Relationship of BDNF and gait in multiple sclerosis

Abstract

Background: Interest in the clinical application of non-invasive neuromodulation is growing. There is research on the therapeutic effects of combining non-invasive neuromodulation with physiotherapy (PT) to improve outcomes in different neurological populations , but with mixed results. One method gaining popularity is translingual neurostimulation (TLNS). In a pilot study, TLNS or SHAM was paired with 14-wks of PT (n=20 MS participants). Post, both groups had a significant mean change in Dynamic Gait Index (DGI) score, with the magnitude of improvement greater for the PT+TLNS group. Although informative, the sample was small, there was no follow-up to determine whether benefits were sustained after treatment had ended, and the bulk of the program took place without objective monitoring so the fidelity of the PT intervention could not be assured. Research suggests that intense PT can help improve walking and balance function, but it is not yet known if there are added benefits from pairing PT with TLNS. Objective: This study is investigating whether PT paired with TLNS enhances improvements in walking and balance for people with MS. Methods: This is a two arm, participant-, interventionist-, and research assessor-blinded RCT that includes the examination of potential underlying neurophysiological mechanisms. 52 MS participants with walking impairment (PDDS 3-6) will complete a 26-wk study (14-wk intervention and 12-wk follow up). An evidence informed PT intervention will be paired with TLNS or control , and monitored for intensity. Demographics, walking (T25FWT, temporal-spatial gait measures, DGI), balance (miniBESTest), patient-reported questionnaires (MSIS-29, MSWS-12, SF-36, Fatigue), and neurophysiological measures (fNIRS, TMS) will be assessed pre, post, and follow-up. Results: Primary analysis will be at follow-up. Discussion: This multi-site RCT is the first study using TLNS in MS that is fully powered, controlling for PT intensity and adherence , using neurophysiological measures and with long-term follow-up.