Format

Send to

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

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

Author information

1
From the McConnell Brain Imaging Center (B.A.-B., V.F., S.N., D.L.A., D.A., D.F., D.L.C.), Montreal Neurological Institute, McGill University; The Hospital for Sick Children (C.T., J.G.S., B.B.), University of Toronto; York University (C.T.), Toronto, Canada; and Children's Hospital of Philadelphia (B.B.), University of Pennsylvania.
2
From the McConnell Brain Imaging Center (B.A.-B., V.F., S.N., D.L.A., D.A., D.F., D.L.C.), Montreal Neurological Institute, McGill University; The Hospital for Sick Children (C.T., J.G.S., B.B.), University of Toronto; York University (C.T.), Toronto, Canada; and Children's Hospital of Philadelphia (B.B.), University of Pennsylvania. banwellb@email.chop.edu.

Abstract

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.

PMID:
25378667
PMCID:
PMC4276405
DOI:
10.1212/WNL.0000000000001045
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center