Abstract
Pediatric-onset multiple sclerosis (POMS) may represent a model of vulnerability to damage occurring during a period of active maturation of the human brain. Whereas adaptive mechanisms seem to take place in the POMS brain in the short-medium term, natural history studies have shown that these patients reach irreversible disability, despite slower progression, at a significantly younger age than adult-onset MS (AOMS) patients. We tested for the first time whether significant brain alterations already occurred in POMS patients in their early adulthood and with no or minimal disability (n = 15) in comparison with age- and disability-matched AOMS patients (n = 14) and to normal controls (NC, n = 20). We used a multimodal MRI approach by modeling, using FSL, voxelwise measures of microstructural integrity of white matter tracts and gray matter volumes with those of intra- and internetwork functional connectivity (FC) (analysis of variance, p ≤ 0.01, corrected for multiple comparisons across space). POMS patients showed, when compared with both NC and AOMS patients, altered measures of diffusion tensor imaging (reduced fractional anisotropy and/or increased diffusivities) and higher probability of lesion occurrence in a clinically eloquent region for physical disability such as the posterior corona radiata. In addition, POMS patients showed, compared with the other two groups, reduced long-range FC, assessed from resting functional MRI, between default mode network and secondary visual network, whose interaction subserves important cognitive functions such as spatial attention and visual learning. Overall, this pattern of structural damage and brain connectivity disruption in early adult POMS patients with no or minimal clinical disability might explain their unfavorable clinical outcome in the long term.
Highlights
Plasticity is an essential asset of the human brain, mainly occurring during development and being able to dynamically act in response to environment and personal experiences through shaping of neural connections
We found for the first time that Pediatriconset Multiple sclerosis (MS) (POMS) patients in their early adulthood and with no or minimal disability showed, despite a similar macroscopic damage to that of adult-onset MS (AOMS) patients with similar age and clinical features, (i) increased lesion frequency and reduced anatomical connectivity (AC) along the posterior corona radiata (PCR) fibers of the CST, a clinically eloquent tract for physical disability, and (ii) reduced long-range functional connectivity (FC) involving a relevant hub for cognition such as default mode network (DMN)
In our early adult POMS with no or minimal disability, both higher lesion frequency and altered diffusivities across the whole brain compared with age- and clinically matched AOMS mapped on the PCR
Summary
Plasticity is an essential asset of the human brain, mainly occurring during development and being able to dynamically act in response to environment and personal experiences through shaping of neural connections. Some functional MRI (fMRI) studies found no change in effective connectivity of the sensorimotor network [5] and a relative preservation of global internetwork functional connectivity (FC) [6], suggesting that preservation of brain adaptive properties may explain the favorable clinical outcome in the short-medium term. It was demonstrated in late adolescent POMS [7] widespread abnormalities of anatomical connectivity (AC), in terms of DTIderived measures of WM microstructure, and associated higher FC in the default mode network (DMN) and frontoparietal network, with a potential compensatory role
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