Pediatric patients with clinically isolated syndromes at high risk of conversion to multiple sclerosis exhibit brain atrophy while those at low risk of conversion exhibit brain growth

Background: Accelerated brain atrophy has been observed in all phases of multiple sclerosis (MS), even following the first attack. Measurement of brain atrophy has been suggested as a marker of axonal loss and disease progression. Objective: To determine whether brain volume change is different among pediatric patients with clinically isolated syndromes (CIS) at high or low risk for progression to MS. Methods: Serial magnetic resonance imaging (MRI) images from 22 children enrolled in the prospective Canadian Pediatric Demyelinating Study were analyzed. Patients were designated as either low risk (n=13) if they remained free of clinical relapse or MRI evidence of new lesions at 12 months, and as high risk (n=9), if new lesions developed on subsequent MRI scans or if they were diagnosed with definite MS based on clinical relapses. Images were acquired using a standardized research protocol on a GE Signa Excite 1.5T scanner at baseline (within 7 days of onset of the initial demyelinating event) and at 3, 6 and 9 months. After pre-processing, percent brain volume change was calculated using SIENA 2.5 from FSL 4.0.1. Brain volume changes were calculated longitudinally relative to the baseline scan. Results: Patient ages were comparable, 10.8 plus or minus 2.3 for the high-risk and 10.2 plus or minus 3.7 for the low-risk groups. Significant differences in brain volume change between the groups were apparent at the 9 month time point relative to the baseline scan. By month 9, the percent brain volume changes were -1.5 plus or minus 1.2% (mean plus or minus SD) in the high-risk group and 0.3 plus or minus 1.1% in the low-risk group. The differences between the low-risk and high-risk groups were statistically significant (p =0.002). Conclusions: In contrast with children with an isolated episode of demyelination who demonstrate stability or age-expected brain growth, brain atrophy can be detected in children at high risk of MS. These findings implicate both a predictive and primary role for neurodegeneration early in the MS disease process and raise concern regarding the implication of brain atrophy on the long-term physical and cognitive outcome in these children.