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Journal of Neurology, Neurosurgery, and... Jul 2017Genetic studies have shown that , , and are the most common mutated genes in amyotrophic lateral sclerosis (ALS). Here, we performed a meta-analysis to determine the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Genetic studies have shown that , , and are the most common mutated genes in amyotrophic lateral sclerosis (ALS). Here, we performed a meta-analysis to determine the mutation frequencies of these major ALS-related genes in patients with ALS.
METHODS
We performed an extensive literature research to identify all original articles reporting frequencies of , , and mutations in ALS. The mutation frequency and effect size of each study were combined. Possible sources of heterogeneity across studies were determined by meta-regression, sensitivity analysis and subgroup analysis.
RESULTS
111 studies were included in the meta-analysis. The overall pooled mutation frequencies of these major ALS-related genes were 47.7% in familial amyotrophic lateral sclerosis (FALS) and 5.2% in sporadic ALS (SALS). A significant difference was identified regarding the frequencies of mutations in major ALS genes between European and Asian patients. In European populations, the most common mutations were the repeat expansions (FALS 33.7%, SALS 5.1%), followed by (FALS 14.8%, SALS 1.2%), (FALS 4.2%, SALS 0.8%) and mutations (FALS 2.8%, SALS 0.3%), while in Asian populations the most common mutations were mutations (FALS 30.0%, SALS 1.5%), followed by (FALS 6.4%, SALS 0.9%), (FALS 2.3%, SALS 0.3%) and (FALS 1.5%, SALS 0.2%) mutations.
CONCLUSIONS
These findings demonstrated that the genetic architecture of ALS in Asian populations is distinct from that in European populations, which need to be given appropriate consideration when performing genetic testing of patients with ALS.
Topics: Amyotrophic Lateral Sclerosis; Asian People; DNA-Binding Proteins; Genetic Predisposition to Disease; Humans; Molecular Epidemiology; Mutation; White People
PubMed: 28057713
DOI: 10.1136/jnnp-2016-315018 -
International Journal of Environmental... Jan 2021the main objective of this study was to analyze the potential short-, medium- and long-term effects of a therapeutic physical exercise (TFE) programme on the... (Review)
Review
BACKGROUND
the main objective of this study was to analyze the potential short-, medium- and long-term effects of a therapeutic physical exercise (TFE) programme on the functionality of amyotrophic lateral sclerosis (ALS) patients, measured with the Revised Amyotrophic Lateral Sclerosis Functional Scale (ALSFRS-R) scale.
METHODS
a systematic review of the PubMed, SCOPUS, Cochrane, Scientific Electronic Library Online (Scielo), Physiotherapy Evidence Database (PEDro), Cumulative Index of Nursing and Allied Health Literature (CINAHL) and Medical Literature Analysis and Retrieval System Online (MEDline) databases was carried out. The information was filtered using the following Medical Subjects Heading (MeSH) terms: "Amyotrophic lateral sclerosis", "Physical Therapy", and "Physical and Rehabilitation Medicine". The internal validity of the selected documents was evaluated using the PEDro scale. The study included clinical trials published in the last 5 years in which one of the interventions was therapeutic physical exercise in patients with ALS, using the ALSFRS-R as the main outcome variable and functional variables as secondary variables.
RESULTS
10 clinical trials were analyzed, with an internal validity of 5-7 points. The TFE groups showed significant short-, medium- and long-term differences, obtaining a mean difference of 5.8 points compared to the 7.6 points obtained by the control groups, at six months, measured with ALSFRS-R. In addition, the participants showed significant improvements in functional abilities in the short, medium and long terms.
CONCLUSIONS
Therapeutic physical exercise could contribute to slowing down the deterioration of the musculature of patients with ALS, thus facilitating their performance in activities of daily living, based on the significant differences shown by these individuals in the short, medium and long term both in subjective perception, measured with ALSFRS-R, and functional capacities.
Topics: Activities of Daily Living; Amyotrophic Lateral Sclerosis; Exercise; Exercise Therapy; Humans; Physical Therapy Modalities
PubMed: 33530383
DOI: 10.3390/ijerph18031074 -
Neurology Aug 2023Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disorder affecting upper and lower motor neurons. Due to its rarity and rapidly progressive nature,...
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.
Topics: Amyotrophic Lateral Sclerosis; Incidence; Prevalence; Humans; Africa; Asia; Europe; North America; South America; Oceania
PubMed: 37308302
DOI: 10.1212/WNL.0000000000207474 -
American Journal of Physical Medicine &... Sep 2020The aim of this study was to systematically review the efficacy and safety of exercise in patients with amyotrophic lateral sclerosis (ALS). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of this study was to systematically review the efficacy and safety of exercise in patients with amyotrophic lateral sclerosis (ALS).
DESIGN
Randomized controlled trials of exercises for ALS were searched in PubMed, EMBASE, Web of Science, Cochrane Library, China Biology Medicine database, China National Knowledge Internet, VIP database, and Wanfang database. The primary outcomes were functional ability, pulmonary function, and quality of life. The secondary outcomes were muscle strength, fatigue and adverse events. Meta-analysis was performed using the RevMan Version 5.3 software.
RESULTS
Seven randomized controlled trials including 322 patients with ALS met the inclusion criteria. Meta-analysis showed that the functional scores at long-term (standardized means difference, 0.47; 95% confidence interval, 0.08-0.86; P = 0.02) and forced vital capacity percentage predicted (mean difference, 1.71; 95% confidence interval, 0.10-3.31; P = 0.04) of patients with ALS in the exercise group were significantly higher than those in the group of no exercise or usual care. No significant difference was observed in muscle strength and quality of life. Endurance or aerobic exercise improved the functional scores of patients with ALS (standardized means difference, 0.36; 95% confidence interval, 0.04-0.68; P = 0.03). Exercise did not aggravate fatigue or result in adverse event.
CONCLUSION
Exercise can significantly improve the functional ability and pulmonary function of patients with ALS safely.
Topics: Activities of Daily Living; Aged; Amyotrophic Lateral Sclerosis; Breathing Exercises; Exercise; Exercise Therapy; Female; Humans; Male; Middle Aged; Muscle Strength; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32452880
DOI: 10.1097/PHM.0000000000001419 -
Physiotherapy Dec 2021The aim of this systematic review and meta-analysis was to assess the effect of aerobic, resistance and combined exercise training in patients with ALS. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The aim of this systematic review and meta-analysis was to assess the effect of aerobic, resistance and combined exercise training in patients with ALS.
DATA SOURCE
A comprehensive systematic search of CENTRAL, CINAHL, SPORTDiscuss, Embase, Scopus, ProQuest was performed from inception to February 2021.
ELIGIBILITY CRITERIA
The systematic review included all studies that examined the effect of exercise training in ALS patients. Meta-analysis was also carried out on randomized controlled trials (RCTs).
DATA EXTRACTION AND DATA SYNTHESIS
Data related to primary outcomes (functional ability, respiratory function, fatigue, pain, quality of life, upper-body strength, lower-body strength and Vopeak) and secondary outcomes (adverse events and feasibility of exercises) was extracted from all studies and systematically reviewed.
RESULTS
16 trials including 532 patients met the inclusion criteria; of these, eight studies were included in this meta-analysis. The meta-analysis found a statistically significant difference in favor of exercise in functional ability (P=0.001), overall quality of life (P=0.03) and Vopeak (P=0.01). The included trials were generally of poor quality and had a risk of bias. However, the results of sensitivity analysis, after omitting studies with high risk of bias, showed no statistically significant difference in functional ability (P=0.05), overall quality of life (P=0.12) and Vo2peak (P=0.13). Finally, no significant difference was found in respiratory function, fatigue, pain, and upper-body and lower-body strength.
CONCLUSIONS
The safety and effectiveness of exercise therapy in ALS patients remains unclear and further high quality RCTs with larger sample size are needed. Systematic Review Registration Number PROSPERO CRD42019140011.
Topics: Activities of Daily Living; Amyotrophic Lateral Sclerosis; Exercise; Exercise Therapy; Humans; Quality of Life; Resistance Training
PubMed: 34555670
DOI: 10.1016/j.physio.2021.04.005 -
Journal of Neurology Apr 2020Amyotrophic lateral sclerosis (ALS) is a global disease, which adversely affects the life quality of patients and significantly increases the burden of families and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Amyotrophic lateral sclerosis (ALS) is a global disease, which adversely affects the life quality of patients and significantly increases the burden of families and society. We aimed to assess the changing incidence, prevalence of ALS around the world.
METHODS
We searched Medline, Embase, Web of Science, and Cochrane library to identify articles published until September 9, 2018. Each included study was independently reviewed for methodological quality by two reviewers. We used a random-effects model to summarize individual studies and assessed heterogeneity (I) with the χ test on Cochrane's Q statistic.
RESULTS
We identified 124 studies that were eligible for final inclusion, including 110 studies of incidence and 58 studies of prevalence. The overall crude worldwide ALS prevalence and incidence were 4.42 (95% CI 3.92-4.96) per 1,00,000 population and 1.59 (95% CI 1.39-1.81) per 1,00,000 person-years, respectively. ALS prevalence and incidence increased by age until the age of 70-79. Since 1957, incidence has been significantly rising year by year, and this upward trend was weakened after standardization. The longest survival time were in Asia (ranging from 3.74 years in South Asia to 9.23 years in West Asia).
CONCLUSIONS
With the aggravation of population aging and the rapid growth of economy, developing regions following the development pattern of the developed regions may suffer rising ALS prevalence and incidence which may increase their disease burden as well. These data highlight the need for research into underlying mechanism and innovations in health-care systems.
Topics: Amyotrophic Lateral Sclerosis; Global Health; Humans; Incidence; Prevalence
PubMed: 31797084
DOI: 10.1007/s00415-019-09652-y -
Neurological Sciences : Official... Feb 2022Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease. There is still no established cost-effective treatment that can improve... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease. There is still no established cost-effective treatment that can improve functional status and survival of ALS patients. Perampanel, by inhibiting neuronal calcium ion influx and preventing dyslocalization of nuclear proteins, has the potential to ameliorate ALS neurodegeneration.
OBJECTIVES
This study aims to determine the efficacy and safety of perampanel among ALS patients in terms of improvement in functional status using a review of relevant studies.
METHODS
MedLine, Cochrane Central Register for Controlled Trials, Scopus, Embase, Literatura Latino-Americana e do Caribe em Ciências da Saúde, ClinicalTrials.gov website, and HERDIN databases were searched from inception to August 2021 for relevant studies.
RESULTS
The search yielded 132 articles; 3 studies were included in the analysis. Pooled evidence shows that perampanel compared to placebo significantly improves cortical motor hyperexcitability but not the ALS functional rating scale-revised score. Perampanel is associated with adverse events such as aggression, somnolence, anger, and dysarthria.
CONCLUSION
There is no sufficient evidence to support the role of perampanel in improving functional status of ALS patients. Although it can ameliorate motor cortical hyperexcitability, its clinical benefit has not yet been elucidated. Perampanel is not well tolerated among ALS patients as it is associated with adverse events such as aggression, somnolence, anger, and dysarthria. Further studies investigating the role of perampanel early in the ALS disease course, excluding ALS patients with frontotemporal lobe degeneration features and C9ORF72 repeat expansion, and using gradual drug titration schedule are needed to evaluate the potential benefit of perampanel in ALS.
Topics: Amyotrophic Lateral Sclerosis; Humans; Neurodegenerative Diseases; Nitriles; Pyridones
PubMed: 34994876
DOI: 10.1007/s10072-022-05867-6 -
Frontiers in Aging Neuroscience 2022Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease whose primary hallmark is the progressive degeneration of motor neurons in the brainstem,...
Mixed Comparison of Different Exercise Interventions for Function, Respiratory, Fatigue, and Quality of Life in Adults With Amyotrophic Lateral Sclerosis: Systematic Review and Network Meta-Analysis.
BACKGROUND
Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease whose primary hallmark is the progressive degeneration of motor neurons in the brainstem, spinal cord, and cerebral cortex that leads to weakness, spasticity, fatigue, skeletal muscle atrophy, paralysis, and even death. Exercise, as a non-pharmacological tool, may generally improve muscle strength, cardiovascular function, and quality of life. However, there are conflicting reports about the effect of exercise training in adults with ALS.
AIMS
This systematic review and network meta-analysis aim to conduct a mixed comparison of different exercise interventions for function, respiratory, fatigue, and quality of life in adults with ALS.
METHODS
Randomized controlled trials with ALS participants were screened and included from the databases of PubMed, Medline, and Web of Science. Physical exercise interventions were reclassified into aerobic exercise, resistance training, passive exercise, expiratory muscle exercise, and standard rehabilitation. Patient-reported outcome measures would be reclassified from perspectives of function, respiratory, fatigue, and quality of life. The effect size would be transferred into the percentage change of the total score.
RESULT
There were 10 studies included, with the agreement between authors reaching a kappa-value of 0.73. The network meta-analysis, which was conducted under the consistency model, identified that a combined program of aerobic exercise, resistance exercise, and standard rehabilitation showed the highest potential to improve quality of life (0.64 to be the best) and reduce the fatigue (0.39 to be the best) for ALS patients, while exercise program of aerobic and resistance training showed the highest potential (0.51 to be the best) to improve ALS patients' physical function. The effect of exercise on the respiratory was still unclear.
CONCLUSION
A multi-modal exercise and rehabilitation program would be more beneficial to ALS patients. However, the safety and guide for practice remain unclear, and further high-quality randomized controlled trials (RCTs) with a larger sample are still needed.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021253442, CRD42021253442.
PubMed: 35898325
DOI: 10.3389/fnagi.2022.919059 -
The Cochrane Database of Systematic... Mar 2012Riluzole is approved for the treatment of amyotrophic lateral sclerosis in most countries. Questions persist about its clinical utility because of high cost and modest... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Riluzole is approved for the treatment of amyotrophic lateral sclerosis in most countries. Questions persist about its clinical utility because of high cost and modest efficacy.
OBJECTIVES
To examine the efficacy of riluzole in prolonging survival and in delaying the use of surrogates (tracheostomy and mechanical ventilation) to sustain survival, and to assess the effect of riluzole upon functional health.
SEARCH METHODS
We searched the Cochrane Neuromuscular Disease Group Specialized Register (20 April 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 2), MEDLINE (1966 to April 2011), EMBASE (1980 to May 2011) and made enquiries of authors of trials, Aventis (manufacturer of riluzole) and other experts in the field.
SELECTION CRITERIA
Types of studies: randomized controlled trials
TYPES OF PARTICIPANTS
adults with a diagnosis of amyotrophic lateral sclerosis Types of interventions: treatment with riluzole or placebo Types of outcome measures: Primary: pooled hazard ratio of tracheostomy-free survival over all time points with riluzole 100 mg. Secondary: per cent mortality with riluzole 50 mg, 100 mg and 200 mg; neurologic function, muscle strength and adverse events.
DATA COLLECTION AND ANALYSIS
One author performed data extraction and two other authors checked them. One author checked the data and entered them into the computer. The other authors verified the data entry. We obtained missing data from the trial authors whenever possible.
MAIN RESULTS
The four trials examining tracheostomy-free survival included a total of 974 riluzole-treated patients and 503 placebo-treated patients. No new randomized controlled trials were found when we updated the searches for this update in 2011. The methodological quality was acceptable and three trials were easily comparable, although one trial (169 participants) included older patients in more advanced stages of amyotrophic lateral sclerosis and one (195 participants) had multiple primary endpoints. Riluzole 100 mg per day provided a benefit for the homogeneous group of patients in the first two trials (hazard ratio (HR) 0.80, 95% confidence internal (CI) 0.64 to 0.99, P= 0.042) and there was no evidence of heterogeneity (P = 0.33). When the third trial (which included older and more seriously affected patients) was added, there was evidence of heterogeneity (P < 0.0001) and the overall treatment effect was reduced but still significant (HR 0.84, 95% CI 0.698 to 0.997, P= 0.046). This represented a 9% gain in the probability of surviving one year (49% in the placebo and 58% in the riluzole group), and increased median survival from 11.8 to 14.8 months. There was a small beneficial effect on both bulbar and limb function, but not on muscle strength. A three-fold increase in serum alanine transferase was more frequent in riluzole-treated patients than controls (mean difference 2.62, 95% CI 1.59 to 4.31).
AUTHORS' CONCLUSIONS
Riluzole 100 mg daily is reasonably safe and probably prolongs median survival by about two to three months in patients with amyotrophic lateral sclerosis.
Topics: Age Factors; Amyotrophic Lateral Sclerosis; Excitatory Amino Acid Antagonists; Humans; Life Expectancy; Neuroprotective Agents; Randomized Controlled Trials as Topic; Riluzole; Tracheostomy
PubMed: 22419278
DOI: 10.1002/14651858.CD001447.pub3 -
The Cochrane Database of Systematic... Jan 2017Motor neuron disease (MND), which is also known as amyotrophic lateral sclerosis (ALS), causes a wide range of symptoms but the evidence base for the effectiveness of... (Review)
Review
BACKGROUND
Motor neuron disease (MND), which is also known as amyotrophic lateral sclerosis (ALS), causes a wide range of symptoms but the evidence base for the effectiveness of the symptomatic treatment therapies is limited.
OBJECTIVES
To summarise the evidence from Cochrane Systematic Reviews of all symptomatic treatments for MND.
METHODS
We searched the Cochrane Database of Systematic Reviews (CDSR) on 15 November 2016 for systematic reviews of symptomatic treatments for MND. We assessed the methodological quality of the included reviews using the Assessment of Multiple Systematic Reviews (AMSTAR) tool and the GRADE approach. We followed standard Cochrane study (review) selection and data extraction procedures. We reported findings narratively and in tables.
MAIN RESULTS
We included nine Cochrane Systematic Reviews of interventions to treat symptoms in people with MND. Three were empty reviews with no included randomised controlled trials (RCTs); however, all three reported on non-RCT evidence and the remaining six included mostly one or two studies. We deemed all of the included reviews of high methodological quality. Drug therapy for painThere is no RCT evidence in a Cochrane Systematic Review exploring the efficacy of drug therapy for pain in MND. Treatment for crampsThere is evidence (13 RCTs, N = 4012) that for the treatment of cramps in MND, compared to placebo:- memantine and tetrahydrocannabinol (THC) are probably ineffective (moderate-quality evidence);- vitamin E may have little or no effect (low-quality evidence); and- the effects of L-threonine, gabapentin, xaliproden, riluzole, and baclofen are uncertain as the evidence is either very low quality or the trial specified the outcome but did not report numerical data.The review reported adverse effects of riluzole, but it is not clear whether other interventions had adverse effects. Treatment for spasticityIt is uncertain whether an endurance-based exercise programme improved spasticity or quality of life, measured at three months after the programme, as the quality of evidence is very low (1 RCT, comparison "usual activities", N = 25). The review did not evaluate other approaches, such as use of baclofen as no RCTs were available. Mechanical ventilation for supporting respiratory functionNon-invasive ventilation (NIV) probably improves median survival and quality of life in people with respiratory insufficiency and normal to moderately impaired bulbar function compared to standard care, and improves quality of life but not survival for people with poor bulbar function (1 RCT, N = 41, moderate-quality evidence; a second RCT did not provide data). The review did not evaluate other approaches such as tracheostomy-assisted ('invasive') ventilation, or assess timing of NIV initiation. Treatment for sialorrhoeaA single session of botulinum toxin type B injections to parotid and submandibular glands probably improves sialorrhoea and quality of life at up to 4 weeks compared to placebo injections, but not at 8 or 12 weeks after the injections (moderate-quality evidence from 1 placebo-controlled RCT, N = 20). The review authors found no trials of other approaches. Enteral tube feeding for supporting nutritionThere is no RCT evidence in a Cochrane Systematic Review to support benefit or harms of enteral tube feeding in supporting nutrition in MND. Repetitive transcranial magnetic stimulationIt is uncertain whether repetitive transcranial magnetic stimulation (rTMS) improves disability or limitation in activity in MND in comparison with sham rTMS (3 RCTs, very low quality evidence, N = 50). Therapeutic exerciseThere is evidence that exercise may improve disability in MND at three months after the exercise programme, but not quality of life, in comparison with "usual activities" or "usual care" including stretching (2 RCTs, low-quality evidence, N = 43). Multidisciplinary careThere is no RCT evidence in a Cochrane Systematic Review to demonstrate any benefit or harm for multidisciplinary care in MND.None of the reviews, other than the review of treatment for cramps, reported that adverse events occurred. However, the trials were too small for reliable adverse event reporting.
AUTHORS' CONCLUSIONS
This overview has highlighted the lack of robust evidence in Cochrane Systematic Reviews on interventions to manage symptoms resulting from MND. It is important to recognise that clinical trials may fail to demonstrate efficacy of an intervention for reasons other than a true lack of efficacy, for example because of insufficient statistical power, the wrong choice of dose, insensitive outcome measures or inappropriate participant eligibility. The trials were mostly too small to reliably assess adverse effects of the treatments. The nature of MND makes it difficult to research clinically accepted or recommended practice, regardless of the level of evidence supporting the practice. It would not be ethical, for example, to design a placebo-controlled trial for treatment of pain in MND or to withhold multidisciplinary care where such care is available. It is therefore highly unlikely that there will ever be classically designed placebo-controlled RCTs in these areas.We need more research with appropriate study designs, robust methodology, and of sufficient duration to address the changing needs-of people with MND and their caregivers-associated with MND disease progression and mortality. There is a significant gap in studies assessing the effectiveness of interventions for symptoms relating to MND, such as pseudobulbar emotional lability and cognitive and behavioural difficulties. Future studies should use appropriate outcome measures that are reliable, have internal and external validity, and are sensitive to change in what is being measured (such as quality of life).
Topics: Amyotrophic Lateral Sclerosis; Enteral Nutrition; Exercise Therapy; Humans; Motor Neuron Disease; Muscle Cramp; Muscle Spasticity; Noninvasive Ventilation; Pain; Respiratory Insufficiency; Review Literature as Topic; Sialorrhea; Transcranial Magnetic Stimulation
PubMed: 28072907
DOI: 10.1002/14651858.CD011776.pub2