Reduced brain volumes in children with radiologically isolated syndrome

Background: Pediatric multiple sclerosis (MS) is associated with reduced brain volumes at first episode compared to healthy controls. Objective: To assess brain volumes in children fulfilling the criteria of radiologically isolated syndrome (RIS) at onset and over time. Methods: Clinical course, laboratory findings, MR-imaging in pediatric RIS were compared to controls from the NIH Pediatric MRI Data Repository and a cohort of patients with pediatric MS. Results: 20 RIS and 37 MS patients were included in the study. Median age at RIS diagnosis was 13.1 years (IQR: 10.3, 14.8) and whole brain volume was reduced by 77 cm 3 , compared to matched healthy controls (1673 cm 3 (1637, 1728) vs 1750 cm 3 (1699, 1802)). Nine RIS patients developed MS (RIS-to-MS) at a median age of 15.8 years (12.7,17.0). Longitudinal volumetry revealed lower brain volume in both non-converting and converting RIS patients compared to controls, similar to the trajectory in pediatric MS (RIS −4.7% (−6.5, −2.9), RIS-to-MS −5.1% (−6.9, −3.4), MS −6.6 % (−7.6, −5.5)). Oligoclonal bands, cerebrospinal fluid (CSF) pleocytosis, and reduced brain volume in RIS at diagnosis increased hazards of conversion to MS. Conclusions: Reduced whole brain volume is already present in pediatric radiologically isolated syndrome (RIS). Longitudinal analysis of RIS patients revealed reduced brain volume over time, similar to MS.