@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.},
}

*Amyotrophic Lateral Sclerosis/genetics/drug therapy/therapy
Humans
*Huntington Disease/genetics/drug therapy/therapy
*Oligonucleotides, Antisense/therapeutic use
Animals
Genetic Therapy/methods/trends

@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.},
}

Humans
*Nervous System Diseases
Animals
Superoxide Dismutase/metabolism
Motor Neuron Disease
Neurons/metabolism
Phase Separation

@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.},
}

Humans
*Caregivers/psychology
*Neurodegenerative Diseases/psychology/complications
*Empathy

@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.},
}

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

@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.},
}

Humans
*Chitinase-3-Like Protein 1/metabolism
*Neurodegenerative Diseases/metabolism/pathology
*Neuroinflammatory Diseases/metabolism
Animals

@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.},
}

*Blood-Brain Barrier/metabolism
Humans
*Neurodegenerative Diseases/metabolism
Animals
*Insulin/metabolism
*Glucose/metabolism
Brain/metabolism

@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.},
}

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

@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.},
}

*Amyotrophic Lateral Sclerosis/epidemiology/complications
Humans
*Venous Thromboembolism/epidemiology/etiology
Incidence
Risk Factors
Male
Female

@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.},
}

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

@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.},
}

*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

@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.},
}

*Amyotrophic Lateral Sclerosis/drug therapy/immunology/genetics
Animals
Mice
*Disease Models, Animal
Mice, Transgenic
Humans
Superoxide Dismutase-1/genetics
Herbal Medicine

@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.},
}

Humans
*Nervous System Diseases/rehabilitation/psychology/diagnosis
*Neurological Rehabilitation/methods
*Psychometrics/methods
*Quality of Life/psychology
Reproducibility of Results

@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.},
}

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

@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.},
}

Humans
*Amyotrophic Lateral Sclerosis/complications/therapy
*Quality of Life
*Physical Therapy Modalities
*Fatigue/therapy/etiology
Randomized Controlled Trials as Topic

@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.},
}

Humans
*Amyotrophic Lateral Sclerosis/blood/genetics/diagnosis
Biomarkers/blood
*Extracellular Vesicles/metabolism/genetics
*MicroRNAs/blood/genetics

@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.},
}

*Amyotrophic Lateral Sclerosis/psychology/therapy/complications
Humans
*Advance Directives/statistics & numerical data/psychology
Advance Care Planning/statistics & numerical data/standards

@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.},
}

Humans
Genetic Predisposition to Disease/genetics
*Genome-Wide Association Study
*Neurodegenerative Diseases/genetics
White People/genetics

@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.},
}

Humans
*Qualitative Research
*Defensive Medicine
Attitude of Health Personnel

@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.},
}

Humans
*HIV Infections/psychology
*Health Knowledge, Attitudes, Practice
Healthcare Disparities

@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.},
}

Humans
*Stem Cell Transplantation/methods
*Immunosuppression Therapy/methods
Retina/immunology
Immunosuppressive Agents/therapeutic use
Clinical Trials as Topic

@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.},
}

*Amyotrophic Lateral Sclerosis/psychology/physiopathology
Humans
*Quality of Life/psychology
Patient Reported Outcome Measures

@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.},
}

Humans
*Neurodegenerative Diseases/drug therapy
*Clinical Trials as Topic
*Patient Participation
Patient Selection

@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.},
}

Child, Preschool
Female
Humans
Infant
*Anemia/epidemiology
Comorbidity
*Developing Countries/statistics & numerical data
*Growth Disorders/epidemiology
*Micronutrients/deficiency
Prevalence
*Wasting Syndrome/epidemiology

@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.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/epidemiology
Genetic Predisposition to Disease/genetics
Mutation
Mutation, Missense
*Neurofilament Proteins/genetics
Protein Domains/genetics

@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.},
}

*Amyotrophic Lateral Sclerosis/therapy/physiopathology
Humans
*Randomized Controlled Trials as Topic
*Quality of Life
*Network Meta-Analysis
Exercise Therapy/methods
Treatment Outcome
Muscle Strength

@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.},
}

*Amyotrophic Lateral Sclerosis/therapy
Humans
*Clinical Trials as Topic/standards
*Research Design

@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).},
}

Humans
*Inflammatory Bowel Diseases/complications
*Neurodegenerative Diseases/epidemiology/etiology
Longitudinal Studies
Risk Factors
Prospective Studies

@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.},
}

Humans
*Thalamus/diagnostic imaging/pathology/physiopathology
*Motor Neuron Disease/diagnostic imaging/pathology/physiopathology
*Magnetic Resonance Imaging
Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology/physiopathology

@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.},
}

Humans
*Carnitine/therapeutic use
Dietary Supplements
*Mental Disorders/drug therapy
*Nervous System Diseases/drug therapy

@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.},
}

Humans
*Amyotrophic Lateral Sclerosis/complications/therapy
*Dyspnea/etiology/therapy
Palliative Care/methods/standards
Noninvasive Ventilation/methods/standards
Quality of Life
Analgesics, Opioid/therapeutic use

@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: Musik- 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.Sechs (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.Zwölf (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).Evidenzen 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.},
}

*Aromatherapy
*Music Therapy
Humans
*Anxiety/therapy
Heart Rate

@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.},
}

Humans
*Amyotrophic Lateral Sclerosis
Quality of Life
*Neurodegenerative Diseases
Exercise Therapy/methods
Muscle Spasticity

@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.},
}

*Amyotrophic Lateral Sclerosis/physiopathology
Humans
*Transcranial Magnetic Stimulation
*Neural Inhibition/physiology
*Motor Cortex/physiopathology
Evoked Potentials, Motor/physiology

@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: Seit 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.Das 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.Wir 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.Neun 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.Auf 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.},
}

Humans
*Mineral Waters/therapeutic use
*Gastroesophageal Reflux/therapy/drug therapy
*Heartburn/drug therapy
*Dyspepsia/drug therapy
Randomized Controlled Trials as Topic

@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: Die 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.Ziel 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.Es 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.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.Die 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.},
}

Humans
*Acupressure
*Anxiety Disorders/therapy
Randomized Controlled Trials as Topic
Auriculotherapy/methods

@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.},
}

Humans
Algorithms
*Alzheimer Disease/diagnostic imaging
*Deep Learning
Machine Learning
*Neurodegenerative Diseases/diagnostic imaging
Datasets as Topic
*Retina/diagnostic imaging

@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.},
}

*Edaravone/therapeutic use
Humans
*Amyotrophic Lateral Sclerosis/drug therapy
Free Radical Scavengers/therapeutic use
Randomized Controlled Trials as Topic/methods
Treatment Outcome

@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: Akupunktur 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.Wir 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.Im 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).Die 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.},
}

Humans
*Amyotrophic Lateral Sclerosis/immunology
Biomarkers
*Neurodegenerative Diseases/immunology
*Parkinson Disease/immunology

@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: Diabetes 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.Es 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.Insgesamt 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.HJD 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.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/genetics
Biomarkers
Machine Learning
*MicroRNAs/genetics

@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.},
}

Humans
Cross-Sectional Studies
*Attention
*Parkinson Disease
Gait
Electroencephalography

@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: Die 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.Wir 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.Von 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.Die Ergebnisse der randomisierten, kontrollierten Studien zeigen, dass die Heiltorftherapie eine vielversprechende Ergänzung in einem multidisziplinären Ansatz der Arthrosetherapie ist.},
}

Humans
*Mud Therapy
*Osteoarthritis, Knee
*Osteoarthritis, Hip
Quality of Life
*Low Back Pain

@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.},
}

Humans
Male
Middle Aged
*Magnetic Resonance Imaging
Electromyography
Motor Neuron Disease/diagnosis/complications

@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: Astragalus 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.Eine 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.Insgesamt 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.Diese 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.},
}

Humans
*Interleukin-10
*Interleukin-2
Interleukin-4
Interleukin-6
Tumor Necrosis Factor-alpha
Biomarkers

@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.},
}

Humans
Action Potentials/physiology
*Amyotrophic Lateral Sclerosis
Axons/physiology
Biomarkers
Prospective Studies
Clinical Protocols

@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: Migräne 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.Die 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.Es 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.Einige 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.},
}

Adult
Humans
*Mindfulness
Treatment Outcome
*Migraine Disorders/prevention & control
Headache
Stress, Psychological

@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.},
}

Humans
*Brain Injuries, Traumatic
Fatigue/therapy/etiology
*Multiple Sclerosis/complications/therapy
*Parkinson Disease
Quality of Life
*Stroke
*Transcranial Direct Current Stimulation/adverse effects

@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.},
}

Humans
*Out-of-Hospital Cardiac Arrest/therapy/mortality
*Emergency Medical Services
*Advanced Cardiac Life Support
Cardiopulmonary Resuscitation
Taiwan
Return of Spontaneous Circulation
Japan

@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.},
}

Humans
Computer Simulation
Educational Status
*High Fidelity Simulation Training
Randomized Controlled Trials as Topic

@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: Ziel 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.Es 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.Insgesamt 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.Dihuang 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.},
}

Humans
*Alzheimer Disease/drug therapy
Treatment Outcome
*Medicine
Medicine, Chinese Traditional
China

@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.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy
Prospective Studies
*Motor Neuron Disease
Diet
Carbohydrates/therapeutic use

@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.},
}

Humans
Australia
Databases, Factual
*Dermatology
Stakeholder Participation
*Urticaria/diagnosis/therapy
Practice Guidelines as Topic

@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.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/complications
*Noninvasive Ventilation/methods
Quality of Life
Respiration, Artificial/adverse effects
*Respiratory Insufficiency/therapy/complications

@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.},
}

Humans
*Culturally Competent Care
*Palliative Care/psychology
Quality of Life/psychology
Respect
Systematic Reviews as Topic

@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.},
}

Humans
*Amyotrophic Lateral Sclerosis
*Sports
*Brain Concussion/epidemiology/etiology
Cohort Studies
Case-Control Studies
*Dementia

@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.},
}

*Amyotrophic Lateral Sclerosis/epidemiology
Incidence
Prevalence
Humans
Africa/epidemiology
Asia/epidemiology
Europe/epidemiology
North America/epidemiology
South America/epidemiology
Oceania/epidemiology

@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.},
}

Humans
*Rare Diseases/diagnosis/epidemiology
*Endpoint Determination
Clinical Studies as Topic

@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.},
}

Humans
*Amyotrophic Lateral Sclerosis
Polysomnography
Sleep
Sleep, REM
Sleep Latency

@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.},
}

Humans
Retrospective Studies
Orthotic Devices
*Tendon Injuries/surgery/rehabilitation
Tendons
Fingers
*Finger Injuries/surgery/rehabilitation
Range of Motion, Articular

@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.},
}

Humans
*Amyotrophic Lateral Sclerosis/cerebrospinal fluid
Lead
*Selenium
Serum
*Neurodegenerative Diseases
Nails
Cross-Sectional Studies
Plasma
Hair

@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.},
}

Humans
*Neuroprotective Agents/pharmacology/therapeutic use
*Amyotrophic Lateral Sclerosis/drug therapy
*Alzheimer Disease/drug therapy
*Parkinson Disease/drug therapy

@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.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics
*Neurodegenerative Diseases/genetics/pathology
*Alzheimer Disease/genetics
*Parkinson Disease/genetics
Epigenesis, Genetic/genetics

@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.},
}

Humans
Quality of Life
Respiration, Artificial
*Noninvasive Ventilation
*Respiratory Insufficiency/etiology/therapy
*Physicians

@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.},
}

Humans
*Amyotrophic Lateral Sclerosis/chemically induced/epidemiology
Solvents/toxicity
*Occupational Exposure/adverse effects
Case-Control Studies
Odds Ratio
Risk Factors
Environmental Exposure

@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.},
}

Adult
Humans
*Amyotrophic Lateral Sclerosis
Patient Reported Outcome Measures
Psychometrics/methods
*Quality of Life/psychology
Reproducibility of Results

@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.},
}

*Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology
*Retinal Vessels/diagnostic imaging/physiopathology
Humans
*Microvessels/diagnostic imaging/physiopathology
Angiography/methods
*Tomography, Optical Coherence
Saccades

@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.},
}

Humans
*Neurodegenerative Diseases/pathology
Interferon-alpha/therapeutic use
Cytokines
Databases, Factual

@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.},
}

Humans
*Air Pollutants/analysis
*Air Pollution/analysis
*Alzheimer Disease/epidemiology
*Dementia, Vascular
Environmental Exposure/analysis
*Parkinson Disease
Particulate Matter/analysis

@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.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis
Biomarkers
Cross-Sectional Studies
Muscle, Skeletal
Reproducibility of Results
*Superficial Back Muscles

@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.},
}

Humans
United States/epidemiology
*Amyotrophic Lateral Sclerosis/epidemiology
Financial Stress
Prevalence
Registries
Databases, Factual
Cost of Illness
Health Care Costs

@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.},
}

Humans
*Neurodegenerative Diseases/drug therapy/genetics/metabolism
*Alzheimer Disease/genetics/metabolism
*Parkinson Disease/drug therapy/genetics/metabolism
RNA, Untranslated/genetics
Phytochemicals/pharmacology/therapeutic use

@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.},
}

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

@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.},
}

Animals
*Amyotrophic Lateral Sclerosis/diagnosis/drug therapy/etiology
*Neurodegenerative Diseases
Biomarkers
Motor Neurons/metabolism
Proteins/therapeutic use

@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.},
}

Male
Female
Humans
*Amyotrophic Lateral Sclerosis
C9orf72 Protein/genetics
*Frontotemporal Dementia/genetics/pathology/psychology
Mutation
*Aphasia, Primary Progressive

@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).},
}

Humans
Edaravone/adverse effects
*Amyotrophic Lateral Sclerosis/drug therapy
Surveys and Questionnaires

@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.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/metabolism
Biomarkers/metabolism
Machine Learning

@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.},
}

Humans
*Mesenchymal Stem Cells/metabolism
*Neurodegenerative Diseases/therapy
Central Nervous System
*Multiple Sclerosis
*Parkinson Disease/metabolism

@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.},
}