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Neurotoxicology Dec 2020Heavy metals are considered to be among the leading environmental factors that trigger amyotrophic lateral sclerosis (ALS). However, no convincing biopathological...
Heavy metals are considered to be among the leading environmental factors that trigger amyotrophic lateral sclerosis (ALS). However, no convincing biopathological mechanism and therapeutic clinical implication of such metals in ALS pathogenesis have been established. This is partly attributable to the technical and scientific difficulties in demonstrating a direct and causative role of heavy metals in the onset of ALS in patients. However, a body of epidemiological, clinical and experimental evidences suggest that lead (Pb), more than other metals, could actually play a major role in the onset and progression of ALS. Here, to clarify the nature of the association and the causative role of Pb in ALS, we comprehensively reviewed the scientific literature of the last decade with objective database searches and the methods typically adopted in systematic reviews, critically analysing and summarising the various scientifically sound evidence on the relationship between ALS and Pb. From these tasks, we noted a number of multidisciplinary associations between ALS and Pb, and specifically the importance of occupational exposure to Pb in ALS development and/or progression. We also report the possible involvement of TAR DNA binding protein (TDP-43)-based molecular mechanism in Pb-mediated ALS, although these data rely on a single study, which included both in vitro experiments and an animal model, and are therefore still preliminary. Finally, we briefly examined whether this knowledge could inspire new targeted therapies and policies in the fight against ALS.
Topics: Amyotrophic Lateral Sclerosis; Animals; Central Nervous System; DNA-Binding Proteins; Disease Progression; Environmental Exposure; Environmental Pollutants; Gene-Environment Interaction; Humans; Lead; Lead Poisoning, Nervous System; Protein Aggregates; Protein Aggregation, Pathological; Risk Assessment; Risk Factors
PubMed: 32941938
DOI: 10.1016/j.neuro.2020.09.003 -
Biomedical Engineering Online Jun 2021The use of machine learning (ML) techniques in healthcare encompasses an emerging concept that envisages vast contributions to the tackling of rare diseases. In this... (Review)
Review
INTRODUCTION
The use of machine learning (ML) techniques in healthcare encompasses an emerging concept that envisages vast contributions to the tackling of rare diseases. In this scenario, amyotrophic lateral sclerosis (ALS) involves complexities that are yet not demystified. In ALS, the biomedical signals present themselves as potential biomarkers that, when used in tandem with smart algorithms, can be useful to applications within the context of the disease.
METHODS
This Systematic Literature Review (SLR) consists of searching for and investigating primary studies that use ML techniques and biomedical signals related to ALS. Following the definition and execution of the SLR protocol, 18 articles met the inclusion, exclusion, and quality assessment criteria, and answered the SLR research questions.
DISCUSSIONS
Based on the results, we identified three classes of ML applications combined with biomedical signals in the context of ALS: diagnosis (72.22%), communication (22.22%), and survival prediction (5.56%).
CONCLUSIONS
Distinct algorithmic models and biomedical signals have been reported and present promising approaches, regardless of their classes. In summary, this SLR provides an overview of the primary studies analyzed as well as directions for the construction and evolution of technology-based research within the scope of ALS.
Topics: Amyotrophic Lateral Sclerosis; Biomarkers; Disease Progression; Humans; Machine Learning
PubMed: 34130692
DOI: 10.1186/s12938-021-00896-2 -
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 -
Amyotrophic Lateral Sclerosis &... 2016Our objective was to systematically analyse the first series of cases of amyotrophic lateral sclerosis (ALS) in Minas Gerais and to review the Brazilian literature about... (Review)
Review
Our objective was to systematically analyse the first series of cases of amyotrophic lateral sclerosis (ALS) in Minas Gerais and to review the Brazilian literature about clinical studies in ALS. This was a cross-sectional and descriptive study of a consecutive series of patients with probable or defined sporadic ALS according to the Awaji criteria, followed at two referral centres of Belo Horizonte (South-east Brazil). Patients underwent full clinical assessment. Comparisons of patient subgroups according to disease duration and initial presentation were performed. A systematic review was performed about Brazilian clinical studies in ALS. Results showed that of the 61 enrolled patients the male/female ratio was 1.6:1. The mean age at onset of symptoms was 54.9 years (SD ± 11.4). Mean age at diagnosis was 56.3 years (SD ± 11.1). Regarding the initial form of presentation, 43 cases (70.5%) were spinal, 12 cases (19.7%) were generalized and six cases (9.8%) were bulbar. Eight studies were found in the systematic review. In conclusion, the profile of our sample was similar to other national and international series, except for fewer cases of bulbar ALS in our series. There are few clinical studies of ALS in Brazil. The national data of prevalence and incidence are still uncertain.
Topics: Aged; Amyotrophic Lateral Sclerosis; Brazil; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Statistics, Nonparametric
PubMed: 26854959
DOI: 10.3109/21678421.2016.1143011 -
Brain and Behavior Sep 2022Increasing evidence suggests Amyotrophic Lateral Sclerosis (ALS) as a widespread pathological process comprising nonmotor features like fatigue, mild sensory symptoms,... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Increasing evidence suggests Amyotrophic Lateral Sclerosis (ALS) as a widespread pathological process comprising nonmotor features like fatigue, mild sensory symptoms, cognitive decline, and visual impairment. Measurements of retinal nerve fiber layer (RNFL) thickness using Optical Coherence Tomography (OCT) may correlate with the neurodegeneration associated with ALS. In addition to RNFL thickness, other OCT parameters have been explored in the context of diagnosing ALS and predicting disease severity. In this study, we explore the possibility that OCT parameters of patients with ALS may differ significantly from those of healthy controls and thus serve as biomarkers for the disease and its progression.
MATERIALS AND METHODS
Between 2010 and 2021, the PubMed and EMBASE databases were examined for English language literature. ALS severity was assessed using the revised ALS functional rating scale (ALSFRS-R). The pooled mean differences in RNFL thickness between ALS patients and controls were calculated using the Standard Mean Difference (Hedges's g) with a 95% confidence interval (CI) in STATA software version 16.
RESULTS
Eleven studies were reviewed for data collection. RNFL thickness was not statistically significantly different between ALS patients (n = 412) and controls (n = 376) (Hedges's g = -0.22; 95% CI: -0.51 to 0.07, I = 73.04%, p = .14). However, the thickness of inner nuclear layer was significantly different between ALS patients and controls (Hedges's g = -0.38; 95% CI: -0.61 to 0.14, I = 14.85%, p = .00).
CONCLUSION
Our meta-analysis found that RNFL thickness as a whole or by individual quadrants was not significantly different between ALS patients and controls while the inner nuclear layer (INL) was substantially thinner.
Topics: Amyotrophic Lateral Sclerosis; Cognitive Dysfunction; Humans; Retina; Tomography, Optical Coherence
PubMed: 35996223
DOI: 10.1002/brb3.2741 -
Frontiers in Neuroscience 2023Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting the upper and lower motor neurons. Though the pathogenesis of ALS is still unclear,...
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.
PubMed: 37284659
DOI: 10.3389/fnins.2023.1196722 -
Journal of Affective Disorders Dec 2020Amyotrophic Lateral Sclerosis (ALS) leads to a drastic reduction in quality of life, generating intense psychological distress and predisposing those affected to mental... (Review)
Review
BACKGROUND
Amyotrophic Lateral Sclerosis (ALS) leads to a drastic reduction in quality of life, generating intense psychological distress and predisposing those affected to mental illness and, in more severe cases, suicidal behavior.
OBJECTIVE
This is a systematic review aiming to estimate the frequency of wish to die, suicide ideation and suicide in individuals with ALS using the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P).
METHODS
The following databases were used: Pubmed/MEDLINE, PsycINFO, Embase, SciELO, Biblioteca Virtual de Saúde (BVS), and Cochrane Library. The choice of appropriate descriptors, or their equivalents, to define the search terms was based on the technical and scientific vocabulary of each database.
RESULTS
13 articles were included in the present systematic review, of which three were cross-sectional studies, nine were cohort-type and there was one case-control study. The studies show that individuals with ALS have a higher risk of suicide in relation to the general population, and there is evidence that this risk is even higher in the early stages of the disease. Major Depressive Disorder was the most prevalent mental disorder in the studies included. This mental health concern is often undertreated, leading to the increased susceptibility of this population to suicide.
LIMITATIONS
In general, the study samples represent a highly heterogeneous population while many instruments used in the data collection were not uniform.
CONCLUSIONS
The high degree of psychological vulnerability of this population, associated with a greater predisposition to suicidal behavior, should be minimized through public health measures.
Topics: Amyotrophic Lateral Sclerosis; Case-Control Studies; Cross-Sectional Studies; Depressive Disorder, Major; Humans; Meta-Analysis as Topic; Quality of Life; Suicidal Ideation; Suicide, Attempted
PubMed: 32911219
DOI: 10.1016/j.jad.2020.08.066 -
Expert Review of Pharmacoeconomics &... Jun 2015Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease for which there is no cure, and the associated economic burden is considerable. In this review,... (Review)
Review
Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease for which there is no cure, and the associated economic burden is considerable. In this review, the authors summarize the existing body of literature pertaining to the costs associated with ALS to demonstrate the scale and scope of the economic burden of this paralyzing disease. Twelve studies from eight countries published between January 2001 and January 2015 met the inclusion criteria and were included in this review. Direct and indirect costs varied significantly across countries. Standardized to the 2015 US$, the annual total cost per patient ranged from US$ 13,667 in Denmark to as high as US$ 69,475 in the USA, with the national economic burden of ALS estimated at US$ 279-472 million in the USA. Costs associated with ALS were greater than that of other neurological diseases, indicating a continued need for medical advances and financial support for patients and families. Regional cost analyses are necessary to determine how best to spend funds that have been raised globally from the ice bucket phenomenon.
Topics: Amyotrophic Lateral Sclerosis; Cost of Illness; Health Care Costs; Health Services Needs and Demand; Humans
PubMed: 25924979
DOI: 10.1586/14737167.2015.1039941 -
Amyotrophic Lateral Sclerosis &... Feb 2023: To determine the frequency and correlates of apathy in amyotrophic lateral sclerosis (ALS) and its influence on the prognosis of the disease.: Three databases were... (Meta-Analysis)
Meta-Analysis Review
: To determine the frequency and correlates of apathy in amyotrophic lateral sclerosis (ALS) and its influence on the prognosis of the disease.: Three databases were searched: MEDLINE, PubMed, and Google Scholar. Quantitative synthesis of the frequency of apathy in ALS was conducted using random effects in Stata (College Station, TX). Meta-regression and subgroup analyses were conducted to investigate the association between frequency of apathy in ALS and different covariates.: Fifty-two studies (51 cohorts) were included in the analysis. The pooled frequency of apathy in ALS was 25% (95% confidence interval (CI) 14-35%) according to the studies that used self-rated tools and 34% (95% CI 27-41%) according to studies that used informant-rated tools. The emergence of apathy was associated with cognitive decline and bulbar onset of the disease. There was no consistent relationship between apathy and disease stage or the severity of depression. Structural brain imaging studies established that ALS patients with apathy exhibited more prominent changes with structural and functional brain imaging particularly involving fronto-subcortical regions of the brain. Overall, apathy worsened the long-term prognosis of ALS.: Apathy affects up to a third of ALS patients аnd develops in the context of progressive neurodegeneration. Increased awareness and understanding of non-motor symptoms in ALS highlights the potential utility of apathy as an outcome measure in future clinical trial design.
Topics: Humans; Apathy; Amyotrophic Lateral Sclerosis; Brain; Cognitive Dysfunction; Prognosis
PubMed: 35352575
DOI: 10.1080/21678421.2022.2053721 -
NeuroRehabilitation 2017Individuals with Amyotrophic Lateral Sclerosis (ALS) exhibit speech disorders since the early stages that decrease the communication rate and interfere in social... (Review)
Review
BACKGROUND
Individuals with Amyotrophic Lateral Sclerosis (ALS) exhibit speech disorders since the early stages that decrease the communication rate and interfere in social participation.
OBJECTIVE
To conduct a literature review on communication vulnerable and Augmentative and Alternative Communication (AAC) in Amyotrophic Lateral Sclerosis.
METHOD
Descriptors of the Health Sciences Descriptors (DeCS) were used: Amyotrophic Lateral Sclerosis, Health Vulnerability, Communication Barriers, Nonverbal Communication, and Communication Aids for Disabled. Articles in Portuguese and English from 2010 to 2015, fully available in the Virtual Health Library, PubMed, and Scopus were used. Duplicate articles and those not related to communication/language were excluded.
RESULTS
Of the 94 articles found, 37 met the criteria. All of them were published in the USA and Europe, none was Brazilian; 27% of 2012 to 2014; 40.5% descriptive studies and 24.3% case studies; 45.9% addressed ALS and 24.3%, other serious motor alterations, including ALS. A large proportion (89.2%) addressed AAC, 70.3% Brain-Computer Interface (BCI).
CONCLUSION
The results show that the researches recurrently addressed communication vulnerable, although not necessarily in these terms. The device which was most employed was the BCI, mainly in advanced stages of the disease.
Topics: Amyotrophic Lateral Sclerosis; Brain-Computer Interfaces; Communication Aids for Disabled; Disabled Persons; Humans; Nonverbal Communication; Periodicals as Topic
PubMed: 28222570
DOI: 10.3233/NRE-171443