Petsas, N;
De Giglio, L;
González-Quintanilla, V;
Giuliani, M;
De Angelis, F;
Tona, F;
Carmellini, M;
... Pantano, P; + view all
(2019)
Functional Connectivity Changes After Initial Treatment With Fingolimod in Multiple Sclerosis.
Frontiers in Neurology
, 10
, Article 153. 10.3389/fneur.2019.00153.
Preview |
Text
fneur-10-00153.pdf - Published Version Download (1MB) | Preview |
Abstract
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 (p < 0.05) in cognitive function, as measured by the Paced Auditory Serial Addition Task, at month 6 compared to initiation. After accounting for test-retest effect, baseline FC significantly decreased at month 6, with respect to initiation (p < 0.05, family-wise error corrected) in bilateral occipito-parietal areas and cerebellum. A task-induced change in FC at month 6 showed a significant increment in all examined sessions, involving not only areas of the sensorimotor network, but also posterior cortical areas (cuneus and precuneus) and areas of the prefrontal and temporal cortices (p < 0.05, family-wise error corrected). Cognitive improvement at month 6 was significantly (p < 0.05) related to baseline FC reduction in posterior cortical areas. This study shows significant changes in functional connectivity, both at baseline and after the execution of a simple motor task following 6 months of fingolimod therapy.
| Type: | Article |
|---|---|
| Title: | Functional Connectivity Changes After Initial Treatment With Fingolimod in Multiple Sclerosis |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fneur.2019.00153 |
| Publisher version: | https://doi.org/10.3389/fneur.2019.00153 |
| Language: | English |
| Additional information: | Copyright © 2019 Petsas, De Giglio, González-Quintanilla, Giuliani, De Angelis, Tona, Carmellini, Mainero, Pozzilli and Pantano. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | multiple scleorsis (MS), resting-state functional MRI, functional connectivity, fingolimod (FTY720), motor task |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neuroinflammation |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10112753 |
Archive Staff Only
 |
View Item |
