TaVNS to improve upper extremity function in MS: a pilot feasibility study

Tia N. Hutchens, Adrienne Ellett, Shayok Dutta, Jeffery Bennett, Cristin G. Welle

DOI: Pending DOI

Synopsis

Upper limb dexterity is an underrecognized source of morbidity in patients with Multiple Sclerosis (MS).1 Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique that may promote motor recovery when paired with rehabilitation (Figure 1A). In this proof-of-concept pilot cohort, we evaluated the use of taVNS paired with the completion of a dexterous motor task, the Grooved Pegboard Test (GPT), a sensitive measure of manual dexterity in MS2. Participants in both the taVNS and sham groups demonstrated improved GPT times over one month of training, with a trend towards greater improvement in the taVNS intervention. This feasibility study lays the foundation for future clinical investigation of taVNS in people with MS.

Background

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system affecting more than 2.5 million people worldwide.3 Upper limb dexterity deficits are common and significantly impact quality of life — over three-quarters of patients with MS show deficits in manual dexterity,1 and upper extremity impairment correlates with reduced arm use in daily life and decreased quality of life.4,5 Disease-modifying treatments reduce relapse frequency but do not restore lost motor function.6 Vagus nerve stimulation (VNS) has emerged as a promising neuromodulation approach: VNS paired with motor rehabilitation is FDA-approved for upper extremity recovery following stroke.7 Preclinical work from our group demonstrates that pairing VNS with successful motor outcomes enhances cortical plasticity, improves motor performance,8 and promotes remyelination in a preclinical model of demyelination.9 Here we present a proof-of-concept pilot study examining the feasibility and preliminary efficacy of closed-loop, reinforcement taVNS in individuals with MS.

Methods

Five individuals with MS (n=3 taVNS, n=2 sham) participated in a six-month pilot study. One additional participant was excluded from analysis due to severe baseline disability (EDSS=8.0) rendering the primary outcome measure insensitive. At baseline, participants completed a full clinical assessment including the Upper Extremity Fugl-Meyer Assessment (UEFMA), Expanded Disability Status Scale (EDSS), MS Impact Scale-29 (MSIS-29), and Timed 25-Foot Walk. During month 1, participants completed the Grooved Pegboard Test (GPT) three times per week paired with taVNS or sham stimulation delivered via the Spark Sparrow device (cymba concha electrode placement). Stimulation parameters were: frequency 15–30 Hz, pulse duration 300 µs, train duration 1 second, and amplitude titrated per participant to 10% below discomfort threshold (≤5 mA). The taVNS group received stimulation following each peg placement; the sham group received stimulation for the first 3-5 peg placements (Figure 1C). GPT was reassessed at months 1, 2, 3, and 6, with full clinical reassessment repeated at month 6 and partial assessment at months 2 and 3 (Figure 1B).

Results

Six individuals with relapsing-remitting MS were enrolled (n=3 taVNS, n=3 sham). One sham participant (EDSS 8.0) was excluded from group comparisons due to severe baseline motor disability, leaving n=3 taVNS and n=2 sham for primary analysis.
At screening, groups were comparable on dominant hand GPT completion time (taVNS: 92.9±10.9s, sham: 99.1±7.9s). Both groups improved over the one-month training period (Figure 1D) . The taVNS group improved from 75.3±6.3s at session 1 to 65.5±2.9s by session 11 (13% reduction), while the sham group improved from 81.1±2.2s to 75.3±9.6s (7% reduction). Performance plateaued by approximately session 5 for both groups. At 6-month follow-up, the taVNS group demonstrated continued improvement (M6: 62.2±5.4s) while sham performance was relatively stable (M6: 70.0±1.0s). Across all training sessions, taVNS participants completed the GPT significantly faster than sham (mean 67.8±4.9s vs. 73.8±5.4s; Mann-Whitney U=261, p<0.0001). Given the small sample size, these findings should be considered preliminary; however, they demonstrate the feasibility of closed-loop taVNS paired with the GPT as a motor rehabilitation paradigm in MS.

Discussion

This proof-of-concept study demonstrates the feasibility of closed-loop, reinforcement taVNS in individuals with MS and provides preliminary evidence of a trend toward improved upper limb dexterity. This study lays the foundation for further clinical study of reinforcement taVNS in MS. In the future study, outcome measure sensitivity will be improved by incorporating the Dellon-Modified Moberg Pick-Up Test (DMMPUT) and kinematic shape-drawing tasks, which may better capture fine motor gains. Second, stimulation paradigms will be refined to more precisely target successful motor events. Third, remyelination will be measured using MR imaging and evoked potential latency, connecting functional motor outcomes to the underlying neurobiological mechanism.¹⁰,¹¹ Together, these refinements position the next cohort to more rigorously evaluate taVNS as a non-invasive motor rehabilitation strategy in MS.

Disclosures

No financial disclosures to report

References

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