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Randomized Controlled Trial
. 2023 Jun;37(6):367-373.
doi: 10.1177/15459683221129274. Epub 2022 Oct 13.

Vagus Nerve Stimulation Paired With Rehabilitation for Upper Limb Motor Impairment and Function After Chronic Ischemic Stroke: Subgroup Analysis of the Randomized, Blinded, Pivotal, VNS-REHAB Device Trial

Jesse Dawson  1 , Navzer D Engineer  2 , Steven C Cramer  3 , Steven L Wolf  4 , Rushna Ali  5 , Michael W O'Dell  6 , David Pierce  2 , Cecília N Prudente  2 , Jessica Redgrave  7 , Wuwei Feng  8 , Charles Y Liu  9 , Gerard E Francisco  10 , Benjamin L Brown  11 , Anand Dixit  12 , Jen Alexander  1 , Louis DeMark  13 , Vibor Krishna  14 , Steven A Kautz  15 , Arshad Majid  16 , Brent Tarver  2 , Duncan L Turner  17 , Teresa J Kimberley  18
Affiliations
Randomized Controlled Trial

Vagus Nerve Stimulation Paired With Rehabilitation for Upper Limb Motor Impairment and Function After Chronic Ischemic Stroke: Subgroup Analysis of the Randomized, Blinded, Pivotal, VNS-REHAB Device Trial

Jesse Dawson et al. Neurorehabil Neural Repair. 2023 Jun.

Abstract

Background: Vagus Nerve Stimulation (VNS) paired with rehabilitation improved upper extremity impairment and function in a recent pivotal, randomized, triple-blind, sham-controlled trial in people with chronic arm weakness after stroke.

Objective: We aimed to determine whether treatment effects varied across candidate subgroups, such as younger age or less injury.

Methods: Participants were randomized to receive rehabilitation paired with active VNS or rehabilitation paired with sham stimulation (Control). The primary outcome was the change in impairment measured by the Fugl-Meyer Assessment Upper Extremity (FMA-UE) score on the first day after completion of 6-weeks in-clinic therapy. We explored the effect of VNS treatment by sex, age (≥62 years), time from stroke (>2 years), severity (baseline FMA-UE score >34), paretic side of body, country of enrollment (USA vs UK) and presence of cortical involvement of the index infarction. We assessed whether there was any interaction with treatment.

Findings: The primary outcome increased by 5.0 points (SD 4.4) in the VNS group and by 2.4 points (SD 3.8) in the Control group (P = .001, between group difference 2.6, 95% CI 1.03-4.2). The between group difference was similar across all subgroups and there were no significant treatment interactions. There was no important difference in rates of adverse events across subgroups.

Conclusion: The response was similar across subgroups examined. The findings suggest that the effects of paired VNS observed in the VNS-REHAB trial are likely to be consistent in wide range of stroke survivors with moderate to severe upper extremity impairment.

Keywords: neuromodulation; rehabilitation; stroke; upper extremity.

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Conflict of interest statement

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SC serves as a consultant for Abbvie, Constant Therapeutics, MicroTransponder, Neurolutions, SanBio, Panaxium, NeuExcell, Elevian, Medtronic, Helius, Omniscient, and TRCare. JD has received reibursement for conference expenses to present trial data. NE, BT, DP, CP are employees of MicroTransponder Inc. SLW is a consultant to Enspire and serves on the Scientific Advisory Board of Saebo. GEF has received research grants, consulting honoraria, or both from Allergan, Ipsen, Merz, MicroTransponder, Ottobock/Hangar Orthopedics, Parker Hannifin, Revance Therapeutics, ReWalk, and Sword Health. The MGH Translational Research Center has a clinical research support agreement with Neuralink, Paradromics, and Synchron, for which LRH provides consultative input. The remaining authors declare no competing interests.

Figures

Figure 1.
Figure 1.
Forest plots showing mean group difference for FMA-UE change in score at day 1 (A) and day 90 (B) post completion of in-clinic therapy across different subgroups. Within each subgroup category, black square shows the mean group difference, and the size of the squares represents the degree of change. Horizontal lines denote 95% confidence. P values are given for the test of interaction between the group difference and subgroup of interest. Values to the right of the zero vertical line show a between group difference in favor of VNS. Abbreviation: FMA-UE, Fugl–Meyer Assessment Upper Extremity; VNS, vagus nerve stimulation.
Figure 2.
Figure 2.
Forest plots showing mean group difference for WMFT change in score at day 1 (A) and day 90 (B) post completion of in-clinic therapy across different subgroups. Within each subgroup category, black square shows the mean group difference, and the size of the squares represents the degree of change. Horizontal lines denote 95% confidence. P values are given for the test of interaction between the group difference and subgroup of interest. Values to the right of the zero vertical line show a between group difference in favor of VNS. Values to the right of the vertical line show a between group difference in favor of VNS. Abbreviations: WMFT, Wolf Motor Function Test; VNS, vagus nerve stimulation.
Figure 3.
Figure 3.
Forest plots showing mean group response rate difference for FMA-UE (A) and WMFT (B) at day 90 post completion of in-clinic therapy across different subgroups. Within each subgroup category, black square shows the mean group difference, and the size of the squares represents the size of the response difference. Horizontal lines denote 95% confidence. Values to the right of the zero vertical line show a between group absolute response rate difference in favor of VNS. Abbreviations: FMA-UE, Fugl–Meyer Assessment Upper Extremity; WMFT, Wolf Motor Function Test; VNS, vagus nerve stimulation; resp, response.
See this image and copyright information in PMC

References

    1. Kelly-Hayes M, Beiser A, Kase CS, Scaramucci A, D’Agostino RB, Wolf PA.The influence of gender and age on disability following ischemic stroke: the Framingham study. J Stroke Cerebrovasc Dis. 2003;12(3):119-126. - PubMed
    1. Pollock A, St George B, Fenton M, Firkins L.Top 10 research priorities relating to life after stroke–consensus from stroke survivors, caregivers, and health professionals. Int J Stroke. 2014;9(3):313-320. - PubMed
    1. Porter BA, Khodaparast N, Fayyaz T, et al.. Repeatedly pairing vagus nerve stimulation with a movement reorganizes primary motor cortex. Cereb Cortex. 2012;22(10):2365-2374. - PubMed
    1. Khodaparast N, Kilgard MP, Casavant R, et al.. Vagus nerve stimulation during rehabilitative training improves forelimb recovery after chronic ischemic stroke in rats. Neurorehabil Neural Repair. 2016;30(7):676-684. - PMC - PubMed
    1. Dawson J, Pierce D, Dixit A, et al.. Safety, feasibility, and efficacy of vagus nerve stimulation paired with upper-limb rehabilitation after ischemic stroke. Stroke. 2016;47(1):143-150. - PMC - PubMed

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