reduce the prevalence of overweight and obesity are a major public health goal.}, }
@article {pmid34871538, year = {2022}, author = {Wang, Q and Li, J and Liu, S and Fang, C and Chen, W}, title = {Efficacy and safety of over-the-scope clips for colorectal leaks and fistulas: a pooled analysis.}, journal = {Minimally invasive therapy & allied technologies : MITAT : official journal of the Society for Minimally Invasive Therapy}, volume = {31}, number = {6}, pages = {825-834}, doi = {10.1080/13645706.2021.2010218}, pmid = {34871538}, issn = {1365-2931}, mesh = {Anastomotic Leak/epidemiology/etiology/surgery ; *Colorectal Neoplasms ; Endoscopy, Gastrointestinal/adverse effects ; *Fistula/complications/surgery ; Humans ; Retrospective Studies ; Surgical Instruments ; Treatment Outcome ; }, abstract = {The development of laparoscopic technologies and continuous improvements in intracavitary anastomosis technology have significantly reduced the incidence of anastomotic leak (AL) following colorectal surgery. However, AL incidence can significantly increase the duration of patient hospitalization, patient medical expenses, and incidence of mortality. The recently developed over-the-scope clip (OTSC) system has been of increasing clinical interest owing to its ease of use, low complication rates, and high rates of technical and clinical success. The PubMed/Medline, EMBASE, and Cochrane PubMed Library were systematically searched for all studies of OTSC system-mediated closure of ALs and fistulas published from January 2010 to January 2021. Two reviewers independently identified relevant studies based on appropriate inclusion and exclusion criteria. A total of nine studies were included in the present analysis, incorporating 114 patients of whom 107 were treated with an OTSC system. The technical success rate for these patients was 84% (95%CI, 73.5-94.5%; I[2] 53%), and the clinical success rate was 74.3% (95%CI, 64.4-84.1%; I[2] 28%) as calculated via a pooled proportion analysis. Complications occurred in two patients. The endoscopic OTSC system is a safe and effective means of treating ALs and fistulas after colorectal surgery.}, }
@article {pmid34786907, year = {2022}, author = {Lazovic, M and Nikolic, D and Boyer, FC and Borg, K and Ceravolo, MG and Zampolini, M and Kiekens, C}, title = {Evidence-based position paper on Physical and Rehabilitation Medicine practice for people with amyotrophic lateral sclerosis.}, journal = {European journal of physical and rehabilitation medicine}, volume = {58}, number = {2}, pages = {271-279}, pmid = {34786907}, issn = {1973-9095}, mesh = {*Amyotrophic Lateral Sclerosis ; Europe ; Humans ; Physical Therapy Modalities ; *Physical and Rehabilitation Medicine ; Professional Practice ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease that affects both upper and lower motor neurons and is fatal in its course. This evidence-based position paper represents the official position of the UEMS PRM Section. The aim of the paper is to define the role of the physical and rehabilitation medicine (PRM) physician and PRM professional practice for people with ALS. A systematic review of the literature and a consensus procedure by means of a Delphi process have been performed involving the delegates of all European countries represented in the UEMS PRM Section. The systematic literature review is reported together with thirty-two recommendations resulting from the Delphi procedure. The responsibility of the PRM physician is functional assessment of persons with ALS and delivering the optimal and most effective PRM program of care. The rehabilitation program of patients with ALS should be delivered and monitored by the multiprofessional team, with the PRM physician as principal coordinator.}, }
@article {pmid34676348, year = {2021}, author = {Jugl, S and Okpeku, A and Costales, B and Morris, EJ and Alipour-Haris, G and Hincapie-Castillo, JM and Stetten, NE and Sajdeya, R and Keshwani, S and Joseph, V and Zhang, Y and Shen, Y and Adkins, L and Winterstein, AG and Goodin, A}, title = {A Mapping Literature Review of Medical Cannabis Clinical Outcomes and Quality of Evidence in Approved Conditions in the USA from 2016 to 2019.}, journal = {Medical cannabis and cannabinoids}, volume = {4}, number = {1}, pages = {21-42}, pmid = {34676348}, issn = {2504-3889}, abstract = {In 2017, a National Academies of Sciences, Engineering, and Medicine (NASEM) report comprehensively evaluated the body of evidence regarding cannabis health effects through the year 2016. The objectives of this study are to identify and map the most recently (2016-2019) published literature across approved conditions for medical cannabis and to evaluate the quality of identified recent systematic reviews, published following the NASEM report. Following the literature search from 5 databases and consultation with experts, 11 conditions were identified for evidence compilation and evaluation: amyotrophic lateral sclerosis, autism, cancer, chronic noncancer pain, Crohn's disease, epilepsy, glaucoma, human immunodeficiency virus/AIDS, multiple sclerosis (MS), Parkinson's disease, and posttraumatic stress disorder. A total of 198 studies were included after screening for condition-specific relevance and after imposing the following exclusion criteria: preclinical focus, non-English language, abstracts only, editorials/commentary, case studies/series, and non-U.S. study setting. Data extracted from studies included: study design type, outcome definition, intervention definition, sample size, study setting, and reported effect size. Few completed randomized controlled trials (RCTs) were identified. Studies classified as systematic reviews were graded using the Assessing the Methodological Quality of Systematic Reviews-2 tool to evaluate the quality of evidence. Few high-quality systematic reviews were available for most conditions, with the exceptions of MS (9 of 9 graded moderate/high quality; evidence for 2/9 indicating cannabis improved outcomes; evidence for 7/9 indicating cannabis inconclusive), epilepsy (3 of 4 graded moderate/high quality; 3 indicating cannabis improved outcomes; 1 indicating cannabis inconclusive), and chronic noncancer pain (12 of 13 graded moderate/high quality; evidence for 7/13 indicating cannabis improved outcomes; evidence from 6/7 indicating cannabis inconclusive). Among RCTs, we identified few studies of substantial rigor and quality to contribute to the evidence base. However, there are some conditions for which significant evidence suggests that select dosage forms and routes of administration likely have favorable risk-benefit ratios (i.e., epilepsy and chronic noncancer pain). The body of evidence for medical cannabis requires more rigorous evaluation before consideration as a treatment option for many conditions, and evidence necessary to inform policy and treatment guidelines is currently insufficient for many conditions.}, }
@article {pmid34528307, year = {2021}, author = {Mohseni, M and Sahebkar, A and Askari, G and Johnston, TP and Alikiaii, B and Bagherniya, M}, title = {The clinical use of curcumin on neurological disorders: An updated systematic review of clinical trials.}, journal = {Phytotherapy research : PTR}, volume = {35}, number = {12}, pages = {6862-6882}, doi = {10.1002/ptr.7273}, pmid = {34528307}, issn = {1099-1573}, support = {199234//Isfahan University of Medical Sciences/ ; }, mesh = {Curcuma ; *Curcumin/therapeutic use ; Dietary Supplements ; Humans ; Inflammation ; *Migraine Disorders ; }, abstract = {Neuroprotective effects of curcumin have been shown in previous studies. This updated systematic review of clinical trials aimed to investigate the effect of curcumin on neurological disorders. Databases including PubMed, Scopus, Web of Science, and Google Scholar were systematically searched to identify clinical trials investigating the effects of curcumin/turmeric supplements alone, or in combination with other ingredients, on neurological diseases. Nineteen studies comprising 1,130 patients met the inclusion criteria. Generally, intervention and study outcomes were heterogeneous. In most of the studies, curcumin had a favorable effect on oxidative stress and inflammation. However, with the exception of AD, curcumin supplementation either alone, or in combination with other ingredients, had beneficial effects on clinical outcomes for the other aforementioned neurodegenerative diseases. For example, the frequency, severity, and duration of migraine attacks, scores on the revised ALS functional rating scale, and the occurrence of motor complications in PD were all significantly improved with curcumin supplementation either alone or in combination with other ingredients. However, in three studies, several adverse side effects (mostly gastrointestinal in nature) were reported. Curcumin supplementation may have favorable effects on inflammatory status and clinical outcomes of patients with neurological disease, although the results were not consistent.}, }
@article {pmid34421792, year = {2021}, author = {Genuis, SK and Luth, W and Campbell, S and Bubela, T and Johnston, WS}, title = {Communication About End of Life for Patients Living With Amyotrophic Lateral Sclerosis: A Scoping Review of the Empirical Evidence.}, journal = {Frontiers in neurology}, volume = {12}, number = {}, pages = {683197}, pmid = {34421792}, issn = {1664-2295}, abstract = {Background: Communication about end of life, including advance care planning, life-sustaining therapies, palliative care, and end-of-life options, is critical for the clinical management of amyotrophic lateral sclerosis patients. The empirical evidence base for this communication has not been systematically examined. Objective: To support evidence-based communication guidance by (1) analyzing the scope and nature of research on health communication about end of life for amyotrophic lateral sclerosis; and (2) summarizing resultant recommendations. Methods: A scoping review of empirical literature was conducted following recommended practices. Fifteen health-related and three legal databases were searched; 296 articles were screened for inclusion/exclusion criteria; and quantitative data extraction and analysis was conducted on 211 articles with qualitative analysis on a subset of 110 articles that focused primarily on health communication. Analyses summarized article characteristics, themes, and recommendations. Results: Analysis indicated a multidisciplinary but limited evidence base. Most reviewed articles addressed end-of-life communication as a peripheral focus of investigation. Generic communication skills are important; however, substantive and sufficient disease-related information, including symptom management and assistive devices, is critical to discussions about end of life. Few articles discussed communication about specific end-of-life options. Communication recommendations in analyzed articles draw attention to communication processes, style and content but lack the systematized guidance needed for clinical practice. Conclusions: This review of primary research articles highlights the limited evidence-base and consequent need for systematic, empirical investigation to inform effective communication about end of life for those with amyotrophic lateral sclerosis. This will provide a foundation for actionable, evidence-based communication guidelines about end of life. Implications for research, policy, and practice are discussed.}, }
@article {pmid34339943, year = {2021}, author = {Manochkumar, J and Doss, CGP and El-Seedi, HR and Efferth, T and Ramamoorthy, S}, title = {The neuroprotective potential of carotenoids in vitro and in vivo.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {91}, number = {}, pages = {153676}, doi = {10.1016/j.phymed.2021.153676}, pmid = {34339943}, issn = {1618-095X}, mesh = {Antioxidants ; *Carotenoids/pharmacology ; Humans ; *Neurodegenerative Diseases/drug therapy ; Neuroprotection ; *Neuroprotective Agents/pharmacology ; Oxidative Stress ; }, abstract = {BACKGROUND: Despite advances in research on neurodegenerative diseases, the pathogenesis and treatment response of neurodegenerative diseases remain unclear. Recent studies revealed a significant role of carotenoids to treat neurodegenerative diseases. The aim of this study was to systematically review the neuroprotective potential of carotenoids in vivo and in vitro and the molecular mechanisms and pathological factors contributing to major neurodegenerative diseases (Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, and stroke).
HYPOTHESIS: Carotenoids as therapeutic molecules to target neurodegenerative diseases.
RESULTS: Aggregation of toxic proteins, mitochondrial dysfunction, oxidative stress, the excitotoxic pathway, and neuroinflammation were the major pathological factors contributing to the progression of neurodegenerative diseases. Furthermore, in vitro and in vivo studies supported the beneficiary role of carotenoids, namely lycopene, β-carotene, crocin, crocetin, lutein, fucoxanthin and astaxanthin in alleviating disease progression. These carotenoids provide neuroprotection by inhibition of neuro-inflammation, microglial activation, excitotoxic pathway, modulation of autophagy, attenuation of oxidative damage and activation of defensive antioxidant enzymes. Additionally, studies conducted on humans also demonstrated that dietary intake of carotenoids lowers the risk of neurodegenerative diseases.
CONCLUSION: Carotenoids may be used as drugs to prevent and treat neurodegenerative diseases. Although, the in vitro and in vivo results are encouraging, further well conducted clinical studies on humans are required to conclude about the full potential of neurodegenerative diseases.}, }
@article {pmid34322852, year = {2022}, author = {Nabizadeh, F and Balabandian, M and Sharafi, AM and Ghaderi, A and Rostami, MR and Naser Moghadasi, A}, title = {Statins and risk of amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Acta neurologica Belgica}, volume = {122}, number = {4}, pages = {979-986}, pmid = {34322852}, issn = {2240-2993}, mesh = {*Amyotrophic Lateral Sclerosis/chemically induced/epidemiology ; Case-Control Studies ; Cohort Studies ; Humans ; *Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects ; Incidence ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a paralytic, heterogeneous and progressive disease characterized by the degeneration of both upper and lower motor neurons. Several studies about the effects of statins drug on the risk of ALS showed contradictory results and evidence for this is inconclusive. So we aimed to perform a meta-analysis on previous studies to clarify the association between statin use and risk of ALS. The databases including PubMed, Scopus, and Web of science were searched in February 2021 for studies that reported the association between statin use and risk of ALS. The eligible studies had to provide a report on the effect of statin and the incidence of ALS while comparing it to the control group. Articles that had low statin exposure time, the absence of a control group and an unknown number of ALS patients were excluded. The rate ratio and 95% confidence interval (CI) were used for association measures in case-control and cohort studies. After full-text and abstract review, data from 8 studies with a total of 547,622 participants and 13,890 cases of ALS were entered in the present meta-analysis. We combined eight studies using a random-effect model and the RR for statin users among groups was 0.98 (95% CI 0.80-1.20) which indicates no association between statin and incidence of ALS. Also high heterogeneity was detected across the studies (Q value = 26.62, P = .00; I[2] = 72.71%). In our meta-analysis study, we found no association between statin use and an increase in ALS incidence. This result is in line with some previous studies and provides strong evidence that denies the possible association between statin uptake and disease induction.}, }
@article {pmid34275566, year = {2021}, author = {Hu, N and Wang, J and Liu, M}, title = {Split hand in amyotrophic lateral sclerosis: A systematic review and meta-analysis.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {90}, number = {}, pages = {293-301}, doi = {10.1016/j.jocn.2021.06.015}, pmid = {34275566}, issn = {1532-2653}, mesh = {Amyotrophic Lateral Sclerosis/*complications/*epidemiology ; Atrophy ; Hand/*pathology ; Humans ; Muscle Weakness/epidemiology/etiology ; Muscle, Skeletal/pathology ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: To investigate the frequency of split hand (SI) and its diagnostic performance in amyotrophic lateral sclerosis (ALS).
METHODS: PubMed, EMBASE, OVID and other databases were searched systematically up to March 2021 for relevant reports about the split hand syndrome. Two reviewers screened and selected the titles and abstracts of the studies independently during the database searches and performed full-text reviews and extracted available data. In our study, AACMAP was calculated by AACMAP = APBCMAP/ADMCMAP and split-hand index (SI) was calculated by SICMAP = (APBCMAP × FDICMAP)/ADMCMAP. The mean differences (MD) in APB/ADMCMAP and SICMAP between patients with ALS and control group were calculated (APB the abductor pollicis brevis muscle; ADM the abductor digiti minimi muscle; CMAP compound muscle action potentials). Meta-analysis was performed to determine summary sensitivity, specificity, and area under the curve (AUC) with 95% confidence intervals (CI) for SICMAP.
RESULTS: Pooled results of five studies including 339 patients showed that 50% (95%CI: 35%-65%) of patients with ALS presented split hand. APB/ADMCMAP in patients with ALS was significantly lower than healthy population (MD: -0.38, 95%CI: -0.48, -0.28). SICMAP in patients with ALS was significantly lower than healthy controls (MD: -5.87, 95%CI: -6.28, -5.46) and neuromuscular controls (MD: -5.60, 95%CI: -5.78, -5.42). Receiver operating characteristic curve analysis showed that the AUC was 0.860 [95%CI: 0.808, 0.911] for SICMAP. The sensitivity and specificity for SICMAP were 78% and 81% (cut-off value: 5.2-11.8), respectively.
CONCLUSION: Half of ALS patients might show split hand sign. SICMAP could be a potential biomarker in the diagnosis of ALS.}, }
@article {pmid34252113, year = {2021}, author = {Liu, Z and Yang, Z and Gu, Y and Liu, H and Wang, P}, title = {The effectiveness of eye tracking in the diagnosis of cognitive disorders: A systematic review and meta-analysis.}, journal = {PloS one}, volume = {16}, number = {7}, pages = {e0254059}, pmid = {34252113}, issn = {1932-6203}, mesh = {Cognition Disorders/*diagnosis ; Confidence Intervals ; *Eye-Tracking Technology ; Humans ; Information Storage and Retrieval ; Likelihood Functions ; Neuropsychological Tests ; Odds Ratio ; Publication Bias ; ROC Curve ; Risk ; }, abstract = {BACKGROUND: Eye tracking (ET) is a viable marker for the recognition of cognitive disorders. We assessed the accuracy and clinical value of ET for the diagnosis of cognitive disorders in patients.
METHODS: We searched the Medline, Embase, Web of Science, Cochrane Library, and Pubmed databases from inception to March 2, 2021, as well as the reference lists of identified primary studies. We included articles written in English that investigated ET for cognitive disorder patients-Mild cognitive impairment (MCI), Alzheimer's disease (AD), Amyotrophic lateral sclerosis (ALS), and dementia. Two independent researchers extracted the data and the characteristics of each study; We calculated pooled sensitivities and specificities. A hierarchical summary of receiver performance characteristics (HSROC) model was used to test the diagnostic accuracy of ET for cognitive impairment (CI).
FINDINGS: 11 studies met the inclusion criteria and were included in qualitative comprehensive analysis. Meta-analysis was performed on 9 trials using Neuropsychological Cognitive Testing (NCT) as the reference standard. The comprehensive sensitivity and specificity of ET for detecting cognitive disorders were 0.75 (95% CI 0.72-0.79) and 0.73 (95% CI 0.70 to 0.76), respectively. The combined positive likelihood ratio (LR+) was 2.74 (95%CI 2.32-3.24) and the negative likelihood ratio (LR-) was 0.27 (95%CI 0.18-0.42).
CONCLUSIONS: This review showed that ET technology could be used to detect the decline in CI, clinical use of ET techniques in combination with other tools to assess CI can be encouraged.}, }
@article {pmid34229610, year = {2021}, author = {Barbalho, I and Valentim, R and Júnior, MD and Barros, D and Júnior, HP and Fernandes, F and Teixeira, C and Lima, T and Paiva, J and Nagem, D}, title = {National registry for amyotrophic lateral sclerosis: a systematic review for structuring population registries of motor neuron diseases.}, journal = {BMC neurology}, volume = {21}, number = {1}, pages = {269}, pmid = {34229610}, issn = {1471-2377}, mesh = {*Amyotrophic Lateral Sclerosis ; Humans ; Motor Neuron Disease ; *Registries ; }, abstract = {BACKGROUND: This article comprises a systematic review of the literature that aims at researching and analyzing the frequently applied guidelines for structuring national databases of epidemiological surveillance for motor neuron diseases, especially Amyotrophic Lateral Sclerosis (ALS).
METHODS: We searched for articles published from January 2015 to September 2019 on online databases as PubMed - U.S. National Institutes of Health's National Library of Medicine, Scopus, Science Direct, and Springer. Subsequently, we analyzed studies that considered risk factors, demographic data, and other strategic data for directing techno-scientific research, calibrating public health policies, and supporting decision-making by managers through a systemic panorama of ALS.
RESULTS: 2850 studies were identified. 2400 were discarded for not satisfying the inclusion criteria, and 435 being duplicated or published in books or conferences. Hence, 15 articles were elected. By applying quality criteria, we then selected six studies to compose this review. Such researches featured registries from the American (3), European (2), and Oceania (1) continent. All the studies specified the methods for data capture and the patients' recruitment process for the registers.
DISCUSSIONS: From the analysis of the selected papers and reported models, it is noticeable that most studies focused on the prospect of obtaining data to characterize research on epidemiological studies. Demographic data (ID01) are present in all the registries, representing the main collected data category. Furthermore, the general health history (ID02) is present in 50% of the registries analyzed. Characteristics such as access control, confidentiality and data curation. We observed that 50% of the registries comprise a patient-focused web-based self-report system.
CONCLUSION: The development of robust, interoperable, and secure electronic registries that generate value for research and patients presents itself as a solution and a challenge. This systematic review demonstrated the success of a population register requires actions with well-defined development methods, as well as the involvement of various actors of civil society.}, }
@article {pmid34200812, year = {2021}, author = {Ferri, L and Ajdinaj, P and Rispoli, MG and Carrarini, C and Barbone, F and D'Ardes, D and Capasso, M and Muzio, AD and Cipollone, F and Onofrj, M and Bonanni, L}, title = {Diabetes Mellitus and Amyotrophic Lateral Sclerosis: A Systematic Review.}, journal = {Biomolecules}, volume = {11}, number = {6}, pages = {}, pmid = {34200812}, issn = {2218-273X}, mesh = {Age Factors ; Amyotrophic Lateral Sclerosis/*metabolism/mortality/pathology ; Diabetes Mellitus/*metabolism/mortality/pathology ; Glucose/*metabolism ; Humans ; }, abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a degenerative disorder which affects the motor neurons. Growing evidence suggests that ALS may impact the metabolic system, including the glucose metabolism. Several studies investigated the role of Diabetes Mellitus (DM) as risk and/or prognostic factor. However, a clear correlation between DM and ALS has not been defined. In this review, we focus on the role of DM in ALS, examining the different hypotheses on how perturbations of glucose metabolism may interact with the pathophysiology and the course of ALS.
METHODS: We undertook an independent PubMed literature search, using the following search terms: ((ALS) OR (Amyotrophic Lateral Sclerosis) OR (Motor Neuron Disease)) AND ((Diabetes) OR (Glucose Intolerance) OR (Hyperglycemia)). Review and original articles were considered.
RESULTS: DM appears not to affect ALS severity, progression, and survival. Contrasting data suggested a protective role of DM on the occurrence of ALS in elderly and an opposite effect in younger subjects.
CONCLUSIONS: The actual clinical and pathophysiological correlation between DM and ALS is unclear. Large longitudinal prospective studies are needed. Achieving large sample sizes comparable to those of common complex diseases like DM is a challenge for a rare disease like ALS. Collaborative efforts could overcome this specific issue.}, }
@article {pmid34143346, year = {2021}, author = {Achtert, K and Kerkemeyer, L}, title = {The economic burden of amyotrophic lateral sclerosis: a systematic review.}, journal = {The European journal of health economics : HEPAC : health economics in prevention and care}, volume = {22}, number = {8}, pages = {1151-1166}, pmid = {34143346}, issn = {1618-7601}, mesh = {*Amyotrophic Lateral Sclerosis ; Cost of Illness ; Cost-Benefit Analysis ; Disease Progression ; Humans ; }, abstract = {OBJECTIVES: This systematic review aimed to comprehensively collect and summarise the current body of knowledge regarding the cost-of-illness of amyotrophic lateral sclerosis, to identify cost-driving factors of the disease and to consider the development of costs over the course of disease. Further, the review sought to assess the methodological quality of the selected studies.
METHODS: A systematic review was performed using the databases MEDLINE, Embase, Cochrane Library and PsycINFO. Studies examining the economic burden of amyotrophic lateral sclerosis on a patient or national level written in English or German published from the year 2001 onwards were included. Additional searches were conducted. Study characteristics and results were extracted and compared.
RESULTS: In summary, 20 studies were included in this review. Most studies investigated costs per patient, amounting to total costs between €9741€ to €114,605. Six studies confirmed a rise in costs with disease progression, peaking close to the death of a patient. National costs for amyotrophic lateral sclerosis varied between €149 million and €1329 million.
CONCLUSION: Most of these studies suggest the economic burden of amyotrophic lateral sclerosis to be considerable. However, further research is needed to establish a cost-effective health policy in consideration of disease severities.}, }
@article {pmid34120226, year = {2022}, author = {Beswick, E and Forbes, D and Hassan, Z and Wong, C and Newton, J and Carson, A and Abrahams, S and Chandran, S and Pal, S}, title = {A systematic review of non-motor symptom evaluation in clinical trials for amyotrophic lateral sclerosis.}, journal = {Journal of neurology}, volume = {269}, number = {1}, pages = {411-426}, pmid = {34120226}, issn = {1432-1459}, support = {MR/L023784/2/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/drug therapy ; Fatigue/etiology ; Humans ; Pain/diagnosis/drug therapy/etiology ; Riluzole/therapeutic use ; Symptom Assessment ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is increasingly recognised as a multi-system disorder, presenting with common and impactful non-motor symptoms, such as neuropsychiatric symtpoms, cognitive and behavioural changes, pain, disordered sleep, fatigue and problematic saliva.
AIM/HYPOTHESIS: We aimed to systematically review 25 years of ALS clinical trials data to identify if non-motor features were evaluated, in addition to the traditional measures of motor functioning and survival, and where evaluated to describe the instruments used to assess. We hypothesised that assessment of non-motor symptoms has been largely neglected in trial design and not evaluated with ALS-suitable instruments.
METHODS: We reviewed clinical trials of investigative medicinal products in ALS, since the licensing of riluzole in 1994. Trial registry databases including WHO International Trials Registry, European Clinical Trials Register, clinicaltrials.gov, and PubMed were systematically searched for Phase II, III or IV trials registered, completed or published between 01/01/1994 and 16/09/2020. No language restrictions were applied.
RESULTS: 237 clinical trials, including over 29,222 participants, were investigated for their use of non-motor outcome measures. These trials evaluated neuropsychiatric symptoms (75, 32%), cognitive impairment (16, 6.8%), behavioural change (34, 14%), pain (55, 23%), sleep disturbances (12, 5%) and fatigue (18, 8%). Problematic saliva was assessed as part of composite ALS-FRS(R) scores in 184 trials (78%) but with no focus on this as an isolated symptom. 31 (13%) trials including 3585 participants did not include any assessment of non-motor symptoms.
CONCLUSIONS: Non-motor symptoms such as neuropsychiatric, cognitive and behavioural changes, pain, disordered sleep, fatigue, and problematic saliva have not been consistently evaluated in trials for people with ALS. Where evaluated, non-symptoms were primarily assessed using instruments and impairment thresholds that are not adapted for people with ALS. Future trials should include non-motor symptom assessments to evaluate the additional potential therapeutic benefit of candidate drugs.
PROPSERO REGISTRATION: CRD42020223648.}, }
@article {pmid34099747, year = {2021}, author = {Filippini, T and Hatch, EE and Vinceti, M}, title = {Residential exposure to electromagnetic fields and risk of amyotrophic lateral sclerosis: a dose-response meta-analysis.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {11939}, pmid = {34099747}, issn = {2045-2322}, mesh = {Amyotrophic Lateral Sclerosis/*diagnosis/etiology ; Electromagnetic Fields/*adverse effects ; Environmental Exposure/*adverse effects ; Housing ; Humans ; Neurodegenerative Diseases/*diagnosis/etiology ; Radiation Dosage ; Residential Facilities ; Risk Assessment/methods/statistics & numerical data ; Risk Factors ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is neurodegenerative disease characterized by a fatal prognosis and still unknown etiology. Some environmental risk factors have been suggested, including exposure to magnetic fields. Studies have suggested positive associations in occupationally-exposed populations, but the link with residential exposure is still debated as is the shape of such relation. Due to recent availability of advanced biostatistical tools for dose-response meta-analysis, we carried out a systematic review in order to assess the dose-response association between ALS and residential exposure to magnetic fields. We performed an online literature searching through April 30, 2021. Studies were included if they assessed residential exposure to electromagnetic fields, based either on distance from overhead power lines or on magnetic field modelling techniques, and if they reported risk estimates for ALS. We identified six eligible studies, four using distance-based and one modelling-based exposure assessment, and one both methods. Both distance-based and particularly modelling-based exposure estimates appeared to be associated with a decreased ALS risk in the highest exposure category, although estimates were very imprecise (summary RRs 0.87, 95% CI 0.63-1.20, and 0.27, 95% CI 0.05-1.36). Dose-response meta-analysis also showed little association between distance from power lines and ALS, with no evidence of any threshold. Overall, we found scant evidence of a positive association between residential magnetic fields exposure and ALS, although the available data were too limited to conduct a dose-response analysis for the modelled magnetic field estimates or to perform stratified analyses.}, }
@article {pmid34077349, year = {2022}, author = {Chen, WN and Shaikh, MF and Bhuvanendran, S and Date, A and Ansari, MT and Radhakrishnan, AK and Othman, I}, title = {Poloxamer 188 (P188), A Potential Polymeric Protective Agent for Central Nervous System Disorders: A Systematic Review.}, journal = {Current neuropharmacology}, volume = {20}, number = {4}, pages = {799-808}, pmid = {34077349}, issn = {1875-6190}, support = {FRGS/1/2020/SKK0/MUSM/02/6//Ministry of Higher Education, Fundamental Research Grant Scheme/ ; }, mesh = {Animals ; *Central Nervous System Diseases/drug therapy ; Humans ; *Neuroprotective Agents/pharmacology/therapeutic use ; Poloxamer/pharmacology ; *Reperfusion Injury ; }, abstract = {Poloxamer 188 (P188) is an FDA-approved biocompatible block copolymer composed of repeating units of Poly(Ethylene Oxide) (PEO) and poly(propylene oxide) (PPO). Due to its amphiphilic nature and high Hydrophile-Lipophile Balance (HLB) value of 29, P188 is used as a stabilizer/emulsifier in many cosmetics and pharmaceutical preparations. While the applications of P188 as an excipient are widely explored, the data on the pharmacological activity of P188 are scarce. Notably, the neuroprotective potential of P188 has gained a lot of interest. Therefore, this systematic review is aimed at summarizing evidence of neuroprotective potential of P188 in CNS disorders. The PRISMA model was used, and five databases (Google Scholar, Scopus, Wiley Online Library, ScienceDirect, and PubMed) were searched with relevant keywords. The search resulted in 11 articles, which met the inclusion criteria. These articles described the protective effects of P188 on traumatic brain injury or mechanical injury in cells, neurotoxicity, Parkinson's disease, Amyotrophic lateral sclerosis (ALS), and ischemia/ reperfusion injury from stroke. All the articles were original research in experimental or pre-clinical stages using animal models or in vitro systems. The reported activities demonstrated the potential of P188 as a neuroprotective agent in improving CNS conditions such as neurodegeneration.}, }
@article {pmid34054018, year = {2021}, author = {Crook, A and Jacobs, C and Newton-John, T and Richardson, E and McEwen, A}, title = {Patient and Relative Experiences and Decision-making About Genetic Testing and Counseling for Familial ALS and FTD: A Systematic Scoping Review.}, journal = {Alzheimer disease and associated disorders}, volume = {35}, number = {4}, pages = {374-385}, doi = {10.1097/WAD.0000000000000458}, pmid = {34054018}, issn = {1546-4156}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/genetics ; Counseling ; *Frontotemporal Dementia/diagnosis/genetics ; Genetic Counseling ; Genetic Testing ; Humans ; }, abstract = {Genetic testing and counseling is an emerging part of care for patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) and their families. This scoping review aimed to map patients' and relatives' experiences of genetic testing and counseling for familial ALS and FTD and the factors influencing their decision to proceed with testing or counseling. Informed by the Joanna Briggs Institute methodology, 5 databases were systematically searched. Thirty studies from 39 references were included. A descriptive numerical summary analysis and narrative synthesis was conducted. Mostly positive diagnostic testing experiences were reported, but issues arose due to progressive disease and discordant results. Predictive testing impacted at-risk relatives, regardless of the result received, and psychosocial sequelae ranged from relief to guilt, worry or contemplating suicide. Four reproductive testing experiences were reported. Personal, familial and practical factors, and the lived experience of disease, informed decision-making. Greater uncertainty and complexity may be faced in familial ALS/FTD than in other late-onset neurodegenerative diseases due to clinical and genetic heterogeneity, and testing limitations. Genetic counseling models of care should consider this difference to ensure that individuals with, or at risk of, ALS/FTD are effectively managed. Implications for research and practice are discussed.}, }
@article {pmid34034049, year = {2021}, author = {Li, N and Wu, X and Zhuang, W and Xia, L and Chen, Y and Wang, Y and Wu, C and Rao, Z and Du, L and Zhao, R and Yi, M and Wan, Q and Zhou, Y}, title = {Green leafy vegetable and lutein intake and multiple health outcomes.}, journal = {Food chemistry}, volume = {360}, number = {}, pages = {130145}, doi = {10.1016/j.foodchem.2021.130145}, pmid = {34034049}, issn = {1873-7072}, mesh = {Cardiovascular Diseases/mortality/pathology ; *Diet ; Humans ; Lutein/chemistry/*metabolism ; Neoplasms/mortality/pathology ; Outcome Assessment, Health Care ; Stroke/mortality/pathology ; Vegetables/chemistry/*metabolism ; }, abstract = {Green leafy vegetables (GLVs) are a key element of healthy eating patterns and are an important source of lutein. To clarify the evidence for associations between GLVs and lutein intake and multiple health outcomes, we performed a review. A total of 24 meta-analyses with 29 health outcomes were identified by eligibility criteria. Dose-response analyses revealed that, per 100 g/d GLV intake was associated with a decreased risk (ca. 25%) of all-cause mortality, coronary heart disease and stroke. Beneficial effects of GLV intake were found for cardiovascular disease and bladder and oral cancer. Dietary lutein intake was inversely associated with age-related macular degeneration, age-related cataracts, coronary heart disease, stroke, oesophageal cancer, non-Hodgkin lymphoma, metabolic syndrome, and amyotrophic lateral sclerosis. Caution was warranted for contamination with potentially pathogenic organisms, specifically Escherichia coli. GLV consumption and lutein intake therein are generally safe and beneficial for multiple health outcomes in humans.}, }
@article {pmid33928846, year = {2021}, author = {Knightly, N and Sullivan, P}, title = {Surgery for Trapeziometacarpal Joint Osteoarthritis: A Meta-Analysis on Efficacy and Safety.}, journal = {The journal of hand surgery Asian-Pacific volume}, volume = {26}, number = {2}, pages = {245-264}, doi = {10.1142/S2424835521500260}, pmid = {33928846}, issn = {2424-8363}, mesh = {Arthrodesis ; Carpometacarpal Joints/*surgery ; Humans ; Ligaments, Articular/surgery ; Osteoarthritis/*surgery ; Postoperative Complications ; Range of Motion, Articular ; Tendons/surgery ; Thumb/surgery ; Trapezium Bone/surgery ; }, abstract = {Background: Osteoarthritis of the thumb base is the second most prevalent arthritis of the hand. Management is primarily conservative, consisting of analgesia, splinting, physiotherapy, and steroid injections. Surgery is considered when conservative measures fail. Methods: The primary objective was to assess the safety and efficacy of the surgical interventions and therein, evaluate whether any superiority exists among the available interventions. Efficacy was evaluated by examining four parameters: pain, function, range of movement and strength of the joint postoperatively. Safety was determined by comparing the rate and severity of postoperative complications. A systematic search of MEDLINE (2014-2019), EMBASE (2014-2019), CINAHL (2014-2019) and CENTRAL (2014-2019) databases was carried out. Abstracts were screened for relevant studies. Randomised controlled trials were only considered. Results: Eight studies were included in the quantitative synthesis. The procedures evaluated are: Trapeziectomy (T), trapeziectomy with ligament reconstruction (T + LR), trapeziectomy with ligament reconstruction and tendon interposition (T + LRTI), trapeziectomy with allograft suspension (T + ALS) and joint arthrodesis (A). Low-moderate quality evidence suggests that T + LRTI yields better range of movement (palmar abduction) when compared with (T) alone; (SMD 0.61, 95% CI 0.22 to 1.00, random-effects, p = 0.002). Comparing adverse events showed that arthrodesis carries a greater risk of adverse events when compared with T + LRTI; (RR 0.33, 95% CI 0.17 to 0.61, random-effects, p = 0.0005). In addition, T + LRTI is preferred over arthrodesis by patients (OR 0.29 95% CI 0.09 to 0.95; p = 0.04). This difference was no seen in the other comparison groups. Conclusions: It is difficult to declare with any degree of certainty which procedure offers the best functional outcome and safety profile. Results suggest T + LRTI yields good postoperative range of movement. Arthrodesis demonstrated an unacceptably high rate of moderate-severe complications and should be considered with careful consideration.}, }
@article {pmid33877561, year = {2021}, author = {Khan, H and Tiwari, P and Kaur, A and Singh, TG}, title = {Sirtuin Acetylation and Deacetylation: a Complex Paradigm in Neurodegenerative Disease.}, journal = {Molecular neurobiology}, volume = {58}, number = {8}, pages = {3903-3917}, pmid = {33877561}, issn = {1559-1182}, mesh = {Acetylation/drug effects ; Animals ; Anti-Inflammatory Agents/pharmacology/*therapeutic use ; Humans ; Neurodegenerative Diseases/*drug therapy/*metabolism ; Neuroprotective Agents/pharmacology/*therapeutic use ; Sirtuins/*metabolism ; }, abstract = {Sirtuins are the class III of histone deacetylases that depend on nicotinamide adenine dinucleotide for their activity. Sirtuins can influence the progression of neurodegenerative disorders by switching between deacetylation and acetylation processes. Histone acetylation occurs when acetyl groups are added to lysine residues on the N-terminal part of histone proteins. Deacetylation, on the other hand, results in the removal of acetyl groups. Pharmacological modulation of sirtuin activity has been shown to influence various neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, Huntington's disease, stroke, and amyotrophic lateral sclerosis. In this review, mechanistic perspective of sirtuins has been discussed in anti-inflammatory, antiapoptotic, and neuroprotective effects in various disorders. We have discussed the structure, neurobiology, and physiology of sirtuins in neurodegenerative disease. Recent preclinical and clinical studies and their outcome have also been elucidated. The aim of this review is to fill in the gaps in our understanding of sirtuins' role in histone acetylation and deacetylation in all neurodegenerative diseases. Here, we emphasized on reviewing all the studies carried out in various labs depicting the role of sirtuin modulators in neuroprotection and highlighted the ideas that can be considered for future perspectives. Taken together, sirtuins may serve as a promising therapeutic target for the treatment of neurodegenerative disorders.}, }
@article {pmid33871294, year = {2022}, author = {Erazo, D and Luna, J and Preux, PM and Boumediene, F and Couratier, P}, title = {Epidemiological and genetic features of amyotrophic lateral sclerosis in Latin America and the Caribbean: a systematic review.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {23}, number = {1-2}, pages = {4-15}, doi = {10.1080/21678421.2021.1909066}, pmid = {33871294}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis/epidemiology/genetics ; Caribbean Region/epidemiology ; Ethnicity ; Humans ; Incidence ; Latin America/epidemiology ; }, abstract = {Introduction: Heterogeneity of amyotrophic lateral sclerosis (ALS) has been suggested in terms of epidemiology, phenotypes and genetics between geographic areas and populations. However, there is limited information in Latin America. We conducted a systematic review that aimed to describe the epidemiology, frequency of genetic mutations, clinical characteristics and survival of ALS patients in this region. Methods: We reviewed Medline, Scopus, Scielo and LILACS databases up to April 2020. The search terms "Amyotrophic Lateral Sclerosis" or "Motor Neuron Disease" were used in combination with the list of Latin American countries from the United Nations. All observational studies were included. A methodological overview was performed using the principles of descriptive epidemiology. Results: Overall, 1364 publications were identified and 36 studies were selected, covering 13 Latin American countries. According to the original reports, ALS occurrence varied among countries with a standardized incidence ranging from 0.3 per 100,000 person-years follow up (PYFU) in Ecuador to 3.6 per 100,000 PYFU in Uruguay. A low proportion of the C9orf72 repeat expansion was reported in Cuba and Brazil. We identified age at onset between 50 and 60 years. Survival time was higher than 40 months in half of the studies. Data from multiethnic populations reported a higher risk of developing ALS in Caucasians compared to admixed and Black populations. Conclusion: This review provides a perspective of ALS variability across Latin America and highlights specific differences when comparing to Europe and North America. However, we cannot draw firm conclusions because of different methodological concerns within the studies.}, }
@article {pmid33842515, year = {2021}, author = {Kondo, Y and Fukuda, T and Uchimido, R and Kashiura, M and Kato, S and Sekiguchi, H and Zamami, Y and Hifumi, T and Hayashida, K}, title = {Advanced Life Support vs. Basic Life Support for Patients With Trauma in Prehospital Settings: A Systematic Review and Meta-Analysis.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {660367}, pmid = {33842515}, issn = {2296-858X}, abstract = {Background: Advanced Life Support (ALS) is regarded to be associated with improved survival in pre-hospital trauma care when compared to Basic Life Support (BLS) irrespective of lack of evidence. The aim of this study is to ascertain ALS improves survival for trauma in prehospital settings when compared to BLS. Methods: We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials for published controlled trials (CTs), and observational studies that were published until Aug 2017. The population of interest were adults (>18 years old) trauma patients who were transported by ground transportation and required resuscitation in prehospital settings. We compared outcomes between the ALS and BLS groups. The primary outcome was in-hospital mortality and secondary outcomes were neurological outcome and time spent on scene. Results: We identified 2,502 studies from various databases and 10 studies were included in the analysis (two CTs, and eight observational studies). The outcomes were not statistically significant between the ALS and BLS groups (pooled OR 1.14; 95% CI 0.95 to 1.36 for mortality, pooled OR 1.12; 95% CI 0.88 to 1.42 for good neurological outcomes, pooled mean difference -0.96; 95% CI-6.64 to 4.72 for on-scene time) in CTs. In observational studies, ALS prolonged on-scene time and increased mortality (pooled OR 1.56; 95% CI: 1.31 to 1.86 for mortality, and pooled mean difference, 1.26; 95% CI: 0.07 to 2.45 for on-scene time). Conclusions: In prehospital settings, the present study showed no advantages of ALS on the outcomes in patients with trauma compared to BLS.}, }
@article {pmid33764559, year = {2021}, author = {Baaken, D and Dechent, D and Blettner, M and Drießen, S and Merzenich, H}, title = {Occupational Exposure to Extremely Low-Frequency Magnetic Fields and Risk of Amyotrophic Lateral Sclerosis: Results of a Feasibility Study for a Pooled Analysis of Original Data.}, journal = {Bioelectromagnetics}, volume = {42}, number = {4}, pages = {271-283}, doi = {10.1002/bem.22335}, pmid = {33764559}, issn = {1521-186X}, support = {3618S82451//Bundesamt für Strahlenschutz/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/epidemiology/etiology ; Electromagnetic Fields ; Feasibility Studies ; Humans ; Magnetic Fields ; *Occupational Exposure/adverse effects ; Risk ; }, abstract = {Previous meta-analyses have suggested an increased risk of amyotrophic lateral sclerosis (ALS) associated with occupational exposure to extremely low-frequency magnetic fields (ELF-MF). However, results should be interpreted with caution since studies were methodologically heterogeneous. Here, we assessed the feasibility of a pooling study to harmonize and re-analyze available original data. A systematic literature search was conducted. Published epidemiological studies were identified in PubMed and EMF-Portal from literature databases' inception dates until January 2019. The characteristics of all studies were described, including exposure metrics, exposure categories, and confounders. A survey among the principal investigators (PI) was carried out to assess their willingness to provide their original data. The statistical power of a pooling study was evaluated. We identified 15 articles published between 1997 and 2019. Studies differed in terms of outcome, study population, exposure assessment, and exposure metrics. Most studies assessed ELF-MF as average magnetic flux density per working day; however, exposure categories varied widely. The pattern of adjustment for confounders was heterogeneous between studies, with age, sex, and socioeconomic status being most frequent. Eight PI expressed their willingness to provide original data. A relative risk of ≥1.14 for ALS and occupational exposure to ELF-MF can be detected with a power of more than 80% in a pooled study. The pooling of original data is recommended and could contribute to a better understanding of ELF-MF in the etiology of ALS based on a large database and reduced heterogeneity due to a standardized analysis protocol with harmonized exposure metrics and exposure categories. Bioelectromagnetics. © 2021 Bioelectromagnetics Society.}, }
@article {pmid33694050, year = {2021}, author = {Xu, L and He, B and Zhang, Y and Chen, L and Fan, D and Zhan, S and Wang, S}, title = {Prognostic models for amyotrophic lateral sclerosis: a systematic review.}, journal = {Journal of neurology}, volume = {268}, number = {9}, pages = {3361-3370}, pmid = {33694050}, issn = {1432-1459}, support = {91646107//National Natural Science Foundation of China/ ; 81973146//National Natural Science Foundation of China/ ; 2018YFC1311704//National Key Research and Development Program of China/ ; DQGG0404//National research program for key issues in air pollution control/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis ; Bias ; Humans ; Machine Learning ; Prognosis ; *Respiratory Insufficiency ; }, abstract = {BACKGROUND: Increasing prognostic models for amyotrophic lateral sclerosis (ALS) have been developed. However, no comprehensive evaluation of these models has been done. The purpose of this study was to map the prognostic models for ALS to assess their potential contribution and suggest future improvements on modeling strategy.
METHODS: Databases including Medline, Embase, Web of Science, and Cochrane library were searched from inception to 20 February 2021. All studies developing and/or validating prognostic models for ALS were selected. Information regarding modelling method and methodological quality was extracted.
RESULTS: A total of 28 studies describing the development of 34 models and the external validation of 19 models were included. The outcomes concerned were ALS progression (n = 12; 35%), change in weight (n = 1; 3%), respiratory insufficiency (n = 2; 6%), and survival (n = 19; 56%). Among the models predicting ALS progression or survival, the most frequently used predictors were age, ALS Functional Rating Scale/ALS Functional Rating Scale-Revised, site of onset, and disease duration. The modelling method adopted most was machine learning (n = 16; 47%). Most of the models (n = 25; 74%) were not presented. Discrimination and calibration were assessed in 12 (35%) and 2 (6%) models, respectively. Only one model by Westeneng et al. (Lancet Neurol 17:423-433, 2018) was assessed with overall low risk of bias and it performed well in both discrimination and calibration, suggesting a relatively reliable model for practice.
CONCLUSIONS: This study systematically reviewed the prognostic models for ALS. Their usefulness is questionable due to several methodological pitfalls and the lack of external validation done by fully independent researchers. Future research should pay more attention to the addition of novel promising predictors, external validation, and head-to-head comparisons of existing models.}, }
@article {pmid33679303, year = {2021}, author = {Ravanfar, P and Loi, SM and Syeda, WT and Van Rheenen, TE and Bush, AI and Desmond, P and Cropley, VL and Lane, DJR and Opazo, CM and Moffat, BA and Velakoulis, D and Pantelis, C}, title = {Systematic Review: Quantitative Susceptibility Mapping (QSM) of Brain Iron Profile in Neurodegenerative Diseases.}, journal = {Frontiers in neuroscience}, volume = {15}, number = {}, pages = {618435}, pmid = {33679303}, issn = {1662-4548}, abstract = {Iron has been increasingly implicated in the pathology of neurodegenerative diseases. In the past decade, development of the new magnetic resonance imaging technique, quantitative susceptibility mapping (QSM), has enabled for the more comprehensive investigation of iron distribution in the brain. The aim of this systematic review was to provide a synthesis of the findings from existing QSM studies in neurodegenerative diseases. We identified 80 records by searching MEDLINE, Embase, Scopus, and PsycInfo databases. The disorders investigated in these studies included Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Wilson's disease, Huntington's disease, Friedreich's ataxia, spinocerebellar ataxia, Fabry disease, myotonic dystrophy, pantothenate-kinase-associated neurodegeneration, and mitochondrial membrane protein-associated neurodegeneration. As a general pattern, QSM revealed increased magnetic susceptibility (suggestive of increased iron content) in the brain regions associated with the pathology of each disorder, such as the amygdala and caudate nucleus in Alzheimer's disease, the substantia nigra in Parkinson's disease, motor cortex in amyotrophic lateral sclerosis, basal ganglia in Huntington's disease, and cerebellar dentate nucleus in Friedreich's ataxia. Furthermore, the increased magnetic susceptibility correlated with disease duration and severity of clinical features in some disorders. Although the number of studies is still limited in most of the neurodegenerative diseases, the existing evidence suggests that QSM can be a promising tool in the investigation of neurodegeneration.}, }
@article {pmid33661072, year = {2021}, author = {Hurwitz, N and Radakovic, R and Boyce, E and Peryer, G}, title = {Prevalence of pain in amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {22}, number = {7-8}, pages = {449-458}, doi = {10.1080/21678421.2021.1892765}, pmid = {33661072}, issn = {2167-9223}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {*Amyotrophic Lateral Sclerosis/complications/epidemiology ; Cross-Sectional Studies ; Humans ; Muscle Cramp ; Pain/epidemiology/etiology ; Prevalence ; }, abstract = {Objectives: Physical pain is a known symptom in amyotrophic lateral sclerosis (ALS), but no systematically derived prevalence estimate is available. The aim of this study was to determine the pooled prevalence of pain in ALS, relative to its method of measurement and pain characteristics. Methods: A systematic search across multiple databases was conducted on January 16, 2020. Random-effects meta-analyses of single proportions were performed on prevalence data. Heterogeneity was determined using the I[2] statistic. Where available, pain location, intensity, and type or source were compared. Results: 2552 articles were identified. Twenty-one eligible studies were included. All studies used observational designs (14 cross-sectional, 6 cohort, 1 case-control). Pooled prevalence of pain in ALS across all studies was 60% (95% CI = 50-69%), with a high degree of heterogeneity (I[2] = 94%, p < .001). Studies that used only validated measures had lower heterogeneity (I[2] = 82%, p = 0.002), compared to those that used tailored measures, or tailored supplemented with validated measures (I[2] = 90%, p < 0.001 and I[2] = 83%, p < 0.001, respectively). In a subset of studies (N = 9), the most commonly reported pain location was the upper limbs including shoulders/extremities (41.5%). A further study subset (N = 7) showed moderate-severe intensity pain was most frequently reported. Type of pain was commonly related to cramp or spasm. Conclusions: Experiencing physical pain in ALS occurs with high prevalence. Deriving consensus on which specific tools should be used to assess, monitor and compare symptoms of pain in this population will reduce current heterogeneity in approaches and increase the likelihood of ameliorating distressing experiences more effectively.}, }
@article {pmid33630135, year = {2021}, author = {Fontana, A and Marin, B and Luna, J and Beghi, E and Logroscino, G and Boumédiene, F and Preux, PM and Couratier, P and Copetti, M}, title = {Time-trend evolution and determinants of sex ratio in Amyotrophic Lateral Sclerosis: a dose-response meta-analysis.}, journal = {Journal of neurology}, volume = {268}, number = {8}, pages = {2973-2984}, pmid = {33630135}, issn = {1432-1459}, mesh = {*Amyotrophic Lateral Sclerosis/epidemiology ; Female ; Humans ; Incidence ; Male ; Sex Ratio ; }, abstract = {BACKGROUND: A noticeable change of the male-to-female sex ratio (SR) has been observed in Amyotrophic Lateral Sclerosis (ALS) leading to an apparent regression of SR with time (SR close to 1:1).
OBJECTIVE: To provide a global SR estimate and investigate its relation with respect to population age.
METHODS: A systematic review and meta-analysis was conducted including only population-based studies with a high-quality methodology in European ancestral origin population. Male-to-female SR was estimated by three different measures: SR number, SR crude incidence and SR standardized incidence. Standard and dose-response meta-analyses were performed to assess the pooled SR measures (irrespective of population age) and the evolution of the SR measures with respect to population age, respectively. Potential sources of heterogeneity were investigated via meta-regression.
RESULTS: Overall, 3254 articles were retrieved in the literature search. Thirty-nine studies stratified by time periods were included. The overall pooled male-to-female ratio was 1.28 (95% CI 1.23-1.32) for SR number, 1.33 (95% CI 1.29-1.38) for SR crude incidence and 1.35 (95% CI 1.31-1.40) for SR standardized incidence. The SR number with respect to population age reveals a progressive reduction of SR at increasing age, while the SR crude incidence in relation to age displays a U-shaped curve.
CONCLUSIONS: The number and the incidence of ALS cases were consistently higher in males than females. Dose-response meta-analysis showed that SR measures change with respect to population age. Further original research is needed to clarify if our findings are reproducible in other populations.}, }
@article {pmid33621971, year = {2021}, author = {Liu, G and Ou, S and Cui, H and Li, X and Yin, Z and Gu, D and Wang, Z}, title = {Head Injury and Amyotrophic Lateral Sclerosis: A Meta-Analysis.}, journal = {Neuroepidemiology}, volume = {}, number = {}, pages = {1-9}, doi = {10.1159/000510987}, pmid = {33621971}, issn = {1423-0208}, abstract = {BACKGROUND: Prior studies have suggested that head injury might be a potential risk factor of amyotrophic lateral sclerosis (ALS). However, the association has not been well established. We aimed to provide a synopsis of the current understanding of head injury's role in ALS.
METHODS: We performed a systematic search in PubMed for observational studies that quantitatively investigated the association between head injury and ALS risk published before April 10, 2020. We used a random-effects model to calculate odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS: Fourteen eligible articles including 10,703 cases and 2,159,324 controls were selected in current meta-analysis. We found that head injury was associated with an increased risk of ALS (OR = 1.38, 95% CI: 1.20-1.60) and the association was slightly stronger concerning severe head injury and ALS risk (OR = 1.69, 95% CI: 1.27-2.23). Considering the number of head injuries (N) and ALS risk, the association was weak (OR = 1.23, 95% CI: 1.10-1.37, N = 1; OR = 1.29, 95% CI: 0.89-1.86, N ≥ 2). In addition, a strong association with ALS risk was found in individuals who suffered head injury <1 year (OR = 4.05, 95% CI: 2.79-5.89), and when the time lag was set at 1-5, 5-10, and >10 years, the pooled OR was 1.13, 1.35, and 1.10, respectively.
CONCLUSION: This meta-analysis indicates that head injury, especially severe head injury, could increase ALS risk. Although a strong association is found between head injury <1 year and ALS risk in the current study, this result suggests a possibility of reverse causation.}, }
@article {pmid33563800, year = {2021}, author = {Yang, T and Hou, Y and Li, C and Cao, B and Cheng, Y and Wei, Q and Zhang, L and Shang, H}, title = {Risk factors for cognitive impairment in amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {92}, number = {7}, pages = {688-693}, doi = {10.1136/jnnp-2020-325701}, pmid = {33563800}, issn = {1468-330X}, mesh = {Amyotrophic Lateral Sclerosis/*complications ; Cognitive Dysfunction/*etiology ; Female ; Humans ; Male ; Risk Factors ; Sex Factors ; }, abstract = {OBJECTIVE: Cognitive impairment is a common, far-reaching but imperceptible manifestation in patients with amyotrophic lateral sclerosis (ALS). We aimed to identify the risk factors for cognitive impairment in ALS.
METHODS: We searched PubMed and EMBASE for cross-sectional, case-control and cohort studies that reported predictors of cognitive impairment in ALS. The obtained data were meta-analysed to generate overall ORs and 95% CIs.
RESULTS: Twenty-seven eligible articles reporting on 6799 individuals were included out of 20 501 records. Nine predictors were identified: C9orf72 (OR 3.62, 95% CI 1.76 to 7.45), dysarthria (OR 2.25, 95% CI 1.20 to 4.22), family history of ALS (OR 1.76, 95% CI 1.18 to 2.61), predominant upper motor neuron (PUMN) phenotype (OR 1.73, 95% CI 1.09 to 2.73) and bulbar onset (OR 1.54, 95% CI 1.28 to 1.87) increased risk factors for cognitive impairment in ALS. ALS Functional Rating Scale-Revised scores, sex, age or education level were not significantly associated with cognitive impairment in ALS. In addition, C9orf72 (OR=5.94) and bulbar onset (OR=2.08) were strong predictors of ALS-frontotemporal dementia. Female sex conferred more susceptibility to executive cognitive impairment than male sex (OR=1.82).
CONCLUSIONS: Patients with C9orf72 repeat expansion, dysarthria, family history of ALS, PUMN phenotype and bulbar onset had a high risk for cognitive impairment in ALS. These associations may contribute to understanding the heterogeneity of ALS.
PROSPERO REGISTRATION NUMBER: CRD42020201085.}, }
@article {pmid33549783, year = {2021}, author = {Pelletier, Y and Lareyre, F and Cointat, C and Raffort, J}, title = {Management of Vascular Complications during Anterior Lumbar Spinal Surgery Using Mini-Open Retroperitoneal Approach.}, journal = {Annals of vascular surgery}, volume = {74}, number = {}, pages = {475-488}, doi = {10.1016/j.avsg.2021.01.077}, pmid = {33549783}, issn = {1615-5947}, mesh = {Blood Loss, Surgical ; Humans ; Lumbar Vertebrae/diagnostic imaging/*surgery ; Planning Techniques ; Preoperative Care ; Retroperitoneal Space/surgery ; Risk Factors ; Spinal Fusion/*adverse effects ; Total Disc Replacement/*adverse effects ; Vascular System Injuries/*etiology ; Venous Thrombosis/etiology ; }, abstract = {BACKGROUND: Anterior retroperitoneal spine exposure has become increasingly performed for the surgical treatment of various spinal disorders. Despite its advantages, the procedure is not riskless and can expose to potentially life-threatening vascular lesions. The aim of this review is to report the vascular lesions that can happen during anterior lumbar spinal surgery using mini-open retroperitoneal approach and to describe their management.
METHODS: A systematic literature search was performed according to PRISMA to identify studies published in English between January 1980 and December 2019 reporting vascular complications during anterior lumbar spinal surgery with mini-open retroperitoneal approach. Three authors independently conducted the literature search on PubMed/Medline database using a combination of the following terms: "spinal surgery", "anterior lumbar surgery (ALS)", "anterior lumbar interbody fusion (ALIF)", "lumbar total disc replacement", "artificial disc replacement", "vascular complications", "vascular injuries". Vascular complications were defined as any peri-operative or post-operative lesions related to an arterial or venous vessel. The management of the vascular injury was extracted.
RESULTS: Fifteen studies fulfilled the inclusion criteria. Venous injuries were observed in 13 studies. Lacerations and deep venous thrombosis ranged from 0.8% to 4.3% of cases. Arterial lesions were observed in 4 studies and ranged from 0.4% to 4.3% of cases. It included arterial thrombosis, lacerations or vasospasms. The estimated blood loss was reported in 10 studies and ranged from 50 mL up to 3000 mL. Vascular complications were identified as a cause of abortion of the procedure in 2 studies, representing respectively 0.3% of patients who underwent ALS and 0.5% of patients who underwent ALIF.
CONCLUSION: Imaging pre-operative planning is of utmost importance to evaluate risk factors and the presence of anatomic variations in order to prevent and limit vascular complications. Cautions should be taken during the intervention when manipulating major vessels and routine monitoring of the limb oxygen saturation should be systematically performed for an early detection of arterial thrombosis. The training of the surgeon access remains a key-point to prevent and manage vascular complications during anterior lumbar spinal surgery with mini-open retroperitoneal.}, }
@article {pmid33435977, year = {2021}, author = {Mentis, AA and Dardiotis, E and Efthymiou, V and Chrousos, GP}, title = {Non-genetic risk and protective factors and biomarkers for neurological disorders: a meta-umbrella systematic review of umbrella reviews.}, journal = {BMC medicine}, volume = {19}, number = {1}, pages = {6}, pmid = {33435977}, issn = {1741-7015}, mesh = {Biomarkers ; Diet, Mediterranean ; Exercise ; Humans ; Hypertension/complications ; Nervous System Diseases/etiology/*genetics/prevention & control ; Protective Factors ; Risk Factors ; }, abstract = {BACKGROUND: The etiologies of chronic neurological diseases, which heavily contribute to global disease burden, remain far from elucidated. Despite available umbrella reviews on single contributing factors or diseases, no study has systematically captured non-purely genetic risk and/or protective factors for chronic neurological diseases.
METHODS: We performed a systematic analysis of umbrella reviews (meta-umbrella) published until September 20th, 2018, using broad search terms in MEDLINE, SCOPUS, Web of Science, Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature, ProQuest Dissertations & Theses, JBI Database of Systematic Reviews and Implementation Reports, DARE, and PROSPERO. The PRISMA guidelines were followed for this study. Reference lists of the identified umbrella reviews were also screened, and the methodological details were assessed using the AMSTAR tool. For each non-purely genetic factor association, random effects summary effect size, 95% confidence and prediction intervals, and significance and heterogeneity levels facilitated the assessment of the credibility of the epidemiological evidence identified.
RESULTS: We identified 2797 potentially relevant reviews, and 14 umbrella reviews (203 unique meta-analyses) were eligible. The median number of primary studies per meta-analysis was 7 (interquartile range (IQR) 7) and that of participants was 8873 (IQR 36,394). The search yielded 115 distinctly named non-genetic risk and protective factors with a significant association, with various strengths of evidence. Mediterranean diet was associated with lower risk of dementia, Alzheimer disease (AD), cognitive impairment, stroke, and neurodegenerative diseases in general. In Parkinson disease (PD) and AD/dementia, coffee consumption, and physical activity were protective factors. Low serum uric acid levels were associated with increased risk of PD. Smoking was associated with elevated risk of multiple sclerosis and dementia but lower risk of PD, while hypertension was associated with lower risk of PD but higher risk of dementia. Chronic occupational exposure to lead was associated with higher risk of amyotrophic lateral sclerosis. Late-life depression was associated with higher risk of AD and any form of dementia.
CONCLUSIONS: We identified several non-genetic risk and protective factors for various neurological diseases relevant to preventive clinical neurology, health policy, and lifestyle counseling. Our findings could offer new perspectives in secondary research (meta-research).}, }
@article {pmid33433755, year = {2021}, author = {Zhou, Q and Yuan, M and Qiu, W and Cao, W and Xu, R}, title = {Preclinical studies of mesenchymal stem cells transplantation in amyotrophic lateral sclerosis: a systemic review and metaanalysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {42}, number = {9}, pages = {3637-3646}, pmid = {33433755}, issn = {1590-3478}, mesh = {Animals ; *Amyotrophic Lateral Sclerosis/therapy ; Disease Models, Animal ; Disease Progression ; *Mesenchymal Stem Cell Transplantation ; *Mesenchymal Stem Cells ; }, abstract = {OBJECTIVES: To assess the quality of preclinical evidence for mesenchymal stromal cell (MSCs) therapy of amyotrophic lateral sclerosis (ALS), decide the effect size of MSCs treatment, and identify clinical parameters that associate with differences in MSCs effects.
METHODS: A literature search identified studies of MSCs in animal models of ALS. Four main indicators (age of onset, disease progression deceleration, survival time, hazard ratio reduction) obtained through specific neurobehavioral assessment, and 14 relative clinical parameters were extracted for metaanalysis and systematic review. Subgroup analysis and metaregression were performed to explore sources of heterogeneity.
RESULTS: A total of 25 studies and 41 independent treated arms were used for systematic review and metaanalysis. After adjusted by sensitivity analysis, the mean effect sizes were significantly improved by 0.28 for the age of onset, 0.25 for the disease progression deceleration, 0.54 for the survival time, and 0.48 for hazard ratio reduction. With further analysis, we demonstrated that both the clinical parameter of animal gender and immunosuppressive drug of cyclosporin A (CSA) had a close correlation with disease progression deceleration effect size.
CONCLUSIONS: These results showed that MSCs transplantation was beneficial for neurobehavioral improvement in the treatment of ALS animal model and recommended that all potential reparative roles of MSCs postdelivery, should be carefully considered and fused to maximize the effectiveness of MSCs therapy in ALS.}, }
@article {pmid33423565, year = {2021}, author = {Gu, D and Ou, S and Tang, M and Yin, Z and Wang, Z and Liu, G}, title = {Trauma and amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {22}, number = {3-4}, pages = {170-185}, doi = {10.1080/21678421.2020.1861024}, pmid = {33423565}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis/epidemiology ; *Craniocerebral Trauma/complications/epidemiology ; Humans ; Observational Studies as Topic ; Odds Ratio ; Risk Factors ; }, abstract = {Background: Trauma especially head trauma is considered a potential risk factor of amyotrophic lateral sclerosis (ALS), but their association has not been well established. We aimed to determine the association of prior trauma with ALS risk. Methods: This study was performed according to the Meta-Analysis of Observational Studies in Epidemiology guideline to assess related literatures, and a random-effects model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Twenty-nine eligible articles involving 18,390 cases and 6,519,391 controls were included in this meta-analysis. The results showed that trauma was associated with an increased risk of ALS (pooled OR = 1.51, 95% CI: 1.32-1.73). Besides, patients with trunk trauma, head trauma and lower limb trauma had an increased risk of ALS, whereas no evidence suggested that upper limb trauma and spine trauma could increase ALS risk. Considering the number of traumatic events, the association between trauma and ALS risk was significant for patients with repeated trauma events (pooled OR = 1.21, 95% CI: 1.07-1.38). The results showed that individuals with a history of trauma within 5 years were more likely to be diagnosed with ALS (pooled OR = 1.84, 95% CI: 1.56-2.17). Importantly, both old trauma and very old trauma were found to be associated with an increased risk of ALS (pooled OR = 1.24, 95% CI: 1.12-1.38; pooled OR = 1.28, 95% CI: 1.10-1.49; respectively). Conclusions: This meta-analysis indicated that trauma could increase ALS risk, which may be applied for the clinicians to tailor targeted treatment regimens and make prophylactic strategies for ALS in traumatic patients.}, }
@article {pmid33419478, year = {2021}, author = {Cheng, Y and Chen, Y and Shang, H}, title = {Aberrations of biochemical indicators in amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Translational neurodegeneration}, volume = {10}, number = {1}, pages = {3}, pmid = {33419478}, issn = {2047-9158}, support = {2016YFC0901504//National Key Research and Development Program of China/International ; }, mesh = {Amyotrophic Lateral Sclerosis/*diagnosis ; Biomarkers ; Creatine Kinase/metabolism ; Energy Metabolism/physiology ; Ferritins/blood ; Humans ; Iron/metabolism ; }, abstract = {Accumulating evidence has suggested that the pathological changes in amyotrophic lateral sclerosis (ALS) are not only confined to the central nervous system but also occur in the peripheral circulating system. Here, we performed a meta-analysis based on the PubMed, EMBASE, EBSCO, and CNKI databases, to find out biochemical indicators associated with energy metabolism, iron homeostasis, and muscle injury that are altered in ALS patients and their correlations with ALS phenotypes. Forty-six studies covering 17 biochemical indicators, representing 5454 ALS patients and 7986 control subjects, were included in this meta-analysis. Four indicators, including fasting blood glucose level (weighted mean difference [WMD] = 0.13, 95% CI [0.06-0.21], p = 0.001), serum ferritin level (WMD = 63.42, 95% CI [48.12-78.73], p < 0.001), transferrin saturation coefficient level (WMD = 2.79, 95% CI [1.52-4.05], p < 0.001), and creatine kinase level (WMD = 80.29, 95% CI [32.90-127.67], p < 0.001), were significantly higher in the ALS patients, whereas the total iron-binding capacity (WMD = - 2.42, 95% CI [- 3.93, - 0.90], p = 0.002) was significantly lower in ALS patients than in the control subjects. In contrast, the other 12 candidates did not show significant differences between ALS patients and controls. Moreover, pooled hazard ratios (HR) showed significantly reduced survival (HR = 1.38, 95% CI [1.02-1.88], p = 0.039) of ALS patients with elevated serum ferritin levels. These findings suggest that abnormalities in energy metabolism and disruption of iron homeostasis are involved in the pathogenesis of ALS. In addition, the serum ferritin level is negatively associated with the overall survival of ALS patients.}, }
@article {pmid33347974, year = {2021}, author = {Noori, A and Mezlini, AM and Hyman, BT and Serrano-Pozo, A and Das, S}, title = {Systematic review and meta-analysis of human transcriptomics reveals neuroinflammation, deficient energy metabolism, and proteostasis failure across neurodegeneration.}, journal = {Neurobiology of disease}, volume = {149}, number = {}, pages = {105225}, pmid = {33347974}, issn = {1095-953X}, support = {K08 AG064039/AG/NIA NIH HHS/United States ; P30 AG062421/AG/NIA NIH HHS/United States ; RF1 AG058674/AG/NIA NIH HHS/United States ; }, mesh = {Alzheimer Disease/genetics/metabolism/pathology ; Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Brain/*metabolism/pathology ; Energy Metabolism/*physiology ; Frontotemporal Dementia/genetics/metabolism/pathology ; Humans ; Inflammation/genetics/metabolism/pathology ; Inflammation Mediators/*metabolism ; Lewy Body Disease/genetics/metabolism/pathology ; Neurodegenerative Diseases/genetics/*metabolism/pathology ; Proteostasis/*physiology ; Transcriptome/*physiology ; }, abstract = {Neurodegenerative disorders such as Alzheimer's disease (AD), Lewy body diseases (LBD), and the amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD) spectrum are defined by the accumulation of specific misfolded protein aggregates. However, the mechanisms by which each proteinopathy leads to neurodegeneration remain elusive. We hypothesized that there is a common "pan-neurodegenerative" gene expression signature driving pathophysiology across these clinically and pathologically diverse proteinopathies. To test this hypothesis, we performed a systematic review of human CNS transcriptomics datasets from AD, LBD, and ALS-FTD patients and age-matched controls in the Gene Expression Omnibus (GEO) and ArrayExpress databases, followed by consistent processing of each dataset, meta-analysis, pathway enrichment, and overlap analyses. After applying pre-specified eligibility criteria and stringent data pre-processing, a total of 2600 samples from 26 AD, 21 LBD, and 13 ALS-FTD datasets were included in the meta-analysis. The pan-neurodegenerative gene signature is characterized by an upregulation of innate immunity, cytoskeleton, and transcription and RNA processing genes, and a downregulation of the mitochondrial electron transport chain. Pathway enrichment analyses also revealed the upregulation of neuroinflammation (including Toll-like receptor, TNF, and NFκB signaling) and phagocytosis, and the downregulation of mitochondrial oxidative phosphorylation, lysosomal acidification, and ubiquitin-proteasome pathways. Our findings suggest that neuroinflammation and a failure in both neuronal energy metabolism and protein degradation systems are consistent features underlying neurodegenerative diseases, despite differences in the extent of neuronal loss and brain regions involved.}, }
@article {pmid33318164, year = {2021}, author = {Warnecke, T and Labeit, B and Schroeder, J and Reckels, A and Ahring, S and Lapa, S and Claus, I and Muhle, P and Suntrup-Krueger, S and Dziewas, R}, title = {Neurogenic Dysphagia: Systematic Review and Proposal of a Classification System.}, journal = {Neurology}, volume = {96}, number = {6}, pages = {e876-e889}, doi = {10.1212/WNL.0000000000011350}, pmid = {33318164}, issn = {1526-632X}, mesh = {Deglutition Disorders/*classification/*diagnosis/etiology ; Humans ; Nervous System Diseases/*complications ; }, abstract = {OBJECTIVE: Introduction and validation of a phenotypic classification of neurogenic dysphagia based on flexible endoscopic evaluation of swallowing (FEES).
METHODS: A systematic literature review was conducted, searching MEDLINE from inception to May 2020 for FEES findings in neurologic diseases of interest. Based on a retrospective analysis of FEES videos in neurologic diseases and considering the results from the review, a classification of neurogenic dysphagia was developed distinguishing different phenotypes. The classification was validated using 1,012 randomly selected FEES videos of patients with various neurologic disorders. Chi-square tests were used to compare the distribution of dysphagia phenotypes between the underlying neurologic disorders.
RESULTS: A total of 159 articles were identified, of which 59 were included in the qualitative synthesis. Seven dysphagia phenotypes were identified: (1) "premature bolus spillage" and (2) "delayed swallowing reflex" occurred mainly in stroke, (3) "predominance of residue in the valleculae" was most common in Parkinson disease, (4) "predominance of residue in the piriform sinus" occurred only in myositis, motoneuron disease, and brainstem stroke, (5) "pharyngolaryngeal movement disorder" was found in atypical Parkinsonian syndromes and stroke, (6) "fatigable swallowing weakness" was common in myasthenia gravis, and (7) "complex disorder" with a heterogeneous dysphagia pattern was the leading mechanism in amyotrophic lateral sclerosis. The interrater reliability showed a strong agreement (kappa = 0.84).
CONCLUSION: Neurogenic dysphagia is not a symptom, but a multietiologic syndrome with different phenotypic patterns depending on the underlying disease. Dysphagia phenotypes can facilitate differential diagnosis in patients with dysphagia of unclear etiology.}, }
@article {pmid33303515, year = {2020}, author = {Giusti, A and Nkhoma, K and Petrus, R and Petersen, I and Gwyther, L and Farrant, L and Venkatapuram, S and Harding, R}, title = {The empirical evidence underpinning the concept and practice of person-centred care for serious illness: a systematic review.}, journal = {BMJ global health}, volume = {5}, number = {12}, pages = {}, pmid = {33303515}, issn = {2059-7908}, mesh = {*Clinical Decision-Making ; Communication ; Delivery of Health Care ; Humans ; *Patient-Centered Care ; *Quality of Life ; Uncertainty ; }, abstract = {INTRODUCTION: Person-centred care has become internationally recognised as a critical attribute of high-quality healthcare. However, the concept has been criticised for being poorly theorised and operationalised. Serious illness is especially aligned with the need for person-centredness, usually necessitating involvement of significant others, management of clinical uncertainty, high-quality communication and joint decision-making to deliver care concordant with patient preferences. This review aimed to identify and appraise the empirical evidence underpinning conceptualisations of 'person-centredness' for serious illness.
METHODS: Search strategy conducted in May 2020. Databases: CINAHL, Embase, PubMed, Ovid Global Health, MEDLINE and PsycINFO. Free text search terms related to (1) person-centredness, (2) serious illness and (3) concept/practice. Tabulation, textual description and narrative synthesis were performed, and quality appraisal conducted using QualSyst tools. Santana et al's person-centred care model (2018) was used to structure analysis.
RESULTS: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow data: n=12,446 studies screened by title/abstract, n=144 full articles assessed for eligibility, n=18 studies retained. All studies (n=18) are from high-income countries, and are largely of high quality (median score 0.82). The findings suggest that person-centred care encompasses the patient and family being respected, given complete information, involved in decision-making and supported in their physical, psychological, social and existential needs. The studies highlight the importance of involving and supporting family/friends, promoting continuation of normality and self-identity, and structuring service organisation to enable care continuity.
CONCLUSION: Person-centred healthcare must value the social network of patients, promote quality of life and reform structurally to improve patients' experience interacting with the healthcare system. Staff must be supported to flexibly adapt skills, communication, routines or environments for individual patients. There remains a need for primary data investigating the meaning and practice of PCC in a greater diversity of diagnostic groups and settings, and a need to ground potential components of PCC within broader universal values and ethical theory.}, }
@article {pmid33300320, year = {2021}, author = {Hinkelbein, J and Schmitz, J and Mathes, A and DE Robertis, E}, title = {Performance of the laryngeal tube for airway management during cardiopulmonary resuscitation.}, journal = {Minerva anestesiologica}, volume = {87}, number = {5}, pages = {580-590}, doi = {10.23736/S0375-9393.20.14446-8}, pmid = {33300320}, issn = {1827-1596}, mesh = {Airway Management ; *Cardiopulmonary Resuscitation ; *Heart Arrest/therapy ; Humans ; Intubation, Intratracheal ; Survival Rate ; }, abstract = {INTRODUCTION: Sudden cardiac arrest is one of the leading causes of death in Europe and the whole world. Effective chest compressions and advanced airway management have been shown to improve survival rates. Supraglottic airway devices such as the laryngeal tube (LT) are a well-known strategy for patients with cardiac arrest during both basic (BLS) and advanced life support (ALS). This systematic literature review aimed to summarize current data for using the LT when performing BLS and ALS.
EVIDENCE ACQUISITION: Recent data on the use of the LT during cardiopulmonary resuscitation (CPR) was gathered by using the Medline database and a specific search strategy. Terms were used in various order and combinations without time restrictions. A total of N.=1005 studies were identified and screened by two experienced anesthesiologists/emergency physicians independently. Altogether, data of N.=19 relevant papers were identified and included in the analysis.
EVIDENCE SYNTHESIS: Using the LT showed fast and easy placement with high success rates (76% to 94%) and was associated with higher short-term survival as compared to other strategies for initial airway management (2.2% vs. 1.4%). Quality of CPR such as chest compression fraction (CCF) before and after LT-insertion is improved (75% vs. 59%). For long-term survival, the LT showed lower survival rates.
CONCLUSIONS: Especially as initial device of airway management (for inexperienced staff), the use of a LT is easy and results in a fast insertion. The advantages of the LT as compared to bag mask ventilation and endotracheal intubation are inhomogeneous in recent literature.}, }
@article {pmid33295415, year = {2020}, author = {Vasconcelos, K and Oliveira, ASB and Fuchs, LFP and Simões, RS and Simoes, MJ and Girão, MJBC and Soares Júnior, JM and Baracat, EC}, title = {Action of hormonal therapy in amyotrophic lateral sclerosis: a systematic review.}, journal = {Revista da Associacao Medica Brasileira (1992)}, volume = {66}, number = {11}, pages = {1589-1594}, doi = {10.1590/1806-9282.66.11.1589}, pmid = {33295415}, issn = {1806-9282}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Female ; Humans ; Male ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a fatal disease characterized by muscle weakness, atrophy, fasciculations, and decreased reflexes due to upper and lower motor neurons death. It can be present in both sexes (55-65 years), but with predominance in males. However, in female patients, ALS presents its first symptoms when they are already postmenopausal, when then the incidence ratio of the disease is practically equal between the sexes, which leads to a probable involvement of sex hormones in the development and protection against ALS. The aim of this systematic review, which used the PRISMA consensus and NOS (New Castle-Ottawa Scale) score, was to evaluate the evidence of the action of hormone therapy in women with ALS. The Medline and Cochrane databases were accessed from March 2019 to June 2019, and only full-text articles in Spanish, English, and Portuguese were included. Only four articles matched our inclusion criteria. Postmenopausal women who used exogenous estrogen did not have the same protective factor as women still under the action of endogenous estrogen in the same age group. There was also no increase in the survival of these women.}, }
@article {pmid33251776, year = {2020}, author = {Woo, A and Tchoe, HJ and Shin, HW and Shin, CM and Lim, CM}, title = {Assisted Breathing with a Diaphragm Pacing System: A Systematic Review.}, journal = {Yonsei medical journal}, volume = {61}, number = {12}, pages = {1024-1033}, pmid = {33251776}, issn = {1976-2437}, support = {/NECA/National Evidence-based Healthcare Collaborating Agency/Korea ; }, mesh = {Amyotrophic Lateral Sclerosis/*complications/diagnosis/*therapy ; Diaphragm/*pathology ; Humans ; Prostheses and Implants/adverse effects ; *Respiration ; Respiration, Artificial/*methods ; Respiratory Insufficiency/diagnosis/*etiology/*therapy ; Spinal Cord Injuries/complications/physiopathology ; Treatment Outcome ; }, abstract = {PURPOSE: Patients with respiratory failure associated with neurological dysfunction often require mechanical ventilator support, which poses increased economic burden and ventilator-associated complications. A diaphragm pacing system (DPS) is an implanted device that provides respiratory support for such patients. In this systematic review, we reviewed the literature to assess the safety and efficacy of DPS for patients with respiratory failure resulting from amyotrophic lateral sclerosis (ALS) or cervical spinal cord injuries.
MATERIALS AND METHODS: The following databases were searched from July 10 to July 30, 2018: MEDLINE, EMBASE, Cochran library, KoreaMed, Research Information Sharing Service, Korean studies Information Service System, Korea Institute of Science and Technology Information, and Korean Medical database. The abstracts and full texts of the searched articles were reviewed by two reviewers.
RESULTS: The search keywords generated 197 articles: two randomized controlled trials, two case-control studies, and one case report involving patients with ALS; one cohort study, one case-control study, and two case reports involving patients with cervical spine injury; and one case report involving patients with both conditions were included. The primary outcome was safety profile (complications and adverse event) and efficacy (overall survival and sleep improvement). Complications and adverse events were more common in patients with ALS and spinal cord injury receiving DPS than in controls. Efficacy outcomes were inconsistent across ALS studies.
CONCLUSION: Based on safety and efficacy results, we do not support using DPS to manage respiratory failure in patients with ALS or cervical spine injury.}, }
@article {pmid33202965, year = {2020}, author = {Oliveira, M and Padrão, A and Ramalho, A and Lobo, M and Teodoro, AC and Gonçalves, H and Freitas, A}, title = {Geospatial Analysis of Environmental Atmospheric Risk Factors in Neurodegenerative Diseases: A Systematic Review.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {22}, pages = {}, pmid = {33202965}, issn = {1660-4601}, mesh = {*Air Pollutants/adverse effects ; Case-Control Studies ; Cross-Sectional Studies ; Humans ; *Neurodegenerative Diseases/epidemiology/etiology ; Nigeria/epidemiology ; Risk Factors ; }, abstract = {Despite the vast evidence on the environmental influence in neurodegenerative diseases, those considering a geospatial approach are scarce. We conducted a systematic review to identify studies concerning environmental atmospheric risk factors for neurodegenerative diseases that have used geospatial analysis/tools. PubMed, Web of Science, and Scopus were searched for all scientific studies that included a neurodegenerative disease, an environmental atmospheric factor, and a geographical analysis. Of the 34 included papers, approximately 60% were related to multiple sclerosis (MS), hence being the most studied neurodegenerative disease in the context of this study. Sun exposure (n = 13) followed by the most common exhaustion gases (n = 10 for nitrogen dioxide (NO2) and n = 5 for carbon monoxide (CO)) were the most studied atmospheric factors. Only one study used a geospatial interpolation model, although 13 studies used remote sensing data to compute atmospheric factors. In 20% of papers, we found an inverse correlation between sun exposure and multiple sclerosis. No consensus was reached in the analysis of nitrogen dioxide and Parkinson's disease, but it was related to dementia and amyotrophic lateral sclerosis. This systematic review (number CRD42020196188 in PROSPERO's database) provides an insight into the available evidence regarding the geospatial influence of environmental factors on neurodegenerative diseases.}, }
@article {pmid33191797, year = {2021}, author = {Lucia, D and McCombe, PA and Henderson, RD and Ngo, ST}, title = {Disorders of sleep and wakefulness in amyotrophic lateral sclerosis (ALS): a systematic review.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {22}, number = {3-4}, pages = {161-169}, doi = {10.1080/21678421.2020.1844755}, pmid = {33191797}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis/complications/epidemiology ; Humans ; Polysomnography ; Sleep ; *Sleep Wake Disorders/etiology ; Wakefulness ; }, abstract = {Disorders of sleep and wakefulness are common among neurodegenerative diseases. While amyotrophic lateral sclerosis (ALS) predominately manifests as motor symptoms, there is emerging evidence that disruptions to sleep and wakefulness also occur. This systematic review aims to report the most common disorders of sleep and wakefulness in ALS. We conducted a qualitative systematic review as per PRISMA guidelines and searched literature assessing the association between disorders of sleep and wakefulness with ALS using the PubMed and Medline database. Overall, 50-63% of patients with ALS have poor sleep quality as reported using the Pittsburgh Sleep Quality Index Questionnaire (PSQI). A higher proportion of ALS patients are categorized as poor sleepers, however there is conflicting evidence as to whether patients with ALS are more likely to exhibit excessive daytime sleepiness. Of the studies that utilized polysomnography, all reported various degrees of impairment to sleep microstructure and architecture among ALS patients. In future, longitudinal clinical studies will be essential for establishing the significance of impaired sleep in ALS. Future studies are also needed to establish whether the self-reported measures of poor sleep and impairment to sleep architecture occurs as a direct consequence of the disease, whether they are an early manifestation of the disease, and/or if they contribute to the neurodegenerative process.}, }
@article {pmid33178110, year = {2020}, author = {Liu, J and Luo, X and Chen, X and Shang, H}, title = {Lipid Profile in Patients With Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.}, journal = {Frontiers in neurology}, volume = {11}, number = {}, pages = {567753}, pmid = {33178110}, issn = {1664-2295}, abstract = {Background: Studies have investigated the lipid profile in amyotrophic lateral sclerosis (ALS), including the levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), and higher low-density lipoprotein (LDL), and the associations with mortality of ALS, but the results were inconsistent. Therefore, we conducted this meta-analysis to systematically answer this unsolved question. Methods: We searched all the related studies that probed into the association between serum lipid levels and ALS based on PubMed, EMBASE, and Cochrane library from January 1990 to July 2020. The quality of the included studies was evaluated by using the Newcastle-Ottawa Scale (NOS). All the statistical analyses of this meta-analysis were performed using the Stata version 12.0 software. Results: Fourteen studies with a total of 3,291 ALS patients and 3,367 controls were included. Among them, 10 studies compared the lipid profile between ALS patients and controls. The results indicated that compared with controls, ALS patients from both Europe and Asia had lower levels of TG and HDL, but the levels of TC and LDL were higher in ALS patients from Europe. However, after systemic analyses, the altered TC level was significant only in Asian ALS patients; the differences of other lipids were not significant. Concerning the effect of lipid profile on mortality of ALS, analyses of four cohort studies showed that the levels of all lipids were not associated with overall mortality in ALS. Conclusion: The results of the present study showed that Asian ALS patients had lower TC levels than controls, and the levels of all lipids were not associated with mortality of ALS.}, }
@article {pmid33138865, year = {2020}, author = {Hinkelbein, J and Kerkhoff, S and Adler, C and Ahlbäck, A and Braunecker, S and Burgard, D and Cirillo, F and De Robertis, E and Glaser, E and Haidl, TK and Hodkinson, P and Iovino, IZ and Jansen, S and Johnson, KVL and Jünger, S and Komorowski, M and Leary, M and Mackaill, C and Nagrebetsky, A and Neuhaus, C and Rehnberg, L and Romano, GM and Russomano, T and Schmitz, J and Spelten, O and Starck, C and Thierry, S and Velho, R and Warnecke, T}, title = {Cardiopulmonary resuscitation (CPR) during spaceflight - a guideline for CPR in microgravity from the German Society of Aerospace Medicine (DGLRM) and the European Society of Aerospace Medicine Space Medicine Group (ESAM-SMG).}, journal = {Scandinavian journal of trauma, resuscitation and emergency medicine}, volume = {28}, number = {1}, pages = {108}, pmid = {33138865}, issn = {1757-7241}, mesh = {Aerospace Medicine/*methods ; Cardiopulmonary Resuscitation/*methods ; *Consensus ; Critical Care/*methods ; Emergencies ; Europe ; Heart Arrest/*therapy ; Humans ; *Societies, Medical ; *Space Flight ; }, abstract = {BACKGROUND: With the "Artemis"-mission mankind will return to the Moon by 2024. Prolonged periods in space will not only present physical and psychological challenges to the astronauts, but also pose risks concerning the medical treatment capabilities of the crew. So far, no guideline exists for the treatment of severe medical emergencies in microgravity. We, as a international group of researchers related to the field of aerospace medicine and critical care, took on the challenge and developed a an evidence-based guideline for the arguably most severe medical emergency - cardiac arrest.
METHODS: After the creation of said international group, PICO questions regarding the topic cardiopulmonary resuscitation in microgravity were developed to guide the systematic literature research. Afterwards a precise search strategy was compiled which was then applied to "MEDLINE". Four thousand one hundred sixty-five findings were retrieved and consecutively screened by at least 2 reviewers. This led to 88 original publications that were acquired in full-text version and then critically appraised using the GRADE methodology. Those studies formed to basis for the guideline recommendations that were designed by at least 2 experts on the given field. Afterwards those recommendations were subject to a consensus finding process according to the DELPHI-methodology.
RESULTS: We recommend a differentiated approach to CPR in microgravity with a division into basic life support (BLS) and advanced life support (ALS) similar to the Earth-based guidelines. In immediate BLS, the chest compression method of choice is the Evetts-Russomano method (ER), whereas in an ALS scenario, with the patient being restrained on the Crew Medical Restraint System, the handstand method (HS) should be applied. Airway management should only be performed if at least two rescuers are present and the patient has been restrained. A supraglottic airway device should be used for airway management where crew members untrained in tracheal intubation (TI) are involved.
DISCUSSION: CPR in microgravity is feasible and should be applied according to the Earth-based guidelines of the AHA/ERC in relation to fundamental statements, like urgent recognition and action, focus on high-quality chest compressions, compression depth and compression-ventilation ratio. However, the special circumstances presented by microgravity and spaceflight must be considered concerning central points such as rescuer position and methods for the performance of chest compressions, airway management and defibrillation.}, }
@article {pmid33095366, year = {2021}, author = {Salari, N and Rasoulpoor, S and Hosseinian-Far, A and Razazian, N and Mansouri, K and Mohammadi, M and Vaisi-Raygani, A and Jalali, R and Shabani, S}, title = {Association between serum paraoxonase 1 activity and its polymorphisms with multiple sclerosis: a systematic review.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {42}, number = {2}, pages = {491-500}, pmid = {33095366}, issn = {1590-3478}, mesh = {Alleles ; *Aryldialkylphosphatase/genetics ; Genotype ; Humans ; Iran ; *Multiple Sclerosis/genetics ; Polymorphism, Genetic ; }, abstract = {BACKGROUND: Human serum paraoxonase (PON) is an enzyme that is synthesized by the liver and enters the bloodstream, and it is transmitted by high-density lipoproteins (HDL). Paraoxonase 1 (PON1) is a hydrolytic enzyme with a wide range of substrates and the ability to protect against lipid oxidation. In this study, due to the activity of PON1 in the brain and its antioxidant effects on the reduction of neurological disorders in the central nervous system, the role of PON1 and its polymorphisms related to multiple sclerosis has been examined to enhance treatment methods.
METHODS: This article is a systematic review. In this study, the role of PON1 and its polymorphisms in multiple sclerosis (MS) has been investigated. Articles published in Persian and international databases of SID, Google Scholar, ISI (WoS), Magiran, PubMed, Scopus, IranDoc, Science Direct, and Iran Medix were examined, using the search keywords of Paraoxonase 1, polymorphism, multiple sclerosis, and PON1.
RESULTS: PON1 is undoubtedly a potential factor in the pathogenesis of multiple sclerosis, and it plays an important role in protecting antioxidants in the blood. Oxidative stress and lipid peroxidation are factors in the pathogenesis of MS. Both inflammatory cytokines and oxidative stress have a detrimental effect on PON1. However, reducing the activity of PON1 may help to restore the pathogenesis of the disease.
CONCLUSION: Decreased PON1 activity and PON1 polymorphism are associated with several neurological diseases, including ischemic stroke, white matter lesions (WMLs), amyotrophic lateral sclerosis (ALS), dementia, and Parkinson's disease. PON1-55M alleles in Italians and PON1-192Q alleles in Poles were associated with a high risk of MS. Moreover, PON1-55 and PON1-192 polymorphisms were not associated with MS onset age, nor its evolutionary type.}, }
@article {pmid33066046, year = {2020}, author = {Gómez-Anca, S and Barros-Dios, JM}, title = {Radon Exposure and Neurodegenerative Disease.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {20}, pages = {}, pmid = {33066046}, issn = {1660-4601}, mesh = {Alzheimer Disease ; Amyotrophic Lateral Sclerosis ; Humans ; Motor Neuron Disease/*chemically induced ; Neurodegenerative Diseases/*chemically induced ; Radon/*adverse effects ; }, abstract = {Background: To carry out a systematic review of scientific literature about the association between radon exposure and neurodegenerative diseases. Methods: We performed a bibliographic search in the following databases: Pub med (Medline), Cochrane, BioMed Central and Web of Science. We collected the data by following a predetermined search strategy in which several terms werecombined. After an initial search, 77 articles were obtained.10 of which fulfilled the inclusion criteria. Five of these 10 studies were related to multiple sclerosis (MS), 2 were about motor neuron diseases (MND), in particular amyotrophic lateral sclerosis (ALS) and 3 were related to both Alzheimer's disease (AD) and Parkinson's disease (PD). Results: The majority of the included articles, suggested a possible association between radon exposure and a subsequent development of neurodegenerative diseases. Some of the studies that obtained statistically significant resultsrevealed a possible association between radon exposure and an increase in MS prevalence. Furthermore, it was also suggested that radon exposure increases MND and AD mortality. Regarding AD and PD, it was observed that certainde cay products of radon-222 ([222]Rn), specifically polonium-210 ([210]Po) and bismuth-210 ([210]Bi), present a characteristic distributionpattern within the brain anatomy. However, the study with the highest scientific evidence included in this review, which investigated a possible association between the concentration of residential radon gas and the MS incidence, revealed no significant results. Conclusions: It cannot be concluded, although it is observed, that there is a possible causal association between radon exposure and neurodegenerative diseases. Most of the available studies are ecological so, studies of higher statistical evidence are needed to establish a causal relationship. Further research is needed on this topic.}, }
@article {pmid33061334, year = {2020}, author = {Maresova, P and Hruska, J and Klimova, B and Barakovic, S and Krejcar, O}, title = {Activities of Daily Living and Associated Costs in the Most Widespread Neurodegenerative Diseases: A Systematic Review.}, journal = {Clinical interventions in aging}, volume = {15}, number = {}, pages = {1841-1862}, pmid = {33061334}, issn = {1178-1998}, mesh = {*Activities of Daily Living ; Aged ; Aged, 80 and over ; Female ; Health Care Costs ; Humans ; Male ; Middle Aged ; Neurodegenerative Diseases/*economics ; Quality of Life ; }, abstract = {Nowadays, the population is rapidly ageing because of increasing life expectancy and decreasing birth rates. Thus, the purpose of this systematic review is to prepare a comprehensive overview which identifies the activities of daily living (ADLs) that are gradually reduced among patients with dementia, as well as explore the therapies applied in relation to dementia and how they effectively improve the quality of life (QoL) of patients and caregivers. Furthermore, we aim to summarise the ADL activities influenced by therapies and examine the treatment costs and care for patients so that recommendations for research and development (R&D) can be made to improve both the QoL of people with dementia and cost-saving measures. The research focuses on four selected neurodegenerative diseases: Alzheimer, Parkinson, vascular dementia, and amyotrophic lateral sclerosis. Therefore, the peer-reviewed English written articles from 2014 to 2019 were searched between September 1 and December 13, 2019. Twenty-seven papers were included in the analysis. The results show that essential assistance occurs in connection with activities: eating, drinking, dressing, bathing, personal hygiene, use of the toilet, and transport. By contrast, shopping or cleaning is not addressed as much. A lower ability to take care of oneself is connected with poor patient health and higher social care costs because the patient requires care from external sources, such as home aid or nurse visits. The challenge that remains is to shift new knowledge from scientific disciplines and connect it with the needs of patients to remove legitimate barriers and increase the acceptance of new solutions by popularisation. Additionally, regarding the burden on caregivers, it would be appropriate to promote this area of education and employment so that family members can use formal caregivers, ensuring them free time and much-needed rest.}, }
@article {pmid33031990, year = {2020}, author = {Wannarong, T and Ungprasert, P}, title = {Diabetes mellitus is associated with a lower risk of amyotrophic lateral sclerosis: A systematic review and meta-analysis.}, journal = {Clinical neurology and neurosurgery}, volume = {199}, number = {}, pages = {106248}, doi = {10.1016/j.clineuro.2020.106248}, pmid = {33031990}, issn = {1872-6968}, mesh = {Amyotrophic Lateral Sclerosis/*diagnosis/*epidemiology/physiopathology ; Case-Control Studies ; Cohort Studies ; Diabetes Mellitus/*diagnosis/*epidemiology/physiopathology ; Humans ; Risk Factors ; }, abstract = {BACKGROUND/AIMS: Previous studies have suggested that diabetes mellitus (DM) could be a protective factor against amyotrophic lateral sclerosis (ALS) although the results are inconsistent. This study aimed to comprehensively investigate this relationship by identifying all available studies and summarizing their results.
METHODS: A systematic review was conducted in MEDLINE and EMBASE database from inception to January 1st, 2020 to identify cohort studies and case-control studies that investigated the risk of development of ALS among patients with DM versus individuals without DM. Point estimates and standard errors from eligible studies were pooled together using the generic inverse variance method, as described by DerSimonian and Laird. Visualization of the funnel plot was used to assess for the presence of publication bias.
RESULTS: A total of 1683 articles were identified by the search strategy. After two rounds of review, three cohort studies and eight case-control studies fulfilled the inclusion criteria and were included in the meta-analysis. The risk of developing ALS was significantly lower among patients with DM than individuals without DM with the pooled relative risk of 0.68 (95 % CI, 0.55 - 0.84; I[2] 81 %). The funnel plot was relatively symmetric and was not suggestive of the presence of publication bias.
CONCLUSION: A significantly decreased risk of ALS among patients with DM was observed in this meta-analysis.}, }
@article {pmid32956536, year = {2020}, author = {Garrison, SR and Korownyk, CS and Kolber, MR and Allan, GM and Musini, VM and Sekhon, RK and Dugré, N}, title = {Magnesium for skeletal muscle cramps.}, journal = {The Cochrane database of systematic reviews}, volume = {9}, number = {9}, pages = {CD009402}, pmid = {32956536}, issn = {1469-493X}, support = {//CIHR/Canada ; }, mesh = {Adult ; Age Factors ; Aged ; Cross-Over Studies ; Female ; Humans ; Magnesium/adverse effects/*therapeutic use ; Male ; Middle Aged ; Muscle Cramp/*drug therapy/etiology ; *Muscle, Skeletal ; Placebos/therapeutic use ; Pregnancy ; Pregnancy Complications/*drug therapy ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: Skeletal muscle cramps are common and often occur in association with pregnancy, advanced age, exercise or motor neuron disorders (such as amyotrophic lateral sclerosis). Typically, such cramps have no obvious underlying pathology, and so are termed idiopathic. Magnesium supplements are marketed for the prophylaxis of cramps but the efficacy of magnesium for this purpose remains unclear. This is an update of a Cochrane Review first published in 2012, and performed to identify and incorporate more recent studies.
OBJECTIVES: To assess the effects of magnesium supplementation compared to no treatment, placebo control or other cramp therapies in people with skeletal muscle cramps. SEARCH METHODS: On 9 September 2019, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, CINAHL Plus, AMED, and SPORTDiscus. We also searched WHO-ICTRP and ClinicalTrials.gov for registered trials that might be ongoing or unpublished, and ISI Web of Science for studies citing the studies included in this review.
SELECTION CRITERIA: Randomized controlled trials (RCTs) of magnesium supplementation (in any form) to prevent skeletal muscle cramps in any patient group (i.e. all clinical presentations of cramp). We considered comparisons of magnesium with no treatment, placebo control, or other therapy.
DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted data. Two review authors assessed risk of bias. We attempted to contact all study authors when questions arose and obtained participant-level data for four of the included trials, one of which was unpublished. We collected all data on adverse effects from the included RCTs.
MAIN RESULTS: We identified 11 trials (nine parallel-group, two cross-over) enrolling a total of 735 individuals, amongst whom 118 cross-over participants additionally served as their own controls. Five trials enrolled women with pregnancy-associated leg cramps (408 participants) and five trials enrolled people with idiopathic cramps (271 participants, with 118 additionally crossed over to control). Another study enrolled 29 people with liver cirrhosis, only some of whom suffered muscle cramps. All trials provided magnesium as an oral supplement, except for one trial which provided magnesium as a series of slow intravenous infusions. Nine trials compared magnesium to placebo, one trial compared magnesium to no treatment, calcium carbonate or vitamin B, and another trial compared magnesium to vitamin E or calcium. We judged the single trial in people with liver cirrhosis and all five trials in participants with pregnancy-associated leg cramps to be at high risk of bias. In contrast, we rated the risk of bias high in only one of five trials in participants with idiopathic rest cramps. For idiopathic cramps, largely in older adults (mean age 61.6 to 69.3 years) presumed to have nocturnal leg cramps (the commonest presentation), differences in measures of cramp frequency when comparing magnesium to placebo were small, not statistically significant, and showed minimal heterogeneity (I² = 0% to 12%). This includes the primary endpoint, percentage change from baseline in the number of cramps per week at four weeks (mean difference (MD) -9.59%, 95% confidence interval (CI) -23.14% to 3.97%; 3 studies, 177 participants; moderate-certainty evidence); and the difference in the number of cramps per week at four weeks (MD -0.18 cramps/week, 95% CI -0.84 to 0.49; 5 studies, 307 participants; moderate-certainty evidence). The percentage of individuals experiencing a 25% or better reduction in cramp rate from baseline was also no different (RR 1.04, 95% CI 0.84 to 1.29; 3 studies, 177 participants; high-certainty evidence). Similarly, no statistically significant difference was found at four weeks in measures of cramp intensity or cramp duration. This includes the number of participants rating their cramps as moderate or severe at four weeks (RR 1.33, 95% CI 0.81 to 2.21; 2 studies, 91 participants; moderate-certainty evidence); and the percentage of participants with the majority of cramp durations of one minute or more at four weeks (RR 1.83, 95% CI 0.74 to 4.53, 1 study, 46 participants; low-certainty evidence). We were unable to perform meta-analysis for trials of pregnancy-associated leg cramps. The single study comparing magnesium to no treatment failed to find statistically significant benefit on a three-point ordinal scale of overall treatment efficacy. Of the three trials comparing magnesium to placebo, one found no benefit on frequency or intensity measures, another found benefit for both, and a third reported inconsistent results for frequency that could not be reconciled. The single study in people with liver cirrhosis was small and had limited reporting of cramps, but found no difference in terms of cramp frequency or cramp intensity. Our analysis of adverse events pooled all studies, regardless of the setting in which cramps occurred. Major adverse events (occurring in 2 out of 72 magnesium recipients and 3 out of 68 placebo recipients), and withdrawals due to adverse events, were not significantly different from placebo. However, in the four studies for which it could be determined, more participants experienced minor adverse events in the magnesium group than in the placebo group (RR 1.51, 95% CI 0.98 to 2.33; 4 studies, 254 participants; low-certainty evidence). Overall, oral magnesium was associated with mostly gastrointestinal adverse events (e.g. diarrhoea), experienced by 11% (10% in control) to 37% (14% in control) of participants.
AUTHORS' CONCLUSIONS: It is unlikely that magnesium supplementation provides clinically meaningful cramp prophylaxis to older adults experiencing skeletal muscle cramps. In contrast, for those experiencing pregnancy-associated rest cramps the literature is conflicting and further research in this population is needed. We found no RCTs evaluating magnesium for exercise-associated muscle cramps or disease-state-associated muscle cramps (for example amyotrophic lateral sclerosis/motor neuron disease) other than a single small (inconclusive) study in people with liver cirrhosis, only some of whom suffered cramps.}, }
@article {pmid32946420, year = {2021}, author = {Jalilian, H and Najafi, K and Khosravi, Y and Röösli, M}, title = {Amyotrophic lateral sclerosis, occupational exposure to extremely low frequency magnetic fields and electric shocks: a systematic review and meta-analysis.}, journal = {Reviews on environmental health}, volume = {36}, number = {1}, pages = {129-142}, doi = {10.1515/reveh-2020-0041}, pmid = {32946420}, issn = {2191-0308}, mesh = {Amyotrophic Lateral Sclerosis/*epidemiology/*etiology ; Electric Injuries/*complications ; Humans ; Magnetic Fields/*adverse effects ; Occupational Exposure/*adverse effects ; Risk Factors ; }, abstract = {Exposure to extremely low frequency magnetic fields (ELF-MF) and electric shocks occurs in many workplaces and occupations but it is unclear whether any of these exposures cause Amyotrophic lateral sclerosis (ALS). The aim of this systematic review and meta-analysis is to explore whether occupational exposure to ELF-MF and/or electric shocks are risk factor for ALS. We searched PubMed, Embase, and Web of Science databases up to the end of 2019. Pooled risk estimates were calculated using random-effects meta-analysis including exploration of the sources of heterogeneity between studies and publication bias. Twenty-seven publications fulfilled the inclusion criteria. We found a weak, significant, association between occupational exposure to ELF-MF and the risk of ALS (RRPooled estimate: 1.20; 95%CI: 1.05, 1.38) with moderate to high heterogeneity (I[2]=66.3%) and indication of publication bias (PEgger's test=0.03). No association was observed between occupational exposure to electric shocks and risk of ALS (RRPooled estimate: 0.97; 95%CI: 0.80, 1.17) with high heterogeneity (I[2]=80.5%), and little indication for publication bias (PEgger's test=0.24). The findings indicate that occupational exposure to ELF-MF, but not electric shocks, might be a risk factor for ALS. However, given the moderate to high heterogeneity and potential publication bias, the results should be interpreted with caution.}, }
@article {pmid32941938, year = {2020}, author = {Farace, C and Fenu, G and Lintas, S and Oggiano, R and Pisano, A and Sabalic, A and Solinas, G and Bocca, B and Forte, G and Madeddu, R}, title = {Amyotrophic lateral sclerosis and lead: A systematic update.}, journal = {Neurotoxicology}, volume = {81}, number = {}, pages = {80-88}, doi = {10.1016/j.neuro.2020.09.003}, pmid = {32941938}, issn = {1872-9711}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/metabolism/physiopathology ; Animals ; Central Nervous System/*drug effects/metabolism/pathology/physiopathology ; DNA-Binding Proteins/metabolism ; Disease Progression ; Environmental Exposure/adverse effects ; Environmental Pollutants/*adverse effects ; Gene-Environment Interaction ; Humans ; Lead/*adverse effects ; *Lead Poisoning, Nervous System/diagnosis/epidemiology/metabolism/physiopathology ; Protein Aggregates ; Protein Aggregation, Pathological ; Risk Assessment ; Risk Factors ; }, abstract = {Heavy metals are considered to be among the leading environmental factors that trigger amyotrophic lateral sclerosis (ALS). However, no convincing biopathological mechanism and therapeutic clinical implication of such metals in ALS pathogenesis have been established. This is partly attributable to the technical and scientific difficulties in demonstrating a direct and causative role of heavy metals in the onset of ALS in patients. However, a body of epidemiological, clinical and experimental evidences suggest that lead (Pb), more than other metals, could actually play a major role in the onset and progression of ALS. Here, to clarify the nature of the association and the causative role of Pb in ALS, we comprehensively reviewed the scientific literature of the last decade with objective database searches and the methods typically adopted in systematic reviews, critically analysing and summarising the various scientifically sound evidence on the relationship between ALS and Pb. From these tasks, we noted a number of multidisciplinary associations between ALS and Pb, and specifically the importance of occupational exposure to Pb in ALS development and/or progression. We also report the possible involvement of TAR DNA binding protein (TDP-43)-based molecular mechanism in Pb-mediated ALS, although these data rely on a single study, which included both in vitro experiments and an animal model, and are therefore still preliminary. Finally, we briefly examined whether this knowledge could inspire new targeted therapies and policies in the fight against ALS.}, }
@article {pmid32905613, year = {2021}, author = {McKay, KA and Smith, KA and Smertinaite, L and Fang, F and Ingre, C and Taube, F}, title = {Military service and related risk factors for amyotrophic lateral sclerosis.}, journal = {Acta neurologica Scandinavica}, volume = {143}, number = {1}, pages = {39-50}, pmid = {32905613}, issn = {1600-0404}, support = {//Försvarsmakten/ ; }, mesh = {Amyotrophic Lateral Sclerosis/chemically induced/diagnosis/*epidemiology ; Case-Control Studies ; Craniocerebral Trauma/diagnosis/epidemiology ; Environmental Exposure/*adverse effects ; Female ; Humans ; Male ; Metals, Heavy/adverse effects ; *Military Personnel ; Pesticides/adverse effects ; Risk Factors ; *Veterans ; War-Related Injuries/diagnosis/*epidemiology ; }, abstract = {BACKGROUND: The cause of amyotrophic lateral sclerosis (ALS) is unknown, but occupations have been explored as a potential proxy measure of risk. There is a substantial body of literature connecting military service to ALS. We aimed to summarize and assess the quality of this evidence.
METHODS: Systematic review of the literature, including observational studies which explored one of the following exposures: general military service (army, air force, marines, or navy); or specific exposures associated with military service measured among military personnel. The outcome of interest was ALS incidence, which could include onset, diagnosis, or death from ALS.
RESULTS: A total of 2642 articles were screened. Following exclusion, 19 articles remained for inclusion in the systematic review, including 1 meta-analysis and 18 original observational studies. Most studies were of moderate quality. In general, the relationship between military service was suggestive of an increased risk, particularly among Gulf War and WWII veterans. Exposure to pesticides (including Agent Orange) certain chemicals (exhaust, burning agents), heavy metals, and head trauma appeared to increase the risk of ALS among military personnel.
CONCLUSIONS: There is a possible association between military service and the subsequent development of ALS; however, the evidence was limited. Studies were generally hindered by small sample sizes and inadequate follow-up time. Future studies should endeavor to objectively measure specific exposures, or combinations thereof, associated with military service, as this will be of vital importance in implementing preventative strategies into military organizations.}, }
@article {pmid32867586, year = {2020}, author = {Adiao, KJB and Espiritu, AI and Bagnas, MAC}, title = {Efficacy and safety of mexiletine in amyotrophic lateral sclerosis: a systematic review of randomized controlled trials.}, journal = {Neurodegenerative disease management}, volume = {10}, number = {6}, pages = {397-407}, doi = {10.2217/nmt-2020-0026}, pmid = {32867586}, issn = {1758-2032}, mesh = {Adult ; Aged ; Amyotrophic Lateral Sclerosis/complications/*drug therapy ; Female ; Humans ; Male ; Mexiletine/*therapeutic use ; Middle Aged ; Muscle Cramp/complications/*drug therapy ; Randomized Controlled Trials as Topic ; Voltage-Gated Sodium Channel Blockers/*therapeutic use ; }, abstract = {Background: Mexiletine is a potential drug in amyotrophic lateral sclerosis (ALS) that has been tested in clinical trials. The objective of this study was to determine the efficacy and safety of mexiletine in ALS via systematic review of existing evidences. Materials & methods: Relevant records were searched using major healthcare electronic databases. Data on functional disability, impairment, survival, muscle cramp frequency and severity, and adverse events were obtained. Results & conclusion: Three relevant randomized controlled trials with 141 patients were included in this review. Mexiletine has no effect on the functional disability, impairment and survival in ALS. However, significant improvement in reducing muscle cramp severity and frequency was shown. The most common adverse effect associated with mexiletine intake among ALS patients are nausea (n = 11, 7.8%) and tremors (n = 5, 3.6%).}, }
@article {pmid32849187, year = {2020}, author = {Lanznaster, D and Bejan-Angoulvant, T and Gandía, J and Blasco, H and Corcia, P}, title = {Is There a Role for Vitamin D in Amyotrophic Lateral Sclerosis? A Systematic Review and Meta-Analysis.}, journal = {Frontiers in neurology}, volume = {11}, number = {}, pages = {697}, pmid = {32849187}, issn = {1664-2295}, abstract = {Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by the progressive loss of motor neurons. Patients usually die 3-5 years after diagnosis from respiratory failure. Several studies investigated the role of vitamin D as a biomarker or a therapeutic option for ALS patients. To clarify the scientific evidence, we performed a systematic review and different meta-analyses regarding the potential role of vitamin D in ALS. Methods: We performed a systematic review of clinical trials, cohorts, and case-control studies retrieved from PubMed, EMBASE, and Cochrane databases reporting vitamin D levels as a putative biomarker for ALS diagnosis or prognosis or the effect of vitamin D supplementation in ALS patients. Whenever possible, data were pooled using a random-effects model, with an assessment of heterogeneity. Results: Out of 2,996 articles retrieved, we finally included 13 research articles, 12 observational studies (50% prospective), and 1 clinical trial. We found that ALS patients had slightly lower levels of vitamin D than controls (mean difference -6 ng/ml, 95% CI [-10.8; -1.3]), but important confounding factors were not considered in the studies analyzed. We found no relationship between vitamin D levels and ALS functional rate score-revised (ALSFRS-R), with highly heterogeneous results. Discordant results were reported in three studies regarding survival. Finally, five studies reported the effects of vitamin D supplementation with discordant results. Two of them showed a small improvement, whereas two others showed a deleterious effect on ALSFRS-R. One very small clinical trial with important methodological limitations showed some improvement in ALSFRS-R with high doses of vitamin D compared with normal doses. Conclusions: Our review did not find evidence to support the role of vitamin D on ALS diagnosis, prognosis, or treatment. Most studies had important limitations, mostly regarding the risk of bias for not considering confounding factors. Vitamin D supplementation should be offered to ALS patients to avoid other health issues related to vitamin D deficiency, but there is not enough evidence to support the use of vitamin D as a therapy for ALS.}, }
@article {pmid32657155, year = {2020}, author = {Poppe, C and Koné, I and Iseli, LM and Schweikert, K and Elger, BS and Wangmo, T}, title = {Differentiating needs of informal caregivers of individuals with ALS across the caregiving course: a systematic review.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {21}, number = {7-8}, pages = {519-541}, doi = {10.1080/21678421.2020.1771735}, pmid = {32657155}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis ; *Caregivers ; Humans ; Qualitative Research ; }, abstract = {BACKGROUND: Informal caregivers of people with amyotrophic lateral sclerosis (ALS) experience a range of needs across the course of the disease. For the provision of adequate support, an examination of the empirical evidence is necessary.
AIM: The purpose of the systematic review was to synthesize evidence of needs of informal caregivers of people with ALS at different stages of caregiving.
METHOD: Systematic review of empirical research on needs of ALS informal caregivers in both English and German, from January 2000 to August 2018. We searched the databases EMBASE, MEDLINE (PubMed), PsycINFO, and CINAHL. Study selection, quality assessment, and data extraction was performed independently. Both quantitative and qualitative studies were included. Of the included studies, we additionally screened citing literature in Google Scholar (citation tracking). We linked the narrative synthesis to four stages of caregiving described by Williams and colleagues and used descriptive inductive thematic analysis to structure data within the stages.
RESULTS: From 3275 abstracts screened, 48 manuscripts met our inclusion criteria. Our data analysis shows that needs differ across the four caregiving stages. While the stage of bereavement (stage 4) includes too little data for separate themes, themes for needs after diagnosis (stage 1), and terminal stage (stage 3) could be specified. As the maintenance (stage 2) stage comprised of themes relevant across the caregiving course, it became an overall stage.
DISCUSSION: Healthcare professionals need to pay attention to current caregiving stages to provide support for informal caregivers. Further research is needed to tease out support needs for the bereavement phase.}, }
@article {pmid32611436, year = {2020}, author = {Yoon, NYS and Ong, YT and Yap, HW and Tay, KT and Lim, EG and Cheong, CWS and Lim, WQ and Chin, AMC and Toh, YP and Chiam, M and Mason, S and Krishna, LKR}, title = {Evaluating assessment tools of the quality of clinical ethics consultations: a systematic scoping review from 1992 to 2019.}, journal = {BMC medical ethics}, volume = {21}, number = {1}, pages = {51}, pmid = {32611436}, issn = {1472-6939}, mesh = {Ethics Committees, Clinical ; *Ethics Consultation ; Ethics, Clinical ; Humans ; }, abstract = {BACKGROUND: Amidst expanding roles in education and policy making, questions have been raised about the ability of Clinical Ethics Committees (CEC) s to carry out effective ethics consultations (CECons). However recent reviews of CECs suggest that there is no uniformity to CECons and no effective means of assessing the quality of CECons. To address this gap a systematic scoping review of prevailing tools used to assess CECons was performed to foreground and guide the design of a tool to evaluate the quality of CECons.
METHODS: Guided by Levac et al's (2010) methodological framework for conducting scoping reviews, the research team performed independent literature reviews of accounts of assessments of CECons published in six databases. The included articles were independently analyzed using content and thematic analysis to enhance the validity of the findings.
RESULTS: Nine thousand sixty-six abstracts were identified, 617 full-text articles were reviewed, 104 articles were analyzed and four themes were identified - the purpose of the CECons evaluation, the various domains assessed, the methods of assessment used and the long-term impact of these evaluations.
CONCLUSION: This review found prevailing assessments of CECons to be piecemeal due to variable goals, contextual factors and practical limitations. The diversity in domains assessed and tools used foregrounds the lack of minimum standards upheld to ensure baseline efficacy. To advance a contextually appropriate, culturally sensitive, program specific assessment tool to assess CECons, clear structural and competency guidelines must be established in the curation of CECons programs, to evaluate their true efficacy and maintain clinical, legal and ethical standards.}, }
@article {pmid32564621, year = {2020}, author = {Liu, J and Luo, X and Chen, X and Shang, H}, title = {Serum creatinine levels in patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {21}, number = {7-8}, pages = {502-508}, doi = {10.1080/21678421.2020.1774610}, pmid = {32564621}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis ; Creatinine ; Humans ; }, abstract = {Serum creatinine (Cr) is a biosynthetic product of creatine phosphate metabolism in muscles and is closely related to total muscle mass, but it is not easily affected by diet. Several studies have tried to explore the role of serum Cr levels in amyotrophic lateral sclerosis (ALS), but the results were inconsistent. Therefore, our study aims to explore the differences of serum Cr levels between ALS patients and controls and whether serum Cr at baseline is an independent predictor of survival. Methods: We searched all the related studies that probed into the association between Serum Cr levels and ALS based on PubMed, EMBASE and Cochrane library from October 1952 to February 2019. The quality of the included studies was evaluated by using Newcastle-Ottawa Scale (NOS), and all the statistical analysis of this meta-analysis was performed by Stata version 12.0. Results: Eight studies with a total of 11377 ALS patients and 937 controls were included. Among them, five studies indicated that ALS patients had lower serum Cr levels (SMD = -0.78, 95%CI [-0.97, -0.60]) compared to controls, and three studies showed that higher serum Cr levels in ALS patients were related to lower overall mortality (HR 0.89, 95%CI [0.80, 0.99]). Conclusion: The levels of serum Cr in ALS patients are significantly lower than those in controls, and they are inversely related to overall mortality in ALS patients. Therefore, the serum Cr, an easily accessible serological factor, may serve as a prognostic biomarker.}, }
@article {pmid32523508, year = {2020}, author = {Elliott, E and Bailey, O and Waldron, FM and Hardingham, GE and Chandran, S and Gregory, JM}, title = {Therapeutic Targeting of Proteostasis in Amyotrophic Lateral Sclerosis-a Systematic Review and Meta-Analysis of Preclinical Research.}, journal = {Frontiers in neuroscience}, volume = {14}, number = {}, pages = {511}, pmid = {32523508}, issn = {1662-4548}, abstract = {Background: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive fatal neurodegenerative condition. There are no effective treatments. The only globally licensed medication, that prolongs life by 2-3 months, was approved by the FDA in 1995. One reason for the absence of effective treatments is disease heterogeneity noting that ALS is clinically heterogeneous and can be considered to exist on a neuropathological spectrum with frontotemporal dementia. Despite this significant clinical heterogeneity, protein misfolding has been identified as a unifying pathological feature in these cases. Based on this shared pathophysiology, we carried out a systematic review and meta-analysis to assess the therapeutic efficacy of compounds that specifically target protein misfolding in preclinical studies of both ALS and FTD. Methods: Three databases: (i) PubMed, (ii) MEDLINE, and (iii) EMBASE were searched. All studies comparing the effect of treatments targeting protein misfolding in pre-clinical ALS or FTD models to a control group were retrieved. Results: Systematic review identified 70 pre-clinical studies investigating the effects of therapies targeting protein misfolding on survival. Meta-analysis revealed that targeting protein misfolding did significantly improve survival compared to untreated controls (p < 0.001, df = 68, α = 0.05, CI 1.05-1.16), with no evidence of heterogeneity between studies (I [2] = 0%). Further subgroup analyses, evaluating the effect of timing of these interventions, showed that, only treating prior to symptom onset (n = 33), significantly improved survival (p < 0.001, df = 31, α = 0.05, CI 1.08-1.29), although this likely reflects the inadequate sample size of later time points. Furthermore, arimoclomol was found to significantly reduce secondary outcome measures including: (i) histological outcomes, (ii) behavioral outcomes, and (iii) biochemical outcomes (p < 0.005). Conclusions: This analysis supports the hypothesis that protein misfolding plays an important role in the pathogenesis of ALS and FTD and that targeting protein misfolding, at least in pre-clinical models, can significantly improve survival, especially if such an intervention is administered prior to symptom onset.}, }
@article {pmid32508736, year = {2020}, author = {Wang, L and Li, C and Chen, X and Li, S and Shang, H}, title = {Abnormal Serum Iron-Status Indicator Changes in Amyotrophic Lateral Sclerosis (ALS) Patients: A Meta-Analysis.}, journal = {Frontiers in neurology}, volume = {11}, number = {}, pages = {380}, pmid = {32508736}, issn = {1664-2295}, abstract = {Background: In recent years, the role of iron metabolism in amyotrophic lateral sclerosis (ALS) attracts more and more attention, and some studies have focused on the link between abnormal serum iron indicators and ALS. However, there are still big conflicts and inconsistency among different studies. To study the possible relationship between ALS and disturbed iron metabolism, we conducted this meta-analysis to conclude characteristics of abnormal serum iron-status indicator changes in ALS patients. Methods: We searched and screened main databases, including the PubMed, Embase, and Cochrane Library, to find studies related to the association between iron metabolism and ALS. The Revman 5.3 software was used to conduct meta-analysis. Results: Eleven studies were finally included in our analysis, composed of 1,599 ALS patients and 1,255 controls in total. The results showed that the ferritin level was much higher in ALS patients compared with controls (MD = 70.48, 95% CI [51.41, 89.55], p < 0.00001), and the transferrin level was decreased in ALS patients compared with controls (SMD = -0.28, 95% CI [-0.38, -0.18], p < 0.00001), while there was no statistical difference in iron levels (SMD = 0.48, 95% CI [-0.07, 1.03], p = 0.09) between ALS patients and controls. Conclusions: Our research finds unusual changes in several indicators representing iron status, which suggest possible iron metabolism abnormalities in ALS patients. That may provide evidence for the link between iron metabolism and the pathogenesis of ALS.}, }
@article {pmid32453096, year = {2020}, author = {Shehee, L and O'Rourke, A and Garand, KL}, title = {The Role of Radiation Therapy and Botulinum Toxin Injections in the Management of Sialorrhea in Patients With Amyotrophic Lateral Sclerosis: A Systematic Review.}, journal = {Journal of clinical neuromuscular disease}, volume = {21}, number = {4}, pages = {205-221}, doi = {10.1097/CND.0000000000000273}, pmid = {32453096}, issn = {1537-1611}, mesh = {Aged ; Amyotrophic Lateral Sclerosis/*physiopathology ; Botulinum Toxins/*therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Neuromuscular Agents/*therapeutic use ; Sialorrhea/*drug therapy/*radiotherapy ; Treatment Outcome ; }, abstract = {OBJECTIVES: Half of patients with amyotrophic lateral sclerosis experience sialorrhea due to facial weakness. Although anticholinergic medications are first-line therapy, they often lead to unacceptable side effects. Radiation therapy and botulinum toxin may be considered when medical management fails. In this systematic review, we investigated the effectiveness of these interventions.
METHODS: Eligible studies were retrieved from PubMed and Scopus databases up to March 2017 along with hand-searching of references from primary articles.
RESULTS: Fourteen studies (N = 138) examined the benefits of botulinum toxin. Studies varied in salivary glands treated, dosages used, and the use of botulinum toxin subtype A or B. A majority of studies showed benefit after treatment. Although most studies reported only mild adverse effects, 2 case studies revealed severe complications including recurrent TMJ dislocations and rapid deterioration in bulbar function. Ten studies (N = 171) examined the benefits of radiation. Most studies reported improvement with only mild adverse events reported.
CONCLUSIONS: Both radiation and botulinum toxin are effective treatments for sialorrhea in patients with amyotrophic lateral sclerosis and should be considered when medical management fails. Radiation may offer longer duration of symptom improvement with fewer complications.}, }
@article {pmid32452880, year = {2020}, author = {Meng, L and Li, X and Li, C and Tsang, RCC and Chen, Y and Ge, Y and Gao, Q}, title = {Effects of Exercise in Patients With Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.}, journal = {American journal of physical medicine & rehabilitation}, volume = {99}, number = {9}, pages = {801-810}, doi = {10.1097/PHM.0000000000001419}, pmid = {32452880}, issn = {1537-7385}, mesh = {Activities of Daily Living ; Aged ; Amyotrophic Lateral Sclerosis/physiopathology/*therapy ; Breathing Exercises/methods ; Exercise/physiology ; Exercise Therapy/*methods ; Female ; Humans ; Male ; Middle Aged ; Muscle Strength ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {OBJECTIVE: The aim of this study was to systematically review the efficacy and safety of exercise in patients with amyotrophic lateral sclerosis (ALS).
DESIGN: Randomized controlled trials of exercises for ALS were searched in PubMed, EMBASE, Web of Science, Cochrane Library, China Biology Medicine database, China National Knowledge Internet, VIP database, and Wanfang database. The primary outcomes were functional ability, pulmonary function, and quality of life. The secondary outcomes were muscle strength, fatigue and adverse events. Meta-analysis was performed using the RevMan Version 5.3 software.
RESULTS: Seven randomized controlled trials including 322 patients with ALS met the inclusion criteria. Meta-analysis showed that the functional scores at long-term (standardized means difference, 0.47; 95% confidence interval, 0.08-0.86; P = 0.02) and forced vital capacity percentage predicted (mean difference, 1.71; 95% confidence interval, 0.10-3.31; P = 0.04) of patients with ALS in the exercise group were significantly higher than those in the group of no exercise or usual care. No significant difference was observed in muscle strength and quality of life. Endurance or aerobic exercise improved the functional scores of patients with ALS (standardized means difference, 0.36; 95% confidence interval, 0.04-0.68; P = 0.03). Exercise did not aggravate fatigue or result in adverse event.
CONCLUSION: Exercise can significantly improve the functional ability and pulmonary function of patients with ALS safely.}, }
@article {pmid32411012, year = {2020}, author = {Momtaz, S and Memariani, Z and El-Senduny, FF and Sanadgol, N and Golab, F and Katebi, M and Abdolghaffari, AH and Farzaei, MH and Abdollahi, M}, title = {Targeting Ubiquitin-Proteasome Pathway by Natural Products: Novel Therapeutic Strategy for Treatment of Neurodegenerative Diseases.}, journal = {Frontiers in physiology}, volume = {11}, number = {}, pages = {361}, pmid = {32411012}, issn = {1664-042X}, abstract = {Misfolded proteins are the main common feature of neurodegenerative diseases, thereby, normal proteostasis is an important mechanism to regulate the neural survival and the central nervous system functionality. The ubiquitin-proteasome system (UPS) is a non-lysosomal proteolytic pathway involved in numerous normal functions of the nervous system, modulation of neurotransmitter release, synaptic plasticity, and recycling of membrane receptors or degradation of damaged and regulatory intracellular proteins. Aberrant accumulation of intracellular ubiquitin-positive inclusions has been implicated to a variety of neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington disease (HD), Amyotrophic Lateral Sclerosis (ALS), and Multiple Myeloma (MM). Genetic mutation in deubiquitinating enzyme could disrupt UPS and results in destructive effects on neuron survival. To date, various agents were characterized with proteasome-inhibitory potential. Proteins of the ubiquitin-proteasome system, and in particular, E3 ubiquitin ligases, may be promising molecular targets for neurodegenerative drug discovery. Phytochemicals, specifically polyphenols (PPs), were reported to act as proteasome-inhibitors or may modulate the proteasome activity. PPs modify the UPS by means of accumulation of ubiquitinated proteins, suppression of neuronal apoptosis, reduction of neurotoxicity, and improvement of synaptic plasticity and transmission. This is the first comprehensive review on the effect of PPs on UPS. Here, we review the recent findings describing various aspects of UPS dysregulation in neurodegenerative disorders. This review attempts to summarize the latest reports on the neuroprotective properties involved in the proper functioning of natural polyphenolic compounds with implication for targeting ubiquitin-proteasome pathway in the neurodegenerative diseases. We highlight the evidence suggesting that polyphenolic compounds have a dose and disorder dependent effects in improving neurological dysfunctions, and so their mechanism of action could stimulate the UPS, induce the protein degradation or inhibit UPS and reduce protein degradation. Future studies should focus on molecular mechanisms by which PPs can interfere this complex regulatory system at specific stages of the disease development and progression.}, }
@article {pmid32293029, year = {2020}, author = {Pecoraro, V and Mandrioli, J and Carone, C and Chiò, A and Traynor, BJ and Trenti, T}, title = {The NGS technology for the identification of genes associated with the ALS. A systematic review.}, journal = {European journal of clinical investigation}, volume = {50}, number = {5}, pages = {e13228}, pmid = {32293029}, issn = {1365-2362}, support = {Z99 AG999999/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Amyotrophic Lateral Sclerosis/*genetics ; Cell Cycle Proteins/genetics ; DNA Helicases/genetics ; *High-Throughput Nucleotide Sequencing ; Humans ; Membrane Transport Proteins/genetics ; Multifunctional Enzymes/genetics ; RNA Helicases/genetics ; RNA-Binding Protein FUS/genetics ; Reproducibility of Results ; *Sequence Analysis, DNA ; Valosin Containing Protein/genetics ; }, abstract = {BACKGROUND: More than 30 causative genes have been identified in familial and sporadic amyotrophic lateral sclerosis (ALS). The next-generation sequencing (NGS) is a powerful and groundbreaking tool to identify disease-associated variants. Despite documented advantages of NGS, its diagnostic reliability needs to be addressed in order to use this technology for specific routine diagnosis.
MATERIAL AND METHODS: Literature database was explored to identify studies comparing NGS and Sanger sequencing for the detection of variants causing ALS. We collected data about patients' characteristics, disease type and duration, NGS and Sanger properties.
RESULTS: More than 200 bibliographic references were identified, of which only 14 studies matching our inclusion criteria. Only 2 out of 14 studies compared results of NGS analysis with the Sanger sequencing. Twelve studies screened causative genes associated to ALS using NGS technologies and confirmed the identified variants with Sanger sequencing. Overall, data about more 2,000 patients were analysed. The number of genes that were investigated in each study ranged from 1 to 32, the most frequent being FUS, OPTN, SETX and VCP. NGS identified already known mutations in 21 genes, and new or rare variants in 27 genes.
CONCLUSIONS: NGS seems to be a promising tool for the diagnosis of ALS in routine clinical practice. Its advantages are represented by an increased speed and a lowest sequencing cost, but patients' counselling could be problematic due to the discovery of frequent variants of unknown significance.}, }
@article {pmid32286157, year = {2020}, author = {Flemming, K and Turner, V and Bolsher, S and Hulme, B and McHugh, E and Watt, I}, title = {The experiences of, and need for, palliative care for people with motor neurone disease and their informal caregivers: A qualitative systematic review.}, journal = {Palliative medicine}, volume = {34}, number = {6}, pages = {708-730}, pmid = {32286157}, issn = {1477-030X}, support = {MCRGS-07-16-16/MCCC_/Marie Curie/United Kingdom ; }, mesh = {*Caregivers/statistics & numerical data ; Hospice Care/statistics & numerical data ; Humans ; *Motor Neuron Disease/therapy ; *Palliative Care/statistics & numerical data ; Qualitative Research ; }, abstract = {BACKGROUND: Despite being a terminal neurodegenerative disease, the role of palliative care is less recognised for motor neurone disease than for other life-limiting conditions. Understanding the experiences of, and need for, palliative care for patients and carers is key to configuring optimal policy and healthcare services.
AIM: To explore the experiences of, and need for, palliative care of people with motor neurone disease and their informal carers across the disease trajectory.
DESIGN: A systematic review of qualitative research conducted using Thematic Synthesis - PROSPERO registration CRD42017075311.
DATA SOURCES: Four electronic databases were searched (MEDLINE, CINAHL, PsycINFO, Social Science Citation Index) using terms for motor neurone disease, amyotrophic lateral sclerosis, palliative care, and qualitative research, from inception to November 2018. Included papers were data extracted and assessed for quality.
RESULTS: A total of 41 papers were included, representing the experiences of 358 people with motor neurone disease and 369 caregivers. Analytical themes were developed detailing patients' and carers' experiences of living with motor neurone disease and of palliative care through its trajectory including response to diagnosis, maintaining control, decision-making during deterioration, engaging with professionals, planning for end-of-life care, bereavement.
CONCLUSION: The review identified a considerable literature exploring the care needs of people with motor neurone disease and their carers; however, descriptions of palliative care were associated with the last days of life. Across the disease trajectory, clear points were identified where palliative care input could enhance patient and carer experience of the disease, particularly at times of significant physical change.}, }
@article {pmid32157912, year = {2020}, author = {Gosselt, IK and Nijboer, TCW and Van Es, MA}, title = {An overview of screening instruments for cognition and behavior in patients with ALS: selecting the appropriate tool for clinical practice.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {21}, number = {5-6}, pages = {324-336}, doi = {10.1080/21678421.2020.1732424}, pmid = {32157912}, issn = {2167-9223}, mesh = {*Amyotrophic Lateral Sclerosis/complications/diagnosis ; Cognition ; *Cognition Disorders/diagnosis/etiology ; Humans ; Neuropsychological Tests ; Quality of Life ; }, abstract = {Objective: Patients with amyotrophic lateral sclerosis (ALS) not only show motor deficits, but may also have cognitive and/or behavioral impairments. Recognizing these impairments is crucial as they are associated with lower quality of life, shorter survival, and increased caregiver burden. Therefore, ALS-specific neuropsychological screening instruments have been developed that can account for motor and speech difficulties. This study provides an overview and comparison of these screeners. Methods: A systematic review was conducted using Medline and Embase. Articles describing cognitive/behavioral screening instruments assessed in ALS patients were included. Screening instruments were compared on multiple factors, such as domains, adaptability, required time, and validation. Results: We included 99 articles, reporting on nine cognitive screeners (i.e. ACE-R, ALS-BCA, ALS-CBS, ECAS, FAB, MMSE, MoCA, PSSFTS, and UCSF-SB), of which five ALS-specific. Furthermore, eight behavioral screeners (i.e. ALS-FTD-Q, AES, BBI, DAS, FBI, FrSBe, MiND-B, and NPI) were reported on, of which three ALS-specific. Conclusion: Considering the broad range of cognitive domains, adaptability, and satisfying validity, the ALS-CBS and ECAS appear to be the most suitable screeners to detect cognitive and behavioral changes in ALS. The BBI appears to be the best option to screen for behavioral changes in ALS, since all relevant domains are assessed, motor-related problems are considered, and has a satisfactory validity. The MiND-B and ALS-FTD-Q are promising as well. In general, all screening instruments would benefit from additional validation research to gain greater insights into test characteristics and to aid clinicians in selecting screening tools for use in clinical practice.}, }
@article {pmid32126556, year = {2019}, author = {Vieira, H and Costa, N and Sousa, T and Reis, S and Coelho, L}, title = {Voice-Based Classification of Amyotrophic Lateral Sclerosis: Where Are We and Where Are We Going? A Systematic Review.}, journal = {Neuro-degenerative diseases}, volume = {19}, number = {5-6}, pages = {163-170}, doi = {10.1159/000506259}, pmid = {32126556}, issn = {1660-2862}, mesh = {Amyotrophic Lateral Sclerosis/*classification/complications/diagnosis ; *Diagnosis, Computer-Assisted/methods ; Humans ; Pattern Recognition, Automated ; Speech Recognition Software ; *Voice ; Voice Disorders/classification/diagnosis/etiology ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal progressive motor neuron disease. People with ALS demonstrate various speech problems.
SUMMARY: We aim to provide an overview of studies concerning the diagnosis of ALS based on the analysis of voice samples. The main focus is on the feasibility of the use of voice and speech assessment as an effective method to diagnose the disease, either in clinical or pre-clinical conditions, and to monitor the disease progression. Specifically, we aim to examine current knowledge on: (a) voice parameters and the data models that can, most effectively, provide robust results; (b) the feasibility of a semi-automatic or automatic diagnosis and outcomes; and (c) the factors that can improve or restrict the use of such systems in a real-world context. Key Messages: The studies already carried out on the possibility of diagnosis of ALS using the voice signal are still sparse but all point to the importance, feasibility and simplicity of this approach. Most cohorts are small which limits the statistical relevance and makes it difficult to infer broader conclusions. The set of features used, although diverse, is quite circumscribed. ALS is difficult to diagnose early because it may mimic several other neurological diseases. Promising results were found for the automatic detection of ALS from speech samples and this can be a feasible process even in pre-symptomatic stages. Improved guidelines must be set in order to establish a robust decision model.}, }
@article {pmid32116647, year = {2020}, author = {Luo, C and Hu, N and Xiao, Y and Zhang, W and Gong, Q and Lui, S}, title = {Comparison of Gray Matter Atrophy in Behavioral Variant Frontal Temporal Dementia and Amyotrophic Lateral Sclerosis: A Coordinate-Based Meta-Analysis.}, journal = {Frontiers in aging neuroscience}, volume = {12}, number = {}, pages = {14}, pmid = {32116647}, issn = {1663-4365}, abstract = {Background: There is growing evidence supporting behavioral variant frontotemporal dementia (bvFTD) and amyotrophic lateral sclerosis (ALS) as extreme points of a disease spectrum. The aim of this study was to delineate the common and different patterns of gray matter atrophy associated with bvFTD and with ALS by pooling together the results of previous voxel-based morphometry (VBM) studies. Methods: We retrieved VBM studies that investigated gray matter atrophy in bvFTD patients vs. controls and in ALS patients vs. controls. Stereotactic data were extracted from those studies and subsequently tested for convergence and differences using activation likelihood estimation (ALE). A behavioral analysis using the BrainMap database was performed to assess the functional roles of the regions affected by bvFTD and/or ALS. Results: Our study demonstrated a convergence of gray matter atrophy in the frontolimbic structures that involve the bilateral anterior insula and anterior cingulate cortex. Comparing the pattern of GM atrophy in bvFTD and ALS patients revealed greater atrophy in the frontomedial cortex, bilateral caudate, left anterior insula, and right thalamus in those with bvFTD and a higher degree of atrophy in the right motor cortex of those with ALS. Behavioral analysis revealed that the pattern of the affected regions contributed to the dysfunction of emotional and cognitive processing in bvFTD patients and the dysfunction of motor execution in ALS patients. Conclusion: Our results revealed a shared neural basis between bvFTD and ALS subjects, as well as a specific and distinct neural signature that underpinned the clinical manifestations of those two diseases. Those findings outlined the role of the frontomedial-caudate circuit in the development of bvFTD-like deficits in ALS patients.}, }
@article {pmid32077368, year = {2021}, author = {Luo, T and Li, MS and Williams, D and Phillippi, S and Yu, Q and Kantrow, S and Kao, YH and Celestin, M and Lin, WT and Tseng, TS}, title = {Using social media for smoking cessation interventions: a systematic review.}, journal = {Perspectives in public health}, volume = {141}, number = {1}, pages = {50-63}, doi = {10.1177/1757913920906845}, pmid = {32077368}, issn = {1757-9147}, mesh = {Behavior Therapy ; Humans ; Smoking ; *Smoking Cessation ; *Social Media ; }, abstract = {BACKGROUND: Previous studies have shown that smoking tobacco significantly increases both incidence and mortality rates for many diseases. Social media has become one of the most influential platforms for various smoking cessation interventions. However, results from smoking cessation interventions have differed from study to study. Limited studies have summarised cessation outcomes from social media-based interventions. Therefore, the objective of this review is to explore the effectiveness of using social media for smoking cessation.
METHODS: We searched PubMed, MEDLINE, PsycINFO, and CINAHL for articles between June 2008 and June 2018, and also assessed the references of selected articles. We included studies that used social media as intervention platforms, provided a baseline assessment before the intervention, and provided smoking cessation outcomes after the intervention.
RESULTS: We identified 13 original studies that enrolled between 16 and 1698 participants; 7-day Point Prevalence Abstinence (PPA) rate was the most frequently used measure of abstinence, with a range of 7%-75%, regardless of the measurement time, study design, and analysis methods. Social media-based smoking cessation interventions were effective, because (1) smokers reported higher 7-day PPA rates after intervention compared to baseline and (2) smokers reported higher 7-day PPA rates in intervention groups than in control groups. Moreover, at each time point, approximately half of all smokers in studies reporting abstinence were found to be biochemically abstinent. There were no significant differences in the effectiveness of smoking cessation outcomes between those that used existing popular social networking platforms (e.g. Pechmann et al's studies) and those that used individually designed interactive platforms (e.g. MyLastDip, iQuit system, Quitxt system).
CONCLUSIONS: This review highlights the effectiveness of social media-based smoking cessation intervention studies. Due to the widespread use of social media, as well as its low cost, we suggest embedding smoking cessation interventions within existing popular social media platforms.}, }
@article {pmid32044239, year = {2020}, author = {Bashford, J and Mills, K and Shaw, C}, title = {The evolving role of surface electromyography in amyotrophic lateral sclerosis: A systematic review.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {131}, number = {4}, pages = {942-950}, pmid = {32044239}, issn = {1872-8952}, support = {BASHFORD/JUN16/947-795/MNDA_/Motor Neurone Disease Association/United Kingdom ; G0500289/MRC_/Medical Research Council/United Kingdom ; MC_PC_17115/MRC_/Medical Research Council/United Kingdom ; MR/P000983/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Action Potentials/*physiology ; Amyotrophic Lateral Sclerosis/*physiopathology ; Biomarkers ; Disease Progression ; Electromyography ; Humans ; Motor Neurons/*physiology ; Muscle, Skeletal/*physiopathology ; Prognosis ; }, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease that leads to inexorable motor decline and a median survival of three years from symptom onset. Surface EMG represents a major technological advance that has been harnessed in the development of novel neurophysiological biomarkers. We have systematically reviewed the current application of surface EMG techniques in ALS.
METHODS: We searched PubMed to identify 42 studies focusing on surface EMG and its associated analytical methods in the diagnosis, prognosis and monitoring of ALS patients.
RESULTS: A wide variety of analytical techniques were identified, involving motor unit decomposition from high-density grids, motor unit number estimation and measurements of neuronal hyperexcitability or neuromuscular architecture. Some studies have proposed specific diagnostic and prognostic criteria however clinical calibration in large ALS cohorts is currently lacking. The most validated method to monitor disease is the motor unit number index (MUNIX), which has been implemented as an outcome measure in two ALS clinical trials.
CONCLUSION: Surface EMG offers significant practical and analytical flexibility compared to invasive techniques. To capitalise on this fully, emphasis must be placed upon the multi-disciplinary collaboration of clinicians, bioengineers, mathematicians and biostatisticians.
SIGNIFICANCE: Surface EMG techniques can enrich effective biomarker development in ALS.}, }
@article {pmid32000403, year = {2020}, author = {Zhang, B and Li, R and Zhang, Y and Gao, X}, title = {Differential role of triggering receptors expressed on myeloid cells 2 R47H in 3 neurodegenerative diseases based on a systematic review and meta-analysis.}, journal = {Medicine}, volume = {99}, number = {5}, pages = {e18921}, pmid = {32000403}, issn = {1536-5964}, mesh = {Alzheimer Disease/*genetics ; Amyotrophic Lateral Sclerosis/*genetics ; Genetic Predisposition to Disease ; Humans ; Membrane Glycoproteins/*genetics ; Parkinson Disease/*genetics ; Polymorphism, Genetic ; Receptors, Immunologic/*genetics ; }, abstract = {BACKGROUND: Recent studies have suggested that the potential functional polymorphism R47H in triggering receptors expressed on myeloid cells 2 (TREM2) is associated with several neurodegenerative diseases, however, the results remain inconclusive. This meta-analysis aimed to investigate the association between TREM2 R47H and the risk for 3 typical neurodegenerative diseases: Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS).
METHODS: A literature review was carried out using PubMed, Medline, and Embase. Data analysis was conducted using Stata 15.0 software. The pooled odds ratio (ORs) and 95% confidence interval (CIs) were calculated.
RESULTS: A total of 35 articles were identified as eligible: 22 on AD, 3 on ALS, 7 on PD, 2 on AD and ALS, and 1 on ALS and PD. The AD set included 23,092 cases and 30,920 controls, the ALS set included 7391 cases and 12,442 controls, and the PD set included 8498 patients and 9161 controls. We found that R47H was associated with an increased risk of AD in the total pooled population (P < .001, OR = 4.02, 95% CI = 3.15-5.13). However, this significant difference existed for Caucasian people (OR = 4.16, 95% CI = 3.24-5.33) but not for Asian or African people. Moreover, we did not find any significant differences in minor allele frequency distribution between the PD and control groups or between the ALS and control groups, not only for the total pooled population but also for the subgroups of different ethnicities.
CONCLUSION: Our study suggested that R47H in the TREM2 gene leads to an increased risk for developing AD, but not for ALS and PD, which adds evidence to the notion that diverse pathogenesis may be involved in different neurogenerative diseases.}, }
@article {pmid31917162, year = {2020}, author = {Rosa Silva, JP and Santiago Júnior, JB and Dos Santos, EL and de Carvalho, FO and de França Costa, IMP and Mendonça, DMF}, title = {Quality of life and functional independence in amyotrophic lateral sclerosis: A systematic review.}, journal = {Neuroscience and biobehavioral reviews}, volume = {111}, number = {}, pages = {1-11}, doi = {10.1016/j.neubiorev.2019.12.032}, pmid = {31917162}, issn = {1873-7528}, mesh = {*Activities of Daily Living ; Amyotrophic Lateral Sclerosis/*physiopathology/*rehabilitation ; Humans ; *Quality of Life ; *Severity of Illness Index ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) leads to functional capacity decline, generating great impact in quality of life. Quality of life is directly related to physical integrity and functional independence. This systematic review aimed to analyze treatment protocols and their outcomes from clinical trials with focus on ALS rehabilitation that evaluated the effects on quality of life and functional independence from their intervention process. A literature search was conducted through MEDLINE-PubMed, Science Direct, Web of Science and Scopus databases. A total of 3630 articles were identified. Eleven studies met the inclusion criteria. They focused on different aspects of quality of life or functional independence, which are: respiratory care, mental health, communication skills and exercises. Use of bipap and inspiratory muscle training, anxiety and depression, communication devices implementation and exercises safety and tolerability were considered as key points. However, the drastic evolution of the disease is a limiting factor to the perception of quality of life improvement by patients. Further studies should be done to validate the benefits on patients' quality of life.}, }
@article {pmid31910072, year = {2020}, author = {Adam, E}, title = {A Systematic Review of the Effectiveness of Oral Baclofen in the Management of Hiccups in Adult Palliative Care Patients.}, journal = {Journal of pain & palliative care pharmacotherapy}, volume = {34}, number = {1}, pages = {43-54}, doi = {10.1080/15360288.2019.1705457}, pmid = {31910072}, issn = {1536-0539}, mesh = {Adult ; Baclofen/*therapeutic use ; Hiccup/*drug therapy/etiology/physiopathology ; Humans ; Palliative Care ; Publications ; Quality of Life ; Randomized Controlled Trials as Topic ; }, abstract = {Hiccup is a recognised symptom amongst the palliative care population. It can be debilitating, with significant impact on quality of life. The pathophysiology is poorly understood and the list of aetiological factors is extensive. The current treatment recommendations are based on a small body of evidence and there remains uncertainty regarding optimal management. The aim of this study was to systematically review the evidence for oral baclofen in the management of hiccups in adult palliative care patients. A search was conducted using MEDLINE, Embase, the Cochrane library and CINAHL, as well as a hand search and review of the grey literature. Relevant articles were identified using pre-defined eligibility criteria. Quality assessment was guided by the SIGN grading system, CASP, Hawker et al's checklist and Cochrane's risk of bias tool. A narrative approach was used for data synthesis. Four relevant articles were identified; one randomised controlled trial and three case series. This gave a combined total of 22 patients, all of whom benefited from the use of oral baclofen in the treatment of hiccups, with few reports of side effects. The dose ranged from 10mg once only to 20mg TDS, and the duration from 1-24 days. However, the overall quality of the evidence was low. While baclofen is an option in the management of hiccups, it is difficult to make recommendations based on the body of evidence presented in this systematic review. There is a lack of RCTs in this field and further research is warranted.}, }
@article {pmid31878794, year = {2020}, author = {Helleman, J and Kruitwagen, ET and van den Berg, LH and Visser-Meily, JMA and Beelen, A}, title = {The current use of telehealth in ALS care and the barriers to and facilitators of implementation: a systematic review.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {21}, number = {3-4}, pages = {167-182}, doi = {10.1080/21678421.2019.1706581}, pmid = {31878794}, issn = {2167-9223}, mesh = {Amyotrophic Lateral Sclerosis/psychology/*therapy ; *Caregivers/psychology/trends ; Health Personnel/psychology/trends ; Humans ; *Patient Acceptance of Health Care/psychology ; Respiratory Insufficiency/psychology/therapy ; Telemedicine/*methods/trends ; *Videoconferencing/trends ; }, abstract = {Objective: We aimed to provide an overview of telehealth used in the care for patients with amyotrophic lateral sclerosis (ALS), and identify the barriers to and facilitators of its implementation. Methods: We searched Pubmed and Embase to identify relevant articles. Full-text articles with original research reporting on the use of telehealth in ALS care, were included. Data were synthesized using the Consolidation Framework for Implementation Research. Two authors independently screened articles based on the inclusion criteria. Results: Sixteen articles were included that investigated three types of telehealth: Videoconferencing, home-based self-monitoring and remote NIV monitoring. Telehealth was mainly used by patients with respiratory impairment and focused on monitoring respiratory function. Facilitators for telehealth implementation were a positive attitude of patients (and caregivers) toward telehealth and the provision of training and ongoing support. Healthcare professionals were more likely to have a negative attitude toward telehealth, due to the lack of personal evaluation/contact and technical issues; this was a known barrier. Other important barriers to telehealth were lack of reimbursement and cost-effectiveness analyses. Barriers and facilitators identified in this review correspond to known determinants found in other healthcare settings. Conclusions: Our findings show that telehealth in ALS care is well-received by patients and their caregivers. Healthcare professionals, however, show mixed experiences and perceive barriers to telehealth use. Challenges related to finance and legislation may hinder telehealth implementation in ALS care. Future research should report the barriers and facilitators of implementation and determine the cost-effectiveness of telehealth.}, }
@article {pmid31870202, year = {2020}, author = {Erber, AC and Cetin, H and Berry, D and Schernhammer, ES}, title = {The role of gut microbiota, butyrate and proton pump inhibitors in amyotrophic lateral sclerosis: a systematic review.}, journal = {The International journal of neuroscience}, volume = {130}, number = {7}, pages = {727-735}, doi = {10.1080/00207454.2019.1702549}, pmid = {31870202}, issn = {1563-5279}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/metabolism/microbiology ; Animals ; Butyrates/*metabolism ; Disease Progression ; Gastrointestinal Microbiome/*physiology ; Humans ; Proton Pump Inhibitors/*therapeutic use ; }, abstract = {Aim of the study: We conducted a systematic review on existing literature in humans and animals, linking the gut microbiome with amyotrophic lateral sclerosis (ALS). Additionally, we sought to explore the role of the bacterially produced metabolite butyrate as well as of proton pump inhibitors (PPIs) in these associations.Materials and methods: Following PRISMA guidelines for systematic literature reviews, four databases (Medline, Scopus, Embase and Web of Science) were searched and screened by two independent reviewers against defined inclusion criteria. Six studies in humans and six animal studies were identified, summarized and reviewed.Results: Overall, the evidence accrued to date is supportive of changes in the gut microbiome being associated with ALS risk, and potentially progression, though observational studies are small (describing a total of 145 patients with ALS across all published studies), and not entirely conclusive.Conclusions: With emerging studies beginning to apply metagenome sequencing, more clarity regarding the importance and promise of the gut microbiome in ALS can be expected. Future studies may also help establish the therapeutic potential of butyrate, and the role of PPIs in these associations.}, }
@article {pmid31853962, year = {2019}, author = {Abdul Wahid, SF and Law, ZK and Ismail, NA and Lai, NM}, title = {Cell-based therapies for amyotrophic lateral sclerosis/motor neuron disease.}, journal = {The Cochrane database of systematic reviews}, volume = {12}, number = {12}, pages = {CD011742}, pmid = {31853962}, issn = {1469-493X}, mesh = {Amyotrophic Lateral Sclerosis/complications/*therapy ; *Cell- and Tissue-Based Therapy ; Disease Progression ; Humans ; Quality of Life ; Randomized Controlled Trials as Topic ; Vital Capacity ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS), which is also known as motor neuron disease (MND), is a fatal disease associated with rapidly progressive disability, for which no definitive treatment exists. Current treatment approaches largely focus on relieving symptoms to improve the quality of life of those affected. The therapeutic potential of cell-based therapies in ALS/MND has not been fully evaluated, given the paucity of high-quality clinical trials. Based on data from preclinical studies, cell-based therapy is a promising treatment for ALS/MND. This review was first published in 2015 when the first clinical trials of cell-based therapies were still in progress. We undertook this update to incorporate evidence now available from randomised controlled trials (RCTs).
OBJECTIVES: To assess the effects of cell-based therapy for people with ALS/MND, compared with placebo or no treatment.
SEARCH METHODS: On 31 July 2019, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, and Embase. We also searched two clinical trials registries for ongoing or unpublished studies.
SELECTION CRITERIA: We included RCTs that assigned people with ALS/MND to receive cell-based therapy versus a placebo or no additional treatment. Co-interventions were allowed, provided that they were given to each group equally.
DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology.
MAIN RESULTS: Two RCTs involving 112 participants were eligible for inclusion in this review. One study compared autologous bone marrow-mesenchymal stem cells (BM-MSC) plus riluzole versus control (riluzole only), while the other study compared combined intramuscular and intrathecal administration of autologous mesenchymal stem cells secreting neurotrophic factors (MSC-NTF) to placebo. The latter study was reported as an abstract and provided no numerical data. Both studies were funded by biotechnology companies. The only study that contributed to the outcome data in the review involved 64 participants, comparing BM-MSC plus riluzole versus control (riluzole only). It reported outcomes after four to six months. It had a low risk of selection bias, detection bias and reporting bias, but a high risk of performance bias and attrition bias. The certainty of evidence was low for all major efficacy outcomes, with imprecision as the main downgrading factor, because the range of plausible estimates, as shown by the 95% confidence intervals (CIs), encompassed a range that would likely result in different clinical decisions. Functional impairment, expressed as the mean change in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score from baseline to six months after cell injection was slightly reduced (better) in the BM-MSC group compared to the control group (mean difference (MD) 3.38, 95% CI 1.22 to 5.54; 1 RCT, 56 participants; low-certainty evidence). ALSFRS-R has a range from 48 (normal) to 0 (maximally impaired); a change of 4 or more points is considered clinically important. The trial did not report outcomes at 12 months. There was no clear difference between the BM-MSC and the no treatment group in change in respiratory function (per cent predicted forced vital capacity; FVC%; MD -0.53, 95% CI -5.37 to 4.31; 1 RCT, 56 participants; low-certainty evidence); overall survival at six months (risk ratio (RR) 1.07, 95% CI 0.94 to 1.22; 1 RCT, 64 participants; low-certainty evidence); risk of total adverse events (RR 0.86, 95% CI 0.62 to 1.19; 1 RCT, 64 participants; low-certainty evidence) or serious adverse events (RR 0.47, 95% CI 0.13 to 1.72; 1 RCT, 64 participants; low-certainty evidence). The study did not measure muscle strength.
AUTHORS' CONCLUSIONS: Currently, there is a lack of high-certainty evidence to guide practice on the use of cell-based therapy to treat ALS/MND. Uncertainties remain as to whether this mode of therapy is capable of restoring muscle function, slowing disease progression, and improving survival in people with ALS/MND. Although one RCT provided low-certainty evidence that BM-MSC may slightly reduce functional impairment measured on the ALSFRS-R after four to six months, this was a small phase II trial that cannot be used to establish efficacy. We need large, prospective RCTs with long-term follow-up to establish the efficacy and safety of cellular therapy and to determine patient-, disease- and cell treatment-related factors that may influence the outcome of cell-based therapy. The major goals of future research are to determine the appropriate cell source, phenotype, dose and method of delivery, as these will be key elements in designing an optimal cell-based therapy programme for people with ALS/MND. Future research should also explore novel treatment strategies, including combinations of cellular therapy and standard or novel neuroprotective agents, to find the best possible approach to prevent or reverse the neurological deficit in ALS/MND, and to prolong survival in this debilitating and fatal condition.}, }
@article {pmid31824397, year = {2019}, author = {Brito, MD and da Silva, GFG and Tilieri, EM and Araujo, BG and Calió, ML and Rosenstock, TR}, title = {Metabolic Alteration and Amyotrophic Lateral Sclerosis Outcome: A Systematic Review.}, journal = {Frontiers in neurology}, volume = {10}, number = {}, pages = {1205}, pmid = {31824397}, issn = {1664-2295}, abstract = {Background: The development of strategies that could not only efficiently detect the onset of Amyotrophic Lateral Sclerosis (ALS), a fatal neurodegenerative disorder with no cure but also predict its development and evaluate therapeutic intervention would be of great value. In this respect, the metabolic status of ALS patients has called attention. Hence, this study aimed to investigate the potential correlation between changes in ALS's metabolic parameters with the disease outcome in a systematic review. Methods: The manuscripts were manually searched within different databases (PubMed, Web of Science and Cochrane). The inclusion criteria were original articles and reviews about individuals with ALS and its survival, disease prognosis and metabolism (weight, cholesterol, hypertension, BMI, and glycaemia). The authors also established three different exclusion criteria: studies including ALS and other degenerative disorders, works including animal models and published before the year 2000. Results: In total, 29 papers were selected. From all manuscripts, only 82.8% ensured the participation of sALS patients. Also, 27.6% of selected studies described the presence of a genetic mutation. Regarding ALS prognosis, patient's age, the age of ALS onset, ALS duration and survival, <50% of the papers addressed these issues. Specifically, regarding metabolism, 65.5% of articles mentioned BMI, 20.7% mentioned any data concerning hypertension, 6.89% cardiovascular risk, 10.3% obesity, 13.78% diabetes and 10.3% glycaemia. Concerning lipid metabolism, more results were gathered, but still, they did not suffice to establish a correlation with ALS development. Conclusions: Altogether, the authors concluded that available information is not enough to establish a link between ALS and metabolism. In reality, less than half of the manuscripts evaluated show an association between both factors. Nonetheless, it is worth mentioning that metabolism does influence ALS, but not in a unique manner. There is a debate about patients' hypo- and hypermetabolism. Thus, to provide a reliable record, a public policy in which all research and clinical centers might assess the parameters discussed herein is suggested. Accordingly, this systematic review attempts to provide a comprehensible database to facilitate multicentered collaboration, validation, and clinical translation.}, }
@article {pmid31811965, year = {2020}, author = {Woodhouse, C and Slobodian, O and Nebor, I and Xu, A and Zhebrykov, D and Montemagno, K and Kashyrina, O and Matern, T and Hoang, S and Mendez-Rosito, D and Cheng, J and Forbes, J}, title = {Risk of Infection Associated with Transmucosal Placement of Instrumentation in Clean-Contaminated Field: Systematic Analysis.}, journal = {World neurosurgery}, volume = {135}, number = {}, pages = {330-334}, doi = {10.1016/j.wneu.2019.11.168}, pmid = {31811965}, issn = {1878-8769}, mesh = {Atlanto-Axial Joint/*surgery ; Atlanto-Occipital Joint/*surgery ; Device Removal/statistics & numerical data ; Humans ; *Mouth Mucosa ; *Nasal Mucosa ; Odontoid Process/*surgery ; Reoperation/statistics & numerical data ; Spinal Cord Compression/surgery ; Spinal Fusion/*methods ; Surgical Wound Infection/*epidemiology ; }, abstract = {Instability of the craniovertebral junction (CVJ) following odontoidectomy is relatively common. Traditionally, separate stage posterior atlantoaxial ± occipitocervical fusion is used for treatment. A transmucosal approach using a clean-contaminated route is associated with hypothetical risks of infectious complications. There is a paucity of information in the literature assessing the risk of surgical site infection (SSI) using the transmucosal approach for hardware placement. The authors conducted a literature search through PubMed identifying patients with pathology requiring transmucosal (i.e., transnasal or transoral) CVJ fixation. Studies that described 1) cases requiring a transmucosal approach and 2) associated infectious complications were included. Rates of SSIs, device removal, unplanned reoperation, and hardware failures were analyzed. Descriptive statistics and odds ratios (ORs) were used to compare complications. Nine studies with a total of 431 patients were identified. There were 4 (0.93%) superficial SSIs and 4 (0.93%) deep SSIs. In total, 1.86% of patients experienced SSI. There were 18 (4.18%) cases of unplanned reoperation, 4 (0.93%) related to SSI. Five (1.16%) patients required removal of their anterior fixation device, 4 (0.93%) related to SSI. ORs comparing our results with Medvedev et al's retrospective National Surgical Quality Improvement Program study assessing the risk associated with posterior cervical fixation showed no statistical difference between postoperative infection rates (OR = 0.72, P = 0.36). An extensive review of the literature found no evidence to suggest placement of spinal hardware via transmucosal corridor is associated with an increased risk of SSI.}, }
@article {pmid31797084, year = {2020}, author = {Xu, L and Liu, T and Liu, L and Yao, X and Chen, L and Fan, D and Zhan, S and Wang, S}, title = {Global variation in prevalence and incidence of amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Journal of neurology}, volume = {267}, number = {4}, pages = {944-953}, pmid = {31797084}, issn = {1432-1459}, support = {91646107//National Natural Science Foundation of China/ ; }, mesh = {Amyotrophic Lateral Sclerosis/*epidemiology/mortality ; Global Health/*statistics & numerical data ; Humans ; Incidence ; Prevalence ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a global disease, which adversely affects the life quality of patients and significantly increases the burden of families and society. We aimed to assess the changing incidence, prevalence of ALS around the world.
METHODS: We searched Medline, Embase, Web of Science, and Cochrane library to identify articles published until September 9, 2018. Each included study was independently reviewed for methodological quality by two reviewers. We used a random-effects model to summarize individual studies and assessed heterogeneity (I[2]) with the χ[2] test on Cochrane's Q statistic.
RESULTS: We identified 124 studies that were eligible for final inclusion, including 110 studies of incidence and 58 studies of prevalence. The overall crude worldwide ALS prevalence and incidence were 4.42 (95% CI 3.92-4.96) per 1,00,000 population and 1.59 (95% CI 1.39-1.81) per 1,00,000 person-years, respectively. ALS prevalence and incidence increased by age until the age of 70-79. Since 1957, incidence has been significantly rising year by year, and this upward trend was weakened after standardization. The longest survival time were in Asia (ranging from 3.74 years in South Asia to 9.23 years in West Asia).
CONCLUSIONS: With the aggravation of population aging and the rapid growth of economy, developing regions following the development pattern of the developed regions may suffer rising ALS prevalence and incidence which may increase their disease burden as well. These data highlight the need for research into underlying mechanism and innovations in health-care systems.}, }
@article {pmid31788795, year = {2020}, author = {Rajabinejad, M and Ranjbar, S and Afshar Hezarkhani, L and Salari, F and Gorgin Karaji, A and Rezaiemanesh, A}, title = {Regulatory T cells for amyotrophic lateral sclerosis/motor neuron disease: A clinical and preclinical systematic review.}, journal = {Journal of cellular physiology}, volume = {235}, number = {6}, pages = {5030-5040}, doi = {10.1002/jcp.29401}, pmid = {31788795}, issn = {1097-4652}, mesh = {Amyotrophic Lateral Sclerosis/genetics/*immunology/pathology ; Humans ; Inflammation/*immunology/pathology ; Motor Neuron Disease/genetics/*immunology/pathology ; Motor Neurons/immunology/metabolism/pathology ; Quality of Life ; T-Lymphocytes, Regulatory/*immunology/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by neuronal degeneration and inflammation in the nerves. The role of the immune system has been concentrated by researchers in the etiopathogenesis of the disease. Given the inhibitory roles of regulatory T cells (Tregs), it is expected that increasing or activating their populations in patients with ALS can have significant therapeutic effects. Here we searched databases, including CENTRAL, MEDLINE, CINAHL Plus, clinicaltrials.gov, and ICTRP for randomized clinical trials (RCTs) and non-RCTs until March 2019. For preclinical studies, we searched PubMed, Scopus, and Google Scholar up to June 2019. We also included preclinical studies, due to the lack of clinical information available, which used Tregs (or directly targeting them) for treating mice models of ALS. We identified 29 records (CENTRAL 7, MEDLINE 4, CINAHL Plus 8, and clinicaltrials.gov 10) and removed 10 duplicated publications. After screening, we identified one RCT which had been published as an abstract, three non-RCTs, and four ongoing studies. We also identified 551 records (PubMed 446, Google Scholar 68, and Scopus 37) for preclinical studies and performed a meta-analysis. Finally, we found three papers that matched our inclusion criteria for preclinical studies. Results indicated the effectiveness of the application of Tregs in the treatment of ALS. Our meta-analysis on preclinical studies revealed that Tregs significantly prolonged survival in mice models of ALS. Overall, our analysis testified that exertion of Tregs in the treatment of ALS is a promising approach, that notwithstanding, requires further evaluations.}, }
@article {pmid31787368, year = {2020}, author = {Essat, M and Archer, R and Williams, I and Zarotti, N and Coates, E and Clowes, M and Beever, D and Hackney, G and White, S and Stavroulakis, T and White, D and Norman, P and McDermott, C and , }, title = {Interventions to promote oral nutritional behaviours in people living with neurodegenerative disorders of the motor system: A systematic review.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {39}, number = {8}, pages = {2547-2556}, doi = {10.1016/j.clnu.2019.11.015}, pmid = {31787368}, issn = {1532-1983}, support = {RP-PG-1016-20006/DH_/Department of Health/United Kingdom ; }, mesh = {Behavior Therapy/*methods ; Breathing Exercises/methods ; Deglutition ; Deglutition Disorders/etiology/therapy ; Diet/*methods ; Electric Impedance ; Feeding Behavior/*physiology ; Functional Status ; Humans ; Motor Neuron Disease/complications/physiopathology/*therapy ; Nutrition Therapy/*methods ; Posture ; Respiratory Muscles/physiopathology ; }, abstract = {BACKGROUND & AIMS: Weight loss is common in people with neurodegenerative diseases of the motor system (NDMS), such as Parkinson's disease and Amyotrophic Lateral Sclerosis, and is associated with reduced quality of life, functional ability and survival. This systematic review aims to identify interventions and intervention components (i.e. behaviour change techniques [BCTs] and modes of delivery [MoDs]) that are associated with increased effectiveness in promoting oral nutritional behaviours that help people with NDMS to achieve a high calorie diet.
METHODS: Eight electronic databases including MEDLINE and CINAHL were searched from inception to May 2018. All interventions from included studies were coded for relevant BCTs and MoDs. Methodological quality of studies was assessed using the Cochrane risk of bias tool.
RESULTS: Fourteen studies were included. Of these, eight studies reported interventions to assist with swallowing difficulties and six studies reported interventions targeting dietary content. Beneficial effects in managing swallowing difficulties were observed with video assisted swallowing therapy, lung volume recruitment and swallowing management clinics with outpatient support. In contrast, studies reporting effectiveness of chin down posture, use of thickened liquids and respiratory muscle training were inconclusive. Positive effects in interventions targeting dietary content included the use of food pyramid tools, individualised nutritional advice with nutritional interventions, electronic health applications, face-to-face dietary counselling and high fat, high carbohydrate and milk whey protein supplements. Individualised nutritional advice with weekly phone contact did not appear to be effective. Most frequently coded BCTs were 'instructions on how to perform the behaviour', 'self-monitoring' and 'behavioural practice/rehearsal'. Most commonly identified MoDs were 'human, face-to-face' and 'somatic therapy'. However, the robustness of these findings are low due to the small number of studies, small sample sizes and large between-study variability.
CONCLUSIONS: Despite the limited evidence, these findings may help inform the development of more effective interventions to promote oral nutritional behaviours in people with NDMS. However, further research is needed to demonstrate which interventions, or intervention components, yield most benefit.}, }
@article {pmid31782132, year = {2020}, author = {Rekatsina, M and Paladini, A and Piroli, A and Zis, P and Pergolizzi, JV and Varrassi, G}, title = {Pathophysiology and Therapeutic Perspectives of Oxidative Stress and Neurodegenerative Diseases: A Narrative Review.}, journal = {Advances in therapy}, volume = {37}, number = {1}, pages = {113-139}, pmid = {31782132}, issn = {1865-8652}, mesh = {Central Nervous System Agents/administration & dosage/adverse effects/*therapeutic use ; Humans ; Inflammation/*physiopathology ; Neurodegenerative Diseases/*drug therapy/*physiopathology ; Oxidative Stress/*physiology ; }, abstract = {INTRODUCTION: Neurodegeneration is the term describing the death of neurons both in the central nervous system and periphery. When affecting the central nervous system, it is responsible for diseases like Alzheimer's disease, Parkinson's disease, Huntington's disorders, amyotrophic lateral sclerosis, and other less frequent pathologies. There are several common pathophysiological elements that are shared in the neurodegenerative diseases. The common denominators are oxidative stress (OS) and inflammatory responses. Unluckily, these conditions are difficult to treat. Because of the burden caused by the progression of these diseases and the simultaneous lack of efficacious treatment, therapeutic approaches that could target the interception of development of the neurodegeneration are being widely investigated. This review aims to highlight the most recent proposed novelties, as most of the previous approaches have failed. Therefore, older approaches may currently be used by healthcare professionals and are not being presented.
METHODS: This review was based on an electronic search of existing literature, using PubMed as primary source for important review articles, and important randomized clinical trials, published in the last 5 years. Reference lists from the most recent reviews, as well as additional sources of primary literature and references cited by relevant articles, were used.
RESULTS: Eighteen natural pharmaceutical substances and 24 extracted or recombinant products, and artificial agents that can be used against OS, inflammation, and neurodegeneration were identified. After presenting the most common neurodegenerative diseases and mentioning some of the basic mechanisms that lead to neuronal loss, this paper presents up to date information that could encourage the development of better therapeutic strategies.
CONCLUSIONS: This review shares the new potential pharmaceutical and not pharmaceutical options that have been recently introduced regarding OS and inflammatory responses in neurodegenerative diseases.}, }
@article {pmid31760837, year = {2020}, author = {Chiaramonte, R and Bonfiglio, M}, title = {Acoustic analysis of voice in bulbar amyotrophic lateral sclerosis: a systematic review and meta-analysis of studies.}, journal = {Logopedics, phoniatrics, vocology}, volume = {45}, number = {4}, pages = {151-163}, doi = {10.1080/14015439.2019.1687748}, pmid = {31760837}, issn = {1651-2022}, mesh = {*Acoustics ; Adult ; Aged ; Amyotrophic Lateral Sclerosis/*complications/diagnosis/physiopathology ; Female ; Humans ; Male ; Middle Aged ; Sound Spectrography ; *Speech Acoustics ; *Speech Production Measurement ; Voice Disorders/diagnosis/*etiology/physiopathology ; *Voice Quality ; }, abstract = {Objective: A systematic review and a meta-analysis were performed to identify the main characteristics of voice disturbances in bulbar amyotrophic lateral sclerosis.Materials and Methods: Literature searches with the keywords: "amyotrophic lateral sclerosis" and "dysarthria" and "intelligibility" were conducted in PubMed, EMBASE, Cochrane Library and Web of Science to perform the systematic review about the articulatory disorders and with the keyword "amyotrophic lateral sclerosis" and "voice" to conduct the meta-analysis about the phonetic changes in patients with bulbar ALS.Results: Seven publications met the inclusion criteria and were included in the meta-analysis, twenty-six publications were included in the systematic review. The data within the meta-analysis revealed that several voice parameters including Jitter, Shimmer, Noise to Harmonic Ratio discriminated best between bulbar amyotrophic lateral sclerosis and healthy controls. On the other hand, significant variations of fundamental frequency were not observed.Conclusion: Acoustic analysis of voice and articulatory analysis contributes to identification of the earliest signs of bulbar degeneration and allows the identification of changes in voice parameters for an early detection, for predicting bulbar involvement and the worsening of disease, for targeting specific intervention. Among the voice parameters, Jitter and Shimmer discriminated better bulbar involvement, they are significantly increased in the patients, on the contrary maximum phonation time is significantly worsened. The careful monitoring of speech symptoms improves diagnostic accuracy and the close cooperation of a multidisciplinary team (physicians as otolaryngologist and physiatrist, speech and language therapists, physiotherapist, dietitians, caregivers, the patients, and their relatives) could be essential.}, }
@article {pmid31760209, year = {2020}, author = {Silva, CS and Rodrigues, FB and Duarte, GS and Costa, J and de Carvalho, M}, title = {Prognostic value of phrenic nerve conduction study in amyotrophic lateral sclerosis: Systematic review and meta-analysis.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {131}, number = {1}, pages = {106-113}, doi = {10.1016/j.clinph.2019.10.016}, pmid = {31760209}, issn = {1872-8952}, mesh = {Amyotrophic Lateral Sclerosis/*mortality/*physiopathology ; Female ; Humans ; Male ; Middle Aged ; Neural Conduction/*physiology ; Observational Studies as Topic ; Phrenic Nerve/*physiopathology ; Prognosis ; Publication Bias ; Vital Capacity/physiology ; }, abstract = {OBJECTIVES: To assess the prognostic value of phrenic nerve conduction (PNC) in amyotrophic lateral sclerosis (ALS).
METHODS: We conducted a systematic review to identify studies reporting on PNC, and mortality and/or forced vital capacity (FVC) in patients with ALS. We searched Medline, EMBASE, and Web of Science. Two independent authors selected studies and extracted data. Risk of bias was assessed using the QUIPS tool. Hazard-ratios and correlation coefficients were pooled using a random effects generic inverse-variance model. Evidence quality was evaluated with GRADE.
RESULTS: In the pooled analysis, patients with CMAP-amplitude equal or below 0.4 mV are 2.021 more likely to die over the studied period (95%CI 1.161-3.522; I[2] = 55.9%; 338 participants). CMAP-amplitude showed a moderate positive correlation with FVC (r = 0.400, 95%CI = 0.226-0.550; I[2] = 69.77%; 381 participants). However, there was a weak negative correlation between CMAP-latency and FVC (r = -0.235; 95%CI = -0.447 to -0.024; I[2] = 15.92%; 112 participants).
CONCLUSIONS: There is moderate-quality evidence that CMAP-amplitude of the PNC is correlated with FVC. Results favour a predictive value for mortality, but the risk of bias is high.
SIGNIFICANCE: PNC is a simple test that should be considered to assess respiratory function in ALS, especially in patients with bulbar involvement or cognitive impairment.}, }
@article {pmid31744001, year = {2019}, author = {Wang, SY and Chen, W and Xu, W and Li, JQ and Hou, XH and Ou, YN and Yu, JT and Tan, L}, title = {Neurofilament Light Chain in Cerebrospinal Fluid and Blood as a Biomarker for Neurodegenerative Diseases: A Systematic Review and Meta-Analysis.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {72}, number = {4}, pages = {1353-1361}, doi = {10.3233/JAD-190615}, pmid = {31744001}, issn = {1875-8908}, mesh = {Biomarkers/blood/cerebrospinal fluid ; Diagnosis, Differential ; Humans ; Neurodegenerative Diseases/blood/cerebrospinal fluid/*diagnosis ; Neurofilament Proteins/blood/cerebrospinal fluid/*metabolism ; }, abstract = {BACKGROUND: Neurofilament light chain (NFL) as a potential biomarker of neurodegenerative diseases has been studied in a number of studies. Thus, a comprehensive meta-analysis is warranted to assess NFL performance in neurodegenerative diseases.
OBJECTIVE: To assess the performance of NFL in blood and cerebrospinal fluid (CSF) as a biomarker for neurodegenerative diseases.
METHODS: A total of 36 studies with comparison of NFL level between individuals with neurodegenerative diseases and controls were retrieved from PubMed, Web of Science and Science Direct, and the ratio of means method and delta method based on the random-effect model were used to analyze the differentiation of NFL between patients and controls.
RESULTS: Differentiation of CSF NFL between patients with neurodegenerative diseases and controls showed significant results. Although a few studies on blood NFL available were included in the meta-analysis, the results still showed a distinct possibility that NFL could be a potential biomarker for neurodegenerative diseases. NFL levels were increased significantly in dementias, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, and Huntington's disease. By contrast, NFL levels were not increased in Parkinson's disease (PD), although they were increased significantly in PD-related disorders (multiple system atrophy and progressive supranuclear palsy).
CONCLUSIONS: In our study, in addition to PD, NFL was suggested to be a global diagnostic biomarker for neurodegenerative diseases. Moreover, it could be used in differential diagnosis of PD and PD-related disorders. However, it was worth noting that NFL was not appropriate for diagnosis or differential diagnosis without clinical symptoms and other auxiliary examinations.}, }
@article {pmid31738367, year = {2020}, author = {Glasmacher, SA and Wong, C and Pearson, IE and Pal, S}, title = {Survival and Prognostic Factors in C9orf72 Repeat Expansion Carriers: A Systematic Review and Meta-analysis.}, journal = {JAMA neurology}, volume = {77}, number = {3}, pages = {367-376}, pmid = {31738367}, issn = {2168-6157}, mesh = {Aged ; Amyotrophic Lateral Sclerosis/*genetics/*mortality ; C9orf72 Protein/*genetics ; DNA Repeat Expansion ; Female ; Frontotemporal Dementia/*genetics/*mortality ; Humans ; Male ; Middle Aged ; Prognosis ; Risk Factors ; }, abstract = {IMPORTANCE: The c9orf72 repeat expansion (c9 or c9orf72RE) confers a survival disadvantage in amyotrophic lateral sclerosis (ALS); its effect on prognosis in frontotemporal dementia (FTD) remains uncertain. Data on prognostic factors in c9orf72RE disorders could inform patient care, genetic counseling, and trial design.
OBJECTIVE: To examine prognostic factors in c9ALS, c9FTD, c9ALS-FTD, and atypical phenotypes.
DATA SOURCES: The MEDLINE, Embase, Amed, ProQuest, PsychINFO, CINAHL, and LILACS databases were searched between January 2011 and January 2019. Keywords used were c9orf72 and chromosome 9 open reading frame 72. Reference lists, citations of eligible studies, and review articles were also searched by hand.
STUDY SELECTION: Studies reporting disease duration for patients with a confirmed c9orf72RE and a neurological and/or psychiatric disorder were included. A second author independently reviewed studies classified as irrelevant by the first author. Analysis began in January 2019.
DATA EXTRACTION AND SYNTHESIS: Data were extracted by 1 author; a further author independently extracted 10% of data. Data were synthesized in univariate and multivariable Cox regression and are displayed as hazard ratios (HR) and 95% confidence intervals.
MAIN OUTCOMES AND MEASURES: Survival after symptom onset.
RESULTS: Overall, 206 studies reporting on 1060 patients were included from 2878 publications identified (c9ALS: n = 455; c9FTD: n = 296; c9ALS-FTD: n = 198; atypical phenotypes: n = 111); 197 duplicate cases were excluded. The median (95% CI) survival (in years) differed significantly between patients with c9ALS (2.8 [2.67-3.00]), c9FTD (9.0 [8.09-9.91]), and c9ALS-FTD (3.0 [2.73-3.27]); survival in atypical phenotypes varied substantially. Older age at onset was associated with shorter survival in c9ALS (HR, 1.03; 95% CI, 1.02-1.04; P < .001), c9FTD (HR, 1.04; 95% CI, 1.02-1.06; P < .001), and c9ALS-FTD (HR, 1.02; 95% CI, 1.004-1.04; P = .016). Bulbar onset was associated with shorter survival in c9ALS (HR, 1.64; 95% CI, 1.27-2.08; P < .001). Age at onset and bulbar onset ALS remained significant in multivariable regression including variables indicating potential diagnostic ascertainment bias, selection bias, and reporting bias. Family history, sex, study continent, FTD subtype, or the presence of additional pathogenic sequence variants were not significantly associated with survival. Clinical phenotypes in patients with neuropathologically confirmed frontotemporal lobar degeneration-TDP-43, motor neuron disease-TDP-43 and frontotemporal lobar degeneration-motor neuron disease-TDP-43 were heterogenous and impacted on survival.
CONCLUSIONS AND RELEVANCE: Several factors associated with survival in c9orf72RE disorders were identified. The inherent limitations of our methodological approach must be considered; nonetheless, the reported prognostic factors were not significantly associated with the bias indicators examined.}, }
@article {pmid31684843, year = {2021}, author = {Bianchi, VE and Herrera, PF and Laura, R}, title = {Effect of nutrition on neurodegenerative diseases. A systematic review.}, journal = {Nutritional neuroscience}, volume = {24}, number = {10}, pages = {810-834}, doi = {10.1080/1028415X.2019.1681088}, pmid = {31684843}, issn = {1476-8305}, mesh = {*Alzheimer Disease ; *Cognitive Dysfunction/prevention & control ; *Fatty Acids, Omega-3 ; Humans ; *Neurodegenerative Diseases/prevention & control ; Nutritional Status ; }, abstract = {Neurodegenerative diseases are characterized by the progressive functional loss of neurons in the brain, causing cognitive impairment and motoneuron disability. Although multifactorial interactions are evident, nutrition plays an essential role in the pathogenesis and evolution of these diseases. A systematic literature search was performed, and the prevalence of studies evaluated the effect of the Mediterranean diet (MeDiet), nutritional support, EPA and DHA, and vitamins on memory and cognition impairment. The data showed that malnutrition and low body mass index (BMI) is correlated with the higher development of dementia and mortality. MeDiet, nutritional support, and calorie-controlled diets play a protective effect against cognitive decline, Alzheimer's disease (AD), Parkinson disease (PD) while malnutrition and insulin resistance represent significant risk factors. Malnutrition activates also the gut-microbiota-brain axis dysfunction that exacerbate neurogenerative process. Omega-3 and -6, and the vitamins supplementation seem to be less effective in protecting neuron degeneration. Insulin activity is a prevalent factor contributing to brain health while malnutrition correlated with the higher development of dementia and mortality.}, }
@article {pmid31675954, year = {2019}, author = {Flannery, C and Fredrix, M and Olander, EK and McAuliffe, FM and Byrne, M and Kearney, PM}, title = {Effectiveness of physical activity interventions for overweight and obesity during pregnancy: a systematic review of the content of behaviour change interventions.}, journal = {The international journal of behavioral nutrition and physical activity}, volume = {16}, number = {1}, pages = {97}, pmid = {31675954}, issn = {1479-5868}, mesh = {*Exercise ; Exercise Therapy ; Female ; *Health Behavior ; Humans ; Obesity/*therapy ; Overweight/*therapy ; Pregnancy ; Pregnancy Complications/*therapy ; Prenatal Care ; }, abstract = {BACKGROUND: Behaviour change techniques (BCTs) employed within PA intervention for pregnant women with a healthy body mass index (BMI) have been previously identified, however, these BCTS may differ for other weight profiles during pregnancy. The aim of this current review was to identify and summarise the evidence for effectiveness of PA interventions on PA levels for pregnant women with overweight and obesity, with an emphasis on the BCTs employed.
METHODS: A systematic review and meta-analysis of PA intervention studies using the PRISMA statement was conducted. Searches were conducted of eight databases in January 2019. Strict inclusion/exclusion criteria were employed. The validity of each included study was assessed using the Cochrane Collaboration's tool for assessing risk of bias. The primary outcome measure was change in PA levels, subjectively or objectively measured, with physical fitness as a secondary outcome. All intervention descriptions were double coded by two authors using Michie's et al's BCT taxonomy V1. Meta-analyses using random effect models assessed the intervention effects on PA. Other PA outcomes were summarised in a narrative synthesis.
RESULTS: From 8389 studies, 19 met the inclusion criteria 13 of which were suitable for inclusion in a meta-analysis. The remaining 6 studies were described narratively due to insufficient data and different outcome measures reported. In the meta-analysis, comparing interventions to a control group, significant increases were found in the intervention group for metabolic equivalent (SMD 0.39 [0.14, 0.64], Z = 3.08 P = 0.002) and physical fitness (VO2 max) (SMD 0.55 [0.34, 0.75], Z = 5.20 P = < 0.001). Of the other six, five studies reported an increase in PA for the intervention group versus the control with the other study reporting a significant decrease for women in their 3rd trimester (p = 0.002). 'Self-monitoring of behaviour' was the most frequently used BCTs (76.5%), with 'social support' being newly identified for this pregnant population with overweight or obesity.
CONCLUSIONS: This review identified a slight increase in PA for pregnant women with overweight and obesity participating in interventions. However, due to the high risk of bias of the included studies, the results should be interpreted with caution. PA measures should be carefully selected so that studies can be meaningfully compared and standardised taxonomies should be used so that BCTs can be accurately assessed.}, }
@article {pmid31658175, year = {2020}, author = {Roda, M and Ciavarella, C and Giannaccare, G and Versura, P}, title = {Biomarkers in Tears and Ocular Surface: A Window for Neurodegenerative Diseases.}, journal = {Eye & contact lens}, volume = {46 Suppl 2}, number = {}, pages = {S129-S134}, doi = {10.1097/ICL.0000000000000663}, pmid = {31658175}, issn = {1542-233X}, mesh = {Biomarkers/metabolism ; Cornea/*metabolism ; Humans ; Neurodegenerative Diseases/diagnosis/*metabolism ; Tears/*metabolism ; }, abstract = {OBJECTIVES: The purpose of this review is to briefly outline current scientific evidence on the potential role of tear analysis and ocular surface evaluation in diagnosis and monitoring of neurodegenerative diseases, especially Alzheimer disease, Parkinson disease, and glaucoma.
METHODS: A systematic computerized search in the electronic databases PubMed, MEDLINE, and the Cochrane Collaborations was conducted to find eligible articles which their main topic was to investigate the tear and ocular surface in neurodegenerative diseases. After a first screening of titles and abstracts and a full-text review, 26 articles met the inclusion criteria (1 about the neurodegenerative diseases, 3 about the Alzheimer disease, 11 about the Parkinson disease, 11 about glaucoma, and 1 about amyotrophic lateral sclerosis).
RESULTS: The ocular surface picture seems to be altered in the setting of neurodegenerative diseases with specific characteristics according to each disease. They seem to be associated with reduced corneal sensitivity and abnormal tear function, and each one presents the expression of specific biomarkers in tears.
CONCLUSIONS: The study of tears and ocular surface appears to be a new and noninvasive promising way to assist in the diagnosis and monitoring of neurodegenerative diseases.}, }
@article {pmid31578652, year = {2020}, author = {Meng, E and Mao, Y and Yao, Q and Han, X and Li, X and Zhang, K and Jin, W}, title = {Population-based study of environmental/occupational lead exposure and amyotrophic lateral sclerosis: a systematic review and meta-analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {41}, number = {1}, pages = {35-40}, pmid = {31578652}, issn = {1590-3478}, support = {YZ2018081//Yangzhou Science and Technology Planning Project (CN)/ ; }, mesh = {Amyotrophic Lateral Sclerosis/*chemically induced/diagnosis/*epidemiology ; Case-Control Studies ; Environmental Exposure/*adverse effects ; Humans ; Lead/*adverse effects ; Occupational Exposure/*adverse effects ; *Population Surveillance/methods ; Risk Factors ; }, abstract = {Lead is a known risk factor for amyotrophic lateral sclerosis (ALS). However, the results of studies exploring the relationship between lead exposure and the occurrence of ALS are inconsistent. To clarify this issue, we conducted a systematic review and meta-analysis of relevant published articles on the relationship between lead exposure and the occurrence of ALS. We searched the PubMed, MEDLINE, Embase, and Science Direct databases for relevant publications. The quality of the articles was judged according to the Newcastle-Ottawa scale, and the meta-analysis was conducted using a random effect model. A total of 583 items were retrieved of which 11 case-control studies were selected. The ratio of maximal/minimal lead exposure yielded a pooled odds ratio (OR) of 1.46 (95% confidence interval (CI) 1.16-1.83) with moderate heterogeneity (I[2] = 51.8%; p = 0.019). Subgroup and sensitivity analyses showed stable results. There was evidence of publication bias, but the recalculated OR after employing the "fill and trim" method was 1.28 (95% CI 1.02-1.63). These results indicated that environmental/occupational lead exposure was positively proportional to the risk of ALS.}, }
@article {pmid31487757, year = {2019}, author = {Silva, IS and Pedrosa, R and Azevedo, IG and Forbes, AM and Fregonezi, GA and Dourado Junior, ME and Lima, SR and Ferreira, GM}, title = {Respiratory muscle training in children and adults with neuromuscular disease.}, journal = {The Cochrane database of systematic reviews}, volume = {9}, number = {9}, pages = {CD011711}, pmid = {31487757}, issn = {1469-493X}, mesh = {Adult ; Breathing Exercises/*methods ; Child ; Exhalation/physiology ; Humans ; Muscle Weakness ; Neuromuscular Diseases/*rehabilitation ; Quality of Life ; Randomized Controlled Trials as Topic ; Vital Capacity ; }, abstract = {BACKGROUND: Neuromuscular diseases (NMDs) are a heterogeneous group of diseases affecting the anterior horn cell of spinal cord, neuromuscular junction, peripheral nerves and muscles. NMDs cause physical disability usually due to progressive loss of strength in limb muscles, and some NMDs also cause respiratory muscle weakness. Respiratory muscle training (RMT) might be expected to improve respiratory muscle weakness; however, the effects of RMT are still uncertain. This systematic review will synthesize the available trial evidence on the effectiveness and safety of RMT in people with NMD, to inform clinical practice.
OBJECTIVES: To assess the effects of respiratory muscle training (RMT) for neuromuscular disease (NMD) in adults and children, in comparison to sham training, no training, standard treatment, breathing exercises, or other intensities or types of RMT.
SEARCH METHODS: On 19 November 2018, we searched the Cochrane Neuromuscular Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase. On 23 December 2018, we searched the US National Institutes for Health Clinical Trials Registry (ClinicalTrials.gov), the World Health Organization International Clinical Trials Registry Platform, and reference lists of the included studies.
SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-RCTs, including cross-over trials, of RMT in adults and children with a diagnosis of NMD of any degree of severity, who were living in the community, and who did not need mechanical ventilation. We compared trials of RMT (inspiratory muscle training (IMT) or expiratory muscle training (EMT), or both), with sham training, no training, standard treatment, different intensities of RMT, different types of RMT, or breathing exercises.
DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodological procedures.
MAIN RESULTS: We included 11 studies involving 250 randomized participants with NMDs: three trials (N = 88) in people with amyotrophic lateral sclerosis (ALS; motor neuron disease), six trials (N = 112) in Duchenne muscular dystrophy (DMD), one trial (N = 23) in people with Becker muscular dystrophy (BMD) or limb-girdle muscular dystrophy, and one trial (N = 27) in people with myasthenia gravis.Nine of the trials were at high risk of bias in at least one domain and many reported insufficient information for accurate assessment of the risk of bias. Populations, interventions, control interventions, and outcome measures were often different, which largely ruled out meta-analysis. All included studies assessed lung capacity, our primary outcome, but four did not provide data for analysis (1 in people with ALS and three cross-over studies in DMD). None provided long-term data (over a year) and only one trial, in ALS, provided information on adverse events. Unscheduled hospitalisations for chest infection or acute exacerbation of chronic respiratory failure were not reported and physical function and quality of life were reported in one (ALS) trial.Amyotrophic lateral sclerosis (ALS)Three trials compared RMT versus sham training in ALS. Short-term (8 weeks) effects of RMT on lung capacity in ALS showed no clear difference in the change of the per cent predicted forced vital capacity (FVC%) between EMT and sham EMT groups (mean difference (MD) 0.70, 95% confidence interval (CI) -8.48 to 9.88; N = 46; low-certainty evidence). The mean difference (MD) in FVC% after four months' treatment was 10.86% in favour of IMT (95% CI -4.25 to 25.97; 1 trial, N = 24; low-certainty evidence), which is larger than the minimal clinically important difference (MCID, as estimated in people with idiopathic pulmonary fibrosis). There was no clear difference between IMT and sham IMT groups, measured on the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALFRS; range of possible scores 0 = best to 40 = worst) (MD 0.85, 95% CI -2.16 to 3.85; 1 trial, N = 24; low-certainty evidence) or quality of life, measured on the EuroQol-5D (0 = worst to 100 = best) (MD 0.77, 95% CI -17.09 to 18.62; 1 trial, N = 24; low-certainty evidence) over the medium term (4 months). One trial report stated that the IMT protocol had no adverse effect (very low-certainty evidence).Duchenne muscular dystrophy (DMD)Two DMD trials compared RMT versus sham training in young males with DMD. In one study, the mean post-intervention (6-week) total lung capacity (TLC) favoured RMT (MD 0.45 L, 95% CI -0.24 to 1.14; 1 trial, N = 16; low-certainty evidence). In the other trial there was no clear difference in post-intervention (18 days) FVC between RMT and sham RMT (MD 0.16 L, 95% CI -0.31 to 0.63; 1 trial, N = 20; low-certainty evidence). One RCT and three cross-over trials compared a form of RMT with no training in males with DMD; the cross-over trials did not provide suitable data. Post-intervention (6-month) values showed no clear difference between the RMT and no training groups in per cent predicted vital capacity (VC%) (MD 3.50, 95% CI -14.35 to 21.35; 1 trial, N = 30; low-certainty evidence).Becker or limb-girdle muscular dystrophyOne RCT (N = 21) compared 12 weeks of IMT with breathing exercises in people with Becker or limb-girdle muscular dystrophy. The evidence was of very low certainty and conclusions could not be drawn.Myasthenia gravisIn myasthenia gravis, there may be no clear difference between RMT and breathing exercises on measures of lung capacity, in the short term (TLC MD -0.20 L, 95% CI -1.07 to 0.67; 1 trial, N = 27; low-certainty evidence). Effects of RMT on quality of life are uncertain (1 trial; N = 27).Some trials reported effects of RMT on inspiratory and/or expiratory muscle strength; this evidence was also of low or very low certainty.
AUTHORS' CONCLUSIONS: RMT may improve lung capacity and respiratory muscle strength in some NMDs. In ALS there may not be any clinically meaningful effect of RMT on physical functioning or quality of life and it is uncertain whether it causes adverse effects. Due to clinical heterogeneity between the trials and the small number of participants included in the analysis, together with the risk of bias, these results must be interpreted very cautiously.}, }
@article {pmid35047680, year = {2019}, author = {Fernandes, JG and Franco, NH and Grierson, AJ and Hultgren, J and Furley, AJW and Olsson, IAS}, title = {Methodological standards, quality of reporting and regulatory compliance in animal research on amyotrophic lateral sclerosis: a systematic review.}, journal = {BMJ open science}, volume = {3}, number = {1}, pages = {e000016}, pmid = {35047680}, issn = {2398-8703}, abstract = {OBJECTIVES: The amyotrophic lateral sclerosis (ALS) research community was one of the first to adopt methodology guidelines to improve preclinical research reproducibility. We here present the results of a systematic review to investigate how the standards in this field changed over the 10-year period during which the guidelines were first published (2007) and updated (2010).
METHODS: We searched for papers reporting ALS research on SOD1 (superoxide dismutase 1) mice published between 2005 and 2015 on the ISI Web of Science database, resulting in a sample of 569 papers to review, after triage. Two scores-one for methodological quality, one for regulatory compliance-were built from weighted sums of separate sets of items, and subjected to multivariable regression analysis, to assess how these related to publication year, type of study, country of origin and journal.
RESULTS: Reporting standards improved over time. Of papers published after the first ALS guidelines were made public, fewer than 9% referred specifically to these. Of key research parameters, only three (genetic background, number of transgenes and group size) were reported in >50% of the papers. Information on housing conditions, randomisation and blinding was absent in over two-thirds of the papers. Group size was among the best reported parameters, but the majority reported using fewer than the recommended sample size and only two studies clearly justified group size.
CONCLUSIONS: General methodological standards improved gradually over a period of 8-10 years, but remained generally comparable with related fields with no specific guidelines, except with regard to severity. Only 11% of ALS studies were classified in the highest severity level (animals allowed to reach death or moribund stages), substantially below the proportion in studies of comparable neurodegenerative diseases such as Huntington's. The existence of field-specific guidelines, although a welcome indication of concern, seems insufficient to ensure adherence to high methodological standards. Other mechanisms may be required to improve methodological and welfare standards.}, }
@article {pmid31356849, year = {2019}, author = {Juźwik, CA and S Drake, S and Zhang, Y and Paradis-Isler, N and Sylvester, A and Amar-Zifkin, A and Douglas, C and Morquette, B and Moore, CS and Fournier, AE}, title = {microRNA dysregulation in neurodegenerative diseases: A systematic review.}, journal = {Progress in neurobiology}, volume = {182}, number = {}, pages = {101664}, doi = {10.1016/j.pneurobio.2019.101664}, pmid = {31356849}, issn = {1873-5118}, mesh = {Animals ; Brain/*metabolism ; Disease Models, Animal ; *Gene Expression Regulation ; Humans ; MicroRNAs/*genetics/metabolism ; Neurodegenerative Diseases/diagnosis/*genetics/*immunology ; }, abstract = {While the root causes for individual neurodegenerative diseases are distinct, many shared pathological features and mechanisms contribute to neurodegeneration across diseases. Altered levels of microRNAs, small non-coding RNAs involved in post transcriptional regulation of gene expression, are reported for numerous neurodegenerative diseases. Yet, comparison between diseases to uncover commonly dysregulated microRNAs during neurodegeneration in general is lagging. We performed a systematic review of peer-reviewed publications describing differential microRNA expression in neurodegenerative diseases and related animal models. We compiled the results from studies covering the prevalent neurodegenerative diseases in the literature: Alzheimer's disease, amyotrophic lateral sclerosis, age-related macular degeneration, ataxia, dementia, myotonic dystrophy, epilepsy, glaucoma, Huntington's disease, multiple sclerosis, Parkinson's disease, and prion disorders. MicroRNAs which were dysregulated most often in these diseases and their models included miR-9-5p, miR-21-5p, the miR-29 family, miR-132-3p, miR-124-3p, miR-146a-5p, miR-155-5p, and miR-223-3p. Common pathways targeted by these predominant miRNAs were identified and revealed great functional overlap across diseases. We also identified a strong role for each microRNA in both the neural and immune components of diseases. microRNAs regulate broad networks of genes and identifying microRNAs commonly dysregulated across neurodegenerative diseases could cultivate novel hypotheses related to common molecular mechanisms underlying neurodegeneration.}, }
@article {pmid31282612, year = {2019}, author = {Paynter, C and Cruice, M and Mathers, S and Gregory, H and Vogel, AP}, title = {Communication and cognitive impairments and health care decision making in MND: A narrative review.}, journal = {Journal of evaluation in clinical practice}, volume = {25}, number = {6}, pages = {1182-1192}, doi = {10.1111/jep.13219}, pmid = {31282612}, issn = {1365-2753}, support = {1133541//Motor Neurone Disease Research Institute of Australia/ ; 1135683//Dementia Fellowship/ ; }, mesh = {Cognitive Dysfunction/*etiology ; *Communication ; *Decision Making, Shared ; Humans ; Motor Neuron Disease/*complications/*therapy ; }, abstract = {RATIONALE: Motor neurone disease (MND) is a neurodegenerative disease presenting with progressive weakness of voluntary muscles. For any condition, person-centred health care relies on the sharing of information and a mutual understanding of the person's needs and preferences. Decision making in MND becomes more complex as there is no cure and a high prevalence of co-morbid communication and/or cognitive difficulties.
OBJECTIVE: To identify the reported impact of communication and/or cognitive impairment on patient and carer involvement in health care decision making in MND.
METHODS: A review and synthesis of studies addressing issues of communication impairment and/or cognitive impairment in relation to decision making focussed on MND was conducted. Articles were excluded if they were reviews, case studies, conference papers, or commentaries. To be included studies needed to address issues of communication impairment or cognitive impairment specifically in relation to decision making. Relevant data were extracted verbatim and subjected to content analysis to support the narrative summary.
RESULTS: Seventy-six articles were identified, and 35 articles screened. Six articles met inclusion criteria each describing examples of decision making in MND. There was limited data related to communication and/or cognitive impairment, and the impact these impairments may have on decision making despite recognition that many people with MND may lose verbal communication or develop subtle cognitive impairments. The literature is primarily from the perspective of others.
CONCLUSION: This review highlights that the current body of literature exploring decision making within the MND population presents us with extremely limited insights into the impact of communication and/or cognitive impairments on health care decision making. Extant literature focuses on interventions (namely, ventilation and gastrostomy), the broad process of decision making, or cognitive assessment of decision-making ability. Whilst most studies acknowledge that deficits in communication or cognition impact the decision-making process, this issue is not the focus of any study.}, }
@article {pmid31281567, year = {2019}, author = {Wang, Z and Bai, Z and Qin, X and Cheng, Y}, title = {Aberrations in Oxidative Stress Markers in Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.}, journal = {Oxidative medicine and cellular longevity}, volume = {2019}, number = {}, pages = {1712323}, pmid = {31281567}, issn = {1942-0994}, mesh = {Amyotrophic Lateral Sclerosis/*blood ; Humans ; Oxidative Stress/*genetics ; }, abstract = {Oxidative stress has been reported to be involved in the onset and development of amyotrophic lateral sclerosis (ALS). Data from clinical studies have highlighted increased peripheral blood oxidative stress markers in patients with ALS, but results are inconsistent. Therefore, we quantitatively pooled data on levels of blood oxidative stress markers in ALS patients from the literature using a meta-analytic technique. A systematic search was performed on PubMed and Web of Science, and we included studies analyzing blood oxidative stress marker levels in patients with ALS and normal controls. We included 41 studies with 4,588 ALS patients and 6,344 control subjects, and 15 oxidative stress marker levels were subjected to random-effects meta-analysis. The results demonstrated that malondialdehyde (Hedges' g, 1.168; 95% CI, 0.812 to 1.523; P < 0.001), 8-hydroxyguanosine (Hedges' g, 2.194; 95% CI, 0.554 to 3.835; P = 0.009), and Advanced Oxidation Protein Product (Hedges' g, 0.555; 95% CI, 0.317 to 0.792; P < 0.001) levels were significantly increased in patients with ALS when compared with control subjects. Uric acid (Hedges' g, -0.798; 95% CI, -1.117 to -0.479; P < 0.001) and glutathione (Hedges' g, -1.636; 95% CI, -3.020 to -0.252; P = 0.02) levels were significantly reduced in ALS patients. In contrast, blood Cu, superoxide dismutase, glutathione peroxidase, ceruloplasmin, triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein, coenzyme-Q10, and transferrin levels were not significantly different between cases and controls. Taken together, our results showed significantly increased blood levels of 8-hydroxyguanosine, malondialdehyde, and Advanced Oxidation Protein Product and decreased glutathione and uric acid levels in the peripheral blood of ALS patients. This meta-analysis helps to clarify the oxidative stress marker profile in ALS patients, supporting the hypothesis that oxidative stress is a central component underpinning ALS pathogenesis.}, }
@article {pmid31273038, year = {2019}, author = {O'Brien, D and Stavroulakis, T and Baxter, S and Norman, P and Bianchi, S and Elliott, M and Johnson, M and Clowes, M and Garcia-Sánchez, A and Hobson, E and McDermott, C}, title = {The optimisation of noninvasive ventilation in amyotrophic lateral sclerosis: a systematic review.}, journal = {The European respiratory journal}, volume = {54}, number = {3}, pages = {}, doi = {10.1183/13993003.00261-2019}, pmid = {31273038}, issn = {1399-3003}, support = {PB-PG-1216-20041/DH_/Department of Health/United Kingdom ; }, mesh = {Amyotrophic Lateral Sclerosis/complications/psychology/*therapy ; Caregivers ; Cough/complications ; Evidence-Based Medicine ; Humans ; Lung/physiopathology ; Monitoring, Ambulatory ; Noninvasive Ventilation/adverse effects/*methods ; Patient Compliance ; Quality of Life ; Reproducibility of Results ; Respiratory Insufficiency/complications ; Risk ; Treatment Outcome ; }, abstract = {BACKGROUND: Noninvasive ventilation (NIV) prolongs survival and quality of life in amyotrophic lateral sclerosis (ALS); however, its benefits depend upon the optimisation of both ventilation and adherence. We aimed to identify factors associated with effective initiation and ongoing use of NIV in ALS to develop evidence-based guidance and identify areas for further research.
METHODS: We searched 11 electronic databases (January 1998 to May 2018) for all types of quantitative and qualitative studies. Supplementary grey literature searches were conducted. Records were screened against eligibility criteria, data were extracted from included studies and risk of bias was assessed. We present findings using a narrative synthesis.
RESULTS: We screened 2430 unique records and included 52 quantitative and six qualitative papers. Factors reported to be associated with NIV optimisation included coordinated multidisciplinary care, place of initiation, selection of interfaces, ventilator modes and settings appropriate for the individual patient, and adequate secretion management. The literature indicated that patients with significant bulbar dysfunction can still derive considerable benefit from NIV if their needs are met. Research emphasises that obstructive airway events, mask leak and uncontrolled secretions should be addressed by adjustments to the interface and machine settings, and the concomitant use of cough augmentation.
CONCLUSION: This review highlights that NIV optimisation requires an individualised approach to respiratory management tailored to the differing needs of each patient. Ultimately, this should lead to improved survival and quality of life. This review expands on recommendations in current international guidelines for NIV use in ALS and identifies areas for future research.}, }
@article {pmid31243460, year = {2019}, author = {Lee, YX and Kwan, YH and Lim, KK and Tan, CS and Lui, NL and Phang, JK and Chew, EH and Ostbye, T and Thumboo, J and Fong, W}, title = {A systematic review of the association of obesity with the outcomes of inflammatory rheumatic diseases.}, journal = {Singapore medical journal}, volume = {60}, number = {6}, pages = {270-280}, pmid = {31243460}, issn = {2737-5935}, mesh = {Arthritis, Rheumatoid/complications/therapy ; Humans ; Obesity/*complications ; Rheumatic Diseases/*complications/therapy ; Treatment Outcome ; }, abstract = {This was a systematic review of the literature on the association between obesity and the outcome of inflammatory rheumatic diseases. We conducted a literature search using PubMed®, Embase and PsycINFO®. Articles were classified into three categories based on the effects of obesity on the outcomes of inflammatory rheumatic diseases. The subject population, country, type of studies, number of patients, measurement of obesity and outcomes assessed were presented. Quality was appraised using Kmet et al's criteria. 4,331 articles were screened and 60 were relevant to the objective. Obesity had a negative, positive and neutral association with outcomes of inflammatory rheumatic diseases in 38 (63.3%) studies with 57,612 subjects, 11 (18.3%) studies with 3,866 subjects, and 11 (18.3%) studies with 3,834 subjects, respectively. In most studies, the disease population had been diagnosed with rheumatoid arthritis (RA). Tumour necrosis factor-α inhibitors were mostly associated with negative outcomes. More studies examining subjects outside Europe and North America and diseases other than RA are warranted.}, }
@article {pmid31204525, year = {2019}, author = {Baxter, SK and Johnson, M and Clowes, M and O'Brien, D and Norman, P and Stavroulakis, T and Bianchi, S and Elliott, M and McDermott, C and Hobson, E}, title = {Optimizing the noninvasive ventilation pathway for patients with amyotrophic lateral sclerosis/motor neuron disease: a systematic review.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {20}, number = {7-8}, pages = {461-472}, doi = {10.1080/21678421.2019.1627372}, pmid = {31204525}, issn = {2167-9223}, support = {PB-PG-1216-20041/DH_/Department of Health/United Kingdom ; }, mesh = {Amyotrophic Lateral Sclerosis/diagnosis/*psychology/*therapy ; Cohort Studies ; Cross-Sectional Studies ; Humans ; Motor Neuron Disease/diagnosis/psychology/therapy ; Noninvasive Ventilation/methods/*standards ; Quality of Life/*psychology ; Retrospective Studies ; }, abstract = {Objective: To systematically review quantitative and qualitative literature on optimal provision of noninvasive ventilation (NIV) for patients with amyotrophic lateral sclerosis/motor neuron disease (MND). Methods: A systematic search of electronic databases, together with supplementary search methods was used to identify relevant literature from the last 20 years. Studies of any empirical design with an English abstract were eligible for inclusion. Data from documents meeting our criteria were extracted and synthesized using narrative and thematic synthesis. A patient pathway of care model was used to integrate data and provide a process perspective to the findings. Results: While the importance of individualizing care was highlighted, factors optimizing use for all patients include: specialized multi-disciplinary team service provision; determining need using respiratory function tests in addition to symptom report; providing adequate information for patients and their family; paying attention to the role of carers in decision-making; adequately managing secretions; considering the most advantageous place of initiation; optimizing the interface, machine mode, and settings for patient comfort and effectiveness; providing supportive interventions where appropriate; regular monitoring and adjustment of settings; and providing opportunities for ongoing discussion of patient wishes. Conclusions: Optimizing use of NIV in people with MND requires consideration of multiple factors as part of a process throughout the patient pathway. Current guidelines predominantly focus on the initiation of NIV and may underplay psychosocial factors. We have made evidence-based recommendations for each step in the pathway, which may help improve optimal uptake, usage, quality of life, and survival outcomes in patients with MND.}, }
@article {pmid31142552, year = {2019}, author = {Ebell, MH and Vellinga, A and Masterson, S and Yun, P}, title = {Meta-analysis of the accuracy of termination of resuscitation rules for out-of-hospital cardiac arrest.}, journal = {Emergency medicine journal : EMJ}, volume = {36}, number = {8}, pages = {479-484}, doi = {10.1136/emermed-2018-207833}, pmid = {31142552}, issn = {1472-0213}, mesh = {Clinical Competence/*standards/statistics & numerical data ; Decision Support Techniques ; Humans ; Out-of-Hospital Cardiac Arrest/*mortality/psychology ; Registries/statistics & numerical data ; *Resuscitation Orders ; }, abstract = {BACKGROUND: Our objective was to perform a systematic review of studies reporting the accuracy of termination of resuscitation rules (TORRs) for out-of-hospital cardiac arrest (OHCA).
METHODS: We performed a comprehensive search of the literature for studies evaluating the accuracy of TORRs, with two investigators abstracting relevant data from each study regarding study design, study quality and the accuracy of the TORRs. Bivariate meta-analysis was performed using the mada procedure in R.
RESULTS: We identified 14 studies reporting the performance of 9 separate TORRs. The sensitivity (proportion of eventual survivors for whom the TORR recommends resuscitation and transport) was generally high: 95% for the European Resuscitation Council (ERC) TORR, 97% for the basic life support (BLS) TORR and 99% for the advanced life support (ALS) TORR. The BLS and ERC TORR were more specific, which would lead to fewer futile transports, and all three of these TORRs had a miss rate of ≤0.13% (defined as a case where a patient is recommended for termination but survives). The pooled proportion of patients for whom each rule recommends TOR was much higher for the ERC and BLS TORRs (93.5% and 74.8%, respectively) than for the ALS TORR (29.0%).
CONCLUSIONS: The BLS and ERC TORRs identify a large proportion of patients who are candidates for termination of resuscitation following OHCA while having a very low rate of misclassifying eventual survivors (<0.1%). Further prospective validation of the ERC TORR and direct comparison with BLS TORR are needed.}, }
@article {pmid31126629, year = {2019}, author = {Marogianni, C and Rikos, D and Provatas, A and Dadouli, K and Ntellas, P and Tsitsi, P and Patrinos, G and Dardiotis, E and Hadjigeorgiou, G and Xiromerisiou, G}, title = {The role of C9orf72 in neurodegenerative disorders: a systematic review, an updated meta-analysis, and the creation of an online database.}, journal = {Neurobiology of aging}, volume = {84}, number = {}, pages = {238.e25-238.e34}, doi = {10.1016/j.neurobiolaging.2019.04.012}, pmid = {31126629}, issn = {1558-1497}, mesh = {C9orf72 Protein/*genetics ; Neurodegenerative Diseases/*genetics ; }, abstract = {A pathologic expansion of a noncoding GGGGCC hexanucleotide repeat of the C9orf72 gene has been strongly associated with familial amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) cases predominantly in Caucasian populations. In the last decade, scientific interest had been drawn to this gene and many studies conducted have shown a possible correlation with other neurodegenerative diseases as well. We performed an extensive literature search for C9orf72 mutation and its frequency in various neurological and psychiatric diseases. In addition, we performed a meta-analysis of the data related to ALS and familial ALS. An online cloud-based database and an interactive map were developed. The overall mutation frequency of C9orf72 is 20% for familial FTD, 16% for familial ALS and around 6%-8% for sporadic ALS and FTD. The updated meta-analysis that we performed showed that the pooled frequency of C9orf72 repeat expansion in patients with familial ALS was 23% (CI: 18%-28%) and in patients with sporadic ALS 3% (CI: 3%-4%). The subgroup analysis regarding the origin of the population revealed significant differences between Caucasian and Asian patients. Our analysis supports the direct causal relation of the C9orf72 expansion in ALS and FTD. On the contrary, the role of C9orf72 in other neurodegenerative disorders remains controversial. The system that we developed-the online database and the interactive map-is hopefully a stepping stone for an ever-growing platform that will aid scientists from all over the world in contributing to the meta-analysis of C9orf72-related publications.}, }
@article {pmid31125839, year = {2019}, author = {Flint, AE and Waterman, MG and Siddell, P and Houston, AL and Vadlamani, G and Chumas, P and Morrall, MCHJ}, title = {Assessing evidence quality in research reporting neurocognitive outcomes following paediatric temporal lobe surgery for epilepsy.}, journal = {Epilepsy research}, volume = {154}, number = {}, pages = {116-123}, doi = {10.1016/j.eplepsyres.2019.03.013}, pmid = {31125839}, issn = {1872-6844}, mesh = {Child ; Cross-Sectional Studies ; Epilepsy, Temporal Lobe/*diagnosis/psychology/*surgery ; Humans ; Mental Status and Dementia Tests/*standards ; Neurocognitive Disorders/*diagnosis/etiology/psychology ; Psychosurgery/adverse effects/psychology/*standards ; *Qualitative Research ; Retrospective Studies ; Temporal Lobe/surgery ; Treatment Outcome ; }, abstract = {PURPOSE: RCTs are the gold standard in determining intervention efficacy with journal impact factor assumed to index research quality. Flint et al's (2017) systematic review examined neurocognitive outcomes following paediatric temporal lobe epilepsy surgery. Retrieved evidence was restricted to non-RCTs, which pose greater risk of bias and thus diminish research quality. The current study evaluated risk of bias in sources retrieved by Flint et al. and explored whether impact factor related to research quality within this selected field.
METHODS: Methodological and reporting bias was evaluated using categories of bias specified by Cochrane. The relationship between the identified number of biases and journal impact factors of retrieved sources was examined.
RESULTS: All studies carried substantial risk for bias. Methodology bias included low sample size (76.71%; 56/73), risk of confounding cognitive outcomes due to failure to report pre-surgery neurocognitive data (21.92%; 16/73) and to determine whether patients were prescribed antiepileptic drugs at follow-up (53.42%; 39/73). Reporting bias included overstating claims based on findings (53.42%; 39/73), failure to report individual patient characteristics (66%; 33/50) and omitting the nature of surgical interventions (15.07%; 11/73). The number of sources of common bias within studies was not associated significantly with journal impact factor (p = .878).
CONCLUSION: This evaluation highlights risk of bias when sources are predominantly uncontrolled non-RCTs and provides evidence that journal impact factor is not a reliable indicator of quality within this field. Authors should limit bias in their methods and reporting of results, to ensure the highest quality evidence possible is used to inform treatment decisions and prognosis.}, }
@article {pmid31037421, year = {2019}, author = {Luo, W and Li, Y and Xu, Q and Gu, R and Zhao, J}, title = {Cervical spondylotic amyotrophy: a systematic review.}, journal = {European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society}, volume = {28}, number = {10}, pages = {2293-2301}, pmid = {31037421}, issn = {1432-0932}, mesh = {*Cervical Vertebrae/surgery ; Conservative Treatment ; Decompression, Surgical ; Diagnosis, Differential ; Humans ; Immobilization ; Physical Therapy Modalities ; Prognosis ; Spinal Fusion ; Spondylosis/classification/*diagnosis/*therapy ; Traction ; }, abstract = {PURPOSE: Cervical spondylotic amyotrophy (CSA) is characterized by upper limb muscle weakness and atrophy, without sensory deficits. The pathophysiology of CSA has been attributed to selective injury to the ventral nerve root and/or anterior horn of the spinal cord. This review aimed to delineate the history of CSA and to describe the epidemiology, etiology, pathophysiology, classification, clinical features, radiological and electrophysiological assessment, diagnosis, differential diagnosis, natural history and treatment of CSA.
METHODS: A comprehensive search of PubMed, EMBASE, Cochrane library and Web of Science databases was conducted, from their inception to April 3, 2018.
RESULTS: Clinically, CSA is classified into three types: a proximal-type (involving the scapular muscles, deltoid and biceps), a distal-type (involving the triceps and muscles of the forearm and hand) and a diffuse-type (involving features of both the distal- and proximal-type). Diagnosis requires documentation of muscle atrophy, without significant sensory deficits, supported by careful neurological, radiological and neurophysiological assessments, with amyotrophic lateral sclerosis, Parsonage-Turner syndrome, rotator cuff tear and Hirayama disease being the principle differential diagnoses. Conservative management of CSA includes cervical traction, neck immobilization and physical therapy, with vitamin B12 or E administration being useful in some patients. Surgical treatment, including anterior decompression and fusion or laminoplasty, with or without foraminotomy, is indicated after conservative treatment failure. Factors associated with a poor outcome include the distal-type CSA, long symptom duration, older age and greater preoperative muscle weakness.
CONCLUSION: Although the disease process of CSA is self-limited, treatment remains challenging, leaving scope for future studies. These slides can be retrieved under Electronic Supplementary Material.}, }
@article {pmid30961401, year = {2019}, author = {Lanznaster, D and Bejan-Angoulvant, T and Patin, F and Andres, CR and Vourc'h, P and Corcia, P and Blasco, H}, title = {Plasma creatinine and amyotrophic lateral sclerosis prognosis: a systematic review and meta-analysis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {20}, number = {3-4}, pages = {199-206}, doi = {10.1080/21678421.2019.1572192}, pmid = {30961401}, issn = {2167-9223}, mesh = {Amyotrophic Lateral Sclerosis/*blood ; Biomarkers/blood ; Creatinine/*blood ; Disease Progression ; Humans ; Prognosis ; }, abstract = {Background: Plasma creatinine has been described as a prognostic biomarker for Amyotrophic Lateral Sclerosis (ALS), but with conflicting results in the literature. We performed a systematic review followed by a meta-analysis to address this question. Methods: We performed a systematic review of Pubmed, Embase and Cochrane databases and retrieved 14 distinct cohorts (19 studies) reporting results regarding the relationship between plasma creatinine and a clinical marker for ALS progression, notably ALSFRS (ALS Functional Rating Scale) and survival. Results: For baseline plasma creatinine, mortality risk was 28% lower when creatinine was higher than 88.4 µmol/L (hazard ratio (HR): 0.72; 95% confidence interval (CI): 0.58 to 0.88; p = 0.0003) and was 25% lower if creatinine was above versus below the median (HR: 0.75; 95% CI: 0.63 to 0.89; p = 0.0008). We found a significant positive correlation between plasma creatinine at baseline and functional score, and between creatinine decline and functional score decline (p < 0.0001 for both); but a negative correlation between plasma creatinine and functional score decline (p = 0.033). The overall quality of the studies was low mainly due to potential attrition bias, and several studies did not report analyzable results raising concern regarding a potential reporting bias. Conclusions: Plasma creatinine seems to be a promising prognostic biomarker for ALS. However, new studies with sound methodology and standardized criteria for the evaluation of ALS progression should be conducted to validate plasma creatinine as a clinical biomarker for ALS prognosis.}, }
@article {pmid30931632, year = {2019}, author = {Ning, P and Yang, B and Li, S and Mu, X and Shen, Q and Hu, F and Tang, Y and Yang, X and Xu, Y}, title = {Systematic review of the prognostic role of body mass index in amyotrophic lateral sclerosis.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {20}, number = {5-6}, pages = {356-367}, doi = {10.1080/21678421.2019.1587631}, pmid = {30931632}, issn = {2167-9223}, mesh = {Amyotrophic Lateral Sclerosis/*diagnosis/*epidemiology ; *Body Mass Index ; Clinical Trials as Topic/methods ; Humans ; Multicenter Studies as Topic/methods ; Obesity/*diagnosis/*epidemiology ; Prognosis ; Risk Factors ; }, abstract = {Studies have suggested that obesity is associated with better prognosis among individuals with various types of neurodegenerative diseases, and while some studies suggest that the same is true of amyotrophic lateral sclerosis (ALS), other works cast doubt on this conclusion. Therefore, we conducted a meta-analysis to systematically evaluate the role of body mass index in the prognosis of ALS. PubMed was systematically searched to identify eligible articles, and data on long-term survival were meta-analyzed in terms of hazard ratios (HR) with corresponding 95% confidence intervals (CI). Level of heterogeneity among studies and publication bias were estimated. A total of 17 studies with 9991 ALS patients were included in the review. Each increase of 1 kg/m[2] in body mass index was associated with significantly better long-term overall survival (HR 0.95, 95%CI 0.93-0.97; p < 0.001). Obesity may also be a strong predictor of favorable long-term prognosis (HR 0.73; 95%CI 0.62-0.86; p < 0.001). Our results suggest that higher body mass index and obesity are associated with better long-term survival of ALS patients.}, }
@article {pmid30928503, year = {2019}, author = {Au, K and Lam, D and Garg, N and Chau, A and Dzwonek, A and Walker, B and Tremblay, L and Boet, S and Bould, MD}, title = {Improving skills retention after advanced structured resuscitation training: A systematic review of randomized controlled trials.}, journal = {Resuscitation}, volume = {138}, number = {}, pages = {284-296}, doi = {10.1016/j.resuscitation.2019.03.031}, pmid = {30928503}, issn = {1873-1570}, mesh = {*Clinical Competence ; Health Personnel/*education ; Humans ; Learning ; *Qualitative Research ; Randomized Controlled Trials as Topic/*methods ; Resuscitation/*education ; }, abstract = {AIMS: To systematically evaluate the literature on interventions that improve skills retention following advanced structured resuscitation training programs designed for healthcare professionals.
METHODS: A systematic review of MEDLINE, EMBASE, CENTRAL, CINAHL, PsycINFO, ERIC, and Scopus was performed. Only randomized controlled trials investigating skills retention following advanced structured resuscitation training programs for healthcare professionals between inception to November 21, 2018 were included. Publications that assessed only knowledge acquisition were excluded. Relevant data from included studies were extracted and study quality was critically appraised, both independently and in duplicate by multiple reviewers. The risk of bias was assessed with the Cochrane Risk of Bias tool and the Medical Education Research Study Quality Instrument (MERSQI). Due to significant clinical heterogeneity in SRT training, study designs and interventions, a qualitative synthesis was used to summarize findings.
MAIN RESULTS: Sixteen studies, with a combined total of 1192 participants, were included in the final analysis. The majority of studies were conducted in North America and involved trainees or novice learners. ACLS was the most extensively studied, followed by NRP, ALS, and ATLS. Skills retention at 6 months was the most commonly used primary endpoint assessed using a simulated resuscitation checklist with either an adopted or created assessment tool. Most studies demonstrated a positive impact on skills retention when an interactive intervention or simulation was used. However, merely having a high-fidelity mannequin alone for simulation was found to have minimal effect on skills retention in the absence of other changes in content delivery. Booster sessions were found to be minimally effective in reinforcing long-term skills retention; however, most studies examining this intervention had small sample sizes and were underpowered.
CONCLUSIONS: Simulation-based interventions, refresher courses and adjustments to the content delivery of advanced structured resuscitation training courses were found to have the greatest impact on skills retention. However, due to significant heterogeneity and methodological flaws in the available studies, no definitive conclusions can be made regarding other interventions. Overall, there is a paucity of skills retention research and further high-quality randomized controlled trials are needed to determine the optimal intervention and design for resuscitation training that would maximize skills retention.}, }
@article {pmid30883352, year = {2019}, author = {Zhou, SL and Tan, CC and Hou, XH and Cao, XP and Tan, L and Yu, JT}, title = {TREM2 Variants and Neurodegenerative Diseases: A Systematic Review and Meta-Analysis.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {68}, number = {3}, pages = {1171-1184}, doi = {10.3233/JAD-181038}, pmid = {30883352}, issn = {1875-8908}, mesh = {Alzheimer Disease/genetics ; Frontotemporal Dementia/genetics ; Genetic Predisposition to Disease/*genetics ; Genetic Variation/genetics ; Humans ; Lipodystrophy/genetics ; Membrane Glycoproteins/*genetics ; Neurodegenerative Diseases/*genetics ; Osteochondrodysplasias/genetics ; Parkinson Disease/genetics ; Polymorphism, Single Nucleotide/genetics ; Receptors, Immunologic/*genetics ; Subacute Sclerosing Panencephalitis/genetics ; }, abstract = {TREM2 (triggering receptor expressed on myeloid cells 2) gene variants were reported to increase the risk of Alzheimer's disease (AD) and even other neurodegenerative diseases (frontotemporal dementia (FTD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS)), but so far, no definite conclusion has been drawn. The aim of our systematic review and meta-analysis was to investigate the role of TREM2 variants in neurodegenerative diseases. A total of 39 papers (including 26 case-control studies and 13 case reports) were retrieved from PubMed, MEDLINE, EMBASE, and the Cochrane library in this study. A fixed effect model was used to pool results in the analysis. Three variants in TREM2 (rs75932628 (R47H), rs2234255 (H157Y), and rs143332484 (R62H)) were significantly associated with AD risk, but the similar associations between rs104894002 (Q33X), rs2234253 (T96K), rs142232675 (D87N), rs2234256 (L211P), and AD were not proven. Rs75932628 also increased risk of PD in North Americans and FTD, but not PD in Europeans or ALS. In the systematic review, 12 biallelic TREM2 mutations (e.g., rs104894002, rs201258663 (T66M), and rs386834144, etc.) have been described to cause Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL) in 14 families. And homozygous mutations also have been reported to cause FTD without typical bone phenotypes in 7 families. This study demonstrates that multiple variants in TREM2 have association with the onset of AD, FTD, and PD in North Americans and also play a key role in the phenotypes of the rare familial genetic disorder.}, }
@article {pmid30863961, year = {2019}, author = {Wei, Q and Chen, X and Chen, Y and Ou, R and Cao, B and Hou, Y and Zhang, L and Shang, HF}, title = {Unique characteristics of the genetics epidemiology of amyotrophic lateral sclerosis in China.}, journal = {Science China. Life sciences}, volume = {62}, number = {4}, pages = {517-525}, doi = {10.1007/s11427-018-9453-x}, pmid = {30863961}, issn = {1869-1889}, mesh = {Amyotrophic Lateral Sclerosis/*genetics ; Asian People/genetics ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease/*genetics ; Humans ; Male ; Mutation ; Mutation Rate ; Polymorphism, Single Nucleotide ; }, abstract = {Continual discoveries of new genes and unraveling the genetic etiology in amyotrophic lateral sclerosis (ALS) have provided greater insight into the underlying pathogenesis in motor neuron degeneration, as well as facilitating the disease modeling and the testing of targeted therapeutics. While, the genetic etiology accounted for two-thirds of FALS and approximately 11% of SALS in Caucasians. However, the contributions of these causative genes to ALS vary among different populations. Furthermore, the prominent difference between Chinese population and other ethnics remains a source of ongoing debate. We systemically reviewed genetics literature of Chinese ALS populations and updated the mutation frequencies of the main ALS-implicated genes aiming to determine the genetic features of ALS in Chinese population. We also reviewed the associations between ALS-implicated single nucleotide polymorphisms (SNPs) and the risk of ALS in Chinese population. A total of 116 studies were included in this analysis (86 gene mutation study articles and 30 SNPs study articles). The results showed that the overall gene mutation rates of ALS-related causative genes were 55.0% in familial ALS (FALS) and 11.7% in sporadic ALS (SALS) in Chinese population. In Chinese FALS, the highest mutation frequency was found in SOD1 gene (25.6%), followed by FUS (5.8%), TARDBP (5.8%), DCTN1 (3.6%) and C9orf72 (3.5%). In Chinese SALS, the highest mutation frequency was also identified in SOD1 gene (1.6%), followed by ANXA11 (1.4%), FUS (1.3%), SQSTM1 (1.0%), OPTN (0.9%) and CCNF (0.8%). The associations between several SNPs and risk of ALS were also reported in Chinese population. The genetic features of ALS in Chinese population are significantly different from those in Caucasian population, indicating an association between genetic susceptibility and origin of population. Further explorations are required to understand the gene complexity of ALS, including the contribution of most minor genes and the molecular mechanisms in ALS pathologies.}, }
@article {pmid30855088, year = {2019}, author = {Yonis, G and Cabalag, CS and Link, E and Duong, CP}, title = {Utility of routine oral contrast study for detecting postesophagectomy anastomotic leak - a systematic review and meta-analysis.}, journal = {Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus}, volume = {32}, number = {7}, pages = {}, doi = {10.1093/dote/doz011}, pmid = {30855088}, issn = {1442-2050}, mesh = {Administration, Oral ; Anastomotic Leak/*diagnostic imaging/etiology ; Contrast Media/administration & dosage ; Esophagectomy/adverse effects ; Humans ; Predictive Value of Tests ; Radiography/methods ; }, abstract = {Oral contrast studies are used to detect anastomotic leak (AL) postesophagectomy. However, recent evidence suggests oral contrast studies have low sensitivity in detecting ALs, and their false positive results can lead to unnecessary prolonged hospital stay. The objective of this study was to determine if oral contrast studies should be used routinely post-esophagectomy for cancer. A systematic literature search was conducted for studies published between January 1990 and June 2018. Data extracted for analyses included type of esophagectomy, operative morbidity (such as AL and pneumonia), mortality rates, timing of contrast study, and type of oral contrast used. The sensitivity, specificity, and positive and negative predictive values of routine oral contrast studies to detect AL were calculated using the aforementioned variables. Two hundred and forty-seven studies were reviewed with 16 studies included in the meta-analysis. Postoperative oral contrast study was performed in 94.0% of cases between day 5 and 7. The rates of early and delayed leaks were 2.4% (1.8%-3.3%) and 2.8% (1.8%-4.4%), respectively. Routine contrast studies have a sensitivity and specificity of 0.44 (0.32-0.57) and 0.98 (0.95-0.99), respectively. Analysis of covariates revealed that sensitivity is reduced in centers with a higher volume of cases (greater than 15 per year: 0.50 [0.34-0.75; p = 0.0008]) and specificity was higher in centers with a lower leak rate. Given its poor sensitivity and inability to detect early/delayed AL, oral contrast study should be used selectively with endoscopy and/or computerized tomography scan to assess surgical anastomoses following esophagectomy.}, }
@article {pmid30844858, year = {2019}, author = {Drain, JP and Virk, SS and Jain, N and Yu, E}, title = {Dropped Head Syndrome: A Systematic Review.}, journal = {Clinical spine surgery}, volume = {32}, number = {10}, pages = {423-429}, doi = {10.1097/BSD.0000000000000811}, pmid = {30844858}, issn = {2380-0194}, mesh = {Aged ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Spinal Diseases/*pathology/surgery ; Syndrome ; Treatment Outcome ; }, abstract = {STUDY DESIGN: This study was a systematic review.
OBJECTIVES: To reveal demographic factors, etiologies, response to treatment, and to propose a novel treatment algorithm for dropped head syndrome (DHS).
SUMMARY OF BACKGROUND DATA: DHS is a rare condition defined by weakness of the cervical paraspinal muscles resulting in passively correctable flexion of the cervical spine. Patients present with neck pain, difficulty eating, and impaired horizontal gaze. Because of the rarity of DHS, a paucity of information exists with regard to demographics, etiology, and relative superiority of medical and surgical treatment.
MATERIALS AND METHODS: We conducted a systematic literature review by searching PubMed for "dropped head syndrome," "chin on chest," "isolated neck extensor myopathy" (INEM), and "camptocephalia." Inclusion criteria were English-language articles that applied a specific treatment regimen with outcome data. A binomial logistic regression analysis was then performed to determine which covariates (age, sex, and treatments) were predictive of a positive response to treatment.
RESULTS: A total of 129 patients were described in 74 studies. Mean age was 63.6 and 63% were female. More than two-thirds of all patients fell into just 4 diagnostic categories (isolated neck extensor myopathy, 31.8%; Parkinson's, 20.2%; myasthenia gravis, 12.4%; amyotrophic lateral sclerosis, 7.0%). Overall positive response to treatment was 64.3%; primary medical treatment (73.5%), immune suppression (78.9%), and a combination of both (87.5%). Surgery was 93.8% successful. A treatment algorithm focused on appropriate diagnosis, initial medical management, with surgical evaluation only after failure of medical treatment was proposed.
CONCLUSIONS: Treatment for DHS starts with accurate diagnosis of the underlying etiology and is often associated with neuromuscular disease. A treatment algorithm for appropriate management of these patients was proposed. A trial of medical management and/or immunomodulators is warranted. Failing nonoperative management, surgery is predictive of a positive outcome.
LEVEL OF EVIDENCE: Level V.}, }
@article {pmid30835675, year = {2019}, author = {Srinivas, S and Wali, AR and Pham, MH}, title = {Efficacy of riluzole in the treatment of spinal cord injury: a systematic review of the literature.}, journal = {Neurosurgical focus}, volume = {46}, number = {3}, pages = {E6}, doi = {10.3171/2019.1.FOCUS18596}, pmid = {30835675}, issn = {1092-0684}, mesh = {Adolescent ; Adult ; Aged ; Animals ; Biological Availability ; Clinical Trials as Topic ; Drug Evaluation ; Drug Evaluation, Preclinical ; Excitatory Amino Acid Antagonists/pharmacokinetics/therapeutic use ; Glutamic Acid/metabolism ; Humans ; Middle Aged ; Neuroprotective Agents/pharmacokinetics/*therapeutic use ; Rabbits ; Rats ; Recovery of Function ; Riluzole/pharmacokinetics/*therapeutic use ; Spinal Cord Injuries/complications/*drug therapy ; Trauma Severity Indices ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVERiluzole is a glutamatergic modulator that has recently shown potential for neuroprotection after spinal cord injury (SCI). While the effects of riluzole are extensively documented in animal models of SCI, there remains heterogeneity in findings. Moreover, there is a paucity of data on the pharmacology of riluzole and its effects in humans. For the present study, the authors systematically reviewed the literature to provide a comprehensive understanding of the effects of riluzole in SCI.METHODSThe PubMed database was queried from 1996 to September 2018 to identify animal studies and clinical trials involving riluzole administration for SCI. Once articles were identified, they were processed for year of publication, study design, subject type, injury model, number of subjects in experimental and control groups, dose, timing/route of administration, and outcomes.RESULTSA total of 37 studies were included in this study. Three placebo-controlled clinical trials were included with a total of 73 patients with a mean age of 39.1 years (range 18-70 years). For the clinical trials included within this study, the American Spinal Injury Association Impairment Scale distributions for SCI were 42.6% grade A, 25% grade B, 26.6% grade C, and 6.2% grade D. Key findings from studies in humans included decreased nociception, improved motor function, and attenuated spastic reflexes. Twenty-six animal studies (24 in vivo, 1 in vitro, and 1 including both in vivo and in vitro) were included. A total of 520 animals/in vitro specimens were exposed to riluzole and 515 animals/in vitro specimens underwent other treatment for comparison. The average dose of riluzole for intraperitoneal, in vivo studies was 6.5 mg/kg (range 1-10 mg/kg). Key findings from animal studies included behavioral improvement, histopathological tissue sparing, and modified electrophysiology after SCI. Eight studies examined the pharmacology of riluzole in SCI. Key findings from pharmacological studies included riluzole dose-dependent effects on glutamate uptake and its modified bioavailability after SCI in both animal and clinical models.CONCLUSIONSSCI has many negative sequelae requiring neuroprotective intervention. While still relatively new in its applications for SCI, both animal and human studies demonstrate riluzole to be a promising pharmacological intervention to attenuate the devastating effects of this condition.}, }
@article {pmid30786027, year = {2019}, author = {Zhou, LY and Tian, ZR and Yao, M and Chen, XQ and Song, YJ and Ye, J and Yi, NX and Cui, XJ and Wang, YJ}, title = {Riluzole promotes neurological function recovery and inhibits damage extension in rats following spinal cord injury: a meta-analysis and systematic review.}, journal = {Journal of neurochemistry}, volume = {150}, number = {1}, pages = {6-27}, doi = {10.1111/jnc.14686}, pmid = {30786027}, issn = {1471-4159}, mesh = {Animals ; Neuroprotective Agents/*pharmacology ; Rats ; Recovery of Function/*drug effects ; Riluzole/*pharmacology ; Spinal Cord/*drug effects/pathology ; *Spinal Cord Injuries/pathology ; }, abstract = {Spinal cord injury (SCI) is a devastating condition that has few treatment options. Riluzole, a sodium channel blocker used to treat amyotrophic lateral sclerosis, has been initially trialed in human SCI. We performed a systematic review to critically assess the efficacy of riluzole in locomotor recovery and damage extension in SCI rat models, and the potential for clinical translation. PubMed, Embase, Cochrane Library, and Chinese databases were searched from their inception date to March 2018. Two reviewers independently selected animal studies that evaluated neurological recovery and lesion area following riluzole treatment in SCI rat models, extracted data and assessed methodological quality. Pairwise meta-analysis, subgroup analysis, and network meta-analysis were performed to assess the effects of riluzole on SCI. Ten eligible studies were included. Two studies had high methodological quality. Overall, the Basso, Beattie, and Bresnahan scores were increased in riluzole-treated animals versus controls, and effect sizes showed a gradual increase from the 1st (five studies, n = 104, mean difference = 1.24, 95% CI = 0.11 to 2.37, p = 0.03) to 6th week after treatment (five studies, n = 120, mean difference = 2.34, 95% CI = 1.26 to 3.42, p < 0.0001). Riluzole was associated with improved outcomes in the inclined plane test and the tissue preservation area. Subgroup analyses suggested an association of locomotor recovery with riluzole dose. Network meta-analysis showed that 5 mg/kg riluzole exhibited greater protection than 2.5 and 8 mg/kg riluzole. Collectively, this review suggests that riluzole has a protective effect on SCI, with good safety and a clear mechanism of action and may be suitable for future clinical trials or applications. However, animal results should be interpreted with caution given the known limitations in animal experimental design and methodological quality.}, }
@article {pmid30691095, year = {2019}, author = {Gunnarsson, LG and Bodin, L}, title = {Occupational Exposures and Neurodegenerative Diseases-A Systematic Literature Review and Meta-Analyses.}, journal = {International journal of environmental research and public health}, volume = {16}, number = {3}, pages = {}, pmid = {30691095}, issn = {1660-4601}, mesh = {Alzheimer Disease/chemically induced ; Amyotrophic Lateral Sclerosis/chemically induced ; Electromagnetic Fields/*adverse effects ; Humans ; Lead/*toxicity ; Neurodegenerative Diseases/*chemically induced ; Occupational Exposure/*adverse effects ; Parkinson Disease ; Pesticides/*toxicity ; Risk ; Risk Factors ; }, abstract = {Objectives: To carry out an integrated and stratified meta-analysis on occupational exposure to electromagnetic fields (EMFs), metals and pesticides and its effects on amyotrophic lateral sclerosis (ALS) and Parkinson's and Alzheimer's disease, and investigate the possibility of publication bias. Methods: In the current study, we updated our recently published meta-analyses on occupational exposures in relation to ALS, Alzheimer's and Parkinson's disease. Based on 66 original publications of good scientific epidemiological standard, according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines, we analysed subgroups by carrying out stratified meta-analyses on publication year, statistical precision of the relative risk (RR) estimates, inspection of the funnel plots and test of bias. Results: Based on 19 studies the weighted RR for occupational exposure to EMFs was 1.26 (95% confidence interval (CI) 1.07[-]1.50) for ALS, 1.33 (95% CI 1.07[-]1.64) for Alzheimer's disease and 1.02 (95% CI 0.83[-]1.26) for Parkinson's disease. Thirty-one studies concerned occupational exposure to pesticides and the weighted RR was 1.35 (95% CI 1.02[-]1.79) for ALS, 1.50 (95% CI 0.98[-]2.29) for Alzheimer's disease and 1.66 (95% CI 1.42[-]1.94) for Parkinson's disease. Finally, 14 studies concerned occupational exposure to metals and only exposure to lead (five studies) involved an elevated risk for ALS or Parkinson's disease and the weighted RR was 1.57 (95% CI 1.11[-]2.20). The weighted RR for all the non-lead exposures was 0.97 (95% CI 0.88[-]1.06). Conclusions: Exposure to pesticides increased the risk of getting the mentioned neurodegenerative diseases by at least 50%. Exposure to lead was only studied for ALS and Parkinson's disease and involved 50% increased risk. Occupational exposure to EMFs seemed to involve some 10% increase in risk for ALS and Alzheimer's disease only.}, }
@article {pmid30585510, year = {2019}, author = {Simon, N and Goldstein, LH}, title = {Screening for cognitive and behavioral change in amyotrophic lateral sclerosis/motor neuron disease: a systematic review of validated screening methods.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {20}, number = {1-2}, pages = {1-11}, doi = {10.1080/21678421.2018.1530264}, pmid = {30585510}, issn = {2167-9223}, mesh = {Amyotrophic Lateral Sclerosis/diagnosis/physiopathology/*psychology ; *Apathy ; Cognitive Dysfunction/*diagnosis/physiopathology/psychology ; Empathy ; *Executive Function ; Frontotemporal Dementia/diagnosis/physiopathology/psychology ; Humans ; Mass Screening ; Reproducibility of Results ; Sensitivity and Specificity ; Social Behavior ; Social Perception ; Stereotyped Behavior ; }, abstract = {OBJECTIVES: Cognitive and behavioral change in Amyotrophic Lateral Sclerosis (ALS) is well-accepted. Several screening tools have been developed to detect such changes. Further guidance on their use may come from a consideration of the rigor with which they were validated. This systematic review set out to critically appraise and present published data pertaining to the validation of six screening tools used to diagnose cognitive and/or behavioral change in patients with ALS.
METHODS: The screening tools considered in this search included: The Edinburgh Cognitive and Behavioural ALS Screen (ECAS), The ALS Cognitive Behavioural Screen (ALS-CBS), The Motor Neuron Disease Behavioural Scale (MiND-B), The Frontal Behavioural Inventory ALS Version, The ALS Frontotemporal Dementia Questionnaire (ALS-FTD-Q), and The Beaumont Behavioural Inventory (BBI). MEDLINE, EMBASE, and PsycINFO were searched until 4th week of June 2017.
RESULTS: Fourteen eligible studies were included in the review. Papers either reported data concerning convergent validity or clinical validity. Validation data concerning the ECAS showed this screening tool to have strong clinical validity, although further work needs to consider how its use will affect diagnosis rates according to current diagnostic guidelines. When screening for behavioral change only, more limited information is available; the BBI may offer greater potential than the ALS-FTD-Q for detecting mild impairment as it assesses a wider range of behavioral changes.
CONCLUSIONS: Scores of sensitivity, specificity, positive predictive values, and negative predictive values should be given considerable importance when considering which screening tools to incorporate into current clinical practice.}, }
@article {pmid30538137, year = {2019}, author = {Poletti, B and Carelli, L and Solca, F and Pezzati, R and Faini, A and Ticozzi, N and Mitsumoto, H and Silani, V}, title = {Sexuality and intimacy in ALS: systematic literature review and future perspectives.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {90}, number = {6}, pages = {712-719}, doi = {10.1136/jnnp-2018-319684}, pmid = {30538137}, issn = {1468-330X}, mesh = {Amyotrophic Lateral Sclerosis/*psychology ; Female ; Humans ; Male ; Sexual Behavior/physiology/psychology ; *Sexuality/physiology/psychology ; }, abstract = {Several features of amyotrophic lateral sclerosis (ALS) impact on sexuality and intimate relationship; however, the issue has received poor attention so far. We performed a systematic literature review in order to provide an up-to-date account of sexuality in ALS. References were identified by searches of PubMed, Web of Science, Scopus and PsycINFO (1970-2017, English literature). The following were the key terms: 'sexual' OR 'sexuality' OR 'intimacy' OR 'marital' AND 'ALS' OR 'Amyotrophic Lateral Sclerosis' OR 'Motor Neuron Disease' OR 'MND'. Titles and abstracts were screened for relevance and a full-text analysis was performed on the selected articles. Studies were included if they referred to sexual well-being/activities/functions or intimate relationship between patients and their partners and management of such topic by clinicians. Eligibility assessment was performed independently by two reviewers. A thematic and level of evidence classification of studies was performed. Studies' design, objectives, measurements and outcomes were summarised. Thirty articles were included and four topics were identified: intimacy in the dyads; sexual activities in patients and with their partners; sexual function disturbances; and sexuality and cognitive-behavioural alterations. The quality of the studies varies, with globally poor level of evidence. Some sexuality issues have been only sparsely addressed, such as gender-related differences, same-sex relationships and sexual activities other than intercourse. Sexuality in ALS is still not adequately considered by clinicians and researchers. We present preliminary recommendations for improving sexuality and intimacy at any ALS multidisciplinary clinics.}, }
@article {pmid30520038, year = {2019}, author = {Urbi, B and Owusu, MA and Hughes, I and Katz, M and Broadley, S and Sabet, A}, title = {Effects of cannabinoids in Amyotrophic Lateral Sclerosis (ALS) murine models: a systematic review and meta-analysis.}, journal = {Journal of neurochemistry}, volume = {149}, number = {2}, pages = {284-297}, doi = {10.1111/jnc.14639}, pmid = {30520038}, issn = {1471-4159}, mesh = {*Amyotrophic Lateral Sclerosis ; Animals ; Cannabinoids/*pharmacology ; Disease Models, Animal ; Mice ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder that results from motor neuron damage. Cannabinoids have been proposed as treatments for ALS because of their anti-excitotoxicity, anti-oxidant and anti-inflammatory effects. Preclinical studies in mice models of ALS have been published using a range of cannabinoid formulations and doses. To date, there has been no rigorous evaluation of these trials to assess a potential cannabinoid treatment effect. This review and meta-analysis was undertaken to provide evidence for or against a treatment effect of cannabinoids in murine ALS models. Evidence of a treatment effect in mice may provide motivation for trials in human ALS. We identified a total of 10 studies; nine studies using cannabinoid treatment in transgenic SOD1-G93A ALS-model mice and one study in TDP-43 transgenic mice. Eight of the nine studies that used SOD1-G93A mice expressed similarly high copy numbers of the transgene while one study used a low-copy number line. Outcomes evaluated were survival time and disease progression. The latter was measured by motor function and bodyweight decline. Meta-analysis of the mean difference in survival time across the seven studies showed an increase in survival of 3.84 days (95% CI: 0.35-7.32 days; p = 0.031) for cannabinoid treated compared to control SOD1-G93A mice. It was not possible to conduct meta-analyses for motor function decline or weight loss. However, eight of nine studies reported significant improvements in measures of motor function decline and one reported non-significant improvements. Weight loss was significantly attenuated in four of five studies reporting this measure while the other study reported a non-significant attenuation. This review provides some evidence for the efficacy of cannabinoids in prolonging survival time in an ALS mouse model. A delay in disease progression is also suggested following cannabinoid treatment though it was not possible to consolidate the results from reviewed studies. However, studies have moderate to high risk of bias and are highly heterogeneous. Although this review provides some evidence to support the conduct of a cannabinoid trial in human ALS, more standardized studies on specific cannabinoids are necessary before supporting therapeutic potential of cannabinoids in treating patients with ALS. OPEN SCIENCE BADGES: This article has received a badge for *Preregistration* because the study was pre-registered at https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=89274. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/. Read the Editorial Highlight for this article on page 168.}, }
@article {pmid30483992, year = {2019}, author = {Luo, L and Song, Z and Li, X and Huiwang, and Zeng, Y and Qinwang, and Meiqi, and He, J}, title = {Efficacy and safety of edaravone in treatment of amyotrophic lateral sclerosis-a systematic review and meta-analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {40}, number = {2}, pages = {235-241}, pmid = {30483992}, issn = {1590-3478}, mesh = {Amyotrophic Lateral Sclerosis/*drug therapy ; Edaravone/*adverse effects/*therapeutic use ; Humans ; Neuroprotective Agents/*adverse effects/*therapeutic use ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: Based on the results of randomized, double-blind, placebo-controlled trials, the benefit and safety of edaravone in the treatment of amyotrophic lateral sclerosis remain controversial. We performed a meta-analysis to evaluate the efficacy and safety of edaravone in the treatment of this disease.
METHODS: We searched PubMed, the Cochrane Library, and Embase from the inception of electronic data to April 2018. We included randomized, double-blind, placebo-controlled trials reporting amyotrophic lateral sclerosis patients receiving 60-mg intravenous edaravone or intravenous saline placebo for 24 weeks. The primary efficacy evaluation was changed in Amyotrophic Lateral Sclerosis Functional Rating Scale score from baseline to after the trial. Measure of safety was the frequency of investigated adverse events and serious adverse events. Data synthesis and analysis and evaluation of risk of bias were performed using RevMan 5.3 software. Heterogeneity among studies was evaluated with the I[2] statistic.
RESULTS: A total of 367 patients were analyzed across three randomized controlled trials (183 patients receiving intravenous edaravone; 184 receiving placebo). A difference in ALSFRS-R score between groups at 24 weeks was found (mean difference [MD] = 1.63, 95% confidence interval [CI] 0.26-3.00, P = .02). No differences in the frequency of adverse events (odds ratio [OR] = 1.22, 95% CI 0.68-2.19, P = .50) or serious adverse events (OR = 0.71, 95% CI 0.43-1.19, P = .20) were found.
CONCLUSION: Intravenous edaravone is efficacious in amyotrophic lateral sclerosis patients, with no severe adverse effects. Additional reliable randomized controlled trials with larger sample sizes will further assess the efficacy and safety of edaravone in amyotrophic lateral sclerosis.
CLINICAL TRIAL REGISTRATION: The systematic review and meta-analysis was registered in the international prospective register of systematic reviews. (PROSPERO registration number: CRD42018096191; http://www.crd.york.ac.uk/PROSPERO .).}, }
@article {pmid30415446, year = {2018}, author = {Dardiotis, E and Aloizou, AM and Siokas, V and Patrinos, GP and Deretzi, G and Mitsias, P and Aschner, M and Tsatsakis, A}, title = {The Role of MicroRNAs in Patients with Amyotrophic Lateral Sclerosis.}, journal = {Journal of molecular neuroscience : MN}, volume = {66}, number = {4}, pages = {617-628}, pmid = {30415446}, issn = {1559-1166}, support = {The author(s) received no specific funding for this work//The author(s) received no specific funding for this work/ ; }, mesh = {Amyotrophic Lateral Sclerosis/blood/*genetics ; Biomarkers/blood ; Humans ; MicroRNAs/*genetics/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a serious neurodegenerative disease that affects motor neurons and leads to death within 2 to 3 years after the first symptoms manifest. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression in fundamental cellular processes and, post-transcriptionally, the translation levels of target mRNA transcripts. We searched PubMed for studies that examined miRNAs in ALS patients and attempted to group the results in order to find the strongest miRNA candidate for servings as an ALS biomarker. The studies on humans so far have been diverse, yielding considerably heterogeneous results, as they were performed on a wide variety of tissues and subjects. Among the miRNAs that were found consistently deregulated are miR-206, miR-133, miR-149, and miR-338-3p. Additively, the deregulation of some specific miRNAs seems to compose a miRNA expression profile that is specific for ALS. More research is required in order for the scientific community to reach a consensus.}, }
@article {pmid30373166, year = {2018}, author = {Gunnarsson, LG and Bodin, L}, title = {Amyotrophic Lateral Sclerosis and Occupational Exposures: A Systematic Literature Review and Meta-Analyses.}, journal = {International journal of environmental research and public health}, volume = {15}, number = {11}, pages = {}, pmid = {30373166}, issn = {1660-4601}, mesh = {Amyotrophic Lateral Sclerosis/chemically induced/*epidemiology/etiology ; Delivery of Health Care ; Electromagnetic Fields/adverse effects ; Humans ; Lead/*adverse effects ; Occupational Exposure/adverse effects ; Pesticides/*adverse effects ; *Physical Exertion ; Risk Factors ; }, abstract = {Objectives: We conducted a systematic literature review to identify studies fulfilling good scientific epidemiological standards for use in meta-analyses of occupational risk factors for amyotrophic lateral sclerosis (ALS). Methods: We identified 79 original publications on associations between work and ALS. The MOOSE (Meta-analysis Of Observational Studies in Epidemiology) and GRADE (Grading of Recommendations, Assessment, Development and Evaluations) guidelines were used to ensure high scientific quality, and reliable protocols were applied to classify the articles. Thirty-seven articles fulfilled good scientific standards, while 42 were methodologically deficient and thus were excluded from our meta-analyses. Results: The weighted relative risks for the various occupational exposures were respectively; 1.29 (95% confidence interval (CI): 0.97[-]1.72; six articles) for heavy physical work, 3.98 (95% CI: 2.04[-]7.77; three articles) for professional sports, 1.45 (95% CI: 1.07[-]1.96; six articles) for metals, 1.19 (95% CI: 1.07[-]1.33; 10 articles) for chemicals, 1.18 (95% CI: 1.07[-]1.31; 16 articles) for electromagnetic fields or working with electricity, and 1.18 (95% CI: 1.05[-]1.34; four articles) for working as a nurse or physician. Conclusions: Meta-analyses based only on epidemiologic publications of good scientific quality show that the risk of ALS is statistically significantly elevated for occupational exposures to excessive physical work, chemicals (especially pesticides), metals (especially lead), and possibly also to electromagnetic fields and health care work. These results are not explained by publication bias.}, }
@article {pmid30283455, year = {2018}, author = {Chen, X and Hu, Y and Cao, Z and Liu, Q and Cheng, Y}, title = {Cerebrospinal Fluid Inflammatory Cytokine Aberrations in Alzheimer's Disease, Parkinson's Disease and Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {2122}, pmid = {30283455}, issn = {1664-3224}, mesh = {Alzheimer Disease/*cerebrospinal fluid/diagnosis ; Amyotrophic Lateral Sclerosis/*cerebrospinal fluid/diagnosis ; Biomarkers/cerebrospinal fluid ; Central Nervous System/metabolism ; Cytokines/*cerebrospinal fluid ; Humans ; Inflammation Mediators/*cerebrospinal fluid ; Parkinson Disease/cerebrospinal fluid/diagnosis ; Vascular Endothelial Growth Factor A/cerebrospinal fluid ; }, abstract = {It has been suggested that cytokine-mediated inflammation plays a key role for the onset and/or development of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS). However, clinical studies have yielded inconsistent results for the aberrant cytokine levels in circulation of patients with AD, PD, and ALS. Previous studies have used meta-analysis to address the inconsistent data for blood cytokine levels in the patients with AD, PD, and ALS. Here, we performed a systemic review of cerebrospinal fluid inflammatory cytokine data in patients with AD, PD and ALS, and sought to quantitatively summarize the CSF inflammatory cytokine data with a meta-analytical technique. The systematic search from Pubmed and Web of Science identified 71 articles with 2629 patients and 2049 controls for the meta-analysis. Random-effects meta-analysis demonstrated that CSF TGF-β, MCP-1, and YKL-40 levels were significantly elevated in AD patients when compared with controls. In addition, patients with PD had heightened levels of TGF-β1, IL-6, and IL-1β in CSF. Furthermore, G-CSF, IL-2, IL-15, IL-17, MCP-1, MIP-1α, TNF-α, and VEGF levels were significantly increased in patients with ALS as compared with controls. Taken together, these results not only strengthen the clinical evidence that neurodegenerative diseases are accompanied by the increased inflammatory response, but also reveal the unique inflammatory response profile in the central nervous system of patients with AD, PD and ALS. Given the robust associations between some cytokines and neurodegenerative diseases found in this meta-analysis, CSF inflammatory cytokines may be used as biomarkers for these diseases in the future.}, }
@article {pmid30052666, year = {2018}, author = {Panda, S and Begley, C and Daly, D}, title = {Clinicians' views of factors influencing decision-making for caesarean section: A systematic review and metasynthesis of qualitative, quantitative and mixed methods studies.}, journal = {PloS one}, volume = {13}, number = {7}, pages = {e0200941}, pmid = {30052666}, issn = {1932-6203}, mesh = {*Cesarean Section ; *Decision Making ; *Health Knowledge, Attitudes, Practice ; Health Personnel/*psychology ; Humans ; Midwifery/statistics & numerical data ; Obstetrics/statistics & numerical data ; }, abstract = {BACKGROUND: Caesarean section rates are increasing worldwide and are a growing concern with limited explanation of the factors that influence the rising trend. Understanding obstetricians' and midwives' views can give insight to the problem. This systematic review aimed to offer insight and understanding, through aggregation, summary, synthesis and interpretation of findings from studies that report obstetricians' and midwives' views on the factors that influence the decision to perform caesarean section.
METHODS: The electronic databases of PubMed (1958-2016), CINAHL (1988-2016), Maternity and Infant Care (1971-2016), PsycINFO (1980-2016) and Web of Science (1991-2016) were searched in September 2016. All quantitative, qualitative and mixed methods studies, published in English, whose aim was to explore obstetricians' and/or midwives' views of factors influencing decision-making for caesarean section were included. Papers were independently reviewed by two authors for selection by title, abstract and full text. Thomas et al's 12 assessment criteria checklist (2003) was used to assess methodological quality of the included studies.
RESULT: The review included 34 studies: 19 quantitative, 14 qualitative, and one using mixed methods, involving 7785 obstetricians and 1197 midwives from 20 countries. Three main themes, each with several subthemes, emerged. Theme 1: "clinicians' personal beliefs"-('Professional philosophies'; 'beliefs in relation to women's request for CS'; 'ambiguous versus clear clinical reasons'); Theme 2: "health care systems"-('litigation'; 'resources'; 'private versus public/insurance/payments'; 'guidelines and management policy'). Theme 3: "clinicians' characteristics" ('personal convenience'; 'clinicians' demographics'; 'confidence and skills').
CONCLUSION: This systematic review and metasynthesis identified clinicians' personal beliefs as a major factor that influenced the decision to perform caesarean section, further contributed by the influence of factors related to the health care system and clinicians' characteristics. Obstetricians and midwives are directly involved in the decision to perform a caesarean section, hence their perspectives are vital in understanding various factors that have influence on decision-making for caesarean section. These results can help clinicians identify and acknowledge their role as crucial members in the decision-making process for caesarean section within their organisation, and to develop intervention studies to reduce caesarean section rates in future.}, }
@article {pmid29989057, year = {2018}, author = {Zhu, Y and Yang, M and Li, F and Li, M and Xu, Z and Yang, F and Liu, Y and Chen, W and Zhang, Y and Xu, R}, title = {Aberrant Levels of Cystatin C in Amyotrophic Lateral Sclerosis: a Systematic Review and Meta Analysis.}, journal = {International journal of biological sciences}, volume = {14}, number = {9}, pages = {1041-1053}, pmid = {29989057}, issn = {1449-2288}, mesh = {Amyotrophic Lateral Sclerosis/*blood/*cerebrospinal fluid ; Animals ; Cystatin C/*blood/*cerebrospinal fluid ; Humans ; }, abstract = {Evidences suggest that Cystatin C (Cys C) levels might be a biomarker in amyotrophic lateral sclerosis (ALS) diagnosis, but the conclusion is still in doubts. We conducted a systematic review and meta analysis of Cys C levels in cerebrospinal cord fluid (CSF) and peripheral blood of patients with ALS in order to further confirm whether or not Cys C levels is a biomarker in ALS diagnosis. The English relevant studies without year limitation were systematically searched in PubMed, EMBASE, Web of Science databases. The searched term contained "Amyotrophic Lateral Sclerosis" or "Motor Neuron Diseases" and "Cystatin C" and "Cerebrospinal fluid" or "CSF" or "Biomarker" or "Serum" or "Plasma" or "Blood". Observational studies reporting the associations between Cys C levels and ALS patients were selected to conduct a systematic review and meta analysis. Two reviewers performed the selection of this study independently. The Newcastle-Ottawa Scale assesses the quality and risk of bias of selected studies. Estimates were pooled using a random-effects model. The Cys C levels of CSF or peripheral blood in ALS patients compared with health controls (HCs) and several relevant neurodegenerative diseases (NDDs). Sixteen studies were included in our systematic review, 9 of them were selected to perform the meta analysis. Of these, eight studies measured Cys C levels in CSF and three studies measured it in blood. Cys C levels in CSF were significantly lower in ALS patients than in HCs (Hedge's g = -1.398, 95%CI: -2.43 to -0.36; p = 0.008), but there was no statistical difference between ALS patients and several relevant NDDs. No statistically significant difference in the Cys C levels of blood in the comparison between ALS and HCs. The correlation meta analysis presented no significant correlation between Cys C levels in CSF and age or disease duration respectively. Cys C levels significantly decrease in the CSF of ALS patients, but are not a specific biomarker for this disease. Cys C levels in CSF might be an auxiliary diagnostic biomarker of ALS.}, }
@article {pmid29985117, year = {2020}, author = {Iacopetta, K and Collins-Praino, LE and Buisman-Pijlman, FTA and Liu, J and Hutchinson, AD and Hutchinson, MR}, title = {Are the protective benefits of vitamin D in neurodegenerative disease dependent on route of administration? A systematic review.}, journal = {Nutritional neuroscience}, volume = {23}, number = {4}, pages = {251-280}, doi = {10.1080/1028415X.2018.1493807}, pmid = {29985117}, issn = {1476-8305}, mesh = {Animals ; Dietary Supplements ; Humans ; Neurodegenerative Diseases/*drug therapy/*prevention & control ; Neuroprotective Agents/*administration & dosage ; Sunlight ; Treatment Outcome ; Vitamin D/*administration & dosage ; }, abstract = {Background: The clinical and preclinical exploration of the therapeutic properties of vitamin D have significantly increased in the past decade, owing to the growing associative evidence suggesting vitamin D is neuroprotective. However, whether depletion of vitamin D contributes to the onset of neurological disorders or is a symptom of neurological disease has yet to be defined. Much remains unclear about the causal role of vitamin D and the method of use and forms of vitamin D.Objectives: We sought to quantitatively assess if neuroprotective benefits from vitamin D in neurodegenerative diseases are dependent on route of administration: comparing the effect of endogenously sourced vitamin D from UV exposure to exogenously derived vitamin D through synthetic supplementation.Design: We systematically searched PubMed, Embase and PsycInfo databases which included both pre-clinical and clinical studies investigating vitamin D in neurodegenerative diseases. Articles were subject to strict inclusion criteria and objectively assessed for quality. Additionally, Medline data was analysed to identify trends in topic publications and linguistic characteristics of papers.Results: From a total of 231 screened articles, we identified 73 appropriate for review based on inclusion criteria: original studies that investigated vitamin D levels or levels of vitamin D supplementation in neurodegenerative diseases or investigated past/present sun exposure in disease cohorts. Results indicate there is insufficient evidence to comprehensively reflect on a potential neuroprotective role for vitamin D and if this was dependent on route of administration. The majority of current data supporting neuroprotective benefits from vitamin D are based on pre-clinical and observational studies. Solid evidence is lacking to support the current hypothesis that the beneficial effect of UV exposure results from the synthesis of vitamin D. Sun exposure, independent of vitamin D production, may be protective against multiple Sclerosis, Parkinson's disease and Alzheimer's disease. Yet, further research is required to elucidate the beneficial mechanism of actions of UV exposure. The literature of vitamin D and amyotrophic lateral sclerosis was limited, and no conclusions were drawn. Therefore, in cases where UV-derived vitamin D was hypothesized to be the beneficial mediator in the neuroprotective effects of sun exposure, we propose results are based only on associative evidence.Conclusion: On the basis of this systematic review, strong recommendations regarding therapeutic benefits of vitamin D in neurodegenerative disease cannot be made. It is unclear if vitamin D mediates a protective benefit in neurodegenerative disease or whether it is an associative marker of UV exposure, which may contribute to as of yet unidentified neuroprotective factors.}, }
@article {pmid29925252, year = {2018}, author = {Wright, ML and Fournier, C and Houser, MC and Tansey, M and Glass, J and Hertzberg, VS}, title = {Potential Role of the Gut Microbiome in ALS: A Systematic Review.}, journal = {Biological research for nursing}, volume = {20}, number = {5}, pages = {513-521}, doi = {10.1177/1099800418784202}, pmid = {29925252}, issn = {1552-4175}, mesh = {Adult ; Aged ; Aged, 80 and over ; Amyotrophic Lateral Sclerosis/*microbiology/*physiopathology ; Animals ; Disease Models, Animal ; Disease Progression ; Dysbiosis/*etiology/*physiopathology ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Intestines/*microbiology ; Male ; Mice ; Middle Aged ; }, abstract = {Amyotrophic lateral sclerosis (ALS) etiology and pathophysiology are not well understood. Recent data suggest that dysbiosis of gut microbiota may contribute to ALS etiology and progression. This review aims to explore evidence of associations between gut microbiota and ALS etiology and pathophysiology. Databases were searched for publications relevant to the gut microbiome in ALS. Three publications provided primary evidence of changes in microbiome profiles in ALS. An ALS mouse model revealed damaged tight junction structure and increased permeability in the intestine versus controls along with a shifted microbiome profile, including decreased levels of butyrate-producing bacteria. In a subsequent publication, again using an ALS mouse model, researchers showed that dietary supplementation with butyrate relieved symptoms and lengthened both time to onset of weight loss and survival time. In a small study of ALS patients and healthy controls, investigators also found decreased levels of butyrate-producing bacteria. Essential for maintaining gut barrier integrity, butyrate is the preferred energy source of intestinal epithelial cells. Ten other articles were reviews and commentaries providing indirect support for a role of gut microbiota in ALS pathophysiology. Thus, these studies provide a modicum of evidence implicating gut microbiota in ALS disease, although more research is needed to confirm the connection and determine pathophysiologic mechanisms. Nurses caring for these patients need to understand the gut microbiome and its potential role in ALS in order to effectively counsel patients and their families about emerging therapies (e.g., prebiotics, probiotics, and fecal microbial transplant) and their off-label uses.}, }
@article {pmid29705950, year = {2018}, author = {Pinto-Grau, M and Hardiman, O and Pender, N}, title = {The Study of Language in the Amyotrophic Lateral Sclerosis - Frontotemporal Spectrum Disorder: a Systematic Review of Findings and New Perspectives.}, journal = {Neuropsychology review}, volume = {28}, number = {2}, pages = {251-268}, pmid = {29705950}, issn = {1573-6660}, support = {HARDIMAN/OCT15/879-792/MNDA_/Motor Neurone Disease Association/United Kingdom ; }, mesh = {Amyotrophic Lateral Sclerosis/*psychology ; Frontotemporal Dementia/*psychology ; Humans ; *Language ; }, abstract = {Amyotrophic Lateral Sclerosis is a neurodegenerative disorder characterized primarily by motor network disruption. Extra-motor manifestations including executive functions, social cognition, and behavioral changes are now well recognized as important features of ALS, and are associated with frontotemporal and frontostriatal network disruption. However, the presence and characterization of language changes has received less attention. This systematic review characterizes the profile of reported language dysfunction in ALS. PRISMA guidelines were implemented to carry out and report the review. Current evidence suggests that areas of neuroanatomical disruption in ALS spread to language centers such as posterior, inferior frontal and superior temporal areas leading to deficits in word retrieval, syntactic and grammatical processing, and spelling. However, the majority of studies of language in ALS have been limited by the recruitment of small clinic-based prevalent samples and important questions remain regarding the incidence and progression of language impairment in ALS. Further studies from population-based incident cohorts will help to determine the range of language deficits in ALS, and how these relate to previously defined executive and behavioral sub-phenotypes.}, }
@article {pmid29679161, year = {2018}, author = {Donatelli, G and Ceravolo, R and Frosini, D and Tosetti, M and Bonuccelli, U and Cosottini, M}, title = {Present and Future of Ultra-High Field MRI in Neurodegenerative Disorders.}, journal = {Current neurology and neuroscience reports}, volume = {18}, number = {6}, pages = {31}, pmid = {29679161}, issn = {1534-6293}, mesh = {Alzheimer Disease/*diagnostic imaging ; Amyotrophic Lateral Sclerosis/*diagnostic imaging ; Brain/diagnostic imaging ; Humans ; Magnetic Resonance Imaging/*methods ; Neuroimaging/methods ; Parkinson Disease/*diagnostic imaging ; }, abstract = {PURPOSE OF REVIEW: With a high signal-to-noise ratio, unparalleled spatial resolution, and improved contrasts, ultra-high field MR (≥ 7 T) has great potential in depicting the normal radiological anatomy of smaller structures in the brain and can also provide more information about morphological, quantitative, and metabolic changes associated with a wide range of brain disorders. By focusing attention on specific brain regions believed to be associated with early pathological change, or by more closely inspecting recognized foci of brain pathology, ultra-high field MR can improve the accuracy and sensitivity of neuroimaging. This article reviews recent studies at ultra-high field about Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS).
RECENT FINDINGS: The research on AD has mainly focused on detecting the thinning of hippocampal layers and the susceptibility effect supposed to be related to beta-amyloid deposition. In patients with PD, atypical parkinsonisms and subjects at risk of developing motor symptoms of Parkinson's disease, the main aim was to detect changes in the substantia nigra, probably related to increased iron deposition. In patients with ALS, both brain and spinal cord were investigated, with the aim of finding changes in the primary motor cortex and corticospinal tract which reflect neurodegeneration and neuroinflammation. Ultra-high field MR was shown to be useful for detecting subtle brain changes in patients with AD, and possible new diagnostic biomarkers in patients with PD and ALS were discovered. The ability of 7 T MR to provide prognostic biomarkers in subjects at risk for developing synucleinopathies is currently under evaluation.}, }
@article {pmid29577362, year = {2018}, author = {Jokubauskas, L and Baltrušaitytė, A}, title = {Efficacy of biofeedback therapy on sleep bruxism: A systematic review and meta-analysis.}, journal = {Journal of oral rehabilitation}, volume = {45}, number = {6}, pages = {485-495}, doi = {10.1111/joor.12628}, pmid = {29577362}, issn = {1365-2842}, mesh = {Biofeedback, Psychology/*methods/*physiology ; Controlled Clinical Trials as Topic ; Electric Stimulation Therapy ; Humans ; Mandibular Advancement ; Sleep Bruxism/*physiopathology/rehabilitation/*therapy ; Treatment Outcome ; }, abstract = {This study updates the review published by Wang et al in 2014 (Sleep Breath 2014;18(2):235-242). The review focuses on the most recent literature on management of sleep bruxism (SB) with biofeedback. An electronic search was conducted in five databases searching for articles published later than the date of Wang et al's search, viz., October 2012. Six articles of 2320 identified citations involving 86 adult participants were included in the qualitative synthesis. Of them, 4 were randomised controlled trials (RCTs) and 2 were uncontrolled before-after studies. Different feedback modalities (electrical, auditory and vibratory stimulus) were investigated. The overall quality of the selected studies was assessed using the GRADE criteria. Due to heterogeneity between studies, the quantitative synthesis was performed out of three RCTs, of which two were retrieved from the previous review. The meta-analysis indicated a non-significant difference in electromyographic-measured SB episodes per hour after one night of contingent electrical stimulation (CES) compared with placebo control, yet a significant difference was shown after five nights of CES. The quality of evidence identified through GRADEpro was from low to moderate, due to imprecision and inconsistency between studies. Qualitative synthesis did not present a reliable reduction in clinical pain levels; however, no substantial sleep disturbances were indicated following the intervention. In conclusion, one of the biofeedback modalities, CES, is effective in reducing SB-related motor activities after a short-term treatment period. However, evidence of long-term effects is lacking. Further longitudinal studies with larger samples are necessary to acknowledge the clinical application of biofeedback.}, }
@article {pmid29443939, year = {2018}, author = {Lance, E and Arnich, N and Maignien, T and Biré, R}, title = {Occurrence of β-N-methylamino-l-alanine (BMAA) and Isomers in Aquatic Environments and Aquatic Food Sources for Humans.}, journal = {Toxins}, volume = {10}, number = {2}, pages = {}, pmid = {29443939}, issn = {2072-6651}, mesh = {Amino Acids, Diamino/*analysis ; Animals ; Cyanobacteria Toxins ; Environmental Monitoring ; Food Contamination/*analysis ; Humans ; Isomerism ; Water Pollutants, Chemical/*analysis ; }, abstract = {The neurotoxin β-N-methylamino-l-alanine (BMAA), a non-protein amino acid produced by terrestrial and aquatic cyanobacteria and by micro-algae, has been suggested to play a role as an environmental factor in the neurodegenerative disease Amyotrophic Lateral Sclerosis-Parkinsonism-Dementia complex (ALS-PDC). The ubiquitous presence of BMAA in aquatic environments and organisms along the food chain potentially makes it public health concerns. However, the BMAA-associated human health risk remains difficult to rigorously assess due to analytical challenges associated with the detection and quantification of BMAA and its natural isomers, 2,4-diamino butyric acid (DAB), β-amino-N-methyl-alanine (BAMA) and N-(2-aminoethyl) glycine (AEG). This systematic review, reporting the current knowledge on the presence of BMAA and isomers in aquatic environments and human food sources, was based on a selection and a score numbering of the scientific literature according to various qualitative and quantitative criteria concerning the chemical analytical methods used. Results from the best-graded studies show that marine bivalves are to date the matrix containing the higher amount of BMAA, far more than most fish muscles, but with an exception for shark cartilage. This review discusses the available data in terms of their use for human health risk assessment and identifies knowledge gaps requiring further investigations.}, }
@article {pmid29439163, year = {2018}, author = {Beeldman, E and Raaphorst, J and Klein Twennaar, M and Govaarts, R and Pijnenburg, YAL and de Haan, RJ and de Visser, M and Schmand, BA}, title = {The cognitive profile of behavioural variant FTD and its similarities with ALS: a systematic review and meta-analysis.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {89}, number = {9}, pages = {995-1002}, doi = {10.1136/jnnp-2017-317459}, pmid = {29439163}, issn = {1468-330X}, mesh = {Aged ; Amyotrophic Lateral Sclerosis/*psychology ; Cognition Disorders/*etiology ; Educational Status ; Female ; Frontotemporal Dementia/*psychology ; Humans ; Male ; Middle Aged ; Neuropsychological Tests ; }, abstract = {Approximately 30% of patients with amyotrophic lateral sclerosis (ALS) have cognitive impairment and 8%-14% fulfil the criteria for behavioural variant frontotemporal dementia (bv-FTD). The cognitive profiles of ALS and bv-FTD have been reported to be comparable, but this has never been systematically investigated. We aimed to determine the cognitive profile of bv-FTD and examine its similarities with that of ALS, to provide evidence for the existence of a cognitive disease continuum encompassing bv-FTD and ALS. We therefore systematically reviewed neuropsychological studies on bv-FTD patients and healthy volunteers. Neuropsychological tests were divided in 10 cognitive domains and effect sizes were calculated for all domains and compared with the cognitive profile of ALS by means of a visual comparison and a Pearson's r correlation coefficient. We included 120 studies, totalling 2425 bv-FTD patients and 2798 healthy controls. All cognitive domains showed substantial effect sizes, indicating cognitive impairment in bv-FTD patients compared to healthy controls. The cognitive domains with the largest effect sizes were social cognition, verbal memory and fluency (1.77-1.53). The cognitive profiles of bv-FTD and ALS (10 cognitive domains, 1287 patients) showed similarities on visual comparison and a moderate correlation 0.58 (p=0.13). When social cognition, verbal memory, fluency, executive functions, language and visuoperception were considered, i.e. the cognitive profile of ALS, Pearson's r was 0.73 (p=0.09), which raised to 0.92 (p=0.03), when language was excluded in this systematic analysis of patients with a non-language subtype of FTD. The cognitive profile of bv-FTD consists of deficits in social cognition, verbal memory, fluency and executive functions and shows similarities with the cognitive profile of ALS. These findings support a cognitive continuum encompassing ALS and bv-FTD.}, }
@article {pmid29330136, year = {2018}, author = {Chen, G and Zhou, B and Zhu, H and Kuang, W and Bi, F and Ai, H and Gu, Z and Huang, X and Lui, S and Gong, Q}, title = {White matter volume loss in amyotrophic lateral sclerosis: A meta-analysis of voxel-based morphometry studies.}, journal = {Progress in neuro-psychopharmacology & biological psychiatry}, volume = {83}, number = {}, pages = {110-117}, doi = {10.1016/j.pnpbp.2018.01.007}, pmid = {29330136}, issn = {1878-4216}, mesh = {Amyotrophic Lateral Sclerosis/*diagnostic imaging/pathology/psychology ; Humans ; Neuroimaging ; Organ Size ; White Matter/*diagnostic imaging/pathology ; }, abstract = {Structural neuroimaging studies of white matter (WM) volume in amyotrophic lateral sclerosis (ALS) using voxel-based morphometry (VBM) have yielded inconsistent findings. This study aimed to perform a quantitative voxel-based meta-analysis using effect-size signed differential mapping (ES-SDM) to establish a statistical consensus between published studies for WM volume alterations in ALS. The pooled meta-analysis revealed significant WM volume losses in the bilateral supplementary motor areas (SMAs), bilateral precentral gyri (PGs), left middle cerebellar peduncle and right cerebellum in patients with ALS, involving the corticospinal tract (CST), interhemispheric fibers, subcortical arcuate fibers, projection fibers to the striatum and cortico-ponto-cerebellar tract. The meta-regression showed that the ALS functional rating scale-revised (ALSFRS-R) was positively correlated with decreased WM volume in the bilateral SMAs, whereas illness duration was negatively correlated with WM volume reduction in the right SMA. This study provides a thorough profile of WM volume loss in ALS and robust evidence that ALS is a multisystem neurodegenerative disease that involves a variety of subcortical WM tracts extending beyond motor cortex involvement.}, }
@article {pmid29125503, year = {2017}, author = {Landfeldt, E and Edström, J and Lindgren, P and Lochmüller, H}, title = {Patient Preferences for Treatments of Neuromuscular Diseases: A Systematic Literature Review.}, journal = {Journal of neuromuscular diseases}, volume = {4}, number = {4}, pages = {285-292}, doi = {10.3233/JND-170271}, pmid = {29125503}, issn = {2214-3599}, mesh = {Humans ; Neuromuscular Diseases/*psychology/*therapy ; *Patient Preference ; }, abstract = {BACKGROUND: Treatment decisions of neuromuscular diseases involve weighing clinical benefits and risks, as well as impact on patient social life, work status, other activities of daily living, and health-related quality of life.
OBJECTIVE: To conduct a systemic literature review of patient preferences for treatments of neuromuscular diseases.
METHODS: We searched Embase, Web of Science, and PubMed for full-text articles reporting results from studies of patient preferences for treatments of neuromuscular diseases. We excluded articles published before the year 2000, articles written in a language other than English, articles only reporting proxy-assessments of patient preferences, and studies reporting results for a sample comprising <5 patients.
RESULTS: The search resulted in the identification of 305 unique publications. Of these, 275 were excluded following title and abstract screening and 23 following full-text review. Seven articles were included for data synthesis. Preference data were identified for a hypothetical treatment with pulmonary benefits of Duchenne muscular dystrophy and Becker muscular dystrophy, pathways for different routes of opioid drug administration in motor neuron disease, wheelchair features in amyotrophic lateral sclerosis (ALS), ankle foot orthoses in patients with Charcot Marie Tooth disease, and mechanical ventilation in ALS and a mixed cohort of patients with neuromuscular diseases.
CONCLUSIONS: Despite considerable research into the development of new health technologies targeting neuromuscular diseases, little is known of patients' preferences for pharmacological interventions. More research is needed to help incorporate patient preferences in clinical decision-making to improve treatment satisfaction, medication compliance, and health outcomes.}, }
@article {pmid28831083, year = {2017}, author = {Hu, Y and Cao, C and Qin, XY and Yu, Y and Yuan, J and Zhao, Y and Cheng, Y}, title = {Increased peripheral blood inflammatory cytokine levels in amyotrophic lateral sclerosis: a meta-analysis study.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {9094}, pmid = {28831083}, issn = {2045-2322}, mesh = {Amyotrophic Lateral Sclerosis/blood/diagnosis/*immunology ; Biomarkers/*blood ; Case-Control Studies ; Cytokines/*blood ; Female ; Humans ; Interleukin-1beta/blood ; Interleukin-6/blood ; Interleukin-8/blood ; Male ; Receptors, Tumor Necrosis Factor, Type I/blood ; Tumor Necrosis Factor-alpha/blood ; *Up-Regulation ; Vascular Endothelial Growth Factor A/blood ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with poorly understood etiology. Increasing evidence suggest that inflammation may play a critical role in the pathogenesis of ALS. Several studies have demonstrated altered levels of blood cytokines in ALS, but results were inconsistent. Therefore, we did a systematic review of studies comparing blood inflammatory cytokines between ALS patients and control subjects, and quantitatively combined the clinical data with a meta-analysis. The systematic review of Pubmed and Web of Science identified 25 studies encompassing 812 ALS patients and 639 control subjects. Random-effects meta-analysis demonstrated that blood tumor necrosis factor-α (TNF; Hedges' g = 0.655; p = 0.001), TNF receptor 1 (Hedges' g = 0.741; p < 0.001), interleukin 6 (IL-6; Hedges' g = 0.25; p = 0.005), IL-1β (Hedges' g = 0.296; p = 0.038), IL-8 (Hedges' g = 0.449; p < 0.001) and vascular endothelial growth factor (Hedges' g = 0.891; p = 0.003) levels were significantly elevated in patients with ALS compared with control subjects. These results substantially enhance our knowledge of the inflammatory response in ALS, and peripheral blood inflammatory cytokines may be used as diagnostic biomarkers for ALS in the future.}, }
@article {pmid28799809, year = {2018}, author = {Kellogg, J and Bottman, L and Arra, EJ and Selkirk, SM and Kozlowski, F}, title = {Nutrition management methods effective in increasing weight, survival time and functional status in ALS patients: a systematic review.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {19}, number = {1-2}, pages = {7-11}, doi = {10.1080/21678421.2017.1360355}, pmid = {28799809}, issn = {2167-9223}, mesh = {Amyotrophic Lateral Sclerosis/complications/*mortality/*therapy ; Body Mass Index ; Body Weight/*physiology ; Disease Progression ; Humans ; Motor Neuron Disease/complications/*mortality ; *Nutrition Therapy ; }, abstract = {Poor prognosis and decreased survival time correlate with the nutritional status of patients with amyotrophic lateral sclerosis (ALS). Various studies were reviewed which assessed weight, body mass index (BMI), survival time and ALS functional rating scale revised (ALSFRS-R) in order to determine the best nutrition management methods for this patient population. A systematic review was conducted using CINAHL, Medline, and PubMed, and various search terms in order to determine the most recent clinical trials and observational studies that have been conducted concerning nutrition and ALS. Four articles met criteria to be included in the review. Data were extracted from these articles and were inputted into the Data Extraction Tool (DET) provided by the Academy of Nutrition and Dietetics (AND). Results showed that nutrition supplementation does promote weight stabilisation or weight gain in individuals with ALS. Given the low risk and low cost associated with intervention, early and aggressive nutrition intervention is recommended. This systematic review shows that there is a lack of high quality evidence regarding the efficacy of any dietary interventions for promoting survival in ALS or slowing disease progression; therefore more research is necessary related to effects of nutrition interventions.}, }
@article {pmid28671483, year = {2018}, author = {de Wit, J and Bakker, LA and van Groenestijn, AC and van den Berg, LH and Schröder, CD and Visser-Meily, JMA and Beelen, A}, title = {Caregiver burden in amyotrophic lateral sclerosis: A systematic review.}, journal = {Palliative medicine}, volume = {32}, number = {1}, pages = {231-245}, pmid = {28671483}, issn = {1477-030X}, mesh = {*Adaptation, Psychological ; Adult ; Aged ; Aged, 80 and over ; Amyotrophic Lateral Sclerosis/*nursing/*psychology ; Anxiety/*psychology ; Caregivers/*psychology ; Family/*psychology ; Female ; Humans ; Male ; Middle Aged ; Quality of Life/*psychology ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Informal caregivers of patients with amyotrophic lateral sclerosis experience increased levels of caregiver burden as the disease progresses. Insight in the factors related to caregiver burden is needed in order to develop supportive interventions.
AIM: To evaluate the evidence on patient and caregiver factors associated with caregiver burden in amyotrophic lateral sclerosis informal caregivers.
DESIGN: A systematic review.
DATA SOURCES: Four electronic databases were searched up to 2017. Studies that investigated quantitative relations between patient or caregiver factors and caregiver burden were included. The overall quality of evidence for factors was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.
RESULTS: A total of 25 articles were included. High quality of evidence was found for the relation between caregiver burden and the factor "behavioral impairments." Moderate quality of evidence was found for the relations between caregiver burden and the factors "feelings of depression" of the caregiver and "physical functioning" of the patient. The remaining rated caregiver factors-"feelings of anxiety," "distress," "social support," "family functioning," and "age"-and patient factors-"bulbar function," "motor function," "respiratory function," "disease duration," "disinhibition," "executive functioning," "cognitive functioning," "feelings of depression," and "age"-showed low to very low quality of evidence for their association with caregiver burden.
CONCLUSION: Higher caregiver burden is associated with greater behavioral and physical impairment of the patient and with more depressive feelings of the caregiver. This knowledge enables the identification of caregivers at risk for caregiver burden and guides the development of interventions to diminish caregiver burden.}, }
@article {pmid27477403, year = {2016}, author = {Nakane, S and Izumi, Y and Oda, M and Kaji, R and Matsuo, H}, title = {A Potential Link between Amyotrophic Lateral Sclerosis and Bullous Pemphigoid: Six New Cases and a Systematic Review of the Literature.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {55}, number = {15}, pages = {1985-1990}, doi = {10.2169/internalmedicine.55.5578}, pmid = {27477403}, issn = {1349-7235}, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/complications ; *Pemphigoid, Bullous/complications ; Time Factors ; }, abstract = {Objective Bullous pemphigoid in amyotrophic lateral sclerosis (BP-ALS) is rare and poorly understood. We herein assessed the association between ALS and BP using clinical and biological findings. Methods The clinical features of six new BP-ALS cases were described and collated with cases from a systematic literature review. Results Our six cases were combined with three other published cases. The mean disease duration (from ALS onset to the occurrence of BP) was 5.6±3.1 years. All patients had limb-onset ALS. Four of the 9 patients received riluzole, with the use of riluzole ranging from a few days to 3 years. When BP occurred, the status of the ALS patients was paretic and/or bedridden in all cases. BP occurred throughout the body, and we confirmed that the bullous lesions were located not only at the compression site, but also at the anterior part of the chest, abdomen, and limbs. Treatment for BP was successful, as oral prednisone and/or local corticosteroids were effective in 8 cases. Conclusion These six new cases, in combination with previous cases, expand our knowledge of the relationship between dermatological lesions and ALS. The pathogenesis of BP-ALS is poorly understood, however, some immunological aberrance is likely.}, }
@article {pmid27212114, year = {2016}, author = {Geevasinga, N and Loy, CT and Menon, P and de Carvalho, M and Swash, M and Schrooten, M and Van Damme, P and Gawel, M and Sonoo, M and Higashihara, M and Noto, Y and Kuwabara, S and Kiernan, MC and Macaskill, P and Vucic, S}, title = {Awaji criteria improves the diagnostic sensitivity in amyotrophic lateral sclerosis: A systematic review using individual patient data.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {127}, number = {7}, pages = {2684-2691}, doi = {10.1016/j.clinph.2016.04.005}, pmid = {27212114}, issn = {1872-8952}, mesh = {Adult ; Aged ; Aged, 80 and over ; Amyotrophic Lateral Sclerosis/*diagnosis ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; Neurologic Examination/*methods/standards ; Sensitivity and Specificity ; Severity of Illness Index ; }, abstract = {OBJECTIVE: To determine the utility of the Awaji criteria in diagnosing amyotrophic lateral sclerosis (ALS) and to propose a novel modification so as to enhance sensitivity based on results of individual patient data (IPD).
METHODS: Individual patient data were available from 8 studies comparing the diagnostic accuracy of Awaji and revised El Escorial (rEEC) criteria. The sensitivity of a novel updated Awaji criteria, incorporating a "probable-laboratory supported" category, was also tested.
RESULTS: Individual patient data were available from 1086 patients, consisting of 881 ALS and 205 patients with disorders mimicking ALS. Summary sensitivities based on random effects logistic regression modelling disclosed a higher sensitivity of the Awaji criteria (0.70, 95% confidence interval [CI] 0.51-0.83) and updated Awaji criteria (0.73, 95% CI 0.56-0.85) when compared to rEEC (0.58, 95% CI 0.48-0.68). Paired analysis revealed higher sensitivities of Awaji criteria in 4 studies, and of updated Awaji criteria in 7 studies, when compared to rEEC.
CONCLUSION: Individual patient data analysis established a higher sensitivity of Awaji criteria when compared to rEEC. The updated Awaji criteria enhanced the diagnostic sensitivity in limb-onset ALS.
SIGNIFICANCE: The updated Awaji criteria should be considered in clinical practice and future therapeutic trials.}, }
@article {pmid26731747, year = {2016}, author = {Belbasis, L and Bellou, V and Evangelou, E}, title = {Environmental Risk Factors and Amyotrophic Lateral Sclerosis: An Umbrella Review and Critical Assessment of Current Evidence from Systematic Reviews and Meta-Analyses of Observational Studies.}, journal = {Neuroepidemiology}, volume = {46}, number = {2}, pages = {96-105}, doi = {10.1159/000443146}, pmid = {26731747}, issn = {1423-0208}, mesh = {Amyotrophic Lateral Sclerosis/*epidemiology ; *Environmental Exposure ; Female ; Humans ; Male ; Meta-Analysis as Topic ; Observational Studies as Topic ; Risk Factors ; Systematic Reviews as Topic ; }, abstract = {BACKGROUND: The pathogenesis of amyotrophic lateral sclerosis (ALS) involves both environmental and genetic factors. Our study aimed at summarising the environmental risk factors for ALS, assessing the evidence for diverse biases, and pinpointing risk factors with high epidemiological credibility.
METHODS: We searched PubMed from inception to August 20, 2015, to identify systematic reviews and meta-analyses of observational studies examining associations between environmental factors and ALS. For each meta-analysis, we estimated the summary effect size by the use of random-effects and fixed-effects models, the 95% CI, the 95% prediction interval (PI), and the between-study heterogeneity. We assessed the evidence of small-study effects and excess significance bias.
RESULTS: Sixteen unique meta-analyses of different risk factors and ALS were considered. Of them, 5 were statistically significant at p < 0.001 under the random-effects model. Only one factor presented robust evidence for a convincing association. This association pertained to chronic occupational exposure to lead (random-effects OR 1.81, 95% CI 1.39-2.35).
CONCLUSIONS: A small number of published meta-analyses on environmental factors and risk of ALS was identified, a phenomenon that could be attributed to the challenges in studying a rare neurological disease. More observational studies with adequate sample size and study design are needed to clarify the environmental component of ALS pathogenesis.}, }
@article {pmid24086552, year = {2013}, author = {Cong, ZJ and Hu, LH and Bian, ZQ and Ye, GY and Yu, MH and Gao, YH and Li, ZS and Yu, ED and Zhong, M}, title = {Systematic review of anastomotic leakage rate according to an international grading system following anterior resection for rectal cancer.}, journal = {PloS one}, volume = {8}, number = {9}, pages = {e75519}, pmid = {24086552}, issn = {1932-6203}, mesh = {Anastomosis, Surgical/*adverse effects ; Anastomotic Leak/*epidemiology ; Databases, Factual ; Humans ; Postoperative Complications/*epidemiology ; Rectal Neoplasms/*surgery ; Surgical Stomas/*adverse effects ; }, abstract = {BACKGROUND: A generally acceptable definition and a severity grading system for anastomotic leakages (ALs) following rectal resection were not available until 2010, when the International Study Group of Rectal Cancer (ISGRC) proposed a definition and a grading system for AL.
METHODS: A search for published data was performed using the MEDLINE database (2000 to December 5, 2012) to perform a systematic review of the studies that described AL, grade AL according to the grading system, pool data, and determine the average rate of AL for each grade after anterior resection (AR) for rectal cancer.
RESULTS: A total of 930 abstracts were retrieved; 40 articles on AR, 25 articles on low AR (LAR), and 5 articles on ultralow AR (ULAR) were included in the review and analysis. The pooled overall AL rate of AR was 8.58% (2,085/24,288); the rate of the asymptomatic leakage (Grade A) was 2.57%, that of AL that required active intervention without relaparotomy (Grade B) was 2.37%, and that of AL that required relaparotomy (Grade C) was 5.40%. The pooled rate of AL that required relaparotomy was higher in AR (5.40%) than in LAR (4.70%) and in ULAR (1.81%), which could be attributed to the higher rate of protective defunctioning stoma in LAR (40.72%) and ULAR (63.44%) compared with that in AR (30.11%).
CONCLUSIONS: The new grading system is simple that the ALs of each grade can be easily extracted from past publications, therefore likely to be accepted and applied in future studies.}, }
@article {pmid22983450, year = {2012}, author = {Benze, G and Geyer, A and Alt-Epping, B and Nauck, F}, title = {[Treatment of nausea and vomiting with 5HT3 receptor antagonists, steroids, antihistamines, anticholinergics, somatostatinantagonists, benzodiazepines and cannabinoids in palliative care patients : a systematic review].}, journal = {Schmerz (Berlin, Germany)}, volume = {26}, number = {5}, pages = {481-499}, pmid = {22983450}, issn = {1432-2129}, mesh = {Adrenal Cortex Hormones/adverse effects/therapeutic use ; Antiemetics/adverse effects/*therapeutic use ; Benzodiazepines/adverse effects/therapeutic use ; Cholinergic Antagonists/adverse effects/therapeutic use ; Drug Therapy, Combination ; Evidence-Based Medicine ; Germany ; Histamine Antagonists/adverse effects/therapeutic use ; Nausea/*drug therapy ; Palliative Care/*methods ; Serotonin 5-HT3 Receptor Antagonists/adverse effects/therapeutic use ; Somatostatin/analogs & derivatives ; Vomiting/*drug therapy ; }, abstract = {BACKGROUND: Various recommendations exist for the treatment of nausea and vomiting in palliative care but only few studies and even less systematic reviews look into antiemetic therapy for patients receiving palliative care.
OBJECTIVES: This systematic review aims to analyze the current evidence for antiemetic treatment with 5HT3 receptor antagonists, steroids, antihistamines, anticholinergics, somatostatin analogs, benzodiazepines and cannabinoids in palliative care patients with far advanced cancer not receiving chemotherapy or radiotherapy, acquired immune deficiency syndrome (AIDS), chronic obstructive pulmonary disease (COPD), progressive heart failure, amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). Results regarding evidence of treatment with prokinetic and neuroleptic agents will be published separately.
METHODS: The electronic databases PubMed and EmBase were systematically searched for studies (published 1966-2011) dealing with antiemetic therapy in palliative care and electronic retrieval was completed by manual searching. Studies with patients undergoing chemotherapy or radiotherapy, pediatric studies and studies published in languages other than English or German were excluded. Studies addressing therapy with 5HT3 receptor antagonists, steroids, antihistamines, anticholinergics, somatostatin analogs, benzodiazepines or cannabinoids were identified and selected for this systematic review.
RESULTS: In the general search 75 relevant studies were found. Of those 36 addressed 5HT3 receptor antagonists, steroids, antihistamines, anticholinergics, somatostatin analogs, benzodiazepines and cannabinoids, 13 considered 5HT3 receptor antagonists, 10 somatostatin antagonists, 9 steroids, 5 cannabinoids, 4 anticholinergics, 1 antihistamines and none benzodiazepines. Furthermore six systematic reviews exist. Evidence for any drug used as an antiemetic is low. Concerning 5HT3 receptor antagonists data are insufficient for recommendations on the treatment of patients with AIDS and MS due to the small size of included patient groups. For patients with cancer contradictory results were published: the larger studies showed a positive effect of 5HT3 receptor antagonists and better efficacy, as compared to metoclopramide, dexamethasone and neuroleptics. Heterogeneous results were found for steroids, with a positive trend for patients with cancer. Data are insufficient for antihistamines. Studies prove effectiveness of butylscopolammonium in the treatment of nausea and vomiting caused by malignant gastrointestinal obstruction, whereas octreotide is superior to butylscopolammonium. Regarding benzodiazepines for symptom control of nausea and vomiting in palliative care patients no studies were detected. Cannabinoids were found to relieve nausea and vomiting in patients with cancer and AIDS but with notable side effects. Furthermore, the studies compared cannabinoids to less recent antiemetic drugs but not, for example to 5HT3 receptor antagonists. Regarding symptom control of nausea and vomiting in patients with COPD, progressive heart failure and ALS no studies were undertaken in patients receiving palliative care.
CONCLUSIONS: In palliative care patients with nausea and vomiting 5HT3 receptor antagonists can be used if treatment with other antiemetics, such as metoclopramide and neuroleptics is not sufficient. There is a trend that steroids in combination with other antiemetics improve symptom relief. Cannabinoids rather have a status as a second line antiemetic. In cases of nausea and vomiting caused by malignant gastrointestinal obstruction octreotide showed the best and butylscopolammonium bromide the second best results. Concerning antihistamines and benzodiazepines insufficient data was found. Recommendations in the literature are mainly based on studies in patients with cancer. The overall strength of evidence is low. More well designed studies in palliative care patients are needed in order to provide evidence-based therapy. The English full text version of this article will be available in SpringerLink as of November 2012 (under "Supplemental").}, }
@article {pmid10499952, year = {1999}, author = {Nichol, G and Stiell, IG and Laupacis, A and Pham, B and De Maio, VJ and Wells, GA}, title = {A cumulative meta-analysis of the effectiveness of defibrillator-capable emergency medical services for victims of out-of-hospital cardiac arrest.}, journal = {Annals of emergency medicine}, volume = {34}, number = {4 Pt 1}, pages = {517-525}, pmid = {10499952}, issn = {0196-0644}, mesh = {*Electric Countershock ; *Emergency Medical Services ; Heart Arrest/mortality/*therapy ; Humans ; Linear Models ; Survival Analysis ; Time Factors ; Treatment Outcome ; United States/epidemiology ; }, abstract = {STUDY OBJECTIVE: More than 1,000 patients experience sudden cardiac arrest each day. Treatment for this includes cardiopulmonary resuscitation (CPR) and emergency medical services (EMS) that provide CPR-basic life support (BLS), BLS with defibrillation (BLS-D), or advanced life support (ALS). Our previous systematic review of treatments for sudden cardiac arrest was limited by suboptimal data. Since then, debate has increased about whether bystander CPR is effective or whether attention should focus instead on rapid defibrillation. Therefore a cumulative meta-analysis was conducted to determine the relative effectiveness of differences in the defibrillation response time interval, proportion of bystander CPR, and type of EMS system on survival after out-of-hospital cardiac arrest.
METHODS: A comprehensive literature search was performed by using a priori exclusion criteria. We considered EMS systems that provided BLS-D, ALS, BLS plus ALS, or BLS-D plus ALS care. A generalized linear model was used with dispersion estimation for random effects.
RESULTS: Thirty-seven eligible articles described 39 EMS systems and included 33,124 patients. Median survival for all rhythm groups to hospital discharge was 6.4% (interquartile range, 3.7 to 10.3). Odds of survival were 1.06 (95% confidence interval [CI], 1.03 to 1.09; P <.01) per 5% increase in bystander CPR. Survival was constant if the defibrillation response time interval was less than 6 minutes, decreased as the interval increased from 6 to 11 minutes, and leveled off after 11 minutes (P <.01). Compared with BLS-D, odds of survival were as follows: ALS, 1. 71 (95% CI, 1.09 to 2.70; P =.01); BLS plus ALS, 1.47 (95% CI, 0.89 to 2.42; P =.07); and BLS with defibrillation plus ALS, 2.31 (95% CI, 1.47 to 3.62; P <.01.)
CONCLUSION: We confirm that greater survival after sudden cardiac arrest is associated with provision of bystander CPR, early defibrillation, or ALS. More research is required to evaluate the relative benefit of early defibrillation versus early ALS.}, }
@article {pmid39578133, year = {2025}, author = {Travaglia, A and Lal, S and Pullagura, SR}, title = {Advancing ALS research: public-private partnerships to accelerate drug and biomarker development.}, journal = {Trends in neurosciences}, volume = {48}, number = {1}, pages = {1-2}, doi = {10.1016/j.tins.2024.10.008}, pmid = {39578133}, issn = {1878-108X}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/therapy ; Humans ; *Public-Private Sector Partnerships ; *Biomarkers ; Drug Development/methods ; Drug Discovery/methods ; Biomedical Research/methods ; Animals ; }, abstract = {Developing effective treatments for amyotrophic lateral sclerosis (ALS) has been hindered by both the complexity of the disease and decentralized research efforts. By fostering collaboration, standardization, and inclusivity, the Accelerating Medicines Partnership® (AMP®) ALS initiative aims to lay the foundation for future discoveries in ALS biomarkers and treatments.}, }
@article {pmid39820861, year = {2025}, author = {van Zundert, B and Montecino, M}, title = {Epigenetics in Neurodegenerative Diseases.}, journal = {Sub-cellular biochemistry}, volume = {108}, number = {}, pages = {73-109}, pmid = {39820861}, issn = {0306-0225}, mesh = {Humans ; *Epigenesis, Genetic ; Animals ; *Neurodegenerative Diseases/genetics/metabolism ; Alzheimer Disease/genetics/metabolism ; DNA Methylation ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; Frontotemporal Dementia/genetics/pathology ; }, abstract = {Healthy brain functioning requires a continuous fine-tuning of gene expression, involving changes in the epigenetic landscape and 3D chromatin organization. Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD) are three multifactorial neurodegenerative diseases (NDDs) that are partially explained by genetics (gene mutations and genetic risk factors) and influenced by non-genetic factors (i.e., aging, lifestyle, and environmental conditions). Examining comprehensive studies of global and locus-specific (epi)genomic and transcriptomic alterations in human and mouse brain samples at the cell-type resolution has uncovered important phenomena associated with AD. First, DNA methylation and histone marks at promoters contribute to transcriptional dysregulation of genes that are directly implicated in AD pathogenesis (i.e., APP), neuroplasticity and cognition (i.e., PSD95), and microglial activation (i.e., TREM2). Second, the presence of AD genetic risk variants in cell-type-specific distal enhancers (i.e., BIN1 in microglia) alters transcription, presumably by disrupting associated enhancer-promoter interactions and chromatin looping. Third, epigenomic erosion is associated with widespread transcriptional disruption and cell identity loss. And fourth, aging, high cholesterol, air pollution, and pesticides have emerged as potential drivers of AD by inducing locus-specific and global epigenetic modifications that impact key AD-related pathways. Epigenetic studies in ALS/FTD also provide evidence that genetic and non-genetic factors alter gene expression profiles in neurons and astrocytes through aberrant epigenetic mechanisms. We additionally overview the recent development of potential new therapeutic strategies involving (epi)genetic editing and the use of small chromatin-modifying molecules (epidrugs).}, }
@article {pmid39819742, year = {2025}, author = {Xu, B and Lei, X and Yang, Y and Yu, J and Chen, J and Xu, Z and Ye, K and Zhang, J}, title = {Peripheral proteinopathy in neurodegenerative diseases.}, journal = {Translational neurodegeneration}, volume = {14}, number = {1}, pages = {2}, pmid = {39819742}, issn = {2047-9158}, support = {82020108012//National Natural Science Foundation of China/ ; 82371250//National Natural Science Foundation of China/ ; LY24H090006//Natural Science Foundation of Zhejiang Province/ ; LZ23H090002//Natural Science Foundation of Zhejiang Province/ ; 2024C03098//Key Research and Development Program of Zhejiang Province/ ; 2024SSYS0018//Key Research and Development Program of Zhejiang Province/ ; ZR2022QH177//Natural Science Foundation of Shandong Province/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/therapy/pathology ; Animals ; Amyloid beta-Peptides/metabolism ; tau Proteins/metabolism ; alpha-Synuclein/metabolism ; }, abstract = {Proteinopathies in neurology typically refer to pathological changes in proteins associated with neurological diseases, such as the aggregation of amyloid β and Tau in Alzheimer's disease, α-synuclein in Parkinson's disease and multiple system atrophy, and TAR DNA-binding protein 43 in amyotrophic lateral sclerosis and frontotemporal dementia. Interestingly, these proteins are also commonly found in peripheral tissues, raising important questions about their roles in neurological disorders. Multiple studies have shown that peripherally derived pathological proteins not only travel to the brain through various routes, aggravating brain pathology, but also contribute significantly to peripheral dysfunction, highlighting their crucial impact on neurological diseases. Investigating how these peripherally derived proteins influence the progression of neurological disorders could open new horizons for achieving early diagnosis and treatment. This review summarizes the distribution, transportation pathways, and pathogenic mechanisms of several neurodegenerative disease-related pathological proteins in the periphery, proposing that targeting these peripheral pathological proteins could be a promising strategy for preventing and managing neurological diseases.}, }
@article {pmid39816800, year = {2025}, author = {Shokr, MM and Badawi, GA and Elshazly, SM and Zaki, HF and Mohamed, AF}, title = {Sigma 1 Receptor and Its Pivotal Role in Neurological Disorders.}, journal = {ACS pharmacology & translational science}, volume = {8}, number = {1}, pages = {47-65}, pmid = {39816800}, issn = {2575-9108}, abstract = {Sigma 1 receptor (S1R) is a multifunctional, ligand-activated protein located in the membranes of the endoplasmic reticulum (ER). It mediates a variety of neurological disorders, including epilepsy, amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease. The wide neuroprotective effects of S1R agonists are achieved by a variety of pro-survival and antiapoptotic S1R-mediated signaling functions. Nonetheless, relatively little is known about the specific molecular mechanisms underlying S1R activity. Many studies on S1R protein have highlighted the importance of maintaining normal cellular homeostasis through its control of calcium and lipid exchange between the ER and mitochondria, ER-stress response, and many other mechanisms. In this review, we will discuss S1R different cellular localization and explain S1R-associated biological activity, such as its localization in the ER-plasma membrane and Mitochondrion-Associated ER Membrane interfaces. While outlining the cellular mechanisms and important binding partners involved in these processes, we also explained how the dysregulation of these pathways contributes to neurodegenerative disorders.}, }
@article {pmid39809929, year = {2025}, author = {Antico, O and Thompson, PW and Hertz, NT and Muqit, MMK and Parton, LE}, title = {Targeting mitophagy in neurodegenerative diseases.}, journal = {Nature reviews. Drug discovery}, volume = {}, number = {}, pages = {}, pmid = {39809929}, issn = {1474-1784}, abstract = {Mitochondrial dysfunction is a hallmark of idiopathic neurodegenerative diseases, including Parkinson disease, amyotrophic lateral sclerosis, Alzheimer disease and Huntington disease. Familial forms of Parkinson disease and amyotrophic lateral sclerosis are often characterized by mutations in genes associated with mitophagy deficits. Therefore, enhancing the mitophagy pathway may represent a novel therapeutic approach to targeting an underlying pathogenic cause of neurodegenerative diseases, with the potential to deliver neuroprotection and disease modification, which is an important unmet need. Accumulating genetic, molecular and preclinical model-based evidence now supports targeting mitophagy in neurodegenerative diseases. Despite clinical development challenges, small-molecule-based approaches for selective mitophagy enhancement - namely, USP30 inhibitors and PINK1 activators - are entering phase I clinical trials for the first time.}, }
@article {pmid39801792, year = {2024}, author = {Ansari, U and Wen, J and Syed, B and Nadora, D and Sedighi, R and Nadora, D and Chen, V and Lui, F}, title = {Analyzing the potential of neuronal pentraxin 2 as a biomarker in neurological disorders: A literature review.}, journal = {AIMS neuroscience}, volume = {11}, number = {4}, pages = {505-519}, pmid = {39801792}, issn = {2373-7972}, abstract = {Neuronal pentraxin 2 (NP2) plays a significant role in synaptic plasticity, neuronal survival, and excitatory synapse regulation. Emerging research suggests that NP2 is implicated in the pathogenesis of various neurological disorders, including neurodegenerative diseases, neuropsychiatric disorders, and neuropathies. This literature review extensively analyzes NP2's role in these conditions, thereby highlighting its contributions to synaptic dysfunction, neuroinflammation, and neurotoxic protein aggregation. In Alzheimer's and Parkinson's diseases, NP2 is linked to amyloid-beta aggregation and dopaminergic neuron degeneration, respectively. Additionally, altered NP2 expression is observed in schizophrenia and bipolar disorder, thus suggesting its involvement in synaptic dysfunction and neurotransmitter imbalance. In neuropathic pain and epilepsy, NP2 modulates the synaptic plasticity and inflammatory responses, with altered levels correlating with disease severity. Furthermore, NP2's involvement in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) emphasizes its broad impact on neuronal health. Understanding NP2's multifaceted roles may reveal novel therapeutic targets and improve the clinical outcomes for these neurological disorders. Though the precise role of NP2 remains uncertain, its clinical potential and initial findings justify further investigations into neuronal pentraxins and other related neuroproteins.}, }
@article {pmid39799559, year = {2025}, author = {Üremiş, N and Üremiş, MM}, title = {Oxidative/Nitrosative Stress, Apoptosis, and Redox Signaling: Key Players in Neurodegenerative Diseases.}, journal = {Journal of biochemical and molecular toxicology}, volume = {39}, number = {1}, pages = {e70133}, pmid = {39799559}, issn = {1099-0461}, support = {//This research was supported by the Türkiye Bilimsel ve Teknolojik Araştırma Kurumu (grant number: TUB1)./ ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology ; *Apoptosis ; *Oxidative Stress ; *Nitrosative Stress ; *Oxidation-Reduction ; Animals ; *Signal Transduction ; Reactive Nitrogen Species/metabolism ; Reactive Oxygen Species/metabolism ; }, abstract = {Neurodegenerative diseases are significant health concerns that have a profound impact on the quality and duration of life for millions of individuals. These diseases are characterized by pathological changes in various brain regions, specific genetic mutations associated with the disease, deposits of abnormal proteins, and the degeneration of neurological cells. As neurodegenerative disorders vary in their epidemiological characteristics and vulnerability of neurons, treatment of these diseases is usually aimed at slowing disease progression. The heterogeneity of genetic and environmental factors involved in the process of neurodegeneration makes current treatment methods inadequate. However, the existence of common molecular mechanisms in the pathogenesis of these diseases may allow the development of new targeted therapeutic strategies. Oxidative and nitrosative stress damages membrane components by accumulating ROS and RNS and disrupting redox balance. This process results in the induction of apoptosis, which is important in the pathogenesis of neurodegenerative diseases through oxidative stress. Studies conducted using postmortem human samples, animal models, and cell cultures have demonstrated that oxidative stress, nitrosative stress, and apoptosis are crucial factors in the development of diseases such as Alzheimer's, Parkinson's, Multiple Sclerosis, amyotrophic lateral sclerosis, and Huntington's disease. The excessive production of reactive oxygen and nitrogen species, elevated levels of free radicals, heightened mitochondrial stress, disturbances in energy metabolism, and the oxidation and nitrosylation of cellular macromolecules are recognized as triggers for neuronal cell death. Challenges in managing and treating neurodegenerative diseases require a better understanding of this field at the molecular level. Therefore, this review elaborates on the molecular mechanisms by which oxidative and nitrosative stress are involved in neuronal apoptosis.}, }
@article {pmid39254482, year = {2025}, author = {García-Parra, B and Guiu, JM and Povedano, M and Modamio, P}, title = {A scoping review of the role of managed entry agreements in upcoming drugs for amyotrophic lateral sclerosis: learning from the case of spinal muscular atrophy.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {26}, number = {1-2}, pages = {48-57}, doi = {10.1080/21678421.2024.2400522}, pmid = {39254482}, issn = {2167-9223}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Muscular Atrophy, Spinal/drug therapy ; }, abstract = {INTRODUCTION: The therapeutic options for spinal muscular atrophy (SMA) are encouraging. However, there is currently no cure for amyotrophic lateral sclerosis (ALS). The clinical and economic uncertainty surrounding innovative treatments for rare neurodegenerative diseases makes it necessary to understand managed entry agreements (MEAs). The aim of this study was to review whether models of MEAs in SMA could be extrapolated to ALS.
METHODS: We performed a scoping review with information on MEAs on SMA in Web of Science (WOS), PubMed, Lyfegen Library, the National Institute for Health and Care Excellence (NICE), and the Canadian Agency for Drugs and Technologies in Health (CADTH).
RESULTS: We found 45 results in WOS and PubMed. After an initial survey, 10 were reviewed to assess eligibility, and three were selected. We obtained 44 results from Lyfegen Library, and three results each from NICE and CADTH.
CONCLUSION: The main objective of MEAs is to reduce uncertainty in the financing of drugs with a high budgetary impact and clinical concerns, as is the case with drugs for SMA and ALS. While the information available on MEAs in SMA is scarce, some conceptual models are publicly available. MEAs for long-term treatments for SMA could be used for the design of MEAs in ALS because of their similarities in economic and clinical uncertainty.}, }
@article {pmid39798853, year = {2025}, author = {Guan, D and Liang, C and Zheng, D and Liu, S and Luo, J and Cai, Z and Zhang, H and Chen, J}, title = {The role of mitochondrial remodeling in neurodegenerative diseases.}, journal = {Neurochemistry international}, volume = {183}, number = {}, pages = {105927}, doi = {10.1016/j.neuint.2024.105927}, pmid = {39798853}, issn = {1872-9754}, abstract = {Neurodegenerative diseases are a group of diseases that pose a serious threat to human health, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and Amyotrophic Lateral Sclerosis (ALS). In recent years, it has been found that mitochondrial remodeling plays an important role in the onset and progression of neurodegenerative diseases. Mitochondrial remodeling refers to the dynamic regulatory process of mitochondrial morphology, number and function, which can affect neuronal cell function and survival by regulating mechanisms such as mitochondrial fusion, division, clearance and biosynthesis. Mitochondrial dysfunction is an important intrinsic cause of the pathogenesis of neurodegenerative diseases. Mitochondrial remodeling abnormalities are involved in energy metabolism in neurodegenerative diseases. Pathological changes in mitochondrial function and morphology, as well as interactions with other organelles, can affect the energy metabolism of dopaminergic neurons and participate in the development of neurodegenerative diseases. Since the number of patients with PD and AD has been increasing year by year in recent years, it is extremely important to take effective interventions to significantly reduce the number of morbidities and to improve people's quality of life. More and more researchers have suggested that mitochondrial remodeling and related dynamics may positively affect neurodegenerative diseases in terms of neuronal and self-adaptation to the surrounding environment. Mitochondrial remodeling mainly involves its own fission and fusion, energy metabolism, changes in channels, mitophagy, and interactions with other cellular organelles. This review will provide a systematic summary of the role of mitochondrial remodeling in neurodegenerative diseases, with the aim of providing new ideas and strategies for further research on the treatment of neurodegenerative diseases.}, }
@article {pmid39796536, year = {2024}, author = {Cuffaro, F and Lamminpää, I and Niccolai, E and Amedei, A}, title = {Nutritional and Microbiota-Based Approaches in Amyotrophic Lateral Sclerosis: From Prevention to Treatment.}, journal = {Nutrients}, volume = {17}, number = {1}, pages = {}, pmid = {39796536}, issn = {2072-6643}, support = {PNRR-MAD-2022-12375798//Ministero della Salute/ ; PE0000006//Ministry of University and Research (MUR)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy ; Humans ; *Gastrointestinal Microbiome ; *Dysbiosis/therapy ; Probiotics/therapeutic use ; Brain-Gut Axis/physiology ; Fecal Microbiota Transplantation ; Fatty Acids, Omega-3 ; Prebiotics/administration & dosage ; Oxidative Stress ; Nutritional Status ; Diet, Mediterranean ; Antioxidants ; }, abstract = {Metabolic alterations, including hypermetabolism, lipid imbalances, and glucose dysregulation, are pivotal contributors to the onset and progression of Amyotrophic Lateral Sclerosis (ALS). These changes exacerbate systemic energy deficits, heighten oxidative stress, and fuel neuroinflammation. Simultaneously, gastrointestinal dysfunction and gut microbiota (GM) dysbiosis intensify disease pathology by driving immune dysregulation, compromising the intestinal barrier, and altering gut-brain axis (GBA) signaling, and lastly advancing neurodegeneration. Therapeutic and preventive strategies focused on nutrition offer promising opportunities to address these interconnected pathophysiological mechanisms. Diets enriched with antioxidants, omega-3 fatty acids, and anti-inflammatory compounds-such as the Mediterranean diet-have shown potential in reducing oxidative stress and systemic inflammation. Additionally, microbiota-targeted approaches, including probiotics, prebiotics, postbiotics, and fecal microbiota transplantation, are emerging as innovative tools to restore microbial balance, strengthen gut integrity, and optimize GBA function. This review highlights the critical need for personalized strategies integrating immunonutrition and microbiota modulation to slow ALS progression, improve quality of life, and develop preventive measures for neurodegenerative and neuroinflammatory diseases. Future research should prioritize comprehensive dietary and microbiota-based interventions to uncover their therapeutic potential and establish evidence-based guidelines for managing ALS and related disorders.}, }
@article {pmid39667295, year = {2025}, author = {Spencer, PS and Berntsson, SG and Buguet, A and Butterfield, P and Calne, DB and Calne, SM and Giménez-Roldán, S and Hugon, J and Kahlon, S and Kisby, GE and Lagrange, E and Landtblom, AE and Ludolph, AC and Nunn, PB and Palmer, VS and Reis, J and Román, GC and Sipilä, JOT and Spencer, SS and Angues, RV and Vernoux, JP and Yabushita, M}, title = {Brain health: Pathway to primary prevention of neurodegenerative disorders of environmental origin.}, journal = {Journal of the neurological sciences}, volume = {468}, number = {}, pages = {123340}, doi = {10.1016/j.jns.2024.123340}, pmid = {39667295}, issn = {1878-5883}, mesh = {Humans ; *Neurodegenerative Diseases/epidemiology/prevention & control/etiology ; *Primary Prevention/methods ; Brain ; Environmental Exposure/adverse effects ; Amyotrophic Lateral Sclerosis/epidemiology/prevention & control ; Environment ; }, abstract = {While rising global rates of neurodegenerative disease encourage early diagnosis and therapeutic intervention to block clinical expression (secondary prevention), a more powerful approach is to identify and remove environmental factors that trigger long-latencybrain disease (primary prevention) by acting on a susceptible genotype or acting alone. The latter is illustrated by the post-World War II decline and disappearance of Amyotrophic Lateral Sclerosis and Parkinsonism-Dementia Complex (ALS/PDC), a prototypical often-familial neurodegenerative disease formerly present in very high incidence on the island of Guam. Lessons learned from 75 years of investigation on the etiology of ALS/PDC include: the importance of focusing field research on the disease epicenter and patients with early-onset disease; soliciting exposure history from patients, family, and community to guide multidisciplinary biomedical investigation; recognition that disease phenotype may vary with exposure history, and that familial brain disease may have a primarily environmental origin. Furthermore, removal from exposure to the environmental trigger effects primary disease prevention.}, }
@article {pmid39792201, year = {2025}, author = {Fu, Z and Feng, B and Akogo, HY and Ma, J and Liu, Y and Quan, H and Zhang, X and Hou, Y and Zhang, X and Ma, J and Cui, H}, title = {Amyotrophic Lateral Sclerosis and Parkinson's Disease: Brain Tissue Transcriptome Analysis Reveals Interactions.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {39792201}, issn = {1559-1182}, support = {81801278//National Natural Science Foundation of China/ ; }, abstract = {This study utilises amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) human brain samples from the GEO database and employs differential expression gene (DEG) analysis to identify genes that are pivotal in both neurodegenerative diseases. Through in depth GO and KEGG enrichment analyses, we elucidated the biological functions and potential pathways associated with these DEGs. Furthermore, by constructing protein‒protein interaction networks, we highlight the significance of shared DEGs in both cellular physiology and disease contexts. Analysis of drug‒gene associations revealed potential therapeutic compounds linked to ALS and PD treatment. Additionally, we explored the interactions between transcription factors, miRNAs, and common DEGs, revealing aspects of gene regulatory networks. This study provides insights into the molecular mechanisms of ALS and PD, offering valuable contributions to ongoing research and potential therapeutic avenues.}, }
@article {pmid39791748, year = {2025}, author = {Moss, KR and Saxena, S}, title = {Schwann Cells in Neuromuscular Disorders: A Spotlight on Amyotrophic Lateral Sclerosis.}, journal = {Cells}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/cells14010047}, pmid = {39791748}, issn = {2073-4409}, mesh = {*Schwann Cells/pathology/metabolism ; *Amyotrophic Lateral Sclerosis/pathology ; Humans ; Animals ; Neuromuscular Diseases/pathology ; Motor Neurons/pathology/metabolism ; Charcot-Marie-Tooth Disease/pathology ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disease primarily affecting motor neurons, leading to progressive muscle atrophy and paralysis. This review explores the role of Schwann cells in ALS pathogenesis, highlighting their influence on disease progression through mechanisms involving demyelination, neuroinflammation, and impaired synaptic function. While Schwann cells have been traditionally viewed as peripheral supportive cells, especially in motor neuron disease, recent evidence indicates that they play a significant role in ALS by impacting motor neuron survival and plasticity, influencing inflammatory responses, and altering myelination processes. Furthermore, advancements in understanding Schwann cell pathology in ALS combined with lessons learned from studying Charcot-Marie-Tooth disease Type 1 (CMT1) suggest potential therapeutic strategies targeting these cells may support nerve repair and slow disease progression. Overall, this review aims to provide comprehensive insights into Schwann cell classification, physiology, and function, underscoring the critical pathological contributions of Schwann cells in ALS and suggests new avenues for targeted therapeutic interventions aimed at modulating Schwann cell function in ALS.}, }
@article {pmid39791705, year = {2024}, author = {Sun, D and Amiri, M and Meng, Q and Unnithan, RR and French, C}, title = {Calcium Signalling in Neurological Disorders, with Insights from Miniature Fluorescence Microscopy.}, journal = {Cells}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/cells14010004}, pmid = {39791705}, issn = {2073-4409}, support = {DP170100363//Australian Research Council under Discovery Project/ ; }, mesh = {*Calcium Signaling ; Humans ; *Nervous System Diseases/metabolism/pathology ; Animals ; *Microscopy, Fluorescence/methods ; Calcium/metabolism ; Neurons/metabolism ; }, abstract = {Neurological disorders (NDs), such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and schizophrenia, represent a complex and multifaceted health challenge that affects millions of people around the world. Growing evidence suggests that disrupted neuronal calcium signalling contributes to the pathophysiology of NDs. Additionally, calcium functions as a ubiquitous second messenger involved in diverse cellular processes, from synaptic activity to intercellular communication, making it a potential therapeutic target. Recently, the development of the miniature fluorescence microscope (miniscope) enabled simultaneous recording of the spatiotemporal calcium activity from large neuronal ensembles in unrestrained animals, providing a novel method for studying NDs. In this review, we discuss the abnormalities observed in calcium signalling and its potential as a therapeutic target for NDs. Additionally, we highlight recent studies that utilise miniscope technology to investigate the alterations in calcium dynamics associated with NDs.}, }
@article {pmid39788313, year = {2025}, author = {Cassina, P and Miquel, E and Martínez-Palma, L and Cassina, A}, title = {Mitochondria and astrocyte reactivity: Key mechanism behind neuronal injury.}, journal = {Neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.neuroscience.2024.12.058}, pmid = {39788313}, issn = {1873-7544}, abstract = {In this special issue to celebrate the 30th anniversary of the Uruguayan Society for Neuroscience (SNU), we find it pertinent to highlight that research on glial cells in Uruguay began almost alongside the history of SNU and contributed to the understanding of neuron-glia interactions within the international scientific community. Glial cells, particularly astrocytes, traditionally regarded as supportive components in the central nervous system (CNS), undergo notable morphological and functional alterations in response to neuronal damage, a phenomenon referred to as glial reactivity. Among the myriad functions of astrocytes, metabolic support holds significant relevance for neuronal function, given the high energy demand of the nervous system. Although astrocytes are typically considered to exhibit low mitochondrial respiratory chain activity, they possess a noteworthy mitochondrial network. Interestingly, both the morphology and activity of these organelles change following glial reactivity. Despite receiving less attention compared to studies on neuronal mitochondria, recent studies indicate that mitochondria play a crucial role in driving the transition of astrocytes from a quiescent to a reactive state in various neurological disorders. Notably, stimulating mitochondria in astrocytes has been shown to reduce damage associated with the neurodegenerative disease amyotrophic lateral sclerosis. Here, we focus on studies supporting the emerging paradigm that metabolic reprogramming occurs in astrocytes following damage, which is associated with their phenotypic shift to a new functional state that significantly influences the progression of pathology. Thus, exploring mitochondrial activity and metabolic reprogramming within glial cells may provide valuable insights for developing innovative therapeutic approaches to mitigate neuronal damage.In this review, we focus on studies supporting the emerging paradigm that metabolic reprogramming occurs in astrocytes following damage, which is associated with their phenotypic shift to a new functional state that significantly influences the progression of pathology. Thus, exploring mitochondrial activity and metabolic reprogramming within glial cells may provide valuable insights for developing innovative therapeutic approaches to mitigate neuronal damage.}, }
@article {pmid39785706, year = {2024}, author = {Esteve, AS}, title = {Biomarkers.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {20 Suppl 2}, number = {}, pages = {e083410}, doi = {10.1002/alz.083410}, pmid = {39785706}, issn = {1552-5279}, mesh = {Humans ; *Biomarkers/cerebrospinal fluid/blood ; DNA-Binding Proteins ; Frontotemporal Dementia/diagnosis ; Neurodegenerative Diseases/diagnosis/cerebrospinal fluid ; Amyotrophic Lateral Sclerosis/diagnosis ; Proteomics ; }, abstract = {Transactive response DNA-binding protein 43 (TDP-43) has emerged as a pivotal player in neurodegenerative diseases, particularly amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and the recently described limbic-predominant age-related TDP-43 encephalopathy (LATE). Detecting TDP-43 pathology in a minimally invasive manner is crucial for early diagnosis, monitoring disease progression and the assessment of therapeutic interventions. This talk explores recent advancements in the discovery and validation of novel biofluid measures aimed at detecting and characterising TDP-43 pathology. The era of proteomics has paved the way for the identification and validation of TDP-43 biomarkers in biofluids. This presentation highlights the latest discoveries, encompassing both established and newly discovered candidates within cerebrospinal fluid (CSF) and blood. As the field progresses, the integration of these measures into clinical practice may revolutionise our approach to neurodegenerative diseases bringing us closer to effective treatments and improved patient care.}, }
@article {pmid39777244, year = {2025}, author = {Moura, FA and Siqueira, AIAN}, title = {Gut-liver axis in sepsis-associated liver injury: Epidemiology, challenges and clinical practice.}, journal = {World journal of gastroenterology}, volume = {31}, number = {1}, pages = {99987}, doi = {10.3748/wjg.v31.i1.99987}, pmid = {39777244}, issn = {2219-2840}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Sepsis/complications/epidemiology ; *Dysbiosis ; *Liver/metabolism/pathology ; Animals ; *Oxidative Stress ; Bacterial Translocation ; Liver Diseases/epidemiology/microbiology ; Critical Illness ; Intensive Care Units/statistics & numerical data ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {Although the liver has a remarkable regenerative capacity, sepsis-associated liver injury (SLI) is a complication often seen in intensive care units. Due to its role in immune and inflammatory regulation, the liver is particularly vulnerable during severe infections. Understanding the global prevalence, causes, and management of SLI is essential to improve outcomes and reduce healthcare costs. This paper aims to explore these factors, with an emphasis on identifying effective strategies for clinical management. Zhang et al's bibliometric analysis of 787 publications (745 original articles and 42 reviews, mostly in animal models) from 2000 to 2023 highlights the growing interest in SLI, focusing on oxidative stress, gut microbiota, and inflammatory processes. Key components such as nuclear factor-kappa B and the NOD-like receptor thermal protein domain associated protein 3 inflammasome pathway, along with their links to gut microbiota imbalance and oxidative stress, are crucial for understanding SLI pathogenesis. The gut-liver axis, particularly the role of intestinal permeability and bacterial translocation in liver inflammation, is emphasized. In this context, bacterial translocation is especially relevant for critically ill patients, as it can exacerbate liver inflammation. The findings underscore the need for integrated care in intensive care units, prioritizing gut health and careful antibiotic use to prevent dysbiosis. Despite extensive research, there remains a lack of clinical trials to validate therapeutic approaches. The abundance of experimental studies highlights potential therapeutic targets, stressing the need for high-quality randomized clinical trials to translate these findings into clinical practice.}, }
@article {pmid39775908, year = {2025}, author = {de Vries, E and Hagbohm, C and Ouellette, R and Granberg, T}, title = {Clinical 7 Tesla magnetic resonance imaging: Impact and patient value in neurological disorders.}, journal = {Journal of internal medicine}, volume = {}, number = {}, pages = {}, doi = {10.1111/joim.20059}, pmid = {39775908}, issn = {1365-2796}, abstract = {Magnetic resonance imaging (MRI) is a cornerstone of non-invasive diagnostics and treatment monitoring, particularly for diseases of the central nervous system. Although 1.5- and 3 Tesla (T) field strengths remain the clinical standard, the advent of 7 T MRI represents a transformative step forward, offering superior spatial resolution, contrast, and sensitivity for visualizing neuroanatomy, metabolism, and function. Recent innovations, including parallel transmission and deep learning-based reconstruction, have resolved many prior technical challenges of 7 T MRI, enabling its routine clinical use. This review examines the diagnostic impact, patient value, and practical considerations of 7 T MRI, emphasizing its role in facilitating earlier diagnoses and improving care in conditions, such as amyotrophic lateral sclerosis (ALS), epilepsy, multiple sclerosis (MS), dementia, parkinsonism, tumors, and vascular diseases. Based on insights from over 1200 clinical scans with a second-generation 7 T system, the review highlights disease-specific biomarkers such as the motor band sign in ALS and the new diagnostic markers in MS, the central vein sign, and paramagnetic rim lesions. The unparalleled ability of 7 T MRI to study neurological diseases ex vivo at ultra-high resolution is also explored, offering new opportunities to understand pathophysiology and identify novel treatment targets. Additionally, the review provides a clinical perspective on patient handling and safety considerations, addressing challenges and practicalities associated with clinical 7 T MRI. By bridging research and clinical practice, 7 T MRI has the potential to redefine neuroimaging and advance the understanding and management of complex neurological disorders.}, }
@article {pmid39770989, year = {2024}, author = {Pekdemir, B and Raposo, A and Saraiva, A and Lima, MJ and Alsharari, ZD and BinMowyna, MN and Karav, S}, title = {Mechanisms and Potential Benefits of Neuroprotective Agents in Neurological Health.}, journal = {Nutrients}, volume = {16}, number = {24}, pages = {}, doi = {10.3390/nu16244368}, pmid = {39770989}, issn = {2072-6643}, mesh = {Humans ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Neurodegenerative Diseases/drug therapy ; Brain/drug effects/metabolism ; Animals ; Flavonoids/pharmacology/therapeutic use ; Apoptosis/drug effects ; Antioxidants/pharmacology/therapeutic use ; Oxidative Stress/drug effects ; }, abstract = {The brain contains many interconnected and complex cellular and molecular mechanisms. Injury to the brain causes permanent dysfunctions in these mechanisms. So, it continues to be an area where surgical intervention cannot be performed except for the removal of tumors and the repair of some aneurysms. Some agents that can cross the blood-brain barrier and reach neurons show neuroprotective effects in the brain due to their anti-apoptotic, anti-inflammatory and antioxidant properties. In particular, some agents act by reducing or modulating the accumulation of protein aggregates in neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, and prion disease) caused by protein accumulation. Substrate accumulation causes increased oxidative stress and stimulates the brain's immune cells, microglia, and astrocytes, to secrete proinflammatory cytokines. Long-term or chronic neuroinflammatory response triggers apoptosis. Brain damage is observed with neuronal apoptosis and brain functions are impaired. This situation negatively affects processes such as motor movements, memory, perception, and learning. Neuroprotective agents prevent apoptosis by modulating molecules that play a role in apoptosis. In addition, they can improve impaired brain functions by supporting neuroplasticity and neurogenesis. Due to the important roles that these agents play in central nervous system damage or neurodegenerative diseases, it is important to elucidate many mechanisms. This review provides an overview of the mechanisms of flavonoids, which constitute a large part of the agents with neuroprotective effects, as well as vitamins, neurotransmitters, hormones, amino acids, and their derivatives. It is thought that understanding these mechanisms will enable the development of new therapeutic agents and different treatment strategies.}, }
@article {pmid39769209, year = {2024}, author = {Xing, C and Chen, H and Bi, W and Lei, T and Hang, Z and Du, H}, title = {Targeting 5-HT Is a Potential Therapeutic Strategy for Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {24}, pages = {}, doi = {10.3390/ijms252413446}, pmid = {39769209}, issn = {1422-0067}, support = {32300682//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Serotonin/metabolism ; *Neurodegenerative Diseases/metabolism/drug therapy ; Animals ; Alzheimer Disease/metabolism/drug therapy ; Amyotrophic Lateral Sclerosis/metabolism/drug therapy ; Parkinson Disease/metabolism/drug therapy ; Receptors, Serotonin/metabolism ; }, abstract = {There is increasing interest in the potential therapeutic role of 5-HT (serotonin) in the treatment of neurodegenerative diseases, which are characterized by the progressive degeneration and death of nerve cells. 5-HT is a vital neurotransmitter that plays a central role in regulating mood, cognition, and various physiological processes in the body. Disruptions in the 5-HT system have been linked to several neurological and psychiatric disorders, making it an attractive target for therapeutic intervention. Although the exact causes of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are not fully understood, researchers believe that regulating the 5-HT system could help alleviate symptoms and potentially slow the progression of these diseases. Here, we delve into the potential of harnessing 5-HT as a therapeutic target for the treatment of neurodegenerative diseases. It is important to note that the current clinical drugs targeting 5-HT are still limited in the treatment of these complex diseases. Therefore, further research and clinical trials are needed to evaluate the feasibility and effectiveness of its clinical application.}, }
@article {pmid39769187, year = {2024}, author = {O'Day, DH}, title = {The Search for a Universal Treatment for Defined and Mixed Pathology Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {24}, pages = {}, doi = {10.3390/ijms252413424}, pmid = {39769187}, issn = {1422-0067}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology/therapy ; *tau Proteins/metabolism ; *Amyloid beta-Peptides/metabolism ; alpha-Synuclein/metabolism ; RNA-Binding Protein FUS/metabolism/genetics ; Huntingtin Protein/metabolism/genetics ; Protein Glutamine gamma Glutamyltransferase 2 ; Biomarkers/metabolism ; Transglutaminases/metabolism ; Superoxide Dismutase-1/metabolism/genetics ; Animals ; Calmodulin/metabolism ; DNA-Binding Proteins/metabolism/genetics ; Alzheimer Disease/metabolism/pathology/drug therapy/therapy ; Parkinson Disease/metabolism/pathology/therapy ; }, abstract = {The predominant neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, dementia with Lewy Bodies, Huntington's disease, amyotrophic lateral sclerosis, and frontotemporal dementia, are rarely pure diseases but, instead, show a diversity of mixed pathologies. At some level, all of them share a combination of one or more different toxic biomarker proteins: amyloid beta (Aβ), phosphorylated Tau (pTau), alpha-synuclein (αSyn), mutant huntingtin (mHtt), fused in sarcoma, superoxide dismutase 1, and TAR DNA-binding protein 43. These toxic proteins share some common attributes, making them potentially universal and simultaneous targets for therapeutic intervention. First, they all form toxic aggregates prior to taking on their final forms as contributors to plaques, neurofibrillary tangles, Lewy bodies, and other protein deposits. Second, the primary enzyme that directs their aggregation is transglutaminase 2 (TGM2), a brain-localized enzyme involved in neurodegeneration. Third, TGM2 binds to calmodulin, a regulatory event that can increase the activity of this enzyme threefold. Fourth, the most common mixed pathology toxic biomarkers (Aβ, pTau, αSyn, nHtt) also bind calmodulin, which can affect their ability to aggregate. This review examines the potential therapeutic routes opened up by this knowledge. The end goal reveals multiple opportunities that are immediately available for universal therapeutic treatment of the most devastating neurodegenerative diseases facing humankind.}, }
@article {pmid39768371, year = {2024}, author = {Orlova, A and Malygin, Y and Gofman, A and Sotulenko, S and Gandalian, V and Kartashov, I and Brylev, L and Bolevich, S and Nikolic Turnic, T and Jakovljevic, V}, title = {Survival Prognostic Factors of Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis: A Systematic Review.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {12}, pages = {}, doi = {10.3390/life14121664}, pmid = {39768371}, issn = {2075-1729}, abstract = {OBJECTIVE: Amyotrophic lateral sclerosis is a neurodegenerative disease with high rates of disability and mortality. Non-invasive ventilation (NIV) is an effective method of treating patients, increasing life expectancy, but currently, predictors available to determine the best outcome of therapy in this category of patients are unknown. This systematic review aimed to determine the impact of prognostic factors on benefits from NIV application compared with non-NIV tools of treatment (invasive ventilation and standard care) in case of survival of ALS patients.
METHOD: We systematically sought relevant longitudinal cohort and case-control studies published in PubMed, CINAHL/EMBASE, Cochrane library, and Scopus.
RESULTS: We included seven prospective studies, published in 2010-2020, in the analysis. According to the evidence base available to date, NIV favors survival compared to non-NIV in patients with bulbar onset ALS. We obtained conflicting data on the significance of spinal onset and bulbar function. Survival depending on patient age, and also for spinal, cervical, and flail limb phenotypes during NIV therapy has not been sufficiently studied and needs further investigation.
CONCLUSIONS: The studies analyzed in this review allow us to state with confidence that NIV is effective in bulbar onset ALS, taking into account recommendations for duration of ventilation and the use of the full range of symptomatic therapy, including mechanically assisted coughing. The effectiveness of NIV on severe bulbar symptoms requires further research.}, }
@article {pmid39768167, year = {2024}, author = {Chen, X and Lv, S and Liu, J and Guan, Y and Xu, C and Ma, X and Li, M and Bai, X and Liu, K and Zhang, H and Yan, Q and Zhou, F and Chen, Y}, title = {Exploring the Role of Axons in ALS from Multiple Perspectives.}, journal = {Cells}, volume = {13}, number = {24}, pages = {}, doi = {10.3390/cells13242076}, pmid = {39768167}, issn = {2073-4409}, support = {82271483//The National Natural Science Foundation of China/ ; ZR2024MH112; ZR2024QH628//Shandong Province Natural Science Foundation of China/ ; 2023YX036; 2022YX043//Weifang Science and Technology Development Plan Project/ ; }, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; *Axons/pathology/metabolism ; Animals ; Axonal Transport ; Motor Neurons/pathology ; Disease Progression ; }, abstract = {Amyotrophic lateral sclerosis (ALS), commonly known as motor neuron disease, is a neurodegenerative disorder characterized by the progressive degeneration of both upper and lower motor neurons. This pathological process results in muscle weakness and can culminate in paralysis. To date, the precise etiology of ALS remains unclear. However, a burgeoning body of research indicates that axonal dysfunction is a pivotal element in the pathogenesis of ALS and significantly influences the progression of disease. Dysfunction of axons in ALS can result in impediments to nerve impulse transmission, leading to motor impairment, muscle atrophy, and other associated complications that severely compromise patients' quality of life and survival prognosis. In this review, we concentrate on several key areas: the ultrastructure of axons, the mechanisms of axonal degeneration in ALS, the impact of impaired axonal transport on disease progression in ALS, and the potential for axonal regeneration within the central nervous system (CNS). Our objective is to achieve a more holistic and profound understanding of the multifaceted role that axons play in ALS, thereby offering a more intricate and refined perspective on targeted axonal therapeutic interventions.}, }
@article {pmid39766450, year = {2024}, author = {Donaghy, R and Pioro, EP}, title = {Neurophysiologic Innovations in ALS: Enhancing Diagnosis, Monitoring, and Treatment Evaluation.}, journal = {Brain sciences}, volume = {14}, number = {12}, pages = {}, doi = {10.3390/brainsci14121251}, pmid = {39766450}, issn = {2076-3425}, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive disease of both upper motor neurons (UMNs) and lower motor neurons (LMNs) leading invariably to decline in motor function. The clinical exam is foundational to the diagnosis of the disease, and ordinal severity scales are used to track its progression. However, the lack of objective biomarkers of disease classification and progression delay clinical trial enrollment, muddle inclusion criteria, and limit accurate assessment of drug efficacy. Ultimately, biomarker evidence of therapeutic target engagement will support, and perhaps supplant, more traditional clinical trial outcome measures. Electrophysiology tools including nerve conduction study and electromyography (EMG) have already been established as diagnostic biomarkers of LMN degeneration in ALS. Additional understanding of the motor manifestations of disease is provided by motor unit number estimation, electrical impedance myography, and single-fiber EMG techniques. Dysfunction of UMN and non-motor brain areas is being increasingly assessed with transcranial magnetic stimulation, high-density electroencephalography, and magnetoencephalography; less common autonomic and sensory nervous system dysfunction in ALS can also be characterized. Although most of these techniques are used to explore the underlying disease mechanisms of ALS in research settings, they have the potential on a broader scale to noninvasively identify disease subtypes, predict progression rates, and assess physiologic engagement of experimental therapies.}, }
@article {pmid39766276, year = {2024}, author = {Wysoczański, B and Świątek, M and Wójcik-Gładysz, A}, title = {Organ-on-a-Chip Models-New Possibilities in Experimental Science and Disease Modeling.}, journal = {Biomolecules}, volume = {14}, number = {12}, pages = {}, doi = {10.3390/biom14121569}, pmid = {39766276}, issn = {2218-273X}, mesh = {*Lab-On-A-Chip Devices ; Humans ; Animals ; Models, Biological ; Liver/metabolism/cytology ; Cell Culture Techniques/methods ; Microphysiological Systems ; }, abstract = {'Organ-on-a-chip' technology is a promising and rapidly evolving model in biological research. This innovative microfluidic cell culture device was created using a microchip with continuously perfused chambers, populated by living cells arranged to replicate physiological processes at the tissue and organ levels. By consolidating multicellular structures, tissue-tissue interfaces, and physicochemical microenvironments, these microchips can replicate key organ functions. They also enable the high-resolution, real-time imaging and analysis of the biochemical, genetic, and metabolic activities of living cells in the functional tissue and organ contexts. This technology can accelerate research into tissue development, organ physiology and disease etiology, therapeutic approaches, and drug testing. It enables the replication of entire organ functions (e.g., liver-on-a-chip, hypothalamus-pituitary-on-a-chip) or the creation of disease models (e.g., amyotrophic lateral sclerosis-on-a-chip, Parkinson's disease-on-a-chip) using specialized microchips and combining them into an integrated functional system. This technology allows for a significant reduction in the number of animals used in experiments, high reproducibility of results, and the possibility of simultaneous use of multiple cell types in a single model. However, its application requires specialized equipment, advanced expertise, and currently incurs high costs. Additionally, achieving the level of standardization needed for commercialization remains a challenge at this stage of development.}, }
@article {pmid39714593, year = {2024}, author = {Eldeeb, MA and Hohman, G and Shahid, M}, title = {Novel Approaches in Targeting Cell Surface and Secreted Proteins for Lysosomal Degradation.}, journal = {Chembiochem : a European journal of chemical biology}, volume = {}, number = {}, pages = {e202400887}, doi = {10.1002/cbic.202400887}, pmid = {39714593}, issn = {1439-7633}, abstract = {Protein degradation is pivotal for all biochemical aspects of cellular function. In mammalian cells, protein degradation is mediated mainly by the ubiquitin proteasome system (UPS) and the autophagic-lysosomal system (ALS). Over the last two decades, different types of targeted protein degradation approaches have been developed including proteolysis targeting chimeras (PROTACs) and lysosome targeting chimeras (LYTACs), which employ the UPS to degrade intracellular proteins and the ALS to degrade extracellular and membrane proteins respectively. Nevertheless, Current targeted membrane protein degradation approaches face some inherent challenges including limited target protein degradation efficacy and cell type specific applicability. Herein, we highlight some recent developments of novel targeted membrane protein degradation modalities that exhibit wide-applicability and high protein degradation efficiency. These novel membrane protein degraders hold tremendous promise as new pharmacological and biochemical tools in targeting membrane and secretory proteins for lysosomal degradation.}, }
@article {pmid39759457, year = {2024}, author = {Ahmad, SR and Zeyaullah, M and Khan, MS and AlShahrani, AM and Altijani, AAG and Ali, H and Dawria, A and Mohieldin, A and Alam, MS and Mohamed, AOA}, title = {Pharmacogenomics for neurodegenerative disorders - a focused review.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1478964}, pmid = {39759457}, issn = {1663-9812}, abstract = {Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) are characterized by the progressive degeneration of neuronal structure and function, leading to severe cognitive and motor impairments. These conditions present significant challenges to healthcare systems, and traditional treatments often fail to account for genetic variability among patients, resulting in inconsistent therapeutic outcomes. Pharmacogenomics aims to tailor medical treatments based on an individual's genetic profile, thereby improving therapeutic efficacy and reducing adverse effects. This focused review explores the genetic factors influencing drug responses in neurodegenerative diseases and the potential of pharmacogenomics to revolutionize their treatment. Key genetic markers, such as the APOE ε4 allele in AD and the CYP2D6 polymorphisms in PD, are highlighted for their roles in modulating drug efficacy. Additionally, advancements in pharmacogenomic tools, including genome-wide association studies (GWAS), next-generation sequencing (NGS), and CRISPR-Cas9, are discussed for their contributions to personalized medicine. The application of pharmacogenomics in clinical practice and its prospects, including ethical and data integration challenges, are also examined.}, }
@article {pmid39756021, year = {2025}, author = {Akaree, N and Secco, V and Levy-Adam, F and Younis, A and Carra, S and Shalgi, R}, title = {Regulation of physiological and pathological condensates by molecular chaperones.}, journal = {The FEBS journal}, volume = {}, number = {}, pages = {}, doi = {10.1111/febs.17390}, pmid = {39756021}, issn = {1742-4658}, support = {//AriSLA/ ; //Giovanni Armenise Harvard Foundation/ ; HT94252310319//Congressionally Directed Medical Research Programs/ ; AHA-MCA 2022//AriAlzh/ ; //Rappaport Family Institute for Research in Medical Sciences/ ; //Prince Center for Neurodegenerative Disorders of the Brain/ ; }, abstract = {Biomolecular condensates are dynamic membraneless compartments that regulate a myriad of cellular functions. A particular type of physiological condensate called stress granules (SGs) has gained increasing interest due to its role in the cellular stress response and various diseases. SGs, composed of several hundred RNA-binding proteins, form transiently in response to stress to protect mRNAs from translation and disassemble when the stress subsides. Interestingly, SGs contain several aggregation-prone proteins, such as TDP-43, FUS, hnRNPA1, and others, which are typically found in pathological inclusions seen in autopsy tissues from amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients. Moreover, mutations in these genes lead to the familial form of ALS and FTD. This has led researchers to propose that pathological aggregation is seeded by aberrant SGs: SGs that fail to properly disassemble, lose their dynamic properties, and become pathological condensates which finally 'mature' into aggregates. Here, we discuss the evidence supporting this model for various ALS/FTD-associated proteins. We further continue to focus on molecular chaperone-mediated regulation of ALS/FTD-associated physiological condensates on one hand, and pathological condensates on the other. In addition to SGs, we review ALS/FTD-relevant nuclear condensates, namely paraspeckles, anisosomes, and nucleolar amyloid bodies, and discuss their emerging regulation by chaperones. As the majority of chaperoning mechanisms regulate physiological condensate disassembly, we highlight parallel themes of physiological and pathological condensation regulation across different chaperone families, underscoring the potential for early disease intervention.}, }
@article {pmid39753993, year = {2025}, author = {Cheng, L and Liu, Z and Shen, C and Xiong, Y and Shin, SY and Hwang, Y and Yang, SB and Chen, Z and Zhang, X}, title = {A Wonderful Journey: The Diverse Roles of Adenosine Deaminase Action on RNA 1 (ADAR1) in Central Nervous System Diseases.}, journal = {CNS neuroscience & therapeutics}, volume = {31}, number = {1}, pages = {e70208}, doi = {10.1111/cns.70208}, pmid = {39753993}, issn = {1755-5949}, support = {20224BAB216045//Youth Foundation of Natural Science Foundation of Jiangxi Province/ ; GJJ211812//Science and Technology Project Funded by the Education Department of Jiangxi Province/ ; GJJ211813//Science and Technology Project Funded by the Education Department of Jiangxi Province/ ; 202131084//Jiangxi Provincial Health Commission Science and Technology Plan Project/ ; 202211982//Jiangxi Provincial Health Commission Science and Technology Plan Project/ ; RZYB202201//Research project of Cognitive Science and Transdisciplinary Studies Center of Jiangxi Province/ ; 20224BAB206040//Provincial Natural Science Foundation of Jiangxi Province/ ; 202411843024//Foundation of Students' Platform for Innovation and Entrepreneurship Training Program/ ; S202411843050//Foundation of Students' Platform for Innovation and Entrepreneurship Training Program/ ; 2022B1010//Administration of Traditional Chinese Medicine of Jiangxi Province/ ; }, abstract = {BACKGROUND: Adenosine deaminase action on RNA 1 (ADAR1) can convert the adenosine in double-stranded RNA (dsRNA) molecules into inosine in a process known as A-to-I RNA editing. ADAR1 regulates gene expression output by interacting with RNA and other proteins; plays important roles in development, including growth; and is linked to innate immunity, tumors, and central nervous system (CNS) diseases.
RESULTS: In recent years, the role of ADAR1 in tumors has been widely discussed, but its role in CNS diseases has not been reviewed. It is worth noting that recent studies have shown ADAR1 has great potential in the treatment of neurodegenerative diseases, but the mechanisms are still unclear. Therefore, it is necessary to elaborate on the role of ADAR1 in CNS diseases.
CONCLUSIONS: Here, we focus on the effects and mechanisms of ADAR1 on CNS diseases such as Aicardi-AicardiGoutières syndrome, Alzheimer's disease, Parkinson's disease, glioblastoma, epilepsy, amyotrophic lateral sclerosis, and autism. We also evaluate the impact of ADAR1-based treatment strategies on these diseases, with a particular focus on the development and treatment strategies of new technologies such as microRNAs, nanotechnology, gene editing, and stem cell therapy. We hope to provide new directions and insights for the future development of ADAR1 gene editing technology in brain science and the treatment of CNS diseases.}, }
@article {pmid39753182, year = {2025}, author = {Swarup, G and Medchalmi, S and Ramachandran, G and Sayyad, Z}, title = {Molecular aspects of cytoprotection by Optineurin during stress and disease.}, journal = {Biochimica et biophysica acta. Molecular cell research}, volume = {}, number = {}, pages = {119895}, doi = {10.1016/j.bbamcr.2024.119895}, pmid = {39753182}, issn = {1879-2596}, abstract = {Optineurin/OPTN is an adapter protein that plays a crucial role in mediating many cellular functions, including autophagy, vesicle trafficking, and various signalling pathways. Mutations of OPTN are linked with neurodegenerative disorders, glaucoma, and amyotrophic lateral sclerosis (ALS). Recent work has shown that OPTN provides cytoprotection from many types of stress, including oxidative stress, endoplasmic reticulum stress, protein homeostasis stress, tumour necrosis factor α, and microbial infection. Here, we discuss the mechanisms involved in cytoprotective functions of OPTN, which possibly depend on its ability to modulate various stress-induced signalling pathways. ALS- and glaucoma-causing mutants of OPTN are altered in this regulation, which may affect cell survival, particularly under various stress conditions. We suggest that OPTN deficiency created by mutations may cooperate with stress-induced signalling to enhance or cause neurodegeneration. Other functions of OPTN, such as neurotrophin secretion and vesicle trafficking, may also contribute to cytoprotection.}, }
@article {pmid39743546, year = {2025}, author = {Faller, KME and Chaytow, H and Gillingwater, TH}, title = {Targeting common disease pathomechanisms to treat amyotrophic lateral sclerosis.}, journal = {Nature reviews. Neurology}, volume = {}, number = {}, pages = {}, pmid = {39743546}, issn = {1759-4766}, abstract = {The motor neuron disease amyotrophic lateral sclerosis (ALS) is a devastating condition with limited treatment options. The past few years have witnessed a ramping up of translational ALS research, offering the prospect of disease-modifying therapies. Although breakthroughs using gene-targeted approaches have shown potential to treat patients with specific disease-causing mutations, the applicability of such therapies remains restricted to a minority of individuals. Therapies targeting more general mechanisms that underlie motor neuron pathology in ALS are therefore of considerable interest. ALS pathology is associated with disruption to a complex array of key cellular pathways, including RNA processing, proteostasis, metabolism and inflammation. This Review details attempts to restore cellular homeostasis by targeting these pathways in order to develop effective, broadly-applicable ALS therapeutics.}, }
@article {pmid39743215, year = {2024}, author = {Chiu, Y and Xia, S and Qiao, H and Zhao, Z}, title = {Genetically Engineered Mouse Models for Alzheimer Disease and Frontotemporal Dementia: New Insights from Single-Cell and Spatial Transcriptomics.}, journal = {The American journal of pathology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajpath.2024.11.006}, pmid = {39743215}, issn = {1525-2191}, abstract = {Neurodegenerative diseases, including Alzheimer disease, frontotemporal dementia, Parkinson disease, Huntington disease, and amyotrophic lateral sclerosis, are often casually linked to protein aggregation and inclusion. As the origins of those proteinopathies have been biochemically traced and genetically mapped, genetically engineered animal models carrying the specific mutations or variants are widely used for investigating the etiology of these diseases, as well as for testing potential therapeutics. This article focuses on the mouse models of Alzheimer disease and closely related frontotemporal dementia, particularly the ones that have provided most valuable knowledge, or are in a trajectory of doing so. More importantly, some of the major findings from these models are summarized, based on the recent single-cell transcriptomics, multiomics, and spatial transcriptomics studies. While no model is perfect, it is hoped that the new insights from these models and the practical use of these models will continue to help to establish a path forward.}, }
@article {pmid39743032, year = {2024}, author = {Li, Y and Zhang, W and Zhang, Q and Li, Y and Xin, C and Tu, R and Yan, H}, title = {Oxidative stress of mitophagy in neurodegenerative diseases: Mechanism and potential therapeutic targets.}, journal = {Archives of biochemistry and biophysics}, volume = {}, number = {}, pages = {110283}, doi = {10.1016/j.abb.2024.110283}, pmid = {39743032}, issn = {1096-0384}, abstract = {Neurodegenerative diseases are now significant chronic progressive neurological conditions that affect individuals' physical health. Oxidative stress is crucial in the development of these diseases. Among the various neurodegenerative diseases, mitochondrial damage has become a major factor in oxidative stress and disease advancement. During this process, oxidative stress and mitophagy plays an important role. In this paper, we introduced the role of mitophagy and oxidative stress in detail, and expounded the relationship between them. In addition, we summarized the pathogenesis of some neurodegenerative diseases and the mechanism of three antioxidants. The former includes AD, PD, HD and ALS, while the latter includes carnosine, adiponectin and resveratrol. Provide goals and directions for further research and treatment of neurodegenerative diseases. This review summarizes the impact of oxidative stress on neurodegenerative diseases by regulating mitophagy, provides a deeper understanding of their pathological mechanisms, and suggests potential new therapeutic targets.}, }
@article {pmid39740575, year = {2024}, author = {Fortuna, A and Sorarù, G}, title = {Cervical lower motor neuron syndromes: A diagnostic challenge.}, journal = {Journal of the neurological sciences}, volume = {468}, number = {}, pages = {123357}, doi = {10.1016/j.jns.2024.123357}, pmid = {39740575}, issn = {1878-5883}, abstract = {Cervical lower motor neuron (LMN) syndromes, also known as brachial paresis, are characterized by muscle atrophy, weakness, and decreased reflexes in the upper limbs, devoid of sensory symptoms. These syndromes can stem from various factors, including degenerative conditions, immune-mediated diseases, infections, toxic exposures, metabolic disorders, and vascular anomalies.[1] Clinical presentations vary, with motor neuron involvement potentially limited to the cervical area or extending to other regions, affecting prognosis. Misdiagnosis is a significant issue, particularly in lower motor neuron presentations, with an error rate nearing 20 %.[2] This review proposes a classification system based on magnetic resonance imaging (MRI) findings, the onset timing of symptoms (acute, subacute, or chronic), the symmetry and distribution of atrophy, and the etiology (sporadic or hereditary). Acute conditions may include spinal ischemia,[3] whereas subacute or chronic forms can manifest as symmetric (e.g., cervical spondylogenic myelopathy)[4] or asymmetric (e.g., Hirayama disease)[5] presentations. Neurophysiological assessments and cervical MRI are crucial for accurate diagnosis, as they reveal patterns that provide lesion localization and additional clues to the underlying cause. A systematic diagnostic approach is essential for navigating the complexities of these syndromes.}, }
@article {pmid39737769, year = {2025}, author = {Akyuz, E and Aslan, FS and Hekimoglu, A and Yilmaz, BN}, title = {Insights Into Retinal Pathologies in Neurological Disorders: A Focus on Parkinson's Disease, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, and Alzheimer's Disease.}, journal = {Journal of neuroscience research}, volume = {103}, number = {1}, pages = {e70006}, doi = {10.1002/jnr.70006}, pmid = {39737769}, issn = {1097-4547}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/pathology ; *Parkinson Disease/diagnosis/diagnostic imaging/pathology ; *Multiple Sclerosis/pathology/diagnosis/diagnostic imaging ; *Alzheimer Disease/pathology/diagnosis ; *Retina/pathology/diagnostic imaging ; Tomography, Optical Coherence/methods ; Retinal Diseases/diagnosis/pathology/etiology ; Animals ; }, abstract = {Neurological diseases are central nervous system (CNS) disorders affecting the whole body. Early diagnosis of the diseases is difficult due to the lack of disease-specific tests. Adding new biomarkers external to the CNS facilitates the diagnosis of neurological diseases. In this respect, the retina has a common embryologic origin with the CNS. Retinal imaging technologies including optical coherence tomography (OCT) can be used in the understanding and processual monitoring of neurological diseases. Retinal imaging has been recently recognized as a potential source of biomarkers for neurological diseases, increasing the number of studies in this direction. In this review, the association of retinal abnormalities with Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and Alzheimer's disease (AD) is explained. Structural and functional abnormalities in retina as a predictive marker may facilitate early diagnosis of diseases. Although not all retinal abnormalities are predictive of neurologic diseases, changes in the retinal layers including retinal pigment epithelium and plexiform layers should suggest the risk of PD, MS, ALS, and AD.}, }
@article {pmid39736783, year = {2024}, author = {Zeng, J and Luo, C and Jiang, Y and Hu, T and Lin, B and Xie, Y and Lan, J and Miao, J}, title = {Decoding TDP-43: the molecular chameleon of neurodegenerative diseases.}, journal = {Acta neuropathologica communications}, volume = {12}, number = {1}, pages = {205}, pmid = {39736783}, issn = {2051-5960}, support = {YNXM2024062//High-quality development project of public hospitals in Baoan District, Shenzhen/ ; YNXM2024015//High-quality development project of public hospitals in Baoan District, Shenzhen/ ; }, mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics ; *Neurodegenerative Diseases/metabolism/genetics/pathology ; Animals ; }, abstract = {TAR DNA-binding protein 43 (TDP-43) has emerged as a critical player in neurodegenerative disorders, with its dysfunction implicated in a wide spectrum of diseases including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and Alzheimer's disease (AD). This comprehensive review explores the multifaceted roles of TDP-43 in both physiological and pathological contexts. We delve into TDP-43's crucial functions in RNA metabolism, including splicing regulation, mRNA stability, and miRNA biogenesis. Particular emphasis is placed on recent discoveries regarding TDP-43's involvement in DNA interactions and chromatin dynamics, highlighting its broader impact on gene expression and genome stability. The review also examines the complex pathogenesis of TDP-43-related disorders, discussing the protein's propensity for aggregation, its effects on mitochondrial function, and its non-cell autonomous impacts on glial cells. We provide an in-depth analysis of TDP-43 pathology across various neurodegenerative conditions, from well-established associations in ALS and FTLD to emerging roles in diseases such as Huntington's disease and Niemann-Pick C disease. The potential of TDP-43 as a therapeutic target is explored, with a focus on recent developments in targeting cryptic exon inclusion and other TDP-43-mediated processes. This review synthesizes current knowledge on TDP-43 biology and pathology, offering insights into the protein's central role in neurodegeneration and highlighting promising avenues for future research and therapeutic interventions.}, }
@article {pmid39735081, year = {2024}, author = {Dost, W and Rasully, MQ and Zaman, MN and Dost, W and Ali, W and Ayobi, SA and Dost, R and Niazi, J and Bakht, K and Iqbal, A and Bokhari, SFH}, title = {Predictive Biomarkers for the Early Detection of Anastomotic Leaks in Colorectal Surgeries: A Systematic Review.}, journal = {Cureus}, volume = {16}, number = {11}, pages = {e74616}, pmid = {39735081}, issn = {2168-8184}, abstract = {Anastomotic leaks (ALs) remain a serious postoperative complication in colorectal surgery, often resulting in significant morbidity, prolonged hospitalization, and increased mortality risk. This systematic review aims to evaluate the role of predictive biomarkers in the early detection of ALs, focusing on their diagnostic accuracy and clinical utility. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive literature search was conducted across MEDLINE, Scopus, CENTRAL, and Web of Science, identifying studies that examined biomarkers such as C-reactive protein (CRP), procalcitonin (PCT), and white blood cell (WBC) count in the context of AL. A total of 20 studies met the inclusion criteria, with sample sizes ranging from 59 to 2,655 patients undergoing colorectal surgeries with primary anastomosis. CRP emerged as the most widely studied and reliable biomarker, with studies suggesting that elevated CRP levels, particularly on postoperative days 3-4, can effectively indicate AL risk, showing high negative predictive value. PCT has also shown promise as a complementary biomarker, offering enhanced specificity for infectious complications. Although WBC count alone was a limited predictor, it may add diagnostic value when used with other markers. In addition, innovative biomarkers, such as inflammatory indices in peritoneal fluid, demonstrated potential for further improving AL detection accuracy.}, }
@article {pmid39728809, year = {2024}, author = {Al Haffar, M and Fajloun, Z and Azar, S and Sabatier, JM and Abi Khattar, Z}, title = {Lesser-Known Cyanotoxins: A Comprehensive Review of Their Health and Environmental Impacts.}, journal = {Toxins}, volume = {16}, number = {12}, pages = {}, pmid = {39728809}, issn = {2072-6651}, mesh = {Humans ; *Cyanobacteria/metabolism ; *Bacterial Toxins/toxicity ; Animals ; Harmful Algal Bloom ; Cyanobacteria Toxins ; Microcystins/toxicity ; }, abstract = {Cyanobacteria, also known as blue-green algae, are a diverse phylum of photosynthetic, Gram-negative bacteria and one of the largest microbial taxa. These organisms produce cyanotoxins, which are secondary metabolites that can have significant impacts on both human health and the environment. While toxins like Microcystins and Cylindrospermopsins are well-documented and have been extensively studied, other cyanotoxins, including those produced by Lyngbya and Nostoc, remain underexplored. These lesser-known toxins can cause various health issues in humans, including neurotoxicity, hepatotoxicity, and dermatotoxicity, each through distinct mechanisms. Moreover, recent studies have shown that cyanobacteria can be aerosolized and transmitted through the air over long distances, providing an additional route for human exposure to their harmful effects. However, it remains an area that requires much more investigation to accurately assess the health risks and develop appropriate public health guidelines. In addition to direct exposure to toxins, cyanobacteria can lead to harmful algal blooms, which pose further risks to human and wildlife health, and are a global concern. There is limited knowledge about these lesser-known cyanotoxins, highlighting the need for further research to understand their clinical manifestations and improve society's preparedness for the associated health risks. This work aims to review the existing literature on these underexplored cyanotoxins, which are associated with human intoxication, elucidate their clinical relevance, address significant challenges in cyanobacterial research, and provide guidance on mitigating their adverse effects.}, }
@article {pmid39728753, year = {2024}, author = {Boziki, M and Theotokis, P and Kesidou, E and Nella, M and Bakirtzis, C and Karafoulidou, E and Tzitiridou-Chatzopoulou, M and Doulberis, M and Kazakos, E and Deretzi, G and Grigoriadis, N and Kountouras, J}, title = {Impact of Mast Cell Activation on Neurodegeneration: A Potential Role for Gut-Brain Axis and Helicobacter pylori Infection.}, journal = {Neurology international}, volume = {16}, number = {6}, pages = {1750-1778}, pmid = {39728753}, issn = {2035-8385}, abstract = {BACKGROUND: The innate immune response aims to prevent pathogens from entering the organism and/or to facilitate pathogen clearance. Innate immune cells, such as macrophages, mast cells (MCs), natural killer cells and neutrophils, bear pattern recognition receptors and are thus able to recognize common molecular patterns, such as pathogen-associated molecular patterns (PAMPs), and damage-associated molecular patterns (DAMPs), the later occurring in the context of neuroinflammation. An inflammatory component in the pathology of otherwise "primary cerebrovascular and neurodegenerative" disease has recently been recognized and targeted as a means of therapeutic intervention. Activated MCs are multifunctional effector cells generated from hematopoietic stem cells that, together with dendritic cells, represent first-line immune defense mechanisms against pathogens and/or tissue destruction.
METHODS: This review aims to summarize evidence of MC implication in the pathogenesis of neurodegenerative diseases, namely, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis.
RESULTS: In view of recent evidence that the gut-brain axis may be implicated in the pathogenesis of neurodegenerative diseases and the characterization of the neuroinflammatory component in the pathology of these diseases, this review also focuses on MCs as potential mediators in the gut-brain axis bi-directional communication and the possible role of Helicobacter pylori, a gastric pathogen known to alter the gut-brain axis homeostasis towards local and systemic pro-inflammatory responses.
CONCLUSION: As MCs and Helicobacter pylori infection may offer targets of intervention with potential therapeutic implications for neurodegenerative disease, more clinical and translational evidence is needed to elucidate this field.}, }
@article {pmid39717968, year = {2024}, author = {Vergini, DE and Hadjipavlou-Litina, D}, title = {"A patent review on arachidonic acid lipoxygenase (LOX) inhibitors for the treatment of neurodegenerative diseases (2018-present)".}, journal = {Expert opinion on therapeutic patents}, volume = {}, number = {}, pages = {1-14}, doi = {10.1080/13543776.2024.2447067}, pmid = {39717968}, issn = {1744-7674}, abstract = {INTRODUCTION: Neuroinflammation is correlated to neurodegenerative diseases like Alzheimer's disease (AD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), Huntington Disease (HD), and Parkinson's disease (PD). A lot of recent research and patents are focused on the design and synthesis of arachidonic acid lipoxygenase (ALOX) inhibitors for the treatment of neurodegenerative diseases.
AREAS COVERED: The survey covers natural products, synthesis, hybrids, and assessments of biological effects in biological studies as ALOX inhibitors. A survey of patent publications from 2018 to present, taken from Google Scholar, Espanet, Web of Science, Drugbank, Scopus, or PubMed is analyzed.
EXPERT OPINION: The authors suggest that (i) numerous areas of biology-pharmacology need to be considered: selectivity, in vivo studies, toxicity, bioavailability, and drug-likeness, the mechanism of action in different animals and humans, evaluation of more efficient and selective biological tests; (ii) synthetic method outbalance in the discovery and production of ALOX inhibitors with greater selectivity. Several ALOX inhibitors show promising results for the treatment of neurological disorders. Their clinical evaluation will be critical to assess therapeutic utility. The compounds for which the mechanism of action and their bioavailability are well defined can be used as lead compounds for the treatment of neurodegenerative diseases.}, }
@article {pmid39705668, year = {2024}, author = {Khandia, R and Gurjar, P and Priyanka, and Romashchenko, V and Al-Hussain, SA and Zaki, MEA}, title = {Recent advances in stem cell therapy: efficacy, ethics, safety concerns, and future directions focusing on neurodegenerative disorders - a review.}, journal = {International journal of surgery (London, England)}, volume = {110}, number = {10}, pages = {6367-6381}, pmid = {39705668}, issn = {1743-9159}, mesh = {Humans ; *Neurodegenerative Diseases/therapy ; *Stem Cell Transplantation/methods ; }, abstract = {Neurodegeneration refers to the gradual loss of neurons and extensive changes in glial cells like tau inclusions in astrocytes and oligodendrocytes, α-synuclein inclusions in oligodendrocytes and SOD1 aggregates in astrocytes along with deterioration in the motor, cognition, learning, and behavior. Common neurodegenerative disorders are Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), spinocerebellar ataxia (SCA), and supranuclear palsy. There is a lack of effective treatment for neurodegenerative diseases, and scientists are putting their efforts into developing therapies against them. Stem cell therapy has emerged as a hope for neurodegenerative disorders since it is not only the damaged neurons that might be replaced, but other neuromodulators and neuroprotectors are secreted. Stem cell terminal differentiation before implantation ensures the implantation of correct cells and molecular markers like carbonic anhydrase II, CNPase (2',3'-cyclic nucleotide 3'-phosphohydrolase), myelin basic protein (MBP), and myelin oligodendrocyte glycoprotein (MOG) elucidate the differentiation. Secretion of various growth factors like epidermal growth factor (EGF), keratinocyte growth factor (KGF), vascular endothelial growth factor-α (VEGF-α), transforming growth factor (TGF), and macrophage inflammatory protein (MIP) supports cell survival, cell proliferation, blood vessel formation, axon regeneration, and neuroglial functional connection formation at the site of degeneration. Adverse effects of stem cell therapy, like teratogenicity and differentiation in different cells other than the desired one under the influence of microenvironment, are a few key concerns. Post-transplantation improved synaptic plasticity, apoptosis inhibition, and reduction in tau-phosphorylation and amyloid beta (Aβ) production has been observed in Alzheimer's patients. A large number of experimental, preclinical, and clinical studies have been conducted, and encouraging results have been obtained. The present review exhaustively discusses various kinds of stem cells, their usage in treating neurodegenerative disorders, limitations and challenges, and ethical issues related to stem cell therapy.}, }
@article {pmid39700696, year = {2024}, author = {Ghaderi, S and Mohammadi, S and Fatehi, F}, title = {Current evidence of arterial spin labeling in amyotrophic lateral sclerosis: A systematic review.}, journal = {Clinical neurology and neurosurgery}, volume = {249}, number = {}, pages = {108691}, doi = {10.1016/j.clineuro.2024.108691}, pmid = {39700696}, issn = {1872-6968}, abstract = {OBJECTIVE: This study aimed to evaluate the utility of arterial spin labeling (ASL) in assessing cerebral blood flow (CBF) changes in amyotrophic lateral sclerosis (ALS), and its potential as a biomarker for early diagnosis.
METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies that employed ASL to compare CBF between ALS patients and healthy controls were included.
RESULTS: Seven studies were included. A consistent finding across these studies was hypoperfusion in both the motor and non-motor regions, particularly in the frontotemporal cortex. Hypoperfusion in motor regions was correlated with functional impairment and was observed prior to structural changes, suggesting its potential as an early biomarker. There is limited evidence to suggest that monitoring changes in CBF patterns in the brain. Besides, limited findings showed initial hyperperfusion in regions not yet involved in the pathological process, and progressing hypoperfusion in regions with increasing pathological burden.
CONCLUSIONS: This review highlights the potential of ASL as a valuable tool for understanding the neurovascular dysfunction in ALS. Further research is required to validate its clinical utility for diagnosing ALS and monitoring disease progression.}, }
@article {pmid39698283, year = {2024}, author = {Kos, JA and Langiu, M and Hellyer, SD and Gregory, KJ}, title = {Pharmacology, Signaling and Therapeutic Potential of Metabotropic Glutamate Receptor 5 Negative Allosteric Modulators.}, journal = {ACS pharmacology & translational science}, volume = {7}, number = {12}, pages = {3671-3690}, pmid = {39698283}, issn = {2575-9108}, abstract = {Metabotropic glutamate receptors are a family of eight class C G protein-coupled receptors regulating higher order brain functions including cognition and motion. Metabotropic glutamate receptors have thus been heavily investigated as potential drug targets for treating neurological disorders. Drug discovery efforts directed toward metabotropic glutamate receptor subtype 5 (mGlu5) have been particularly fruitful, with a wealth of drug candidates and pharmacological tools identified. mGlu5 negative allosteric modulators (NAMs) are promising novel therapeutics for developmental, neuropsychiatric and neurodegenerative disorders (e.g., Alzheimer's Disease, Huntington's Disease, Parkinson's Disease, amyotrophic lateral sclerosis, autism spectrum disorders, substance use disorders, stroke, anxiety and depression) and show promise in ameliorating adverse effects induced by other medications (e.g., L-dopa induced dyskinesia in Parkinson's Disease). However, despite preclinical success, mGlu5 NAMs are yet to reach the market due to poor safety and efficacy profiles in clinical trials. Herein, we review the physiology and signal transduction of mGlu5. We provide a comprehensive critique of therapeutic options with respect to mGlu5 inhibitors, spanning from orthosteric antagonists to NAMs. Finally, we address the challenges associated with drug development and highlight future directions to guide rational drug discovery of safe and effective novel therapeutics.}, }
@article {pmid39691422, year = {2024}, author = {Fang, K}, title = {Modulation of the central nervous system immune response and neuroinflammation via Wnt signaling in health and neurodegenerative diseases.}, journal = {Ibrain}, volume = {10}, number = {4}, pages = {462-476}, pmid = {39691422}, issn = {2769-2795}, abstract = {The immune response in the central nervous system (CNS) is a highly specialized and tightly regulated process essential for maintaining neural health and protecting against pathogens and injuries. The primary immune cells within the CNS include microglia, astrocytes, T cells, and B cells. They work together, continuously monitor the CNS environment for signs of infection, injury, or disease, and respond by phagocytosing debris, releasing cytokines, and recruiting other immune cells. In addition to providing neuroprotection, these immune responses must be carefully balanced to prevent excessive inflammation that can lead to neuronal damage and contribute to neurodegenerative diseases. Dysregulated immune responses in the CNS are implicated in various neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Wnt signaling is a crucial pathway in the CNS that regulates various cellular processes critical for brain development, function, and maintenance. Despite enhancing immune responses in the health CNS, dysregulated Wnt signaling exacerbates neuroinflammation in the neurodegenerative brains. This review summarized the role of Wnt signaling in regulating immune response under different conditions. We then examined the role of immune response in healthy brains and during the development of neurodegenerative diseases. We also discussed therapeutic intervention in various neurodegenerative diseases through the modulation of the Wnt signaling pathway and neuroinflammation and highlighted challenges and limitations in current clinical trials.}, }
@article {pmid39690343, year = {2024}, author = {Lamichhane, S and Seo, JE and Jeong, JH and Lee, S and Lee, S}, title = {Ideal animal models according to multifaceted mechanisms and peculiarities in neurological disorders: present and challenges.}, journal = {Archives of pharmacal research}, volume = {}, number = {}, pages = {}, pmid = {39690343}, issn = {1976-3786}, support = {Research grant 2024//Chung-Ang University/ ; NRF-2016R1A6A1A03011325//Ministry of Education/ ; }, abstract = {Neurological disorders, encompassing conditions such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), pose a significant global health challenge, affecting millions worldwide. With an aging population and increased life expectancy, the prevalence of these disorders is escalating rapidly, leading to substantial economic burdens exceeding trillions of dollars annually. Animal models play a crucial role in understanding the underlying mechanisms of these disorders and developing effective treatments. Various species, including rodents, non-human primates, and fruit flies, are utilized to replicate specific aspects of human neurological conditions. However, selecting the ideal animal model requires careful consideration of its proximity to human disease conditions and its ability to mimic disease pathobiology and pharmacological responses. An Animal Model Quality Assessment (AMQA) tool has been developed to facilitate this selection process, focusing on assessing models based on their similarity to human conditions and disease pathobiology. Therefore, integrating intrinsic and extrinsic factors linked to the disease into the study's objectives aids in constructing a biological information matrix for comparing disease progression between the animal model and human disease. Ultimately, selecting an ideal animal disease model depends on its predictive, face, and construct validity, ensuring relevance and reliability in translational research efforts.}, }
@article {pmid39688317, year = {2024}, author = {Tseriotis, VS and Eleftheriadou, K and Mavridis, T and Konstantis, G and Falkenburger, B and Arnaoutoglou, M}, title = {Is the Swallow Tail Sign a Useful Imaging Biomarker in Clinical Neurology? A Systematic Review.}, journal = {Movement disorders clinical practice}, volume = {}, number = {}, pages = {}, doi = {10.1002/mdc3.14304}, pmid = {39688317}, issn = {2330-1619}, support = {//Hellenic Academic Libraries Link/ ; }, abstract = {BACKGROUND: Loss of dorsolateral nigral hyperintensity (DNH) in iron-sensitive sequences of Magnetic Resonance Imaging (MRI), also described as "swallow tail sign" (STS) loss, has shown promising diagnostic value in Parkinson's Disease (PD) and Atypical Parkinsonian Syndromes (APS).
OBJECTIVE: To conduct a bibliometric analysis on substantia nigra MRI and a systematic review on the clinical utility of STS visual assessment on Susceptibility-Weighted Imaging in various clinical entities.
METHODS: VOSviewer's keyword co-occurrence network was employed using Web of Science (WOS). Complying with the PRISMA statement, we searched MEDLINE, WOS, SCOPUS, ProQuest and Google Scholar for peer-reviewed studies conducted in vivo, excluding quantitative imaging techniques.
RESULTS: DNH is a relatively novel parameter in substantia nigra MRI literature. Our SWI-focused review included 42 studies (3281 patients). Diagnostic accuracy of STS loss for PD/APS differentiation from controls and for Lewy Body Dementia differentiation from other dementias was 47.8-98.5% and 76-90%, respectively, with poorer capacity, however, in delineating PD from APS. STS evaluation in idiopathic REM sleep behavior disorder, a sign of prodromal PD, was typically concordant with nuclear scans, identifying subjects with high conversion risk. Iron deposition can affect STS in Multiple Sclerosis and STS loss in Amyotrophic Lateral Sclerosis is linked with multisystem degeneration, with poorer prognosis. In healthy individuals iron-induced microvessel changes are suspected for false positive results.
CONCLUSION: STS assessment exhibits potential in different settings, with a possibly intermediate role in the diagnostic work-up of various conditions. Its clinical utility should be explored further, through standardized MRI protocols on larger cohorts.}, }
@article {pmid39684324, year = {2024}, author = {Toader, C and Tataru, CP and Munteanu, O and Serban, M and Covache-Busuioc, RA and Ciurea, AV and Enyedi, M}, title = {Decoding Neurodegeneration: A Review of Molecular Mechanisms and Therapeutic Advances in Alzheimer's, Parkinson's, and ALS.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684324}, issn = {1422-0067}, mesh = {Humans ; *Alzheimer Disease/therapy/metabolism/genetics ; *Parkinson Disease/therapy/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/therapy/genetics/metabolism ; Animals ; Neurodegenerative Diseases/therapy/metabolism/genetics ; Drug Delivery Systems ; Gene Editing ; }, abstract = {Neurodegenerative diseases, such as Alzheimer's, Parkinson's, ALS, and Huntington's, remain formidable challenges in medicine, with their relentless progression and limited therapeutic options. These diseases arise from a web of molecular disturbances-misfolded proteins, chronic neuroinflammation, mitochondrial dysfunction, and genetic mutations-that slowly dismantle neuronal integrity. Yet, recent scientific breakthroughs are opening new paths to intervene in these once-intractable conditions. This review synthesizes the latest insights into the underlying molecular dynamics of neurodegeneration, revealing how intertwined pathways drive the course of these diseases. With an eye on the most promising advances, we explore innovative therapies emerging from cutting-edge research: nanotechnology-based drug delivery systems capable of navigating the blood-brain barrier, gene-editing tools like CRISPR designed to correct harmful genetic variants, and stem cell strategies that not only replace lost neurons but foster neuroprotective environments. Pharmacogenomics is reshaping treatment personalization, enabling tailored therapies that align with individual genetic profiles, while molecular diagnostics and biomarkers are ushering in an era of early, precise disease detection. Furthermore, novel perspectives on the gut-brain axis are sparking interest as mounting evidence suggests that microbiome modulation may play a role in reducing neuroinflammatory responses linked to neurodegenerative progression. Taken together, these advances signal a shift toward a comprehensive, personalized approach that could transform neurodegenerative care. By integrating molecular insights and innovative therapeutic techniques, this review offers a forward-looking perspective on a future where treatments aim not just to manage symptoms but to fundamentally alter disease progression, presenting renewed hope for improved patient outcomes.}, }
@article {pmid39684308, year = {2024}, author = {Ścibior, A and Llopis, J and Dobrakowski, PP and Męcik-Kronenberg, T}, title = {Magnesium (Mg) and Neurodegeneration: A Comprehensive Overview of Studies on Mg Levels in Biological Specimens in Humans Affected Some Neurodegenerative Disorders with an Update on Therapy and Clinical Trials Supplemented with Selected Animal Studies.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684308}, issn = {1422-0067}, mesh = {Humans ; *Magnesium/therapeutic use ; Animals ; *Neurodegenerative Diseases/drug therapy ; Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; Clinical Trials as Topic ; Disease Models, Animal ; Neuroprotective Agents/therapeutic use/pharmacology ; Parkinson Disease/drug therapy/metabolism ; Alzheimer Disease/drug therapy/metabolism ; }, abstract = {Neurodegenerative diseases, characterized by neuron loss, are a group of neurological disorders that adversely affect the lives of millions of people worldwide. Although several medicines have been approved for managing neurodegenerative diseases, new therapies allowing for a significant slowdown in the progression of neurodegenerative syndromes are constantly being sought. Magnesium (Mg), a crucial mineral necessary for the functioning of organisms, is important to normal central nervous system (CNS) activity. Although the effects of this bioelement on the CNS are relatively well recognized, its role in the pathophysiology of neurological disorders in humans is not yet well characterized. Therefore, the main goal of this review is to collect data about a possible association between Mg and neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's Disease (PD), and Amyotrophic lateral sclerosis (ALS) in humans. Hence, the levels of Mg in blood, cerebrospinal fluid (CSF), urine, and hair from subjects with AD, PD, and ALS are compiled to detect possible variations in the levels of this mineral in the biological specimens of people with neurodegenerative illnesses. Additionally, the findings from an animal model are summarized to offer the reader a deeper insight into studies on Mg in the context of neuroprotection and neurodegeneration. Data provided in the present review indicate that Mg, due to its neuroprotective, antioxidant, anti-inflammatory, and mitochondrial-supportive properties, could be a potential therapeutic agent for AD, PD, and ALS. However, more epidemiological studies with standardized methods of dietary assessment and Mg measurement are necessary to recognize its exact role in neurodegenerative disorders. Moreover, extensive well-designed clinical trials are also needed to establish definitive therapeutic protocols and optimal dosages, and to ensure long-term safety of this mineral supplementation in AD, PD, and ALS patients.}, }
@article {pmid39684197, year = {2024}, author = {García-González, N and Gonçalves-Sánchez, J and Gómez-Nieto, R and Gonçalves-Estella, JM and López, DE}, title = {Advances and Challenges in Gene Therapy for Neurodegenerative Diseases: A Systematic Review.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684197}, issn = {1422-0067}, mesh = {Humans ; *Genetic Therapy/methods ; *Neurodegenerative Diseases/therapy/genetics ; Animals ; Amyotrophic Lateral Sclerosis/therapy/genetics ; }, abstract = {This review explores recent advancements in gene therapy as a potential treatment for neurodegenerative diseases, focusing on intervention mechanisms, administration routes, and associated limitations. Following the PRISMA procedure guidelines, we systematically analyzed studies published since 2020 using the PICO framework to derive reliable conclusions. The efficacy of various gene therapies was evaluated for Parkinson's disease (n = 12), spinal muscular atrophy (n = 8), Huntington's disease (n = 3), Alzheimer's disease (n = 3), and amyotrophic lateral sclerosis (n = 6). For each condition, we assessed the therapeutic approach, curative or disease-modifying potential, delivery methods, advantages, drawbacks, and side effects. Results indicate that gene therapies targeting specific genes are particularly effective in monogenic disorders, with promising clinical outcomes expected in the near future. In contrast, in polygenic diseases, therapies primarily aim to promote cell survival. A major challenge remains: the translation of animal model success to human clinical application. Additionally, while intracerebral delivery methods enhance therapeutic efficacy, they are highly invasive. Despite these hurdles, gene therapy represents a promising frontier in the treatment of neurodegenerative diseases, underscoring the need for continued research to refine and personalize treatments for each condition.}, }
@article {pmid39681722, year = {2024}, author = {Weiner, HL}, title = {Immune mechanisms and shared immune targets in neurodegenerative diseases.}, journal = {Nature reviews. Neurology}, volume = {}, number = {}, pages = {}, pmid = {39681722}, issn = {1759-4766}, abstract = {The immune system plays a major part in neurodegenerative diseases. In some, such as multiple sclerosis, it is the primary driver of the disease. In others, such as Alzheimer disease, amyotrophic lateral sclerosis and Parkinson disease, it has an amplifying role. Immunotherapeutic approaches that target the adaptive and innate immune systems are being explored for the treatment of almost all neurological diseases, and the targets and approaches are often common across diseases. Microglia are the primary immune cells in the brain that contribute to disease pathogenesis, and are consequently a common immune target for therapy. Other therapeutic approaches target components of the peripheral immune system, such as regulatory T cells and monocytes, which in turn act within the CNS. This Review considers in detail how microglia, monocytes and T cells contribute to the pathogenesis of multiple sclerosis, Alzheimer disease, amyotrophic lateral sclerosis and Parkinson disease, and their potential as shared therapeutic targets across these diseases. The microbiome is also highlighted as an emerging therapeutic target that indirectly modulates the immune system. Therapeutic approaches being developed to target immune function in neurodegenerative diseases are discussed, highlighting how immune-based approaches developed to treat one disease could be applicable to multiple other neurological diseases.}, }
@article {pmid39678458, year = {2024}, author = {Sulek, A}, title = {Secretome - the role of extracellular vesicles in the pathogenesis and therapy of neurodegenerative diseases.}, journal = {Postepy psychiatrii neurologii}, volume = {33}, number = {3}, pages = {147-162}, pmid = {39678458}, issn = {2720-5371}, abstract = {PURPOSE: Extracellular vesicles are the subject of many studies in various medical specialties. Their role in neurodegenerative diseases is increasing and they worth introducing in more detail.
METHODS: This review was performed following an electronic search of the database PubMed/Medline and Web of Science for English-language articles between 2010 and 2024 in the fields of medicine, molecular biology, and biochemistry. Keywords searches included combinations of the following terms: "extracellular vesicles" OR "exosomes" AND "neurodeg*" AND "microRNA" OR "miRNA" AND "AD" OR "PD" OR "ALS" OR "HD". Articles had to be original work or reviews.
RESULTS: The classification of extracellular vesicles is based on their size or origin. Their content is of key importance in communication between cells and can be treated as a physiological determinant of the normal or pathological condition of a body. The cargo transported in the extracellular space and over longer distances in various body fluids is diversified and may be nucleic acids (DNA, RNA, miRNA) as well as proteins and lipids, and, in the case of apoptotic bodies also a cell's organelles. Exosomes are the most thoroughly studied extracellular vesicles and the most often considered for therapeutic applications. Vesicles carrying biological substances in the body perform three basic functions: participation in a pathological mechanism, a biomarker role that also has diagnostic and prognostic functions, and a role in therapeutic activities. In the case of neurodegenerative diseases, it appears that extracellular vesicles can transport misfolded proteins, initiating pathological processes in previously normal cells.
CONCLUSIONS: The transport of various substances enclosed in vesicles seems to be very promising in therapeutic prospects in various diseases, and the possibility of their crossing the blood-brain barrier particularly indicates diseases of the central nervous system. Despite many years of research on extracellular vesicles in the context of neurodegenerative diseases, their practical use is currently limited to studies on animal and cellular models, and their practical application in clinical trials in neurodegenerative diseases is to date extremely rare.}, }
@article {pmid39672208, year = {2024}, author = {Liu, Y and Wu, L and Peng, W and Mao, X}, title = {Glial polarization in neurological diseases: Molecular mechanisms and therapeutic opportunities.}, journal = {Ageing research reviews}, volume = {104}, number = {}, pages = {102638}, doi = {10.1016/j.arr.2024.102638}, pmid = {39672208}, issn = {1872-9649}, abstract = {Glial cell polarization plays a pivotal role in various neurological disorders. In response to distinct stimuli, glial cells undergo polarization to either mitigate neurotoxicity or facilitate neural repair following injury, underscoring the importance of glial phenotypic polarization in modulating central nervous system function. This review presents an overview of glial cell polarization, focusing on astrocytes and microglia. It explores the involvement of glial polarization in neurological diseases such as Alzheimer's disease, Parkinson's disease, stroke, epilepsy, traumatic brain injury, amyotrophic lateral sclerosis, multiple sclerosis and meningoencephalitis. Specifically, it emphasizes the role of glial cell polarization in disease pathogenesis through mechanisms including neuroinflammation, neurodegeneration, calcium signaling dysregulation, synaptic dysfunction and immune response. Additionally, it summarizes various therapeutic strategies including pharmacological treatments, dietary supplements and cell-based therapies, aimed at modulating glial cell polarization to ameliorate brain dysfunction. Future research focused on the spatio-temporal manipulation of glial polarization holds promise for advancing precision diagnosis and treatment of neurological diseases.}, }
@article {pmid39666202, year = {2024}, author = {van Eijk, RPA and van Loon, FT and van Unnik, JWJ and Weemering, DN and Seitidis, G and Mavridis, D and van den Berg, LH and Nikolakopoulos, S}, title = {Attrition and discontinuation in amyotrophic lateral sclerosis clinical trials: a meta-analysis.}, journal = {Journal of neurology}, volume = {272}, number = {1}, pages = {40}, pmid = {39666202}, issn = {1432-1459}, support = {EVIDENCE//Stichting ALS Nederland/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy ; Humans ; *Randomized Controlled Trials as Topic ; Patient Dropouts/statistics & numerical data ; }, abstract = {OBJECTIVES: Attrition due to adverse events and disease progression impacts the integrity and generalizability of clinical trials. The aim of this study is to provide evidence-based estimates of attrition for clinical trials in amyotrophic lateral sclerosis (ALS), and identify study-related predictors, through a comprehensive systematic review and meta-analysis.
METHODS: We systematically reviewed the literature to identify all randomized, placebo-controlled clinical trials in ALS and determined the number of patients who discontinued the study per randomized arm. Subsequently, we meta-analyzed attrition rates across studies, evaluated the difference between study arms, and explored the impact of study-level characteristics. Finally, a meta-regression model predicting study discontinuation for future clinical trials was translated into a web application.
RESULTS: In total, 60 randomized placebo-controlled clinical trials were included in the meta-analysis, randomizing 14,493 patients with ALS. Attrition varied significantly between studies, ranging from 3.1% to 75.7% of all randomized patients, with a pooled effect of 32.0% (90% prediction interval 6.1% to 66.3%). Attrition was similar between the intervention and placebo arm (odds ratio 1.08, 95% CI 0.89 to 1.31, p = 0.43). The follow-up duration was identified as the sole study-level predictor (0.032, 95% CI 0.026 to 0.039, p < 0.001), resulting in predicted attrition of 19.3% for 6-month, 36.4% for 12-month, and 55.6% for 18-month clinical trials.
CONCLUSIONS: ALS clinical trials encounter high attrition, which increases with the follow-up duration. These findings underscore the need to refine our strategies to manage attrition, preserving the integrity and generalizability of ALS clinical trials.}, }
@article {pmid39662855, year = {2024}, author = {Yang, ZF and Jiang, XC and Gao, JQ}, title = {Present insights into the progress in gene therapy delivery systems for central nervous system diseases.}, journal = {International journal of pharmaceutics}, volume = {669}, number = {}, pages = {125069}, doi = {10.1016/j.ijpharm.2024.125069}, pmid = {39662855}, issn = {1873-3476}, abstract = {Central nervous system (CNS) diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), spinal cord injury (SCI), and ischemic strokes and certain rare diseases, such as amyotrophic lateral sclerosis (ALS) and ataxia, present significant obstacles to treatment using conventional molecular pharmaceuticals. Gene therapy, with its ability to target previously "undruggable" proteins with high specificity and safety, is increasingly utilized in both preclinical and clinical research for CNS ailments. As our comprehension of the pathophysiology of these conditions deepens, gene therapy stands out as a versatile and promising strategy with the potential to both prevent and treat these diseases. Despite the remarkable progress in refining and enhancing the structural design of gene therapy agents, substantial obstacles persist in their effective and safe delivery within living systems. To surmount these obstacles, a diverse array of gene delivery systems has been devised and continuously improved. Notably, Adeno-Associated Virus (AAVs)-based viral gene vectors and lipid-based nanocarriers have each advanced the in vivo delivery of gene therapies to various extents. This review aims to concisely summarize the pathophysiological foundations of CNS diseases and to shed light on the latest advancements in gene delivery vector technologies. It discusses the primary categories of these vectors, their respective advantages and limitations, and their specialized uses in the context of gene therapy delivery.}, }
@article {pmid39662651, year = {2024}, author = {Keethedeth, N and Anantha Shenoi, R}, title = {Mitochondria-targeted nanotherapeutics: A new Frontier in neurodegenerative disease treatment.}, journal = {Mitochondrion}, volume = {}, number = {}, pages = {102000}, doi = {10.1016/j.mito.2024.102000}, pmid = {39662651}, issn = {1872-8278}, abstract = {Mitochondria are the seat of cellular energy and play key roles in regulating several cellular processes such as oxidative phosphorylation, respiration, calcium homeostasis and apoptotic pathways. Mitochondrial dysfunction results in error in oxidative phosphorylation, redox imbalance, mitochondrial DNA mutations, and disturbances in mitochondrial dynamics, all of which can lead to several metabolic and degenerative diseases. A plethora of studies have provided evidence for the involvement of mitochondrial dysfunction in the pathogenesis of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Hence mitochondria have been used as possible therapeutic targets in the regulation of neurodegenerative diseases. However, the double membranous structure of mitochondria poses an additional barrier to most drugs even if they are able to cross the plasma membrane. Most of the drugs acting on mitochondria also required very high doses to exhibit the desired mitochondrial accumulation and therapeutic effect which in-turn result in toxic effects. Mitochondrial targeting has been improved by direct conjugation of drugs to mitochondriotropic molecules like dequalinium (DQA) and triphenyl phosphonium (TPP) cations. But being cationic in nature, these molecules also exhibit toxicity at higher doses. In order to further improve the mitochondrial localization with minimal toxicity, TPP was conjugated with various nanomaterials like liposomes. inorganic nanoparticles, polymeric nanoparticles, micelles and dendrimers. This review provides an overview of the role of mitochondrial dysfunction in neurodegenerative diseases and various nanotherapeutic strategies for efficient targeting of mitochondria-acting drugs in these diseases.}, }
@article {pmid39645221, year = {2025}, author = {Bajpai, A and Bharathi, V and Patel, BK}, title = {Therapeutic targeting of the oxidative stress generated by pathological molecular pathways in the neurodegenerative diseases, ALS and Huntington's.}, journal = {European journal of pharmacology}, volume = {987}, number = {}, pages = {177187}, doi = {10.1016/j.ejphar.2024.177187}, pmid = {39645221}, issn = {1879-0712}, mesh = {Humans ; *Oxidative Stress/drug effects ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology/genetics ; *Huntington Disease/metabolism/drug therapy/pathology/genetics ; Animals ; Antioxidants/pharmacology/therapeutic use ; Molecular Targeted Therapy ; Neurodegenerative Diseases/metabolism/drug therapy/pathology ; }, abstract = {Neurodegenerative disorders are characterized by a progressive decline of specific neuronal populations in the brain and spinal cord, typically containing aggregates of one or more proteins. They can result in behavioral alterations, memory loss and a decline in cognitive and motor abilities. Various pathways and mechanisms have been outlined for the potential treatment of these diseases, where redox regulation is considered as one of the most common druggable targets. For example, in amyotrophic lateral sclerosis (ALS) with superoxide dismutase-1 (SOD1) pathology, there is a downregulation of the antioxidant response nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. TDP-43 proteinopathy in ALS is associated with elevated levels of reactive oxygen species and mitochondrial dyshomeostasis. In ALS with mutant FUS, poly ADP ribose polymerase-dependent X ray repair cross complementing 1/DNA-ligase recruitment to the sites of oxidative DNA damage is affected, thereby causing defects in DNA damage repair. Oxidative stress in Huntington's disease (HD) with mutant huntingtin accumulation manifests as protein oxidation, metabolic energetics dysfunction, metal ion dyshomeostasis, DNA damage and mitochondrial dysfunction. The impact of oxidative stress in the progression of these diseases further warrants studies into the role of antioxidants in their treatment. While an antioxidant, edaravone, has been approved for therapeutics of ALS, numerous antioxidant molecules failed to pass the clinical trials despite promising initial studies. In this review, we summarize the oxidative stress pathways and redox modulators that are investigated in ALS and HD using various models.}, }
@article {pmid39639468, year = {2024}, author = {Arango-Cortes, ML and Giraldo-Cadavid, LF and Latorre Quintana, M and Forero-Cubides, JD and Gonzalez-Bermejo, J}, title = {Diaphragm pacing compared with mechanical ventilation in patients with chronic respiratory failure caused by diaphragmatic dysfunction: a systematic review and meta-analysis.}, journal = {Expert review of respiratory medicine}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/17476348.2024.2421846}, pmid = {39639468}, issn = {1747-6356}, abstract = {BACKGROUND: The effectiveness of diaphragmatic electrical stimulation (DES) compared to mechanical ventilation (MV) in improving clinical outcomes such as quality-of-life (QOL) and hospital stay remains inconsistent.
METHODS: We conducted a systematic review and meta-analysis by searching PubMed, Scopus, Google Scholar, LILACS, and IEEE Xplore. We included comparative studies (randomized controlled trials and observational studies) of DES administered via the phrenic nerve or intramuscular electrodes, compared with MV in adults with diaphragmatic paralysis or paresis. Two authors independently extracted data and assessed bias, with discrepancies resolved by a senior author. Results were pooled using the inverse variance method.
RESULTS: Out of 1,290 articles, nine were included in the systematic review, totaling 852 subjects. In spinal cord injury (SCI), one study reported lower mortality with DES, while three found no difference compared to MV. In these patients, DES was associated with shorter hospital stay, similar QOL, and heterogeneous results on respiratory infections. In amyotrophic lateral sclerosis (ALS), DES was associated with higher mortality and similar QOL compared to MV. Most SCI studies had a serious risk of bias.
CONCLUSION: DES shows potential in reducing hospital stay and respiratory infections in SCI but is associated with higher mortality in ALS.}, }
@article {pmid39636751, year = {2025}, author = {Desai, AB and Agarwal, A and Mohamed, AS and Mohamed, KH and Middlebrooks, EH and Bhatt, AA and Gupta, V and Kumar, N and Sechi, E and Flanagan, EP and López Chiriboga, S}, title = {Motor Neuron Diseases and Central Nervous System Tractopathies: Clinical-Radiologic Correlation and Diagnostic Approach.}, journal = {Radiographics : a review publication of the Radiological Society of North America, Inc}, volume = {45}, number = {1}, pages = {e240067}, doi = {10.1148/rg.240067}, pmid = {39636751}, issn = {1527-1323}, mesh = {Humans ; *Motor Neuron Disease/diagnostic imaging ; Diagnosis, Differential ; Magnetic Resonance Imaging/methods ; Pyramidal Tracts/diagnostic imaging ; }, abstract = {White matter tracts within the central nervous system are organized into ascending and descending pathways that transmit sensory input and motor output, respectively. Tractopathy, or damage to these tracts, can impair sensory or motor functions. Motor neuron diseases are pathologic processes affecting the upper or lower motor neurons. Amyotrophic lateral sclerosis (ALS) is the most common form of acquired motor neuron disease. Traditionally, ALS has affected upper and lower motor neurons of the extremities, torso, and head and neck. There are several ALS variants, some of which affect only the upper motor neurons (eg, primary lateral sclerosis), lower motor neurons (eg, progressive muscular atrophy), or motor neurons of the head and neck (eg, progressive bulbar palsy). Characteristic imaging features of ALS include abnormal T2 hyperintensity within the brain along the corticospinal tract, as well as cortical susceptibility signal intensity along the precentral gyrus, termed the "motor band" sign. Spinal muscular atrophy is a less common primary motor neuron disease and appears on images as atrophy of the anterior horn of the spinal cord, as well as proximal muscle atrophy. In addition to pure motor neuron diseases, there are numerous toxic and metabolic conditions, genetic disorders, infectious diseases, and immune-mediated disorders that can secondarily affect the corticospinal tracts (corticospinal tractopathies), producing symptoms of upper motor neuron injury. These tractopathies are visible at MRI as T2-hyperintense lesions along varying segments of the corticospinal tract. A comprehensive diagnostic approach that integrates clinical symptoms with radiologic and laboratory findings is crucial to distinguish among these varied conditions. [©]RSNA, 2024 Supplemental material is available for this article.}, }
@article {pmid39628659, year = {2024}, author = {Ye, Q and Li, X and Gao, W and Gao, J and Zheng, L and Zhang, M and Yang, F and Li, H}, title = {Role of Rho-associated kinases and their inhibitor fasudil in neurodegenerative diseases.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1481983}, pmid = {39628659}, issn = {1662-4548}, abstract = {Neurodegenerative diseases (NDDs) are prevalent in the elderly. The pathogenesis of NDDs is complex, and currently, there is no cure available. With the increase in aging population, over 20 million people are affected by common NDDs alone (Alzheimer's disease and Parkinson's disease). Therefore, NDDs have profound negative impacts on patients, their families, and society, making them a major global health concern. Rho-associated kinases (ROCKs) belong to the serine/threonine protein kinases family, which modulate diverse cellular processes (e.g., apoptosis). ROCKs may elevate the risk of various NDDs (including Huntington's disease, Parkinson's disease, and Alzheimer's disease) by disrupting synaptic plasticity and promoting inflammatory responses. Therefore, ROCK inhibitors have been regarded as ideal therapies for NDDs in recent years. Fasudil, one of the classic ROCK inhibitor, is a potential drug for treating NDDs, as it repairs nerve damage and promotes axonal regeneration. Thus, the current review summarizes the relationship between ROCKs and NDDs and the mechanism by which fasudil inhibits ROCKs to provide new ideas for the treatment of NDDs.}, }
@article {pmid39627617, year = {2024}, author = {Wiersema, AF and Rennenberg, A and Smith, G and Varderidou-Minasian, S and Pasterkamp, RJ}, title = {Shared and distinct changes in the molecular cargo of extracellular vesicles in different neurodegenerative diseases.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {81}, number = {1}, pages = {479}, pmid = {39627617}, issn = {1420-9071}, support = {XS grant//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; GoALS//Stichting ALS Nederland/ ; TOTALS//Stichting ALS Nederland/ ; MUSALS//Stichting ALS Nederland/ ; ATAXALS//Stichting ALS Nederland/ ; MAXOMOD//E-rare3/ ; INTEGRALS//Rare-3/ ; TRIAGE//JPND/ ; }, mesh = {Animals ; Humans ; Alzheimer Disease/metabolism/pathology ; Amyloid beta-Peptides/metabolism ; Amyotrophic Lateral Sclerosis/metabolism/pathology ; Biomarkers/analysis/metabolism ; *Cell Communication ; *Extracellular Vesicles/metabolism ; MicroRNAs/metabolism/genetics ; *Neurodegenerative Diseases/diagnosis/metabolism/pathology ; Parkinson Disease/metabolism/pathology ; tau Proteins/metabolism ; }, abstract = {Neurodegenerative disorders such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) affect millions of people worldwide. Curative treatment for these neurodegenerative disorders is still lacking and therefore a further understanding of their cause and progression is urgently needed. Extracellular vesicles (EVs) are nanosized vesicles loaded with cargo, such as proteins and miRNAs, that are released by cells and play an important role in intercellular communication. Intercellular communication through EVs can contribute to the spread of pathological proteins, such as amyloid-beta and tau, or cause pathogenesis through other mechanisms. In addition, EVs may serve as potential biomarkers for diagnosis and for monitoring disease progression. In this review, we summarize and discuss recent advances in our understanding of the role of EVs in AD, ALS an PD with an emphasis on dysregulated cargo in each disease. We highlight shared dysregulated cargo between these diseases, discuss underlying pathways, and outline future implications for therapeutic strategies.}, }
@article {pmid39624969, year = {2024}, author = {Yuan, D and Jiang, S and Xu, R}, title = {Clinical features and progress in diagnosis and treatment of amyotrophic lateral sclerosis.}, journal = {Annals of medicine}, volume = {56}, number = {1}, pages = {2399962}, pmid = {39624969}, issn = {1365-2060}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/therapy/epidemiology/genetics ; Humans ; Prognosis ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of the central nervous system. Despite a large number of studies, the current prognosis of ALS is still not ideal. This article briefly describes the clinical features including epidemiology, genetic structure and clinical manifestations, as well as the progress of new diagnostic criteria and treatment of ALS. Meanwhile, we also discussed further both developments and improvements to enhance understanding and accelerating the introduction of the effective treatments of ALS.}, }
@article {pmid39622292, year = {2024}, author = {Ojo, O and Boateng, J and Pacella, R and Hanrahan, A and Essex, R and Dibley, L}, title = {Factors Influencing the Care and Management of Diabetic Foot Ulcers: A Scoping Review.}, journal = {Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.eprac.2024.11.010}, pmid = {39622292}, issn = {1530-891X}, abstract = {OBJECTIVE: The objective of this scoping review is to explore the experiences of patients' and healthcare practitioners on the factors that influence the care and management of diabetes-related foot ulcers (DFUs).
METHODS: Levac et al's 6-stage framework and the Preferred Reporting Items for Systematic Review and Meta-analysis extension for scoping reviews, guided the review. The SPIDER tool was used to define key elements of the review question. Searches for relevant articles were conducted in electronic databases (PUBMED, CINAHL, AMED, Embase, Cochrane Database of Systematic Reviews, and PsycINFO), Google Scholar, and hand searches of reference lists.
RESULTS: Eight articles met the inclusion criteria and were included in the review. Three themes were identified: Communication and Education about DFUs; Challenges of managing DFUs; and Barriers to treatment and management. The themes are presented as a narrative synthesis.
CONCLUSION: Inadequate knowledge of diabetic foot care by patients and inconsistent communication by healthcare professionals were primary factors affecting the effective management of diabetes-related foot ulcers. Consistent, patient-focused education that is supported by knowledgeable health care professionals should form the foundation of effective diabetic foot ulcer care.}, }
@article {pmid39614020, year = {2024}, author = {Shi, DL and Grifone, R and Zhang, X and Li, H}, title = {Rbm24-mediated post-transcriptional regulation of skeletal and cardiac muscle development, function and regeneration.}, journal = {Journal of muscle research and cell motility}, volume = {}, number = {}, pages = {}, pmid = {39614020}, issn = {1573-2657}, support = {23545//the French Muscular Dystrophy Association/ ; 23545//the French Muscular Dystrophy Association/ ; }, abstract = {RNA-binding proteins are critically involved in the post-transcriptional control of gene expression during embryonic development and in adult life, contributing to regulating cell differentiation and maintaining tissue homeostasis. Compared to the relatively well documented functions of transcription factors, the regulatory roles of RNA-binding proteins in muscle development and function remain largely elusive. However, deficiency of many RNA-binding proteins has been associated with muscular defects, neuromuscular disorders and heart diseases, such as myotonic dystrophy, amyotrophic lateral sclerosis, and cardiomyopathy. Rbm24 is highly conserved among vertebrates and is one of the best characterized RNA-binding proteins with crucial implication in the myogenic and cardiomyogenic programs. It presents the distinctive particularity of displaying highly restricted expression in both skeletal and cardiac muscles, with changes in subcellular localization during the process of differentiation. Functional analyses using different vertebrate models have clearly demonstrated its requirement for skeletal muscle differentiation and regeneration as well as for myocardium organization and cardiac function, by regulating the expression of both common and distinct target genes in these tissues. The challenge remains to decipher the dynamic feature of post-transcriptional circuits regulated by Rbm24 during skeletal myogenesis, cardiomyogenesis, and muscle repair. This review discusses current understanding of its function in striated muscles and its possible implication in human disease, with the aim of identifying research gaps for future investigation.}, }
@article {pmid39608699, year = {2024}, author = {Kale, MB and Wankhede, NL and Bishoyi, AK and Ballal, S and Kalia, R and Arya, R and Kumar, S and Khalid, M and Gulati, M and Umare, M and Taksande, BG and Upaganlawar, AB and Umekar, MJ and Kopalli, SR and Fareed, M and Koppula, S}, title = {Emerging biophysical techniques for probing synaptic transmission in neurodegenerative disorders.}, journal = {Neuroscience}, volume = {565}, number = {}, pages = {63-79}, doi = {10.1016/j.neuroscience.2024.11.055}, pmid = {39608699}, issn = {1873-7544}, abstract = {Plethora of research has shed light on the critical role of synaptic dysfunction in various neurodegenerative disorders (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). Synapses, the fundamental units for neural communication in the brain, are highly vulnerable to pathological conditions and are central to the progression of neurological diseases. The presynaptic terminal, a key component of synapses responsible for neurotransmitter release and synaptic communication, undergoes structural and functional alterations in these disorders. Understanding synaptic transmission abnormalities is crucial for unravelling the pathophysiological mechanisms underlying neurodegeneration. In the quest to probe synaptic transmission in NDDs, emerging biophysical techniques play a pivotal role. These advanced methods offer insights into the structural and functional changes occurring at nerve terminals in conditions like AD, PD, HD & ALS. By investigating synaptic plasticity and alterations in neurotransmitter release dynamics, researchers can uncover valuable information about disease progression and potential therapeutic targets. The review articles highlighted provide a comprehensive overview of how synaptic vulnerability and pathology are shared mechanisms across a spectrum of neurological disorders. In major neurodegenerative diseases, synaptic dysfunction is a common thread linking these conditions. The intricate molecular machinery involved in neurotransmitter release, synaptic vesicle dynamics, and presynaptic protein regulation are key areas of focus for understanding synaptic alterations in neurodegenerative diseases.}, }
@article {pmid39598374, year = {2024}, author = {Li, Y and Fu, J and Wang, H}, title = {Advancements in Targeting Ion Channels for the Treatment of Neurodegenerative Diseases.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {17}, number = {11}, pages = {}, pmid = {39598374}, issn = {1424-8247}, support = {2023YFF1205500//National Key Research and Development Program of China/ ; 82471465//NSFC/ ; C2024202005//Distinguished Young Scholars Science Fund of the Natural Science Foundation of Hebei Province/ ; JZX2023002//Technology Project of Hebei Education Department/ ; 22JCQNJC01110//Tianjin Applied Basic Research Project/ ; 236Z2602G, 246Z2605G, 236Z2401G//the central government guides local funds for science and technology development for Hebei Province/ ; NV20230015//The Key Laboratory of Neural and Vascular Biology, Ministry of Education/ ; }, abstract = {Ion channels are integral membrane proteins embedded in biological membranes, and they comprise specific proteins that control the flow of ion transporters in and out of cells, playing crucial roles in the biological functions of different cells. They maintain the homeostasis of water and ion metabolism by facilitating ion transport and participate in the physiological processes of neurons and glial cells by regulating signaling pathways. Neurodegenerative diseases are a group of disorders characterized by the progressive loss of neurons in the central nervous system (CNS) or peripheral nervous system (PNS). Despite significant progress in understanding the pathophysiological processes of various neurological diseases in recent years, effective treatments for mitigating the damage caused by these diseases remain inadequate. Increasing evidence suggests that ion channels are closely associated with neuroinflammation; oxidative stress; and the characteristic proteins in neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Therefore, studying the pathogenic mechanisms closely related to ion channels in neurodegenerative diseases can help identify more effective therapeutic targets for treating neurodegenerative diseases. Here, we discuss the progress of research on ion channels in different neurodegenerative diseases and emphasize the feasibility and potential of treating such diseases from the perspective of ion channels.}, }
@article {pmid39596864, year = {2024}, author = {McKenna, MC and Kleinerova, J and Power, A and Garcia-Gallardo, A and Tan, EL and Bede, P}, title = {Quantitative and Computational Spinal Imaging in Neurodegenerative Conditions and Acquired Spinal Disorders: Academic Advances and Clinical Prospects.}, journal = {Biology}, volume = {13}, number = {11}, pages = {}, pmid = {39596864}, issn = {2079-7737}, support = {2023//Spastic Paraplegia Foundation/ ; }, abstract = {Introduction: Quantitative spinal cord imaging has facilitated the objective appraisal of spinal cord pathology in a range of neurological conditions both in the academic and clinical setting. Diverse methodological approaches have been implemented, encompassing a range of morphometric, diffusivity, susceptibility, magnetization transfer, and spectroscopy techniques. Advances have been fueled both by new MRI platforms and acquisition protocols as well as novel analysis pipelines. The quantitative evaluation of specific spinal tracts and grey matter indices has the potential to be used in diagnostic and monitoring applications. The comprehensive characterization of spinal disease burden in pre-symptomatic cohorts, in carriers of specific genetic mutations, and in conditions primarily associated with cerebral disease, has contributed important academic insights. Methods: A narrative review was conducted to examine the clinical and academic role of quantitative spinal cord imaging in a range of neurodegenerative and acquired spinal cord disorders, including hereditary spastic paraparesis, hereditary ataxias, motor neuron diseases, Huntington's disease, and post-infectious or vascular disorders. Results: The clinical utility of specific methods, sample size considerations, academic role of spinal imaging, key radiological findings, and relevant clinical correlates are presented in each disease group. Conclusions: Quantitative spinal cord imaging studies have demonstrated the feasibility to reliably appraise structural, microstructural, diffusivity, and metabolic spinal cord alterations. Despite the notable academic advances, novel acquisition protocols and analysis pipelines are yet to be implemented in the clinical setting.}, }
@article {pmid39596609, year = {2024}, author = {Luglio, A and Maggi, E and Riviello, FN and Conforti, A and Sorrentino, U and Zuccarello, D}, title = {Hereditary Neuromuscular Disorders in Reproductive Medicine.}, journal = {Genes}, volume = {15}, number = {11}, pages = {}, pmid = {39596609}, issn = {2073-4425}, support = {PNRR-MR1-2022-12376108//European Union/ ; }, mesh = {Humans ; *Neuromuscular Diseases/genetics/diagnosis ; Female ; Pregnancy ; Reproductive Medicine/methods ; Genetic Testing/methods ; Prenatal Diagnosis ; Preimplantation Diagnosis ; Muscular Atrophy, Spinal/genetics ; Charcot-Marie-Tooth Disease/genetics/diagnosis ; }, abstract = {Neuromuscular disorders (NMDs) encompass a broad range of hereditary and acquired conditions that affect motor units, significantly impacting patients' quality of life and reproductive health. This narrative review aims to explore in detail the reproductive challenges associated with major hereditary NMDs, including Charcot-Marie-Tooth disease (CMT), dystrophinopathies, Myotonic Dystrophy (DM), Facioscapulohumeral Muscular Dystrophy (FSHD), Spinal Muscular Atrophy (SMA), Limb-Girdle Muscular Dystrophy (LGMD), and Amyotrophic Lateral Sclerosis (ALS). Specifically, it discusses the stages of diagnosis and genetic testing, recurrence risk estimation, options for preimplantation genetic testing (PGT) and prenatal diagnosis (PND), the reciprocal influence between pregnancy and disease, potential obstetric complications, and risks to the newborn.}, }
@article {pmid39596445, year = {2024}, author = {Jiang, LL and Zhang, XL and Hu, HY}, title = {Co-Aggregation of TDP-43 with Other Pathogenic Proteins and Their Co-Pathologies in Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {22}, pages = {}, pmid = {39596445}, issn = {1422-0067}, support = {31670782, 31700669//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology ; *DNA-Binding Proteins/metabolism ; *Protein Aggregation, Pathological/metabolism ; Animals ; Amyotrophic Lateral Sclerosis/metabolism/pathology ; Protein Aggregates ; }, abstract = {Pathological aggregation of a specific protein into insoluble aggregates is a common hallmark of various neurodegenerative diseases (NDDs). In the earlier literature, each NDD is characterized by the aggregation of one or two pathogenic proteins, which can serve as disease-specific biomarkers. The aggregation of these specific proteins is thought to be a major cause of or deleterious result in most NDDs. However, accumulating evidence shows that a pathogenic protein can interact and co-aggregate with other pathogenic proteins in different NDDs, thereby contributing to disease onset and progression synergistically. During the past years, more than one type of NDD has been found to co-exist in some individuals, which may increase the complexity and pathogenicity of these diseases. This article reviews and discusses the biochemical characteristics and molecular mechanisms underlying the co-aggregation and co-pathologies associated with TDP-43 pathology. The TDP-43 aggregates, as a hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), can often be detected in other NDDs, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and spinocerebellar ataxia type 2 (SCA2). In many cases, TDP-43 is shown to interact and co-aggregate with multiple pathogenic proteins in vitro and in vivo. Furthermore, the co-occurrence and co-aggregation of TDP-43 with other pathogenic proteins have important consequences that may aggravate the diseases. Thus, the current viewpoint that the co-aggregation of TDP-43 with other pathogenic proteins in NDDs and their relevance to disease progression may gain insights into the patho-mechanisms and therapeutic potential of various NDDs.}, }
@article {pmid39595895, year = {2024}, author = {Pongrácová, E and Buratti, E and Romano, M}, title = {Prion-like Spreading of Disease in TDP-43 Proteinopathies.}, journal = {Brain sciences}, volume = {14}, number = {11}, pages = {}, pmid = {39595895}, issn = {2076-3425}, abstract = {TDP-43 is a ubiquitous nuclear protein that plays a central role in neurodegenerative disorders collectively known as TDP-43 proteinopathies. Under physiological conditions, TDP-43 is primarily localized to the nucleus, but in its pathological form it aggregates in the cytoplasm, contributing to neuronal death. Given its association with numerous diseases, particularly ALS and FTLD, the mechanisms underlying TDP-43 aggregation and its impact on neuronal function have been extensively investigated. However, little is still known about the spreading of this pathology from cell to cell. Recent research has unveiled the possibility that TDP-43 may possess prion-like properties. Specifically, misfolded TDP-43 aggregates can act as templates inducing conformational changes in native TDP-43 molecules and propagating the misfolded state across neural networks. This review summarizes the mounting and most recent evidence from in vitro and in vivo studies supporting the prion-like hypothesis and its underlying mechanisms. The prion-like behavior of TDP-43 has significant implications for diagnostics and therapeutics. Importantly, emerging strategies such as small molecule inhibitors, immunotherapies, and gene therapies targeting TDP-43 propagation offer promising avenues for developing effective treatments. By elucidating the mechanisms of TDP-43 spreading, we therefore aim to pave the way for novel therapies for TDP-43-related neurodegenerative diseases.}, }
@article {pmid39595812, year = {2024}, author = {Zhang, S and Yang, Y and Lv, X and Zhou, X and Zhao, W and Meng, L and Zhu, S and Zhang, Z and Wang, Y}, title = {Exosome Cargo in Neurodegenerative Diseases: Leveraging Their Intercellular Communication Capabilities for Biomarker Discovery and Therapeutic Delivery.}, journal = {Brain sciences}, volume = {14}, number = {11}, pages = {}, pmid = {39595812}, issn = {2076-3425}, support = {82171871//National Natural Science Foundation of China/ ; BK20230488//Youth Fund Project of the Jiangsu Province Basic Research Program (Natural Science Foundation)/ ; None//Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)/ ; }, abstract = {The inexorable progression of neurodegenerative diseases (NDs), including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis, is closely related to irreversible brain decline. Accurately characterizing pathophysiological features and identifying reliable biomarkers for early diagnosis and optimized treatment are critical. Hindered by the blood-brain barrier (BBB), obtaining sensitive monitoring indicators for disease progression and achieving efficient drug delivery remain significant challenges. Exosomes, endogenous nanoscale vesicles that carry key bioactive substances, reflect the intracellular environment and play an important role in cell signaling. They have shown promise in traversing the BBB, serving dual roles as potential biomarkers for NDs and vehicles for targeted drug delivery. However, the specific mechanisms by which exosome influence NDs are not fully understood, necessitating further investigation into their attributes and functionalities in the context of NDs. This review explores how exosomes mediate multifaceted interactions, particularly in exacerbating pathogenic processes such as oxidative stress, neuronal dysfunction, and apoptosis integral to NDs. It provides a comprehensive analysis of the profound impact of exosomes under stress and disease states, assessing their prospective utility as biomarkers and drug delivery vectors, offering new perspectives for tackling these challenging diseases.}, }
@article {pmid39595543, year = {2024}, author = {Stoccoro, A and Coppedè, F}, title = {Exposure to Metals, Pesticides, and Air Pollutants: Focus on Resulting DNA Methylation Changes in Neurodegenerative Diseases.}, journal = {Biomolecules}, volume = {14}, number = {11}, pages = {}, pmid = {39595543}, issn = {2218-273X}, mesh = {*DNA Methylation/drug effects ; Humans ; *Pesticides/toxicity/adverse effects ; *Neurodegenerative Diseases/genetics/metabolism/chemically induced ; *Epigenesis, Genetic/drug effects ; *Air Pollutants/toxicity/adverse effects ; Environmental Exposure/adverse effects ; Animals ; Metals, Heavy/toxicity/adverse effects ; Metals/toxicity/metabolism/adverse effects ; }, abstract = {Individuals affected by neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are dramatically increasing worldwide. Thus, several efforts are being made to develop strategies for stopping or slowing the spread of these illnesses. Although causative genetic variants linked to the onset of these diseases are known, they can explain only a small portion of cases. The etiopathology underlying the neurodegenerative process in most of the patients is likely due to the interplay between predisposing genetic variants and environmental factors. Epigenetic mechanisms, including DNA methylation, are central candidates in translating the effects of environmental factors in genome modulation, and they play a critical role in the etiology of AD, PD, and ALS. Among the main environmental exposures that have been linked to an increased risk for these diseases, accumulating evidence points to the role of heavy metals, pesticides, and air pollutants. These compounds could trigger neurodegeneration through different mechanisms, mainly neuroinflammation and the induction of oxidative stress. However, increasing evidence suggests that they are also capable of inducing epigenetic alterations in neurons. In this article, we review the available literature linking exposure to metals, pesticides, and air pollutants to DNA methylation changes relevant to neurodegeneration.}, }
@article {pmid39593881, year = {2024}, author = {Favier, G and Rocha, DS}, title = {Overview of Tensor-Based Cooperative MIMO Communication Systems-Part 2: Semi-Blind Receivers.}, journal = {Entropy (Basel, Switzerland)}, volume = {26}, number = {11}, pages = {}, pmid = {39593881}, issn = {1099-4300}, abstract = {Cooperative MIMO communication systems play an important role in the development of future sixth-generation (6G) wireless systems incorporating new technologies such as massive MIMO relay systems, dual-polarized antenna arrays, millimeter-wave communications, and, more recently, communications assisted using intelligent reflecting surfaces (IRSs), and unmanned aerial vehicles (UAVs). In a companion paper, we provided an overview of cooperative communication systems from a tensor modeling perspective. The objective of the present paper is to provide a comprehensive tutorial on semi-blind receivers for MIMO one-way two-hop relay systems, allowing the joint estimation of transmitted symbols and individual communication channels with only a few pilot symbols. After a reminder of some tensor prerequisites, we present an overview of tensor models, with a detailed, unified, and original description of two classes of tensor decomposition frequently used in the design of relay systems, namely nested CPD/PARAFAC and nested Tucker decomposition (TD). Some new variants of nested models are introduced. Uniqueness and identifiability conditions, depending on the algorithm used to estimate the parameters of these models, are established. Two families of algorithms are presented: iterative algorithms based on alternating least squares (ALS) and closed-form solutions using Khatri-Rao and Kronecker factorization methods, which consist of SVD-based rank-one matrix or tensor approximations. In a second part of the paper, the overview of cooperative communication systems is completed before presenting several two-hop relay systems using different codings and configurations in terms of relaying protocol (AF/DF) and channel modeling. The aim of this presentation is firstly to show how these choices lead to different nested tensor models for the signals received at destination. Then, by capitalizing on these models and their correspondence with the generic models studied in the first part, we derive semi-blind receivers to jointly estimate the transmitted symbols and the individual communication channels for each relay system considered. In a third part, extensive Monte Carlo simulation results are presented to compare the performance of relay systems and associated semi-blind receivers in terms of the symbol error rate (SER) and channel estimate normalized mean-square error (NMSE). Their computation time is also compared. Finally, some perspectives are drawn for future research work.}, }
@article {pmid39592088, year = {2024}, author = {Mahakalakar, N and Mohariya, G and Taksande, B and Kotagale, N and Umekar, M and Vinchurney, M}, title = {"Nattokinase as a potential therapeutic agent for preventing blood-brain barrier dysfunction in neurodegenerative disorders".}, journal = {Brain research}, volume = {1849}, number = {}, pages = {149352}, doi = {10.1016/j.brainres.2024.149352}, pmid = {39592088}, issn = {1872-6240}, abstract = {Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis are characterized by progressive destruction of neurons and cognitive impairment, and thorough studies have provided evidence that these pathologies have a close relationship to the failure of the blood-brain barrier (BBB). Nattokinase (NK), a protease found in fermented soybeans, has been extensively studied because it displays powerful neuroprotective abilities, which is why current research was reviewed in the present article. It was concluded that there is enough evidence in preclinical studies using experimental animals that NK supplementation can alleviate the condition related to BBB dysfunction, reduce brain inflammation, and improve cognitive ability. Furthermore, the study of NK on the cardiovascular system leads to certain assumptions, which include the impact on vasculature function and the ability to manage blood flow, which is the key feature of BBB integrity. Such assumed mechanisms are fibrinolytic action, anti-inflammatory and antioxidant action, and endothelium function modulation. There are many positive research findings, and it seems that NK may serve as an effective opponent for BBB breakdown; however, a new research level should be taken to disclose the application and therapeutic use of NK in brain neurodegenerative disease.}, }
@article {pmid39592063, year = {2024}, author = {Lorenc, F and Dupuis, L and Cassel, R}, title = {Impairments of inhibitory neurons in amyotrophic lateral sclerosis and frontotemporal dementia.}, journal = {Neurobiology of disease}, volume = {203}, number = {}, pages = {106748}, doi = {10.1016/j.nbd.2024.106748}, pmid = {39592063}, issn = {1095-953X}, mesh = {*Amyotrophic Lateral Sclerosis/pathology/physiopathology ; *Frontotemporal Dementia/pathology/physiopathology ; Humans ; Animals ; *Neurons/pathology ; *Neural Inhibition/physiology ; }, abstract = {Amyotrophic lateral sclerosis and frontotemporal dementia are two fatal neurodegenerative disorders. They are part of a pathophysiological continuum, displaying clinical, neuropathological, and genetic overlaps. There is compelling evidence that neuronal circuit dysfunction is an early feature of both diseases. Impaired neuronal excitability, imbalanced excitatory and inhibitory influences, and altered functional connectivity have been reported. These phenomena are likely due to combined alterations in the various cellular components involved in the functioning of neuronal networks. This review focuses on one of these cellular components: inhibitory neurons. We assess the evidence for inhibitory neuron impairments in amyotrophic lateral sclerosis and frontotemporal dementia, as well as the mechanisms leading to the loss of inhibition. We also discuss the contributions of these alterations to symptoms, and the potential therapeutic strategies for targeting inhibitory neuron deficits.}, }
@article {pmid39585162, year = {2024}, author = {Savvidis, C and Kouroglou, E and Kallistrou, E and Ragia, D and Dionysopoulou, S and Gavriiloglou, G and Tsiama, V and Proikaki, S and Belis, K and Ilias, I}, title = {IGFBP-2 in Critical Illness: A Prognostic Marker in the Growth Hormone/Insulin-like Growth Factor Axis.}, journal = {Pathophysiology : the official journal of the International Society for Pathophysiology}, volume = {31}, number = {4}, pages = {621-630}, pmid = {39585162}, issn = {1873-149X}, abstract = {Critical illness (CI) triggers complex disruptions in the growth hormone (GH)/insulin-like growth factor (IGF) axis, significantly affecting the dynamics of insulin-like growth-factor-binding proteins (IGFBPs). Among these, IGFBP-2 shows a sustained elevation during CI, which inversely correlates with serum levels of IGF-1, IGFBP-3, and the acid-labile subunit (ALS). Although IGFBP-2 does not directly interact with ALS, it may influence the availability of IGFs by competing with other IGFBPs for binding to IGF-1 and IGF-2. Research suggests that this persistent elevation of IGFBP-2 is largely driven by cytokine activity during CI, reflecting an adaptive response rather than a direct result of GH/IGF axis dysregulation. The clinical importance of IGFBP-2 is emphasized by its correlation with disease severity in conditions like sepsis and coronavirus disease 2019 (COVID-19), where its levels are markedly elevated compared to healthy controls and are similar to those observed in sepsis from various causes. Beyond its role in endocrine regulation, IGFBP-2 appears to play a part in metabolic and inflammatory pathways. Elevated IGFBP-2 levels have been linked to increased mortality and longer hospital stays, indicating its potential utility as a prognostic marker. Furthermore, measuring plasma IGFBP-2 may have other diagnostic applications, aiding in the assessment of CI when traditional biomarkers are inconclusive.}, }
@article {pmid39584466, year = {2024}, author = {Daneshpour, A and Rezvanimehr, A and Niktalab, P and Sharif, H and Yazdanpanah, N and Saleki, K and Rezaei, N}, title = {Exploring the role of vault complex in the nervous system: a literature review.}, journal = {Reviews in the neurosciences}, volume = {}, number = {}, pages = {}, pmid = {39584466}, issn = {2191-0200}, abstract = {Vault RNAs (vtRNAs) are a novel group of non-coding RNAs that are involved in various signaling mechanisms. vtRNAs are joined by three proteins major vault protein (MVP), vault poly (ADP-ribose) polymerase (VPARP), and telomerase-associated protein 1 (TEP1) to form the vault complex. In humans, only four vtRNA including vtRNA 1-1, vtRNA 1-2, vtRNA 1-3, vtRNA 2-1) have been discovered. In nerve cells, vtRNA is involved in synapse formation through MAPK signaling. vtRNA travels to the distal area of neurites as a key unit in the vault complex. Moreover, tRNA is detached from the vault complex in the neurite via a mitotic kinase Aurora-A-reliant MVP phosphorylation. Several molecules contribute to the formation of vtRNAs. For instance, SRSF2 and NSUN2 and their attachment to vtRNA1-1 determines the production of small-vtRNAs. Through the same factors, vtRNAs could play a role in neurodevelopmental deficits. Addition the role of vtRNA expression and vault proteins has been recently studied in neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) as well as brain cancers. While the mechanisms of vtRNA involvement in neurological disorders is not well-demonstrated, we believe this could be related to the impact of vtRNA regulation in autophagy, immunoregulation, RNA stability, cellular stress, apoptosis, and regulation of other epigenetic pathways. The present review captures the state-of-the-art regarding the role of vtRNAs in neurodevelopment, normal nervous system function, and neurological disorders.}, }
@article {pmid39579963, year = {2024}, author = {Carracedo, S and Launay, A and Dechelle-Marquet, PA and Faivre, E and Blum, D and Delarasse, C and Boué-Grabot, E}, title = {Purinergic-associated immune responses in neurodegenerative diseases.}, journal = {Progress in neurobiology}, volume = {243}, number = {}, pages = {102693}, doi = {10.1016/j.pneurobio.2024.102693}, pmid = {39579963}, issn = {1873-5118}, mesh = {Humans ; *Neurodegenerative Diseases/immunology/metabolism ; Animals ; *Receptors, Purinergic/metabolism ; }, abstract = {The chronic activation of immune cells can participate in the development of pathological conditions such as neurodegenerative diseases including Alzheimer's disease (AD), Multiple Sclerosis (MS), Parkinson's disease (PD), Huntington's disease (HD) and Amyotrophic Lateral Sclerosis (ALS). In recent years, compelling evidence indicates that purinergic signaling plays a key role in neuro-immune cell functions. The extracellular release of adenosine 5'-triphosphate (ATP), and its breakdown products (ADP and adenosine) provide the versatile basis for complex purinergic signaling through the activation of several families of receptors. G-protein coupled adenosine A2A receptors, ionotropic P2X and G-protein coupled P2Y receptors for ATP and other nucleotides are abundant and widely distributed in neurons, microglia, and astrocytes of the central nervous system as well as in peripheral immune cells. These receptors are strongly linked to inflammation, with a functional interplay that may influence the intricate purinergic signaling involved in inflammatory responses. In the present review, we examine the roles of the purinergic receptors in neuro-immune cell functions with particular emphasis on A2AR, P2X4 and P2X7 and their possible relevance to specific neurodegenerative disorders. Understanding the molecular mechanisms governing purinergic receptor interaction will be crucial for advancing the development of effective immunotherapies targeting neurodegenerative diseases.}, }
@article {pmid39578404, year = {2024}, author = {Phrathep, DD and Abdo, Z and Tadros, M and Lewandowski, E and Evans, J}, title = {The role of osteopathic manipulative treatment for dystonia: a literature review.}, journal = {Journal of osteopathic medicine}, volume = {}, number = {}, pages = {}, pmid = {39578404}, issn = {2702-3648}, abstract = {CONTEXT: Dystonia is a movement disorder that causes involuntary muscle contractions leading to abnormal movements and postures, such as twisting. Dystonia is the third most common movement disorder in the United States, with as many as 250,000 people affected. Because of its complexity, dystonia presents a significant challenge in terms of management and treatment. Despite limited research, osteopathic manipulative treatment (OMT) has been considered as an adjunctive treatment due to its inexpensive and noninvasive nature, as opposed to other modalities such as botulinum toxin injections, deep brain stimulation (DBS), and transcranial magnetic stimulation, which are often expensive and inaccessible. OMT treatments performed in case studies and series such as balanced ligamentous tension/articular ligamentous strain (BLT/ALS), muscle energy (ME), high-velocity low-amplitude (HVLA), and myofascial release (MFR) have shown reduction of pain and muscle hypertonicity, including in patients with dystonia.
OBJECTIVES: The studies reviewed in this paper provide a snapshot of the literature regarding the current evidence of OMT's role for dystonia.
METHODS: A medical reference librarian conducted a thorough literature search across multiple databases including PubMed and Google Scholar to find articles relevant to the use of OMT for dystonia. The search employed a combination of Medical Subject Headings (MeSH) terms and keywords related to osteopathic medicine and dystonia to ensure precise retrieval of relevant articles within the last 20 years. Despite limited research on the topic, all four relevant reports found in the literature were selected for review.
RESULTS: Of the four relevant reports, case series and studies highlighted the potential benefits of OMT in managing dystonia, particularly cervical dystonia and foot dystonia. OMT has shown promising results addressing pain, stiffness, and impaired motor function. In cases of foot dystonia in Parkinson's disease, OMT has helped improve gait and reduce pain by targeting somatic dysfunctions (SDs) associated with dystonia, such as abnormalities in foot progression angle (FPA) and musculoskeletal imbalances. Also, OMT has been found to alleviate symptoms of cervical dystonia, including tremors, muscle spasms, and neck stiffness. These interventions performed in case studies and series led to improvements in gait biomechanics in foot dystonia and overall symptom severity in patients with cervical dystonia.
CONCLUSIONS: Currently, botulinum toxin, oral medications, physical therapy, and rehabilitation are commonly utilized in managing dystonia. The studies reviewed in this paper suggest that these treatments may lead to improvements in pain and muscle hypertonicity in patients with dystonia. It is important to investigate whether factors such as the type of dystonia (eg, focal vs. segmental) and its underlying cause (eg, idiopathic, trauma, infection, autoimmune, medication side effects) influence treatment outcomes. Further research is recommended to explore the role of OMT in managing dystonia.}, }
@article {pmid39577774, year = {2025}, author = {Olesen, MA and Villavicencio-Tejo, F and Cuevas-Espinoza, V and Quintanilla, RA}, title = {Unknown roles of tau pathology in neurological disorders. Challenges and new perspectives.}, journal = {Ageing research reviews}, volume = {103}, number = {}, pages = {102594}, doi = {10.1016/j.arr.2024.102594}, pmid = {39577774}, issn = {1872-9649}, mesh = {Humans ; *tau Proteins/metabolism ; Animals ; *Nervous System Diseases/metabolism/pathology ; Tauopathies/metabolism/pathology ; Aging/metabolism/pathology ; }, abstract = {Aging presents progressive changes that increase the susceptibility of the central nervous system (CNS) to suffer neurological disorders (NDs). Several studies have reported that an aged brain suffering from NDs shows the presence of pathological forms of tau protein, a microtubule accessory protein (MAP) critical for neuronal function. In this context, accumulative evidence has shown a pivotal contribution of pathological forms of tau to Alzheimer's disease (AD) and tauopathies. However, current investigations have implicated tau toxicity in other NDs that affect the central nervous system (CNS), including Parkinson's disease (PD), Huntington's disease (HD), Traumatic brain injury (TBI), Multiple sclerosis (MS), and Amyotrophic lateral sclerosis (ALS). These diseases are long-term acquired, affecting essential functions such as motor movement, cognition, hearing, and vision. Previous evidence indicated that toxic forms of tau do not have a critical contribution to the genesis or progression of these diseases. However, recent studies have shown that these tau forms contribute to neuronal dysfunction, inflammation, oxidative damage, and mitochondrial impairment events that contribute to the pathogenesis of these NDs. Recent studies have suggested that these neuropathologies could be associated with a prion-like behavior of tau, which induces a pathological dissemination of these toxic protein forms to different brain areas. Moreover, it has been suggested that this toxic propagation of tau from neurons into neighboring cells impairs the function of glial cells, oligodendrocytes, and endothelial cells by affecting metabolic function and mitochondrial health and inducing oxidative damage by tau pathology. Therefore, in this review, we will discuss current evidence demonstrating the critical role of toxic tau forms on NDs not related to AD and how its propagation and induced-bioenergetics failure may contribute to the pathogenic mechanism present in these NDs.}, }
@article {pmid39577228, year = {2025}, author = {Sojdeh, S and Safarkhani, M and Daneshgar, H and Aldhaher, A and Heidari, G and Nazarzadeh Zare, E and Iravani, S and Zarrabi, A and Rabiee, N}, title = {Promising breakthroughs in amyotrophic lateral sclerosis treatment through nanotechnology's unexplored frontier.}, journal = {European journal of medicinal chemistry}, volume = {282}, number = {}, pages = {117080}, doi = {10.1016/j.ejmech.2024.117080}, pmid = {39577228}, issn = {1768-3254}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/therapy ; Humans ; *Nanotechnology ; Genetic Therapy ; Animals ; Drug Delivery Systems ; Neuroprotective Agents/chemistry/therapeutic use/pharmacology ; }, abstract = {This review explores the transformative potential of nanotechnology in the treatment and diagnosis of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disorder characterized by motor neuron degeneration, muscle weakness, and eventual paralysis. Nanotechnology offers innovative solutions across various domains, including targeted drug delivery, neuroprotection, gene therapy and editing, biomarker detection, advanced imaging techniques, and tissue engineering. By enhancing the precision and efficacy of therapeutic interventions, nanotechnology facilitates key advancements such as crossing the blood-brain barrier, targeting specific cell types, achieving sustained therapeutic release, and enabling combination therapies tailored to the complex pathophysiology of ALS. Despite its immense promise, the clinical translation of these approaches faces challenges, including potential cytotoxicity, biocompatibility, and regulatory compliance, which must be addressed through rigorous research and testing. This review emphasizes the application of nanotechnology in targeted drug delivery and gene therapy/editing for ALS, drawing on the author's prior work with various nanotechnological platforms to illustrate strategies for overcoming similar obstacles in drug and gene delivery. By bridging the gap between cutting-edge technology and clinical application, this article aims to highlight the vital role of nanotechnology in shaping the future of ALS treatment.}, }
@article {pmid39575748, year = {2024}, author = {Xu, Z and He, S and Begum, MM and Han, X}, title = {Myelin Lipid Alterations in Neurodegenerative Diseases: Landscape and Pathogenic Implications.}, journal = {Antioxidants & redox signaling}, volume = {41}, number = {16-18}, pages = {1073-1099}, doi = {10.1089/ars.2024.0676}, pmid = {39575748}, issn = {1557-7716}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; *Myelin Sheath/metabolism ; *Lipid Metabolism ; Animals ; Lipids ; }, abstract = {Significance: Lipids, which constitute the highest portion (over 50%) of brain dry mass, are crucial for brain integrity, energy homeostasis, and signaling regulation. Emerging evidence revealed that lipid profile alterations and abnormal lipid metabolism occur during normal aging and in different forms of neurodegenerative diseases. Moreover, increasing genome-wide association studies have validated new targets on lipid-associated pathways involved in disease development. Myelin, the protective sheath surrounding axons, is crucial for efficient neural signaling transduction. As the primary site enriched with lipids, impairments of myelin are increasingly recognized as playing significant and complex roles in various neurodegenerative diseases, beyond simply being secondary effects of neuronal loss. Recent Advances: With advances in the lipidomics field, myelin lipid alterations and their roles in contributing to or reflecting the progression of diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, and others, have recently caught great attention. Critical Issues: This review summarizes recent findings of myelin lipid alterations in the five most common neurodegenerative diseases and discusses their implications in disease pathogenesis. Future Directions: By highlighting myelin lipid abnormalities in neurodegenerative diseases, this review aims to encourage further research focused on lipids and the development of new lipid-oriented therapeutic approaches in this area. Antioxid. Redox Signal. 00, 000-000.}, }
@article {pmid39572211, year = {2024}, author = {Benatar, M and Heiman-Patterson, TD and Cooper-Knock, J and Brickman, D and Casaletto, KB and Goutman, SA and Vinceti, M and Dratch, L and Arias, JJ and Swidler, J and Turner, MR and Shefner, J and Westeneng, HJ and van den Berg, LH and Al-Chalabi, A and , and , }, title = {Guidance for clinical management of pathogenic variant carriers at elevated genetic risk for ALS/FTD.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {}, number = {}, pages = {}, doi = {10.1136/jnnp-2024-334339}, pmid = {39572211}, issn = {1468-330X}, abstract = {There is a growing understanding of the presymptomatic stages of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) and nascent efforts aiming to prevent these devastating neurodegenerative diseases have emerged. This progress is attributable, in no small part, to the altruism of people living with pathogenic variants at elevated genetic risk for ALS/FTD via their willingness to participate in natural history studies and disease prevention trials. Increasingly, this community has also highlighted the urgent need to develop paradigms for providing appropriate clinical care for those at elevated risk for ALS and FTD. This manuscript summarises recommendations emanating from a multi-stakeholder Workshop (Malvern, Pennsylvania, 2023) that aimed to develop guidance for at-risk carriers and their treating physicians. Clinical care recommendations span genetic testing (including counselling and sociolegal implications); monitoring for the emergence of early motor, cognitive and behavioural signs of disease; and the use of Food and Drug Administration-approved small molecule drugs and gene-targeting therapies. Lifestyle recommendations focus on exercise, smoking, statin use, supplement use, caffeine intake and head trauma, as well as occupational and environmental exposures. While the evidence base to inform clinical and lifestyle recommendations is limited, this guidance document aims to appraise carriers and clinicians of the issues and best available evidence, and also to define the research agenda that could yield more evidence-informed guidelines.}, }
@article {pmid39569894, year = {2024}, author = {Brannigan, JFM and Liyanage, K and Horsfall, HL and Bashford, L and Muirhead, W and Fry, A}, title = {Brain-computer interfaces patient preferences: a systematic review.}, journal = {Journal of neural engineering}, volume = {21}, number = {6}, pages = {}, doi = {10.1088/1741-2552/ad94a6}, pmid = {39569894}, issn = {1741-2552}, mesh = {*Brain-Computer Interfaces ; Humans ; *Patient Preference ; Adult ; Middle Aged ; Spinal Cord Injuries/rehabilitation/psychology/physiopathology ; Amyotrophic Lateral Sclerosis/psychology/rehabilitation/physiopathology ; }, abstract = {Objective. Brain-computer interfaces (BCIs) have the potential to restore motor capabilities and functional independence in individuals with motor impairments. Despite accelerating advances in the performance of implanted devices, few studies have identified patient preferences underlying device design, and each study typically captures a single aetiology of motor impairment. We aimed to characterise BCI patient preferences in a large cohort across multiple aetiologies.Approach. We performed a systematic review of all published studies reporting patient preferences for BCI devices, including both qualitative and quantitative data. We searched MEDLINE, Embase, and CINAHL from inception to 18 April 2023. Two reviewers independently screened articles and extracted data on demographic information, device use, invasiveness preference, device design, and functional preferences.Main results. From 1316 articles identified, 28 studies met inclusion criteria, capturing preferences from 1701 patients (mean age 42.1-64.3 years). The most represented conditions were amyotrophic lateral sclerosis (n= 15 studies, 53.6%) and spinal cord injury (n= 13 studies 46.4%). Individuals with motor impairments prioritised device accuracy over other design characteristics. In four studies where patients ranked performance characteristics, accuracy was ranked first each time. We found that the speed and accuracy of BCI systems in recent publications exceeds reported patient preferences, however this performance has been achieved with a level of training and setup burden that would not be tolerated by most patients. Preferences varied by disease aetiology and severity; amyotrophic lateral sclerosis patients typically prioritised communication functions, whereas spinal cord injury patients emphasised limb control and sphincteric functions.Significance.Our findings highlight that despite advances in BCI performance exceeding patient expectations, there remains a need to reduce training and setup burdens to enhance usability. Moreover, patient preferences differ across conditions and impairment severities, underscoring the importance of personalised BCI configurations and tailored training regimens to meet individual needs.}, }
@article {pmid39567497, year = {2024}, author = {Zhu, Z and Song, M and Ren, J and Liang, L and Mao, G and Chen, M}, title = {Copper homeostasis and cuproptosis in central nervous system diseases.}, journal = {Cell death & disease}, volume = {15}, number = {11}, pages = {850}, pmid = {39567497}, issn = {2041-4889}, mesh = {Humans ; *Copper/metabolism ; *Homeostasis ; *Central Nervous System Diseases/metabolism/pathology ; Animals ; }, abstract = {Copper (Cu), an indispensable micronutrient for the sustenance of living organisms, contributes significantly to a vast array of fundamental metabolic processes. The human body maintains a relatively low concentration of copper, which is mostly found in the bones, liver, and brain. Despite its low concentration, Cu plays a crucial role as an indispensable element in the progression and pathogenesis of central nervous system (CNS) diseases. Extensive studies have been conducted in recent years on copper homeostasis and copper-induced cell death in CNS disorders, including glioma, Alzheimer's disease, Amyotrophic lateral sclerosis, Huntington's disease, and stroke. Cuproptosis, a novel copper-induced cell death pathway distinct from apoptosis, necrosis, pyroptosis, and ferroptosis, has been identified as potentially intricately linked to the pathogenic mechanisms underlying various CNS diseases. Therefore, a systematic review of copper homeostasis and cuproptosis and their relationship with CNS disorders could deepen our understanding of the pathogenesis of these diseases. In addition, it may provide new insights and strategies for the treatment of CNS disorders.}, }
@article {pmid39567371, year = {2024}, author = {Nuzum, ND and Deady, C and Kittel-Schneider, S and Cryan, JF and O'Mahony, SM and Clarke, G}, title = {More than just a number: the gut microbiota and brain function across the extremes of life.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2418988}, pmid = {39567371}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Brain/microbiology ; Animals ; Brain-Gut Axis/physiology ; Alzheimer Disease/microbiology/physiopathology ; Neurodegenerative Diseases/microbiology ; }, abstract = {Understanding the interrelationship between the gut microbiota and host physiology, although still in its relative infancy, has taken important steps forward over the past decade. In the context of brain disorders including those characterized by neurodevelopmental and neurodegenerative changes there have been important advances. However, initially research involved correlational analyses, had limited translational scope, and lacked functional assessments. Thus, largescale longitudinal clinical investigations that assess causation and underlying mechanisms via in depth analysis methods are needed. In neurodegeneration research, strong causal evidence now links the gut microbiome to Alzheimer's (AD), and Parkinson's Disease (PD), as supported by human-to-animal transplantation studies. Longitudinal interventions are being conducted in AD, PD, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. Neurodevelopmental research has also seen a boon in microbiome-related clinical research including in autism, Attention-deficit/hyperactivity disorder, and schizophrenia, which is confirming prior animal model work regarding the key time-windows in the gut microbiome important for infant cognition. While recent research advances represent important progress, fundamental knowledge gaps and obstacles remain. Knowing how and why the gut microbiome changes at the extremes of life will develop our mechanistic understanding and help build the evidence base as we strive toward counteracting microbial missteps with precision therapeutic interventions.}, }
@article {pmid39557152, year = {2025}, author = {Yu, H and Ren, K and Jin, Y and Zhang, L and Liu, H and Huang, Z and Zhang, Z and Chen, X and Yang, Y and Wei, Z}, title = {Mitochondrial DAMPs: Key mediators in neuroinflammation and neurodegenerative disease pathogenesis.}, journal = {Neuropharmacology}, volume = {264}, number = {}, pages = {110217}, doi = {10.1016/j.neuropharm.2024.110217}, pmid = {39557152}, issn = {1873-7064}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology/immunology ; *Neuroinflammatory Diseases/metabolism/immunology/pathology ; Animals ; *Mitochondria/metabolism ; *Alarmins/metabolism ; Inflammasomes/metabolism ; DNA, Mitochondrial/metabolism ; Reactive Oxygen Species/metabolism ; }, abstract = {Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) are increasingly linked to mitochondrial dysfunction and neuroinflammation. Central to this link are mitochondrial damage-associated molecular patterns (mtDAMPs), including mitochondrial DNA, ATP, and reactive oxygen species, released during mitochondrial stress or damage. These mtDAMPs activate inflammatory pathways, such as the NLRP3 inflammasome and cGAS-STING, contributing to the progression of neurodegenerative diseases. This review delves into the mechanisms by which mtDAMPs drive neuroinflammation and discusses potential therapeutic strategies targeting these pathways to mitigate neurodegeneration. Additionally, it explores the cross-talk between mitochondria and the immune system, highlighting the complex interplay that exacerbates neuronal damage. Understanding the role of mtDAMPs could pave the way for novel treatments aimed at modulating neuroinflammation and slowing disease progression, ultimately improving patient outcome.}, }
@article {pmid39556113, year = {2024}, author = {Yeganeh Markid, T and Pourahmadiyan, A and Hamzeh, S and Sharifi-Bonab, M and Asadi, MR and Jalaiei, A and Rezazadeh, M and Ghafouri-Fard, S}, title = {A special focus on polyadenylation and alternative polyadenylation in neurodegenerative diseases: A systematic review.}, journal = {Journal of neurochemistry}, volume = {}, number = {}, pages = {}, doi = {10.1111/jnc.16255}, pmid = {39556113}, issn = {1471-4159}, abstract = {Neurodegenerative diseases (NDDs) are one of the prevailing conditions characterized by progressive neuronal loss. Polyadenylation (PA) and alternative polyadenylation (APA) are the two main post-transcriptional events that regulate neuronal gene expression and protein production. This systematic review analyzed the available literature on the role of PA and APA in NDDs, with an emphasis on their contributions to disease development. A comprehensive literature search was performed using the PubMed, Scopus, Cochrane, Google Scholar, Embase, Web of Science, and ProQuest databases. The search strategy was developed based on the framework introduced by Arksey and O'Malley and supplemented by the inclusion and exclusion criteria. The study selection was performed by two independent reviewers. Extraction and data organization were performed in accordance with the predefined variables. Subsequently, quantitative and qualitative analyses were performed. Forty-seven studies were included, related to a variety of NDDs, namely Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Disease induction was performed using different models, including human tissues, animal models, and cultured cells. Most investigations were related to PA, although some were related to APA or both. Amyloid precursor protein (APP), Tau, SNCA, and STMN2 were the major genes identified; most of the altered PA patterns were related to mRNA stability and translation efficiency. This review particularly underscores the key roles of PA and APA in the pathogenesis of NDDs through their mechanisms that contribute to gene expression dysregulation, protein aggregation, and neuronal dysfunction. Insights into these mechanisms may lead to new therapeutic strategies focused on the modulation of PA and APA activities. Further research is required to investigate the translational potential of targeting these pathways for NDD treatment.}, }
@article {pmid39551788, year = {2024}, author = {Sadeghdoust, M and Das, A and Kaushik, DK}, title = {Fueling neurodegeneration: metabolic insights into microglia functions.}, journal = {Journal of neuroinflammation}, volume = {21}, number = {1}, pages = {300}, pmid = {39551788}, issn = {1742-2094}, support = {MS220110//U.S. Department of Defense/ ; 916184//Multiple Sclerosis Society of Canada/ ; }, mesh = {*Microglia/metabolism/pathology ; Humans ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; }, abstract = {Microglia, the resident immune cells of the central nervous system, emerge in the brain during early embryonic development and persist throughout life. They play essential roles in brain homeostasis, and their dysfunction contributes to neuroinflammation and the progression of neurodegenerative diseases. Recent studies have uncovered an intricate relationship between microglia functions and metabolic processes, offering fresh perspectives on disease mechanisms and possible treatments. Despite these advancements, there are still significant gaps in our understanding of how metabolic dysregulation affects microglial phenotypes in these disorders. This review aims to address these gaps, laying the groundwork for future research on the topic. We specifically examine how metabolic shifts in microglia, such as the transition from oxidative phosphorylation and mitochondrial metabolism to heightened glycolysis during proinflammatory states, impact the disease progression in Alzheimer's disease, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Additionally, we explore the role of iron, fatty and amino acid metabolism in microglial homeostasis and repair. Identifying both distinct and shared metabolic adaptations in microglia across neurodegenerative diseases could reveal common therapeutic targets and provide a deeper understanding of disease-specific mechanisms underlying multiple CNS disorders.}, }
@article {pmid39547910, year = {2024}, author = {Khamaysa, M and El Mendili, M and Marchand, V and Querin, G and Pradat, PF}, title = {Quantitative spinal cord imaging: Early ALS diagnosis and monitoring of disease progression.}, journal = {Revue neurologique}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.neurol.2024.10.005}, pmid = {39547910}, issn = {0035-3787}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of motor neurons in the cortex, brainstem, and spinal cord. This degeneration leads to muscular weakness, progressively impairing motor functions and ultimately resulting in respiratory failure. The clinical, genetic, and pathological heterogeneity of ALS, combined with the absence of reliable biomarkers, significantly challenge the efficacy of therapeutic trials. Despite these hurdles, neuroimaging, and particularly spinal cord imaging, has emerged as a promising tool. It provides insights into the involvement of both upper and lower motor neurons. Quantitative spinal imaging has the potential to facilitate early diagnosis, enable accurate monitoring of disease progression, and refine the design of clinical trials. In this review, we explore the utility of spinal cord imaging within the broader context of developing spinal imaging biomarkers in ALS. We focus on a both diagnostic and prognostic biomarker in ALS, highlighting its pivotal role in elucidating the disease's underlying pathology. We also discuss the existing limitations and future avenues for research, aiming to bridge the translational gap between academic research and its application in clinical practice and therapeutic trials.}, }
@article {pmid39546178, year = {2024}, author = {Li, N and Zhang, Z and Shen, L and Song, G and Tian, J and Liu, Q and Ni, J}, title = {Selenium metabolism and selenoproteins function in brain and encephalopathy.}, journal = {Science China. Life sciences}, volume = {}, number = {}, pages = {}, pmid = {39546178}, issn = {1869-1889}, abstract = {Selenium (Se) is an essential trace element of the utmost importance to human health. Its deficiency induces various disorders. Se species can be absorbed by organisms and metabolized to hydrogen selenide for the biosynthesis of selenoproteins, selenonucleic acids, or selenosugars. Se in mammals mainly acts as selenoproteins to exert their biological functions. The brain ranks highest in the specific hierarchy of organs to maintain the level of Se and the expression of selenoproteins under the circumstances of Se deficiency. Dyshomeostasis of Se and dysregulation of selenoproteins result in encephalopathy such as Alzheimer's disease, Parkinson's disease, depression, amyotrophic lateral sclerosis, and multiple sclerosis. This review provides a summary and discussion of Se metabolism, selenoprotein function, and their roles in modulating brain diseases based on the most currently published literature. It focuses on how Se is utilized and transported to the brain, how selenoproteins are biosynthesized and function physiologically in the brain, and how selenoproteins are involved in neurodegenerative diseases. At the end of this review, the perspectives and problems are outlined regarding Se and selenoproteins in the regulation of encephalopathy.}, }
@article {pmid39545606, year = {2024}, author = {A Virata, MC and Catahay, JA and Lippi, G and Henry, BM}, title = {Neurofilament light chain: a biomarker at the crossroads of clarity and confusion for gene-directed therapies.}, journal = {Neurodegenerative disease management}, volume = {}, number = {}, pages = {1-13}, doi = {10.1080/17582024.2024.2421738}, pmid = {39545606}, issn = {1758-2032}, abstract = {Neurofilament light chain (NfL) is a promising biomarker for neurodegenerative diseases, measurable in both CSF and blood upon neuroaxonal damage. While CSF analysis was traditionally used, blood-based assays now offer a less invasive alternative. NfL levels correlate with disease severity and progression in conditions like Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis and Huntington's disease. Clinical trials demonstrate its utility as a pharmacodynamic biomarker in MS and ALS. The FDA's approval of Tofersen for SOD1-ALS based on NfL reduction underscores its growing acceptance as surrogate marker. However, challenges remain in standardizing assays, interpreting clinical correlations, low specificity and understanding the dynamics between CSF and blood NfL levels. Addressing these issues is crucial for maximizing NfL's potential in neurodegenerative disease management.}, }
@article {pmid39542176, year = {2024}, author = {Tian, Z and Zhang, Q and Wang, L and Li, M and Li, T and Wang, Y and Cao, Z and Jiang, X and Luo, P}, title = {Progress in the mechanisms of pain associated with neurodegenerative diseases.}, journal = {Ageing research reviews}, volume = {102}, number = {}, pages = {102579}, doi = {10.1016/j.arr.2024.102579}, pmid = {39542176}, issn = {1872-9649}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/physiopathology ; *Pain/physiopathology/metabolism/etiology ; Animals ; Neuroinflammatory Diseases ; }, abstract = {Neurodegenerative diseases (NDDs) represent a class of neurological disorders characterized by the progressive degeneration or loss of neurons, impacting millions of individuals globally. In addition to the typical manifestations, pain is a prevalent symptom associated with NDDs, seriously impacting the quality of life for patients. The pathogenesis of pain associated with NDDs is intricate and multifaceted. Currently, the clinical management of NDDs-related pain symptoms predominantly relies on conventional pharmacological agents or physical therapy. However, these approaches often fail to produce satisfactory outcomes. This article summarizes the underlying mechanisms of major NDDs-associated pain: Neuroinflammation, Brain and spinal cord dysfunctions, Mitochondrial dysfunction, Risk gene and pathological protein, as well as Receptor, channel, and neurotransmitter. While numerous studies have investigated the downstream pathological processes associated with these mechanisms, there remains a significant gap in identifying the key initiating factors. Specifically, there is insufficient evidence for the upstream elements that activate microglia and astrocytes in neuroinflammation leading to pain in NDDs. Likewise, there is an absence of upstream factors elucidating how dysfunctions in the brain and spinal cord, as well as mitochondrial impairments, contribute to the development of pain. Furthermore, the specific mechanisms through which hallmark pathological proteins related to NDDs contribute to these pathological processes remain inadequately understood. The objective of this article is to synthesize the existing mechanisms underlying pain associated with NDDs, including Alzheimer's disease, Parkinson's disease, Huntington's disease, Schizophrenia, Amyotrophic lateral sclerosis, and Multiple sclerosis, while also identifying gaps and deficiencies in these mechanisms. This paper offers insights for future research trajectories. Given the intricate pathogenesis of NDDs-related pain, it emphasizes that a promising short-term strategy is combination therapy-intervening concurrently in multiple pathological processes-akin to the cocktail approach utilized in treating acquired immunodeficiency syndrome (AIDS). For long-term advancements, achieving breakthroughs in the treatment of the NDDs themselves will remain essential for alleviating accompanying pain symptoms.}, }
@article {pmid39524179, year = {2024}, author = {Trinh, QD and Mai, HN and Pham, DT}, title = {Application of mesenchymal stem cells for neurodegenerative diseases therapy discovery.}, journal = {Regenerative therapy}, volume = {26}, number = {}, pages = {981-989}, pmid = {39524179}, issn = {2352-3204}, abstract = {Neurodegenerative diseases are central or peripheral nervous system disorders associated with progressive brain cell degeneration. Common neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis have been widely studied. However, current therapeutics only reduce the symptoms and do not ameliorate the pathogenesis of these diseases. Recent studies suggested the roles of neuroinflammation, apoptosis, and oxidative stress in neurodegenerative diseases. Mesenchymal stem cells (MSCs) exert anti-apoptotic, anti-inflammatory, and antioxidative effects. Therefore, investigating the effects of MSCs and their applications may lead to the discovery of more effective therapies for neurodegenerative diseases. In this study, we review different approaches used to identify therapies for neurodegenerative diseases using MSCs.}, }
@article {pmid39534483, year = {2024}, author = {Sbarigia, C and Rome, S and Dini, L and Tacconi, S}, title = {New perspectives of the role of skeletal muscle derived extracellular vesicles in the pathogenesis of amyotrophic lateral sclerosis: the 'dying back' hypothesis.}, journal = {Journal of extracellular biology}, volume = {3}, number = {11}, pages = {e70019}, pmid = {39534483}, issn = {2768-2811}, abstract = {Amyotrophic lateral sclerosis (ALS), is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord, and is characterized by muscle weakness, paralysis and ultimately, respiratory failure. The exact causes of ALS are not understood, though it is believed to combine genetic and environmental factors. Until now, it was admitted that motor neurons (MN) in the brain and spinal cord degenerate, leading to muscle weakness and paralysis. However, as ALS symptoms typically begin with muscle weakness or stiffness, a new hypothesis has recently emerged to explain the development of the pathology, that is, the 'dying back hypothesis', suggesting that this degeneration starts at the connections between MN and muscles, resulting in the loss of muscle function. Over time, this damage extends along the length of the MN, ultimately affecting their cell bodies in the spinal cord and brain. While the dying back hypothesis provides a potential framework for understanding the progression of ALS, the exact mechanisms underlying the disease remain complex and not fully understood. In this review, we are positioning the role of extracellular vesicles as new actors in ALS development.}, }
@article {pmid39523617, year = {2024}, author = {Iguchi, Y and Katsuno, M}, title = {[Current Status of Drug Development for Amyotrophic Lateral Sclerosis].}, journal = {Brain and nerve = Shinkei kenkyu no shinpo}, volume = {76}, number = {11}, pages = {1241-1249}, doi = {10.11477/mf.1416202766}, pmid = {39523617}, issn = {1881-6096}, mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; *Drug Development ; Clinical Trials as Topic ; Animals ; Riluzole/therapeutic use ; Neuroprotective Agents/therapeutic use ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease of motor neuron. Although riluzole and edaravone have been approved for the treatment of ALS, it remains a lethal disease that causes rapid motor impairment, and there is an urgent need to develop more effective treatments. Advances in understanding the pathomechanisms of ALS, efficient clinical trial design, and research support programs have led to many clinical trials for ALS both domestically and internationally.}, }
@article {pmid39523614, year = {2024}, author = {Yamakawa, I and Urushitani, M}, title = {[Gold Coast Criteria: A New Diagnostic Paradigm in the Era of Disease-Modifying Therapy for Amyotrophic Lateral Sclerosis].}, journal = {Brain and nerve = Shinkei kenkyu no shinpo}, volume = {76}, number = {11}, pages = {1217-1223}, doi = {10.11477/mf.1416202763}, pmid = {39523614}, issn = {1881-6096}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/drug therapy ; Humans ; }, abstract = {Significant progress has been made in the development of disease-modifying drugs for amyotrophic lateral sclerosis (ALS), with the introduction of tofersen, an antisense oligonucleotide drug for familial ALS, marking a turning point in the treatment. These drugs are most effective when administered early in the disease course, highlighting the need for improved diagnostic sensitivity. The 2020 Gold Coast Diagnostic Criteria allow ALS diagnosis in cases without upper motor neuron symptoms, potentially increasing early detection rates. However, careful differential diagnoses are necessary when applying these criteria to maintain diagnostic specificity. This review outlines the key points to consider when using the Gold Coast Criteria, balancing the need for an early diagnosis with caution to avoid overdiagnosis.}, }
@article {pmid39522697, year = {2024}, author = {Gao, L and Yang, XN and Dong, YX and Han, YJ and Zhang, XY and Zhou, XL and Liu, Y and Liu, F and Fang, JS and Ji, JL and Gao, ZR and Qin, XM}, title = {The potential therapeutic strategy in combating neurodegenerative diseases: Focusing on natural products.}, journal = {Pharmacology & therapeutics}, volume = {264}, number = {}, pages = {108751}, doi = {10.1016/j.pharmthera.2024.108751}, pmid = {39522697}, issn = {1879-016X}, mesh = {Humans ; *Biological Products/therapeutic use/pharmacology ; *Neurodegenerative Diseases/drug therapy ; Animals ; *Neuroprotective Agents/therapeutic use/pharmacology ; }, abstract = {Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington disease (HD), and Multiple sclerosis (MS), pose a significant global health challenge due to their intricate pathology and limited therapeutic interventions. Natural products represent invaluable reservoirs for combating these neurodegenerative diseases by targeting key pathological hallmarks such as protein aggregation, synaptic dysfunction, aberrant proteostasis, cytoskeletal abnormalities, altered energy homeostasis, inflammation, and neuronal cell death. This review provides an in-depth analysis of the mechanisms and therapeutic targets of natural products for their neuroprotective effects. Furthermore, it elucidates the current progress of clinical trials investigating the potential of natural products in delaying neurodegeneration. The objective of this review is to enhance the comprehension of natural products in the prevention and treatment of neurodegenerative diseases, offering new insights and potential avenues for future pharmaceutical research.}, }
@article {pmid39520508, year = {2024}, author = {Larose, A and Miller, CCJ and Mórotz, GM}, title = {The lemur tail kinase family in neuronal function and disfunction in neurodegenerative diseases.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {81}, number = {1}, pages = {447}, pmid = {39520508}, issn = {1420-9071}, mesh = {Humans ; *Neurodegenerative Diseases/pathology/metabolism/enzymology ; Animals ; *Neurons/metabolism/pathology ; Cyclin-Dependent Kinase 5/metabolism/genetics ; Signal Transduction ; Synapses/metabolism/pathology ; Protein-Tyrosine Kinases/metabolism/genetics ; Phosphorylation ; Axonal Transport ; Glycogen Synthase Kinase 3 beta/metabolism ; }, abstract = {The complex neuronal architecture and the long distance of synapses from the cell body require precisely orchestrated axonal and dendritic transport processes to support key neuronal functions including synaptic signalling, learning and memory formation. Protein phosphorylation is a major regulator of both intracellular transport and synaptic functions. Some kinases and phosphatases such as cyclin dependent kinase-5 (cdk5)/p35, glycogen synthase kinase-3β (GSK3β) and protein phosphatase-1 (PP1) are strongly involved in these processes. A primary pathological hallmark of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis/frontotemporal dementia, is synaptic degeneration together with disrupted intracellular transport. One attractive possibility is that alterations to key kinases and phosphatases may underlie both synaptic and axonal transport damages. The brain enriched lemur tail kinases (LMTKs, formerly known as lemur tyrosine kinases) are involved in intracellular transport and synaptic functions, and are also centrally placed in cdk5/p35, GSK3β and PP1 signalling pathways. Loss of LMTKs is documented in major neurodegenerative diseases and thus can contribute to pathological defects in these disorders. However, whilst function of their signalling partners became clearer in modulating both synaptic signalling and axonal transport progress has only recently been made around LMTKs. In this review, we describe this progress with a special focus on intracellular transport, synaptic functions and neurodegenerative diseases.}, }
@article {pmid39520111, year = {2024}, author = {Walls, M and Claffey, A and Mockler, D and Galvin, M}, title = {Working with people living with motor neurone disease and the impact on professionals' emotional and psychological well-being: A scoping review.}, journal = {Palliative medicine}, volume = {}, number = {}, pages = {2692163241291745}, doi = {10.1177/02692163241291745}, pmid = {39520111}, issn = {1477-030X}, abstract = {BACKGROUND: Integrated multidisciplinary care is required to manage the progressive and debilitating symptoms associated with motor neurone disease. Professionals can find providing the level of care required by this population clinically and emotionally challenging. To support those working with these patients it is important to understand the experience of the entire multidisciplinary team involved and the impact of working with motor neurone disease on their emotional and psychological well-being.
AIM: To identify what is known about (1) healthcare professionals' experience of working with motor neurone disease and (2) the impact of this work on their emotional and psychological well-being.
DESIGN: Scoping review. Review protocol registered on Open Science Framework.
SOURCES: Five electronic databases were searched in January 2023 and 2024. Grey literature and hand searches were completed.
RESULTS: Fifty-one sources published between 1990 and 2023 were included. A total of 1692 healthcare professionals are represented. Three main categories were identified: (1) The demands of providing motor neurone disease care. (2) Factors influencing professionals' ability to provide desired levels of care. (3) The emotional impact of working with motor neurone disease. Subcategories are depicted within these.
CONCLUSION: Positive experiences included job satisfaction, enhanced perspective and receiving gratitude, while negative implications such as stress, emotional exhaustion and burnout also featured. The demands of motor neurone disease patient care, the organisation of services and resources required to meet patient and family needs and the emotional burden for professionals involved, warrant greater recognition in clinical practice, guidelines and future research.}, }
@article {pmid39519213, year = {2024}, author = {Bova, V and Mannino, D and Capra, AP and Lanza, M and Palermo, N and Filippone, A and Esposito, E}, title = {CK and LRRK2 Involvement in Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {21}, pages = {}, pmid = {39519213}, issn = {1422-0067}, mesh = {Humans ; *Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/metabolism/genetics ; *Neurodegenerative Diseases/metabolism/genetics ; Animals ; Mutation ; Phosphorylation ; Autophagy/genetics ; }, abstract = {Neurodegenerative diseases (NDDs) are currently the most widespread neuronal pathologies in the world. Among these, the most widespread are Alzheimer's disease (AD), dementia, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD)-all characterized by a progressive loss of neurons in specific regions of the brain leading to varied clinical symptoms. At the basis of neurodegenerative diseases, an emerging role is played by genetic mutations in the leucine-rich repeat kinase 2 (LRRK2) gene that cause increased LRRK2 activity with consequent alteration of neuronal autophagy pathways. LRRK2 kinase activity requires GTPase activity which functions independently of kinase activity and is required for neurotoxicity and to potentiate neuronal death. Important in the neurodegeneration process is the upregulation of casein kinase (CK), which causes the alteration of the AMPK pathway by enhancing the phosphorylation of α-synuclein and huntingtin proteins, known to be involved in PD and HD, and increasing the accumulation of the amyloid-β protein (Aβ) for AD. Recent research has identified CK of the kinases upstream of LRRK2 as a regulator of the stability of the LRRK2 protein. Based on this evidence, this review aims to understand the direct involvement of individual kinases in NDDs and how their crosstalk may impact the pathogenesis and early onset of neurodegenerative diseases.}, }
@article {pmid39519209, year = {2024}, author = {Firdaus, Z and Li, X}, title = {Epigenetic Explorations of Neurological Disorders, the Identification Methods, and Therapeutic Avenues.}, journal = {International journal of molecular sciences}, volume = {25}, number = {21}, pages = {}, pmid = {39519209}, issn = {1422-0067}, support = {DK129241 DK126662/GF/NIH HHS/United States ; }, mesh = {Humans ; *Epigenesis, Genetic ; *DNA Methylation ; Neurodegenerative Diseases/genetics/therapy ; Animals ; Nervous System Diseases/genetics/therapy ; Histones/metabolism/genetics ; Epigenomics/methods ; Histone Code/genetics ; }, abstract = {Neurodegenerative disorders are major health concerns globally, especially in aging societies. The exploration of brain epigenomes, which consist of multiple forms of DNA methylation and covalent histone modifications, offers new and unanticipated perspective into the mechanisms of aging and neurodegenerative diseases. Initially, chromatin defects in the brain were thought to be static abnormalities from early development associated with rare genetic syndromes. However, it is now evident that mutations and the dysregulation of the epigenetic machinery extend across a broader spectrum, encompassing adult-onset neurodegenerative diseases. Hence, it is crucial to develop methodologies that can enhance epigenetic research. Several approaches have been created to investigate alterations in epigenetics on a spectrum of scales-ranging from low to high-with a particular focus on detecting DNA methylation and histone modifications. This article explores the burgeoning realm of neuroepigenetics, emphasizing its role in enhancing our mechanistic comprehension of neurodegenerative disorders and elucidating the predominant techniques employed for detecting modifications in the epigenome. Additionally, we ponder the potential influence of these advancements on shaping future therapeutic approaches.}, }
@article {pmid39511939, year = {2024}, author = {Eisen, A and Vucic, S and Kiernan, MC}, title = {Amyotrophic lateral sclerosis represents corticomotoneuronal system failure.}, journal = {Muscle & nerve}, volume = {}, number = {}, pages = {}, doi = {10.1002/mus.28290}, pmid = {39511939}, issn = {1097-4598}, abstract = {Several decades have passed since the anterograde corticomotoneuronal hypothesis for amyotrophic lateral sclerosis (ALS) was proposed. The intervening years have witnessed its emergent support based on anatomical, pathological, physiological, neuroimaging, and molecular biological studies. The evolution of an extensive corticomotoneuronal system appears restricted to the human species, with ALS representing a uniquely human disease. While some, very select non-human primates have limited corticomotoneuronal projections, these tend to be absent in all other animals. From a general perspective, the early clinical features of ALS may be considered to reflect failure of the corticomotoneuronal system. The characteristic loss of skilled motor dexterity involving the limbs, and speech impairment through progressive bulbar dysfunction specifically involve those motor units having the strongest corticomotoneuronal projections. A similar explanation likely underlies the unique "split phenotypes" that have now been well characterized in ALS. Large Betz cells and other pyramidal corticomotoneuronal projecting neurons, with their extensive dendritic arborization, are particularly vulnerable to the elements of the ALS exposome such as aging, environmental stress and lifestyle changes. Progressive failure of the proteosome impairs nucleocytoplasmic shuffling and induces toxic but soluble TDP-43 to aggregate in corticomotoneurons. Betz cell failure is further accentuated through dysfunction of its profuse dendritic arborizations. Clarification of system specific genomes and neural networks will likely promote the initiation of precision medicine approaches directed to support the key structure that underlies the neurological manifestations of ALS, the corticomotoneuronal system.}, }
@article {pmid39511821, year = {2024}, author = {Grady, A and Lorch, R and Giles, L and Lamont, H and Anderson, A and Pearson, N and Romiti, M and Lum, M and Stuart, A and Leigh, L and Yoong, SL}, title = {The impact of early childhood education and care-based interventions on child physical activity, anthropometrics, fundamental movement skills, cognitive functioning, and social-emotional wellbeing: A systematic review and meta-analysis.}, journal = {Obesity reviews : an official journal of the International Association for the Study of Obesity}, volume = {}, number = {}, pages = {e13852}, doi = {10.1111/obr.13852}, pmid = {39511821}, issn = {1467-789X}, support = {APP1170042//National Health and Medical Research Council/ ; Heart Foundation Postdoctoral Fellowship 102518//National Heart Foundation of Australia/ ; Heart Foundation Future Leader Fellowship 106654//National Heart Foundation of Australia/ ; }, abstract = {This review assessed the effectiveness of ECEC-based interventions to improve child physical activity, and intervention impact on child weight-based anthropometrics, fundamental movement skills (FMS), cognitive functioning, and social-emotional wellbeing. Adverse effects and costs were assessed. Finch et al's 2014 systematic review was updated. Electronic databases were searched 10 September 2014 to 27 October 2022. Included studies were randomized controlled trials of ECEC interventions targeting physical activity among children aged 0-6 years. The methodological quality of studies was assessed using Cochrane's Risk of Bias tool v2. Standardized mean differences (SMD) were calculated for each outcome with meta-analysis undertaken; otherwise, findings were described narratively. Fifty-three studies were included. ECEC-based interventions were found to significantly improve child physical activity (SMD 0.193, 95% confidence interval [CI] 0.09 to 0.3; p < 0.001) and FMS (SMD 0.544, 95% CI 0.1 to 0.98; p = 0.015), compared to control. Small positive, but non-significant, effects were found for weight-based anthropometrics, cognitive functioning, and social-emotional wellbeing. Few studies reported adverse effects (n = 10), and no studies reported formal economic analyses. While ECEC-based interventions can significantly improve child physical activity and FMS, further evidence of their impact on cognitive functioning, social-emotional wellbeing, and the cost-effectiveness of such interventions is required to inform policy and practice.}, }
@article {pmid39510899, year = {2024}, author = {Kaul, M and Mukherjee, D and Weiner, HL and Cox, LM}, title = {Gut microbiota immune cross-talk in amyotrophic lateral sclerosis.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {21}, number = {6}, pages = {e00469}, pmid = {39510899}, issn = {1878-7479}, support = {R01 NS115951/NS/NINDS NIH HHS/United States ; R21 NS126866/NS/NINDS NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/immunology/microbiology ; *Gastrointestinal Microbiome/immunology/physiology ; Humans ; Animals ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the loss of motor neurons. While there has been significant progress in defining the genetic contributions to ALS, greater than 90 % of cases are sporadic, which suggests an environmental component. The gut microbiota is altered in ALS and is an ecological factor that contributes to disease by modulating immunologic, metabolic, and neuronal signaling. Depleting the microbiome worsens disease in the SOD1 ALS animal model, while it ameliorates disease in the C9orf72 model of ALS, indicating critical subtype-specific interactions. Furthermore, administering beneficial microbiota or microbial metabolites can slow disease progression in animal models. This review discusses the current state of microbiome research in ALS, including interactions with different ALS subtypes, evidence in animal models and human studies, key immunologic and metabolomic mediators, and a path toward microbiome-based therapies for ALS.}, }
@article {pmid39505137, year = {2024}, author = {Abbasi, H and Jourabchi-Ghadim, N and Asgarzade, A and Mirshekari, M and Ebrahimi-Mameghani, M}, title = {Unveiling the veil of adipokines: A meta-analysis and systematic review in amyotrophic lateral sclerosis.}, journal = {Neuroscience}, volume = {563}, number = {}, pages = {1-9}, doi = {10.1016/j.neuroscience.2024.11.003}, pmid = {39505137}, issn = {1873-7544}, mesh = {*Amyotrophic Lateral Sclerosis/blood/metabolism ; Humans ; *Adipokines/blood ; Ghrelin/blood ; Leptin/blood ; Adiponectin/blood ; Disease Progression ; }, abstract = {BACKGROUND: Adipokines are proposed to be associated with ALS progression through assorted pathways. Therefore, The present meta-analysis explored the link between various adipokines and ALS progression.
METHOD: International database like PubMed, Scopus, and Web of Science databases were searched to achieve eligible papers published before December 2023. The following PICO structure was utilized: Population (patients with ALS); Intervention (serum concentrations of ghrelin, leptin, and adiponectin), Comparison (with or without controls), and Outcome (ALS progression). the risk of bias of selected papers was assessed through the Newcastle-Ottawa Scale (NOS) tool.
RESULTS: 11 out of 240 papers were selected for this study which were published between 2010 and 2024. Lower serum leptin concentrations were detected in the ALS compared to control groups (WMD: -0.91, 95% CI:-1.77, -0.05). Serum concentrations of adiponectin were higher in ALS compared to control groups (WMD: 0.41, 95% CI:-0.7, 0.89). Ultimately, The serum concentrations of ghrelin in the ALS groups were lower than control groups (WMD: -1.21, 95% CI: -2.95, 0.53).
CONCLUSION: Our findings revealed that serum concentrations of ghrelin and leptin were higher in ALS patients compared to control, unlike adiponectin.}, }
@article {pmid39503319, year = {2024}, author = {Bedlack, R and Li, X and Evangelista, BA and Panzetta, ME and Kwan, J and Gittings, LM and Sattler, R}, title = {The Scientific and Therapeutic Rationale for Off-Label Treatments in Amyotrophic Lateral Sclerosis.}, journal = {Annals of neurology}, volume = {97}, number = {1}, pages = {15-27}, pmid = {39503319}, issn = {1531-8249}, support = {//ALS Association/ ; }, abstract = {There are no dramatically effective pharmacological treatments for most patients with amyotrophic lateral sclerosis, a complex disease with multiple underlying mechanisms, such as neuroinflammation, oxidative stress, mitochondrial dysfunction, microbiome alteration, and antiretroviral activity. We sifted through 15 years of reviews by a group called ALSUntangled to identify 8 alternative and off-label treatments that target ≥1 of these mechanisms, and have ≥1 human trial suggesting meaningful benefits. Given the overlapping pathological mechanisms of the highlighted products, we suggest that combinations of these treatments targeting diverse mechanisms might be worthwhile for future amyotrophic lateral sclerosis therapy development. ANN NEUROL 2024.}, }
@article {pmid39503018, year = {2024}, author = {Rennie, O and Sharma, M and Helwa, N}, title = {Hepatobiliary anastomotic leakage: a narrative review of definitions, grading systems, and consequences of leaks.}, journal = {Translational gastroenterology and hepatology}, volume = {9}, number = {}, pages = {70}, pmid = {39503018}, issn = {2415-1289}, abstract = {BACKGROUND AND OBJECTIVE: Hepatobiliary diseases are a longstanding and significant medical challenge which, despite advances in surgical techniques, still carry risks for postoperative complications such as anastomotic leaks (ALs), which can include both postoperative pancreatic fistula (POPF) and bile leaks (BL). These complications incur significant human and economic costs on all those involved, including the patient, healthcare providers, and hospital systems. The aim of this study was to construct a narrative review of literature surrounding definitions and grading systems for ALs in the context of hepato-pancreato-biliary (HPB) procedures, and consequences of POPF and BL.
METHODS: A literature review was conducted by examining databases including PubMed, Web of Science, OVID Embase, Google Scholar, and Cochrane library databases. Searches were performed with the following search criteria: (((((((anastomosis) OR (anastomotic leak*)) OR (postoperative pancreatic fistula)) OR (bile leak*)) OR (pancreaticoduodenectomy)) OR (whipple)) AND ((hepatobiliary) OR (hepato-pancreato-biliary)) AND ((definition) OR (grading system*) OR (consequences) OR (outcomes) OR (risk factor*) OR (morbidity) OR (mortality))). Publications that were retrieved underwent further assessment to ensure other relevant publications were identified and included.
KEY CONTENT AND FINDINGS: A universally accepted definition and grading system for POPF and BL continues to be lacking, leading to variability in reported incidence in the literature. Various groups have worked to publish guidelines for defining and grading POPF and BL, with the International Study Group in Pancreatic Surgery (ISGPS) and International Study Group for Liver Surgery (ISGLS) definitions the current most recommended definitions for POPF and BL, respectively. The burden of AL on patients, healthcare providers, and hospitals is well documented in evidence from leak consequences, such as increased morbidity and mortality, higher reoperation rates, and increased readmission rates, among others.
CONCLUSIONS: AL remains a significant challenge in HPB surgery, despite medical advancements. Understanding the progress made in defining and grading leaks, as well as the range of negative outcomes that arise from AL, is crucial in improving patient care, reduce surgical mortality, and drive further advancements in earlier detection and treatment of AL.}, }
@article {pmid39501538, year = {2024}, author = {Bampton, A and McHutchison, C and Talbot, K and Benatar, M and Thompson, AG and Turner, MR}, title = {The Basis of Cognitive and Behavioral Dysfunction in Amyotrophic Lateral Sclerosis.}, journal = {Brain and behavior}, volume = {14}, number = {11}, pages = {e70115}, pmid = {39501538}, issn = {2162-3279}, support = {MR/T006927/1/MRC_/Medical Research Council/United Kingdom ; Thompson/Jan20/952-795//Motor Neurone Disease Association Lady Edith Wolfson Clinician Scientist Fellowship/ ; //Foulkes Foundation/ ; //National Institutes of Health (NIH)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/physiopathology ; Humans ; Cognitive Dysfunction/etiology/physiopathology ; }, abstract = {OBJECTIVE: To summarize and evaluate evidence pertaining to the clinical, genetic, histopathological, and neuroimaging correlates of cognitive and behavioral dysfunction in amyotrophic lateral sclerosis (ALS).
METHODOLOGY: We comprehensively reviewed the literature on cognitive and behavioral manifestations of ALS, narrating findings from both cross-sectional and longitudinal studies. We discussed knowledge gaps in the evidence base and key limitations affecting studies to date, before formulating a framework for future research paradigms aimed at investigating clinicopathological correlates of neuropsychological dysfunction in ALS.
RESULTS: Studies have demonstrated clinical associations with cognitive dysfunction in ALS e.g., bulbar-onset of symptoms, pathological associations (extramotor TDP-43 deposition), and imaging associations (frontotemporal involvement). The most common behavioral deficit, apathy, is highly associated with verbal fluency, but longitudinal studies assessing behavioral dysfunction in ALS are comparatively lacking.
CONCLUSION: Longitudinal studies have been helpful in identifying several potential correlates of cognitive and behavioral dysfunction but have frequently been confounded by selection bias and inappropriate testing platforms. This review provides a framework for more robust assessment of clinicopathological associations of neuropsychological abnormalities in ALS in the future, advocating for greater utilization of pre-symptomatic C9orf72 repeat expansion-carrying cohorts.}, }
@article {pmid39501102, year = {2024}, author = {Howard, J and Chaouch, A and Douglas, AGL and MacLeod, R and Roggenbuck, J and McNeill, A}, title = {Genetic testing for monogenic forms of motor neuron disease/amyotrophic lateral sclerosis in unaffected family members.}, journal = {European journal of human genetics : EJHG}, volume = {}, number = {}, pages = {}, pmid = {39501102}, issn = {1476-5438}, abstract = {Motor neuron disease (MND), also referred to as amyotrophic lateral sclerosis (ALS), is a monogenic disease in a minority of cases, with autosomal dominant inheritance. Increasing numbers of people with MND are requesting genetic testing, and indeed receiving a genetic diagnosis. Consequently, requests for genetic counselling and predictive testing (i.e. of unaffected family members) are similarly expected to rise, alongside pre-symptomatic clinical trials. Despite this, there is no evidence-based guideline for predictive genetic testing in MND. This paper provides an overview of the genomic basis of MND, focusing specifically on the most common monogenic causes of MND. It then lays out the complexities of MND predictive testing, including the genetic landscape characterised by incomplete penetrance, clinical and genetic heterogeneity, and an oligogenic mechanism of pathogenesis in some cases. Additionally, there is limited research on the psychosocial impact of predictive genetic testing for MND, with studies suggesting potential difficulty in adjusting to the news, in part due to a lack of support and follow-up. This underscores a case for evidence-based, disease-specific guidance for predictive testing in MND.}, }
@article {pmid39492438, year = {2023}, author = {Hamzeh, O and Rabiei, F and Shakeri, M and Parsian, H and Saadat, P and Rostami-Mansoor, S}, title = {Mitochondrial dysfunction and inflammasome activation in neurodegenerative diseases: Mechanisms and therapeutic implications.}, journal = {Mitochondrion}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.mito.2023.10.003}, pmid = {39492438}, issn = {1872-8278}, abstract = {Impaired mitochondrial function is crucial to the pathogenesis of several neurodegenerative diseases. It causes the release of mitochondrial DNA (mtDNA), mitochondrial reactive oxygen species (mtROS), ATP, and cardiolipin, which activate the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome. NLRP3 inflammasome is an important innate immune system element contributing to neuroinflammation and neurodegeneration. Therefore, targeting the NLRP3 inflammasome has become an interesting therapeutic approach for treating neurodegenerative diseases. This review describes the role of mitochondrial abnormalities and over-activated inflammasomes in the progression of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Multiple sclerosis (MS), Amyotrophic lateral sclerosis (ALS), and Friedrich ataxia (FRDA). We also discuss the therapeutic strategies focusing on signaling pathways associated with inflammasome activation, which potentially alleviate neurodegenerative symptoms and impede disease progression.}, }
@article {pmid39492095, year = {2023}, author = {Mohammadi, S and Mohammadi, M and Ghaderi, S}, title = {Sleep-related regions in neurodegenerative diseases by central nervous system localization using magnetic resonance imaging.}, journal = {Psychiatry research. Neuroimaging}, volume = {336}, number = {}, pages = {111727}, doi = {10.1016/j.pscychresns.2023.111727}, pmid = {39492095}, issn = {1872-7506}, abstract = {Sleep disruptions associated with neurodegenerative diseases (NDDs) damage the brain's sleep-regulating regions. Advanced magnetic resonance imaging (MRI) techniques can characterize the signature of each neurodegenerative pathology. We performed an evaluation of sleep-related regions in NDDs using MRI to localize the central nervous system (CNS). In the initial search, 61 related papers were discovered using predetermined inclusion and exclusion criteria. Finally, 30 articles were included in this study. The study included patients with Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), rapid eye movement (REM) sleep behavior disorder (RBD), idiopathic RBD (iRBD), amyotrophic lateral sclerosis (ALS), and mild cognitive impairment (MCI). Sleep-related regions recognized by CNS localization in NDDs can be linked to important regions. MRI also revealed cortical thinning, GM atrophy, WM, and tract loss, changes in diffusion tensor imaging (DTI) biomarkers (fractional anisotropy (FA), axial diffusivity (Da), and radial diffusivity (Dr)), a decrease in DMN connectivity, a reduction in functional connectivity (FC), and amplitude of low-frequency fluctuation (ALFF) alterations. Sleep plays an important role in predicting future risks for the development of NDDs. Other neuroimaging, cognitive-behavioral, and clinical research can use the information found in this research about the brain regions, MRI biomarker changes, and their relationships.}, }
@article {pmid39491718, year = {2024}, author = {Sharma, R and Khan, Z and Mehan, S and Das Gupta, G and Narula, AS}, title = {Unraveling the multifaceted insights into amyotrophic lateral sclerosis: Genetic underpinnings, pathogenesis, and therapeutic horizons.}, journal = {Mutation research. Reviews in mutation research}, volume = {794}, number = {}, pages = {108518}, doi = {10.1016/j.mrrev.2024.108518}, pmid = {39491718}, issn = {1388-2139}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/therapy ; Mutation/genetics ; RNA-Binding Protein FUS/genetics ; C9orf72 Protein/genetics ; Animals ; Superoxide Dismutase-1/genetics ; DNA-Binding Proteins/genetics ; Genetic Predisposition to Disease ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS), a progressive neurodegenerative disease, primarily impairs upper and lower motor neurons, leading to debilitating motor dysfunction and eventually respiratory failure, widely known as Lou Gehrig's disease. ALS presents with diverse symptomatology, including dysarthria, dysphagia, muscle atrophy, and hyperreflexia. The prevalence of ALS varies globally, with incidence rates ranging from 1.5 to 3.8 per 100,000 individuals, significantly affecting populations aged 45-80. A complex interplay of genetic and environmental factors underpins ALS pathogenesis. Key genetic contributors include mutations in chromosome 9 open reading frame 72 (C9ORF72), superoxide dismutase type 1 (SOD1), Fusedin sarcoma (FUS), and TAR DNA-binding protein (TARDBP) genes, accounting for a considerable fraction of both familial (fALS) and sporadic (sALS) cases. The disease mechanism encompasses aberrant protein folding, mitochondrial dysfunction, oxidative stress, excitotoxicity, and neuroinflammation, contributing to neuronal death. This review consolidates current insights into ALS's multifaceted etiology, highlighting the roles of environmental exposures (e.g., toxins, heavy metals) and their interaction with genetic predispositions. We emphasize the polygenic nature of ALS, where multiple genetic variations cumulatively influence disease susceptibility and progression. This aspect underscores the challenges in ALS diagnosis, which currently lacks specific biomarkers and relies on symptomatology and familial history. Therapeutic strategies for ALS, still in nascent stages, involve symptomatic management and experimental approaches targeting molecular pathways implicated in ALS pathology. Gene therapy, focusing on specific ALS mutations, and stem cell therapy emerge as promising avenues. However, effective treatments remain elusive, necessitating a deeper understanding of ALS's genetic architecture and the development of targeted therapies based on personalized medicine principles. This review aims to provide a comprehensive understanding of ALS, encouraging further research into its complex genetic underpinnings and the development of innovative, effective treatment modalities.}, }
@article {pmid39491419, year = {2023}, author = {Talebi, M and Sadoughi, MM and Ayatollahi, SA and Ainy, E and Kiani, R and Zali, A and Miri, M}, title = {Therapeutic potentials of cannabidiol: Focus on the Nrf2 signaling pathway.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {168}, number = {}, pages = {115805}, doi = {10.1016/j.biopha.2023.115805}, pmid = {39491419}, issn = {1950-6007}, abstract = {Cannabidiol (CBD), a cannabinoid that does not create psychoactive activities, has been identified as having a multitude of therapeutic benefits. This study delves into the chemical properties, pharmacokinetics, safety and toxicity, pharmacological effects, and most importantly, the association between the therapeutic potential of CBD and the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. The relationship between Nrf2 and CBD is closely linked to certain proteins that are associated with cardiovascular dysfunctions, cancers, and neurodegenerative conditions. Specifically, Nrf2 is connected to the initiation and progression of diverse health issues, including nephrotoxicity, bladder-related diseases, oral mucositis, cancers, obesity, myocardial injury and angiogenesis, skin-related inflammations, psychotic disorders, neuropathic pain, Huntington's disease, Alzheimer's disease, Parkinson's disease, neuroinflammation, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis. The association between CBD and Nrf2 is a zone of great interest in the medical field, as it has the potential to significantly impact the treatment and prevention of wide-ranging health conditions. Additional investigation is necessary to entirely apprehend the mechanisms underlying this crucial interplay and to develop effective therapeutic interventions.}, }
@article {pmid39490400, year = {2024}, author = {Zhang, Y and Zou, M and Wu, H and Zhu, J and Jin, T}, title = {The cGAS-STING pathway drives neuroinflammation and neurodegeneration via cellular and molecular mechanisms in neurodegenerative diseases.}, journal = {Neurobiology of disease}, volume = {202}, number = {}, pages = {106710}, doi = {10.1016/j.nbd.2024.106710}, pmid = {39490400}, issn = {1095-953X}, mesh = {Humans ; *Nucleotidyltransferases/metabolism ; *Membrane Proteins/metabolism ; *Neurodegenerative Diseases/metabolism ; *Signal Transduction/physiology ; Animals ; *Neuroinflammatory Diseases/metabolism ; }, abstract = {Neurodegenerative diseases (NDs) are a type of common chronic progressive disorders characterized by progressive damage to specific cell populations in the nervous system, ultimately leading to disability or death. Effective treatments for these diseases are still lacking, due to a limited understanding of their pathogeneses, which involve multiple cellular and molecular pathways. The triggering of an immune response is a common feature in neurodegenerative disorders. A critical challenge is the intricate interplay between neuroinflammation, neurodegeneration, and immune responses, which are not yet fully characterized. In recent years, the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) pathway, a crucial immune response for intracellular DNA sensing, has gradually gained attention. However, the specific roles of this pathway within cellular types such as immune cells, glial and neuronal cells, and its contribution to ND pathogenesis, remain not fully elucidated. In this review, we systematically explore how the cGAS-STING signaling links various cell types with related cellular effector pathways under the context of NDs for multifaceted therapeutic directions. We emphasize the discovery of condition-dependent cellular heterogeneity in the cGAS-STING pathway, which is integral for understanding the diverse cellular responses and potential therapeutic targets. Additionally, we review the pathogenic role of cGAS-STING activation in Parkinson's disease, ataxia-telangiectasia, and amyotrophic lateral sclerosis. We focus on the complex bidirectional roles of the cGAS-STING pathway in Alzheimer's disease, Huntington's disease, and multiple sclerosis, revealing their double-edged nature in disease progression. The objective of this review is to elucidate the pivotal role of the cGAS-STING pathway in ND pathogenesis and catalyze new insights for facilitating the development of novel therapeutic strategies.}, }
@article {pmid39489397, year = {2024}, author = {Desouky, MA and Michel, HE and Elsherbiny, DA and George, MY}, title = {Recent pharmacological insights on abating toxic protein species burden in neurological disorders: Emphasis on 26S proteasome activation.}, journal = {Life sciences}, volume = {359}, number = {}, pages = {123206}, doi = {10.1016/j.lfs.2024.123206}, pmid = {39489397}, issn = {1879-0631}, mesh = {*Proteasome Endopeptidase Complex/metabolism ; Humans ; Animals ; Neurodegenerative Diseases/metabolism/drug therapy ; Nervous System Diseases/drug therapy/metabolism ; Proteolysis/drug effects ; Signal Transduction/drug effects ; Proteostasis/drug effects ; Ubiquitin/metabolism ; }, abstract = {Protein homeostasis (proteostasis) refers to the plethora of mechanisms that safeguard the proper folding of the newly synthesized proteins. It entails various intricately regulated cues that demolish the toxic protein species to prevent their aggregation. The ubiquitin-proteasome system (UPS) is recognized as a salient protein degradation system, with a substantial role in maintaining proteostasis. However, under certain circumstances the protein degradation capacity of the UPS is overwhelmed, leading to the accumulation of misfolded proteins. Several neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, Huntington disease, and amyotrophic lateral sclerosis are characterized with the presence of protein aggregates and proteinopathy. Accordingly, enhancing the 26S proteasome degradation activity might delineate a pioneering approach in targeting various proteotoxic disorders. Regrettably, the exact molecular approaches that enhance the proteasomal activity are still not fully understood. Therefore, this review aimed to underscore several signaling cascades that might restore the degradation capacity of this molecular machine. In this review, we discuss the different molecular components of the UPS and how 26S proteasomes are deleteriously affected in many neurodegenerative diseases. Moreover, we summarize different signaling pathways that can be utilized to renovate the 26S proteasome functional capacity, alongside currently known druggable targets in this circuit and various classes of proteasome activators.}, }
@article {pmid39474168, year = {2024}, author = {Sandler, AB and Wells, ME and Tran, C and Arakawa, R and Klahs, KJ and Scanaliato, JP and Green, CK and Hettrich, CM and Dunn, JC and Adler, A and Parnes, N}, title = {High rates of return to sport after suprascapular nerve decompression: an updated systematic review.}, journal = {JSES reviews, reports, and techniques}, volume = {4}, number = {4}, pages = {654-661}, pmid = {39474168}, issn = {2666-6391}, abstract = {BACKGROUND: Suprascapular nerve decompression (SSND) remains a controversial procedure. In 2018, Momaya et al published the first systematic review of SSND noting satisfactory outcomes with low rates of complications; however, numerous studies published since have noted no benefit in routinely adding SSND to other arthroscopic surgeries, contributing to existing contention regarding the procedure. The purpose of this study is to provide an updated assessment of outcomes after SSND.
METHODS: To conduct this updated systematic review, a search of PubMed (MEDLINE) for relevant studies published prior to January 21, 2023 was conducted. Outcomes including patient-reported clinical outcomes, return to sport, preoperative and postoperative electrodiagnostic testing, and adverse events were collected and pooled for assessment. Studies were eligible for inclusion if they met Momaya et al's inclusion criteria and/or reported outcomes following SSND at either the suprascapular notch or spinoglenoid notch.
RESULTS: In total, 730 patients from 33 studies were eligible for inclusion. All patient-reported outcome measure scores including American Shoulder Elbow Surgeon Standardized Shoulder Assessment; Constant-Murley score; Disabilities of the Arm, Shoulder, and Hand; Subjective Shoulder Value; University of California-Los Angeles shoulder; and visual analog scale pain scores improved significantly postoperatively, with improvements ranging from 53.5% to 102.6% of preoperative values. Ultimately, 98% (n = 90/92) of patients returned to sport or military duty and 96% of these patients returned at their previous level of activity (n = 48/50) without heterogeneity among rates between studies (P = .176, P = .238, respectively). Preoperative electrodiagnostic testing was conducted in 93% of patients, and 90% had associated abnormal findings. Continued symptoms were noted among 12% of patients (n = 39/322) with significantly different rates observed between studies. Complications from operative management not limited to SSND occurred in 11% of patients (n = 64/576) and reoperations occurred in 3.3% of patients (n = 15/455).
CONCLUSION: Suprascapular neuropathy treated with SSND significantly improves patient-reported outcomes and is noninferior to similar procedures without SSND. Appropriate clinical diagnosis of suprascapular neuropathy is required as opposed to a routine adjunct procedure with other arthroscopic shoulder surgery. Ultimately, SSND is associated with high rates of return to sport and relatively low rates of adverse events; however, the risk of continued symptoms and electrodiagnostic test-related complications is an important point on preoperative counseling.}, }
@article {pmid39473490, year = {2024}, author = {Fei, Y and Ding, Y}, title = {The role of ferroptosis in neurodegenerative diseases.}, journal = {Frontiers in cellular neuroscience}, volume = {18}, number = {}, pages = {1475934}, pmid = {39473490}, issn = {1662-5102}, abstract = {Ferroptosis represents an iron[-] and lipid peroxidation (LPO)-mediated form of regulated cell death (RCD). Recent evidence strongly suggests the involvement of ferroptosis in various neurodegenerative diseases (NDs), particularly Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), among others. The treatment of ferroptosis poses both opportunities and challenges in the context of ND. This review provides a comprehensive overview of characteristic features, induction and inhibition of ferroptosis, highlighting the ferroptosis inhibitor and the underlying mechanisms responsible for its occurrence. Moreover, the review explores how these mechanisms contribute to the pathogenesis and progression of major neurodegenerative disorders. Additionally, it presents novel insights into the role of ferroptosis in ND and summarizes recent advancements in the development of therapeutic approaches targeting ferroptosis. These insights and advancements hold potential to guide future strategies aimed at effectively managing these debilitating medical conditions.}, }
@article {pmid39473221, year = {2024}, author = {Ito, D and Okada, K}, title = {Rethinking antisense oligonucleotide therapeutics for amyotrophic lateral sclerosis.}, journal = {Annals of clinical and translational neurology}, volume = {11}, number = {12}, pages = {3054-3063}, pmid = {39473221}, issn = {2328-9503}, support = {21H02812//Ministry of Education, Culture, Sports, Science and Technology of Japan/ ; }, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/therapy ; *Oligonucleotides, Antisense/administration & dosage/genetics ; Superoxide Dismutase-1/genetics ; }, abstract = {Antisense oligonucleotides, which are used to silence target genes, are gaining attention as a novel drug discovery modality for proteinopathies. However, while clinical trials for neurodegenerative diseases like amyotrophic lateral sclerosis have been conducted in recent years, the results have not always been favorable. The results from a Phase III trial of the antisense oligonucleotide, that is, tofersen, which targets SOD1 mRNA, showed decreased levels of cerebrospinal fluid SOD1 and plasma neurofilament light chain but no improvements in primary clinical endpoint. Moreover, case reports pertaining to patients with amyotrophic lateral sclerosis carrying FUS and C9orf72 mutations who received antisense oligonucleotide-based treatments have demonstrated a notable reduction in the targeted protein (thus providing the proof of mechanism) but with no discernible clinical benefits. There are several possible reasons why antisense oligonucleotides knockdown fails to achieve proof of concept, which need to be addressed: on-target adverse effects resulting from the loss of function of target gene and irreversible neuronal death cascade due to toxic protein accumulation, among other factors. This review provides an overview of the current status and discusses the prospects of antisense oligonucleotides treatment for amyotrophic lateral sclerosis.}, }
@article {pmid39472796, year = {2024}, author = {Zheng, K and Chen, M and Xu, X and Li, P and Yin, C and Wang, J and Liu, B}, title = {Chemokine CXCL13-CXCR5 signaling in neuroinflammation and pathogenesis of chronic pain and neurological diseases.}, journal = {Cellular & molecular biology letters}, volume = {29}, number = {1}, pages = {134}, pmid = {39472796}, issn = {1689-1392}, support = {82474625//National Natural Science Foundation of China/ ; 82305368//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Chemokine CXCL13/metabolism/genetics ; *Chronic Pain/metabolism/immunology ; *Receptors, CXCR5/metabolism ; *Signal Transduction ; *Nervous System Diseases/metabolism ; Animals ; *Neuroinflammatory Diseases/metabolism ; }, abstract = {Chronic pain dramatically affects life qualities of the sufferers. It has posed a heavy burden to both patients and the health care system. However, the current treatments for chronic pain are usually insufficient and cause many unwanted side effects. Chemokine C-X-C motif ligand 13 (CXCL13), formerly recognized as a B cell chemokine, binds with the cognate receptor CXCR5, a G-protein-coupled receptor (GPCR), to participate in immune cell recruitments and immune modulations. Recent studies further demonstrated that CXCL13-CXCR5 signaling is implicated in chronic pain via promoting neuroimmune interaction and neuroinflammation in the sensory system. In addition, some latest work also pointed out the involvement of CXCL13-CXCR5 in the pathogenesis of certain neurological diseases, including ischemic stroke and amyotrophic lateral sclerosis. Therefore, we aim to outline the recent findings in regard to the involvement of CXCL13-CXCR5 signaling in chronic pain as well as certain neurological diseases, with the focus on how this chemokine signaling contributes to the pathogenesis of these neurological diseases via regulating neuroimmune interaction and neuroinflammation. Strategies that can specifically target CXCL13-CXCR5 signaling in distinct locations may provide new therapeutic options for these neurological diseases.}, }
@article {pmid39470866, year = {2024}, author = {Liu, Y and Fu, R and Jia, H and Yang, K and Ren, F and Zhou, MS}, title = {GHRH and its analogues in central nervous system diseases.}, journal = {Reviews in endocrine & metabolic disorders}, volume = {}, number = {}, pages = {}, pmid = {39470866}, issn = {1573-2606}, support = {82270434//National Natural Science Foundation of China/ ; }, abstract = {Growth hormone-releasing hormone (GHRH) is primarily produced by the hypothalamus and stimulates the release of growth hormone (GH) in the anterior pituitary gland, which subsequently regulates the production of hepatic insulin-like growth factor-1 (IGF-1). GH and IGF-1 have potent effects on promoting cell proliferation, inhibiting cell apoptosis, as well as regulating cell metabolism. In central nerve system (CNS), GHRH/GH/IGF-1 promote brain development and growth, stimulate neuronal proliferation, and regulate neurotransmitter release, thereby participating in the regulation of various CNS physiological activities. In addition to hypothalamus-pituitary gland, GHRH and GHRH receptor (GHRH-R) are also expressed in other brain cells or tissues, such as endogenous neural stem cells (NSCs) and tumor cells. Alternations in GHRH/GH/IGF-1 axis are associated with various CNS diseases, for example, Alzheimer's disease, amyotrophic lateral sclerosis and emotional disorders manifest GHRH, GH or IGF-1 deficiency, and GH or IGF-1 supplementation exerts beneficial therapeutic effects on these diseases. CNS tumors, such as glioma, can express GHRH and GHRH-R, and activating this signaling pathway promotes tumor cell growth. The synthesized GHRH antagonists have shown to inhibit glioma cell growth and may hold promising as an adjuvant therapy for treating glioma. In addition, we have shown that GHRH agonist MR-409 can improve neurological sequelae after ischemic stroke by activating extrapituitary GHRH-R signaling and promoting endogenous NSCs-derived neuronal regeneration. This article reviews the involvement of GHRH/GH/IGF-1 in CNS diseases, and potential roles of GHRH agonists and antagonists in treating CNS diseases.}, }
@article {pmid39470847, year = {2024}, author = {Jellinger, KA}, title = {Mild cognitive impairment in amyotrophic lateral sclerosis: current view.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {}, number = {}, pages = {}, pmid = {39470847}, issn = {1435-1463}, support = {Society for the Promotion of Research in Experimental Neurology, Vienna, Austria//Society for the Promotion of Research in Experimental Neurology, Vienna, Austria/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal multi-system neurodegenerative disorder with no effective treatment or cure. Although primarily characterized by motor degeneration, cognitive dysfunction is an important non-motor symptom that has a negative impact on patient and caregiver burden. Mild cognitive deficits are present in a subgroup of non-demented patients with ALS, often preceding motor symptoms. Detailed neuropsychological assessments reveal deficits in a variety of cognitive domains, including those of verbal fluency and retrieval, language, executive function, attention and verbal memory. Mild cognitive impairment (MCI), a risk factor for developing dementia, affects between 10% and over 50% of ALS patients. Neuroimaging revealed atrophy of frontal and temporal cortices, disordered white matter Integrity, volume reduction in amygdala and thalamus, hypometabolism in the frontal and superior temporal gyrus and anterior insula. Neuronal loss in non-motor brain areas, associated with TDP-43 deposition, one of the morphological hallmarks of ALS, is linked to functional disruption of frontostriatal and frontotemporo-limbic connectivities as markers for cognitive deficits in ALS, the pathogenesis of which is still poorly understood. Early diagnosis by increased cerebrospinal fluid or serum levels of neurofilament light/heavy chain or glial fibrillary acidic protein awaits confirmation for MCI in ALS. These fluid biomarkers and early detection of brain connectivity signatures before structural changes will be helpful not only in establishing early premature diagnosis but also in clarifying the pathophysiological mechanisms of MCI in ALS, which might serve as novel targets for prohibition/delay and future adequate treatment of this debilitating disorder.}, }
@article {pmid39470153, year = {2024}, author = {Xu, R}, title = {Overview of nomenclature and diagnosis of amyotrophic lateral sclerosis.}, journal = {Annals of medicine}, volume = {56}, number = {1}, pages = {2422572}, pmid = {39470153}, issn = {1365-2060}, mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/classification/physiopathology ; Humans ; *Terminology as Topic ; Electromyography/methods ; Motor Neurons/pathology ; }, abstract = {The nomenclature of amyotrophic lateral sclerosis (ALS) currently is blurred, indistinct and no accurate and haven't been properly updated since the first description, which is far from being suitable for the current implementation of clinical practise and scientific research of ALS, and urgently need an solution. Furthermore, the current diagnostic criteria need also further been improved, because the current clinical diagnosis of ALS majorly depends on the clinical manifestations yet. Up to now, no any objective clinical auxiliary examination can be helpful to diagnose ALS besides the electromyogram identifying the lower motor neuron damage, which isn't conducive to early diagnosis and prolongs the time of ALS confirmed diagnosis. In this mini review, we discussed the current doubt about the nomenclature and diagnostic criteria of ALS, and prospected in order to further improve and normalize the nomenclature and diagnosis of ALS.}, }
@article {pmid39459534, year = {2024}, author = {Nakhal, MM and Yassin, LK and Alyaqoubi, R and Saeed, S and Alderei, A and Alhammadi, A and Alshehhi, M and Almehairbi, A and Al Houqani, S and BaniYas, S and Qanadilo, H and Ali, BR and Shehab, S and Statsenko, Y and Meribout, S and Sadek, B and Akour, A and Hamad, MIK}, title = {The Microbiota-Gut-Brain Axis and Neurological Disorders: A Comprehensive Review.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {10}, pages = {}, pmid = {39459534}, issn = {2075-1729}, support = {12M159//UAEU/ ; G00004325//UAEU/ ; 12M142//UAEU/ ; }, abstract = {Microbes have inhabited the earth for hundreds of millions of years longer than humans. The microbiota-gut-brain axis (MGBA) represents a bidirectional communication pathway. These communications occur between the central nervous system (CNS), the enteric nervous system (ENS), and the emotional and cognitive centres of the brain. The field of research on the gut-brain axis has grown significantly during the past two decades. Signalling occurs between the gut microbiota and the brain through the neural, endocrine, immune, and humoral pathways. A substantial body of evidence indicates that the MGBA plays a pivotal role in various neurological diseases. These include Alzheimer's disease (AD), autism spectrum disorder (ASD), Rett syndrome, attention deficit hyperactivity disorder (ADHD), non-Alzheimer's neurodegeneration and dementias, fronto-temporal lobe dementia (FTLD), Wilson-Konovalov disease (WD), multisystem atrophy (MSA), Huntington's chorea (HC), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), temporal lobe epilepsy (TLE), depression, and schizophrenia (SCZ). Furthermore, the bidirectional correlation between therapeutics and the gut-brain axis will be discussed. Conversely, the mood of delivery, exercise, psychotropic agents, stress, and neurologic drugs can influence the MGBA. By understanding the MGBA, it may be possible to facilitate research into microbial-based interventions and therapeutic strategies for neurological diseases.}, }
@article {pmid39459030, year = {2024}, author = {Al-Khayri, JM and Ravindran, M and Banadka, A and Vandana, CD and Priya, K and Nagella, P and Kukkemane, K}, title = {Amyotrophic Lateral Sclerosis: Insights and New Prospects in Disease Pathophysiology, Biomarkers and Therapies.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {17}, number = {10}, pages = {}, pmid = {39459030}, issn = {1424-8247}, support = {GRANT0000//Deanship of Scientific Research, King Faisal University/ ; }, abstract = {Amyotrophic Lateral Sclerosis (ALS) is a severe neurodegenerative disorder marked by the gradual loss of motor neurons, leading to significant disability and eventual death. Despite ongoing research, there are still limited treatment options, underscoring the need for a deeper understanding of the disease's complex mechanisms and the identification of new therapeutic targets. This review provides a thorough examination of ALS, covering its epidemiology, pathology, and clinical features. It investigates the key molecular mechanisms, such as protein aggregation, neuroinflammation, oxidative stress, and excitotoxicity that contribute to motor neuron degeneration. The role of biomarkers is highlighted for their importance in early diagnosis and disease monitoring. Additionally, the review explores emerging therapeutic approaches, including inhibitors of protein aggregation, neuroinflammation modulators, antioxidant therapies, gene therapy, and stem cell-based treatments. The advantages and challenges of these strategies are discussed, with an emphasis on the potential for precision medicine to tailor treatments to individual patient needs. Overall, this review aims to provide a comprehensive overview of the current state of ALS research and suggest future directions for developing effective therapies.}, }
@article {pmid39457513, year = {2024}, author = {Montiel-Troya, M and Mohamed-Mohamed, H and Pardo-Moreno, T and González-Díaz, A and Ruger-Navarrete, A and de la Mata Fernández, M and Tovar-Gálvez, MI and Ramos-Rodríguez, JJ and García-Morales, V}, title = {Advancements in Pharmacological Interventions and Novel Therapeutic Approaches for Amyotrophic Lateral Sclerosis.}, journal = {Biomedicines}, volume = {12}, number = {10}, pages = {}, pmid = {39457513}, issn = {2227-9059}, support = {PID2019-110960GB-I00//Ministry of Science and Innovation, Spain./ ; }, abstract = {(1) Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease in which the patient suffers from an affection of both upper and lower motor neurons at the spinal and brainstem level, causing a progressive paralysis that leads to the patient's demise. Gender is also considered a predisposing risk factor for developing the disease. A brief review of the pathophysiological mechanisms of the disease is also described in this work. Despite the fact that a cure for ALS is currently unknown, there exists a variety of pharmacological and non-pharmacological therapies that can help reduce the progression of the disease over a certain period of time and alleviate symptoms. (2) We aim to analyze these pharmacological and non-pharmacological therapies through a systematic review. A comprehensive, multidisciplinary approach to treatment is necessary. (3) Drugs such as riluzole, edaravone, and sodium phenylbutyrate, among others, have been investigated. Additionally, it is important to stay updated on research on new drugs, such as masitinib, from which very good results have been obtained. (4) Therapies aimed at psychological support, speech and language, and physical therapy for the patient are also available, which increase the quality of life of the patients.}, }
@article {pmid39457470, year = {2024}, author = {Trabacca, A and Ferrante, C and Oliva, MC and Fanizza, I and Gallo, I and De Rinaldis, M}, title = {Update on Inherited Pediatric Motor Neuron Diseases: Clinical Features and Outcome.}, journal = {Genes}, volume = {15}, number = {10}, pages = {}, pmid = {39457470}, issn = {2073-4425}, support = {2024//The Italian Health Ministry - Ricerca Corrente/ ; }, mesh = {Humans ; *Motor Neuron Disease/genetics/pathology ; Child ; Mutation ; Muscular Atrophy, Spinal/genetics/pathology/diagnosis ; Exome Sequencing ; }, abstract = {BACKGROUND: Inherited pediatric motor neuron diseases (MNDs) are a group of neurodegenerative disorders characterized by the degeneration of motor neurons in the brain and the spinal cord. These diseases can manifest as early as infancy and originate from inherited pathogenic mutations in known genes. Key clinical features of MNDs include muscle weakness, hypotonia, and atrophy due to the degeneration of lower motor neurons or spasticity, hypertonia, and hyperreflexia caused by upper motor neuron dysfunction. The course of the disease varies among individuals and is influenced by the specific subtype.
METHODS: We performed a non-systematic, narrative clinical review, employing a systematic methodology for the literature search and article selection to delineate the features of hereditary pediatric motor neuron diseases.
RESULTS: The growing availability of advanced molecular testing, such as whole-exome sequencing (WES) and whole-genome sequencing (WGS), has expanded the range of identified genetic factors. These advancements provide insights into the genetic complexity and underlying mechanisms of these disorders. As more MND-related genes are discovered, the accumulating genetic data will help prioritize promising candidate genes for future research. In some cases, targeted treatments based on specific genetic mechanisms have already emerged, underscoring the critical role of early and timely diagnosis in improving patient outcomes. Common MNDs include amyotrophic lateral sclerosis, spinal muscular atrophy, and bulbar spinal muscular atrophy.
CONCLUSION: This narrative clinical review covers the clinical presentation, genetics, molecular features, and pathophysiology of inherited pediatric MNDs.}, }
@article {pmid39457468, year = {2024}, author = {Boura, I and Giannopoulou, IA and Pavlaki, V and Xiromerisiou, G and Mitsias, P and Spanaki, C}, title = {FIG4-Related Parkinsonism and the Particularities of the I41T Mutation: A Review of the Literature.}, journal = {Genes}, volume = {15}, number = {10}, pages = {}, pmid = {39457468}, issn = {2073-4425}, mesh = {Humans ; *Parkinsonian Disorders/genetics/pathology/diagnostic imaging ; *Charcot-Marie-Tooth Disease/genetics/pathology ; *Flavoproteins/genetics ; Female ; Male ; Mutation, Missense ; Middle Aged ; Mutation ; Adult ; Phosphoric Monoester Hydrolases ; }, abstract = {Background/Objectives: The genetic underpinnings of Parkinson's disease (PD) and parkinsonism have drawn increasing attention in recent years. Mutations in the Factor-Induced Gene 4 (FIG4) have been implicated in various neurological disorders, including Charcot-Marie-Tooth disease type 4J (CMT4J), amyotrophic lateral sclerosis (ALS), and Yunis-Varón syndrome. This review aims to explore the association between FIG4 mutations and parkinsonism, with a specific focus on the rare missense mutation p.Ile41Thr (I41T). Methods: We identified 12 cases from 10 different families in which parkinsonism was reported in conjunction with CMT4J polyneuropathy. All cases involved the I41T mutation in a compound heterozygous state, combined with a FIG4 loss-of-function mutation. Data from clinical observations, neuroimaging studies, and genetic analyses were evaluated to understand the characteristics of parkinsonism in these patients. Results: In all 12 cases, parkinsonism developed either concurrently or following the onset of CMT4J neuropathy, but was never observed in isolation. Cases of both early- and late-onset parkinsonism were identified, reflecting similarities to genetic forms of parkinsonism with autosomal recessive inheritance. Imaging studies, including Dopamine transporter Single Photon Emission Computed Tomography (DaTscan) and brain magnetic resonance imaging (MRI), revealed abnormalities indicative of neurodegeneration, consistent with findings in other neurodegenerative disorders. Conclusions: The co-occurrence of parkinsonism with CMT4J in patients carrying the I41T mutation suggests an expanded spectrum of FIG4-related disorders, potentially implicating the same molecular mechanisms seen in other neurodegenerative disorders. Further research into FIG4-mediated pathways may offer valuable insights into potential therapeutic targets for disorders of both the central and peripheral nervous systems.}, }
@article {pmid39457466, year = {2024}, author = {Moriyama, H and Yokota, T}, title = {Recent Progress of Antisense Oligonucleotide Therapy for Superoxide-Dismutase-1-Mutated Amyotrophic Lateral Sclerosis: Focus on Tofersen.}, journal = {Genes}, volume = {15}, number = {10}, pages = {}, pmid = {39457466}, issn = {2073-4425}, mesh = {*Amyotrophic Lateral Sclerosis/genetics/drug therapy/therapy ; Humans ; *Superoxide Dismutase-1/genetics ; *Oligonucleotides, Antisense/therapeutic use/genetics ; *Mutation ; Animals ; Oligonucleotides/therapeutic use/genetics ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a refractory neurodegenerative disease characterized by the degeneration and loss of motor neurons, typically resulting in death within five years of onset. There have been few effective treatments, making the development of robust therapies an urgent challenge. Genetic mutations have been identified as contributors to ALS, with mutations in superoxide dismutase 1 (SOD1), which neutralizes the harmful reactive oxygen species superoxide, accounting for approximately 2% of all ALS cases. To counteract the toxic gain of function caused by SOD1 mutations, therapeutic strategies aimed at suppressing SOD1 gene expression have shown promise. Antisense oligonucleotide (ASO) is an artificially synthesized, short, single-stranded DNA/RNA molecule that binds to target RNA to alter gene expression, representing a next-generation therapeutic approach. In 2023, tofersen became the first ASO drug approved by the FDA for ALS. Administered intrathecally, tofersen specifically binds to SOD1 mRNA, inhibiting the production of toxic SOD1 protein, thereby improving biomarkers of ALS. The long-term efficacy and safety of tofersen require further validation, and the development of more optimized treatment protocols is essential. A series of studies and therapeutic developments related to SOD1 mutations have advanced the understanding of ALS pathophysiology and significantly contributed to treatment strategies for central nervous system disorders. This review focuses on an overview of SOD1 mutations and the development process of tofersen, aiming to deepen the understanding of advancements in ALS research and discuss future challenges and directions for ASO therapy.}, }
@article {pmid39456682, year = {2024}, author = {Alshehri, RS and Abuzinadah, AR and Alrawaili, MS and Alotaibi, MK and Alsufyani, HA and Alshanketi, RM and AlShareef, AA}, title = {A Review of Biomarkers of Amyotrophic Lateral Sclerosis: A Pathophysiologic Approach.}, journal = {International journal of molecular sciences}, volume = {25}, number = {20}, pages = {}, pmid = {39456682}, issn = {1422-0067}, mesh = {*Amyotrophic Lateral Sclerosis/metabolism/physiopathology/diagnosis ; Humans ; *Biomarkers/metabolism ; Motor Neurons/metabolism/pathology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons. The heterogeneous nature of ALS at the clinical, genetic, and pathological levels makes it challenging to develop diagnostic and prognostic tools that fit all disease phenotypes. Limitations associated with the functional scales and the qualitative nature of mainstay electrophysiological testing prompt the investigation of more objective quantitative assessment. Biofluid biomarkers have the potential to fill that gap by providing evidence of a disease process potentially early in the disease, its progression, and its response to therapy. In contrast to other neurodegenerative diseases, no biomarker has yet been validated in clinical use for ALS. Several fluid biomarkers have been investigated in clinical studies in ALS. Biofluid biomarkers reflect the different pathophysiological processes, from protein aggregation to muscle denervation. This review takes a pathophysiologic approach to summarizing the findings of clinical studies utilizing quantitative biofluid biomarkers in ALS, discusses the utility and shortcomings of each biomarker, and highlights the superiority of neurofilaments as biomarkers of neurodegeneration over other candidate biomarkers.}, }
@article {pmid39456257, year = {2024}, author = {Perni, M and Mannini, B}, title = {Targeting Protein Aggregation in ALS.}, journal = {Biomolecules}, volume = {14}, number = {10}, pages = {}, pmid = {39456257}, issn = {2218-273X}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/drug therapy ; *Protein Aggregation, Pathological/metabolism ; Protein Aggregates ; Animals ; }, abstract = {Proteinopathies involve the abnormal accumulation of specific proteins. Maintaining the balance of the proteome is a finely regulated process managed by a complex network of cellular machinery responsible for protein synthesis, folding, and degradation. However, stress and ageing can disrupt this balance, leading to widespread protein aggregation. Currently, several therapies targeting protein aggregation are in clinical trials for ALS. These approaches mainly focus on two strategies: addressing proteins that are prone to aggregation due to mutations and targeting the cellular mechanisms that maintain protein homeostasis to prevent aggregation. This review will cover these emerging drugs. Advances in ALS research not only offer hope for better outcomes for ALS patients but also provide valuable insights and methodologies that can benefit the broader field of neurodegenerative disease drug discovery.}, }
@article {pmid39455963, year = {2024}, author = {Alexander, E and Leong, KW}, title = {Discovery of nanobodies: a comprehensive review of their applications and potential over the past five years.}, journal = {Journal of nanobiotechnology}, volume = {22}, number = {1}, pages = {661}, pmid = {39455963}, issn = {1477-3155}, mesh = {*Single-Domain Antibodies/chemistry ; Humans ; Animals ; *SARS-CoV-2/immunology ; COVID-19/virology/immunology ; Neurodegenerative Diseases/drug therapy ; }, abstract = {Nanobodies (Nbs) are antibody fragments derived from heavy-chain-only IgG antibodies found in the Camelidae family as well as cartilaginous fish. Their unique structural and functional properties, such as their small size, the ability to be engineered for high antigen-binding affinity, stability under extreme conditions, and ease of production, have made them promising tools for diagnostics and therapeutics. This potential was realized in 2018 with the approval of caplacizumab, the world's first Nb-based drug. Currently, Nbs are being investigated in clinical trials for a broad range of treatments, including targeted therapies against PDL1 and Epidermal Growth Factor Receptor (EGFR), cardiovascular diseases, inflammatory conditions, and neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. They are also being studied for their potential for detecting and imaging autoimmune conditions and infectious diseases such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A variety of methods are now available to generate target-specific Nbs quickly and efficiently at low costs, increasing their accessibility. This article examines these diverse applications of Nbs and their promising roles. Only the most recent articles published in the last five years have been used to summarize the most advanced developments in the field.}, }
@article {pmid39451992, year = {2024}, author = {Ozdinler, PH}, title = {Sleep Apnea and Amyotrophic Lateral Sclerosis: Cause, Correlation, Any Relation?.}, journal = {Brain sciences}, volume = {14}, number = {10}, pages = {}, pmid = {39451992}, issn = {2076-3425}, abstract = {Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with progressive neurodegeneration, affecting both the cortical and the spinal component of the motor neuron circuitry in patients. The cellular and molecular basis of selective neuronal vulnerability is beginning to emerge. Yet, there are no effective cures for ALS, which affects more than 200,000 people worldwide each year. Recent studies highlight the importance of the glymphatic system and its proper function for the clearance of the cerebral spinal fluid, which is achieved mostly during the sleep period. Therefore, a potential link between problems with sleep and neurodegenerative diseases has been postulated. This paper discusses the present understanding of this potential correlation.}, }
@article {pmid39451238, year = {2024}, author = {Crescioli, C and Paronetto, MP}, title = {The Emerging Role of Phosphodiesterase 5 Inhibition in Neurological Disorders: The State of the Art.}, journal = {Cells}, volume = {13}, number = {20}, pages = {}, pmid = {39451238}, issn = {2073-4409}, mesh = {Humans ; *Phosphodiesterase 5 Inhibitors/therapeutic use/pharmacology ; *Nervous System Diseases/drug therapy ; Animals ; Cyclic Nucleotide Phosphodiesterases, Type 5/metabolism ; Neuroinflammatory Diseases/drug therapy/metabolism ; }, abstract = {Growing evidence suggests that neuroinflammation is not just a consequence of neurodegeneration in pathologies such as Alzheimer's disease, Parkinson's disease, Huntington's disease or Amyotrophic lateral sclerosis, but it is rather a determinant factor, which plays a pivotal role in the onset and progression of these disorders. Neuroinflammation can affect cells and processes in the central nervous system (CNS) as well as immune cells, and might precede protein aggregation, which is a hallmark of the neurodegenerative process. Standard treatment methods are far from being able to counteract inflammation and delay neurodegeneration. Remarkably, phosphodiesterase 5 inhibitors (PDE5is), which represent potent vasoactive drugs used as a first-line treatment for erectile dysfunction (ED), display important anti-inflammatory effects through cyclic guanosine monophosphate (cGMP) level stabilization. Since PDE5 hydrolyzes cGMP, several studies positioned PDE5 as a therapeutic target, and more specifically, PDE5is as potential alternative strategies for the treatment of a variety of neurological disorders. Indeed, PDE5is can limit neuroinflammation and enhance synaptic plasticity, with beneficial effects on cognitive function and memory. The aim of this review is to provide an overview of some of the main processes underlying neuroinflammation and neurodegeneration which may be potential targets for PDE5is, focusing on sildenafil, the most extensively studied. Current strategies using PDEis for the treatment of neurodegenerative diseases will be summarized.}, }
@article {pmid39449457, year = {2024}, author = {Rosa, D and Ingrande, L and Marcomini, I and Poliani, A and Villa, G and Sodano, M and Manara, DF}, title = {Perceived Pain in People Living with Amyotrophic Lateral Sclerosis-A Scoping Review.}, journal = {Nursing reports (Pavia, Italy)}, volume = {14}, number = {4}, pages = {3023-3039}, pmid = {39449457}, issn = {2039-4403}, abstract = {(1) Background: Pain is a common symptom in patients with Amyotrophic Lateral Sclerosis (ALS). There are no evidence-based pharmacological treatments for pain in ALS; recommendations are based on guidelines for chronic non-oncological pain and clinical experience. The aim is to map the literature on how people with ALS experience pain, and how this affects their daily activities and social relationships. (2) Methods: This scoping review included studies concerning patients with spinal/bulbar ALS aged ≥ 18 years who experience pain, focusing on perception, characteristics, treatment, and impact on quality of life. Temporal and linguistic criteria were applied when searching the MEDLINE, CINAHL, and SCOPUS databases. (3) Results: The management of pain in these patients is complex and involves the use of anti-inflammatory drugs, analgesics, and opioids. Pain is associated with other conditions such as depression and anxiety, which contribute to a deterioration in the quality of life. Moreover, pain may also negatively influence patient compliance with prescribed treatment regimens and the quality of care they perceive themselves to be receiving. (4) Conclusions: It is of the most importance to identify effective ways to assess and treat this issue, with health care professionals taking an active role in this process.}, }
@article {pmid39439710, year = {2024}, author = {Kelser, BM and Teichner, EM and Subtirelu, RC and Hoss, KN}, title = {A review of proposed mechanisms for neurodegenerative disease.}, journal = {Frontiers in aging neuroscience}, volume = {16}, number = {}, pages = {1370580}, pmid = {39439710}, issn = {1663-4365}, abstract = {Neurodegenerative diseases, such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis (ALS) affect millions and present significant challenges in healthcare and treatment costs. The debate in the field pivots around two hypotheses: synaptic spread and selective vulnerability. Pioneers like Virginia Lee and John Trojanowski have been instrumental in identifying key proteins (tau, alpha-synuclein, TDP-43) central to these diseases. The synaptic spread hypothesis suggests a cell-to-cell propagation of pathogenic proteins across neuronal synapses, influencing disease progression, with studies highlighting the role of proteins like alpha-synuclein and amyloid-beta in this process. In contrast, the selective vulnerability hypothesis proposes inherent susceptibility of certain neurons to degeneration due to factors like metabolic stress, leading to protein aggregation. Recent advancements in neuroimaging, especially PET/MRI hybrid imaging, offer new insights into these mechanisms. While both hypotheses offer substantial evidence, their relative contributions to neurodegenerative processes remain to be fully elucidated. This uncertainty underscores the necessity for continued research, with a focus on these hypotheses, to develop effective treatments for these devastating diseases.}, }
@article {pmid39432435, year = {2024}, author = {Anjaneyulu, J and Godbole, A}, title = {Small organism models for mode of action research on anti-ageing and nootropic herbs, foods, and formulations.}, journal = {Nutritional neuroscience}, volume = {}, number = {}, pages = {1-19}, doi = {10.1080/1028415X.2024.2409128}, pmid = {39432435}, issn = {1476-8305}, abstract = {With global increase in ageing population along with increasing age-related neurodegenerative diseases (NDs), development of sustainable, safe and effective solutions for promoting healthy ageing and preventing diseases has become a priority. Traditional healthcare systems/medicines prescribe several herbs, foods and formulations to promote healthy ageing and prevent and/or treat age-related diseases. However, the scientific data elucidating their mechanism of action is very limited and deeper research using different models is warranted for timely and wider use. The clinical studies and research with higher model organisms, although useful, have several practical, technical, and financial limitations. Conversely, small organism models like Yeast, Roundworm, Fruit fly, and Zebrafish, which have genetic similarities to humans, can replicate the disease features and provide behavioural, cellular and molecular insights. The common features of ageing and NDs, like amyloid protein aggregations, oxidative stress, energy dysregulation, inflammation and neurodegeneration can be mimicked in the small organism models for Alzheimer's, Parkinson's, Huntington's diseases, and Amyotrophic Lateral Sclerosis. This review focuses on small organism model- based research unveiling interesting modes of action and synergistic effects of herbal extracts, foods, and formulations, which are indicated especially for healthy ageing and management of NDs. This will provide leads for the quick and sustainable development of scientifically evaluated solutions for clinically relevant, age-related conditions.}, }
@article {pmid39428248, year = {2024}, author = {Luo, N and Wang, J and Zhang, ZY and Zhao, XY and Huang, RR and Wu, QY}, title = {[Research progress on Pb-induced neurotoxicity through glial cells].}, journal = {Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine]}, volume = {58}, number = {10}, pages = {1610-1615}, doi = {10.3760/cma.j.cn112150-20240513-00382}, pmid = {39428248}, issn = {0253-9624}, support = {8217348282, 82173554, 82101593//National Natural Science Foundation of China/ ; }, mesh = {*Neuroglia/drug effects ; Humans ; *Lead/toxicity ; }, abstract = {Lead is one of the most important occupational hazards in China, and occupational exposure is the leading cause of lead poisoning. Lead can be absorbed by the body through air, food, drinking water and skin, and accumulate in multiple organs in the body, posing health risks to humans, especially to lead workers. Many previous studies have shown that lead can affect the function of glial cells such as microglia, astrocytes and oligodendrocytes, resulting in irreversible neurological damage. This article provides an overview of the neurotoxic mechanism induced by lead through glial cells, elucidates that lead can induce neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, and reviews the relationship between lead and glial cells, in order to provide reference for further research on the neurotoxic mechanism of lead on glial cells.}, }
@article {pmid39424648, year = {2024}, author = {Chartier, C and Godard, J and Durand, S and Humeau-Heurtier, A and Menetrier, E and Allain, P and Besnard, J}, title = {Combinations of physical and cognitive training for subcortical neurodegenerative diseases with physical, cognitive and behavioral symptoms: a systematic review.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {12}, pages = {5571-5589}, pmid = {39424648}, issn = {1590-3478}, mesh = {Humans ; *Neurodegenerative Diseases/therapy ; Behavioral Symptoms/therapy/etiology ; Cognitive Behavioral Therapy/methods ; Exercise Therapy/methods ; Cognitive Dysfunction/therapy/rehabilitation/etiology ; Cognitive Training ; }, abstract = {BACKGROUND: The onset of the symptoms of subcortical NDs is due to a unique part of the brain which strengthens the idea of reciprocal influence of physical activity and cognitive training in improving clinical symptoms. Consequently, protocols combining the two stimulations are becoming increasingly popular in NDs. Our threefold aim was to (A) describe the different combinations of physical and cognitive training used to alleviate the motor and cognitive symptoms of patients with subcortical neurodegenerative disorders, (B) compare the effects of these different combinations (sequential, dual tasking, synergical) on symptoms, and (C) recommend approaches for further studies.
METHODS: We conducted literature searches of PubMed, BASE and ACM, to carry out a systematic review of randomized controlled trials and controlled trials of combined physical and cognitive training among patients with Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, Lewy body dementia, spinocerebellar ataxia, Friedreich's ataxia, and progressive supranuclear palsy. Physical, neuropsychological, behavioral outcomes were considered. The Cochrane risk-of-bias tool was used to verify the critical appraisal.
RESULTS: Twenty-one studies focused on Parkinson's disease with 940 participants were included. Despites promising benefits on cognitive and physical function, our results revealed discrepant findings for research on combined training.
DISCUSSION: Inconsistencies were linked to the choice of tests, the functions that were targeted, disease progression, and trainings. There was a dearth of follow-up data.
CONCLUSIONS: Differences between combined training are unclear, particularly regarding the role of cognitive load. Future studies should focus on comparing the feasibility, tolerability, and effectiveness of different combinations of motor-cognitive training.}, }
@article {pmid39424561, year = {2024}, author = {Crow, YJ}, title = {CNS disease associated with enhanced type I interferon signalling.}, journal = {The Lancet. Neurology}, volume = {23}, number = {11}, pages = {1158-1168}, pmid = {39424561}, issn = {1474-4465}, support = {786142/ERC_/European Research Council/International ; MC_UU_00035/11/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Interferon Type I/metabolism/immunology ; *Signal Transduction ; Animals ; Central Nervous System Diseases/immunology/metabolism ; }, abstract = {The ability to mount an interferon-mediated innate immune response is essential in protection against neurotropic viruses, but antiviral type I interferons also have neurotoxic potential. The production of type I interferons can be triggered by self-derived nucleic acids, and the brain can be susceptible to inappropriate upregulation of type I interferon signalling. Homoeostatic dysregulation of type I interferons has been implicated in rare inborn errors of immunity (referred to as type I interferonopathies) and more common neurodegenerative disorders (eg, Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis). Recent developments include new insights into the pathogenesis of these disorders that involve dysregulated type I interferon signalling, as well as advances in their diagnosis and management. The role of type I interferons in brain cellular health suggests the future therapeutic potential of approaches that target these interferons and their signalling.}, }
@article {pmid39423873, year = {2024}, author = {Thapa, R and Moglad, E and Afzal, M and Gupta, G and Bhat, AA and Hassan Almalki, W and Kazmi, I and Alzarea, SI and Pant, K and Singh, TG and Singh, SK and Ali, H}, title = {The role of sirtuin 1 in ageing and neurodegenerative disease: A molecular perspective.}, journal = {Ageing research reviews}, volume = {102}, number = {}, pages = {102545}, doi = {10.1016/j.arr.2024.102545}, pmid = {39423873}, issn = {1872-9649}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Sirtuin 1/metabolism ; *Aging/metabolism/genetics ; Animals ; Oxidative Stress/physiology ; }, abstract = {Sirtuin 1 (SIRT1), an NAD+-dependent deacetylase, has emerged as a key regulator of cellular processes linked to ageing and neurodegeneration. SIRT1 modulates various signalling pathways, including those involved in autophagy, oxidative stress, and mitochondrial function, which are critical in the pathogenesis of neurodegenerative diseases. This review explores the therapeutic potential of SIRT1 in several neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS). Preclinical studies have demonstrated that SIRT1 activators, such as resveratrol, SRT1720, and SRT2104, can alleviate disease symptoms by reducing oxidative stress, enhancing autophagic flux, and promoting neuronal survival. Ongoing clinical trials are evaluating the efficacy of these SIRT1 activators, providing hope for future therapeutic strategies targeting SIRT1 in neurodegenerative diseases. This review explores the role of SIRT1 in ageing and neurodegenerative diseases, with a particular focus on its molecular mechanisms, therapeutic potential, and clinical applications.}, }
@article {pmid39422938, year = {2024}, author = {Pappolla, MA and Wu, P and Fang, X and Poeggeler, B and Sambamurti, K and Wisniewski, T and Perry, G}, title = {Stem Cell Interventions in Neurology: From Bench to Bedside.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {101}, number = {s1}, pages = {S395-S416}, doi = {10.3233/JAD-230897}, pmid = {39422938}, issn = {1875-8908}, mesh = {Humans ; Animals ; *Stem Cell Transplantation/methods/trends ; Nervous System Diseases/therapy ; Neurology/trends/methods ; Translational Research, Biomedical/trends ; Neural Stem Cells/transplantation ; }, abstract = {Stem cell therapies are progressively redefining the treatment landscape for a spectrum of neurological and age-related disorders. This review discusses the molecular and functional attributes of stem cells, emphasizing the roles of neural stem cells and mesenchymal stem cells in the context of neurological diseases such as stroke, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, Parkinson's disease, and Alzheimer's disease. The review also explores the potential of stem cells in addressing the aging process. The paper analyzes stem cells' intrinsic properties of self-renewal, differentiation, and paracrine effects, alongside the importance of laboratory-modified stem cells like induced pluripotent stem cells and transgenic stem cells. Insights into disease-specific stem cell treatments are offered, reviewing both successes and challenges in the field. This includes the translational difficulties from rodent studies to human trials. The review concludes by acknowledging the uncharted territories that warrant further investigation, emphasizing the potential roles of stem cell-derived exosomes and indole-related molecules, and aiming at providing a basic understanding of stem cell therapies.}, }
@article {pmid39418491, year = {2024}, author = {Kumar, R and Ghai, S and Finelli, A and Klotz, L and Kinnaird, A and Mannas, M and Bhindi, B and Sanchez-Salas, R and Anidjar, M and Ahmad, A and Chin, J and Inman, B and Perlis, N}, title = {The use of focal therapy for the treatment of prostate cancer in Canada: Where are we, how did we get here, and where are we going?.}, journal = {Canadian Urological Association journal = Journal de l'Association des urologues du Canada}, volume = {}, number = {}, pages = {}, doi = {10.5489/cuaj.8888}, pmid = {39418491}, issn = {1911-6470}, abstract = {INTRODUCTION: Focal therapy is an emerging treatment for localized prostate cancer. The objectives of this review were to: 1) review how focal therapies are regulated and approved; 2) summarize the scope and quality of the literature regarding safety, efficacy, and side-effects; and 3) outline ongoing clinical trials of focal therapy in Canada.
METHODS: Using the PRISMA framework for scoping reviews, we searched PubMed, Embase, and Cochrane from 2021-2024, complementing Hopstaken et al's search up functional and oncologic outcomes. Additionally, we examined the FDA database for regulatory details and ongoing trials in Canada via ClinicalTrial.gov.
RESULTS: FDA approval for prostate tissue ablation was granted to high-intensity focused ultrasound (HIFU) in 2015 via the de novo pathway; other therapies followed the 510(k) route, citing equivalence to predicate devices. Most studies are in early stages, primarily single-arm, prospective cohort designs. Oncologic outcomes like cancer detection and survival rates, alongside functional data, such as adverse events and erectile function, were assessed. Recurrence-free survival at 48 months ranged from 58-92%, pad-free rates were greater than 95%, and rates of new-onset erectile dysfunction were variable, ranging from no change to 50%. Rates of serious adverse events (SAEs) were low, ranging from 0-14%. Three Canadian clinical trials are actively enrolling participants, and five private clinics were found offering private HIFU, irreversible electroporation (IRE), or transurethral ultrasound ablation (TULSA).
CONCLUSIONS: Focal therapy technologies have gained regulatory approval for prostate tissue ablation, and, aside from provincial support for cryoablation in Alberta, are available to Canadians through private payment or clinical trials. Many studies demonstrate promising cancer control and impressive functional outcomes but are limited by their short followup and lack of comparator group. Clinical trial or registry participation should be prioritized to ensure an evidence-based integration into current prostate cancer treatment approaches.}, }
@article {pmid39405005, year = {2024}, author = {Cheng, JL and Cook, AL and Talbot, J and Perry, S}, title = {How is Excitotoxicity Being Modelled in iPSC-Derived Neurons?.}, journal = {Neurotoxicity research}, volume = {42}, number = {5}, pages = {43}, pmid = {39405005}, issn = {1476-3524}, mesh = {*Induced Pluripotent Stem Cells/drug effects/physiology ; Humans ; *Neurons/drug effects/metabolism ; Animals ; *Amyotrophic Lateral Sclerosis/pathology/metabolism ; Cell Differentiation/drug effects/physiology ; }, abstract = {Excitotoxicity linked either to environmental causes (pesticide and cyanotoxin exposure), excitatory neurotransmitter imbalance, or to intrinsic neuronal hyperexcitability, is a pathological mechanism central to neurodegeneration in amyotrophic lateral sclerosis (ALS). Investigation of excitotoxic mechanisms using in vitro and in vivo animal models has been central to understanding ALS mechanisms of disease. In particular, advances in induced pluripotent stem cell (iPSC) technologies now provide human cell-based models that are readily amenable to environmental and network-based excitotoxic manipulations. The cell-type specific differentiation of iPSC, combined with approaches to modelling excitotoxicity that include editing of disease-associated gene variants, chemogenetics, and environmental risk-associated exposures make iPSC primed to examine gene-environment interactions and disease-associated excitotoxic mechanisms. Critical to this is knowledge of which neurotransmitter receptor subunits are expressed by iPSC-derived neuronal cultures being studied, how their activity responds to antagonists and agonists of these receptors, and how to interpret data derived from multi-parameter electrophysiological recordings. This review explores how iPSC-based studies have contributed to our understanding of ALS-linked excitotoxicity and highlights novel approaches to inducing excitotoxicity in iPSC-derived neurons to further our understanding of its pathological pathways.}, }
@article {pmid39402174, year = {2024}, author = {Jellinger, KA}, title = {The spectrum of behavioral disorders in amyotrophic lateral sclerosis: current view.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {}, number = {}, pages = {}, pmid = {39402174}, issn = {1435-1463}, support = {Society for the Promotion of Research in Experimental Neurology, Vienna, Austria//Society for the Promotion of Research in Experimental Neurology, Vienna, Austria/ ; }, abstract = {Behavioral disorders, with an average prevalence of 30-60% are important non-motor symptoms in amyotrophic lateral sclerosis (ALS) that have a negative impact on prognosis, management and quality of life, yet the underlying neurobiology is poorly understood. Among people with ALS, apathy, fatigue, anxiety, irritability and other behavioral symptoms are the most prominent, although less frequent than cognitive impairment. The present review explores the current understanding of behavioral changes in ALS with particular emphasis on our current knowledge about their structural and functional brain correlates, substantiating a multisystem degeneration with particular dysfunction of frontal-subcortical circuits and dysfunction of fronto-striatal, frontotemporal and other essential brain systems. The natural history of behavioral dysfunctions in ALS and their relationship to frontotemporal lobe degeneration (FTLD) are not fully understood, although they form a clinical continuum, suggesting a differential vulnerability of non-motor brain networks, ALS being considered a brain network disorder. An assessment of risks or the early detection of brain connectivity signatures before structural changes may be helpful in investigating the pathophysiological mechanisms of behavioral impairment in ALS. Treatment of both ALS and co-morbid behavioral disorders is a multidisciplinary task, but whereas no causal or disease-modifying therapies for ALS are available, symptomatic treatment of a variety of behavioral symptoms plays a pivotal role in patient care, although the management of behavioral symptoms in clinical care still remains limited.}, }
@article {pmid39396709, year = {2024}, author = {Wu, J and Wu, J and Chen, T and Cai, J and Ren, R}, title = {Protein aggregation and its affecting mechanisms in neurodegenerative diseases.}, journal = {Neurochemistry international}, volume = {180}, number = {}, pages = {105880}, doi = {10.1016/j.neuint.2024.105880}, pmid = {39396709}, issn = {1872-9754}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; Protein Aggregation, Pathological/metabolism ; alpha-Synuclein/metabolism ; Amyloid beta-Peptides/metabolism ; Protein Aggregates/physiology ; tau Proteins/metabolism ; }, abstract = {Protein aggregation serves as a critical pathological marker in a spectrum of neurodegenerative diseases (NDs), including the formation of amyloid β (Aβ) and Tau neurofibrillary tangles in Alzheimer's disease, as well as α-Synuclein (α-Syn) aggregates in Parkinson's disease, Parkinson's disease-related dementia (PDD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). A significant proportion of patients with amyotrophic lateral sclerosis (ALS) exhibit TDP-43 aggregates. Moreover, a confluence of brain protein pathologies, such as Aβ, Tau, α-Syn, and TDP-43, has been identified in individual NDs cases, highlighting the intricate interplay among these proteins that is garnering heightened scrutiny. Importantly, protein aggregation is modulated by an array of factors, with burgeoning evidence suggesting that it frequently results from perturbations in protein homeostasis, influenced by the cellular membrane milieu, metal ion concentrations, post-translational modifications, and genetic mutations. This review delves into the pathological underpinnings of protein aggregation across various NDs and elucidates the intercommunication among disparate proteins within the same disease context. Additionally, we examine the pathogenic mechanisms by which diverse factors impinge upon protein aggregation, offering fresh perspectives for the future therapeutic intervention of NDs.}, }
@article {pmid39395841, year = {2024}, author = {Tran, M and Rhee, J and Hu, W and Magin, P and Shulruf, B}, title = {General practice trainee, supervisor and educator perspectives on the transitions in postgraduate training: a scoping review.}, journal = {Family medicine and community health}, volume = {12}, number = {4}, pages = {}, pmid = {39395841}, issn = {2009-8774}, mesh = {Humans ; *General Practice/education ; Education, Medical, Graduate ; General Practitioners/education ; Students, Medical/psychology ; }, abstract = {UNLABELLED: Transitions are a period and a process, through which there is a longitudinal adaptation in response to changing circumstances in clinical practice and responsibilities. While the experience of the transition in medical student learning and in hospital-based specialty training programmes are well described and researched, the experience of the transition in community-based postgraduate general practitioner (GP) training has not been described comprehensively.
OBJECTIVE: We aimed to identify, and categorise, the formative experiences of transitions in GP training and their impacts on personal and professional development.
DESIGN: We adopted Levac et al's scoping review methodology. Of 1543 retrieved records, 76 were selected for data extraction. Based on a combined model of the socioecological and multiple and multi-dimensional theories of transitions, data relating to the experiences of transitions were organised into contextual themes: being physical, psychosocial, organisational culture and chronological.
ELIGIBILITY CRITERIA: Empirical studies focused on general practice trainees or training, that discussed the transitions experienced in general practice training and that were published in English were included.
INFORMATION SOURCES: PubMed, MEDLINE and Web of Science databases were searched in January 2024 with no date limits for empirical studies on the transition experiences of GP into, and through, training.
RESULTS: Our findings describe context-dependent formative experiences which advance, or impede, learning and development. Time is a significant modulator of the factors contributing to more negative experiences, with some initially adverse experiences becoming more positive. Identification of the inflection point that represents a shift from initially adverse to more positive experiences of transitions may help moderate expectations for learning and performance at different stages of training.
CONCLUSION: Challenges in training can either advance development and contribute positively to professional identity formation and clinical competency, or detract from learning and potentially contribute to burnout and attrition from training programmes. These findings will assist future research in identifying predictive factors of positive and adverse experiences of transitions and may strengthen existing and nascent GP training programmes. The findings are transferable to other community-based specialty training programmes.}, }
@article {pmid39393594, year = {2024}, author = {Coppieters, R and Bouzigues, A and Jiskoot, L and Montembeault, M and Tee, BL and , and Rohrer, JD and Bruffaerts, R}, title = {A systematic review of the quantitative markers of speech and language of the frontotemporal degeneration spectrum and their potential for cross-linguistic implementation.}, journal = {Neuroscience and biobehavioral reviews}, volume = {167}, number = {}, pages = {105909}, doi = {10.1016/j.neubiorev.2024.105909}, pmid = {39393594}, issn = {1873-7528}, mesh = {Humans ; *Frontotemporal Dementia/physiopathology/diagnosis ; *Speech/physiology ; Linguistics ; Language ; Biomarkers ; }, abstract = {Frontotemporal dementia (FTD) is a neurodegenerative disease spectrum with an urgent need for reliable biomarkers for early diagnosis and monitoring. Speech and language changes occur in the early stages of FTD and offer a potential non-invasive, early, and accessible diagnostic tool. The use of speech and language markers in this disease spectrum is limited by the fact that most studies investigate English-speaking patients. This systematic review examines the literature on psychoacoustic and linguistic features of speech that occur across the FTD spectrum across as many different languages as possible. 76 papers were identified that investigate psychoacoustic and linguistic markers in discursive speech. 75 % of these papers studied English-speaking patients. The most generalizable features found across different languages, are speech rate, articulation rate, pause frequency, total pause duration, noun-verb ratio, and total number of nouns. While there are clear interlinguistic differences across patient groups, the results show promise for implementation of cross-linguistic markers of speech and language across the FTD spectrum particularly for psychoacoustic features.}, }
@article {pmid39390661, year = {2024}, author = {Howard, IM and Babu, S and Carter, C and Sakowski, SA and Kurent, JE and Cudkowicz, ME and Feldman, EL}, title = {Priorities and Recommendations to Make ALS a Livable Disease Emanating from the 2024 National Academies of Sciences, Engineering, and Medicine Report Living with ALS.}, journal = {Annals of neurology}, volume = {96}, number = {6}, pages = {1035-1039}, pmid = {39390661}, issn = {1531-8249}, support = {R01 TS000327/TS/ATSDR CDC HHS/United States ; OT2 NS136938/NS/NINDS NIH HHS/United States ; U01 NS077179/NS/NINDS NIH HHS/United States ; U01 NS136020/NS/NINDS NIH HHS/United States ; //Charles H. Abdalian, Jr. ALS Research Fund/ ; OT2 NS136939/NS/NINDS NIH HHS/United States ; //NeuroNetwork for Emerging Therapies/ ; R01 ES030049/ES/NIEHS NIH HHS/United States ; R01TS000344//Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry/ ; //American Academy of Neurology/ ; //ALS One/ ; //ALS Association/ ; UF1 NS131791/NS/NINDS NIH HHS/United States ; R01TS000327//Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry/ ; 1U01NS136021-01/NH/NIH HHS/United States ; 1U01NS136020-01/NH/NIH HHS/United States ; R01NS127188/NH/NIH HHS/United States ; R01ES030049/NH/NIH HHS/United States ; //Scott L. Pranger/ ; //The Sean M. Healey & AMG Center for ALS/ ; 1U01NS077179-01/NH/NIH HHS/United States ; //Muscular Dystrophy Association/ ; U01 NS136021/NS/NINDS NIH HHS/United States ; R01 NS127188/NS/NINDS NIH HHS/United States ; //The Neurological Clinical Research Institute/ ; UF1NS131791-01/NH/NIH HHS/United States ; 1OT2NS136938-1/NH/NIH HHS/United States ; R01 TS000344/TS/ATSDR CDC HHS/United States ; //ALS Finding a Cure/ ; OT2NS136939/NH/NIH HHS/United States ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy/diagnosis ; Humans ; United States ; Quality of Life ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a relentless, fatal neurodegenerative disease. The progressive loss of voluntary muscle function, diagnostic delays, lack of effective treatments, and challenges accessing multidisciplinary care and resources have tremendous impact on quality of life. The congressionally directed ALS committee of the National Academies of Science, Engineering, and Medicine, in their 2024 report "Living with ALS," recommends critical actions for specific United States stakeholders to make ALS a livable disease over the next decade. This review summarizes the context and recommendations of the report. Advocacy efforts are critical to make these recommendations a reality for the ALS community. ANN NEUROL 2024;96:1035-1039.}, }
@article {pmid39385461, year = {2024}, author = {Li, X and Wicks, P and Brown, A and Shivaprasad, A and Greene, M and Crayle, J and Barnes, B and Jhooty, S and Ratner, D and Olby, N and Glass, JD and Jackson, C and Cole, N and Armon, C and Mascias Cadavid, J and Pattee, G and Mcdermott, CJ and Chang, V and Maragakis, N and Bertorini, T and Bowser, R and Bedlack, R}, title = {ALSUntangled #76: Wahls protocol.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-5}, doi = {10.1080/21678421.2024.2407407}, pmid = {39385461}, issn = {2167-9223}, abstract = {The Wahls diet is a modified Paleolithic diet that emphasizes dark green leafy vegetables, colorful fruits, high-quality animal proteins, and omega-3 polyunsaturated fatty acids, while limiting grains, legumes, dairy products, sugar, and processed foods containing proinflammatory omega-6 fatty acids. The Wahls diet may reduce inflammation, oxidative stress, and mitochondrial dysfunction and has plausible mechanisms for slowing amyotrophic lateral sclerosis (ALS) progression. However, research on its dietary components in the ALS animal models has yielded conflicting results. Though multiple cohort studies suggest high carotenoids, omega-3 fatty acids and fruit intake are associated with reduced ALS risks, neither the diet nor its components has been demonstrated to slow down ALS progression in case studies or clinical trials. On the contrary, the Wahls diet, a restrictive, low-carbohydrate and low glycemic index diet, caused an average weight loss of 7.2% BMI in multiple sclerosis clinical trials, which is a significant concern for people living with amyotrophic lateral sclerosis (PALS) as weight loss is associated with faster ALS progression and shorter survival. Considering the above, we cannot endorse the Wahls diet for slowing ALS progression.}, }
@article {pmid39377567, year = {2024}, author = {Rani, P and Rajak, BK and Mahato, GK and Rathore, RS and Chandra, G and Singh, DV}, title = {Strategic lead compound design and development utilizing computer-aided drug discovery (CADD) to address herbicide-resistant Phalaris minor in wheat fields.}, journal = {Pest management science}, volume = {}, number = {}, pages = {}, doi = {10.1002/ps.8455}, pmid = {39377567}, issn = {1526-4998}, support = {//Science and Engineering Research Board, India/ ; //Department of Biotechnology, Ministry of Science and Technology, India/ ; //Department of Science and Technology, Ministry of Science and Technology, India/ ; }, abstract = {Wheat (Triticum aestivum) is a vital cereal crop and a staple food source worldwide. However, wheat grain productivity has significantly declined as a consequence of infestations by Phalaris minor. Traditional weed control methods have proven inadequate owing to the physiological similarities between P. minor and wheat during early growth stages. Consequently, farmers have turned to herbicides, targeting acetyl-CoA carboxylase (ACCase), acetolactate synthase (ALS) and photosystem II (PSII). Isoproturon targeting PSII was introduced in mid-1970s, to manage P. minor infestations. Despite their effectiveness, the repetitive use of these herbicides has led to the development of herbicide-resistant P. minor biotypes, posing a significant challenge to wheat productivity. To address this issue, there is a pressing need for innovative weed management strategies and the discovery of novel herbicide molecules. The integration of computer-aided drug discovery (CADD) techniques has emerged as a promising approach in herbicide research, that facilitates the identification of herbicide targets and enables the screening of large chemical libraries for potential herbicide-like molecules. By employing techniques such as homology modelling, molecular docking, molecular dynamics simulation and pharmacophore modelling, CADD has become a rapid and cost-effective medium to accelerate the herbicide discovery process significantly. This approach not only reduces the dependency on traditional experimental methods, but also enhances the precision and efficacy of herbicide development. This article underscores the critical role of bioinformatics and CADD in developing next-generation herbicides, offering new hope for sustainable weed management and improved wheat cultivation practices. © 2024 Society of Chemical Industry.}, }
@article {pmid39374680, year = {2024}, author = {Tirassa, P and Rosso, P and Fico, E and Marenco, M and Mallone, F and Gharbiya, M and Lambiase, A and Severini, C}, title = {Perspective role of Substance P in Amyotrophic Lateral Sclerosis: From neuronal vulnerability to neuroprotection.}, journal = {Neuroscience and biobehavioral reviews}, volume = {167}, number = {}, pages = {105914}, doi = {10.1016/j.neubiorev.2024.105914}, pmid = {39374680}, issn = {1873-7528}, mesh = {*Substance P/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism/physiopathology ; Humans ; Animals ; Receptors, Neurokinin-1/metabolism ; Neuroprotection/physiology ; Motor Neurons/metabolism/physiology ; }, abstract = {The neuropeptide Substance P (SP) and its preferred Neurokinin1 Receptor (NK1R) are known to participate in the physiopathology of neurodegenerative diseases and mainly exert a neuroprotective role. In the present work, we have described the involvement of SP and NK1R in Amyotrophic Lateral Sclerosis (ALS). This was demonstrated by the detection of altered levels of SP in the brain, spinal cord and cerebrospinal fluid (CSF) of patients and preclinical models of ALS, and by its ability to inhibit excitotoxicity-induced neurodegeneration in ALS animal models. These data are supported by results indicating an excitatory effect of SP at the motor neuron (MN) level, which promotes locomotor activity. ALS patients are characterized by a differential susceptibility to MNs degeneration, since sphincters and extraocular muscles are classically spared. It is hypothesized that SP may play a role in the maintenance of the ocular system and the innervation of the pelvic floor by contributing directly or indirectly to the selective resistance of this subset of MNs.}, }
@article {pmid39372031, year = {2024}, author = {Pillai, M and Jha, SK}, title = {Conformational Enigma of TDP-43 Misfolding in Neurodegenerative Disorders.}, journal = {ACS omega}, volume = {9}, number = {39}, pages = {40286-40297}, pmid = {39372031}, issn = {2470-1343}, abstract = {Misfolding and aggregation of the protein remain some of the most common phenomena observed in neurodegeneration. While there exist multiple neurodegenerative disorders characterized by accumulation of distinct proteins, what remains particularly interesting is the ability of these proteins to undergo a conformational change to form aggregates. TDP-43 is one such nucleic acid binding protein whose misfolding is associated with many neurogenerative diseases including amyotrophic lateral sclerosis (ALS) and fronto-temporal lobar degeneration (FTLD). TDP-43 protein assumes several different conformations and oligomeric states under the diseased condition. In this review, we explore the intrinsic relationship between the conformational variability of TDP-43 protein, with a particular focus on the RRM domains, and its propensity to undergo aggregation. We further emphasize the probable mechanism behind the formation of these conformations and suggest a potential diagnostic and therapeutic strategy in the context of these conformational states of the protein.}, }
@article {pmid39370211, year = {2024}, author = {Kajitani, GS and Xavier, G and Villena-Rueda, BE and Karia, BTR and Santoro, ML}, title = {Extracellular vesicles in neurodegenerative, mental, and other neurological disorders: Perspectives into mechanisms, biomarker potential, and therapeutic implications.}, journal = {Current topics in membranes}, volume = {94}, number = {}, pages = {299-336}, doi = {10.1016/bs.ctm.2024.06.002}, pmid = {39370211}, issn = {1063-5823}, mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Neurodegenerative Diseases/metabolism/pathology/therapy ; *Biomarkers/metabolism ; Mental Disorders/metabolism/drug therapy/therapy ; Animals ; Nervous System Diseases/metabolism/pathology ; }, abstract = {Extracellular vesicles (EVs) are produced, secreted, and targeted by most human cells, including cells that compose nervous system tissues. EVs carry several types of biomolecules, such as lipids, proteins and microRNA, and can function as signaling agents in physiological and pathological processes. In this chapter, we will focus on EVs and their cargo secreted by brain cells, especially neurons and glia, and how these aspects are affected in pathological conditions. The chapter covers neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, as well as several psychiatric disorders, namely schizophrenia, autism spectrum disorder and major depressive disorder. This chapter also addresses other types of neurological dysfunctions, epilepsy and traumatic brain injury. EVs can cross the blood brain barrier, and thus brain EVs may be detected in more accessible peripheral tissue, such as circulating blood. Alterations in EV composition and contents can therefore impart valuable clues into the molecular etiology of these disorders, and serve biomarkers regarding disease prevalence, progression and treatment. EVs can also be used to carry drugs and biomolecules into brain tissue, considered as a promising drug delivery agent for neurological diseases. Therefore, although this area of research is still in its early development, it offers great potential in further elucidating and in treating neurological disorders.}, }
@article {pmid39361871, year = {2025}, author = {Fernandes, JPM and Garcia, LP and Gouhie, FA and Pereira, RC and Santos, DFD}, title = {Association between motor neuron disease and HIV infection: A systematic review of case reports.}, journal = {International journal of STD & AIDS}, volume = {36}, number = {1}, pages = {24-35}, doi = {10.1177/09564624241288283}, pmid = {39361871}, issn = {1758-1052}, mesh = {Humans ; *HIV Infections/drug therapy/complications ; *Motor Neuron Disease/complications ; Adult ; Male ; *Amyotrophic Lateral Sclerosis/drug therapy/complications ; Female ; Middle Aged ; Riluzole/therapeutic use ; }, abstract = {BACKGROUND: Motor neuron disease (MND) is a well-known group of neurodegenerative diseases, with amyotrophic lateral sclerosis (ALS) being the most common form. Since 1985, a possible association between MND/ALS and HIV infection has been described.
METHODS: We performed a systematic review of case reports and case series involving people living with HIV with MND/ALS through PubMed, Bireme, Embase, and Lilacs databases. The risk of bias was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Tool for Case Reports.
RESULTS: We analyzed 36 articles presenting 88 cases. The mean age was 41.6 years. Antiretroviral therapy (ART) was used by 89.8% and riluzole by 16.9%. First signs and symptoms were similarly present on cervical/upper (25%) and lumbosacral/lower limbs (23.9%), mostly with fasciculations (69.8%) and hyperreflexia (58.8%). MND had a progressive course in 32.9% patients and a clinical improve in 54.6% following ART. The mean survival of the 32 patients who died was 12.3 months and the mean survival of the living patients was 62 months. Respiratory failure was the main cause of death (35.7%).
CONCLUSIONS: MND/ALS may present differently in the people living with HIV as a rapidly progressive disease in younger people but with the potential to improve weakness and survival through antiretroviral therapy.}, }
@article {pmid39347334, year = {2024}, author = {Aljehani, NS and Al-Gunaid, ST and Hobani, AH and Alhinti, MF and Khubrani, YA and Abu-Hamoud, LM and Alrayes, AA and Alharbi, LB and Sultan, AA and Turkistani, DA and Naiser, SS and Albraik, L and Alakel, AM and Alotaibi, M and Asiri, AY}, title = {Ultrasound Blood-Brain Barrier Opening and Aducanumab in Alzheimer's Disease: A Systematic Review and Meta-Analysis.}, journal = {Cureus}, volume = {16}, number = {8}, pages = {e68008}, pmid = {39347334}, issn = {2168-8184}, abstract = {The blood-brain barrier (BBB) presents a significant challenge in treating Alzheimer's disease, as it restricts the delivery of therapeutic medications to brain tissue. Reversible breaking of the BBB using low-intensity focused ultrasound guided by magnetic resonance imaging (MRI) may benefit patients with Alzheimer's disease and other neurological illnesses, such as brain tumors, amyotrophic lateral sclerosis, and Parkinson's disease. This systematic study and meta-analysis aimed to assess aducanumab and the ultrasonography of BBB opening in Alzheimer's patients. According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), the study was conducted by searching six digital repositories for relevant scholarly literature, focusing on English papers published between 2015 and 2024; the data was extracted using an Excel sheet, and data was analyzed using Revman 5.4.1 software. The study's findings indicate that the groups receiving ultrasound and aducanumab treatment benefited from it; however, overall, the effect was not statistically significant (P=0.29) at 95% CI 0.86 (0.75, 1.00). With regard to side effects, the results indicate that the treatment had fewer side effects compared to the control group; however, the difference was not statistically significant (p=0.94) at 95% CI 0.93 (0.70, 1.22). The study found a positive effect of ultrasound and aducanumab on the treatment groups, but it was not statistically significant. The control group had less side effects than the treatment group. Therefore, future studies should focus on the quantity or combination of the drug that yields more effective results.}, }
@article {pmid39346681, year = {2024}, author = {Fisher, RMA and Torrente, MP}, title = {Histone post-translational modification and heterochromatin alterations in neurodegeneration: revealing novel disease pathways and potential therapeutics.}, journal = {Frontiers in molecular neuroscience}, volume = {17}, number = {}, pages = {1456052}, pmid = {39346681}, issn = {1662-5099}, support = {R15 NS125394/NS/NINDS NIH HHS/United States ; }, abstract = {Alzheimer's disease (AD), Parkinson's disease (PD), Frontotemporal Dementia (FTD), and Amyotrophic lateral sclerosis (ALS) are complex and fatal neurodegenerative diseases. While current treatments for these diseases do alleviate some symptoms, there is an imperative need for novel treatments able to stop their progression. For all of these ailments, most cases occur sporadically and have no known genetic cause. Only a small percentage of patients bear known mutations which occur in a multitude of genes. Hence, it is clear that genetic factors alone do not explain disease occurrence. Chromatin, a DNA-histone complex whose basic unit is the nucleosome, is divided into euchromatin, an open form accessible to the transcriptional machinery, and heterochromatin, which is closed and transcriptionally inactive. Protruding out of the nucleosome, histone tails undergo post-translational modifications (PTMs) including methylation, acetylation, and phosphorylation which occur at specific residues and are connected to different chromatin structural states and regulate access to transcriptional machinery. Epigenetic mechanisms, including histone PTMs and changes in chromatin structure, could help explain neurodegenerative disease processes and illuminate novel treatment targets. Recent research has revealed that changes in histone PTMs and heterochromatin loss or gain are connected to neurodegeneration. Here, we review evidence for epigenetic changes occurring in AD, PD, and FTD/ALS. We focus specifically on alterations in the histone PTMs landscape, changes in the expression of histone modifying enzymes and chromatin remodelers as well as the consequences of these changes in heterochromatin structure. We also highlight the potential for epigenetic therapies in neurodegenerative disease treatment. Given their reversibility and pharmacological accessibility, epigenetic mechanisms provide a promising avenue for novel treatments. Altogether, these findings underscore the need for thorough characterization of epigenetic mechanisms and chromatin structure in neurodegeneration.}, }
@article {pmid39344228, year = {2024}, author = {Li, P and Tao, Z and Zhao, X}, title = {The Role of Osteopontin (OPN) in Regulating Microglia Phagocytosis in Nervous System Diseases.}, journal = {Journal of integrative neuroscience}, volume = {23}, number = {9}, pages = {169}, doi = {10.31083/j.jin2309169}, pmid = {39344228}, issn = {0219-6352}, mesh = {*Osteopontin/metabolism/physiology ; *Microglia/metabolism/physiology ; *Phagocytosis/physiology ; Animals ; Humans ; Nervous System Diseases/metabolism ; }, abstract = {Phagocytosis is the process by which certain cells or organelles internalise foreign substances by engulfing them and then digesting or disposing of them. Microglia are the main resident phagocytic cells in the brain. It is generally believed that microglia/macrophages play a role in guiding the brain's repair and functional recovery processes. However, the resident and invading immune cells of the central nervous system can also exacerbate tissue damage by stimulating inflammation and engulfing viable neurons. The functional consequences of microglial phagocytosis remain largely unexplored. Overall, phagocytosis is considered a beneficial phenomenon in acute brain injury because it eliminates dead cells and induces an anti-inflammatory response. Osteopontin (OPN) is a phosphorylated glycoprotein induced by injury in various tissues, including brain tissue. In acute brain injuries such as hemorrhagic stroke and ischemic stroke, OPN is generally believed to have anti-inflammatory effects. OPN can promote the reconstruction of the blood-brain barrier and up-regulate the scavenger receptor CD36. But in chronic diseases such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), OPN can cause microglia to engulf neurons and worsen disease progression. We explored the role of OPN in promoting microglial phagocytosis in nervous system disorders.}, }
@article {pmid39344189, year = {2024}, author = {Khorshidi, Z and Adibi, I and Ghasemi, M}, title = {Association between cerebrospinal fluid chitotriosidase level and amyotrophic lateral sclerosis: a systematic review.}, journal = {Hormone molecular biology and clinical investigation}, volume = {}, number = {}, pages = {}, pmid = {39344189}, issn = {1868-1891}, abstract = {INTRODUCTION: One of the fatal and debilitating neurodegenerative diseases is amyotrophic lateral sclerosis (ALS). Increasing age is one of the risk factors of ALS. Considering that the elderly population in the world is increasing, it is very important to identify useful and effective diagnostic and treatment methods. The purpose of this systematic review is to determine the relationship between chitotriosidase (CHIT1) level and ALS disorder.
CONTENT: Keywords "Amyotrophic Lateral Sclerosis", "Gehrig* Disease", "Charcot Disease", "Guam Disease", ALS, CHIT1 and chitotriosidase were searched in PubMed, Scopus, Web of Science and Science Direct databases without time limit on September 2023. Hundred twenty studies were obtained by searching, and finally, 14 studies were included in this study using the inclusion and exclusion criteria. In all 14 selected studies, the level of biomarker CHIT1 in the CSF of ALS patients was significantly higher than that of healthy control and disease control groups. But, in 8 studies that included 3 groups, no significant difference was observed between the CHIT1 levels in the two control groups. Six studies have reported the amount of CHIT1 level quantitatively. Among these 6 studies, in 5 studies CHIT1 level in disease control was higher than healthy control (not significant) and in only one study CHIT1 level was higher in healthy control compared to disease control (not significant).
SUMMARY AND OUTLOOK: In all 14 studies, a multifold increase in CHIT1 levels has been observed in patients compared to healthy and disease control groups. Therefore, based on the findings of the studies, this study confirms the relationship between CHIT1 increase and ALS disorder.}, }
@article {pmid39343990, year = {2024}, author = {Xia, L and Qiu, Y and Li, J and Xu, M and Dong, Z}, title = {The Potential Role of Artemisinins Against Neurodegenerative Diseases.}, journal = {The American journal of Chinese medicine}, volume = {52}, number = {6}, pages = {1641-1660}, doi = {10.1142/S0192415X24500642}, pmid = {39343990}, issn = {1793-6853}, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; *Artemisinins/pharmacology ; *Neuroprotective Agents/pharmacology ; Alzheimer Disease/drug therapy/metabolism ; Animals ; Oxidative Stress/drug effects ; Signal Transduction/drug effects ; Parkinson Disease/drug therapy/metabolism ; Ferroptosis/drug effects ; Amyotrophic Lateral Sclerosis/drug therapy ; Huntington Disease/drug therapy/metabolism ; Autophagy/drug effects ; }, abstract = {Artemisinin (ART) and its derivatives, collectively referred to as artemisinins (ARTs), have been approved for the treatment of malaria for decades. ARTs are converted into dihydroartemisinin (DHA), the only active form, which is reductive in vivo. In this review, we provide a brief overview of the neuroprotective potential of ARTs and the underlying mechanisms on several of the most common neurodegenerative diseases, particularly considering their potential application in those associated with cognitive and motor impairments including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). ARTs act as autophagy balancers to alleviate AD and PD. They inhibit neuroinflammatory responses by regulating phosphorylation of signal transduction proteins, such as AKT, PI3K, ERK, NF-κB, p38 MAPK, IκBα. In addition, ARTs regulate GABAergic signaling in a dose-dependent manner. Although they competitively inhibit the binding of gephyrin to GABAergic receptors, low doses of ARTs enhance GABAergic signaling. ARTs can also inhibit ferroptosis, activate the Akt/Bcl-2, AMPK, or ERK/CREB pathways to reduce oxidative stress, and maintain mitochondrial homeostasis, protecting neurons from oxidative stress injury. More importantly, ARTs structurally combine with and suppress β-Amyloid (A[Formula: see text]-induced neurotoxicity, reduce P-tau, and maintain O-GlcNAcylation/Phosphorylation balance, leading to relieved pathological changes in neurodegenerative diseases. Collectively, these natural properties endow ARTs with unique potential for application in neurodegenerative diseases.}, }
@article {pmid39343443, year = {2024}, author = {O'Brien, D and Shaw, PJ}, title = {New developments in the diagnosis and management of motor neuron disease.}, journal = {British medical bulletin}, volume = {152}, number = {1}, pages = {4-15}, doi = {10.1093/bmb/ldae010}, pmid = {39343443}, issn = {1471-8391}, support = {NIHR 203321//NIHR Sheffield Biomedical Research Centre/ ; 972-797//AMBRoSIA Biosampling Programme/ ; 764-780//MNDA (Sheffield Care and Research Centre for Motor Neuron Disorders/ ; }, mesh = {Humans ; *Motor Neuron Disease/therapy/diagnosis ; Neuroprotective Agents/therapeutic use ; Riluzole/therapeutic use ; }, abstract = {INTRODUCTION: Motor neuron disease (MND) is a devastating neurodegenerative disease characterized by progressive muscle weakness.
SOURCES OF DATA: PubMed, MEDLINE, and Cochrane databases were searched for articles to March 2024. Searches involved the terms 'motor neuron disease' or 'amyotrophic lateral sclerosis' and 'epidemiology', 'diagnosis', 'clinical', 'genetic', 'management', 'treatment', or 'trial'.
AREAS OF AGREEMENT: Evidence-based management involves riluzole, multidisciplinary care, provision of noninvasive ventilation and gastrostomy, and symptomatic treatments. Tofersen should be offered to treat SOD1-MND.
AREAS OF CONTROVERSY: Edaravone and Relyvrio are approved treatments in the USA, but insufficient evidence was found to support approval in the UK and Europe.
GROWING POINTS: The discovery of neurofilaments as MND biomarkers, growth of platform trials and development of novel therapies provide optimism for more powerful neuroprotective therapies.
Further work should focus on the elucidation of environmental causes of MND, gene-environment interactions, and advanced cellular models of disease.}, }
@article {pmid39341656, year = {2024}, author = {Paris, A and Lakatos, A}, title = {Cell and gene therapy for amyotrophic lateral sclerosis.}, journal = {Handbook of clinical neurology}, volume = {205}, number = {}, pages = {217-241}, doi = {10.1016/B978-0-323-90120-8.00017-4}, pmid = {39341656}, issn = {0072-9752}, mesh = {*Amyotrophic Lateral Sclerosis/therapy/genetics ; Humans ; *Genetic Therapy/methods ; Animals ; Cell- and Tissue-Based Therapy/methods/trends ; Disease Models, Animal ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disorder with rapidly progressive skeletal muscle weakness, which can also cause a variable cognitive deficit. Genetic causes are only identified in approximately 10% of all cases, with complex genotype-phenotype associations, making it challenging to identify treatment targets. What further hampers therapeutic development is a broad heterogeneity in mechanisms, possible targets, and disturbances across various cell types, aside from the cortical and spinal motor neurons that lie at the heart of the pathology of ALS. Over the last decade, significant progress in biotechnologic techniques, cell and ribonucleic acid (RNA) engineering, animal models, and patient-specific human stem cell and organoid models have accelerated both mechanistic and therapeutic discoveries. The growing number of clinical trials mirrors this. This chapter reviews the current state of human preclinical models supporting trial strategies as well as recent clinical cell and gene therapy approaches.}, }
@article {pmid39341507, year = {2024}, author = {Sivalingam, AM}, title = {Advances in understanding biomarkers and treating neurological diseases - Role of the cerebellar dysfunction and emerging therapies.}, journal = {Ageing research reviews}, volume = {101}, number = {}, pages = {102519}, doi = {10.1016/j.arr.2024.102519}, pmid = {39341507}, issn = {1872-9649}, mesh = {Humans ; *Biomarkers/metabolism ; Animals ; *Cerebellar Diseases/therapy/diagnosis/metabolism/genetics ; Genetic Therapy/methods/trends ; Nervous System Diseases/therapy/diagnosis/metabolism ; Cerebellum/metabolism/pathology ; }, abstract = {Cerebellar dysfunction is increasingly recognized as a critical factor in various neurological diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Research has revealed distinct cerebellar atrophy patterns in conditions such as AD and multiple system atrophy, and studies in mice have highlighted its impact on motor control and cognitive functions. Emerging research into autism spectrum disorder (ASD) has identified key targets, such as elevated levels of chemokine receptors and ZIC family genes. Biomarkers, including cerebrospinal fluid (CSF), genetic markers, and advances in AI and bioinformatics, are enhancing early diagnosis and personalized treatment across neurodegenerative disorders. Notable advancements include improved diagnostic tools, gene therapy, and novel clinical trials. Despite progress, challenges such as the bloodbrain barrier and neuroinflammation persist. Current therapies for AD, PD, HD, and ALS, including antisense oligonucleotides and stem cell treatments, show promise but require further investigation. A comprehensive approach that integrates diagnostic methods and innovative therapies is essential for effective management and improved patient outcomes.}, }
@article {pmid39340928, year = {2024}, author = {Dahl, R and Bezprozvanny, I}, title = {SERCA pump as a novel therapeutic target for treating neurodegenerative disorders.}, journal = {Biochemical and biophysical research communications}, volume = {734}, number = {}, pages = {150748}, doi = {10.1016/j.bbrc.2024.150748}, pmid = {39340928}, issn = {1090-2104}, support = {R01 AG071310/AG/NIA NIH HHS/United States ; R56 AG078337/AG/NIA NIH HHS/United States ; R42 AG062001/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; *Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism/antagonists & inhibitors ; Calcium Signaling/drug effects ; Molecular Targeted Therapy/methods ; Allosteric Regulation/drug effects ; }, abstract = {The neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and Spinocerebellar ataxias (SCAs), present an enormous medical, social, financial and scientific problem. Despite intense research into the causes of these disorders, only marginal progress has been made in the clinic and no cures exist for any of them. Most of the scientific effort has been focused on identification of the major causes of these diseases and on developing ways to target them, such as targeting amyloid accumulation for AD or targeting expression of mutant Huntingtin for HD. Calcium (Ca[2+]) signaling has long been proposed to play an important role in the pathogenesis of neurodegenerative disorders, but blockers of Ca[2+] channels and Ca[2+] signaling proteins have not been translated to clinic primarily due to side effects related to the important roles of target molecules for these compounds at the peripheral tissues. In this review article, we would like to discuss an idea that recently identified positive allosteric modulators (PAMs) of the sarco-endoplasmic reticulum calcium (SERCA) pump may provide a promising approach to develop therapeutic compounds for treatment of these disorders. This hypothesis is supported by the preclinical data obtained with animal models of AD and PD. The first critical test of this idea will be an imminent phase I study that will offer an opportunity to evaluate potential side effects of this class of compounds in humans.}, }
@article {pmid39340590, year = {2024}, author = {Ghiasvand, K and Amirfazli, M and Moghimi, P and Safari, F and Takhshid, MA}, title = {The role of neuron-like cell lines and primary neuron cell models in unraveling the complexity of neurodegenerative diseases: a comprehensive review.}, journal = {Molecular biology reports}, volume = {51}, number = {1}, pages = {1024}, pmid = {39340590}, issn = {1573-4978}, mesh = {Humans ; *Neurodegenerative Diseases/pathology ; *Neurons/metabolism ; Animals ; Coculture Techniques/methods ; Cell Line ; Models, Biological ; Alzheimer Disease/pathology/genetics ; }, abstract = {Neurodegenerative diseases (NDs) are characterized by the progressive loss of neurons. As to developing effective therapeutic interventions, it is crucial to understand the underlying mechanisms of NDs. Cellular models have become invaluable tools for studying the complex pathogenesis of NDs, offering insights into disease mechanisms, determining potential therapeutic targets, and aiding in drug discovery. This review provides a comprehensive overview of various cellular models used in ND research, focusing on Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Cell lines, such as SH-SY5Y and PC12 cells, have emerged as valuable tools due to their ease of use, reproducibility, and scalability. Additionally, co-culture models, involving the growth of distinct cell types like neurons and astrocytes together, are highlighted for simulating brain interactions and microenvironment. While cell lines cannot fully replicate the complexity of the human brain, they provide a scalable method for examining important aspects of neurodegenerative diseases. Advancements in cell line technologies, including the incorporation of patient-specific genetic variants and improved co-culture models, hold promise for enhancing our understanding and expediting the development of effective treatments. Integrating multiple cellular models and advanced technologies offers the potential for significant progress in unraveling the intricacies of these debilitating diseases and improving patient outcomes.}, }
@article {pmid39338563, year = {2024}, author = {Dow, CT and Pierce, ES and Sechi, LA}, title = {Mycobacterium paratuberculosis: A HERV Turn-On for Autoimmunity, Neurodegeneration, and Cancer?.}, journal = {Microorganisms}, volume = {12}, number = {9}, pages = {}, pmid = {39338563}, issn = {2076-2607}, abstract = {Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections that, over millions of years, became integrated into the human genome. While normally inactive, environmental stimuli such as infections have contributed to the transcriptional reactivation of HERV-promoting pathological conditions, including the development of autoimmunity, neurodegenerative disease and cancer. What infections trigger HERV activation? Mycobacterium avium subspecies paratuberculosis (MAP) is a pluripotent driver of human disease. Aside from granulomatous diseases, Crohn's disease, sarcoidosis and Blau syndrome, MAP is associated with autoimmune disease: type one diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis (RA) and autoimmune thyroiditis. MAP is also associated with Alzheimer's disease (AD) and Parkinson's disease (PD). Autoimmune diabetes, MS and RA are the diseases with the strongest MAP/HERV association. There are several other diseases associated with HERV activation, including diseases whose epidemiology and/or pathology would prompt speculation for a causal role of MAP. These include non-solar uveal melanoma, colon cancer, glioblastoma and amyotrophic lateral sclerosis (ALS). This article further points to MAP infection as a contributor to autoimmunity, neurodegenerative disease and cancer via the un-silencing of HERV. We examine the link between the ever-increasing number of MAP-associated diseases and the MAP/HERV intersection with these diverse medical conditions, and propose treatment opportunities based upon this association.}, }
@article {pmid39337908, year = {2024}, author = {Wang, R and Chen, L and Zhang, Y and Sun, B and Liang, M}, title = {Expression Changes of miRNAs in Humans and Animal Models of Amyotrophic Lateral Sclerosis and Their Potential Application for Clinical Diagnosis.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {9}, pages = {}, pmid = {39337908}, issn = {2075-1729}, support = {YJXJ-JZ-2021-0014//Scientific Research Project of Beijing Yicheng Cooperative Development Foundation in 2021-Public welfare projects of rare disease related topics/ ; KM202310858001//R&D Program of Beijing Municipal Education Commission/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease. Current detection methods can only confirm the diagnosis at the onset of the disease, missing the critical window for early treatment. Recent studies using animal models have found that detecting changes in miRNA sites can predict the onset and severity of the disease in its early stages, facilitating early diagnosis and treatment. miRNAs show expression changes in motor neurons that connect the brain, spinal cord, and brain stem, as well as in the skeletal muscle in mouse models of ALS. Clinically, expression changes in some miRNAs in patients align with those in mouse models, such as the upregulation of miR-29b in the brain and the upregulation of miR-206 in the skeletal muscle. This study provides an overview of some miRNA study findings in humans as well as in animal models, including SOD1, FUS, TDP-43, and C9orf72 transgenic mice and wobbler mice, highlighting the potential of miRNAs as diagnostic markers for ALS. miR-21 and miR-206 are aberrantly expressed in both mouse model and patient samples, positioning them as key potential diagnostic markers in ALS. Additionally, miR-29a, miR-29b, miR-181a, and miR-142-3p have shown aberrant expression in both types of samples and show promise as clinical targets for ALS. Finally, miR-1197 and miR-486b-5p have been recently identified as aberrantly expressed miRNAs in mouse models for ALS, although further studies are needed to determine their viability as diagnostic targets.}, }
@article {pmid39337696, year = {2024}, author = {Niazi, SK}, title = {Bioavailability as Proof to Authorize the Clinical Testing of Neurodegenerative Drugs-Protocols and Advice for the FDA to Meet the ALS Act Vision.}, journal = {International journal of molecular sciences}, volume = {25}, number = {18}, pages = {}, pmid = {39337696}, issn = {1422-0067}, mesh = {Humans ; *United States Food and Drug Administration ; United States ; *Drug Approval ; *Biological Availability ; *Amyotrophic Lateral Sclerosis/drug therapy ; Neurodegenerative Diseases/drug therapy ; Blood-Brain Barrier/metabolism ; Clinical Trials as Topic ; }, abstract = {Although decades of intensive drug discovery efforts to treat neurodegenerative disorders (NDs) have failed, around half a million patients in more than 2000 studies continue being tested, costing over USD 100 billion, despite the conclusion that even those drugs which have been approved have no better effect than a placebo. The US Food and Drug Administration (FDA) has established multiple programs to innovate the treatment of rare diseases, particularly NDs, providing millions of USD in funding primarily by encouraging novel clinical trials to account for issues related to study sizes and adopting multi-arm studies to account for patient dropouts. Instead, the FDA should focus on the primary reason for failure: the poor bioavailability of drugs reaching the brain (generally 0.1% at most) due to the blood-brain barrier (BBB). There are several solutions to enhance entry into the brain, and the FDA must require proof of significant entry into the brain as the prerequisite to approving Investigational New Drug (IND) applications. The FDA should also rely on factors other than biomarkers to confirm efficacy, as these are rarely relevant to clinical use. This study summarizes how the drugs used to treat NDs can be made effective and how the FDA should change its guidelines for IND approval of these drugs.}, }
@article {pmid39337560, year = {2024}, author = {Malaguarnera, M and Cabrera-Pastor, A}, title = {Emerging Role of Extracellular Vesicles as Biomarkers in Neurodegenerative Diseases and Their Clinical and Therapeutic Potential in Central Nervous System Pathologies.}, journal = {International journal of molecular sciences}, volume = {25}, number = {18}, pages = {}, pmid = {39337560}, issn = {1422-0067}, support = {PI23/00204//Instituto de Salud Carlos III (ISCIII) through the project "PI23/00204" and co-funded by the European Union; and Conselleria de Educación/Innovación, Universidades, Ciencia y Sociedad Digital, subvenciones para la realización de proyectos de I+D+i desarro/ ; CIGE/083//This research was funded by Instituto de Salud Carlos III (ISCIII) through the project "PI23/00204" and co-funded by the European Union; and Conselleria de Educación/Innovación, Universidades, Ciencia y Sociedad Digital, subvenciones para la realización d/ ; }, mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Biomarkers/metabolism ; *Neurodegenerative Diseases/therapy/metabolism/diagnosis ; Animals ; Central Nervous System Diseases/metabolism/therapy/diagnosis ; Blood-Brain Barrier/metabolism ; }, abstract = {The emerging role of extracellular vesicles (EVs) in central nervous system (CNS) diseases is gaining significant interest, particularly their applications as diagnostic biomarkers and therapeutic agents. EVs are involved in intercellular communication and are secreted by all cell types. They contain specific markers and a diverse cargo such as proteins, lipids, and nucleic acids, reflecting the physiological and pathological state of their originating cells. Their reduced immunogenicity and ability to cross the blood-brain barrier make them promising candidates for both biomarkers and therapeutic agents. In the context of CNS diseases, EVs have shown promise as biomarkers isolable from different body fluids, providing a non-invasive method for diagnosing CNS diseases and monitoring disease progression. This makes them useful for the early detection and monitoring of diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis, where specific alterations in EVs content can be detected. Additionally, EVs derived from stem cells show potential in promoting tissue regeneration and repairing damaged tissues. An evaluation has been conducted on the current clinical trials studying EVs for CNS diseases, focusing on their application, treatment protocols, and obtained results. This review aims to explore the potential of EVs as diagnostic markers and therapeutic carriers for CNS diseases, highlighting their significant advantages and ongoing clinical trials evaluating their efficacy.}, }
@article {pmid39337454, year = {2024}, author = {Rizea, RE and Corlatescu, AD and Costin, HP and Dumitru, A and Ciurea, AV}, title = {Understanding Amyotrophic Lateral Sclerosis: Pathophysiology, Diagnosis, and Therapeutic Advances.}, journal = {International journal of molecular sciences}, volume = {25}, number = {18}, pages = {}, pmid = {39337454}, issn = {1422-0067}, mesh = {*Amyotrophic Lateral Sclerosis/therapy/diagnosis/physiopathology/metabolism/genetics ; Humans ; Biomarkers ; Genetic Therapy/methods ; Oxidative Stress ; Animals ; Mitochondria/metabolism ; }, abstract = {This review offers an in-depth examination of amyotrophic lateral sclerosis (ALS), addressing its epidemiology, pathophysiology, clinical presentation, diagnostic techniques, and current as well as emerging treatments. The purpose is to condense key findings and illustrate the complexity of ALS, which is shaped by both genetic and environmental influences. We reviewed the literature to discuss recent advancements in understanding molecular mechanisms such as protein misfolding, mitochondrial dysfunction, oxidative stress, and axonal transport defects, which are critical for identifying potential therapeutic targets. Significant progress has been made in refining diagnostic criteria and identifying biomarkers, leading to earlier and more precise diagnoses. Although current drug treatments provide some benefits, there is a clear need for more effective therapies. Emerging treatments, such as gene therapy and stem cell therapy, show potential in modifying disease progression and improving the quality of life for ALS patients. The review emphasizes the importance of continued research to address challenges such as disease variability and the limited effectiveness of existing treatments. Future research should concentrate on further exploring the molecular foundations of ALS and developing new therapeutic approaches. The implications for clinical practice include ensuring the accessibility of new treatments and that healthcare systems are equipped to support ongoing research and patient care.}, }
@article {pmid39337436, year = {2024}, author = {Guo, D and Liu, Z and Zhou, J and Ke, C and Li, D}, title = {Significance of Programmed Cell Death Pathways in Neurodegenerative Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {18}, pages = {}, pmid = {39337436}, issn = {1422-0067}, support = {2023Y9415//Joint Funds for the innovation of science and Technology, Fujian province/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology ; *Signal Transduction ; Animals ; *Apoptosis ; Ferroptosis ; Neurons/metabolism/pathology ; }, abstract = {Programmed cell death (PCD) is a form of cell death distinct from accidental cell death (ACD) and is also referred to as regulated cell death (RCD). Typically, PCD signaling events are precisely regulated by various biomolecules in both spatial and temporal contexts to promote neuronal development, establish neural architecture, and shape the central nervous system (CNS), although the role of PCD extends beyond the CNS. Abnormalities in PCD signaling cascades contribute to the irreversible loss of neuronal cells and function, leading to the onset and progression of neurodegenerative diseases. In this review, we summarize the molecular processes and features of different modalities of PCD, including apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, and other novel forms of PCD, and their effects on the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), multiple sclerosis (MS), traumatic brain injury (TBI), and stroke. Additionally, we examine the key factors involved in these PCD signaling pathways and discuss the potential for their development as therapeutic targets and strategies. Therefore, therapeutic strategies targeting the inhibition or facilitation of PCD signaling pathways offer a promising approach for clinical applications in treating neurodegenerative diseases.}, }
@article {pmid39336146, year = {2024}, author = {Duranti, E and Villa, C}, title = {From Brain to Muscle: The Role of Muscle Tissue in Neurodegenerative Disorders.}, journal = {Biology}, volume = {13}, number = {9}, pages = {}, pmid = {39336146}, issn = {2079-7737}, abstract = {Neurodegenerative diseases (NDs), like amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and Parkinson's disease (PD), primarily affect the central nervous system, leading to progressive neuronal loss and motor and cognitive dysfunction. However, recent studies have revealed that muscle tissue also plays a significant role in these diseases. ALS is characterized by severe muscle wasting as a result of motor neuron degeneration, as well as alterations in gene expression, protein aggregation, and oxidative stress. Muscle atrophy and mitochondrial dysfunction are also observed in AD, which may exacerbate cognitive decline due to systemic metabolic dysregulation. PD patients exhibit muscle fiber atrophy, altered muscle composition, and α-synuclein aggregation within muscle cells, contributing to motor symptoms and disease progression. Systemic inflammation and impaired protein degradation pathways are common among these disorders, highlighting muscle tissue as a key player in disease progression. Understanding these muscle-related changes offers potential therapeutic avenues, such as targeting mitochondrial function, reducing inflammation, and promoting muscle regeneration with exercise and pharmacological interventions. This review emphasizes the importance of considering an integrative approach to neurodegenerative disease research, considering both central and peripheral pathological mechanisms, in order to develop more effective treatments and improve patient outcomes.}, }
@article {pmid39335395, year = {2024}, author = {Ore, A and Angelastro, JM and Giulivi, C}, title = {Integrating Mitochondrial Biology into Innovative Cell Therapies for Neurodegenerative Diseases.}, journal = {Brain sciences}, volume = {14}, number = {9}, pages = {}, pmid = {39335395}, issn = {2076-3425}, abstract = {The role of mitochondria in neurodegenerative diseases is crucial, and recent developments have highlighted its significance in cell therapy. Mitochondrial dysfunction has been implicated in various neurodegenerative disorders, including Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and Huntington's diseases. Understanding the impact of mitochondrial biology on these conditions can provide valuable insights for developing targeted cell therapies. This mini-review refocuses on mitochondria and emphasizes the potential of therapies leveraging mesenchymal stem cells, embryonic stem cells, induced pluripotent stem cells, stem cell-derived secretions, and extracellular vesicles. Mesenchymal stem cell-mediated mitochondria transfer is highlighted for restoring mitochondrial health in cells with dysfunctional mitochondria. Additionally, attention is paid to gene-editing techniques such as mito-CRISPR, mitoTALENs, mito-ZNFs, and DdCBEs to ensure the safety and efficacy of stem cell treatments. Challenges and future directions are also discussed, including the possible tumorigenic effects of stem cells, off-target effects, disease targeting, immune rejection, and ethical issues.}, }
@article {pmid39334720, year = {2024}, author = {Munteanu, C and Galaction, AI and Turnea, M and Blendea, CD and Rotariu, M and Poștaru, M}, title = {Redox Homeostasis, Gut Microbiota, and Epigenetics in Neurodegenerative Diseases: A Systematic Review.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {13}, number = {9}, pages = {}, pmid = {39334720}, issn = {2076-3921}, abstract = {Neurodegenerative diseases encompass a spectrum of disorders marked by the progressive degeneration of the structure and function of the nervous system. These conditions, including Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), Amyotrophic lateral sclerosis (ALS), and Multiple sclerosis (MS), often lead to severe cognitive and motor deficits. A critical component of neurodegenerative disease pathologies is the imbalance between pro-oxidant and antioxidant mechanisms, culminating in oxidative stress. The brain's high oxygen consumption and lipid-rich environment make it particularly vulnerable to oxidative damage. Pro-oxidants such as reactive nitrogen species (RNS) and reactive oxygen species (ROS) are continuously generated during normal metabolism, counteracted by enzymatic and non-enzymatic antioxidant defenses. In neurodegenerative diseases, this balance is disrupted, leading to neuronal damage. This systematic review explores the roles of oxidative stress, gut microbiota, and epigenetic modifications in neurodegenerative diseases, aiming to elucidate the interplay between these factors and identify potential therapeutic strategies. We conducted a comprehensive search of articles published in 2024 across major databases, focusing on studies examining the relationships between redox homeostasis, gut microbiota, and epigenetic changes in neurodegeneration. A total of 161 studies were included, comprising clinical trials, observational studies, and experimental research. Our findings reveal that oxidative stress plays a central role in the pathogenesis of neurodegenerative diseases, with gut microbiota composition and epigenetic modifications significantly influencing redox balance. Specific bacterial taxa and epigenetic markers were identified as potential modulators of oxidative stress, suggesting novel avenues for therapeutic intervention. Moreover, recent evidence from human and animal studies supports the emerging concept of targeting redox homeostasis through microbiota and epigenetic therapies. Future research should focus on validating these targets in clinical settings and exploring the potential for personalized medicine strategies based on individual microbiota and epigenetic profiles.}, }
@article {pmid39332091, year = {2024}, author = {Sharma, O and Kaur Grewal, A and Khan, H and Gurjeet Singh, T}, title = {Exploring the nexus of cGAS STING pathway in neurodegenerative terrain: A therapeutic odyssey.}, journal = {International immunopharmacology}, volume = {142}, number = {Pt B}, pages = {113205}, doi = {10.1016/j.intimp.2024.113205}, pmid = {39332091}, issn = {1878-1705}, mesh = {Humans ; *Membrane Proteins/metabolism/genetics ; Animals ; *Neurodegenerative Diseases/drug therapy/immunology/metabolism ; *Nucleotidyltransferases/metabolism/genetics ; *Signal Transduction ; Immunity, Innate ; }, abstract = {By detecting and responding to cytosolic DNA, the cGAS STING pathway regulates the innate immune responses bymediatinginflammatory reactions and antiviral defense. Thederegulation and modification of this system have been linked to variousneurodegenerative diseases like AD, PD and ALS. Accumulation of tau protein and Aβ aggregates to activate the pathway and releases neuroinflammatory cytokines which accelerates neuronal dysfunction and cognitive impairment as the symptom of AD. Similarly, in PD Alpha-synuclein aggregates activate the cGAS STING pathway and regulate the neuroinflammation and oxidative stress. In ALS, mutation of the genes causes the activation of the pathway which leads to motor neuron degeneration. Alteration of the cGAS STING pathway also leads to mitochondrial dysfunction and impaired autophagy. Preclinical investigations of AD, PD, and ALS animal models showed that STING pathway inhibitors reduced inflammation and improved neurological outcomes and modulators of the cGAS STING pathway may treat these neurodegenerative disorders. In this review we focus on the fact thatneuroinflammation, neuronal dysfunction, and various disease progressions can be treated byaltering the cGAS STING pathway. Understanding the processes and creating specific interventions for this route may offer new treatments for these terrible illnesses.}, }
@article {pmid39330700, year = {2024}, author = {Everett, WH and Bucelli, RC}, title = {Tofersen for SOD1 ALS.}, journal = {Neurodegenerative disease management}, volume = {14}, number = {5}, pages = {149-160}, pmid = {39330700}, issn = {1758-2032}, mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Oligonucleotides/therapeutic use ; *Superoxide Dismutase-1/antagonists & inhibitors ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition affecting the motor system. The heterogenous nature of ALS complicates trial design. Genetic forms of ALS present an opportunity to intervene in a less heterogeneous population. ALS associated with gain of function mutations in SOD1 make 'knock-down' strategies an attractive therapeutic approach. Tofersen, an antisense oligonucleotide that reduces expression of SOD1 via RNAase mediated degradation of SOD1 mRNA, has shown robust effects on ALS biomarkers. While a Phase III trial of tofersen failed to meet its primary end point, open label extension data suggests that tofersen slows progression of SOD1 ALS.}, }
@article {pmid39323817, year = {2024}, author = {Zeng, A and Huang, Y and Xin, J and Li, J and Qiu, W and Zhang, M}, title = {Progress and recommendations of developing occupational exposure limits for noise-A systematic review.}, journal = {Heliyon}, volume = {10}, number = {18}, pages = {e37878}, pmid = {39323817}, issn = {2405-8440}, abstract = {OBJECTIVE: Noise exposure limit is one of the critical measures to prevent noise-induced hearing loss (NIHL). This review aimed to review the progress and recommendations for developing occupational exposure limits (OELs) for workplace noise.
METHODS: A systematic review was used. Thirty-eight national or international organizations' noise exposure standards (including OEL) and laws, regulations, and guidelines for noise exposure control were analyzed. Articles on recommendations for revising noise OEL standards between 2000 and 2023 were selected.
RESULTS: The definition of different noise types (especially for non-steady and impulsive noise) varied worldwide, and the used 8-h OEL varied from 80 to 90 dB(A). Maximum sound pressure level (Lmax) and noise dose for industrial noise and peak sound pressure level (Lpeak) for impulsive noise have been incorporated into the OELs. Countries developed noise risk management measures based on OELs, action levels (ALs), and exposure risk ratio or classification. The risk of co-exposure to noise and ototoxic organic substances and the effects of noise on susceptible populations were concerns in EU country standards. Scholars suggested revising the existing noise exposure standards based on noise's temporal structure (expressed by kurtosis), effective noise level, impulsive noise OEL, action level, and key factors of risk assessment.
CONCLUSIONS: Indicators such as Lmax, noise dose, Lpeak, and action level can be incorporated into noise OELs. Developing noise OEL standards should consider the co-exposure of noise and ototoxic substances, HPD's noise attenuation, susceptible groups, and noise's temporal structure.}, }
@article {pmid39322357, year = {2024}, author = {Mehta, RI and Ranjan, M and Haut, MW and Carpenter, JS and Rezai, AR}, title = {Focused Ultrasound for Neurodegenerative Diseases.}, journal = {Magnetic resonance imaging clinics of North America}, volume = {32}, number = {4}, pages = {681-698}, doi = {10.1016/j.mric.2024.03.001}, pmid = {39322357}, issn = {1557-9786}, mesh = {Humans ; *Neurodegenerative Diseases/diagnostic imaging ; Ultrasonic Therapy/methods ; Brain/diagnostic imaging ; Animals ; }, abstract = {Neurodegenerative diseases are a leading cause of death and disability and pose a looming global public health crisis. Despite progress in understanding biological and molecular factors associated with these disorders and their progression, effective disease modifying treatments are presently limited. Focused ultrasound (FUS) is an emerging therapeutic strategy for Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. In these contexts, applications of FUS include neuroablation, neuromodulation, and/or blood-brain barrier opening with and without facilitated intracerebral drug delivery. Here, the authors review preclinical evidence and current and emerging applications of FUS for neurodegenerative diseases and summarize future directions in the field.}, }
@article {pmid39321879, year = {2024}, author = {Lei, T and Zhang, X and Fu, G and Luo, S and Zhao, Z and Deng, S and Li, C and Cui, Z and Cao, J and Chen, P and Yang, H}, title = {Advances in human cellular mechanistic understanding and drug discovery of brain organoids for neurodegenerative diseases.}, journal = {Ageing research reviews}, volume = {102}, number = {}, pages = {102517}, doi = {10.1016/j.arr.2024.102517}, pmid = {39321879}, issn = {1872-9649}, mesh = {Humans ; *Organoids/drug effects/pathology ; *Neurodegenerative Diseases/pathology/drug therapy ; *Drug Discovery/methods ; *Brain/pathology/drug effects ; Animals ; }, abstract = {The prevalence of neurodegenerative diseases (NDs) is increasing rapidly as the aging population accelerates, and there are still no treatments to halt or reverse the progression of these diseases. While traditional 2D cultures and animal models fail to translate into effective therapies benefit patients, 3D cultured human brain organoids (hBOs) facilitate the use of non-invasive methods to capture patient data. The purpose of this study was to review the research and application of hBO in disease models and drug screening in NDs. The pluripotent stem cells are induced in multiple stages to form cerebral organoids, brain region-specific organoids and their derived brain cells, which exhibit complex brain-like structures and perform electrophysiological activities. The brain region-specific organoids and their derived neurons or glial cells contribute to the understanding of the pathogenesis of NDs and the efficient development of drugs, including Alzheimer's disease, Parkinson's disease, Huntington's disease and Amyotrophic lateral sclerosis. Glial-rich brain organoids facilitate the study of glial function and neuroinflammation, including astrocytes, microglia, and oligodendrocytes. Further research on the maturation enhancement, vascularization and multi-organoid assembly of hBO will help to enhance the research and application of NDs cellular models.}, }
@article {pmid39318842, year = {2024}, author = {Emary, PC and Turner, AJ}, title = {Cervical spondylotic myelopathy in a 68-year-old man diagnosed with amyotrophic lateral sclerosis.}, journal = {The Journal of the Canadian Chiropractic Association}, volume = {68}, number = {2}, pages = {172-176}, pmid = {39318842}, issn = {0008-3194}, abstract = {Owing to similar clinical presentations, cervical spondylotic myelopathy can mimic other neurological disorders. In this imaging case review (ICR), we describe a case of cervical spondylotic myelopathy in a patient diagnosed with amyotrophic lateral sclerosis. The key clinical features, imaging findings and differential diagnoses of cervical spondylotic myelopathy compared with amyotrophic lateral sclerosis are also presented.}, }
@article {pmid39317854, year = {2024}, author = {Khoshdooz, S and Abbasi, H and Abbasi, MM}, title = {Iron-Status Indicators and HFE Gene Polymorphisms in Individuals with Amyotrophic Lateral Sclerosis: An Umbrella Review of Meta-analyses and Systematic Reviews.}, journal = {Biological trace element research}, volume = {}, number = {}, pages = {}, pmid = {39317854}, issn = {1559-0720}, abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of motor neurons. Recent meta-analyses and systematic reviews suggest that HFE gene polymorphisms and iron-associated biomarkers may play a key role in the risk and occurrence of ALS. This umbrella study aimed to explore the roles of HFE gene polymorphisms and iron-associated biomarkers in individuals with ALS. A thorough search of three online scientific databases, namely Scopus, Web of Science, and PubMed, was conducted from their inception until September 13, 2024. The screening and selection processes were executed based on the PICO framework and eligibility criteria, followed by two independent reviewers. The Assessment of Multiple Systematic Reviews (AMSTAR)-2 and GRADE tools were utilized to assess the methodological quality and the certainty of evidence. Through an advanced search, 101 records were retrieved, of which eight meta-analyses and systematic reviews were selected for this umbrella review. A significant increase in iron concentrations was found in individuals with ALS compared to healthy controls (SMD, 0.26; 95% CI - 0.05, 0.57). Conversely, selected meta-analyses reported that serum transferrin concentrations in ALS patients were lower compared to healthy controls (SMD, - 0.15; 95% CI - 0.36, 0.05). Furthermore, mutations in H63D polymorphisms resulted in a 13% significant increase in the risk of ALS (OR, 1.13; 95% CI 1.05, 1.22). Our umbrella study of meta-analyses and systematic reviews reveals that individuals with ALS have lower serum concentrations of transferrin compared to healthy controls. Additionally, the H63D polymorphism in the HFE gene is associated with a slight increase in the risk of ALS. Future research should investigate broader aspects of iron-related biomarkers and HFE genes to elucidate their roles in ALS pathogenesis. Registration: Our umbrella study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with the identification number CRD42024559032 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024559032).}, }
@article {pmid39317352, year = {2024}, author = {Kleinerova, J and Garcia-Gallardo, A and Tacheva, A and Bede, P}, title = {Subcortical grey matter involvement in ALS and PLS - vulnerable hubs of cortico-cortical and cortico-basal circuits: extrapyramidal, cognitive, bulbar and respiratory correlates.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {}, number = {}, pages = {1-4}, doi = {10.1080/21678421.2024.2405130}, pmid = {39317352}, issn = {2167-9223}, abstract = {Evidence from neuroimaging studies suggests that the cardinal clinical manifestations of ALS stem from the dysfunction of specific neural networks. The majority of cortico-cortical and cortico-basal networks are physiologically relayed by deep cerebral and cerebellar grey matter nuclei which have been increasingly implicated in the pathophysiology of ALS. A series of recent human imaging papers revealed volume reductions, shape deformations, metabolic alterations and more recently, susceptibility changes in hippocampal subfields, thalamic, striatal, amygdalar and cerebellar nuclei. Thalamic changes have been identified in presymptomatic mutation carriers long before symptom onset and longitudinal studies have consistently confirmed progressive subcortical degeneration during the symptomatic phase of the disease. The dysfunction of circuits relayed by specific subcortical nuclei has been associated with apathy, amnestic deficits, limbic symptoms, extrapyramidal manifestations, sensory disturbances, pseudobulbar affect and cerebellar deficits. In light of emerging imaging data, the clinical heterogeneity of ALS is probably best approached from a network integrity perspective. Accordingly, the comprehensive assessment of subcortical grey matter nuclei seems imperative to untangle complex clinical phenomena in ALS.}, }
@article {pmid39313512, year = {2024}, author = {Khan, AF and Iturria-Medina, Y}, title = {Beyond the usual suspects: multi-factorial computational models in the search for neurodegenerative disease mechanisms.}, journal = {Translational psychiatry}, volume = {14}, number = {1}, pages = {386}, pmid = {39313512}, issn = {2158-3188}, mesh = {Humans ; *Neurodegenerative Diseases/diagnostic imaging/physiopathology ; *Neuroimaging/methods ; *Brain/diagnostic imaging/physiopathology ; Disease Progression ; Biomarkers ; Alzheimer Disease/diagnostic imaging/physiopathology ; Computer Simulation ; }, abstract = {From Alzheimer's disease to amyotrophic lateral sclerosis, the molecular cascades underlying neurodegenerative disorders remain poorly understood. The clinical view of neurodegeneration is confounded by symptomatic heterogeneity and mixed pathology in almost every patient. While the underlying physiological alterations originate, proliferate, and propagate potentially decades before symptomatic onset, the complexity and inaccessibility of the living brain limit direct observation over a patient's lifespan. Consequently, there is a critical need for robust computational methods to support the search for causal mechanisms of neurodegeneration by distinguishing pathogenic processes from consequential alterations, and inter-individual variability from intra-individual progression. Recently, promising advances have been made by data-driven spatiotemporal modeling of the brain, based on in vivo neuroimaging and biospecimen markers. These methods include disease progression models comparing the temporal evolution of various biomarkers, causal models linking interacting biological processes, network propagation models reproducing the spatial spreading of pathology, and biophysical models spanning cellular- to network-scale phenomena. In this review, we discuss various computational approaches for integrating cross-sectional, longitudinal, and multi-modal data, primarily from large observational neuroimaging studies, to understand (i) the temporal ordering of physiological alterations, i(i) their spatial relationships to the brain's molecular and cellular architecture, (iii) mechanistic interactions between biological processes, and (iv) the macroscopic effects of microscopic factors. We consider the extents to which computational models can evaluate mechanistic hypotheses, explore applications such as improving treatment selection, and discuss how model-informed insights can lay the groundwork for a pathobiological redefinition of neurodegenerative disorders.}, }
@article {pmid39311426, year = {2024}, author = {Azzolino, D and Piras, R and Zulueta, A and Lucchi, T and Lunetta, C}, title = {Amyotrophic lateral sclerosis as a disease model of sarcopenia.}, journal = {Age and ageing}, volume = {53}, number = {9}, pages = {}, doi = {10.1093/ageing/afae209}, pmid = {39311426}, issn = {1468-2834}, mesh = {Humans ; *Sarcopenia/physiopathology/diagnosis ; *Amyotrophic Lateral Sclerosis/physiopathology/complications/diagnosis ; *Muscle, Skeletal/pathology/physiopathology ; Aging/pathology ; Animals ; Age Factors ; Aged ; Risk Factors ; }, abstract = {Sarcopenia, the progressive decline of muscle mass and function, has traditionally been viewed as an age-related process leading to a broad range of adverse outcomes. However, it has been widely reported that sarcopenia can occur earlier in life in association with various conditions (i.e. disease-related sarcopenia), including neuromuscular disorders. As early as 2010, the European Working Group on Sarcopenia in Older People included neurodegenerative diseases characterised by motor neuron loss among the mechanisms underlying sarcopenia. Despite some differences in pathogenetic mechanisms, both amyotrophic lateral sclerosis (ALS) and age-related sarcopenia share common characteristics, such as the loss of motor units and muscle fibre atrophy, oxidative stress, mitochondrial dysfunction and inflammation. The histology of older muscle shows fibre size heterogeneity, fibre grouping and a loss of satellite cells, similar to what is observed in ALS patients. Regrettably, the sarcopenic process in ALS patients has been largely overlooked, and literature on the condition in this patient group is very scarce. Some instruments used for the assessment of sarcopenia in older people could also be applied to ALS patients. At this time, there is no approved specific pharmacological treatment to reverse damage to motor neurons or cure ALS, just as there is none for sarcopenia. However, some agents targeting the muscle, like myostatin and mammalian target of rapamycin inhibitors, are under investigation both in the sarcopenia and ALS context. The development of new therapeutic agents targeting the skeletal muscle m