Efficacy of combined vagus nerve stimulation and exercise training for upper limb recovery in people with stroke: a systematic review and meta-analysis

Background: Recent emerging evidence suggests that vagus nerve stimulation combined with exercise training (VNS+training) is effective in improving upper limb recovery in people with stroke. The current study aimed (1) to conduct a meta-analysis of the effectiveness VNS+training on upper limb recovery and (2) to identify potential factors that may affect the effect size (ES)of VNS+training in people with stroke. Methods: The electronic databases CINAHL, Medline, Cochrane Library, EMBASE, PubMed, Scopus, Web of Science, CINAHL, CNKI, and WANFANG, were systematically searched from inception to July 2025. Studies investigating the effectiveness of VNS+training on upper limb recovery in people with stroke were included. Results: A total of 13 articles were included in the systematic review, and data from 10 discrete studies with 424 participants were included in the meta-analysis. The ES of VNS+training was large in motor impairment (g = 1.264, 95% CI = 0.727-1.800) and in motor function (g = 0.728, 95% CI = 0.354-1.102) and was moderate in activities of daily living (ADL) (g = 0.508, 95% CI = 0.190-0.826). Subgroup analyses revealed larger effects for participants who received VNS prior to exercise training (with transcutaneous auricular VNS and at acute/subacute phase of stroke). Conclusion: The effectiveness of VNS+training in improving upper limb impairment, function, and ADL in people with stroke were found to be significantly higher than that of control group. The larger ES suggests that prior taVNS may have a more beneficial effect than concurrent taVNS. Further well-designed, adequately powered studies are needed to confirm these findings and directly compare prior versus concurrent taVNS.