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In this prospective population-based cohort study, in a cohort largely on immunomodulatory therapy, higher 25-OH-D levels were associated with a reduced hazard of relapse. This occurred in a dose-dependent linear fashion, with each 10 nmol/l increase in 25-OH-D resulting in up to a 12% reduction in risk of relapse. Clinically, raising 25-OH-D levels by 50 nmol/l could halve the hazard of a relapse.

ObjectiveTo generate a national multiple sclerosis (MS) prevalence estimate for the United States by applying a validated algorithm to multiple administrative health claims (AHC) datasets.MethodsA validated algorithm was applied to private, military, and public AHC datasets to identify adult cases of MS between 2008 and 2010. In each dataset, we determined the 3-year cumulative prevalence overall and stratified by age, sex, and census region. We applied insurance-specific and stratum-specific estimates to the 2010 US Census data and pooled the findings to calculate the 2010 prevalence of MS in the United States cumulated over 3 years. We also estimated the 2010 prevalence cumulated over 10 years using 2 models and extrapolated our estimate to 2017.ResultsThe estimated 2010 prevalence of MS in the US adult population cumulated over 10 years was 309.2 per 100,000 (95% confidence interval [CI] 308.1–310.1), representing 727,344 cases. During the same time period, the MS prevalence was 450.1 per 100,000 (95% CI 448.1–451.6) for women and 159.7 (95% CI 158.7–160.6) for men (female:male ratio 2.8). The estimated 2010 prevalence of MS was highest in the 55- to 64-year age group. A US north-south decreasing prevalence gradient was identified. The estimated MS prevalence is also presented for 2017.ConclusionThe estimated US national MS prevalence for 2010 is the highest reported to date and provides evidence that the north-south gradient persists. Our rigorous algorithm-based approach to estimating prevalence is efficient and has the potential to be used for other chronic neurologic conditions.

Background Alterations in the gut microbial community composition maybe influential in neurological disease. Microbial community profiles were compared between early onset pediatric multiple sclerosis (MS) and control children similar for age and sex. Methods Children ≤18 years old within two years of MS onset, or controls without autoimmune disorders attending a University of California, San Francisco, USA pediatric clinic were examined for fecal bacterial community composition and predicted function by 16S ribosomal RNA sequencing and Phylogenetic Reconstruction of Unobserved States (PICRUST) analysis. Associations between subject characteristics and the microbiota, including beta diversity and taxa abundance were identified using non-parametric tests, permutational multivariate analysis of variance and negative binomial regression. Results Eighteen relapsing-remitting MS cases and 17 controls (mean age 13 years; range 4-18) were studied. Cases had a short disease duration (mean=11 months; range 2-24) and half were immunomodulatory (IMD) drug naïve. While overall gut bacterial beta diversity was not significantly related to MS status, IMD exposure was (Canberra, p<0.02). However relative to controls, MS cases had a significant enrichment in relative abundance for members of the Desulfovibrionaceae (Bilophila, Desulfovibrio and Christensenellaceae) and depletion in Lachnospiraceae and Ruminococcaceae (all p and q<0.000005). Microbial genes predicted as enriched in MS vs. controls included those involved in glutathione metabolism (Mann-Whitney, p=0.017); findings that were consistent regardless of IMD exposure. Conclusions In recent onset pediatric MS, perturbations in the gut microbiome composition were observed, in parallel with predicted enrichment of metabolic pathways associated with neurodegeneration. Findings were suggestive of a pro-inflammatory milieu.

Almost half the cells and 1% of the unique genes found in our bodies are human, the rest are from microbes, predominantly bacteria, archaea, fungi, and viruses. These microorganisms collectively form the human microbiota, with most colonizing the gut. Recent technological advances, open access data libraries, and application of high-throughput sequencing have allowed these microbes to be identified and their contribution to neurological health to be examined. Emerging evidence links perturbations in the gut microbiota to neurological disease, including disease risk, activity, and progression. This review provides an overview of the recent advances in microbiome research in relation to neuro(auto)immune and neurodegenerative conditions affecting humans, such as multiple sclerosis, neuromyelitis optica spectrum disorders, Parkinson disease, Alzheimer disease, Huntington disease, and amyotrophic lateral sclerosis. Study design and terminology used in this rapidly evolving, highly multidisciplinary field are summarized to empower and engage the neurology community in this "newly discovered organ." Ann Neurol 2017;81:369-382.

Disability progression in multiple sclerosis (MS) accrued more slowly than found in earlier longitudinal studies. The authors also challenged two fundamental concepts in MS, demonstrating that neither male sex nor older onset age was associated with worse disease outcome.

ULTIPLE SCLEROSIS (MS) IS a chronic disease that often affects people in the prime of their lives. A key feature of MS is clinical progression of the disease over time manifested by the accumulation of disability. Interferon beta drugs are the most widely prescribed disease-modifying drugs (DMDs) approved by the US Food and Drug Administration for the treatment of relapsing-onset MS, the most common MS disease course. Although a substantial reduction in brain lesion development, as evidenced by magnetic resonance imaging (MRI), 1 and a one-third relative reduction in relapse frequency were demonstrated in the pivotal clinical trials of interferon beta for relapsing-remitting MS, 2 there is a lack of well-controlled longitudinal studies investigating the effect of in-terferon beta on disability progression. Typically, drug efficacy (as established through randomized clinical trials conducted under optimal conditions) is greater than drug effectiveness (as measured in "real-world" settings). 3 Patients participating in clinical trials tend to be highly selected in For editorial comment see p 290.

A retrospective chart review of patients in British Columbia with multiple sclerosis prescribed beta-interferon (IFNbeta) between 1995 and 2001 was carried out to investigate reasons for the interruption of therapy. The highest proportion of interruptions (76/281; 27%) occurred in the first 6 months. The single most common reason was perceived lack of efficacy, cited by 84 of 281 (30%). Gender, disability, and disease duration were identified as factors influencing interruption of IFNbeta therapy.