Physical trauma and risk of multiple sclerosis: A systematic review and meta-analysis of observational studies

BackgroundWe aimed to examine physical trauma as a risk factor for the subsequent diagnosis of MS.MethodsWe searched for observational studies that evaluated the risk for developing MS after physical trauma that occurred in childhood (≤ 20 years) or “premorbid” (> 20 years). We performed a meta-analysis using a random effects model.ResultsWe identified 1362 individual studies, of which 36 case–control studies and 4 cohort studies met the inclusion criteria for the review. In high quality case–control studies, there were statistically significant associations between those sustaining head trauma in childhood (OR = 1.27; 95% CI, 1.12–1.44; p < 0.001), premorbid head trauma (OR = 1.40; 95% CI, 1.08–1.81; p = 0.01), and other traumas during childhood (OR = 2.31; 95% CI, 1.06–5.04; p = 0.04) and the risk of being diagnosed with MS. In lesser quality studies, there was a statistical association between “other traumas” premorbid and spinal injury premorbid. No association was found between spinal injury during childhood, or fractures and burns at any age and the diagnosis of MS. The pooled OR of four cohort studies looking at premorbid head trauma was not statistically significant.ConclusionsThe result of the meta-analyses of high quality case–control studies suggests a statistically significant association between premorbid head trauma and the risk for developing MS. However, cohort studies did not. Future prospective studies that define trauma based on validated instruments, and include frequency of traumas per study participant, are needed.     

Oral and intravenous steroids for multiple sclerosis relapse: a systematic review and meta-analysis

Glucocorticoids are the standard of care for multiple sclerosis (MS) relapses, but the most desirable route of administration is still matter of debate. The aim of the study was to compare the efficacy and safety of oral versus intravenous steroids for treatment of acute relapses in patients with MS. Randomized or quasi-randomized, parallel group trials with direct comparison between oral and intravenous steroid treatment in MS patients with acute relapse were identified through a systematic literature search. Six trials were included involving 419 participants, 210 for oral, and 209 for intravenous groups, respectively. The weighted mean differences (WMDs) in the Kurtzke’s Expanded Disability Status Scale (EDSS) score reduction between the oral and intravenous groups were 0.32 [(?0.09 to 0.73); p = 0.129] and 0.11 [(?0.12 to 0.33); p = 0.355] at 1 and 4 weeks after treatment, respectively. The risk ratios (RRs) for improvement by at least one EDSS point were 0.79 [(0.37–1.68); p = 0.539] at week 1 and 0.92 (0.76–1.12); p = 0.400] at week 4. There were no differences in the relapse rate and relapse freedom at 6 months between groups. The WMDs in the mean percentage reduction of Gadolinium-enhancing lesions between oral and intravenous arms were 0.14 (?0.02, 0.29); p = 0.083] and 0.04 (?0.19, 0.28); p = 0.705] at 1 and 4 weeks from treatment. Among the adverse events, insomnia was significantly associated with the oral route of steroid administration [RR 1.25 (1.07–1.46); p = 0.005]. In adult patients with acute MS relapse, there were no clear-cut differences in the efficacy and overall tolerability between oral and intravenous steroids.     

Prevalence of multiple sclerosis (MS) in Iran: a systematic review and meta-analysis

Neurological Sciences - Prevalence of multiple sclerosis (MS) is increasing world-wide. Iran is not exception. As the prevalence reported differently in various provinces, we designed this...     

Vaccines and multiple sclerosis: a systematic review

Vaccinations are often the most effective tool against some disease known to mankind. This study offers a literature review on the role of vaccines regarding the risk of developing multiple sclerosis (MS) and MS relapse. The method used in this study is a systematic literature review on the database PubMed. The study found no change in risk of developing multiple sclerosis (MS) after vaccination against hepatitis B virus, human papillomavirus, seasonal influenza, measles–mumps–rubella, variola, tetanus, Bacillus Calmette-Guérin (BCG), polio, or diphtheria. No change in risk of relapse was found for influenza. Further research is needed for the potential therapeutic use of the BCG vaccine in patients in risk of developing MS and for the preventive potential of the tetanus and diphtheria vaccine.     

Risk factors for unprovoked epileptic seizures in multiple sclerosis: a systematic review and meta-analysis

The role of different factors in influencing the risk of seizures during multiple sclerosis (MS) is not known. To perform a systematic review and meta-analysis of risk factors for epilepsy during MS. Pubmed, Google scholar, and Scopus databases were searched. Articles published in English (1986–2016) were included. Nine studies were included (3 retrospective cohort and 6 case–control) enrolling 2845 MS patients (217 with epilepsy; 7.6%). MS patients with epilepsy had a younger age at onset compared to MS patients without seizures (difference in means = ?5.42 years, 95% CI ?7.19 to ?3.66, p < 0.001). Mean EDSS value at inclusion tended to be higher in patients with epilepsy, without reaching statistical significance (difference in means = 0.45, 95% CI ?0.01 to 0.91, p = 0.054). No differences were observed in sex distribution (OR = 0.94, 95% CI 0.51–1.72, p = 0.83) and clinical form (OR = 1.03, 95% CI 0.33–3.21, p = 0.96). Two studies evaluated presence and number of cortical lesions as a risk factor for epilepsy in MS using different MRI techniques: in one study, cortical lesions were more frequently observed in patients with epilepsy (OR = 7.06, 95% CI 2.39–20.8; p < 0.001). In the other, cortico-juxtacortical lesions were more frequently observed in patients with epilepsy (OR = 2.6, 95% CI 1.0–6.5; p = 0.047). Studies about risk factors for epilepsy during MS are heterogeneous. Compared to MS patients without seizures, patients with epilepsy have an earlier MS onset and a higher EDSS score after similar disease duration. Clinical form of MS and sex do not predict the appearance of seizures.     

Association between VDR polymorphisms and multiple sclerosis: systematic review and updated meta-analysis of case-control studies

Vitamin D receptor (VDR) polymorphisms have been inconsistently investigated in multiple sclerosis (MS). However, published studies demonstrated differences concerning design and effect size. A meta-analysis is necessary to determine the magnitude of the association between VDR polymorphisms and MS risk. The aim of the current study was to quantify the magnitude of the association between BsmI, FokI, ApaI, and TaqI VDR polymorphisms and MS risk. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic search and meta-analysis of the VDR gene polymorphisms and the risk of MS. The pooled odds ratios (OR) and 95% confidence interval (CI) were calculated by using Stata Version 11.0 with dominant and recessive models and allele analyses. A total of 4013 cases and 4218 controls in 24 case-control studies were included in the meta-analyses. The results did not indicate an association between any of the VDR polymorphisms and the risk of MS among overall populations, Asians, and Caucasians. However, our subgroup analysis suggests that the A allele was associated with MS risk in Asian populations (P = 0.005, OR = 1.267, 95% CI 1.074–1.496). Interestingly, the sensitivity analysis excluding studies with controls not in HWE showed insignificant association between the A allele and MS risk (P = 0.211), which was different from those in the non-sensitivity analysis. Our preliminary results indicate the VDR gene ApaI, BsmI, FokI, and TaqI polymorphisms may not be associated with elevated MS risk among overall populations. But ApaI polymorphism may confer different susceptibility to MS among different populations, and more well-designed studies with a large sample size are still needed to validate our results.     

Autoimmune disease in people with multiple sclerosis and their relatives: a systematic review and meta-analysis

Additional autoimmune diseases in people with multiple sclerosis (MS) and their relatives have been studied many times. Studies have employed different designs, and yielded conflicting results. We performed a systematic review, and calculated overall risk of additional autoimmune diseases in people with MS and their first-degree relatives. PubMed and Web of Science were searched. Thyroid disease, diabetes, inflammatory bowel disease, psoriasis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) were studied. A generic inverse variance model was used, and subgroup analysis was used to explore heterogeneity. The OR of thyroid disease was increased in both people with MS (OR 1.66; p < 0.00001) and their relatives (OR 2.38; p < 0.00001). A similar association was seen between MS and inflammatory bowel disease (OR 1.56; p < 0.0001) and psoriasis (OR 1.31; p < 0.0001), although not in relatives. There was no increase in the rate of either SLE or RA. Studies examining diabetes showed significant heterogeneity and evidence of publication bias. There is an increase in the rate of certain autoimmune diseases in people with MS and their first-degree relatives. However, this does not extend to all conditions studied. Given the nonspecific clinical presentation of thyroid disease, it should be considered in all people with MS presenting with nonspecific symptoms.     

The prevalence of migraine in multiple sclerosis (MS): A systematic review and meta-analysis

ObjectivesWe designed this systematic review to estimate pooled prevalence of migraine in patients with multiple sclerosis (MS).MethodsWe searched PubMed, Scopus, EMBASE, CINAHL, Web of Science, google scholar and gray literature including references from identified studies, conference abstracts which were published up to December 2019.The search strategy included the MeSH and text words as ((Disorder, Migraine OR Disorders, Migraine Disorder OR Migraine OR Migraines, OR Migraine Headache OR Migraine Headaches) AND (Multiple Sclerosis OR Sclerosis, Multiple) OR Sclerosis, Disseminated) OR Disseminated Sclerosis) OR MS (Multiple Sclerosis)) OR Multiple Sclerosis, Acute Fulminating).ResultsThe literature search found 2100 articles. After eliminating duplicates, 1500 articles remained. Eleven articles and twelve abstract conference papers were included for final analysis.A total of 11,372 MS cases and 2627 MS patients with migraine included in the analysis. The prevalence of migraine ranged from 2% to 67%.The pooled prevalence of migraine in included studies was 31% (95%CI: 22%–40%) (I² = 99.3%, p < 0.001). The pooled prevalence of migraine in different continents were significantly different (p < 0.001).The pooled prevalence was 24% in Asian countries, 43% in American countries, 25% in European countries and 43% in African countries.ConclusionThe results of this systematic review shows that the prevalence of migraine in MS patients is 31% while the prevalence differs significantly among residents of different continents.     

Exercise therapy and multiple sclerosis: a systematic review

Multiple sclerosis (MS) is an incurable disease, and despite current pharmacologic treatment being effective in reducing relapse rates and lesion burden, there is little evidence that these treatments work as effectively in preventing disability progression. In such cases, non-pharmacologic techniques such as exercise therapy with rehabilitation purposes may play an important role. This systematic review of randomised controlled trials (RCTs) aims at investigating the effects of exercise therapy in MS patients. The electronic database PubMed was searched for studies indexed between February 2004 and June 2012. Studies eligibility criteria included: clinical diagnosis of MS free of exacerbation; and intervention with exercise therapy, measured as activities of daily living (ADL). Two reviewers independently screened the titles and abstracts of the references retrieved. The methodological quality of the RCTs was assessed using the Physiotherapy Evidence Database scale (PEDro scale). The PubMed search resulted in a total of 72 articles, 11 of which were included in this review. The analysis included 591 participants, of which 358 (60.6 %) were women. Patients had a mean age between 37.1 and 54.6 years. Duration of MS since diagnosis was reported in nine of the 11 studies and varied between 5.2 and 15.9 years. According to PEDro scale, nine of the 11 included studies were considered to be of high methodological quality, with scores ranging from 7 to 10. In eight of the 11 included studies, the effectiveness of exercise therapy was compared to standard care, in two it was compared to those on a waiting list, and in one, to control treatment. The results of this review suggest that exercise therapy may have a beneficial effect in patients with MS, and therefore may be recommended for the rehabilitation of these patients.     

Enlarged perivascular spaces in multiple sclerosis on magnetic resonance imaging: a systematic review and meta-analysis

Journal of Neurology - Perivascular spaces can become detectable on magnetic resonance imaging (MRI) upon enlargement, referred to as enlarged perivascular spaces (EPVS) or Virchow-Robin spaces....     

A systematic review of several potential non-genetic risk factors for multiple sclerosis

We reviewed the literature published in the English language to determine the weight of evidence for several potential non-genetic risk factors for multiple sclerosis, including solar ultraviolet radiation (UVR), sex hormones and dietary fat/fatty acids. We ranked the plausibility of each factor and graded the methodological rigour of case-control and cohort studies to determine whether there was a sufficient number of high-quality studies to weigh the evidence. Based on our criteria, the plausibility for solar UVR and sex hormones is good and fair for dietary fat/fatty acids. However, the body of epidemiologic evidence is insufficient for these three sets of risk factors. We did not find a sufficient number of methodologically rigorous studies to weigh the evidence for any of the potential risk factors we examined.     

Infectious mononucleosis and risk for multiple sclerosis: a meta-analysis

OBJECTIVE: To characterize the association between infectious mononucleosis (IM), a frequent clinical manifestation of primary Epstein-Barr virus infection after childhood, and the risk for multiple sclerosis (MS). METHODS: We conducted a systematic review and meta-analysis of case-control and cohort studies of IM and MS. RESULTS: The combined relative risk of MS after IM from 14 studies was 2.3 (95% confidence interval, 1.7-3.0; p < 10(-8)). Potential sources of heterogeneity (ie, study design, MS definition, and latitude) barely influenced our results. INTERPRETATION: We conclude that Epstein-Barr virus infection manifesting as IM in adolescents and young adults is a risk factor for MS.     

Perampanel for amyotrophic lateral sclerosis: A systematic review and meta-analysis

Neurological Sciences - Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease. There is still no established cost-effective treatment that can improve functional...     

Prevalence of depression in multiple sclerosis: a review and meta-analysis

INTRODUCTION: The aim of this paper was to review and summarize the data about the frequency of depression during multiple sclerosis (MS). MATERIAL AND METHODS: We performed a metaanalysis to combine the results of the studies which compared the frequency of depression in MS patients with the prevalence in patients with other chronic diseases. Eight controlled studies were identified via manual and computerized search of the Medline and PsychInfo databases. Given the various ways these studies reported their results, we used statistical procedures based on the combination of significance levels (the method of adding Zs and the method of adding ts). An additional statistical procedure, Cohen's d, was performed to estimate the effect of size. RESULTS: The two statistical methods yielded highly significant summary statistics: z=4.15 and z=3.98, respectively (p<0.0001). The effect of size (Cohen's d), which ranged from 0.02 to 0.70 with an average of 0.29 (95 percent confidence interval: 0.09-0.49), can be considered as medium and hence clinically meaningful. CONCLUSION: These results suggest that the association between MS and depression is specific, that is not just casual nor due to the nonspecific factors inherent in every chronic disease.