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Brain Research Bulletin Mar 2023MicroRNAs (miRNAs) exhibit a crucial role in the pathogenesis and progress of neurodegenerative disorders. Recent studies have shown abnormal levels of miRNA expression... (Meta-Analysis)
Meta-Analysis Review
MicroRNAs (miRNAs) exhibit a crucial role in the pathogenesis and progress of neurodegenerative disorders. Recent studies have shown abnormal levels of miRNA expression in patients with amyotrophic lateral sclerosis (ALS). Clinical data also confirmed that miRNAs in these patients are inconsistent across studies. A comprehensive systematic review and meta-analysis of current studies can help recognize the important roles of miRNAs during ALS development. Therefore, we initially aimed to perform a systematic literature review on the muscle or serum miRNAs in patients with ALS and healthy individuals. Subsequently, we quantitatively summarized the clinical data of muscle or serum miRNA of patients with ALS and healthy individuals using a meta-analytical technique. 11 studies comprising 281 patients with ALS and 244 healthy control (HC) controls were identified from PubMed and Web of Science for meta-analysis. A systematic review revealed that miRNA levels are closely associated with the occurrence of ALS disease. The expression levels of the most relevant miRNAs were either increased or decreased. The random-effects meta-analysis indicated that the levels of miR-206, miR-133b, and miR-338-3p were significantly elevated in patients with ALS than in HC subjects. By contrast, there was no significant differences in the miR-133a levels between patients with ALS and HC subjects. Collectively, our outcomes demonstrated that serum miR-206, miR-133b, and miR-338-3p were significantly increased in patients with ALS. We speculated that the increased expression levels of miR-206, miR-133b and miR-338-3p are potential promising biomarkers for ALS.
Topics: Humans; MicroRNAs; Amyotrophic Lateral Sclerosis; Biomarkers
PubMed: 36681253
DOI: 10.1016/j.brainresbull.2023.01.005 -
Journal of Korean Medical Science Dec 2014The aim of this study was to examine the relationship between the risk of amyotrophic lateral sclerosis (ALS) and exposure to rural environments. Studies were identified... (Meta-Analysis)
Meta-Analysis Review
The aim of this study was to examine the relationship between the risk of amyotrophic lateral sclerosis (ALS) and exposure to rural environments. Studies were identified through OVID MEDLINE and EMBASE search up to September 2013 using as keywords rural residence, farmers, and pesticide exposure. Twenty-two studies were included for this meta-analysis. Summary odds ratios (ORs) were calculated using random effect model by type of exposure index, and subgroup analyses were conducted according to study design, gender, region, case ascertainment, and exposure assessment. The risk of ALS was significantly increased with pesticide exposure (OR, 1.44; 95% CI, 1.22-1.70) and with farmers (OR, 1.42; 95% CI, 1.17-1.73), but was not significant with rural residence (OR, 1.25; 95% CI, 0.84-1.87). The risk estimates for subgroup analysis between pesticide exposure and ALS indicated a significant positive association with men (OR, 1.96), and in studies using El Escorial criteria for ALS definition (OR, 1.63) and expert judgment for pesticide exposure (OR, 2.04) as well. No significant publication bias was observed. Our findings support the association of pesticide exposure and an increased risk for ALS, stressing that the use of more specific exposure information resulted in more significant associations.
Topics: Age Distribution; Agriculture; Amyotrophic Lateral Sclerosis; Environmental Exposure; Female; Humans; Incidence; Male; Occupational Diseases; Pesticides; Proportional Hazards Models; Risk Factors; Sex Distribution
PubMed: 25469059
DOI: 10.3346/jkms.2014.29.12.1610 -
Muscle & Nerve Dec 2022Loss of appetite is related to undesirable loss of weight in amyotrophic lateral sclerosis (ALS) and affects up to two thirds of people with this disease. Little is... (Review)
Review
Loss of appetite is related to undesirable loss of weight in amyotrophic lateral sclerosis (ALS) and affects up to two thirds of people with this disease. Little is known about the instruments used to measure appetite loss, its impact on quality of life (QoL), or strategies used to improve loss of appetite. In this study we aim to characterize the existing literature on the symptom of appetite loss in ALS through a systematic scoping review following the framework by Arksey and O'Malley and PRISMA guidelines. Studies assessing appetite in people with ALS (pALS) published in English and indexed on Web of Science, PubMed, and Scopus databases were included. A total of 156 full references were identified, of which 10 articles met the inclusion criteria and were eligible for data synthesis after screening. Seven unique instruments were used to assess appetite across the included studies, most commonly the Council of Nutrition Appetite Questionnaire. No studies included a subjective assessment of appetite loss. A total of 12 unique potential associated factors across five studies were identified. QoL was measured in seven studies using nine different QoL measurement tools. Few studies measure appetite in pALS and there is no consensus on the assessment tool used. Few studies evaluated the impact of appetite as a symptom on QoL. Furthermore, the heterogeneity of outcomes and risk factors of the existing data limit the clinical application of these findings. Future studies are needed to guide clinical management and interventions for people with ALS and appetite loss.
Topics: Humans; Amyotrophic Lateral Sclerosis; Quality of Life; Appetite; Surveys and Questionnaires; Nutritional Status
PubMed: 35986916
DOI: 10.1002/mus.27694 -
Brain Communications 2021Amyotrophic lateral sclerosis is a progressive and devastating neurodegenerative disease. Despite decades of clinical trials, effective disease-modifying drugs remain... (Review)
Review
Amyotrophic lateral sclerosis is a progressive and devastating neurodegenerative disease. Despite decades of clinical trials, effective disease-modifying drugs remain scarce. To understand the challenges of trial design and delivery, we performed a systematic review of Phase II, Phase II/III and Phase III amyotrophic lateral sclerosis clinical drug trials on trial registries and PubMed between 2008 and 2019. We identified 125 trials, investigating 76 drugs and recruiting more than 15 000 people with amyotrophic lateral sclerosis. About 90% of trials used traditional fixed designs. The limitations in understanding of disease biology, outcome measures, resources and barriers to trial participation in a rapidly progressive, disabling and heterogenous disease hindered timely and definitive evaluation of drugs in two-arm trials. Innovative trial designs, especially adaptive platform trials may offer significant efficiency gains to this end. We propose a flexible and scalable multi-arm, multi-stage trial platform where opportunities to participate in a clinical trial can become the default for people with amyotrophic lateral sclerosis.
PubMed: 34901853
DOI: 10.1093/braincomms/fcab242 -
Neuroepidemiology Feb 2021Prior studies have suggested that head injury might be a potential risk factor of amyotrophic lateral sclerosis (ALS). However, the association has not been well...
BACKGROUND
Prior studies have suggested that head injury might be a potential risk factor of amyotrophic lateral sclerosis (ALS). However, the association has not been well established. We aimed to provide a synopsis of the current understanding of head injury's role in ALS.
METHODS
We performed a systematic search in PubMed for observational studies that quantitatively investigated the association between head injury and ALS risk published before April 10, 2020. We used a random-effects model to calculate odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS
Fourteen eligible articles including 10,703 cases and 2,159,324 controls were selected in current meta-analysis. We found that head injury was associated with an increased risk of ALS (OR = 1.38, 95% CI: 1.20-1.60) and the association was slightly stronger concerning severe head injury and ALS risk (OR = 1.69, 95% CI: 1.27-2.23). Considering the number of head injuries (N) and ALS risk, the association was weak (OR = 1.23, 95% CI: 1.10-1.37, N = 1; OR = 1.29, 95% CI: 0.89-1.86, N ≥ 2). In addition, a strong association with ALS risk was found in individuals who suffered head injury <1 year (OR = 4.05, 95% CI: 2.79-5.89), and when the time lag was set at 1-5, 5-10, and >10 years, the pooled OR was 1.13, 1.35, and 1.10, respectively.
CONCLUSION
This meta-analysis indicates that head injury, especially severe head injury, could increase ALS risk. Although a strong association is found between head injury <1 year and ALS risk in the current study, this result suggests a possibility of reverse causation.
PubMed: 33621971
DOI: 10.1159/000510987 -
Neurological Sciences : Official... Mar 2021Multidisciplinary care (MDC) has been the most recommended approach for symptom management in amyotrophic lateral sclerosis (ALS) but there is conflicting evidence about... (Meta-Analysis)
Meta-Analysis Review
Multidisciplinary care (MDC) has been the most recommended approach for symptom management in amyotrophic lateral sclerosis (ALS) but there is conflicting evidence about its effectiveness on survival and quality of life (QoL) of ALS patients. We conducted a systematic review to determine the effects of multidisciplinary care compared to general neurological care in survival and quality of life of ALS patients. A comprehensive literature search using Scopus, MEDLINE-PubMed, Cochrane, Web of Science, PEDro, and Science Direct was undertaken. Studies related to multidisciplinary care or general neurological care in ALS patients that assessed survival and quality of life and were published in the period up to and including January 2020 were included. A total of 1192 studies were initially identified, but only 6 were included. All studies that investigated survival showed and advantage of MDC over NC, and this benefit was even greater for bulbar onset patients. A meta-analysis was performed and showed a mean difference of 141.67 (CI 95%, 61.48 to 221.86), indicating that patients who received MDC had longer survival than those who underwent NC (p = 0.0005). Concerning QoL, only one study found better mental health scores related to QoL for patients under MDC. Multidisciplinary care is more effective than general neurology care at improving survival of patients with ALS, but only improves mental health outcomes related to quality of life of these patients.
Topics: Amyotrophic Lateral Sclerosis; Humans; Interdisciplinary Studies; Palliative Care; Quality of Life
PubMed: 33443670
DOI: 10.1007/s10072-020-05011-2 -
Journal of Internal Medicine Oct 2021Amyotrophic lateral sclerosis (ALS), characterized by a loss of motor neurons in the brain and spinal cord, is a relatively rare but currently incurable... (Review)
Review
Amyotrophic lateral sclerosis (ALS), characterized by a loss of motor neurons in the brain and spinal cord, is a relatively rare but currently incurable neurodegenerative disease. The global incidence of ALS is estimated as 1.75 per 100,000 person-years and the global prevalence is estimated as 4.1-8.4 per 100,000 individuals. Contributions from outside the central nervous system to the etiology of ALS have been increasingly recognized. Gut microbiome is one of the most quickly growing fields of research for ALS. In this article, we performed a comprehensive review of the results from existing animal and human studies, to provide an up-to-date summary of the current research on gut microbiome and ALS. In brief, we found relatively consistent results from animal studies, suggesting an altered gut microbiome composition in experimental ALS. Publication bias might however be a concern. Findings from human studies are largely inconclusive. A few animal and human studies demonstrated the usefulness of intervention with microbial-derived metabolites in modulating the disease progression of ALS. We discussed potential methodological concerns in these studies, including study design, statistical power, handling process of biospecimens and sequencing data, as well as statistical methods and interpretation of results. Finally, we made a few proposals for continued microbiome research in ALS, with the aim to provide valid, reproducible, and translatable findings.
Topics: Amyotrophic Lateral Sclerosis; Animals; Disease Progression; Gastrointestinal Microbiome; Humans
PubMed: 34080741
DOI: 10.1111/joim.13336 -
BMC Medicine Aug 2022Studying whether medications act as potential risk factors for amyotrophic lateral sclerosis (ALS) can contribute to the understanding of disease etiology as well as the...
BACKGROUND
Studying whether medications act as potential risk factors for amyotrophic lateral sclerosis (ALS) can contribute to the understanding of disease etiology as well as the identification of novel therapeutic targets. Therefore, we conducted a systematic review to summarize the existing evidence on the association between medication use and the subsequent ALS risk.
METHODS
A systematic review was conducted in Medline, Embase, and Web of Science from the date of database establishment to December 10, 2021. References of identified articles were further searched for additional relevant articles. Studies were included if (1) published in English, (2) explored medication use as exposure and development of ALS as outcome, and (3) the design was a human observational study. Clinical trials, reviews, comments, editorials, and case reports were excluded. Quality assessment was performed using a pre-validated tool for non-randomized studies, the Newcastle-Ottawa Assessment Scale (NOS).
RESULTS
Of the 4760 studies identified, 25 articles, including 13 case-control studies, five nested case-control studies, six cohort studies, and one retrospective chart review, were included in the review. Among these studies, there were 22 distinct study populations that included 171,407 patients with ALS, seven classes of medication examined, and 23 studies with a NOS ≥ 5. There was a general lack of agreement between studies on the associations of cholesterol-lowering drugs, anti-inflammatory drugs, immunosuppressants, antibiotics, oral contraceptives (OCs) or hormone replacement therapy (HRT), antihypertensive drugs, antidiabetics, and drugs for psychiatric and neurological disorders with the subsequent risk of ALS. However, it appeared that statins, aspirin, OCs/HRT, antihypertensives, and antidiabetics were unlikely related to a higher risk of ALS. The positive associations noted for antibiotics, antidepressants, and skeletal muscle relaxants might be attributable to prodromal symptoms of ALS.
CONCLUSIONS
There is currently no strong evidence to link any medication use with ALS risk.
Topics: Amyotrophic Lateral Sclerosis; Anti-Bacterial Agents; Case-Control Studies; Humans; Hypoglycemic Agents; Observational Studies as Topic; Retrospective Studies
PubMed: 35927763
DOI: 10.1186/s12916-022-02442-w -
The Cochrane Database of Systematic... Aug 2023Maintaining adequate nutrition is critical for people with amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND). Enteral tube feeding is offered... (Review)
Review
BACKGROUND
Maintaining adequate nutrition is critical for people with amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND). Enteral tube feeding is offered to people experiencing difficulty swallowing (dysphagia) to prevent weight loss and aspiration pneumonia. Among the types of enteral tube feeding, percutaneous endoscopic gastrostomy (PEG) is the typical procedure offered to people with ALS and will be mainly discussed here.
OBJECTIVES
To examine the effectiveness of percutaneous endoscopic gastrostomy or other enteral tube feeding in people with ALS, compared to oral feeds without enteral tube feeding on: 1. survival; 2. nutritional status; 3. quality of life. To examine the incidence of minor and major complications of percutaneous endoscopic gastrostomy (PEG) and other enteral tube feeding procedures in people with ALS.
SEARCH METHODS
On 3 January 2020 and 6 February 2021, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE. Embase, ClinicalTrials.gov and WHO ICTRP. We screened the results to identify randomized controlled studies on enteral tube feeding in ALS. We reviewed all references from the search in published articles to identify any additional references.
SELECTION CRITERIA
We included randomized controlled trials (RCTs), quasi-RCTs, and cross-over trials evaluating the effectiveness and complications of PEG or other enteral tube feeding placement in ALS.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We found no RCTs or quasi-RCTs comparing the effectiveness of enteral tube feeding versus oral feeds without enteral tube feeding.
AUTHORS' CONCLUSIONS
There are no RCTs or quasi-RCTs to indicate whether enteral tube feeding is effective compared to continuation of oral feeding for any of the outcome measures. Such RCTs are very unlikely to be performed for ethical reasons. RCTs evaluating the effect of different enteral tube insertion techniques and timings of tube placement on survival and quality of life of people with ALS dysphagia are feasible and warranted.
Topics: Humans; Amyotrophic Lateral Sclerosis; Deglutition Disorders; Enteral Nutrition; Intubation, Gastrointestinal; Motor Neuron Disease
PubMed: 37579081
DOI: 10.1002/14651858.CD004030.pub4 -
Biomolecules Jun 2021Amyotrophic Lateral Sclerosis (ALS) is a degenerative disorder which affects the motor neurons. Growing evidence suggests that ALS may impact the metabolic system,...
BACKGROUND
Amyotrophic Lateral Sclerosis (ALS) is a degenerative disorder which affects the motor neurons. Growing evidence suggests that ALS may impact the metabolic system, including the glucose metabolism. Several studies investigated the role of Diabetes Mellitus (DM) as risk and/or prognostic factor. However, a clear correlation between DM and ALS has not been defined. In this review, we focus on the role of DM in ALS, examining the different hypotheses on how perturbations of glucose metabolism may interact with the pathophysiology and the course of ALS.
METHODS
We undertook an independent PubMed literature search, using the following search terms: ((ALS) OR (Amyotrophic Lateral Sclerosis) OR (Motor Neuron Disease)) AND ((Diabetes) OR (Glucose Intolerance) OR (Hyperglycemia)). Review and original articles were considered.
RESULTS
DM appears not to affect ALS severity, progression, and survival. Contrasting data suggested a protective role of DM on the occurrence of ALS in elderly and an opposite effect in younger subjects.
CONCLUSIONS
The actual clinical and pathophysiological correlation between DM and ALS is unclear. Large longitudinal prospective studies are needed. Achieving large sample sizes comparable to those of common complex diseases like DM is a challenge for a rare disease like ALS. Collaborative efforts could overcome this specific issue.
Topics: Age Factors; Amyotrophic Lateral Sclerosis; Diabetes Mellitus; Glucose; Humans
PubMed: 34200812
DOI: 10.3390/biom11060867