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Onset of multiple sclerosis in childhood and adolescence leads to failure of age-expected brain grow

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


​Aubert-Broche B, Fonov V, Narayanan S, Arnold DL, Araujo D, Fetco D, Till C, Sled JG, Banwell B, Collins DL


Neurology


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.




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