Long-Term Outcomes of Vagus Nerve Stimulation Paired With Upper Extremity Rehabilitation After Stroke

BACKGROUND: Persistent upper extremity (UE) impairment is common after stroke. Durable treatment benefits for chronic ischemic stroke are needed. The purpose of this report is to determine the long-term effects of vagus nerve stimulation paired with rehabilitation on impairment, activity, and participation in people with UE impairment after ischemic stroke.

METHODS: This is a post hoc analysis of data from the VNS-REHAB (A Pivotal Randomized Study Assessing Vagus Nerve Stimulation [VNS] During Rehabilitation for Improved Upper Limb Motor Function After Stroke) randomized clinical trial. Here, we report unblinded, partial crossover, and pooled 1-year outcomes. Initially, 108 participants across 19 sites with chronic ischemic stroke and moderate-to-severe UE impairment were enrolled in VNS-REHAB. Participants received 18 sessions of in-clinic intensive task-specific rehabilitation and 3 months of self-initiated home-based exercise with either real (active) or sham (control) vagus nerve stimulation. Thereafter, Control participants crossed over to receive in-clinic therapy paired with active stimulation. All participants performed home-based exercises paired with self-initiated active stimulation for 1 year. The Fugl-Meyer Assessment UE, Wolf Motor Function Test, and participation outcomes were assessed through 12 months.

RESULTS: Seventy-four participants (69%; 51 male; age, mean±SD, 59.6±8.9) completed 1-year follow-up and provided pooled data through 1 year. At 1 year, compared with baseline, there were improvements in impairment (Fugl-Meyer Assessment UE, 5.23 [95% CI, 4.08-6.39]; P<0.001) activity (Wolf Motor Function Test, 0.50 [95% CI, 0.41-0.59]; P<0.001) and patient-reported outcomes (Motor Activity Log-Quality of Movement: 0.64 [95% CI, 0.46-0.82], P<0.001; Motor Activity Log-Amount of Use: 0.64 [95% CI, 0.46-0.82], P<0.001; Stroke Impact Scale-Activities of Daily Living: 7.43 [95% CI, 5.09-9.77], P<0.001; Stroke Impact Scale-Hand: 17.89 [95% CI, 14.16-21.63], P<0.001; EQ-5D: 5.76 [95% CI, 2.08-9.45], P<0.05; and Stroke Specific-Quality of Life: 0.29 [95% CI, 0.19-0.39], P<0.001) compared with baseline.

CONCLUSIONS: People treated with paired vagus nerve stimulation maintained improvements in UE impairment, activity, participation, and quality-of-life measures at 1 year. Paired vagus nerve stimulation is a Food and Drug Administration-approved, beneficial treatment option for long-term benefit in individuals with chronic UE limitations after ischemic stroke.

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03131960.