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Iranian Journal of Basic Medical... Sep 2017Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Riboflavin plays an important role in myelin formation, and its... (Review)
Review
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Riboflavin plays an important role in myelin formation, and its deficiency is implicated as a risk factor for multiple sclerosis. Here, we systematically reviewed the literature concerning the health benefits of riboflavin on MS. The literature recorded within four main databases, including relevant clinical trials, experimental, and case-control studies from 1976 to 2017 were considered. Both human and animal studies were included for review, with no restrictions on age, gender, or ethnicity. Experimental studies demonstrated that riboflavin deficiency triggers neurologic abnormalities related to peripheral neuropathies such as demyelinating neuropathy. Moreover, randomized controlled trials (RCT) and case-control studies in which MS patients received riboflavin supplementation or had higher dietary riboflavin intake showed improvements in neurological motor disability. Riboflavin is a cofactor of xanthine oxidase and its deficiency exacerbates low uric acid caused by high copper levels, leading to myelin degeneration. The vitamin additionally plays a significant role in the normal functioning of glutathione reductase (GR) as an antioxidant enzyme, and conditions of riboflavin deficiency lead to oxidative damage. Riboflavin promotes the gene and protein levels of brain-derived neurotrophic factor (BDNF) in the CNS of an animal model of MS, suggesting that BDNF mediates the beneficial effect of riboflavin on neurological motor disability. Research to date generally supports the role of riboflavin in MS outcomes. However, further observational and interventional studies on human populations are warranted to validate the effects of riboflavin.
PubMed: 29085589
DOI: 10.22038/IJBMS.2017.9257 -
Environmental Research May 2021Air pollution is a major public health threat. The present study is the first systematic review (SR) to determine the association of exposure to air pollution and... (Review)
Review
Air pollution is a major public health threat. The present study is the first systematic review (SR) to determine the association of exposure to air pollution and Multiple Sclerosis (MS) Progression. A Literature search was carried out using relevant keywords within several international databases. A comprehensive literature search was carried out systematically and yielded 24 eligible studies concerning the relationship of exposure to air pollution including criteria air pollutants such as particulate matter, NOx and SOx, CO, traffic noise, etc. and MS disease. The results of the included studies reveal that there was a significant relationship between exposure to air pollution and MS development and progression. Although the effect of air pollution in the pathogenesis of MS is notfully known, according to the results of the included studies exposure to polluted air can stimulate several mechanisms that act as risk factors for developing MS and for having disease relapses or neurological disability. The major potential mechanism is Dysimmune inflammatory responses subsequent oxidative stress (OS), which leads to neuroinflammation and breakdown of the normal balance between immunity and self-tolerance. Air pollutants induce and sustain chemical reactions that produce reactive oxygen species (ROSs) and nitrogen reactive species (RNSs) which can initiate inflammatory cascades via the redox-sensitive mitogen-activated protein kinase (MAPK) and NF-κB that recruit and activate neutrophils, monocytes, and dendritic cells that stimulate the adaptive immune responses such as Th1 and Th17 inflammatory responses. The uncontrolled inflammatory responses following these events cause cell death and the release of self-antigens capable of stimulating the production of auto-aggressive T-cells via enhancing antigen presentation and facilitate entry of these cells to the central nervous system. Thus, oxidative stress is the culprit in the systemic inflammation and immune imbalance development and progression, powerful risk factors in MS.
Topics: Air Pollutants; Air Pollution; Central Nervous System; Environmental Exposure; Humans; Multiple Sclerosis; Particulate Matter
PubMed: 33129851
DOI: 10.1016/j.envres.2020.110386 -
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 -
The European Journal of Neuroscience Aug 2023Mendelian randomization (MR) is a powerful approach for assessing the causal effect of putative risk factors on an outcome, using genetic variants as instrumental...
Mendelian randomization (MR) is a powerful approach for assessing the causal effect of putative risk factors on an outcome, using genetic variants as instrumental variables. The methodology and application developed in the framework of MR have been dramatically improved, taking advantage of the many public genome-wide association study (GWAS) data. The availability of summary-level data allowed to perform numerous MR studies especially for complex diseases, pinpointing modifiable exposures causally related to increased or decreased disease risk. Multiple sclerosis (MS) is a complex multifactorial disease whose aetiology involves both genetic and non-genetic risk factors and their interplay. Previous observational studies have revealed associations between candidate modifiable exposures and MS risk; although being prone to confounding, and reverse causation, these studies were unable to draw causal conclusions. MR analysis addresses the limitations of observational studies and allows to establish reliable and accurate causal conclusions. Here, we systematically reviewed the studies evaluating the causal effect, through MR, of genetic and non-genetic exposures on MS risk. Among 107 papers found, only 42 were eligible for final evaluation and qualitative synthesis. We found that, above all, low vitamin D levels and high adult body mass index (BMI) appear to be uncontested risk factors for increased MS risk.
Topics: Mendelian Randomization Analysis; Multiple Sclerosis; Humans; Causality; Risk Factors
PubMed: 37463755
DOI: 10.1111/ejn.16088 -
Journal of the Neurological Sciences Sep 2014The geographic distribution of multiple sclerosis (MS) is classically divided into three zones based on frequency that were established by Kurtzke in the early 1970s. In... (Review)
Review
BACKGROUND
The geographic distribution of multiple sclerosis (MS) is classically divided into three zones based on frequency that were established by Kurtzke in the early 1970s. In recent years, an increasing number of epidemiological studies have shown significantly higher MS prevalence and incidence rates.
OBJECTIVE
The aim of this study was to review and update the geographic distribution of MS using incidence, prevalence and disease duration from the latest epidemiology surveys.
METHODS
We conducted a systematic review of articles on MS epidemiology published between January 1, 1990 and December 31, 2012.
RESULTS
MS studies were grouped by continent: the Americas, Europe, Asia, Australia/New Zealand, and Africa. A total of 101 studies were identified according to the inclusion criteria, and 58 reported incidence estimates. Globally, the median estimated incidence of MS was 5.2 (range: 0.5-20.6) per 100,000 p-yrs, the median estimated prevalence of MS was 112.0 (with a range of 5.2-335) per 100,000 p-yrs, and the average disease duration was 20.2 years (range: 7.6-36.2).
CONCLUSION
In the past few decades, the global prevalence and incidence patterns of MS have changed dramatically. Regardless of the reason of increasing prevalence and incidence rate, we suggest the need for a novel classification system based on global MS disease burden. Adopting such a system would improve economic efficiency and prioritization in health policy planning for MS.
Topics: Female; Global Health; Humans; Incidence; Male; Multiple Sclerosis; Prevalence; Retrospective Studies
PubMed: 25062946
DOI: 10.1016/j.jns.2014.06.051 -
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 -
European Journal of Neurology Aug 2023Treatment options for chronic inflammatory demyelinating polyneuropathy (CIDP) are intravenous immunoglobulin, plasmapheresis, corticosteroids and immunosuppressive... (Meta-Analysis)
Meta-Analysis Review
Efficacy of hematopoietic stem cell transplantation treatment in refractory chronic inflammatory demyelinating polyradiculoneuropathy: a systematic review and meta-analysis.
BACKGROUND AND PURPOSE
Treatment options for chronic inflammatory demyelinating polyneuropathy (CIDP) are intravenous immunoglobulin, plasmapheresis, corticosteroids and immunosuppressive drugs. However, a substantial proportion of patients with CIDP remain refractory to treatment and develop severe functional disability. A systematic review and a meta-analysis of the efficacy of hematopoietic stem cell transplantation (HSCT) treatment in refractory CIDP patients was performed.
METHODS
The study is based on queries in the PubMed, Cochrane Central Register of Controlled Trials, Embase, Web of Science and clinicaltrials.gov databases on 4 December 2022. Articles that met our eligibility criteria were included after screening. Patients' characteristics, treatment regime and outcome measures were extracted.
RESULTS
Eighty-nine patients in 11 studies were included. The pooled estimate of responsiveness amongst the four included studies was 87.04% (95% confidence interval 66.7%-99.5%) and the pooled estimate of freedom of all immune modulating or suppressive drugs was 80.75% (95% confidence interval 71.2%-90.2%).
CONCLUSION
This meta-analysis and systematic review suggested that HSCT can be effective in the treatment of refractory CIDP. Whilst there are risks involved, HSCT may be a beneficial and viable therapy for refractory CIDP when carefully evaluated.
Topics: Humans; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Immunoglobulins, Intravenous; Immunosuppressive Agents; Adrenal Cortex Hormones; Hematopoietic Stem Cell Transplantation
PubMed: 37170791
DOI: 10.1111/ene.15857 -
Reviews in the Neurosciences Aug 2021Multiple sclerosis (MS) is a neurodegenerative disease associated with inflammatory demyelination and astroglial activation, with neuronal and axonal damage as the... (Meta-Analysis)
Meta-Analysis
Multiple sclerosis (MS) is a neurodegenerative disease associated with inflammatory demyelination and astroglial activation, with neuronal and axonal damage as the leading factors of disability. We aimed to perform a meta-analysis to determine changes in CSF levels of neuronal and glial biomarkers, including neurofilament light chain (NFL), total tau (t-tau), chitinase-3-like protein 1 (CHI3L1), glial fibrillary acidic protein (GFAP), and S100B in various groups of MS (MS versus controls, clinically isolated syndrome (CIS) versus controls, CIS versus MS, relapsing-remitting MS (RRMS) versus progressive MS (PMS), and MS in relapse versus remission. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we included 64 articles in the meta-analysis, including 4071 subjects. For investigation of sources of heterogeneity, subgroup analysis, meta-regression, and sensitivity analysis were conducted. Meta-analyses were performed for comparisons including at least three individual datasets. NFL, GFAP, t-tau, CHI3L1, and S100B were higher in MS and NFL, t-tau, and CHI3L1 were also elevated in CIS patients than controls. CHI3L1 was the only marker with higher levels in MS than CIS. GFAP levels were higher in PMS versus RRMS, and NFL, t-tau, and CHI3L1 did not differ between different subtypes. Only levels of NFL were higher in patients in relapse than remission. Meta-regression showed influence of sex and disease severity on NFL and t-tau levels, respectively and disease duration on both. Added to the role of these biomarkers in determining prognosis and treatment response, to conclude, they may serve in diagnosis of MS and distinguishing different subtypes.
Topics: Biomarkers; Humans; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Neurodegenerative Diseases; Neuroglia
PubMed: 33594840
DOI: 10.1515/revneuro-2020-0145 -
Journal of Psychosomatic Research Sep 2022Adverse Childhood Experiences (ACEs), such as physical, emotional, and sexual abuse trigger inflammatory changes and have been associated with many causes of morbidity... (Review)
Review
OBJECTIVE
Adverse Childhood Experiences (ACEs), such as physical, emotional, and sexual abuse trigger inflammatory changes and have been associated with many causes of morbidity and mortality, including autoimmune diseases. Although Multiple Sclerosis (MS) is a debilitating neurological autoimmune disease, literature linking ACEs and MS is understudied. The aim of this review was to examine the 1) state of the literature, and 2) relationships between childhood adversity and the prevalence and physical clinical features of MS (e.g., age at onset, relapses, pain, fatigue, disability).
METHODS
A comprehensive search was preformed through five databases and by hand using the ancestry and descendancy approach for connections to papers published through January 20th, 2022. Studies were screened by independent reviewers using Rayyan.ai, and critically appraised for both quality and reporting transparency.
RESULTS
Twelve studies examined relationships between any ACE(s) and the prevalence or physical clinical features of MS. There was considerable variance in the measurement of stressors, confounders, and categorization of MS; however most studies (n = 10) demonstrated an association between ACEs and MS (alone or grouped with other similar diagnoses), or physical clinical features.
CONCLUSION
Although there are few studies in this area, it is of quickly growing interest. These results should be cautiously interpreted, yet highlight the need for continued work to disentangle and discern true associations.
Topics: Adverse Childhood Experiences; Age of Onset; Child; Child Abuse; Humans; Multiple Sclerosis; Prevalence
PubMed: 35779440
DOI: 10.1016/j.jpsychores.2022.110981 -
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