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Amyotrophic Lateral Sclerosis &... Feb 2023Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with loss of upper and lower motor neurones. It leads to death by respiratory failure and... (Meta-Analysis)
Meta-Analysis
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with loss of upper and lower motor neurones. It leads to death by respiratory failure and has a typical prognosis of 2-3 years. The immune system has been shown to play a role in the pathophysiology of ALS. Some of the most important immune genes are within the human leukocyte antigen (HLA) region, and a recent genome-wide association study (GWAS) has identified a risk allele for ALS within the HLA region. Older studies have also suggested an HLA association with ALS, with certain HLA alleles showing differing expression between patients and controls. This systematic review and meta-analysis examines the previous studies performed in this field. We used established publication search engines. Findings were excluded if they did not meet the selection criteria. We then undertook statistical meta-analysis on the eligible papers, using a fixed effects model. There were eight eligible papers. There were three statistically significant meta-analysis findings, although these would not be significant after correction for multiple comparisons. The frequencies of HLA-A9 and HLA-DR4 genotypes were lower in ALS subjects than controls, and HLA-B35 was higher in ALS subjects. This systematic review and meta-analysis do not confirm all the previously reported associations of HLA with ALS, but shows three alleles of interest. However, there are limitations to the studies, which include the use of older serotyping methodology and the small numbers of subjects. Given the recent GWAS association with HLA, further modern HLA studies are warranted.
Topics: Humans; Amyotrophic Lateral Sclerosis; Genome-Wide Association Study; Neurodegenerative Diseases; HLA Antigens; Motor Neurons
PubMed: 35616250
DOI: 10.1080/21678421.2022.2078665 -
Clinical Therapeutics Mar 2015Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in adults. It is almost invariably lethal within a few years after the onset of symptoms. No... (Review)
Review
PURPOSE
Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in adults. It is almost invariably lethal within a few years after the onset of symptoms. No effective treatment is currently available beyond supportive care and riluzole, a putative glutamate release blocker linked to modestly prolonged survival. This review provides a general overview of preclinical and clinical advances during recent years and summarizes the literature regarding emerging therapeutic approaches, focusing on their molecular targets.
METHODS
A systematic literature review of PubMed was performed, identifying key clinical trials involving molecular therapies for ALS. In addition, the ALS Therapy Development Institute website was carefully analyzed, and a selection of ALS clinical trials registered at ClinicalTrials.gov has been included.
FINDINGS
In the last several years, strategies have been developed to understand both the genetic and molecular mechanisms of ALS. Several therapeutic targets have been actively pursued, including kinases, inflammation inhibitors, silencing of key genes, and modulation or replacement of specific cell populations. The majority of ongoing clinical trials are investigating the safety profiles and tolerability of pharmacologic, gene, and cellular therapies, and have begun to assess their effects on ALS progression.
IMPLICATIONS
Currently, no therapeutic effort seems to be efficient, but recent findings in ALS could help accelerate the discovery of an effective treatment for this disease.
Topics: Adult; Amyotrophic Lateral Sclerosis; Disease Progression; Humans; Riluzole; Treatment Outcome
PubMed: 25666449
DOI: 10.1016/j.clinthera.2014.12.020 -
Amyotrophic Lateral Sclerosis &... May 2022Amyotrophic lateral sclerosis (ALS) causes dysphagia and consequent poor nutrition. Sometimes enteral feeding is offered. Percutaneous endoscopic gastrostomy (PEG) is... (Review)
Review
Amyotrophic lateral sclerosis (ALS) causes dysphagia and consequent poor nutrition. Sometimes enteral feeding is offered. Percutaneous endoscopic gastrostomy (PEG) is currently the technique of choice for enteral nutrition of these patients. This systematic review addresses the role of PEG and other enteral feeding techniques in maintaining ALS patients' survival and quality of life and in identifying prognostic factors for survival, in order to optimize their usefulness. We also evaluated the mortality of enteral feeding in the first 30 days after each procedure and its complications. Studies were retrieved from Pubmed, Google Scholar, and Cochrane databases, using the relevant keywords, and by hand search. The inclusion criteria were prospective and retrospective designs of studies of people with clinically diagnosed ALS in whom gastrostomy or nasogastric enteral feeding were used in management, published in English. Studies with sample sizes <40, or which focused on a specific gastrostomy technique utilizing less than 30 subjects were excluded in order to avoid small sample bias. We conclude that PEG is safe and probably prolongs survival in non-malnourished ALS patients. However, older age at onset, marked loss of weight or reduced body mass index from symptomatic onset, and marked respiratory dysfunction negatively influence the outcome after PEG insertion. The currently available evidence does not meaningfully address the impact of PEG on quality of life in ALS. The literature about other enteral feeding techniques is insufficient for reliable conclusions. The optimum time for PEG insertion and preferences for specific gastrostomy techniques also require more investigation.
Topics: Amyotrophic Lateral Sclerosis; Gastrostomy; Humans; Prospective Studies; Quality of Life; Retrospective Studies
PubMed: 34196236
DOI: 10.1080/21678421.2021.1946089 -
Trends in Psychiatry and Psychotherapy 2016Studies assessing symptoms of depression and anxiety in individuals with amyotrophic lateral sclerosis (ALS) have reported contradictory results. The objective of this... (Review)
Review
INTRODUCTION
Studies assessing symptoms of depression and anxiety in individuals with amyotrophic lateral sclerosis (ALS) have reported contradictory results. The objective of this systematic review is to identify the prevalence of these mood disorders in the literature.
METHODS
We searched the PubMed, HighWire, MEDLINE, SciELO, LILACS and ScienceDirect databases. Literature was selected for review in two stages, according to eligibility criteria. The first stage involved searching databases and checking titles and abstracts. The second step consisted of reading complete articles and excluding those that did not meet the inclusion criteria. The inclusion criteria were articles written in Portuguese, English or Spanish, published in the last five years and involving people with ALS diagnosed according to the El Escorial criteria.
RESULTS
The database searches returned a total of 1,135 titles and abstracts and then 1,117 of these were excluded. Eighteen articles were selected for review. The 12-item Amyotrophic Lateral Sclerosis Depression Inventory (ADI-12) was the only instrument designed specifically to assess depression in ALS, but it was only used in three studies. No instruments specifically designed for anxiety in ALS were used. A large number of studies found presence and slight increase of anxiety disorders. There was considerable large variation in the results related to depressive disorders, ranging from moderate depression to an absence of symptoms.
CONCLUSIONS
Patients with ALS may exhibit symptoms of depression and anxiety at different levels, but there is a need for studies using specific instruments with larger samples in order to ascertain the prevalence of symptoms in ALS and the factors associated with it.
Topics: Amyotrophic Lateral Sclerosis; Anxiety; Depression; Humans
PubMed: 27007942
DOI: 10.1590/2237-6089-2015-0030 -
Amyotrophic Lateral Sclerosis &... May 2021: Trauma especially head trauma is considered a potential risk factor of amyotrophic lateral sclerosis (ALS), but their association has not been well established. We... (Meta-Analysis)
Meta-Analysis
: Trauma especially head trauma is considered a potential risk factor of amyotrophic lateral sclerosis (ALS), but their association has not been well established. We aimed to determine the association of prior trauma with ALS risk. This study was performed according to the Meta-Analysis of Observational Studies in Epidemiology guideline to assess related literatures, and a random-effects model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Twenty-nine eligible articles involving 18,390 cases and 6,519,391 controls were included in this meta-analysis. The results showed that trauma was associated with an increased risk of ALS (pooled OR = 1.51, 95% CI: 1.32-1.73). Besides, patients with trunk trauma, head trauma and lower limb trauma had an increased risk of ALS, whereas no evidence suggested that upper limb trauma and spine trauma could increase ALS risk. Considering the number of traumatic events, the association between trauma and ALS risk was significant for patients with repeated trauma events (pooled OR = 1.21, 95% CI: 1.07-1.38). The results showed that individuals with a history of trauma within 5 years were more likely to be diagnosed with ALS (pooled OR = 1.84, 95% CI: 1.56-2.17). Importantly, both old trauma and very old trauma were found to be associated with an increased risk of ALS (pooled OR = 1.24, 95% CI: 1.12-1.38; pooled OR = 1.28, 95% CI: 1.10-1.49; respectively). This meta-analysis indicated that trauma could increase ALS risk, which may be applied for the clinicians to tailor targeted treatment regimens and make prophylactic strategies for ALS in traumatic patients.
Topics: Amyotrophic Lateral Sclerosis; Craniocerebral Trauma; Humans; Observational Studies as Topic; Odds Ratio; Risk Factors
PubMed: 33423565
DOI: 10.1080/21678421.2020.1861024 -
Neurological Sciences : Official... Oct 2023The study aims to increase understanding of edaravone's efficacy and safety as an amyotrophic lateral sclerosis (ALS) treatment and provide significant insights... (Meta-Analysis)
Meta-Analysis Review
AIM
The study aims to increase understanding of edaravone's efficacy and safety as an amyotrophic lateral sclerosis (ALS) treatment and provide significant insights regarding this field's future research.
METHODS
We conducted a comprehensive search of the Embase, PubMed, Cochrane Library, Web of Science, and Scopus databases for randomized controlled trials and observational studies up until September 2022. We evaluated the studies' quality using the Cochrane risk of bias tool and the National Institutes of Health tool.
RESULTS
We included 11 studies with 2845 ALS patients. We found that edaravone improved the survival rate at 18, 24, and 30 months (risk ratio (RR) = 1.03, 95% confidence interval (CI) [1.02 to 1.24], P = 0.02), (RR = 1.22, 95% CI [1.06 to 1.41], P = 0.007), and (RR = 1.17, 95% CI [1.01 to 1.34], P = 0.03), respectively. However, the administration of edaravone did not result in any significant difference in adverse effects or efficacy outcomes between the two groups, as indicated by a P value greater than 0.05.
CONCLUSION
Edaravone improves survival rates of ALS patients at 18, 24, and 30 months with no adverse effects. However, edaravone does not affect functional outcomes. In order to ensure the validity of our findings and assess the results in accordance with the disease stage, it is essential to carry out additional prospective, rigorous, and high-quality clinical trials. The current study offers preliminary indications regarding the effectiveness and safety of edaravone. However, further comprehensive research is required to establish the generalizability and sustainability of the findings.
Topics: United States; Humans; Edaravone; Amyotrophic Lateral Sclerosis; Prospective Studies; Quality of Life; Severity of Illness Index
PubMed: 37249667
DOI: 10.1007/s10072-023-06869-8 -
Journal of Neurology Sep 2021Increasing prognostic models for amyotrophic lateral sclerosis (ALS) have been developed. However, no comprehensive evaluation of these models has been done. The purpose...
BACKGROUND
Increasing prognostic models for amyotrophic lateral sclerosis (ALS) have been developed. However, no comprehensive evaluation of these models has been done. The purpose of this study was to map the prognostic models for ALS to assess their potential contribution and suggest future improvements on modeling strategy.
METHODS
Databases including Medline, Embase, Web of Science, and Cochrane library were searched from inception to 20 February 2021. All studies developing and/or validating prognostic models for ALS were selected. Information regarding modelling method and methodological quality was extracted.
RESULTS
A total of 28 studies describing the development of 34 models and the external validation of 19 models were included. The outcomes concerned were ALS progression (n = 12; 35%), change in weight (n = 1; 3%), respiratory insufficiency (n = 2; 6%), and survival (n = 19; 56%). Among the models predicting ALS progression or survival, the most frequently used predictors were age, ALS Functional Rating Scale/ALS Functional Rating Scale-Revised, site of onset, and disease duration. The modelling method adopted most was machine learning (n = 16; 47%). Most of the models (n = 25; 74%) were not presented. Discrimination and calibration were assessed in 12 (35%) and 2 (6%) models, respectively. Only one model by Westeneng et al. (Lancet Neurol 17:423-433, 2018) was assessed with overall low risk of bias and it performed well in both discrimination and calibration, suggesting a relatively reliable model for practice.
CONCLUSIONS
This study systematically reviewed the prognostic models for ALS. Their usefulness is questionable due to several methodological pitfalls and the lack of external validation done by fully independent researchers. Future research should pay more attention to the addition of novel promising predictors, external validation, and head-to-head comparisons of existing models.
Topics: Amyotrophic Lateral Sclerosis; Bias; Humans; Machine Learning; Prognosis; Respiratory Insufficiency
PubMed: 33694050
DOI: 10.1007/s00415-021-10508-7 -
Frontiers in Pharmacology 2022The effect of herbal medicine (HM) on amyotrophic lateral sclerosis (ALS) is controversial. Clinical trials investigating HMs continue; however, the use of HM is still...
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. 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. Twenty studies ( = 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; and were commonly used in nine, eight, and six trials, respectively. For delaying activity limitation, injection (MD, 2.84; 95% CI, 1.21 to 4.46; = 0.0006) and injection (SMD, 1.07; 0.69 to 1.45; < 0.00001) were significantly more efficacious than Riluzole, but the evidence was low quality. For ameliorating motor neuron loss, injection [right abductor pollicis brevis (APB): MD, 32.42; 7.91 to 56.93; = 0.01 and left APB: MD, 34.44; 12.85 to 56.03; = 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. 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. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021277443.
PubMed: 36120351
DOI: 10.3389/fphar.2022.946548 -
International Review of Neurobiology 2017ALS is a progressive neurodegenerative disease with no curative treatment. Nonmotor symptoms presenting in ALS may cause significant distress, worsen prognosis, and... (Review)
Review
BACKGROUND
ALS is a progressive neurodegenerative disease with no curative treatment. Nonmotor symptoms presenting in ALS may cause significant distress, worsen prognosis, and affect survival.
OBJECTIVE
To systematically review evidence for the prevalence of nonmotor ALS symptoms, and treatment options.
METHODS
Multiple medical literature databases were searched and studies screened using predefined inclusion criteria. Of 4580 studies, 44 were eligible for inclusion with 25 relating to treatment and 19 to the prevalence of nonmotor symptoms in ALS.
RESULTS
Nonmotor symptoms involve neuropsychiatric, autonomic, gastrointestinal, and vascular systems, and affect between 5% and 80% of people with ALS. Screening tools for individual nonmotor symptoms are useful in classifying symptom severity and to compare between treatment options. Several methods to relieve nonmotor symptoms have been trialed with varying success rates.
CONCLUSIONS
Many of the current studies of nonmotor symptoms in ALS have small sample sizes, requiring more evidence to increase precision in prevalence estimates. Further research is needed to assess the efficacy of current treatments and to find new therapies. Symptom relief or treatment of these nonmotor symptoms should therefore be considered during the clinical management of ALS.
Topics: Amyotrophic Lateral Sclerosis; Autonomic Nervous System Diseases; Gastrointestinal Diseases; Humans; Mental Disorders; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies
PubMed: 28805578
DOI: 10.1016/bs.irn.2017.04.009 -
Journal of Neurology May 2023Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with rapid progression and high mortality. Physical activity (PA) has been identified as a... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with rapid progression and high mortality. Physical activity (PA) has been identified as a major risk factor for ALS. However, the results across studies are still controversial. We aimed to explore the association between different types of PA and ALS.
METHODS
The PubMed, EMBASE, Cochrane and Web of Science databases were systematically searched for case-control and cohort studies which explored the relationship between PA and ALS from inception to October 2022. The data were analyzed to generate a pooled effect and 95% confidence interval (CI).
RESULTS
A total of 16,686 articles were included in the systematic search. After filtering, 28 studies from online database and 6 studies from references of relevant articles remained in the analysis. Individuals with a history of vigorous physical activity (OR 1.26, 95% CI 1.06-1.49), occupational-related activity (OR 1.14, 95% CI 1.04-1.25), leisure time activity (OR 1.08, 95% CI 1.04-1.12), unclassified PA (OR 1.05 95% CI 1.02-1.09) and professional athletes (SMR 5.23, 95% CI 2.67-10.25; SIR 2.54, 95% CI 1.37-4.69) were in higher risk of developing ALS. In contrast, sport-related activity (OR 0.97, 95% CI 0.76-1.26) was not associated with ALS.
CONCLUSIONS
Vigorous physical activity, occupational-related activity, leisure time activity, unclassified PA and professional athletes were associated with a higher risk of ALS, while sport-related activity showed no association with ALS. Our findings clarified the relation between different types of PA and ALS and provided some practicable advice for the lifestyle of high-risk populations.
Topics: Humans; Amyotrophic Lateral Sclerosis; Risk Factors; Exercise; Cohort Studies; Life Style
PubMed: 36670248
DOI: 10.1007/s00415-022-11555-4