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Nutrients Apr 2023The link between vitamin D and multiple sclerosis (MS) has been suggested in epidemiological, genetic, immunological, and clinical studies. The aim of the present... (Review)
Review
The link between vitamin D and multiple sclerosis (MS) has been suggested in epidemiological, genetic, immunological, and clinical studies. The aim of the present systematic review of the literature was to assess the effects of vitamin D supplementation on clinical and imaging outcomes in patients with MS. The outcomes we assessed included relapse events, disability progression, and magnetic resonance imaging (MRI) lesions. The search was conducted using PubMed, ClinicalTrials.gov, and EudraCT databases, and it included records published up until 28 February 2023. The systematic review was reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines. Nineteen independent clinical studies (corresponding to 24 records) were included in the systematic review. The risk of bias in randomized controlled trials (RCTs) was analyzed using the Cochrane risk-of-bias tool. Fifteen trials investigated relapse events, and most of them reported no significant effect of vitamin D supplementation. Eight of 13 RCTs found that vitamin D supplementation had no effect on disability [assessed by Expanded Disability Status Scale (EDSS) scores] compared to controls. Interestingly, recent RCTs reported a significant reduction in new MRI lesions in the central nervous system of MS patients during supplementation with vitamin D3.
Topics: Humans; Vitamins; Vitamin D; Multiple Sclerosis; Dietary Supplements; Recurrence
PubMed: 37111166
DOI: 10.3390/nu15081945 -
The Cochrane Database of Systematic... Apr 2016Multiple sclerosis (MS) is an autoimmune, T-cell-dependent, inflammatory, demyelinating disease of the central nervous system, with an unpredictable course. Current MS... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple sclerosis (MS) is an autoimmune, T-cell-dependent, inflammatory, demyelinating disease of the central nervous system, with an unpredictable course. Current MS therapies focus on treating exacerbations, preventing new exacerbations and avoiding the progression of disability. However, at present there is no effective treatment that is capable of safely and effectively reaching these objectives. This has led to the development and investigation of new drugs. Recent clinical trials suggest that alemtuzumab, a humanised monoclonal antibody against cell surface CD52, could be a promising option for MS.
OBJECTIVES
To assess the safety and effectiveness of alemtuzumab used alone or associated with other treatments to decrease disease activity in patients with any form of MS.
SEARCH METHODS
We searched the Trials Register of the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group (30 April 2015), which contains trials from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, LILACS and the trial registry databases ClinicalTrials.gov and WHO International Clinical Trials Registry Platform. There was no restriction on the source, publication date or language.
SELECTION CRITERIA
All randomised clinical trials (RCTs) involving adults diagnosed with any form of MS according to the McDonald criteria, comparing alemtuzumab alone or associated with other medications, at any dose and for any duration, versus placebo or any other active drug therapy or alemtuzumab in other dose, regimen or duration. The co-primary outcomes were relapse-free survival, sustained disease progression and number of participants with at least one of any adverse events, including serious adverse events.
DATA COLLECTION AND ANALYSIS
Two independent review authors performed study selection, data extraction and 'Risk of bias' assessment. A third review author checked the process for accuracy. We used the Cochrane 'Risk of bias' tool to assess the risk of bias of the studies included in the review. We used the GRADE system to assess the quality of the body of evidence. To measure the treatment effect on dichotomous outcomes we used the risk ratio (RR); for the treatment effect on continuous outcomes, we used the mean difference (MD) and for time-to-event outcomes we used hazard ratio (HR). We calculated 95% confidence intervals (CI) for these measures. When there was no heterogeneity, we used a fixed-effect model to pool data.
MAIN RESULTS
Three RCTs (1713 participants) fulfilled the selection criteria and we included them in the review. All three trials compared alemtuzumab versus subcutaneous interferon beta-1a for patients with relapsing-remitting MS. Patients were treatment-naive in the CARE-MS and CAMMS223 studies. The CARE-MS II study included patients with at least one relapse while being treated with interferon beta or glatiramer acetate. Alemtuzumab was given for 12 or 24 months; for some outcomes, the follow-up period reached 36 months. The regimens were (a) 12 mg or 24 mg per day administered intravenously, once a day for five consecutive days at month 0 and 12 or (b) 24 mg per day, intravenously, once a day for three consecutive days at month 12 and 24. The patients in the other arm of the trials received interferon beta-1a 44 μg subcutaneously three times weekly after dose titration.At 24 months, alemtuzumab 12 mg was associated with: (a) higher relapse-free survival (hazard ratio (HR) 0.50, 95% CI 0.41 to 0.60; 1248 participants, two studies, moderate quality evidence); (b) higher sustained disease progression-free survival (HR 0.62, 95% CI 0.44 to 0.87; 1191 participants; two studies; moderate quality evidence); (c) a slightly higher number of participants with at least one adverse event (RR 1.04, 95% CI 1.01 to 1.06; 1248 participants; two studies; moderate quality evidence); (d) a lower number of participants with new or enlarging T2-hyperintense lesions on magnetic resonance imaging (MRI) (RR 0.74, 95% CI 0.59 to 0.91; 1238 participants; two studies; I(2) = 80%); and (e) a lower number of dropouts (RR 0.31, 95% CI 0.23 to 0.41; 1248 participants; two studies, I(2) = 29%; low quality evidence).At 36 months, alemtuzumab 24 mg was associated with: (a) higher relapse-free survival (45 versus 17; HR 0.21, 95% CI 0.11 to 0.40; one study; 221 participants); (b) a higher sustained disease progression-free survival (HR 0.33, 95% CI 0.16 to 0.69; one study; 221 participants); and (c) no statistical difference in the rate of participants with at least one adverse event. We did not find any study that reported any of the following outcomes: rate of participants free of clinical disease activity, quality of life, fatigue or change in the numbers of MRI T2- and T1-weighted lesions after treatment. It was not possible to perform subgroup analyses according to disease type and disability at baseline due to lack of data.
AUTHORS' CONCLUSIONS
In patients with relapsing-remitting MS, alemtuzumab 12 mg was better than subcutaneous interferon beta-1a for the following outcomes assessed at 24 months: relapse-free survival, sustained disease progression-free survival, number of participants with at least one adverse event and number of participants with new or enlarging T2-hyperintense lesions on MRI. The quality of the evidence for these results was low to moderate. Alemtuzumab 24 mg seemed to be better than subcutaneous interferon beta-1a for relapse-free survival and sustained disease progression-free survival, at 36 months.More randomised clinical trials are needed to evaluate the effects of alemtuzumab on other forms of MS and compared with other therapeutic options. These new studies should assess additional relevant outcomes such as the rate of participants free of clinical disease activity, quality of life, fatigue and adverse events (individual rates, serious adverse events and long-term adverse events). Moreover, these new studies should evaluate other doses and durations of alemtuzumab course.
Topics: Adult; Alemtuzumab; Antibodies, Monoclonal, Humanized; Disease-Free Survival; Humans; Interferon beta-1a; Multiple Sclerosis, Relapsing-Remitting; Randomized Controlled Trials as Topic
PubMed: 27082500
DOI: 10.1002/14651858.CD011203.pub2 -
Neurological Sciences : Official... May 2023To exp lore changes in immunoglobulin (Ig) levels for people with relapsing-multiple sclerosis (RMS) treated with ocrelizumab or ofatumumab and the relationship between... (Review)
Review
OBJECTIVE
To exp lore changes in immunoglobulin (Ig) levels for people with relapsing-multiple sclerosis (RMS) treated with ocrelizumab or ofatumumab and the relationship between Ig levels and infections.
METHODS
A systematic literature review (SLR) was conducted to identify clinical trials and real-world evidence (RWE) studies on Ig levels over time and studies on associations with infections for ocrelizumab and ofatumumab for people with RMS through 10 September 2021. Searches were conducted in Embase, MEDLINE, Cochrane Library, trial registries, and recent conference abstracts.
RESULTS
Of 1,580 articles identified, 30 reporting on 11 trials and 5 RWE studies were included. Ocrelizumab trials (n = 4) had 24-336 weeks of follow-up and reported decreasing Ig G (IgG) levels, while RWE (n = 5) had 52-78 weeks of follow-up and reported IgG to be stable or decrease only slightly. IgG levels were stable in ofatumumab trials (n = 5; 104-168 weeks of follow-up), but no RWE or longer-term studies were identified. No apparent association between decreased Ig levels and infections was observed during ofatumumab treatment (ASCLEPIOS I/II), while for ocrelizumab, the only data on apparent associations between decreased IgG levels and serious infection rates were for a pooled population of people with RMS or primary progressive MS.
CONCLUSION
Decreasing IgG levels have been correlated with increased infection risk over time. IgG levels appeared to decrease over time in ocrelizumab trials but remained relatively stable over time in ofatumumab trials. Additional research is needed to understand differences between ocrelizumab and ofatumumab and identify people at risk of decreasing IgG levels and infection.
Topics: Humans; Multiple Sclerosis; Antibodies, Monoclonal; Antineoplastic Agents; Immunoglobulin G; Multiple Sclerosis, Relapsing-Remitting
PubMed: 36648561
DOI: 10.1007/s10072-022-06582-y -
Neuropsychology Review Sep 2022Fatigue is one of the most debilitating symptoms for people with multiple sclerosis (PwMS). By consolidating a diverse and conflicting evidence-base, this systematic... (Meta-Analysis)
Meta-Analysis Review
Fatigue is one of the most debilitating symptoms for people with multiple sclerosis (PwMS). By consolidating a diverse and conflicting evidence-base, this systematic review and meta-analysis aimed to gain new insights into the neurobiology of MS fatigue. MEDLINE, ProQuest, CINAHL, Web of Science databases and grey literature were searched using Medical Subject Headings. Eligible studies compared neuroimaging and neurophysiological data between people experiencing high (MS-HF) versus low (MS-LF) levels of perceived MS fatigue, as defined by validated fatigue questionnaire cut-points. Data were available from 66 studies, with 46 used for meta-analyses. Neuroimaging studies revealed lower volumetric measures in MS-HF versus MS-LF for whole brain (-22.74 ml; 95% CI: -37.72 to -7.76 ml; p = 0.003), grey matter (-18.81 ml; 95% CI: -29.60 to -8.03 ml; p < 0.001), putamen (-0.40 ml; 95% CI: -0.69 to -0.10 ml; p = 0.008) and acumbens (-0.09 ml; 95% CI: -0.15 to -0.03 ml; p = 0.003) and a higher volume of T1-weighted hypointense lesions (1.10 ml; 95% CI: 0.47 to 1.73 ml; p < 0.001). Neurophysiological data showed reduced lower-limb maximum voluntary force production (-19.23 N; 95% CI: -35.93 to -2.53 N; p = 0.02) and an attenuation of upper-limb (-5.77%; 95% CI:-8.61 to -2.93%; p < 0.0001) and lower-limb (-2.16%; 95% CI:-4.24 to -0.07%; p = 0.04) skeletal muscle voluntary activation, accompanied by more pronounced upper-limb fatigability (-5.61%; 95% CI: -9.57 to -1.65%; p = 0.006) in MS-HF versus MS-LF. Results suggest that MS fatigue is characterised by greater cortico-subcortical grey matter atrophy and neural lesions, accompanied by neurophysiological decrements, which include reduced strength and voluntary activation. Prospero registration Prospero registration number: CRD42016017934.
Topics: Brain; Cross-Sectional Studies; Fatigue; Humans; Multiple Sclerosis; Organ Size
PubMed: 33961198
DOI: 10.1007/s11065-021-09508-1 -
PloS One 2017The interaction between genetic and environmental factors is crucial to multiple sclerosis (MS) pathogenesis. Human Endogenous Retroviruses (HERVs) are endogenous viral... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The interaction between genetic and environmental factors is crucial to multiple sclerosis (MS) pathogenesis. Human Endogenous Retroviruses (HERVs) are endogenous viral elements of the human genome whose expression is associated with MS.
OBJECTIVE
To perform a systematic review and meta-analysis and to assess qualitative and quantitative evidence on the expression of HERV families in MS patients.
METHODS
Medline, Embase and the Cochrane Library were searched for published studies on the association of HERVs and MS. Meta-analysis was performed on the HERV-W family. Odds Ratio (OR) and 95% confidence interval (CI) were calculated for association.
RESULTS
43 reports were extracted (25 related to HERV-W, 13 to HERV-H, 9 to HERV-K, 5 to HRES-1 and 1 to HER-15 family). The analysis showed an association between expression of all HERV families and MS. For HERV-W, adequate data was available for meta-analysis. Results from meta-analyses of HERV-W were OR = 22.66 (95%CI 6.32 to 81.20) from 4 studies investigating MSRV/HERV-W (MS-associated retrovirus) envelope mRNA in peripheral blood mononuclear cells, OR = 44.11 (95%CI 12.95 to 150.30) from 6 studies of MSRV/HERV-W polymerase mRNA in serum/plasma and OR = 6.00 (95%CI 3.35 to 10.74) from 4 studies of MSRV/HERV-W polymerase mRNA in CSF.
CONCLUSIONS
This systematic review and meta-analysis shows an association between expression of HERVs, and in particular the HERV-W family, and MS.
Topics: Endogenous Retroviruses; Humans; Multiple Sclerosis
PubMed: 28207850
DOI: 10.1371/journal.pone.0172415 -
Arthritis Research & Therapy Sep 2015Infection with Epstein-Barr virus (EBV) has been suggested to contribute to the pathogenesis of autoimmune diseases, including rheumatoid arthritis (RA). We sought to... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Infection with Epstein-Barr virus (EBV) has been suggested to contribute to the pathogenesis of autoimmune diseases, including rheumatoid arthritis (RA). We sought to determine whether prior infection with the virus occurs more frequently in patients with RA compared to controls.
METHODS
We performed a systematic review and meta-analyses of studies that reported the prevalence of anti-EBV antibodies in the sera of cases with RA and controls by searching Medline and Embase databases from 1946 to 2014, with no language restriction. Mantel-Haenszel odds ratios for the detection of anti-EBV antibodies were calculated, and meta-analyses conducted. Quality assessments were performed using a modified version of the Newcastle-Ottawa scale.
RESULTS
Twenty-three studies were included. Quality assessment found most studies reported acceptable selection criteria but poor descriptions of how cases and controls were recruited. When all studies were included, there was a statistically significant higher seroprevalence of anti-VCA IgG in patients with RA compared to controls with an odds ratio (OR) of 1.61 (95 % confidence interval (CI) 1.05-2.46, p = 0.03), which is a similar-sized summary OR to that reported for systemic lupus erythematosus (SLE). However, when studies were restricted to those reporting more plausible levels of exposure to EBV in the control groups, no significant association was apparent, OR 1.47 (95 % CI 0.88-2.46, p = 0.14). Using anti-EBNA 1 or anti-EA IgG as markers of previous infection also did not yield significant associations (OR 1.05, 95 % CI 0.68-1.61, p = 0.82; OR 2.2, 95 % CI 0.86-5.65, p = 0.10 respectively).
CONCLUSIONS
Overall, these findings do not demonstrate an association between EBV seroprevalence and RA and therefore do not support the hypothesis that prior infection with EBV predisposes to the development of RA. This contrasts with meta-analyses that indicate EBV infection is associated with multiple sclerosis and SLE.
Topics: Antibodies, Viral; Arthritis, Rheumatoid; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Immunoglobulin G; Lupus Erythematosus, Systemic; Multiple Sclerosis; Odds Ratio; Seroepidemiologic Studies
PubMed: 26416719
DOI: 10.1186/s13075-015-0755-6 -
BMJ Open Jul 2022To update the knowledge on the occupational outcomes associated with multiple sclerosis (MS), systematically examine the extent, scope and nature of the pre-existing...
OBJECTIVES
To update the knowledge on the occupational outcomes associated with multiple sclerosis (MS), systematically examine the extent, scope and nature of the pre-existing literature and identify research gaps in the existing literature.
DESIGN
Scoping review.
DATA SOURCES
A comprehensive database search of PubMed/MEDLINE, Scopus, SciVerse ScienceDirect and Web of Science was performed. There were no time limits.
ELIGIBILITY CRITERIA
We included any peer-reviewed original article reporting the occupational outcomes of people with MS between the ages of 18 and 65 years. We excluded those off-topic and with insufficient information.
METHODS
This review was conducted following the Joanna Briggs Institute recommendations and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for scoping review checklist. Screening, reading of full-texts and data extraction was performed in a standardised way by expert reviewers from 14 July 2021 to 31 October 2021. We provided a narrative synthesis and an overview of findings.
RESULTS
The initial systematic search yielded 104 228 results. After removing duplicates and applying the exclusion criteria, 403 articles were included in the review. In total, the studies evaluated 492 062 subjects with MS. One hundred fifty-four (38.2%) articles were published in the last 5 years, mostly from Europe and North America (50.9% and 33.0%, respectively). Concerning the occupational outcomes, studies mostly addressed unemployment (311, 77.2%), early retirement (120, 29.8%), disability pension (117, 29.0%), sick leave (77, 19.1%), the indirect cost of MS (74, 18.4%) and work characteristics (57, 14.1%). The results were categorised into seven subtopics: 'Changes in work and occupational status due to MS', 'work-related socio-economic consequences of MS', 'risk factors for unfavourable occupational outcomes', 'reported barriers to employment', 'reported job accommodations and vocational rehabilitation strategies', 'job satisfaction, stigma, and disclosing the diagnosis in the workplace' and 'rating clinical scales'.
CONCLUSIONS
There are several issues that deserve further in-depth study by the scientific community in order to improve the occupational outcomes of people with MS.
Topics: Adolescent; Adult; Aged; Employment; Humans; Middle Aged; Multiple Sclerosis; Rehabilitation, Vocational; Research Report; Retirement; Young Adult
PubMed: 35777874
DOI: 10.1136/bmjopen-2021-058948 -
World Neurosurgery Mar 2018Patients with trigeminal neuralgia (TN) and multiple sclerosis (MS) are often treated with medications or a surgical procedure. However, there is little evidence that... (Review)
Review
BACKGROUND AND OBJECTIVE
Patients with trigeminal neuralgia (TN) and multiple sclerosis (MS) are often treated with medications or a surgical procedure. However, there is little evidence that such treatments result in 50% pain reduction and improvement in quality of life. The aim of this systematic review is to evaluate the clinical effectiveness of treatments in patients with MS and trigeminal neuralgia.
METHODS
We searched Medline, EMBASE, and the Cochrane Collaboration database from inception until October 2016. Two authors independently selected studies for inclusions, data extraction, and bias assessment.
RESULTS
All studies were of low quality using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. For medical management, 10 studies were included, of which one was a randomized controlled trial. Two studies were on the use of misopropol, unique to patients with MS. For surgical therapy, 26 studies with at least 10 patients and a minimum of 2 years follow-up were included. All types of surgical procedures are reported and the results are poorer for TN with MS, with 50% having a recurrence by 2 years. The main complication was sensory loss. Many patients had to undergo further procedures to become pain free and there were no agreed prognostic factors.
CONCLUSIONS
There was insufficient evidence to support any 1 medical therapy and so earlier surgery may be preferable. A patient with TN and MS has therefore to make a decision based on low-level evidence, beginning with standard drug therapy and then choosing a surgical procedure.
Topics: Disease Management; Humans; Multiple Sclerosis; Trigeminal Neuralgia
PubMed: 29294398
DOI: 10.1016/j.wneu.2017.12.147 -
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 -
Annals of Clinical and Translational... Feb 2022Multiple sclerosis (MS) and inflammatory bowel disease (IBD) are two autoimmune diseases that seriously affect patients' quality of life. Previous studies have... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Multiple sclerosis (MS) and inflammatory bowel disease (IBD) are two autoimmune diseases that seriously affect patients' quality of life. Previous studies have established an association between MS and IBD, including Crohn's disease (CD) and ulcerative colitis (UC), but the results were inconsistent. The aim of this study was to quantify the prevalences of and the association between MS and IBD.
METHODS
The PubMed, Web of Science, and Embase databases were searched through November 2020 for studies reporting data on MS among patients with IBD and vice versa. The main outcomes were the proportion of MS in patients with IBD and vice versa, as well as the association (risk ratio [RR]) of IBD in MS and that of MS in IBD.
RESULTS
Based on the analysis of 17 studies, the prevalence of MS in patients with IBD was 0.2% (95% CI 0.1-0.4%), while the prevalence of IBD in patients with MS was 0.6% (95% CI 0.4-0.9%). Patients with MS had a higher prevalence of IBD than controls (RR = 1.53, 95% CI 1.38-1.70, p < 0.00001). There was a similarly high risk of developing CD (RR 1.41, 95% CI 1.14-1.74, p = 0.001) or UC (RR 1.42, 95% CI 1.17-1.71, p = 0.0003) in patients with MS (p for subgroup differences: 0.97). Patients with IBD had a higher prevalence of MS than controls (RR = 1.91, 95% CI 1.06-3.45, p = 0.03).
CONCLUSIONS
Clinicians should be aware of the increased risk of IBD or MS comorbidity during the diagnostic process. Systematic diagnosis and management at an earlier stage are suggested.
Topics: Comorbidity; Humans; Inflammatory Bowel Diseases; Multiple Sclerosis
PubMed: 35092169
DOI: 10.1002/acn3.51495