Dynamic gray matter volume changes in pediatric multiple sclerosis: a 3.5 year MRI study

OBJECTIVES: To assess, using MRI, the spatial patterns of gray matter (GM) atrophy in pediatric patients with multiple sclerosis (MS), their dynamic changes over time, and their clinical relevance. METHODS: Sixty-eight pediatric patients with MS (30 with a clinical and MRI follow-up after 3.5 years) and 26 healthy controls (HC) underwent clinical and MRI evaluation. To overcome difficulties in obtaining longitudinal scans in pediatric HC, a group of 317 pediatric HC from an NIH-funded MRI Study of Normal Brain Development was used to estimate GM developmental trajectories. In pediatric patients with MS, deviations from normative GM volume values at the voxel level were assessed at baseline and during the follow-up, using linear mixed-effects models. Correlations between GM volume deviations and disability, IQ, and white matter (WM) lesion volumes (LV) were estimated. RESULTS: Pediatric patients with MS showed failures in GM development in several cortical and subcortical regions, as well as GM atrophy progression in most of these regions, which were only partially related to focal WM LV. Significant correlations were found between regional GM atrophy (particularly of deep GM regions) and disability, whereas higher IQ was associated with reduced deviations from age-expected GM volumes of specific GM regions at baseline and during the follow-up. CONCLUSIONS: Impaired GM maturation occurs in pediatric patients with MS, which is only partially driven by WM inflammation, suggesting that early neurodegenerative phenomena contribute to disability. High IQ, a measure of reserve, may offer protection by promoting remodeling of GM pruning in this young age.