Faculty Bibliography

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) (2.2% vs 5.7%, respectively). Children with disease onset before age 11 versus onset at 11 years or after were more likely to need an individualized education plan ( P = .002), reading assistance ( P = .0003), and math assistance ( P = .001). Children with multiple sclerosis onset prior to age 18 are not delayed in meeting the 2 major early developmental milestones but do have a significantly increased use of special services or learning assistance at school. Further research will need to address whether other measures of development (eg, rate of language acquisition or fine motor skills) differ between pediatric multiple sclerosis and controls.

Background: Approximately 3-5% of multiple sclerosis (MS) cases manifest in childhood and adolescence, characteristically with highly active inflammatory disease course. Paediatric-onset MS (POMS) has an impact on brain integrity and may increase brain volume loss (BVL) above age-expected rates. This study assessed the effect of oral fingolimod up to 0.5mg daily versus intramuscular interferon (IFN) beta-1a 30 micro g once weekly on MRI outcomes in POMS patients. Method(s): In this double-blind, double-dummy, active-controlled, multicentre study, patients with POMS (aged 10-<18 Years) received either fingolimod (dose adjusted for body weight; n = 107) or IFN beta-1a (n = 107) for up to 2 years. MRI was performed at baseline and every 6 months until the end of the study (EOS) core phase. Key MRI outcomes were the number of new/newly enlarging T2 (N/NET2) lesions and gd-enhancing T1 (Gd+T1) lesions, annual rate of brain volume change (ARBVC), annualised rate of number of new T1 hypointense lesions, change in total T2 hyperintense lesion volume (T2LV) and the number of combined unique active lesions (CUAL). Result(s): At the EOS, compared with IFN beta-1a, fingolimod significantly reduced the annualised rate of N/NET2 lesions (52.6%; p < 0.001), number of Gd+T1 lesions per scan (66.0%; p < 0.001), ARBVC (-0.48% vs. -0.80%, p = 0.014), annualised rate of number of new T1 hypointense lesions (62.8%; p < 0.001), T2LV (percent change from baseline: 18.4% vs. 32.4%, p < 0.001) and CUAL per scan (60.7%; p < 0.001). Conclusion(s): Fingolimod significantly reduced MRI activity and slowed BVL for up to 2 years vs. IFN beta-1a in paediatric-onset MS.

BACKGROUND:/UNASSIGNED:Fatigue is one of the most common and distressing symptoms among persons with multiple sclerosis (pwMS). OBJECTIVE:/UNASSIGNED:The aim of this study is to evaluate fatigue as a predictor for disease worsening among pwMS. METHODS:/UNASSIGNED:, categorized participants into two groups: those with stable/improved outcomes and those who worsened. In a subgroup of patients with longitudinal data ( n = 1951), sustained EDSS worsening was analyzed using Cox proportional hazards modeling to explore the effect of fatigue. RESULTS:/UNASSIGNED:The median survival time from study enrollment to sustained EDSS worsening was 8.7 years (CI: 7.2-10.1). Participants who reported fatigue at baseline were more likely to experience sustained EDSS worsening during follow-up (HR: 1.4, 95% CI: 1.2-1.7). Patients who were fatigued at baseline were also more likely to report worsening psychosocial limitations (all ps ⩽ 0.01). CONCLUSION:/UNASSIGNED:In addition to being a common symptom of MS, severe fatigue was a significant predictor for EDSS worsening in the NYSMSC.

Background/UNASSIGNED: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/UNASSIGNED:= 442) were included as part of an ongoing case-control study. We used the National Emissions Inventory system to estimate particulate exposure by county of residence for each participant. Proximity to Toxic Release Inventory (TRI) sites was also assessed using ArcGIS mapping tools. Risk-Screening Environmental Indicators (RSEI) classified counties at risk to exposure of environmental toxic releases. Results/UNASSIGNED:= 0.002). Average RSEI scores did not differ significantly between cases and controls. Conclusion/UNASSIGNED:, CO, and lead) were statistically associated with higher odds for pediatric MS.

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/CONCLUSIONS: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.