Dynamic gray matter volume changes in pediatric multiple sclerosis
A 3.5 year MRI study
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Abstract
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.
Glossary
- DARTEL=
- diffeomorphic anatomical registration using exponentiated lie algebra;
- DE=
- dual-echo;
- EDSS=
- Expanded Disability Status Scale;
- ETL=
- echo train length;
- FOV=
- field of view;
- GM=
- gray matter;
- HC=
- healthy controls;
- HSR=
- Hospital San Raffaele;
- IPL=
- inferior parietal lobule;
- LV=
- lesion volumes;
- MFS=
- magnetic field strength;
- MNI=
- Montreal Neurological Institute;
- MS=
- multiple sclerosis;
- NIH HC=
- NIH-funded MRI Study of Normal Brain Development;
- PCG=
- precentral gyrus;
- PoCG=
- postcentral gyrus;
- RRMS=
- relapsing-remitting multiple sclerosis;
- TE=
- echo time;
- TSE=
- turbo spin-echo;
- TR=
- repetition time;
- WM=
- white matter
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Editorial, page 694
- Received August 6, 2018.
- Accepted in final form November 29, 2018.
- © 2019 American Academy of Neurology
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