Functional and structural connectivity of the motor network in pediatric and adult-onset relapsing-remitting multiple sclerosis.
OBJECTIVE
To elucidate the factors associated with the preservation of function in relapsing-remitting (RR) multiple sclerosis (MS) by investigating effective connectivity changes of the sensorimotor network in pediatric RR MS patients in comparison with adult patients with either clinically isolated syndromes (CIS) suggestive of MS or RR MS and in adult healthy control subjects by using functional magnetic resonance imaging (MR) imaging and a dynamic causal model approach and to assess the correlation between effective connectivity changes and structural damage to the corpus callosum and the corticospinal tracts (CSTs).


METHODS
The study was conducted with institutional review board approval. Written informed consent was obtained from each participant. Dual-echo, diffusion-tensor, and functional MR images were acquired from 17 pediatric RR MS patients, 16 adult patients with CIS, 14 adult RR MS patients, and 10 age-matched pediatric healthy control subjects during a simple motor task. Whole-brain, corpus callosum, and CST T2 lesion loads, as well as corpus callosum and CST diffusivity measures were determined. Functional MR imaging data were analyzed by using statistical parametric mapping.


RESULTS
Coefficients of effective connectivity of the sensorimotor network were similar in control subjects and pediatric MS patients. In adult patients with CIS and even more evidently in those with RR MS, an increase of intra- and interhemispheric strengths of coefficients of effective connectivity was found (P = .05-.008). The increases in such coefficients were correlated with corpus callosum and CST damage, in terms of T2 lesion load and diffusion-tensor MR imaging quantities (r = -0.34 to 0.40).


CONCLUSIONS
The preservation of brain adaptive properties might explain the favorable medium-term clinical outcome of pediatric MS patients. The progressive recruitment of cortical networks over time in patients with the adult RR forms of the disease might result in a loss of their plastic reservoir, thus possibly contributing to subsequent disease evolution.
Rocca
Maria A
MA
Neuroimaging Research Unit, Institute of Experimental Neurology, Department of Neurology, University Hospital San Raffaele, Via Olgettina 60, 20132 Milan, Italy.
Absinta
Martina
M
Moiola
Lucia
L
Ghezzi
Angelo
A
Colombo
Bruno
B
Martinelli
Vittorio
V
Comi
Giancarlo
G
Filippi
Massimo
M
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000704:Analysis of Variance; D016022:Case-Control Studies; D003337:Corpus Callosum / Q000473:pathology; D005260:Female; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009043:Motor Activity / Q000502:physiology*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology* / Q000503:physiopathology*; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009434:Neural Pathways / Q000473:pathology* / Q000503:physiopathology*; D012189:Retrospective Studies