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Amyotrophic Lateral Sclerosis &... Nov 2021Physical pain is a known symptom in amyotrophic lateral sclerosis (ALS), but no systematically derived prevalence estimate is available. The aim of this study was to... (Meta-Analysis)
Meta-Analysis
Physical pain is a known symptom in amyotrophic lateral sclerosis (ALS), but no systematically derived prevalence estimate is available. The aim of this study was to determine the pooled prevalence of pain in ALS, relative to its method of measurement and pain characteristics. : A systematic search across multiple databases was conducted on January 16, 2020. Random-effects meta-analyses of single proportions were performed on prevalence data. Heterogeneity was determined using the statistic. Where available, pain location, intensity, and type or source were compared. 2552 articles were identified. Twenty-one eligible studies were included. All studies used observational designs (14 cross-sectional, 6 cohort, 1 case-control). Pooled prevalence of pain in ALS across all studies was 60% (95% CI = 50-69%), with a high degree of heterogeneity ( = 94%, < .001). Studies that used only validated measures had lower heterogeneity ( = 82%, = 0.002), compared to those that used tailored measures, or tailored supplemented with validated measures ( = 90%, < 0.001 and = 83%, < 0.001, respectively). In a subset of studies ( = 9), the most commonly reported pain location was the upper limbs including shoulders/extremities (41.5%). A further study subset ( = 7) showed moderate-severe intensity pain was most frequently reported. Type of pain was commonly related to cramp or spasm. Experiencing physical pain in ALS occurs with high prevalence. Deriving consensus on which specific tools should be used to assess, monitor and compare symptoms of pain in this population will reduce current heterogeneity in approaches and increase the likelihood of ameliorating distressing experiences more effectively.
Topics: Amyotrophic Lateral Sclerosis; Cross-Sectional Studies; Humans; Muscle Cramp; Pain; Prevalence
PubMed: 33661072
DOI: 10.1080/21678421.2021.1892765 -
Acta Neurologica Belgica Jun 2024The effectiveness and long-term efficacy of edaravone, a recommended treatment for amyotrophic lateral sclerosis (ALS), has not been examined in real-world settings.... (Meta-Analysis)
Meta-Analysis
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.
Topics: Edaravone; Humans; Amyotrophic Lateral Sclerosis; Free Radical Scavengers; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 38347315
DOI: 10.1007/s13760-024-02476-2 -
PloS One 2016To allow early diagnosis and monitoring of disease progression, there is a need for biomarkers in amyotrophic lateral sclerosis (ALS). Neurofilaments (NF) are emerging... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To allow early diagnosis and monitoring of disease progression, there is a need for biomarkers in amyotrophic lateral sclerosis (ALS). Neurofilaments (NF) are emerging protein biomarkers in other neurological diseases, and are of possible use in ALS.
OBJECTIVE
The aim of this study is to evaluate the utility of NF levels as blood or cerebrospinal fluid (CSF) biomarker in patients with ALS.
METHODS
A systematic search of Pubmed, Embase and Scopus was performed. Methodological quality assessment was applied to refine the final search results. Meta-analysis of the data was performed.
RESULTS
Level of NF heavy chain and light chains were significantly elevated in the CSF of ALS patients compared to healthy controls/controls without parenchymal central nervous system (CNS) involvement and ALS mimic disease patients. NF light chain level in CSF was higher in ALS patients than in neurological patients with CNS involvement (SMD = 1.352, P = 0.01). NF light chain concentration in blood was higher in ALS patients than healthy controls/controls without CNS involvement (SMD = 1.448, P<0.0001). NF heavy chain levels in CSF were negatively correlated disease duration and ALSFRS-R ((r = -0.447, P<0.0001; r = -0.486, P<0.0001). NF light chain levels in CSF were negatively correlated with disease duration (r = -0.273, P = 0.011).
CONCLUSION
NF heavy and light chain levels have potential use as a marker of neural degeneration in ALS, but are not specific for the disease, and are more likely to be used as measures of disease progression.
Topics: Amyotrophic Lateral Sclerosis; Biomarkers; Disease Progression; Humans; Neurofilament Proteins
PubMed: 27732645
DOI: 10.1371/journal.pone.0164625 -
Neurological Sciences : Official... Apr 2023To investigate the differences of the level of homocysteine (Hcy) between ALS patients and controls. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To investigate the differences of the level of homocysteine (Hcy) between ALS patients and controls.
METHODS
PubMed, EMBASE, OVID, and other databases were searched systematically up to October 2022 for relevant reports about the level of Hcy, folic acid, and vitamin B12 (VB12) among ALS patients. Two reviewers screened and selected the titles and abstracts of the studies independently during the database searches and performed full-text reviews and extracted available data. The MD (mean difference) and 95%CI (credibility interval) of the level of Hcy, folic acid, and VB12 between ALS group and control group were calculated.
RESULTS
Pooled results of nine studies including 812 ALS patients and 2632 controls showed that the MD in plasma levels of HCY between ALS patients and controls was 1.56 (95%CI: - 0.07, 3.19) μmol/L with remarkable heterogeneity (I = 94%). The mean CSF levels of Hcy among ALS patients were significantly higher than that of controls (MD: 0.23, 95%CI: 0.21, 0.24 μmol/L) with no significant heterogeneity (I = 0%). No significant difference in the plasma level of folic acid (MD: - 0.52, 95%CI: - 1.89, 0.84 ng/mL) or VB12 (MD: - 9.76, 95%CI: - 83.41, 63.89) was found between ALS patients and controls.
CONCLUSION
There was no significant difference in the plasma level of Hcy, folic acid, or VB12 between ALS patients and controls. The CSF level of Hcy among ALS population was remarkably higher than that among controls. Vitamin supplements including folate and VB12 might be recommended to ALS patients with the complication of deficiencies.
Topics: Humans; Amyotrophic Lateral Sclerosis; Homocysteine; Vitamin B 12; Folic Acid; Dietary Supplements
PubMed: 36422727
DOI: 10.1007/s10072-022-06518-6 -
Journal of Affective Disorders May 2021Amyotrophic lateral sclerosis (ALS) people have a high risk of severe mental disorders, like depression, which impacts their function, quality of life, and mobility.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Amyotrophic lateral sclerosis (ALS) people have a high risk of severe mental disorders, like depression, which impacts their function, quality of life, and mobility. However, there are no estimates of depression based paper published. This study aimed conduct a systematic review and meta-analysis of the prevalence of depression in ALS patients around the world.
METHODS
PubMed/Medline, Web of science, Scopus, Embase, and Ovid are searched to identify papers that reporting the prevalence of depression. Studies are included in random-effects meta-analyses of the prevalence of depression. Subgroup analyses are performed on the severity of depression, instruments of depression, type of studies, and study regions.
RESULTS
46 eligible studies reported prevalence of depression. The pooled prevalence of depression among ALS people was 34% (27%-41%). According to the severity of depression, mild, moderate, and severe depression were 29%, 16%, and 8%, respectively. For studies using BDI, PHQ, and HADS, the pooled prevalence of depression was 50%, 20%, and 15%, respectively.
CONCLUSIONS
ALS people have a high prevalence of depression. The high prevalence of depression causes a reduction of quality of life and mobility. The study identifies a population group at high risk needing special attention in clinical practice.
Topics: Amyotrophic Lateral Sclerosis; Depressive Disorder; Humans; Prevalence; Quality of Life
PubMed: 33799036
DOI: 10.1016/j.jad.2021.03.015 -
Journal of Molecular Neuroscience : MN Nov 2020Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder and is characterized by degeneration and axon loss from the upper motor neuron, that descends from... (Review)
Review
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder and is characterized by degeneration and axon loss from the upper motor neuron, that descends from the lower motor neuron in the brain. Over the period, assorted outcomes from medical findings, molecular pathogenesis, and structural and biophysical studies have abetted in providing thoughtful insights underlying the importance of disease-causing genes in ALS. Consequently, numerous mechanisms were proposed for the pathogenesis of ALS, considering protein mutations, aggregation, and misfolding. Besides, the answers to the majority of ALS cases that happen to be sporadic still remain obscure. The application in discovering susceptibility factors in ALS contemplating the genetic factors is to be further dissevered in the future years with innovation in research studies. Hence, this review targets in revisiting the breakthroughs on the disease-causing genes related with ALS.
Topics: Amyotrophic Lateral Sclerosis; Animals; C9orf72 Protein; Genetic Predisposition to Disease; Humans; Profilins; RNA-Binding Protein FUS; Superoxide Dismutase-1
PubMed: 32415434
DOI: 10.1007/s12031-020-01569-w -
Neurological Sciences : Official... Aug 2023Studies focusing on the association between environmental and occupational solvent exposure and amyotrophic lateral sclerosis (ALS) have yielded inconsistent results.... (Meta-Analysis)
Meta-Analysis
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 = 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.
Topics: Humans; Amyotrophic Lateral Sclerosis; Solvents; Occupational Exposure; Case-Control Studies; Odds Ratio; Risk Factors; Environmental Exposure
PubMed: 36897461
DOI: 10.1007/s10072-023-06718-8 -
Artificial Intelligence in Medicine Aug 2023Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder characterised by the progressive loss of motor neurons in the brain and spinal cord. The fact... (Review)
Review
BACKGROUND
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder characterised by the progressive loss of motor neurons in the brain and spinal cord. The fact that ALS's disease course is highly heterogeneous, and its determinants not fully known, combined with ALS's relatively low prevalence, renders the successful application of artificial intelligence (AI) techniques particularly arduous.
OBJECTIVE
This systematic review aims at identifying areas of agreement and unanswered questions regarding two notable applications of AI in ALS, namely the automatic, data-driven stratification of patients according to their phenotype, and the prediction of ALS progression. Differently from previous works, this review is focused on the methodological landscape of AI in ALS.
METHODS
We conducted a systematic search of the Scopus and PubMed databases, looking for studies on data-driven stratification methods based on unsupervised techniques resulting in (A) automatic group discovery or (B) a transformation of the feature space allowing patient subgroups to be identified; and for studies on internally or externally validated methods for the prediction of ALS progression. We described the selected studies according to the following characteristics, when applicable: variables used, methodology, splitting criteria and number of groups, prediction outcomes, validation schemes, and metrics.
RESULTS
Of the starting 1604 unique reports (2837 combined hits between Scopus and PubMed), 239 were selected for thorough screening, leading to the inclusion of 15 studies on patient stratification, 28 on prediction of ALS progression, and 6 on both stratification and prediction. In terms of variables used, most stratification and prediction studies included demographics and features derived from the ALSFRS or ALSFRS-R scores, which were also the main prediction targets. The most represented stratification methods were K-means, and hierarchical and expectation-maximisation clustering; while random forests, logistic regression, the Cox proportional hazard model, and various flavours of deep learning were the most widely used prediction methods. Predictive model validation was, albeit unexpectedly, quite rarely performed in absolute terms (leading to the exclusion of 78 eligible studies), with the overwhelming majority of included studies resorting to internal validation only.
CONCLUSION
This systematic review highlighted a general agreement in terms of input variable selection for both stratification and prediction of ALS progression, and in terms of prediction targets. A striking lack of validated models emerged, as well as a general difficulty in reproducing many published studies, mainly due to the absence of the corresponding parameter lists. While deep learning seems promising for prediction applications, its superiority with respect to traditional methods has not been established; there is, instead, ample room for its application in the subfield of patient stratification. Finally, an open question remains on the role of new environmental and behavioural variables collected via novel, real-time sensors.
Topics: Humans; Amyotrophic Lateral Sclerosis; Artificial Intelligence; Brain; Cluster Analysis; Databases, Factual
PubMed: 37316101
DOI: 10.1016/j.artmed.2023.102588 -
Amyotrophic Lateral Sclerosis &... May 2021Disorders of sleep and wakefulness are common among neurodegenerative diseases. While amyotrophic lateral sclerosis (ALS) predominately manifests as motor symptoms,...
Disorders of sleep and wakefulness are common among neurodegenerative diseases. While amyotrophic lateral sclerosis (ALS) predominately manifests as motor symptoms, there is emerging evidence that disruptions to sleep and wakefulness also occur. This systematic review aims to report the most common disorders of sleep and wakefulness in ALS. We conducted a qualitative systematic review as per PRISMA guidelines and searched literature assessing the association between disorders of sleep and wakefulness with ALS using the PubMed and Medline database. Overall, 50-63% of patients with ALS have poor sleep quality as reported using the Pittsburgh Sleep Quality Index Questionnaire (PSQI). A higher proportion of ALS patients are categorized as poor sleepers, however there is conflicting evidence as to whether patients with ALS are more likely to exhibit excessive daytime sleepiness. Of the studies that utilized polysomnography, all reported various degrees of impairment to sleep microstructure and architecture among ALS patients. In future, longitudinal clinical studies will be essential for establishing the significance of impaired sleep in ALS. Future studies are also needed to establish whether the self-reported measures of poor sleep and impairment to sleep architecture occurs as a direct consequence of the disease, whether they are an early manifestation of the disease, and/or if they contribute to the neurodegenerative process.
Topics: Amyotrophic Lateral Sclerosis; Humans; Polysomnography; Sleep; Sleep Wake Disorders; Wakefulness
PubMed: 33191797
DOI: 10.1080/21678421.2020.1844755 -
International Journal of Environmental... Oct 2018We conducted a systematic literature review to identify studies fulfilling good scientific epidemiological standards for use in meta-analyses of occupational risk... (Meta-Analysis)
Meta-Analysis
We conducted a systematic literature review to identify studies fulfilling good scientific epidemiological standards for use in meta-analyses of occupational risk factors for amyotrophic lateral sclerosis (ALS). : We identified 79 original publications on associations between work and ALS. The MOOSE (Meta-analysis Of Observational Studies in Epidemiology) and GRADE (Grading of Recommendations, Assessment, Development and Evaluations) guidelines were used to ensure high scientific quality, and reliable protocols were applied to classify the articles. Thirty-seven articles fulfilled good scientific standards, while 42 were methodologically deficient and thus were excluded from our meta-analyses. : The weighted relative risks for the various occupational exposures were respectively; 1.29 (95% confidence interval (CI): 0.97⁻1.72; six articles) for heavy physical work, 3.98 (95% CI: 2.04⁻7.77; three articles) for professional sports, 1.45 (95% CI: 1.07⁻1.96; six articles) for metals, 1.19 (95% CI: 1.07⁻1.33; 10 articles) for chemicals, 1.18 (95% CI: 1.07⁻1.31; 16 articles) for electromagnetic fields or working with electricity, and 1.18 (95% CI: 1.05⁻1.34; four articles) for working as a nurse or physician. : Meta-analyses based only on epidemiologic publications of good scientific quality show that the risk of ALS is statistically significantly elevated for occupational exposures to excessive physical work, chemicals (especially pesticides), metals (especially lead), and possibly also to electromagnetic fields and health care work. These results are not explained by publication bias.
Topics: Amyotrophic Lateral Sclerosis; Delivery of Health Care; Electromagnetic Fields; Humans; Lead; Occupational Exposure; Pesticides; Physical Exertion; Risk Factors
PubMed: 30373166
DOI: 10.3390/ijerph15112371