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

Well you blithering idiots it has been proven to work a long time ago.  All your mentors and senior researchers had to do was to tell you to create a protocol on this and get it distributed to all 10 million yearly stroke survivors  now and into the future. And they completely failed at their job, thus wasting all this time and money.

• vagus nerve (59 posts to July 2012)

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, MD https://orcid.org/0000-0001-7532-2475 Jesse.dawson@glasgow.ac.uk, Navzer D. Engineer, PhD, […], Steven C. Cramer, MD https://orcid.org/0000-0002-6214-6211, Steven L. Wolf, PhD https://orcid.org/0000-0002-9446-8995, Rushna Ali, MD, Michael W. O’Dell, MD, David Pierce, MSEE, Cecília N. Prudente, PhD https://orcid.org/0000-0003-1296-8062, Jessica Redgrave, MD, Wuwei Feng, MD https://orcid.org/0000-0001-6230-4905, Charles Y. Liu, PhD, Gerard E. Francisco, MD, Benjamin L. Brown, MD, Anand Dixit, MD, Jen Alexander, MSc, Louis DeMark, DPT https://orcid.org/0000-0001-7998-0969, Vibor Krishna, MD, Steven A. Kautz, PhD https://orcid.org/0000-0003-3151-8235, Arshad Majid, MD, Brent Tarver, MSEE, Duncan L. Turner, PhD, and Teresa J. Kimberley, PhD https://orcid.org/0000-0001-6397-4054, +19 -19View all authors and affiliations

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https://doi.org/10.1177/15459683221129274

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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.

Introduction

Stroke is a leading cause of adult disability. Upper limb impairment and inability to effectively use the arm and hand for functional daily tasks are common and persists in approximately half of people who have upper limb impairment at onset.¹ These limitations have a detrimental impact on quality of life and improving upper limb impairment and function are a priority for stroke survivors.²

The use of vagus nerve stimulation (VNS) paired with rehabilitation to improve moderate to severe upper limb motor deficits associated with chronic ischemic stroke was recently approved the U.S. Food and Drug Administration. VNS augments task specific neuroplasticity by providing rapid cholinergic, noradrenergic, and serotonergic modulation.³ VNS paired with rehabilitation leads to greater recovery of forelimb function in rodent models than either motor training or VNS alone.^3,4 A combined analysis of data from 2 pilot feasibility trials of VNS paired with rehabilitation therapy^5,6 found an improvement in impairment following VNS in people with long-term arm weakness after ischemic stroke.⁷ In the recently published pivotal VNS-REHAB trial, there was a significant difference in change in Fugl–Meyer Assessment Upper Extremity (FMA-UE) score in favor of paired VNS following 6 weeks of in-clinic therapy.⁸ There was also a higher clinically important response rate, defined as a greater than 6-point improvement in the FMA-UE score, and improvements in functional measures with paired VNS at 90 days after completion of in-clinic therapy. However, participants did not have a uniform response to VNS, so identifying those with a higher chance of responding could optimize prescription of this therapy. Pooled analysis of data from both pilot trials did not find any clear relationship between baseline variables and change in FMA-UE score with VNS, although lower baseline Fugl–Meyer score was associated with greater improvement across both treatment groups.⁷ However, this analysis was based on a small sample size.

Here we perform a post-hoc subgroup analysis of data from the VNS-REHAB trial. We identified variables of interest based on known predictors of upper limb outcome. We examined whether the effect of paired VNS treatment differs by reported sex, age, time from stroke, severity of upper limb impairment, country of enrollment, paretic side, and whether there was cortical involvement of the index infarction.

 

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