Is a preserved functional reserve a mechanism limiting clinical impairment in pediatric MS patients?

Abstract

We evaluated the functional magnetic resonance imaging (fMRI) correlates of simple movement performance in patients with pediatric multiple sclerosis (MS) and their relation with the extent of T2 lesion volume (LV), to improve our understanding of the mechanisms leading to their short/medium term favorable clinical course. We obtained fMRI during repetitive flexion-extension of the last four fingers of the right hand and brain dual-echo scans from 17 right-handed patients with pediatric relapsing-remitting MS and 9 sex- and age-matched right-handed healthy controls. T2 LV was measured using a local thresholding segmentation technique. fMRI activations and functional connectivity analysis were performed using SPM2. Compared to controls, pediatric MS patients had an increased recruitment of the left (L) primary sensorimotor cortex (SMC). They also showed reduced functional connectivity between the L primary SMC and the L thalamus (P = 0.03), the L insula and the L secondary sensorimotor cortex (SII) (P = 0.02), the supplementary motor area and the L SII (P = 0.02), the L thalamus and the L insula (P = 0.01) and the L thalamus and the L SII (P = 0.003). In patients with pediatric MS, the activity of the L primary SMC was significantly correlated with brain T2 LV (r = 0.78). No correlation was found between coefficients of abnormal connectivity and structural MRI measures. The maintenance of a selective and strictly lateralized pattern of movement-associated brain activations and a modulation of its functional connections suggest a preserved functional reserve in patients with pediatric MS, which, in turn, might contribute to explain their favorable clinical evolution at short/medium term.

Figure 1

Cortical activations on a rendered brain from right‐handed healthy subjects (top row) and patients with pediatric MS (middle row) during the performance of a simple motor task with their clinically unimpaired and fully normal functioning right hands (within‐group analysis, one‐sample t tests, P < 0.05 corrected for multiple comparisons). In the bottom row, the between‐groups differences are shown: the left primary sensorimotor cortex was more significantly activated in pediatric MS patients than controls. Images are in neurological convention. See text for further details.

Figure 2

Dynamic causal model showing the results of the between‐group analysis of connectivity. Reduced strength of connection in pediatric MS patients vs. controls are reported as dotted black lines. See text for further details.