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Sensors (Basel, Switzerland) Mar 2023Central nervous system diseases (CNSDs) lead to significant disability worldwide. Mobile app interventions have recently shown the potential to facilitate monitoring and... (Review)
Review
Central nervous system diseases (CNSDs) lead to significant disability worldwide. Mobile app interventions have recently shown the potential to facilitate monitoring and medical management of patients with CNSDs. In this direction, the characteristics of the mobile apps used in research studies and their level of clinical effectiveness need to be explored in order to advance the multidisciplinary research required in the field of mobile app interventions for CNSDs. A systematic review of mobile app interventions for three major CNSDs, i.e., Parkinson's disease (PD), multiple sclerosis (MS), and stroke, which impose significant burden on people and health care systems around the globe, is presented. A literature search in the bibliographic databases of PubMed and Scopus was performed. Identified studies were assessed in terms of quality, and synthesized according to target disease, mobile app characteristics, study design and outcomes. Overall, 21 studies were included in the review. A total of 3 studies targeted PD (14%), 4 studies targeted MS (19%), and 14 studies targeted stroke (67%). Most studies presented a weak-to-moderate methodological quality. Study samples were small, with 15 studies (71%) including less than 50 participants, and only 4 studies (19%) reporting a study duration of 6 months or more. The majority of the mobile apps focused on exercise and physical rehabilitation. In total, 16 studies (76%) reported positive outcomes related to physical activity and motor function, cognition, quality of life, and education, whereas 5 studies (24%) clearly reported no difference compared to usual care. Mobile app interventions are promising to improve outcomes concerning patient's physical activity, motor ability, cognition, quality of life and education for patients with PD, MS, and Stroke. However, rigorous studies are required to demonstrate robust evidence of their clinical effectiveness.
Topics: Humans; Mobile Applications; Quality of Life; Multiple Sclerosis; Parkinson Disease; Stroke
PubMed: 37050456
DOI: 10.3390/s23073396 -
CNS Neuroscience & Therapeutics Mar 2022Lipoic acid (LA) is an endogenous antioxidant that exists widely in nature. Supplementation with LA is a promising approach to improve the outcomes of patients with... (Review)
Review
Lipoic acid (LA) is an endogenous antioxidant that exists widely in nature. Supplementation with LA is a promising approach to improve the outcomes of patients with multiple sclerosis (MS). This systematic review aimed to provide a comprehensive overview of both in vitro and in vivo studies describing the pharmacokinetics, efficacy, safety, and mechanism of LA in MS-related experiments and clinical trials. A total of 516 records were identified by searching five databases, including PubMed, Web of Science, Embase, Scopus, and Cochrane Library. Overall, we included 20 studies reporting LA effects in cell and mouse models of MS and 12 studies reporting LA effects in patients with MS. Briefly, cell experiments revealed that LA protected neurons by inhibiting the expression of inflammatory mediators and activities of immune cells. Experimental autoimmune encephalomyelitis mouse experiments demonstrated that LA consistently reduced the number of infiltrating immune cells in the central nervous system and decreased the clinical disability scores. Patients with MS showed relatively stable Expanded Disability Status Scale scores and better walking performance with few adverse events after the oral administration of LA. Notably, heterogeneity of this evidence existed among modeling methods, LA usage, MS stage, and trial duration. In conclusion, this review provides evidence for the anti-inflammatory and antioxidative effects of LA in both in vitro and in vivo experiments; therefore, patients with MS may benefit from LA administration. Whether LA can be a routine supplementary therapy warrants further study.
Topics: Animals; Antioxidants; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Humans; Mice; Multiple Sclerosis; Thioctic Acid
PubMed: 34964271
DOI: 10.1111/cns.13793 -
Cureus May 2023CANOMAD, characterized by chronic ataxic neuropathy, ophthalmoplegia, immunoglobulin M (IgM) paraprotein, cold agglutinins, and disialosyl antibodies, encompasses a... (Review)
Review
CANOMAD, characterized by chronic ataxic neuropathy, ophthalmoplegia, immunoglobulin M (IgM) paraprotein, cold agglutinins, and disialosyl antibodies, encompasses a clinical, radiological, and laboratory diagnosis. CANOMAD is a rare condition, with fewer than 100 cases reported in the literature. The understanding and diagnosis of the disease have improved in the last few years, but the treatment of CANOMAD is mainly unknown, and there is not a clear consensus about it. We conducted a systematic review regarding the efficacy of rituximab in CANOMAD's treatment to investigate the clinical and biological response of CANOMAD in patients treated with rituximab. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-Analyses of Observational Studies in Epidemiology (MOOSE) reporting guidelines for this systematic review. To analyze the bias of the study, we used the Joanna Briggs Institute's (JBI) Critical Appraisal Checklist to analyze the bias of the case reports, and we used the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool for the observational studies. We only included case reports, case series, and observational studies written in English with patients formally diagnosed with CANOMAD and treated with rituximab. We excluded systematic reviews, literature reviews, and meta-analyses. We investigated the clinical and biological responses of the patients to rituximab. The clinical response was classified as complete recovery (CR), partial response (PR), stable disease (SD), and non-response (NR). We gathered 34 patients. The literature uses a modified Rankin score to define complete improvement (CR), partial response (PR), stable disease (SD), and progression. Clinically, there were three patients with CR, five with PR, 15 with SD, and 11 with progression. The biological response was assessed by measuring the decrease in antibody titers in 27 patients. Among those, six patients had CR, 12 had PR, eight had SD, and one had progression. Among 15 patients with neurological evaluation, 10 had ocular symptoms, and two presented with bulbar symptoms. Seven of the ten patients with ocular symptoms had SD, two had PR, and one had progression. Only 14 patients had a report of demyelinating features. Three had an axonal pattern, six had a demyelinating pattern, and five had a mixed pattern. Among patients with an axonal pattern, three had an SD. Among patients with a demyelinating pattern, three had a PR, two had an SD, and one had progression. Among patients with a mixed pattern, four had SD, and one had progression. We concluded that patients with CR have a shorter disease duration than patients with PR, SD, or progression. In addition, patients with CR had longer follow-ups than the other groups, suggesting that being treated early with rituximab improves the clinical outcome and has a sustained effect. There were no differences in the frequency of ocular and bulbar symptoms among patients with CANOMAD. The axonal pattern is more common in patients with SD, suggesting that axonal and mixed patterns could be markers of a bad prognosis.
PubMed: 37337500
DOI: 10.7759/cureus.39237 -
Journal of Neurology Feb 2022Since the declaration of COVID-19 pandemic, several case reports of demyelination of both peripheral and central nervous systems have been published. The association... (Review)
Review
BACKGROUND
Since the declaration of COVID-19 pandemic, several case reports of demyelination of both peripheral and central nervous systems have been published. The association between CNS demyelination and viral infection has long been documented, and this link was recently reported following SARS-CoV-2 infection as well.
OBJECTIVES
In this systematic review, we aim to investigate the existing literature on CNS demyelination associated with SARS-CoV-2, and the proposed pathophysiological mechanisms.
METHODS
We conducted a systematic review of articles in PubMed, SCOPUS, EMBASE, Cochrane, Google Scholar and Ovid databases, from 1 January 2020 until June 15, 2021. The following keywords were used: "COVID-19", "SARS-CoV-2", "demyelination", "demyelinating disease", "multiple sclerosis", "neuromyelitis optica", and "transverse myelitis".
RESULTS
A total of 60 articles were included in the final analysis of this systematic review and included 102 patients: 52 (51%) men and 50 (49%) women, with a median age of 46.5 years. The demyelination mimicked a variety of conditions with a picture of encephalitis/encephalomyelitis being the most common. At the same time other patterns were less frequently reported such as MS, NMOSD and even MOGAD. Longitudinally extensive transverse myelitis (LETM) was the most frequently reported pattern of spinal cord involvement.
CONCLUSION
A growing body of literature has shown an association between SARS-CoV-2 infection and the development of different types of CNS demyelination. Although causality cannot readily be inferred, this review may suggest a probable causal relationship, through a para-infectious or post-infectious immune-mediated etiology in COVID-19 patients. This relationship needs to be clarified in future research.
Topics: COVID-19; Female; Humans; Male; Middle Aged; Myelitis, Transverse; Neuromyelitis Optica; Pandemics; SARS-CoV-2
PubMed: 34386902
DOI: 10.1007/s00415-021-10752-x -
Journal of Neurology Sep 2021Neurofilament proteins have been extensively studied in relapsing-remitting multiple sclerosis, where they are promising biomarkers of disease activity and treatment... (Review)
Review
BACKGROUND
Neurofilament proteins have been extensively studied in relapsing-remitting multiple sclerosis, where they are promising biomarkers of disease activity and treatment response. Their role in progressive multiple sclerosis, where there is a particularly urgent need for improved biomarkers, is less clear. The objectives of this systematic review are to summarise the literature on neurofilament light and heavy in progressive multiple sclerosis, addressing key questions.
METHODS
A systematic search of PubMed, Embase, Web of Science and Scopus identified 355 potential sources. 76 relevant sources were qualitatively reviewed using QUADAS-2 criteria, and 17 were identified as at low risk of bias. We summarise the findings from all relevant sources, and separately from the 17 high-quality studies.
RESULTS
Differences in neurofilament light between relapsing-remitting and progressive multiple sclerosis appear to be explained by differences in covariates. Neurofilament light is consistently associated with current inflammatory activity and future brain atrophy in progressive multiple sclerosis, and is consistently shown to be a marker of treatment response with immunosuppressive disease-modifying therapies. Associations with current or future disability are inconsistent, and there is no evidence of NFL being a responsive marker of purportedly neuroprotective treatments. Evidence on neurofilament heavy is more limited and inconsistent.
CONCLUSIONS
Neurofilament light has shown consistent utility as a biomarker of neuroinflammation, future brain atrophy and immunosuppressive treatment response at a group level. Neither neurofilament light or heavy has shown a consistent treatment response to neuroprotective disease-modifying therapies, which will require further data from successful randomised controlled trials.
Topics: Biomarkers; Humans; Intermediate Filaments; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting; Neurofilament Proteins
PubMed: 32447549
DOI: 10.1007/s00415-020-09917-x -
Neurologia Mar 2024To identify the neurological diseases for which euthanasia and assisted suicide are most frequently requested in the countries where these medical procedures are legal... (Review)
Review
OBJECTIVE
To identify the neurological diseases for which euthanasia and assisted suicide are most frequently requested in the countries where these medical procedures are legal and the specific characteristics of euthanasia in some of these diseases, and to show the evolution of euthanasia figures.
METHODS
We conducted a systematic literature review.
RESULTS
Dementia, motor neuron disease, multiple sclerosis, and Parkinson's disease are the neurological diseases that most frequently motivate requests for euthanasia or assisted suicide. Requests related to dementia constitute the largest group, are growing, and raise additional ethical and legal issues due to these patients' diminished decision-making capacity. In some countries, the ratios of euthanasia requests to all cases of multiple sclerosis, motor neuron disease, or Huntington disease are higher than for any other disease.
CONCLUSIONS
After cancer, neurological diseases are the most frequent reason for requesting euthanasia or assisted suicide.
Topics: Humans; Suicide, Assisted; Euthanasia; Nervous System Diseases; Huntington Disease; Multiple Sclerosis; Motor Neuron Disease
PubMed: 38272260
DOI: 10.1016/j.nrleng.2024.01.007 -
Cells Jun 2023Multiple sclerosis (MS) is a chronic, progressive neuroinflammatory disease with a complex pathophysiological background. A variety of diverse factors have been... (Review)
Review
Multiple sclerosis (MS) is a chronic, progressive neuroinflammatory disease with a complex pathophysiological background. A variety of diverse factors have been attributed to the propagation of inflammation and neurodegeneration in MS, mainly genetic, immunological, and environmental factors such as vitamin D deficiency, infections, or hormonal disbalance. Recently, the importance of the gut-brain axis for the development of many neurological conditions, including stroke, movement disorders, and neuroinflammatory disorders, has been postulated. The purpose of our paper was to summarize current evidence confirming the role of the gut microbiome in the pathophysiology of MS and related disorders, such as neuromyelitis optica spectrum disorder (NMO-SD). For this aim, we conducted a systematic review of the literature listed in the following databases: Medline, Pubmed, and Scopus, and were able to identify several studies demonstrating the involvement of the gut microbiome in the pathophysiology of MS and NMO-SD. It seems that the most relevant bacteria for the pathophysiology of MS are those belonging to , , , , , , , and , while and have been demonstrated to play a role in the pathophysiology of NMO-SD. Following this line of evidence, there is also some preliminary data supporting the use of probiotics or other agents affecting the microbiome that could potentially have a beneficial effect on MS/NMO-SD symptoms and prognosis. The topic of the gut microbiome in the pathophysiology of MS is therefore relevant since it could be used as a biomarker of disease development and progression as well as a potential disease-modifying therapy.
Topics: Humans; Multiple Sclerosis; Gastrointestinal Microbiome; Neuromyelitis Optica; Vitamin D Deficiency; Inflammation
PubMed: 37443793
DOI: 10.3390/cells12131760 -
Nutrients Jun 2023Vitamin D supplementation has been considered a possible treatment to reduce the risk of disease activity and progression in people with multiple sclerosis (MS).... (Meta-Analysis)
Meta-Analysis Review
Vitamin D supplementation has been considered a possible treatment to reduce the risk of disease activity and progression in people with multiple sclerosis (MS). However, its effect on disease symptoms remains unclear. The aim of this meta-analysis was to conduct a systematic review to assess the effect of vitamin D on fatigue in this population. The systematic review was conducted using the MEDLINE, Cochrane Library, Embase and Web of Science databases from inception to May 2023. Randomized controlled trials (RCTs) reporting pre-post changes in fatigue after vitamin D supplementation were included. Pooled effect sizes and 95% confidence intervals (95% CIs) were calculated by applying a random effects model with Stata/SE (Version 16.0; StataCorp., College Station, TX, USA). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A total of five studies with 345 individuals (271 females; age range: 25.4-41.1 years) were included. A significant reduction in fatigue was perceived when vitamin D supplementation was compared with a control group: -0.18 (95% CI: -0.36 to -0.01; I = 0%). Thus, our findings show that the therapeutic use of vitamin D on fatigue in people with MS could be considered. Nevertheless, due to the lack of agreement on the dose to be applied, it is recommended to use it under medical prescription.
Topics: Adult; Female; Humans; Dietary Supplements; Fatigue; Multiple Sclerosis; Vitamin D; Male
PubMed: 37447189
DOI: 10.3390/nu15132861 -
Journal of Integrative Neuroscience Feb 2024Several results support the hypothesis that a group of pathologies falling within the Neuromyelitis Optica Spectrum Disorders (NMOSD) diagnostic criteria may coexist... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several results support the hypothesis that a group of pathologies falling within the Neuromyelitis Optica Spectrum Disorders (NMOSD) diagnostic criteria may coexist with Connective Tissue Diseases (CTD) in patients with a high susceptibility to autoimmune conditions. However, the relationship between NMOSD and rheumatologic diseases deserves further investigations to clarify all clinical aspects of this coexistence. We designed a systematic review and a proportional meta-analysis to estimate the association between CTD and MNOSD, with the aim of helping to plan the best strategy to achieve the most significant public health benefit for these conditions.
METHODS
We conducted a systematic review of the literature published until February 2023, searching in four databases: PubMed, Web of Science, EmBase, and OVID. Then, we conducted a random-effects proportional meta-analysis and assessed the risk of bias of the included studies using the Joanna Briggs Institute checklist.
RESULTS
The literature search yielded an overall result of 3176 publications (272 from PubMed, 880 from Web of Science, 634 from EmBase and 1390 from OVID). Of these, 29 were included in this systematic review. Analyzing studies that recruited unselected patients with Systemic Lupus Erythematosus (SLE) and Sjogren Syndrome (SjS), the pooled percentages of NMOSD overlapping were 0.6% (95% Confidence Interval [95% CI]: 0.1%-1.4%,) and 6.5% (95% CI: 4.7-8.6), respectively. Studies enrolling rheumatologic patients with nervous system symptoms involvement reported higher percentage of NMOSD (i.e., among SjS patients, a pooled percentage of 26.5%, 95% CI: 5.5-54.6%, was found). Similarly, recruiting patients with NMOSD, we found pooled percentages of SjS or SLE respectively of 7.0% and 3.5%.
CONCLUSIONS
Our research found that the coexistence of these two disorders was more frequent in female rheumatologic patients with a SjS diagnosis with neurological manifestations and in neurologic patients for whom a SjS diagnosis was suspected. Similarly, NMOSD are less frequently found in SLE and very rarely incident in Mixed Connective Tissue Disease (MCTD) patients. These considerations should be taken into account in clinical experience of rheumatologists and neurologists, since early diagnosis of both conditions may influence the timing of immunosuppressive therapy and the prevention of systemic disabilities.
Topics: Humans; Female; Neuromyelitis Optica; Aquaporin 4; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Arthritis, Rheumatoid
PubMed: 38419451
DOI: 10.31083/j.jin2302035 -
The Cochrane Database of Systematic... Nov 2021Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, with an unpredictable course. Current MS therapies such as disease-modifying... (Review)
Review
BACKGROUND
Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, with an unpredictable course. Current MS therapies such as disease-modifying therapies focus on treating exacerbations, preventing new exacerbations and avoiding the progression of disability. Siponimod (BAF312) is an oral treatment, a selective sphingosine-1-phosphate (S1P) receptor modulator, for the treatment of adults with relapsing forms of MS including active, secondary progressive MS with relapses.
OBJECTIVES
To assess the benefits and adverse effects of siponimod as monotherapy or combination therapy versus placebo or any active comparator for people diagnosed with MS.
SEARCH METHODS
On 18 June 2020, we searched the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Trials Register, which contains studies from CENTRAL, MEDLINE and Embase, and the trials registry databases ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP). We also handsearched relevant journals and screened the reference lists of published reviews and retrieved articles and searched reports (2004 to June 2020) from the MS societies in Europe and America.
SELECTION CRITERIA
We included randomised parallel controlled clinical trials (RCTs) that evaluated siponimod, as monotherapy or combination therapy, versus placebo or any active comparator in people with MS. There were no restrictions on dose or administration frequency.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. We discussed disagreements and resolved them by consensus among the review authors. Our primary outcomes wereworsening disability , relapse and adverse events, and secondary outcomes were annualised relapse rate, gadolinium-enhancing lesions, new lesions or enlarged pre-existing lesions and mean change of brain volume. We independently evaluated the certainty of evidence using the GRADE approach. We contacted principal investigators of included studies for additional data or confirmation of data.
MAIN RESULTS
Two studies (1948 participants) met our selection criteria, 608 controls and 1334 treated with siponimod. The included studies compared siponimod with placebo. Overall, all studies had a high risk of bias due to selective reporting and attrition bias. Comparing siponimod administered at a dose of 2 mg to placebo, we found that siponimod may reduce the number of participants with disability progression at six months (56 fewer people per 1000; risk ratio (RR) 0.78, 95% confidence interval (CI) 0.65 to 0.94; 1 study, 1641 participants; low-certainty evidence) and annualised relapse rate (RR 0.43, 95% CI 0.34 to 0.56; 2 studies, 1739 participants; low-certainty evidence). But it might lead to little reduction in the number of participants with new relapse (166 fewer people per 1000; RR 0.38, 95% CI 0.15 to 1.00; 1 study, 94 participants; very low-certainty evidence). We observed no evidence of a difference due to adverse events for siponimod at 2 mg compared to placebo (14 more people per 1000; RR 1.52, 95% CI 0.85 to 2.71; 2 studies, 1739 participants, low-certainty evidence). In addition, due to the high risk of inaccurate magnetic resonance imaging (MRI) data in the two included studies, we could not combine data for active lesions on MRI scans. Both studies had high attrition bias resulting from the unbalanced reasons for dropouts among groups and high risk of bias due to conflicts of interest. Siponimod may reduce the number of gadolinium-enhancing T1-weighted lesions at two years of follow-up (RR 0.14, 95% CI 0.10 to 0.19; P < 0.0001; 1 study, 1641 participants; very low-certainty evidence). There may be no evidence of a difference between groups in the number of participants with at least one serious adverse event excluding relapses (113 more people per 1000; RR 1.80, 95% CI 0.37 to 8.77; 2 studies, 1739 participants; low-certainty evidence) at six months. No data were available regarding cardiac adverse events. In terms of safety profile, the most common adverse events associated with siponimod were headache, back pain, bradycardia, dizziness, fatigue, influenza, urinary tract infection, lymphopenia, nausea, alanine amino transferase increase and upper respiratory tract infection. These adverse events have dose-related effects and rarely led to discontinuation of treatment.
AUTHORS' CONCLUSIONS
Based on the findings of the RCTs included in this review, we are uncertain whether siponimod interventions are beneficial for people with MS. There was low-certainty evidence to support that siponimod at a dose of 2 mg orally once daily as monotherapy compared with placebo may reduce the annualised relapse rate and the number of participants who experienced disability worsening, at 6 months. However, the certainty of the evidence to support the benefit in reducing the number of people with a relapse is very low. The risk of withdrawals due to adverse events requires careful monitoring of participants over time. The duration of all studies was less than 24 months, so the efficacy and safety of siponimod over 24 months are still uncertain, and further exploration is needed in the future. There is no high-certainty data available to evaluate the benefit on MRI outcomes. We assessed the certainty of the body of evidence for all outcomes was low to very low, downgraded due to serious study limitations, imprecision and indirectness. We are uncertain whether siponimod is beneficial for people with MS. More new studies with robust methodology and longer follow-up are needed to evaluate the benefit of siponimod for the management of MS and to observe long-term adverse effects. Also, in addition to comparing with placebo, more new studies are needed to evaluate siponimod versus other therapeutic options.
Topics: Adult; Azetidines; Benzyl Compounds; Humans; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive
PubMed: 34783010
DOI: 10.1002/14651858.CD013647.pub2