Changes in structural and functional connectivity during two years of fingolimod therapy for multiple sclerosis

Abstract

Background: Fingolimod, an oral drug, has been reported to reduce relapse rate in multiple sclerosis (MS). However disease progression may still occur in spite of control of inflammation. Functional imbalances within and between cerebral networks associated with disruption of structural and functional network integrity, have been reported in MS. An effective therapy is expected to stabilize such functional network integrity.

Objective: The purpose of this study was to investigate changes in structural and resting-state functional connectivity of motor and cognitive networks, and associated changes in neurologic scores in MS, during 2 years of fingolimod therapy.

Methods: Twenty five subjects with MS were recruited for this study. Subjects were scanned with diffusion tensor imaging (DTI) and resting-state functional connectivity MRI (fcMRI) scan protocol at 3 T with 6-month interval over a period of 2 years. Neurologic performance scores of motor and cognitive performances were also obtained.

Results: DTI measures worsened during the 1st year and then stabilized; any trend of stabilization of fcMRI was delayed until the 2nd year. While motor performance did not change, cognitive performance showed improvement. Several baseline DTI measures correlated with relevant neurologic scores.

Conclusion: Initial worsening of motor and cognitive network was reported after 1 year of treatment, but seems DTI and fcMRI measures seem to stabilize after around one year fingolimod therapy.

Keywords: Diffusion tensor imaging; Fingolimod; Frontoparietal network; Functional connectivity; Motor network.