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Neurology

Neurodegenerative Elements of Pediatric Multiple Sclerosis

June 20, 2016
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Pediatric-onset multiple sclerosis (onset that occurs prior to age 18) hinders age-expected brain development, suggesting that multiple sclerosis’s neurodegenerative symptoms are early onset processes. This can have serious implications for the diagnosis and even the therapeutic outlooks of those affected.

SOURCE: Aubert-Broche B, et al. Onset of multiple sclerosis before adulthood leads to failure of age-expected brain growth. Neurology 2014;83:2140-2146.

As an inflammatory disease of the central nervous system, multiple sclerosis’s attacks on the CNS’s myelin sheaths and its disastrous effects have traditionally been well documented. More recently, symptoms of progressive deep gray matter atrophy have proven that MS partially comprises a neurodegenerative component. Moreover, reduced thalamic and whole brain volumes demonstrated in pediatric onset MS parallel this neurodegeneration. The authors in this study compared brain growth trajectory of patients with pediatric and adolescent onset MS with age matched controls by analyzing MR based brain volumetrics. This study also investigated the relative contribution of “T2 lesion burden” and the relationship between the onset of puberty and brain growth. The authors hypothesized that identified differences found in growth curves would reveal regional brain volume differences that could be accounted for by stunted brain growth, gradual brain atrophy, or a combination of the two. As such, this study was pursued to determine the possibility of early onset regional neurodegeneration in pediatric MS patients.

The study included 185 MRI scans of 36 pediatric MS patients, comparing them to a control group 25 pediatric patients. The control group, however, was scanned three times each over the course of 1 to 2 years. Both groups used the same MR scanner during the study. As a reference, the authors relied upon a publically-available normative brain growth data set from the NIH-funded MRI Study of Normal Brain Development (NIHPD). In the normative data set, the average age of first scan was 11 years, with follow-up scans taken at 2-3 year intervals.

Low “T2 lesion burden” was chosen arbitrarily as 0.35% of normal brain volume. Puberty was defined as reaching 11 years of age — the average for boys and girls —— arbitrarily chosen again, to further understanding of the effect of MS’s onset both before and after that time.

The study’s results showed no significant difference between the regional brain volumes of the NC group and the NIHPD group, thus demonstrating the NC group’s representativeness of the larger sample population NIHPD group. The MS brain and thalamic brain volume curves, meanwhile, were significantly vitiated when contrasted with the NIHPD group. As there was no significant discontinuity found before and after age 11 in either whole or regional brain volumes, puberty appeared to have no effect on longitudinal brain growth.

The presence of T2 lesion burden between most of the regions of the tested brains’ volumes did not differ between MS patients with high inter-scan lesion-to brain ratios (>0.35%) and MS patients with low lesion-to brain ratios (< 0.35%). Higher lesion load non-unique to the thalamus, however, was strongly correlated with gradually smaller thalamic volume.

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