Effects of Vagus Nerve Stimulation on Upper-Limb Motor Function After Stroke: A Systematic Review and Meta-Analysis of RCTs

Background
Stroke results in persistent upper-limb motor impairment, and survivors experience incomplete recovery despite standard rehabilitation. Vagus nerve stimulation (VNS) has emerged as a potential neuromodulatory adjunct capable of enhancing training-dependent plasticity. This meta-analysis evaluated the effectiveness of VNS combined with upper-limb rehabilitation in improving motor outcomes after stroke.
Methods
A systematic search of PubMed, the Cochrane Library, and CNKI from 2010 to November 2025 identified randomized controlled trials evaluating rehabilitation paired with implanted or transcutaneous VNS. The primary outcome was upper-limb motor recovery measured by Fugl-Meyer Assessment–Upper Extremity (FMA-UE) at the longest follow-up. Standardized mean differences (SMDs) were pooled using a random-effects model, and certainty of evidence was appraised with the GRADE approach.
Results
Eight RCTs involving 262 participants met inclusion criteria. Across all VNS modalities, rehabilitation paired with VNS significantly improved upper-limb motor function (SMD = 0.886, 95% CI: 0.098–1.674, p = 0.028). Subgroup analysis demonstrated that transcutaneous VNS showed a significant pooled effect (SMD = 1.332, 95% CI: 0.034–2.629, p = 0.044), whereas implanted VNS yielded a smaller, nonsignificant effect (SMD = 0.161, 95% CI: −0.166–0.487, p = 0.335). Improvements were directionally consistent across trials, though heterogeneity and small sample sizes limited certainty of evidence.
Conclusions
Vagus nerve stimulation paired with structured upper-limb rehabilitation enhance motor recovery after stroke. While the overall evidence remains constrained by heterogeneity and modest trial sizes, this review synthesizes emerging data supporting VNS as a promising adjunct to post-stroke neurorehabilitation and highlights the need for larger, standardized RCTs.