Functional Connectivity Changes After Initial Treatment With Fingolimod in Multiple Sclerosis.

On the basis of recent functional MRI studies, Multiple Sclerosis (MS) has been interpreted as a multisystem disconnection syndrome. Compared to normal subjects, MS patients show alterations in functional connectivity (FC). However, the mechanisms underlying these alterations are still debated. The aim of the study is to investigate resting state (RS) FC changes after initial treatment with fingolimod, a proven anti-inflammatory and immunomodulating agent for MS. We studied 32 right-handed relapsing-remitting MS patients (median Expanded Disability Status Scale: 2.0, mean disease duration: 8.8 years) who underwent both functional and conventional MRI with a 3 Tesla magnet. All assessments were performed 3 weeks before starting fingolimod, then, at therapy-initiation stage and at month 6. Each imaging session included scans at baseline (run1) and after (run2) a 25-min, within-session, motor-practice task, consisting of a paced right-thumb flexion. FC was assessed using a seed on the left primary motor cortex to obtain parametric maps at run1 and task-induced FC change (run2-run1). Comparison between 3-week before- and fingolimod start sessions accounted for a test-retest effect. The main outcome was the changes in both baseline and task-induced changes in FC, between initiation and 6 months. MRI contrast enhancement was detected in 14 patients at initiation and only in 3 at month 6. There was a significant improvement (