Translingual Neurostimulation By Portable Neuromodulation Stimulator System As a New Rehabilitation Therapy for Improving Gait in People with Multiple Sclerosis

Background: Translingual neurostimulation (TLNS) delivered by a portable neuromodulation stimulator system promotes neuromodulation by stimulating the trigeminal (CN-V) and facial (CN-VII) nerves exciting a natural flow of neural impulses to the brainstem (pons Varolii and medulla) and cerebellum. Although gait impairment is a disabling symptom in MS leading to reduced mobility and impacting quality of life, current interventions (eg, rehabilitation therapy and pharmacological management) only marginally improve gait function. Recent studies have shown that noninvasive activation of cranial nerves by TLNS when combined with targeted therapeutic exercise programs can modulate neural pathways and improve gait function.

Objectives: Using pooled analysis of real-world data (RWD) and data from 2 double-blind randomized controlled trials (RCTs), this study assessed the effect of TLNS in combination with targeted therapeutic exercise to improve gait function in persons with MS.

Methods: In 2 separate clinical studies, subjects with an identified gait disturbance due to mild to moderate MS participated in 14-week intervention programs in which they received TLNS in conjunction with physical therapy. The results of these 2 studies were combined with RWD from 42 patients with MS using the same 14-week program as used in the trials. Subjects were assessed with the Functional Gait Assessment (FGA) or Dynamic Gait Index (DGI). DGI was used in the clinical trials, hence a modified DGI was derived from the FGA data obtained in the RWD dataset by scaling the 7 of 8 questions in common. A mixed model for repeated measures (MMRM) was used to estimate mean FGA total scores over time, based on all available subject data, and to estimate mean improvements in DGI, controlling for baseline.

Results: Analysis of RWD using MMRM showed that at Week 14 the mean improvement from baseline in the FGA was 4.63 points (95% CI:3.61 to 5.65).Median improvement was 5 points, exceeding the accepted threshold for clinical significance; 58.3% of patients had an improvement of ≥4 points at Week 14. Analysis of RWD pooled with data from both clinical trials showed an MMRM-adjusted mean improvement in DGI from baseline to Week 14 of 4.58 (95% CI: 3.62 to 5.54). These results were statistically significant and showed a clinically meaningful improvement in DGI. Overall, among 53 subjects with 14-week data treated with TLNS and physical therapy, 29 (55%) experienced ≥4-point improvement in DGI. Minimal adverse events were reported, with all determined to be typical for this patient population with or without use of the TLNS device.

Conclusions: Evidence from real-word data pooled with data from 2 randomized clinical trials demonstrated, consistent with RCT data, that TLNS combined with a targeted therapeutic exercise program is safe and effective for improving gait in individuals with mild and moderate symptoms from MS.