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Frontiers in Neurology 2022Viral infections are a proposed possible cause of inflammatory central nervous system (CNS) demyelinating diseases, including multiple sclerosis (MS), neuromyelitis...
BACKGROUND
Viral infections are a proposed possible cause of inflammatory central nervous system (CNS) demyelinating diseases, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). During the past 2 years, CNS demyelinating events associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported, but causality is unclear.
OBJECTIVE
To investigate the relationship between CNS demyelinating disease development and exacerbation with antecedent and/or concurrent SARS-CoV-2 infection.
METHODS
A systematic literature review of all publications describing either a new diagnosis or relapse of CNS demyelinating diseases (MS, NMOSD, MOGAD) in association with SARS-CoV-2 infection was performed utilizing PRISMA guidelines. Descriptive statistics were used for data analysis, using a case analysis approach.
RESULTS
Sixty-seven articles met the inclusion criteria for the study. Most of the reported cases of NMOSD ( = 13, 72.2% of reported cases) and MOGAD ( = 27, 96.5% of reported cases) were of new disease onset, presenting with typical clinical and radiographic features of these conditions, respectively. In contrast, reported MS cases varied amongst newly diagnosed cases ( = 10, 10.5% of reported cases), relapses ( = 63, 66.4%) and pseudo-relapses ( = 22, 23.2%). The median duration between COVID-19 infection and demyelinating event onset was 11.5 days (range 0-90 days) in NMOSD, 6 days (range-7 to +45 days) in MOGAD, and 13.5 days (range-21 to +180 days) in MS. Most cases received high-dose corticosteroids with a good clinical outcome.
CONCLUSION
Based upon available literature, the rate of CNS demyelinating events occurring in the setting of preceding or concurrent SARS-CoV-2 infection is relatively low considering the prevalence of SARS-CoV-2 infection. The clinical outcomes of new onset or relapsing MS, NMOSD, or MOGAD associated with antecedent or concurrent infection were mostly favorable. Larger prospective epidemiological studies are needed to better delineate the impact of COVID-19 on CNS demyelinating diseases.
PubMed: 36203986
DOI: 10.3389/fneur.2022.970383 -
European Journal of Neurology Dec 2021According to the hygiene hypothesis, infections by agents such as parasites have a protective role against the risk of developing multiple sclerosis (MS). Among... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
According to the hygiene hypothesis, infections by agents such as parasites have a protective role against the risk of developing multiple sclerosis (MS). Among parasites, Toxoplasma gondii, an intracellular parasite, showed evidence of a protective effect. This study was undertaken to summarize the available evidence on the association between T. gondii infection and MS.
METHODS
A systematic review of all the available articles published up to November 2020 has been conducted independently by two investigators in the following databases: PubMed, Scopus, Lissa, and SciELO. The association between T. gondii infection and MS has been pooled with a random effects model.
RESULTS
From 562 articles, seven were included in the systematic review and meta-analysis for a global population of 752 MS cases and 1282 controls. T. gondii infection was associated with MS with a pooled odds ratio of 0.68 (95% confidence interval = 0.50-0.93).
CONCLUSIONS
The available evidence supports the hypothesis that T. gondii infection represents a protective factor against the development of MS.
Topics: Antibodies, Protozoan; Humans; Multiple Sclerosis; Risk Factors; Seroepidemiologic Studies; Toxoplasma; Toxoplasmosis
PubMed: 34374174
DOI: 10.1111/ene.15055 -
Journal of Thrombosis and Thrombolysis Oct 2023A number of studies have suggested that multiple sclerosis (MS) can be associated with serious vascular complications, for which pulmonary thromboembolism (PTE) is a... (Meta-Analysis)
Meta-Analysis Review
A number of studies have suggested that multiple sclerosis (MS) can be associated with serious vascular complications, for which pulmonary thromboembolism (PTE) is a potentially lethal complication. The purpose of this study is to establish a current literature-based estimate of the incidence of venous thromboembolism (VTE), deep vein thrombosis (DVT), and PTE in patients with MS (pwMS) due to the lack of systematic reviews and meta-analyses on this topic. In this systematic review and meta-analysis, studies were assessed regarding the association between MS and the incidence of VTE. The studies were identified through a systematic search of major electronic databases spanning the period from 1950 to February 2022. A random-effects analysis was conducted to calculate the pooled effect size (ES) and 95% confidence intervals (CI) using STATA software. Nine out of 4605 studies were included in the meta-analysis, with an overall sample size of 158,546 individuals. Meta-analysis revealed that the pooled incidence of VTE was 1.8% (95% CI 1.4-2.3) among pwMS. Also, there was an incidence of 0.9% (95% CI 0.4-1.4) and 1.5% (95% CI 1-2.2) for PTE and DVT, respectively in pwMS. Analysis showed MS would be significantly associated with a twofold increased risk of VTE [risk ratios (RR) = 2.12 (95% CI 1.53-2.93)]. Although MS is not typically considered a major risk factor for VTE, the meta-analysis of cohort studies shows that MS has a relative association with an increased incidence of VTE. Future research should focus on the investigation of the effects of MS and its treatments on VTE risk, and also a full range of confounding adjustments will be needed.
Topics: Humans; Venous Thromboembolism; Venous Thrombosis; Incidence; Multiple Sclerosis; Pulmonary Embolism; Risk Factors
PubMed: 37394561
DOI: 10.1007/s11239-023-02848-0 -
Frontiers in Immunology 2023Inflammatory processes are involved in the pathophysiology of both Alzheimer's disease (AD) and multiple sclerosis (MS) but their exact contribution to disease... (Review)
Review
UNLABELLED
Inflammatory processes are involved in the pathophysiology of both Alzheimer's disease (AD) and multiple sclerosis (MS) but their exact contribution to disease progression remains to be deciphered. Biomarkers are needed to define pathophysiological processes of these disorders, who may increasingly co-exist in the elderly generations of the future, due to the rising prevalence in both and ameliorated treatment options with improved life expectancy in MS. The purpose of this review was to provide a systematic overview of inflammatory biomarkers, as measured in the cerebrospinal fluid (CSF), that are associated with clinical disease progression. International peer-reviewed literature was screened using the PubMed and Web of Science databases. Disease progression had to be measured using clinically validated tests representing baseline functional and/or cognitive status, the evolution of such clinical scores over time and/or the transitioning from one disease stage to a more severe stage. The quality of included studies was systematically evaluated using a set of questions for clinical, neurochemical and statistical characteristics of the study. A total of 84 papers were included (twenty-five for AD and 59 for MS). Elevated CSF levels of chitinase-3-like protein 1 (YKL-40) were associated with disease progression in both AD and MS. Osteopontin and monocyte chemoattractant protein-1 were more specifically related to disease progression in AD, whereas the same was true for interleukin-1 beta, tumor necrosis factor alpha, C-X-C motif ligand 13, glial fibrillary acidic protein and IgG oligoclonal bands in MS. We observed a broad heterogeneity of studies with varying cohort characterization, non-disclosure of quality measures for neurochemical analyses and a lack of adequate longitudinal designs. Most of the retrieved biomarkers are related to innate immune system activity, which seems to be an important mediator of clinical disease progression in AD and MS. Overall study quality was limited and we have framed some recommendations for future biomarker research in this field.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42021264741.
Topics: Humans; Aged; Alzheimer Disease; Biomarkers; Disease Progression; Multiple Sclerosis
PubMed: 37520580
DOI: 10.3389/fimmu.2023.1162340 -
The Cochrane Database of Systematic... May 2022Ocrelizumab is a humanised anti-CD20 monoclonal antibody developed for the treatment of multiple sclerosis (MS). It was approved by the Food and Drug Administration... (Review)
Review
BACKGROUND
Ocrelizumab is a humanised anti-CD20 monoclonal antibody developed for the treatment of multiple sclerosis (MS). It was approved by the Food and Drug Administration (FDA) in March 2017 for using in adults with relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS). Ocrelizumab is the only disease-modifying therapy (DMT) approved for PPMS. In November 2017, the European Medicines Agency (EMA) also approved ocrelizumab as the first drug for people with early PPMS. Therefore, it is important to evaluate the benefits, harms, and tolerability of ocrelizumab in people with MS.
OBJECTIVES
To assess the benefits, harms, and tolerability of ocrelizumab in people with RRMS and PPMS.
SEARCH METHODS
We searched MEDLINE, Embase, CENTRAL, and two trials registers on 8 October 2021. We screened reference lists, contacted experts, and contacted the main authors of studies.
SELECTION CRITERIA
All randomised controlled trials (RCTs) involving adults diagnosed with RRMS or PPMS according to the McDonald criteria, comparing ocrelizumab alone or associated with other medications, at the approved dose of 600 mg every 24 weeks for any duration, versus placebo or any other active drug therapy.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
Four RCTs met our selection criteria. The overall population included 2551 participants; 1370 treated with ocrelizumab 600 mg and 1181 controls. Among the controls, 298 participants received placebo and 883 received interferon beta-1a. The treatment duration was 24 weeks in one study, 96 weeks in two studies, and at least 120 weeks in one study. One study was at high risk of allocation concealment and blinding of participants and personnel; all four studies were at high risk of bias for incomplete outcome data. For RRMS, compared with interferon beta-1a, ocrelizumab was associated with: 1. lower relapse rate (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.52 to 0.73; 2 studies, 1656 participants; moderate-certainty evidence); 2. a lower number of participants with disability progression (hazard ratio (HR) 0.60, 95% CI 0.43 to 0.84; 2 studies, 1656 participants; low-certainty evidence); 3. little to no difference in the number of participants with any adverse event (RR 1.00, 95% CI 0.96 to 1.04; 2 studies, 1651 participants; moderate-certainty evidence); 4. little to no difference in the number of participants with any serious adverse event (RR 0.79, 95% CI 0.57 to 1.11; 2 studies, 1651 participants; low-certainty evidence); 5. a lower number of participants experiencing treatment discontinuation caused by adverse events (RR 0.58, 95% CI 0.37 to 0.91; 2 studies, 1651 participants; low-certainty evidence); 6. a lower number of participants with gadolinium-enhancing T1 lesions on magnetic resonance imaging (MRI) (RR 0.27, 95% CI 0.22 to 0.35; 2 studies, 1656 participants; low-certainty evidence); 7. a lower number of participants with new or enlarging T2-hyperintense lesions on MRI (RR 0.63, 95% CI 0.57 to 0.69; 2 studies, 1656 participants; low-certainty evidence) at 96 weeks. For PPMS, compared with placebo, ocrelizumab was associated with: 1. a lower number of participants with disability progression (HR 0.75, 95% CI 0.58 to 0.98; 1 study, 731 participants; low-certainty evidence); 2. a higher number of participants with any adverse events (RR 1.06, 95% CI 1.01 to 1.11; 1 study, 725 participants; moderate-certainty evidence); 3. little to no difference in the number of participants with any serious adverse event (RR 0.92, 95% CI 0.68 to 1.23; 1 study, 725 participants; low-certainty evidence); 4. little to no difference in the number of participants experiencing treatment discontinuation caused by adverse events (RR 1.23, 95% CI 0.55 to 2.75; 1 study, 725 participants; low-certainty evidence) for at least 120 weeks. There were no data for number of participants with gadolinium-enhancing T1 lesions on MRI and number of participants with new or enlarging T2-hyperintense lesions on MRI.
AUTHORS' CONCLUSIONS
For people with RRMS, ocrelizumab probably results in a large reduction in relapse rate and little to no difference in adverse events when compared with interferon beta-1a at 96 weeks (moderate-certainty evidence). Ocrelizumab may result in a large reduction in disability progression, treatment discontinuation caused by adverse events, number of participants with gadolinium-enhancing T1 lesions on MRI, and number of participants with new or enlarging T2-hyperintense lesions on MRI, and may result in little to no difference in serious adverse events (low-certainty evidence). For people with PPMS, ocrelizumab probably results in a higher rate of adverse events when compared with placebo for at least 120 weeks (moderate-certainty evidence). Ocrelizumab may result in a reduction in disability progression and little to no difference in serious adverse events and treatment discontinuation caused by adverse events (low-certainty evidence). Ocrelizumab was well tolerated clinically; the most common adverse events were infusion-related reactions and nasopharyngitis, and urinary tract and upper respiratory tract infections.
Topics: Adult; Antibodies, Monoclonal, Humanized; Gadolinium; Humans; Interferon beta-1a; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Recurrence
PubMed: 35583174
DOI: 10.1002/14651858.CD013247.pub2 -
Neuromuscular Disorders : NMD Aug 2022Chronic immune mediated neuropathy is a heterogenous group of peripheral nerve diseases, encompassing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP),...
Chronic immune mediated neuropathy is a heterogenous group of peripheral nerve diseases, encompassing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), autoimmune nodopathy, multifocal motor neuropathy (MMN), and anti-myelin-associated glycoprotein (MAG) neuropathy. Rituximab (RTX) is a chimeric monoclonal antibody targeting the CD20 antigen, which has been used in the treatment of autoimmune neuropathies, although the efficacy of RTX remains unclear. A literature search was performed using Medline, Embase and Cochrane Register for studies between 2000 and 2021 using the search terms "Chronic inflammatory demyelinating polyneuropathy" OR "Multifocal motor neuropathy" OR "Myelin associated glycoprotein" OR "Distal acquired demyelinating neuropathy" OR "Multifocal acquired demyelinating sensory and motor neuropathy" OR "demyelinating neuropathy" AND "Rituximab". Twenty-three studies were included, of which two were randomised controlled trials, 6 prospective studies and 15 retrospective studies. RTX was effective in 63% of CIDP patients, 48% of anti-MAG neuropathy, and 96% of patients with autoimmune nodopathy. Neurophysiological improvement was evident in 58% of CIDP and 40% of anti-MAG neuropathy patients. Low rates of serious adverse events (2.6%) were observed. These results indicate that RTX has potential as a treatment in immune mediated polyneuropathy, although the quality of evidence supporting its use it poor. Randomized controlled trials are required to reliably establish the efficacy and safety of RTX. Trial registration number: CRD42020179666.
Topics: Humans; Polyneuropathies; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Prospective Studies; Retrospective Studies; Rituximab
PubMed: 35672205
DOI: 10.1016/j.nmd.2022.05.013 -
Multiple Sclerosis and Related Disorders Dec 2023Persons with multiple sclerosis (MS) engage in less physical activity than the general population, and the disease manifestations and comorbidity conditions might... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Persons with multiple sclerosis (MS) engage in less physical activity than the general population, and the disease manifestations and comorbidity conditions might further predispose them toward sedentary behavior (SB) among this population. We performed a systematic review with meta-analysis of studies that compared SB in persons with MS and non-MS controls, and examined factors that may moderate the difference in SB between the two groups.
METHODS
We conducted a systematic search using PubMed, PsycINFO, Scopus, and CINAHL from inception up to August 2022, and identified studies that involved group comparison of SB outcomes between MS and non-MS controls. Effect sizes were calculated as standardized mean differences (SMDs) using Hedge's g. We generated a multilevel random-effects model for estimating an overall effect, and performed moderator analyses. Methodological quality was assessed using the Appraisal Tool for Cross-Sectional Studies (AXIS tool).
RESULTS
Eleven studies were included (1403 MS vs. 449 controls) and yielded 17 effects for meta-analysis. Results indicated an overall small, but significant effect (SMD [95% CI] = 0.27 [0.02, 0.53], p = 0.03) with significant heterogeneity (Q = 72.2, p < 0.01; I = 75.8%). There were larger effects when the MS sample had a higher proportion of females, or when SB was reported as percent sedentary time per day compared with other SB outcomes (p = 0.03 and 0.05, respectively). The included studies achieved fairly good quality (91.4%) using the AXIS tool.
CONCLUSIONS
The cumulative evidence supports that persons with MS engage in more SB than non-MS controls. Our findings may support the design of targeted behavioral change interventions for reducing SB and improving health and function in the MS population.
Topics: Female; Humans; Sedentary Behavior; Multiple Sclerosis; Cross-Sectional Studies; Exercise
PubMed: 37956522
DOI: 10.1016/j.msard.2023.105124 -
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 -
Acta Neurologica Belgica Dec 2022Multiple Sclerosis (MS) relapses are episodes of transient disease exacerbation. There are contradictory findings regarding seasonal variation in MS relapses. In this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple Sclerosis (MS) relapses are episodes of transient disease exacerbation. There are contradictory findings regarding seasonal variation in MS relapses. In this systematic review and meta-analysis, we aimed to investigate the seasonal and monthly variation in relapse rates among patients with MS.
METHODS
We systematically queried PubMed, Scopus, and Web of Science for published papers until February 30, 2022.
RESULTS
A total of 24 studies were included in this systematic review and meta-analysis with a total of 29,106 patients with MS. We found that the relapse rate was significantly lower in fall compared to the average relapse rate in other seasons with a risk ratio (RR) of 0.97 (95% CI 0.95-0.98). Furthermore, patients with MS experienced a higher number of relapses in April (RR: 1.06, 95% CI 1.01-1.11) and March (RR: 1.08, 95% CI 1.00-1.16) compared to other months. Also, the risk of relapse was lower in August (RR: 0.92, 95% CI.85-0.98), September (RR: 0.97, 95% CI.94-0.99), October (RR: 0.92, 95% CI.89-0.96), and November (RR: 0.93, 95% CI.89-0.97).
CONCLUSION
Our systematic review and meta-analysis confirm the temporal fluctuations in the relapse of MS through a comprehensive review of the existing literature, with a lower relapse rate during late summer and fall and a higher relapse rate during early spring.
Topics: Humans; Multiple Sclerosis; Seasons; Recurrence; Disease Progression
PubMed: 36171477
DOI: 10.1007/s13760-022-02103-y -
Multiple Sclerosis and Related Disorders Aug 2021Many studies have been conducted investigating a range of environmental factors which have been implicated in the pathogenesis of multiple sclerosis (MS). We collated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many studies have been conducted investigating a range of environmental factors which have been implicated in the pathogenesis of multiple sclerosis (MS). We collated available data about exposure to domestic animals before symptom onset in MS to perform a systematic review and meta-analysis.
METHODS
Medline, Embase and Cinahl were searched for relevant articles, based on pre-defined inclusion and exclusion criteria and reference lists were hand-searched. Data were extracted and critical analysis was conducted using the Newcastle-Ottawa criteria. Meta-analysis used random effects.
RESULTS
Study heterogeneity was high and study quality was variable. Random effects meta-analysis showed no associations with any pet ownership and development of MS.
CONCLUSION
It is not possible to draw definitive conclusions from this work. The studies included had a high level of heterogeneity. There are many variables involved in pet ownership and exposure and the nature of the way these have been studied makes the analysis challenging.
Topics: Animals; Child; Humans; Multiple Sclerosis; Ownership
PubMed: 34090130
DOI: 10.1016/j.msard.2021.103046