-
Multiple Sclerosis and Related Disorders Nov 2021This systematic review and meta-analysis aims to evaluate efficacy of deep brain stimulation (DBS) in treating MS-related tremor. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This systematic review and meta-analysis aims to evaluate efficacy of deep brain stimulation (DBS) in treating MS-related tremor.
METHODS
We systematically searched PubMed, Web of Science, Embase, Scopus, Google Scholar, and gray literature using a search strategy including the MeSH and text words as (((Brain Stimulations) OR (Deep Brain Stimulations) OR (Deep Brain Stimulations) OR (Deep Brain Brain Stimulation) OR (Deep Electrical Stimulation of the Brain)) AND (Multiple Sclerosis OR Sclerosis, Multiple) OR Sclerosis, Disseminated) OR Disseminated Sclerosis) OR MS (Multiple Sclerosis)) OR Multiple Sclerosis, Acute Fulminating).
RESULTS
The literature search revealed 1663 articles, 1027 of which remained after removing duplicates. Seventeen articles, published between 1999-2018, were included for the meta-analysis, including overall 168 patients. Follow-up time ranged between 6-62 months. The pooled frequency of tremor improvement among the enrolled patients was 73%, (95% CI:64-83%) (I=84.1%, p<0.001). The pooled standardized mean difference (SMD) (after -before) was -2.9, (95% CI:-4.8, -0.98) (I=89.8%, p<0.001).
CONCLUSION
The results of this systematic review and meta-analysis demonstrate MS-related tremor improvement after DBS.
Topics: Deep Brain Stimulation; Humans; Multiple Sclerosis; Tremor
PubMed: 34517191
DOI: 10.1016/j.msard.2021.103256 -
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 -
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 -
Multiple Sclerosis and Related Disorders Nov 2023Cognitive reserve (CR) describes an individual's ability to adapt cognitive processes in response to brain atrophy, and has been reported to explain some of the... (Review)
Review
BACKGROUND
Cognitive reserve (CR) describes an individual's ability to adapt cognitive processes in response to brain atrophy, and has been reported to explain some of the discrepancy between brain atrophy and cognitive functioning outcomes in multiple sclerosis (MS). CR in MS is typically investigated by assessing an individual's pre- and/or post-diagnosis enrichment, which includes premorbid intellectual abilities, educational level, occupational attainment, and engagement in cognitively enriching leisure activities. Common MS symptoms (e.g., physical disability, fatigue, depression, anxiety) may impact an individual's ability to engage in various CR-enhancing activities post-diagnosis. It is unknown to what extent these MS symptoms have been taken into account in MS research on CR. As such, we identified whether studies assessed CR using measures of premorbid or continuous (including post-diagnosis) enrichment. For studies investigating continuous enrichment, we identified whether studies accounted for MS-impact, which MS symptoms were accounted for, and how, and whether studies acknowledged MS symptoms as potential CR-confounds.
METHODS
Three electronic databases (PsycINFO, PubMed, Scopus) were searched. Eligible studies investigated CR proxies (e.g., estimated premorbid intellectual abilities, vocabulary knowledge, educational level, occupational attainment, cognitively enriching leisure activities, or a combination thereof) in relation to cognitive, brain atrophy or connectivity, or daily functioning outcomes in adult participants with MS. We extracted data on methods and measures used, including any MS symptoms taken into account. Objectives were addressed using frequency analyses and narrative synthesis.
RESULTS
115 studies were included in this review. 47.8% of all studies investigated continuous enrichment. Approximately half of the studies investigating continuous enrichment accounted for potential MS-impact in their analyses, with only 31.0% clearly identifying that they treated MS symptoms as potential confounds for CR-enhancement. A narrative synthesis of studies which investigated CR with and without controlling statistically for MS-impact indicated that accounting for MS symptoms may impact findings concerning the protective nature of CR.
CONCLUSION
Fewer than half of the studies investigating CR proxies in MS involved continuous enrichment. Just over half of these studies accounted for potential MS-impact in their analyses. To achieve a more complete and accurate understanding of CR in MS, future research should investigate both pre-MS and continuous enrichment. In doing so, MS symptoms and their potential impact should be considered. Establishing greater consistency and rigour across CR research in MS will be crucial to produce an evidence base for the development of interventions aimed at improving quality of care and life for pwMS.
Topics: Adult; Humans; Multiple Sclerosis; Cognitive Reserve; Brain; Depression; Anxiety; Atrophy; Fatigue
PubMed: 37806233
DOI: 10.1016/j.msard.2023.105017 -
Journal of Neurology, Neurosurgery, and... Sep 2022Studies among people with multiple sclerosis (pwMS) receiving disease-modifying therapies (DMTs) have provided adequate evidence for an appraisal of COVID-19 vaccination... (Meta-Analysis)
Meta-Analysis Review
Studies among people with multiple sclerosis (pwMS) receiving disease-modifying therapies (DMTs) have provided adequate evidence for an appraisal of COVID-19 vaccination policies among them. To synthesise the available evidence addressing the effect of MS DMTs on COVID-19 vaccines' immunogenicity and effectiveness, following the Cochrane guidelines, we systematically reviewed all observational studies available in MEDLINE, Scopus, Web of Science, MedRxiv and Google Scholar from January 2021 to January 2022 and extracted their relevant data. Immunogenicity data were then synthesised in a quantitative, and other data in a qualitative manner. Evidence from 28 studies suggests extensively lower B-cell responses in sphingosine-1-phosphate receptor modulator (S1PRM) treated and anti-CD20 (aCD20) treated, and lower T-cell responses in interferon-treated, S1PRM-treated and cladribine-treated pwMS-although most T cell evidence currently comprises of low or very low certainty. With every 10-week increase in aCD20-to-vaccine period, a 1.94-fold (95% CI 1.57 to 2.41, p<0.00001) increase in the odds of seroconversion was observed. Furthermore, the evidence points out that B-cell-depleting therapies may accelerate postvaccination humoral waning, and boosters' immunogenicity is predictable with the same factors affecting the initial vaccination cycle. Four real-world studies further indicate that the comparative incidence/severity of breakthrough COVID-19 has been higher among the pwMS treated with S1PRM and aCD20-unlike the ones treated with other DMTs. S1PRM and aCD20 therapies were the only DMTs reducing the real-world effectiveness of COVID-19 vaccination among pwMS. Hence, it could be concluded that optimisation of humoral immunogenicity and ensuring its durability are the necessities of an effective COVID-19 vaccination policy among pwMS who receive DMTs.
Topics: COVID-19; COVID-19 Vaccines; Cladribine; Humans; Immunologic Factors; Multiple Sclerosis
PubMed: 35688629
DOI: 10.1136/jnnp-2022-329123 -
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 Magnetic Resonance Imaging :... Oct 2023Diffusion-weighted imaging has been applied to investigate alterations in multiple sclerosis (MS). In the last years, advanced diffusion models were used to identify... (Review)
Review
Diffusion-weighted imaging has been applied to investigate alterations in multiple sclerosis (MS). In the last years, advanced diffusion models were used to identify subtle changes and early lesions in MS. Among these models, neurite orientation dispersion and density imaging (NODDI) is an emerging approach, quantifying specific neurite morphology in both grey (GM) and white matter (WM) tissue and increasing the specificity of diffusion imaging. In this systematic review, we summarized the NODDI findings in MS. A search was conducted on PubMed, Scopus, and Embase, which yielded a total number of 24 eligible studies. Compared to healthy tissue, these studies identified consistent alterations in NODDI metrics involving WM (neurite density index), and GM lesions (neurite density index), or normal-appearing WM tissue (isotropic volume fraction and neurite density index). Despite some limitations, we pointed out the potential of NODDI in MS to unravel microstructural alterations. These results might pave the way to a deeper understanding of the pathophysiological mechanism of MS. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 3.
Topics: Humans; Neurites; Diffusion Tensor Imaging; Diffusion Magnetic Resonance Imaging; Multiple Sclerosis; White Matter; Brain
PubMed: 37042392
DOI: 10.1002/jmri.28727 -
Journal of Neurology Feb 2022Multiple sclerosis (MS) and functional neurological disorder (FND) are both diagnostically challenging conditions which can present with similar symptoms. We... (Review)
Review
Multiple sclerosis (MS) and functional neurological disorder (FND) are both diagnostically challenging conditions which can present with similar symptoms. We systematically reviewed the literature to identify patients with MS who were misdiagnosed with FND, patients with FND who were misdiagnosed with MS, and reports of patients with both conditions. In addition to FND, we included studies of patients with other functional and psychiatric disorders where these caused symptoms leading to investigation for or a diagnosis of MS, which in a different context would likely have been labeled as FND. Our review suggests that MS is one of the most common causes of misdiagnosis of FND and vice versa. We discuss the clinical errors that appear to result in misdiagnoses, such as over-reliance on psychiatric comorbidity when making a diagnosis of FND or over-reliance on neuroimaging for the diagnosis of MS, and practical ways to avoid them. Comorbidity between these two conditions is also likely common, has been poorly studied, and adds complexity to diagnosis and treatment in patients with both MS and FND. Misdiagnosis and comorbidity in a landscape of emerging evidence-based treatments for both MS and FND are issues not only of clinical importance to the care of these patients, but also to treatment trials, especially of MS, where FND could be a hidden confounder.
Topics: Comorbidity; Conversion Disorder; Diagnostic Errors; Humans; Multiple Sclerosis; Nervous System Diseases; Neuroimaging
PubMed: 33611631
DOI: 10.1007/s00415-021-10436-6 -
Multiple Sclerosis and Related Disorders Jan 2022The prevalence of Trigeminal Neuralgia (TN) in patients diagnosed with multiple sclerosis (MS) is insufficiently understood and controversially reported. This study... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The prevalence of Trigeminal Neuralgia (TN) in patients diagnosed with multiple sclerosis (MS) is insufficiently understood and controversially reported. This study focused on providing a better understanding of the prevalence of TN in MS patients.
METHOD
We systematically searched PubMed, Scopus, EMBASE, Web of Science, and Google Scholar to identify studies published from January 1, 1990, to December 30, 2020. We included studies reporting the TN prevalence among MS patients and exclude case reports/series and editorial studies, review studies, and non-English written articles. We used pooled prevalence estimates to determine the TN prevalence among MS patients.
RESULTS
Pooled overall TN prevalence among 19 studies and 30,348 MS patients was estimated as 3.4% (95% CI: 1.5%-5.9%) with a high level of heterogeneity among studies (I2=98.92%; p<0.001). The pooled prevalence of TN in male and female patients across 9 surveys was 2.4% (95% CI: 0.5%-5.4%) and 3.8% (95% CI: 0.8%-8.7%), respectively. No heterogeneity between the two groups was observed (p = 0.558). A meta-regression was performed to explore the source of the heterogeneity. None of the candidate covariates, including the year of a study publication, the sample size, the average age of patients, and the disease duration, were significant in the model.
CONCLUSION
Our results showed that TN is a common problem among patients with MS, predominantly male patients. Future studies should target the general prevalence of pain in MS patients.
Topics: Female; Humans; Male; Multiple Sclerosis; Pain; Prevalence; Trigeminal Neuralgia
PubMed: 34986455
DOI: 10.1016/j.msard.2021.103472 -
Multiple Sclerosis and Related Disorders Apr 2023The incidence, prevalence and outcomes of multiple sclerosis (MS) are unclear in Indigenous Peoples (IP) who are more likely to be underrepresented in research. We... (Review)
Review
INTRODUCTION
The incidence, prevalence and outcomes of multiple sclerosis (MS) are unclear in Indigenous Peoples (IP) who are more likely to be underrepresented in research. We completed a systematic review of MS in IP of the Americas.
METHODS
A systematic review was conducted using PubMed, Web of Science, and Cochrane databases as well as references of retrieved papers. Inclusion criteria were: peer-reviewed publications (January 1990- December 2021), incidence, prevalence, or clinical outcome measures of MS in self-identified IP in the Americas. Incidence, prevalence, morbidity and mortality data were summarized and stratified by location and year of publication. Study quality was evaluated by risk of bias or confounding.
RESULTS
Out of 416 titles, thirteen studies met inclusion criteria. Four studies evaluated incidence, seven prevalence, three clinical outcomes and one mortality. Most studies were completed in Canada or the United States (US). Incidence rates per 100,000 ranged from 0.48 (in US Indian Health Service records) to 8.15 (First Nations Manitoban Canadians). Prevalence ranged from 0 (Lacandonian Mexicans and Panamanians) to 188.5 (First Nations Manitoban Canadians). Incidence and prevalence are consistently lower in IP than comparator White populations. IP with MS were reported to have higher disability and faster disability progression than non-Indigenous comparators. MS-related mortality is low compared to White people.
CONCLUSION
There is an absence of high-quality studies evaluating MS in IP. Available evidence indicates low, but increasing incidence and prevalence of MS in IP of the Americas. IP with MS may have worse disability than non-Indigenous comparators. Future studies should evaluate the factors influencing the increases in incidence and prevalence as well as better characterize possible disparities in MS care among IP.
Topics: United States; Humans; Multiple Sclerosis; Incidence; Canada; Prevalence; Indigenous Peoples
PubMed: 36917888
DOI: 10.1016/j.msard.2023.104612