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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 -
Journal of Neurology, Neurosurgery, and... May 2021Pregnancy largely affects disease activity and clinical course in women with immune-mediated neurological disorders. Chronic inflammatory demyelinating polyneuropathy... (Review)
Review
Pregnancy largely affects disease activity and clinical course in women with immune-mediated neurological disorders. Chronic inflammatory demyelinating polyneuropathy (CIDP) is rare but the most common chronic immune-mediated neuropathy; however, the effects of pregnancy on CIDP have never been investigated except case reports or series. We here provide a systematic review of the literature from 1 January 1969 to 30 June 2020 that revealed 24 women with CIDP, who had onset or relapse during pregnancy. Of these, 17 (71%) developed CIDP during the first pregnancy, and 8 (47%) had a relapse during subsequent pregnancies. Of the 17 patients, in whom the CIDP subtypes were determined, all of them had typical CIDP. First-line treatments for CIDP, such as corticosteroids, immunoglobulin and plasma exchange were efficacious and safe. We suggest that pregnancy can trigger typical CIDP in some women, and women with CIDP have a higher risk of relapse during pregnancy. The onset or relapse of CIDP during pregnancy is a rare but challenging constellation for physicians.
Topics: Adrenal Cortex Hormones; Female; Humans; Immunoglobulins, Intravenous; Plasma Exchange; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Pregnancy; Pregnancy Complications; Treatment Outcome
PubMed: 33563801
DOI: 10.1136/jnnp-2020-325321 -
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 -
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 -
Neurological Sciences : Official... Jun 2023Neuromyelitis optica spectrum disorder (NMOSD) is a progressive demyelinating disease of the central nervous system that has overlapping symptoms with multiple sclerosis... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neuromyelitis optica spectrum disorder (NMOSD) is a progressive demyelinating disease of the central nervous system that has overlapping symptoms with multiple sclerosis (MS) but differs from it in a variety of ways. Previous studies have reported conflicting results trying to estimate the number of individuals affected by them which is why we designed this systematic review and meta-analysis to estimate the worldwide prevalence and incidence of NMOSD/NMO based on current evidence.
METHODS
We searched PubMed, Scopus, EMBASE, Web of Science, and gray literature including references from the identified studies, review studies, and conference abstracts which were published up to February 1, 2022. We used all MeSH terms pertaining to "NMOSD," "NMO," and all the terms on "prevalence," "incidence," and "epidemiology" to identify the search components. Pooled effect sizes were measured using random-effect model by DerSimonian-Laird.
RESULTS
The prevalence and incidence rates of NMOSD/NMO ranged from 0.07 to 10 and 0.029 to 0.880 per 100,000 population, respectively. The overall pooled prevalence of NMO per 100,000 population was 1.54 (I: 98.4%, 95% CI: 1.13-1.96, P< 0.001) based on the 2006 criteria, 1.51 (I: 99.4%, 95% CI: 1.21-1.81, P < 0.001) based on the 2015 criteria and 2.16 (I: 89.4%, 95% CI: 1.46-2.86, P < 0.001) based on the 2006/2015 criteria. The overall annual incidence of NMO per 100,000 population was 0.155 (I: 95%, 95% CI: 0.115-0.195, P < 0.001) based on the 2006 criteria and 0.278 (I: 100%, 95% CI: 0.135-0.420, P < 0.001) based on the 2015 criteria. The prevalence rates were highest in French West Indies and South Korea, and lowest in Cuba and Australia, based on the 2006 and 2015 criteria, respectively. Also, the highest annual incidence rates were obtained for Sweden and Slovak republic and the lowest for Cuba and Australia based on the 2006 and 2015 criteria, respectively. All estimated rates were higher among females compared to males.
CONCLUSION
Although rare, NMOSD/NMO impact affected individuals in devastating ways. Several large-scale prospective studies are required to reach a comprehension of the epidemiological aspects of these notorious demyelinating conditions.
Topics: Male; Female; Humans; Neuromyelitis Optica; Prevalence; Multiple Sclerosis; Central Nervous System; Incidence
PubMed: 36745300
DOI: 10.1007/s10072-023-06617-y -
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 -
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 -
Multiple Sclerosis and Related Disorders Sep 2021Multiple sclerosis (MS) is an inflammatory demyelinating CNS disease and the most common neurological immune-mediated disorder. Due to its progressive format, it affects... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple sclerosis (MS) is an inflammatory demyelinating CNS disease and the most common neurological immune-mediated disorder. Due to its progressive format, it affects patients' quality of life (QoL) significantly. This study aimed to evaluate epidemiologic parameters of MS in the Asia and Oceania continents.
METHODS
A comprehensive literature search on October 1st, 2020, was performed in PubMed, Scopus, and Web of Science to retrieve original population-based studies on MS epidemiology in the Asian and Oceanian countries, published between January 1st, 1985 and October 1st, 2020. The designed search strategy was repeated for each country, and the relevant referenced articles were added to our database. A random-effect model was used to combine the epidemiological estimates, and subgroup analysis was also performed by continent, region, and country, when possible. Meta-regression analysis was done to evaluate the effects of Human Developmental Index (HDI), latitude, and study period on the epidemiologic parameters.
RESULTS
A total of 3,109 publications were found, of which 89 articles met the eligibility criteria and were included for data extraction. These articles provided data on prevalence, incidence, and mean age at disease onset in 18 countries in Asia and Oceania, including Iran, Turkey, Cyprus, Kuwait, Saudi Arabia, Qatar, UAE, Jordan, Israel, India, Malaysia, China, Hong Kong, Taiwan, Republic of Korea, Japan, Australia, and New Zealand. The pooled total prevalence, incidence, and mean age of onset in Asia and Oceania were 37.89/100000 (95% CI: 35.65 - 40.142), 2.40/100000 (95% CI: 2.22 - 2.58), and 28.21 (95% CI: 27.55 - 28.88), respectively. MS prevalence and incidence in the female gender (68.7/100000 and 4.42/100000, respectively) were infinitely higher than in the male gender (24.52/100000 and 2.06/100000, respectively). Our subgroup analysis showed that MS was much more prevalent in Australia and West Asia among the studied area. The meta-regression showed that the total incidence decreased with an increase in the HDI, and the total prevalence in Asia increased with increasing latitude gradients. Also, the study period had a positive effect on the total prevalence and incidence in Asia and Oceania.
CONCLUSION
MS prevalence and incidence have increased in recent decades. This study highlights the need for further studies to elucidate MS's geographical and temporal variations' exact etiologies.
Topics: Asia; Female; Humans; Incidence; Male; Multiple Sclerosis; Oceania; Quality of Life
PubMed: 34247103
DOI: 10.1016/j.msard.2021.103119 -
Acta Neurologica Scandinavica Apr 2022Management of multiple sclerosis (MS) may comprise clinical interventions and self-management strategies, including complementary therapies and modifiable lifestyle... (Review)
Review
Management of multiple sclerosis (MS) may comprise clinical interventions and self-management strategies, including complementary therapies and modifiable lifestyle factors such as exercise and smoking cessation. Lifestyle modifications and complementary therapies with proven safety and efficacy are essential as part of best-practice MS management, especially when faced with limited access to healthcare services. However, it is unclear to what extent MS clinical practice guidelines and consensus statements address these strategies. A systematic review was conducted, wherein MEDLINE, EMBASE, PsycINFO, CINAHL, Scopus, Web of Science, guideline databases and developer sites were searched for guidelines and consensus statements that addressed lifestyle modifications and complementary therapies of interest. Two researchers independently screened articles, extracted data and assessed guideline quality using the Appraisal of Guidelines for Research and Evaluation version II. Thirty-one guidelines and consensus statements were included. Quality was high for 'clarity of presentation' (77%) and 'scope and purpose' (73%), moderate for 'stakeholder development' (56%), 'rigour of development' (48%) and 'editorial independence' (47%), and low for 'applicability' (29%). Two guidelines, related to physical activity and exercise, mindfulness, smoking cessation, and vitamin D and polyunsaturated fatty acid supplementation, scored high in all domains. These guidelines were two of only four guidelines intended for use by people with MS. High-quality guidelines and consensus statements to guide lifestyle modifications and complementary therapies in MS management are limited. Our findings indicate the need for more guidelines intended for use by people with MS, and a further focus on implementation resources.
Topics: Complementary Therapies; Consensus; Humans; Life Style; Multiple Sclerosis; Smoking Cessation
PubMed: 35037722
DOI: 10.1111/ane.13574 -
Reviews on Environmental Health Dec 2021Some studies have shown that environmental risk factors, including air pollution, might be related to the incidence or recurrence of multiple sclerosis (MS). This... (Review)
Review
OBJECTIVES
Some studies have shown that environmental risk factors, including air pollution, might be related to the incidence or recurrence of multiple sclerosis (MS). This systematic review was conducted to investigate the relation between air pollution and MS.
METHODS
A systematic search was conducted in PubMed, Scopus, Science Direct, Embase, and Web of Science; until January 2020 with no restrictions. The search strategy was conducted with air pollution key words such as CO, PM, PM, SO, and NO, for exposure and the key word "Multiple sclerosis" as the outcome.
RESULTS
Eventually, after applying the inclusion and exclusion criteria, 17 articles were included. The methodologies and outcomes reported were heterogeneous and different metrics had been used in the results; therefore conducting a meta-analysis was not possible. Eight studies had analyzed the relation between particulate matter (PM) and the prevalence or relapse of MS and had observed a significant relation. NO and NOx were associated with recurrence or prevalence of MS in three studies. But, in three cohort studies, no association was observed between air pollution and recurrence or occurrence of MS.
CONCLUSIONS
The results of this systematic review show that outdoor air pollution, especially PM and nitrogen oxides might be related to the prevalence or relapse of MS.
Topics: Air Pollutants; Air Pollution; Environmental Exposure; Humans; Multiple Sclerosis; Particulate Matter
PubMed: 34821118
DOI: 10.1515/reveh-2020-0079