Onset of multiple sclerosis before adulthood leads to failure of age-expected brain growth

Neurology. 2014 Dec 2;83(23):2140-6. doi: 10.1212/WNL.0000000000001045. Epub 2014 Nov 5.


Objective: To determine the impact of pediatric-onset multiple sclerosis (MS) on age-expected brain growth.

Methods: Whole brain and regional volumes of 36 patients with relapsing-remitting MS onset prior to 18 years of age were segmented in 185 longitudinal MRI scans (2-11 scans per participant, 3-month to 2-year scan intervals). MRI scans of 25 age- and sex-matched healthy normal controls (NC) were also acquired at baseline and 2 years later on the same scanner as the MS group. A total of 874 scans from 339 participants from the NIH-funded MRI study of normal brain development acquired at 2-year intervals were used as an age-expected healthy growth reference. All data were analyzed with an automatic image processing pipeline to estimate the volume of brain and brain substructures. Mixed-effect models were built using age, sex, and group as fixed effects.

Results: Significant group and age interactions were found with the adjusted models fitting brain volumes and normalized thalamus volumes (p < 10(-4)). These findings indicate a failure of age-normative brain growth for the MS group, and an even greater failure of thalamic growth. In patients with MS, T2 lesion volume correlated with a greater reduction in age-expected thalamic volume. To exclude any scanner-related influence on our data, we confirmed no significant interaction of group in the adjusted models between the NC and NIH MRI Study of Normal Brain Development groups.

Conclusions: Our results provide evidence that the onset of MS during childhood and adolescence limits age-expected primary brain growth and leads to subsequent brain atrophy, implicating an early onset of the neurodegenerative aspect of MS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Atrophy / pathology
  • Brain / growth & development
  • Brain / pathology*
  • Brain / physiopathology
  • Cross-Sectional Studies
  • Disability Evaluation
  • Disease Progression
  • Female
  • Humans
  • Image Processing, Computer-Assisted / methods
  • Magnetic Resonance Imaging / methods
  • Male
  • Multiple Sclerosis / diagnosis
  • Multiple Sclerosis / pathology*
  • Multiple Sclerosis / physiopathology*
  • Young Adult