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Updated: Jan 27, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Dynamic gray matter volume changes in pediatric multiple sclerosis: A 3.5 year MRI study
Ermelinda De Meo1, Alessandro Meani1, Lucia Moiola1
1From the Neuroimaging Research Unit (E.D.M., A.M., M.F., M.A.R.) and Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience (E.D.M., L.M., M.F., M.A.R.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan; Multiple Sclerosis Center (A.G.), Ospedale di Gallarate; Pediatric Neurology Unit (P.V.), V. Buzzi Children's Hospital, Milan; and Biomedical and Clinical Science Department (P.V.), University of Milan, Italy.
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.
Insights
Pediatric multiple sclerosis (MS) impairs gray matter (GM) development and causes atrophy, partly due to white matter lesions. Higher IQ may protect developing brains in pediatric MS patients.
Area of Science:
- Neuroscience
- Pediatric Neurology
- Radiology
Background:
- Multiple sclerosis (MS) in children presents unique challenges compared to adults.
- Gray matter (GM) changes are increasingly recognized as important in MS pathology.
- Understanding early neurodevelopmental trajectories in pediatric MS is crucial.
Purpose of the Study:
- To assess spatial patterns and temporal changes of GM atrophy in pediatric MS using MRI.
- To investigate the clinical relevance of GM changes in relation to disability and IQ.
- To compare GM development in pediatric MS patients with normative data.
Main Methods:
- Longitudinal MRI scans were acquired in pediatric MS patients and compared to normative GM developmental trajectories from healthy controls (HC).
- Linear mixed-effects models assessed deviations in GM volume at baseline and follow-up.
- Correlations between GM volume deviations, disability, IQ, and white matter lesion volume (LV) were analyzed.
Main Results:
- Pediatric MS patients exhibited impaired GM development and progressive atrophy in cortical and subcortical regions.
- GM atrophy was only partially linked to focal white matter lesions.
- Significant correlations were observed between regional GM atrophy (especially deep GM) and disability; higher IQ correlated with reduced GM volume deviations.
Conclusions:
- Impaired GM maturation in pediatric MS is not solely driven by white matter inflammation, indicating early neurodegenerative processes.
- Higher IQ may confer a protective effect by influencing GM remodeling and pruning in young patients.
- These findings highlight the importance of early neurodegenerative phenomena in pediatric MS disability.
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