Faculty Bibliography

Pediatric multiple sclerosis is associated with challenges in prompt diagnosis and uncertainty regarding optimal treatment. This review aimed to identify treatment guidelines or consensus statements for pediatric patients with multiple sclerosis, US Food and Drug Administration (FDA)-approved treatment options for pediatric multiple sclerosis, and any randomized controlled trials and observational studies examining available pharmacologic treatments in the pediatric multiple sclerosis population. Literature searches were performed in MEDLINE (1946-2016), EMBASE (1974-2016), and the Cochrane Central Register of Controlled Trials to identify treatment guidelines or consensus statements, pediatric multiple sclerosis treatment approvals, and randomized controlled trials and observation studies that examine the safety and effectiveness of available disease-modifying therapies. Only 3 consensus statements provided recommendations for pharmacologic treatments for children, all 3 published before the most recent revisions of the pediatric multiple sclerosis diagnostic guidelines. Despite the changes to the clinical landscape of pediatric multiple sclerosis with the introduction of diagnostic guidelines, fingolimod is the only FDA-approved treatment for pediatric multiple sclerosis in the United States. The effectiveness and safety of other disease-modifying therapies suggested by consensus statements have been reported in relatively small prospective and retrospective observational studies. Clinical evidence from a recently completed randomized controlled trial and future global registries can inform treatment decisions for the pediatric multiple sclerosis population.

Background: Adult MS research has identified an increased prevalence of various autoimmune conditions among family members of diagnosed patients. There has not been comparable studies of pediatric MS populations, while this cohort may represent a unique population from a risk factors perspective.
Objective(s): This study was undertaken to quantify the incidence of autoimmune conditions among first and second degree relatives of pediatric MS patients as compared to controls. The study sought to quantify both the rate, type and patterns of diagnoses seen throughout family members of pediatric MS patients.
Method(s): A multi center case-control study of risk factors for pediatric MS has been ongoing for since 2011. Pediatric patients with a diagnosis of MS and pediatric controls were recruited to provide data and biologic specimens for a number of research projects. Included in this effort was the acquisition of family history questionnaires. The medical data from these questionnaires were analyzed for the presence of certain medical diagnoses among first and second degree relatives. Logistic regression models were used to test for differences between cases and controls in reporting a family history of autoimmune diseases, when adjusting for sex, race, age, ethnicity, and mother's education level. Odds ratios and 95% confidence intervals were calculated based on the logistic regression models.
Result(s): Several conditions were found to have statistically significant differences in prevalence among first and second degree family members of MS patients as compared to controls. Diabetes, thyroid disorders and rheumatoid arthritis has the most notable differences between patients and controls while eczema and psoriasis were not different. The odds ratio of any family history of autoimmune disease was 2.27 among cases compared to controls. The odds ratio of an autoimmune disease among family members was significantly higher among paternal relatives as compared to maternal relatives (eg OR of 6.37 compared to 2.64).
Conclusion(s): This study has identified an increased prevalence of certain autoimmune disorders among first and second degree family members of pediatric MS patients. This aligns with prior findings among adult populations that found higher rates of autoimmune disorders among family members of adult onset MS patients. Novel to this study was the difference in relative risk of autoimmune conditions occurring in paternal versus maternal family members