In this study, 45 fatigued patients with multiple sclerosis (MS) were randomly assigned to undergo treatment with fampridine, amantadine or placebo and underwent clinical, neuropsychological and 3T resting state (RS) functional MRI at baseline and after four weeks of treatment. We found that treatment with fampridine (and, to a lesser extent, with amantadine) ameliorates fatigue in MS. Concomitant increase of RS functional connectivity (FC) in inferior frontal and parietal cortical regions, and decrease of abnormally high intra-thalamic FC were detected, suggesting an improved regulation of cortico-subcortical functional circuits.
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