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Frontiers in Digital Health 2024Amyotrophic Lateral Sclerosis (ALS) significantly impacts the lives of people with the diagnosis and their families. A supportive social environment is important for... (Review)
Review
BACKGROUND
Amyotrophic Lateral Sclerosis (ALS) significantly impacts the lives of people with the diagnosis and their families. A supportive social environment is important for people with ALS to adopt effective coping strategies and health behaviours, and reduce depressive symptoms. Peer support can provide a supportive social environment and can happen in-person and online. Advantages of online peer support are that people can engage from their own home, at their own time and pace, and that it offers a variety of different platforms and modes of communication.
OBJECTIVES
To (1) explore the benefits and challenges of online peer support for people with ALS, and (2) identify successful elements of online peer support for people with ALS.
METHODS
The method selected for this systematic review was a narrative synthesis. Six databases were systematically searched in April 2020 for articles published between 1989 and 2020. The search was updated in June 2022. The quality of the included studies was assessed with the Critical Appraisal Skills Programme qualitative research checklist.
RESULTS
10,987 unique articles were identified through the systematic database search. Of those, 9 were included in this review. One of the main benefits of online peer support was that people could communicate using text rather than needing verbal communication, which can be challenging for some with ALS. Successful elements included using profile pages and graphics to identify others with similar or relevant experiences. Challenges included ALS symptoms which could make it difficult to use technological devices.
CONCLUSIONS
Peer support can provide a non-judgmental and supportive environment for people with ALS, in which they can exchange experiences and emotional support, which can help people in developing adaptive coping strategies. However, ALS symptoms may make it more difficult for people to use technological devices and engage in online peer support. More research is needed to identify what kind of specific barriers people with ALS experience, and how these could be overcome.
PubMed: 38357638
DOI: 10.3389/fdgth.2024.1138530 -
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 -
CNS Neuroscience & Therapeutics Feb 2024Amyotrophic lateral sclerosis (ALS) is a progressive motor and extra-motor neurodegenerative disease. This systematic review aimed to examine MRI biomarkers and... (Review)
Review
BACKGROUND AND OBJECTIVE
Amyotrophic lateral sclerosis (ALS) is a progressive motor and extra-motor neurodegenerative disease. This systematic review aimed to examine MRI biomarkers and neuropsychological assessments of the hippocampal and parahippocampal regions in patients with ALS.
METHODS
A systematic review was conducted in the Scopus and PubMed databases for studies published between January 2000 and July 2023. The inclusion criteria were (1) MRI studies to assess hippocampal and parahippocampal regions in ALS patients, and (2) studies reporting neuropsychological data in patients with ALS.
RESULTS
A total of 46 studies were included. Structural MRI revealed hippocampal atrophy, especially in ALS-FTD, involving specific subregions (CA1, dentate gyrus). Disease progression and genetic factors impacted atrophy patterns. Diffusion tensor imaging (DTI) showed increased mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and decreased fractional anisotropy (FA) in the hippocampal tracts and adjacent regions, indicating loss of neuronal and white matter integrity. Functional MRI (fMRI) revealed reduced functional connectivity (FC) between the hippocampus, parahippocampus, and other regions, suggesting disrupted networks. Perfusion MRI showed hypoperfusion in parahippocampal gyri. Magnetic resonance spectroscopy (MRS) found changes in the hippocampus, indicating neuronal loss. Neuropsychological tests showed associations between poorer memory and hippocampal atrophy or connectivity changes. CA1-2, dentate gyrus, and fimbria atrophy were correlated with worse memory.
CONCLUSIONS
The hippocampus and the connected regions are involved in ALS. Hippocampal atrophy disrupted connectivity and metabolite changes correlate with cognitive and functional decline. Specific subregions can be particularly affected. The hippocampus is a potential biomarker for disease monitoring and prognosis.
Topics: Humans; Diffusion Tensor Imaging; Amyotrophic Lateral Sclerosis; Neurodegenerative Diseases; Frontotemporal Dementia; Magnetic Resonance Imaging; Hippocampus; Biomarkers; Neuropsychological Tests; Atrophy
PubMed: 38334254
DOI: 10.1111/cns.14578 -
Effects and mechanisms of bisphenols exposure on neurodegenerative diseases risk: A systemic review.The Science of the Total Environment Apr 2024Environmental bisphenols (BPs) pose a global threat to human health because of their extensive use as additives in plastic products. BP residues are increasing in... (Review)
Review
Environmental bisphenols (BPs) pose a global threat to human health because of their extensive use as additives in plastic products. BP residues are increasing in various environmental media (i.e., water, soil, and indoor dust) and biological and human samples (i.e., serum and brain). Both epidemiological and animal studies have determined an association between exposure to BPs and an increased risk of neurodegenerative diseases (e.g., Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis), including cognitive abnormalities and behavioral disturbances. Hence, understanding the biological responses to different BPs is essential for prevention, and treatment. This study provides an overview of the underlying pathogenic molecular mechanisms as a valuable basis for understanding neurodegenerative disease responses to BPs, including accumulation of misfolded proteins, reduction of tyrosine hydroxylase and dopamine, abnormal hormone signaling, neuronal death, oxidative stress, calcium homeostasis, and inflammation. These findings provide new insights into the neurotoxic potential of BPs and ultimately contribute to a comprehensive health risk evaluation.
Topics: Animals; Humans; Neurodegenerative Diseases; Alzheimer Disease; Parkinson Disease; Brain; Oxidative Stress
PubMed: 38325473
DOI: 10.1016/j.scitotenv.2024.170670 -
Journal of Neuroimmunology Mar 2024Recent studies have revealed the link between immune activation and neurodegenerative diseases. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recent studies have revealed the link between immune activation and neurodegenerative diseases.
METHODS
By employing meta-analysis, we estimated the standardized mean difference (SMD) and their corresponding 95% confidence intervals (CIs) between the groups.
RESULTS
According to the pre-set criteria, a total of 21 published articles including 2377 ALS patients and 1244 HCs, as well as 60 articles including 5111 PD patients and 4237 HCs, were identified. This study provided evidence of peripheral immune activation in the pathogenesis of ALS and PD.
CONCLUSION
Our results suggested monitoring changes in peripheral blood immune cell populations, particularly lymphocyte subsets, will benefit understanding the developments and exploring reliable and specific biomarkers of these two diseases.
Topics: Humans; Amyotrophic Lateral Sclerosis; Biomarkers; Neurodegenerative Diseases; Parkinson Disease
PubMed: 38301596
DOI: 10.1016/j.jneuroim.2024.578290 -
Critical Reviews in Toxicology Jan 2024Although studies show that pesticides, especially insecticides, may be toxic to humans, publications on the neurological effects of fungicides are scarce. As fungicides... (Review)
Review
Although studies show that pesticides, especially insecticides, may be toxic to humans, publications on the neurological effects of fungicides are scarce. As fungicides are used widely in Brazil, it is necessary to gather evidence to support actions aimed at safely using of these chemicals. We investigated through a systematic review of publications on the use of fungicides and consequences of exposure related to nervous system diseases or neurological disorders in humans. The protocol review was registered on PROSPERO and followed the guidelines of the PRISMA-Statement. As far as it is known, there is no apparent systematic review in the literature on this topic. The search was comprised of the following databases: PubMed; Web of Science; Scopus and EMBASE, using groups of Mesh terms and strategies specific to each database. Thirteen articles were selected for this review. Regarding the substances analyzed in the studies, some reported the use of fungicides in general, without separating them by type, while others summarized the categories of all pesticides by their function (insecticides, herbicides, fungicides, etc.) or chemical class (dithiocarbamate, dicarboximide, inorganic, etc.). However, most of the articles referred to fungicides that contain the metal manganese (Mn) in their composition. As for neurological disorders, articles addressed Parkinson's disease (PD), neurodevelopmental outcomes, extrapyramidal syndrome resembling PD, cognitive disorders, depression, neural tube defects, motor neurone disease, and amyotrophic lateral sclerosis. Most investigations pointed to exposure to fungicides, mainly maneb and mancozeb, leading to the development of at least one neurological disease, which suggests the need for further multicentric clinical trials and prospective studies for greater clarity of the research problem.
Topics: Humans; Fungicides, Industrial; Insecticides; Prospective Studies; Pesticides; Nervous System Diseases; Risk Factors
PubMed: 38288970
DOI: 10.1080/10408444.2024.2303481 -
Biomolecules Dec 2023Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons in the brain and spinal cord. The early...
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons in the brain and spinal cord. The early diagnosis of ALS can be challenging, as it usually depends on clinical examination and the exclusion of other possible causes. In this regard, the analysis of miRNA expression profiles in biofluids makes miRNAs promising non-invasive clinical biomarkers. Due to the increasing amount of scientific literature that often provides controversial results, this work aims to deepen the understanding of the current state of the art on this topic using a machine-learning-based approach. A systematic literature search was conducted to analyze a set of 308 scientific articles using the MySLR digital platform and the Latent Dirichlet Allocation (LDA) algorithm. Two relevant topics were identified, and the articles clustered in each of them were analyzed and discussed in terms of biomolecular mechanisms, as well as in translational and clinical settings. Several miRNAs detected in the tissues and biofluids of ALS patients, including blood and cerebrospinal fluid (CSF), have been linked to ALS diagnosis and progression. Some of them may represent promising non-invasive clinical biomarkers. In this context, future scientific priorities and goals have been proposed.
Topics: Humans; Amyotrophic Lateral Sclerosis; Biomarkers; Machine Learning; MicroRNAs
PubMed: 38254647
DOI: 10.3390/biom14010047 -
Tobacco Induced Diseases 2024Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder primarily affecting the voluntary motor nervous system. Several observational studies...
INTRODUCTION
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder primarily affecting the voluntary motor nervous system. Several observational studies have provided conflicting results regarding the association between smoking and ALS. Therefore, our objective was to investigate this association through a systematic review, meta-analysis, and dose-response analysis.
METHODS
On 16 January 2023, we initially extracted records from medical databases, which included Medline, Embase, Web of Science, Scopus, and ScienceDirect. We included case-control and cohort studies as eligible studies. Subgroup analyses were performed based on sex, study design, and current smoking. Restricted cubic-spline analysis was utilized to assess the dose-response relationship between smoking (pack-years) and ALS.
RESULTS
Twenty-eight case-control and four cohort studies met the inclusion criteria. The unadjusted OR for the overall association between smoking and ALS was 1.14 (95% CI: 1.06-1.22, I=44%, p<0.001), and the adjusted OR (AOR) was 1.12 (95% CI: 1.03-1.21, I=49%, p=0.009). Subgroup analysis revealed a more pronounced association among current smokers, with an AOR of 1.28 (95% CI: 1.10-1.49, I=66%, p<0.001) and AOR of 1.28 (95% CI: 1.10-1.48, I=58%, p=0.001). In the dose-response analysis, the non-linear model revealed an inverted U-shaped curve.
CONCLUSIONS
Our study provides evidence of a positive relationship between smoking and the risk of ALS. To mitigate the risk of developing ALS, discontinuing smoking, which is a modifiable risk factor, may be crucial. The study was registered in PROSPERO. CRD42023388822.
PubMed: 38239315
DOI: 10.18332/tid/175731 -
Neurological Sciences : Official... Jun 2024Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the degeneration of motor neurons, and there is currently a lack of reliable... (Meta-Analysis)
Meta-Analysis Review
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the degeneration of motor neurons, and there is currently a lack of reliable diagnostic biomarkers. This meta-analysis aimed to evaluate CHIT1, CHI3L1, and CHI3L2 levels in the cerebrospinal fluid (CSF) or blood and their diagnostic potential in ALS patients. A systematic, comprehensive search was performed of peer-reviewed English-language articles published before April 1, 2023, in PubMed, Scopus, Embase, Cochrane Library, and Web of Science. After a thorough screening, 13 primary articles were included, and their chitinases-related data were extracted for systematic review and meta-analysis. In ALS patients, the CSF CHIT1 levels were significantly elevated compared to controls with healthy control (HC) (SMD, 1.92; 95% CI, 0.78 - 3.06; P < 0.001). CHIT1 levels were elevated in the CSF of ALS patients compared to other neurodegenerative diseases (ONDS) control (SMD, 0.74; 95% CI, 0.22 - 1.27; P < 0.001) and exhibited an even more substantial increase when compared to ALS-mimicking diseases (AMDS) (SMD, 1.15; 95% CI, 0.35 - 1.94, P < 0.001). Similarly, the CSF CHI3L1 levels were significantly higher in ALS patients compared to HC (SMD, 3.16; 95% CI, 1.26 - 5.06, P < 0.001). CHI3L1 levels were elevated in the CSF of ALS patients compared to ONDS (SMD, 0.75; 95% CI, 0.32 - 1.19; P = 0.017) and exhibited a more pronounced increase when compared to AMDS (SMD, 1.92; 95% CI, 0.41 - 3.42; P < 0.001). The levels of CSF chitinases in the ALS patients showed a significant increase, supporting the role of CSF chitinases as diagnostic biomarkers for ALS.
Topics: Amyotrophic Lateral Sclerosis; Humans; Biomarkers; Chitinases; Prognosis; Hexosaminidases; Chitinase-3-Like Protein 1
PubMed: 38194198
DOI: 10.1007/s10072-024-07301-5 -
Neurological Sciences : Official... May 2024Masitinib, originally developed as a tyrosine kinase inhibitor for cancer treatment, has shown potential neuroprotective effects in various neurological disorders by... (Review)
Review
OBJECTIVES
Masitinib, originally developed as a tyrosine kinase inhibitor for cancer treatment, has shown potential neuroprotective effects in various neurological disorders by modulating key pathways implicated in neurodegeneration. This scoping review aimed to summarize the current evidence of masitinib's neuroprotective activities from preclinical to clinical studies.
METHODS
This scoping review was conducted following the guidelines described by Arksey and O'Malley and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The inclusion criteria covered all original studies reporting on the neuroprotective effects of masitinib, including clinical studies, animal studies, and in vitro studies.
RESULTS
A total of 16 studies met the inclusion criteria and were included in the review. These comprised five randomized controlled trials (RCTs), one post-hoc analysis study, one case report, and nine animal studies. The RCTs focused on Alzheimer's disease (two studies), multiple sclerosis (two studies), and amyotrophic lateral sclerosis (one study). Across all included studies, masitinib consistently demonstrated neuroprotective properties. However, the majority of RCTs reported concerns regarding the safety profile of masitinib. Preclinical studies revealed the neuroprotective mechanisms of masitinib, which include inhibition of certain kinases interfering with cell proliferation and survival, reduction of neuroinflammation, and exhibition of antioxidant activity.
CONCLUSION
The current evidence suggests a promising therapeutic benefit of masitinib in neurodegenerative diseases. However, further research is necessary to validate and expand upon these findings, particularly regarding the precise mechanisms through which masitinib exerts its therapeutic effects. Future studies should also focus on addressing the safety concerns associated with masitinib use.
Topics: Animals; Neuroprotective Agents; Piperidines; Pyridines; Benzamides; Thiazoles
PubMed: 38105307
DOI: 10.1007/s10072-023-07259-w