Characteristics and predictors of disease course in children initially presenting with ADEM.

ADEM is an inflammatory disease, with new onset polyfocal neurologic symptoms, encephalopathy and multifocal demyelination, typically in childhood. Initial diagnosis of ADEM is challenging and up to 20 % of children with MS or NMOSD are initially diagnosed with ADEM. We describe characteristics of patients with monophasic ADEM vs.

Early Adversity and Socioeconomic Factors in Pediatric Multiple Sclerosis: A Case-Control Study.

Background And Objectives: Psychosocial adversity and stress, known to predispose adults to neurodegenerative and inflammatory immune disorders, are widespread among children who experience socioeconomic disadvantage, and the associated neurotoxicity and proinflammatory profile may predispose these children to multiple sclerosis (MS). We sought to determine associations of socioeconomic disadvantage and psychosocial adversity with odds of pediatric-onset MS (POMS), age at POMS onset, and POMS disease activity.

Methods: This case-control study used data collected across 17 sites in the United States by the Environmental and Genetic Risk Factors for Pediatric Multiple Sclerosis Study.

A new look at cognitive functioning in pediatric MS.

Objective: Cognitive involvement in pediatric multiple sclerosis (MS) relative to adult MS is less defined. This study advances our understanding by measuring cognitive performances in pediatric MS, adult MS, and pediatric healthy controls.

Methods: Consecutive relapsing pediatric MS participants from the United States Network of Pediatric MS Centers were compared with pediatric healthy controls and adults with relapsing MS.

Gut microbiome is associated with multiple sclerosis activity in children.

Objective: To identify features of the gut microbiome associated with multiple sclerosis activity over time.

Methods: We used 16S ribosomal RNA sequencing from stool of 55 recently diagnosed pediatric-onset multiple sclerosis patients. Microbiome features included the abundance of individual microbes and networks identified from weighted genetic correlation network analyses.

Familial History of Autoimmune Disorders Among Patients With Pediatric Multiple Sclerosis.

Background And Objective: The objective of this study was to determine whether family members of patients with pediatric multiple sclerosis (MS) have an increased prevalence of autoimmune conditions compared with controls.

Methods: Data collected during a pediatric MS case-control study of risk factors included information about various autoimmune diseases in family members. The frequency of these disorders was compared between cases and controls.

Improved relapse recovery in paediatric compared to adult multiple sclerosis.

Incomplete relapse recovery contributes to disability accrual and earlier onset of secondary progressive multiple sclerosis. We sought to investigate the effect of age on relapse recovery. We identified patients with multiple sclerosis from two longitudinal prospective studies, with an Expanded Disability Status Scale (EDSS) score within 30 days after onset of an attack, and follow-up EDSS 6 months after attack.

Pediatric Multiple Sclerosis Severity Score in a large US cohort.

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.

Real-World Effectiveness of Initial Disease-Modifying Therapies in Pediatric Multiple Sclerosis.

Objective: To assess real-world effectiveness of initial treatment with newer compared to injectable disease-modifying therapies (DMTs) on disease activity in pediatric multiple sclerosis (MS) and clinically isolated syndrome (CIS).

Methods: This is a cohort study of children with MS/CIS followed at 12 clinics in the US Network of Pediatric MS Centers, who received initial therapy with newer (fingolimod, dimethyl fumarate, teriflunomide, natalizumab, rituximab, ocrelizumab) or injectable (interferon-β, glatiramer acetate) DMTs. Propensity scores (PSs) were computed, including preidentified confounders.

Cognitive processing speed in pediatric-onset multiple sclerosis: Baseline characteristics of impairment and prediction of decline.

Background: Cognitive impairment occurs in approximately one-third of pediatric-onset multiple sclerosis (POMS) patients. The Symbol Digit Modalities Test (SDMT), a widely used cognitive screen in adults, has yet to be incorporated early into the standard care of POMS.

Objective: To screen for cognitive impairment early in the course of POMS and analyze predictive factors.

miRNA contributions to pediatric-onset multiple sclerosis inferred from GWAS.

Objective: Onset of multiple sclerosis (MS) occurs in childhood for approximately 5% of cases (pediatric MS, or ped-MS). Epigenetic influences are strongly implicated in MS pathogenesis in adults, including the contribution from microRNAs (miRNAs), small noncoding RNAs that affect gene expression by binding target gene mRNAs. Few studies have specifically examined miRNAs in ped-MS, but individuals developing MS at an early age may carry a relatively high burden of genetic risk factors, and miRNA dysregulation may therefore play a larger role in the development of ped-MS than in adult-onset MS.

Vitamin D genes influence MS relapses in children.

Objective: The aim of this study was to determine whether a vitamin D genetic risk score (vitDGRS) is associated with 25-hydroxyvitamin D (25(OH)D) level and multiple sclerosis (MS) relapses in children.

Methods: DNA samples were typed for single nucleotide polymorphisms (SNPs) from four genes previously identified to be associated with 25(OH)D levels. SNPs with strong associations with 25(OH)D after multiple comparison correction were used to create a genetic risk score (vitDGRS).

Admixture mapping reveals evidence of differential multiple sclerosis risk by genetic ancestry.

Multiple sclerosis (MS) is an autoimmune disease with high prevalence among populations of northern European ancestry. Past studies have shown that exposure to ultraviolet radiation could explain the difference in MS prevalence across the globe. In this study, we investigate whether the difference in MS prevalence could be explained by European genetic risk factors.

Several household chemical exposures are associated with pediatric-onset multiple sclerosis.

Background: There is limited information about the potential associations of multiple sclerosis (MS) and commonly used household chemicals.

Methods: We performed a case-control study of exposures to common household chemicals during childhood in children with MS and healthy pediatric controls. Exposures to household products were collected from a comprehensive questionnaire (http://www.

Acquisition of Early Developmental Milestones and Need for Special Education Services in Pediatric Multiple Sclerosis.

Children with pediatric-onset multiple sclerosis and pediatric controls were enrolled across 16 pediatric multiple sclerosis centers in the United States and completed questionnaires that addressed time of first unaided walking and acquisition of 2-word phrases. A total of 467 (308 female) cases and 428 (209 female) controls were enrolled. Pediatric multiple sclerosis (n = 467) were not delayed in walking or using 2-word phrases compared to healthy controls (n = 428) (2.

Heterogeneity in association of remote herpesvirus infections and pediatric MS.

Objective: While prior Epstein-Barr virus (EBV) infection has been consistently associated with subsequent risk of developing multiple sclerosis (MS), the association with other common herpesviruses has been more controversial. Our objectives were to determine whether remote infection with EBV and other common herpesviruses affect the susceptibility to pediatric MS and if there are interactions between genetic and demographic factors and viral infections.

Methods: Cases with pediatric-onset MS or clinically isolated syndrome within 4 years of disease onset, and controls were recruited from 16 American pediatric MS centers.

Urban air quality and associations with pediatric multiple sclerosis.

Background: We previously identified air quality as a risk factor of interest for pediatric multiple sclerosis. The purpose of this study is to more closely examine the association between the six criteria air pollutants and pediatric MS as well as identify specific areas of toxic release using data from the Toxic Release Inventory.

Methods: Pediatric MS cases ( = 290) and healthy controls ( = 442) were included as part of an ongoing case-control study.

Early infectious exposures are not associated with increased risk of pediatric-onset multiple sclerosis.

Objective: We sought to determine if early infectious exposures such as daycare, early use of antibiotics, vaccinations and other germ exposures including pacifier use and playing on grass are associated with multiple sclerosis (MS) risk in children.

Methods: This was a case-control study of children with MS or clinically isolated syndrome (CIS) and healthy controls enrolled at sixteen clinics participating in the US Network of Pediatric MS Centers. Parents completed a comprehensive environmental questionnaire that captured early infectious exposures, habits, and illnesses in the first five years of life.

The multiple sclerosis risk allele within the AHI1 gene is associated with relapses in children and adults.

Background: While common variant non-HLA (human leukocyte antigen) alleles have been associated with MS risk, their role in disease course is less clear. We sought to determine whether established multiple sclerosis (MS) genetic susceptibility factors are associated with relapse rate in children and an independent cohort of adults with MS.

Methods: Genotyping was performed for 182 children with MS or clinically isolated syndrome with high risk for MS from two Pediatric MS Centers.

Examining the contributions of environmental quality to pediatric multiple sclerosis.

Background: Multiple sclerosis (MS) is a presumed autoimmune disease caused by genetic and environmental factors. It is hypothesized that environmental exposures (such as air and water quality) trigger the innate immune response thereby activating a pro-inflammatory cascade.

Objective: To examine potential environmental factors in pediatric MS using geographic information systems (GIS).

Contribution of dietary intake to relapse rate in early paediatric multiple sclerosis.

Objective: The role of diet in multiple sclerosis (MS) course remains largely unknown. Children with MS have a higher relapse rate compared with MS in adults. Thus, studying the effect of diet on relapse rate in this age group is likely to provide more robust answers.

Genetic risk factors for pediatric-onset multiple sclerosis.

Background: Strong evidence supports the role of both genetic and environmental factors in pediatric-onset multiple sclerosis (POMS) etiology.

Objective: We comprehensively investigated the association between established major histocompatibility complex (MHC) and non-MHC adult multiple sclerosis (MS)-associated variants and susceptibility to POMS.

Methods: Cases with onset <18 years ( = 569) and controls ( = 16,251) were included from the United States and Sweden.

Genetic variation in the gene increases relapse risk in multiple sclerosis.

Background: Due to the lack of prospective studies with longitudinal data on relapse, past genetic studies have not attempted to identify genetic factors that predict relapse risk (the primary endpoint of many pivotal clinical trials testing the efficacy of multiple sclerosis (MS) disease-modifying drugs) at a genome-wide scale.

Methods: We conducted a genome-wide association analysis (GWAS) to identify genetic variants that predict MS relapse risk, using a three-stage approach. First, GWAS was conducted using the southern Tasmania MS Longitudinal Study with 141 cases followed prospectively for a mean of 2.

Dietary factors and pediatric multiple sclerosis: A case-control study.

Background: The role of diet in multiple sclerosis (MS) is largely uncharacterized, particularly as it pertains to pediatric-onset disease.

Objective: To determine the association between dietary factors and MS in children.

Methods: Pediatric MS patients and controls were recruited from 16 US centers (MS or clinically isolated syndrome onset before age 18, <4 years from symptom onset and at least 2 silent lesions on magnetic resonance imaging).

Evidence for a causal relationship between low vitamin D, high BMI, and pediatric-onset MS.

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.