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:/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:There is limited information about the potential associations of multiple sclerosis (MS) and commonly used household chemicals. Methods/UNASSIGNED: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.usnpmsc.org/Documents/EnvironmentalAssessment.pdf) completed by parents at the time of enrollment in the study. Cases included children diagnosed with MS or clinically isolated syndrome with at least two silent T2 bright lesions on MRI, recruited within 4 years of disease onset from 16 pediatric MS clinics in the USA. Multivariate analyses using logistic regression were adjusted for possible confounders including age, sex, race, ethnicity, mother's highest level of education, and urban versus rural living. Results/UNASSIGNED: ≤ 0.001) anytime during childhood were associated with an increased risk for pediatric-onset MS in adjusted and multiple comparisons analyses. Conclusions/UNASSIGNED:Our findings suggest that exposure to specific household chemicals during early childhood is associated with the risk of developing pediatric-onset MS. Future studies are needed to elucidate a causal relationship and the exact agents involved.

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.

PURPOSE/OBJECTIVE:To promote understanding of cognitive impairment in multiple sclerosis (MS), recommend optimal screening, monitoring, and treatment strategies, and address barriers to optimal management. METHODS:The National MS Society ("Society") convened experts in cognitive dysfunction (clinicians, researchers, and lay people with MS) to review the published literature, reach consensus on optimal strategies for screening, monitoring, and treating cognitive changes, and propose strategies to address barriers to optimal care. RECOMMENDATIONS/CONCLUSIONS:Based on current evidence, the Society makes the following recommendations, endorsed by the Consortium of Multiple Sclerosis Centers and the International Multiple Sclerosis Cognition Society: Increased professional and patient awareness/education about the prevalence, impact, and appropriate management of cognitive symptoms. For adults and children (8+ years of age) with clinical or magnetic resonance imaging (MRI) evidence of neurologic damage consistent with MS: As a minimum, early baseline screening with the Symbol Digit Modalities Test (SDMT) or similarly validated test, when the patient is clinically stable; Annual re-assessment with the same instrument, or more often as needed to (1) detect acute disease activity; (2) assess for treatment effects (e.g. starting/changing a disease-modifying therapy) or for relapse recovery; (3) evaluate progression of cognitive impairment; and/or (4) screen for new-onset cognitive problems. For adults (18+ years): more comprehensive assessment for anyone who tests positive on initial cognitive screening or demonstrates significant cognitive decline, especially if there are concerns about comorbidities or the individual is applying for disability due to cognitive impairment. For children (<18 years): neuropsychological evaluation for any unexplained change in school functioning (academic or behavioral). Remedial interventions/accommodations for adults and children to improve functioning at home, work, or school.

BACKGROUND: Fatigue is a common and debilitating feature of multiple sclerosis (MS) that remains without reliably effective treatment. Transcranial direct current stimulation (tDCS) is a promising option for fatigue reduction. We developed a telerehabilitation protocol that delivers tDCS to participants at home using specially designed equipment and real-time supervision (remotely supervised transcranial direct current stimulation (RS-tDCS)). OBJECTIVE: To evaluate whether tDCS can reduce fatigue in individuals with MS. METHODS: Dorsolateral prefrontal cortex left anodal tDCS was administered using a RS-tDCS protocol, paired with 20 minutes of cognitive training. Here, two studies are considered. Study 1 delivered 10 open-label tDCS treatments (1.5 mA; n = 15) compared to a cognitive training only condition ( n = 20). Study 2 was a randomized trial of active (2.0 mA, n = 15) or sham ( n = 12) delivered for 20 sessions. Fatigue was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue Short Form. RESULTS AND CONCLUSION: In Study 1, there was modest fatigue reduction in the active group (-2.5 +/- 7.4 vs -0.2 +/- 5.3, p = 0.30, Cohen's d = -0.35). However, in Study 2 there was statistically significant reduction for the active group (-5.6 +/- 8.9 vs 0.9 +/- 1.9, p = 0.02, Cohen's d = -0.71). tDCS is a potential treatment for MS-related fatigue.

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: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.

Introduction: In PARADIGMS, a double-blind phase 3 trial of 215 paediatric MS patients (age 10-< 18 years), fingolimod administered up to 2 years significantly reduced the annualised relapse rate by 81.9%, the annualised rate of new/newly enlarged T2 lesions by 52.6%, and the number of Gadolinium-enhancing T1 lesions by 66.0% compared to interferon (IFN) beta-1a.
Objective(s): To evaluate the effect of fingolimod versus IFN beta-1a on quality of life in this paediatric MS population.
Method(s): Health-related quality of life was assessed using the Pediatric Quality of Life (PedsQL) inventory. Summary statistics of change in patient-or parent-reported PedsQL scores from baseline until study end (up to 2 years) were pre-planned. Inferential testing on between group differences in PedsQL scores was performed as a post-hoc analysis. The change from baseline in Total Scale score, Physical Health Summary score, and Psychosocial Health Summary score was compared by visit for patient-and parent-reported PedsQL using a parametric analysis of covariance (ANCOVA) model adjusted by treatment, region, pubertal status, and the corresponding baseline score.
Result(s): Numerical improvements in PedsQL scores in both patient-and parent-reported Total Scale, Physical Health, and Psychosocial Health Summary scores were observed in fingolimod-treated patients compared with consistent worsening observed in the IFN beta-1a-treated patients. The post-hoc inferential statistical analysis confirmed that treatment with fingolimod resulted in a positive effect on quality of life in both patient-and parent-reported Total score and Physical Health Summary score, as well as in patient-reported Psychosocial Health Summary score compared with IFN beta-1a (all p< 0.05).
Conclusion(s): Consistent with the primary efficacy results, treatment with fingolimod versus IFN beta-1a was associated with a significant improvement in all measures of health-related quality of life as reported by the patients, and in Total score and Physical Health score as reported by their parents