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Background and purpose Ethnicity-related differences in the incidence of acute disseminated encephalomyelitis ( ADEM) and other demyelinating diseases including multiple sclerosis and neuromyelitis optica spectrum disorders have been reported. Little is reported on the influence of ethnicity and geographical location in ADEM. Methods Medical records of patients who presented with ADEM ( ICD-9 323.61 and 323.81) at large referral hospitals in China, Singapore and Japan (years 1992-2015) were retrospectively reviewed and data were collected in a centralized database. Presenting features and outcomes of ADEM were compared between this multi-country Asian cohort and a uniformly collected US cohort using risk differences and risk ratios. Both cohorts were standardized to a 35% pediatric population to facilitate the comparison. Results There were 83 Asian patients (48 male, 16 pediatric) followed for a median of 2 (25th-75th percentile 1-10) months. Asian patients exhibited a 26% higher prevalence of spinal cord involvement on magnetic resonance imaging [95% confidence interval (CI) 0-52%; P = 0.05; 63% vs. 37%], a 39% lower prevalence of preceding events (95% CI 12-65%; P < 0.01; 33% vs. 72%) and a 23% lower prevalence of corpus callosum involvement (95% CI 7-39%; P < 0.01; 8% vs. 31%). No difference was observed between the two cohorts in the probability of relapse over the first year after disease onset. Conclusions It is hypothesized that the high proportion of Asian patients with spinal cord lesions relates to genetic vulnerability or the higher incidence of neuromyelitis optica spectrum disorders in Asia or could be a spurious association. ADEM presentations most probably vary across geographical settings or ethnicities. [ABSTRACT FROM AUTHOR]

Background and Objectives: This study aims to determine the contributions of sun exposure and ultraviolet radiation (UVR) exposure to risk of pediatric-onset multiple sclerosis (MS)., Methods: Children with MS and controls recruited from multiple centers in the United States were matched on sex and age. Multivariable conditional logistic regression was used to investigate the association of time spent outdoors daily in summer, use of sun protection, and ambient summer UVR dose in the year before birth and the year before diagnosis with MS risk, with adjustment for sex, age, race, birth season, child's skin color, mother's education, tobacco smoke exposure, being overweight, and Epstein-Barr virus infection., Results: Three hundred thirty-two children with MS (median disease duration 7.3 months) and 534 controls were included after matching on sex and age. In a fully adjusted model, compared to spending <30 minutes outdoors daily during the most recent summer, greater time spent outdoors was associated with a marked reduction in the odds of developing MS, with evidence of dose-response (30 minutes-1 hour: adjusted odds ratio [AOR] 0.48, 95% confidence interval [CI] 0.23-0.99, p = 0.05; 1-2 hours: AOR 0.19, 95% CI 0.09-0.40, p < 0.001). Higher summer ambient UVR dose was also protective for MS (AOR 0.76 per 1 kJ/m 2 , 95% CI 0.62-0.94, p = 0.01)., Discussion: If this is a causal association, spending more time in the sun during summer may be strongly protective against developing pediatric MS, as well as residing in a sunnier location., (© 2021 American Academy of Neurology.)

Objective: To characterize disease severity and distribution of disability in pediatric-onset multiple sclerosis (POMS) and to develop an optimized modeling scale for measuring disability, we performed a multicenter retrospective analysis of disability scores in 873 persons with POMS over time and compared this to previously published data in adults with multiple sclerosis (MS)., Methods: This was a retrospective analysis of prospectively collected data collected from 12 centers of the US Network of Pediatric MS Centers. Patients were stratified by the number of years from first symptoms of MS to Expanded Disability Status Scale (EDSS) assessment and an MS severity score (Pediatric Multiple Sclerosis Severity Score [Ped-MSSS]) was calculated per criteria developed by Roxburgh et al. in 2005., Results: In total, 873 patients were evaluated. In our cohort, 52%, 19.4%, and 1.5% of all patients at any time point reached an EDSS of 2.0, 3.0, and 6.0. Comparison of our Ped-MSSS scores and previously published adult Multiple Sclerosis Severity Scores (MSSS) showed slower progression of Ped-MSSS with increasing gaps between higher EDSS score and years after diagnosis. Decile scores in our POMS cohort for EDSS of 2.0, 3.0, and 6.0 were 8.00/9.46/9.94, 7.86/9.39/9.91, and 7.32/9.01/9.86 at 2, 5, and 10 years, respectively. Notable predictors of disease progression in both EDSS and Ped-MSSS models were ever having a motor relapse and EDSS at year 1. Symbol Digit Modalities Test (SDMT) scores were inversely correlated with duration of disease activity and cerebral functional score., Conclusions: Persons with POMS exhibit lower EDSS scores compared to persons with adult-onset MS. Use of a Ped-MSSS model may provide an alternative to EDSS scoring in clinical assessment of disease severity and disability accrual., (© 2020 American Academy of Neurology.)

Objective: To characterize the use and safety of newer disease-modifying therapies (DMTs) in children with multiple sclerosis (MS) and clinically isolated syndrome (CIS) treated under 18 years of age., Methods: This is a cohort study including children with MS or CIS followed at 12 outpatient practices participating in the US Network of Pediatric MS Centers. DMT use, including duration, dose, and side effects, was analyzed. Newer DMTs were defined as agents receiving Food and Drug Administration approval or with increased use in adult MS after 2005., Results: As of July 2017, 1,019 pediatric patients with MS (n = 748) or CIS (n = 271) were enrolled (65% female, mean onset 13.0 ± 3.9 years, mean follow-up 3.5 ± 3.1 years, median 1.6 visits per year). Of these, 78% (n = 587) with MS and 11% (n = 31) with CIS received DMT before 18 years of age. This consisted of at least one newer DMT in 42%, including dimethyl fumarate (n = 102), natalizumab (n = 101), rituximab (n = 57), fingolimod (n = 37), daclizumab (n = 5), and teriflunomide (n = 3). Among 17%, the initial DMT prescribed was a newer agent (36 dimethyl fumarate, 30 natalizumab, 22 rituximab, 14 fingolimod, 2 teriflunomide). Over the last 10 years, the use of newer agents has increased, particularly in those ≥12 years and to lesser extent in those <12 years. The short-term side effect profiles of newer DMTs did not differ from those reported in adults., Conclusion: Newer DMTs are often used in pediatric MS, and have similar short-term safety, tolerability, and side effect profiles as in adults. These findings may help inform pediatric MS management., (© 2018 American Academy of Neurology.)

Objective: To utilize Mendelian randomization to estimate the causal association between low serum vitamin D concentrations, increased body mass index (BMI), and pediatric-onset multiple sclerosis (MS) using genetic risk scores (GRS)., Methods: We constructed an instrumental variable for vitamin D (vitD GRS) by computing a GRS for 3 genetic variants associated with levels of 25(OH)D in serum using the estimated effect of each risk variant. A BMI GRS was also created that incorporates the cumulative effect of 97 variants associated with BMI. Participants included non-Hispanic white individuals recruited from over 15 sites across the United States (n = 394 cases, 10,875 controls) and Sweden (n = 175 cases, 5,376 controls; total n = 16,820)., Results: Meta-analysis findings demonstrated that a vitD GRS associated with increasing levels of 25(OH)D in serum decreased the odds of pediatric-onset MS (odds ratio [OR] 0.72, 95% confidence interval [CI] 0.55, 0.94; p = 0.02) after controlling for sex, genetic ancestry, HLA-DRB1*15:01 , and over 100 non-human leukocyte antigen MS risk variants. A significant association between BMI GRS and pediatric disease onset was also demonstrated (OR 1.17, 95% CI 1.05, 1.30; p = 0.01) after adjusting for covariates. Estimates for each GRS were unchanged when considered together in a multivariable model., Conclusions: We provide evidence supporting independent and causal effects of decreased vitamin D levels and increased BMI on susceptibility to pediatric-onset MS., (© 2017 American Academy of Neurology.)