Effects of Transcutaneous Auricular Vagus Nerve Stimulation With Rehabilitation on the Recovery of Upper Extremity Function After Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Upper limb motor dysfunction after stroke can significantly impede activities of daily living and quality of life. Transcutaneous auricular vagus nerve stimulation (taVNS) is a novel noninvasive treatment for stroke. Its combination with rehabilitation is a growing trend. OBJECTIVE: To explore the effects of taVNS combined with rehabilitation on upper limb function poststroke. METHODS: PubMed, EMBASE, Web of Science, EBSCO, CINAHL, and the Cochrane Library databases were searched up to September 16th, 2024. Two reviewers screened studies from these databases for eligible randomized controlled trials (RCTs) and extracted the data independently. The Cochrane collaboration tool (RoB 2.0) was used to assess the risk of bias. RESULTS: Four studies with 129 participants were included. Compared to controls, augmented treatment with taVNS had preferable effect on improving upper limb motor function after stroke (all outcomes: standardized mean difference [SMD] = 1.28, 95% CI: 0.65-1.90, I 2 = 72%, and p  < 0.0001; Fugl-Meyer assessment [FMA]: MD = 3.66, 95% CI: 0.50-6.83, I 2 = 90%, and p=0.02; Wolf Motor Function Test [WMFT]: MD = 6.77, 95% CI: -0.07 to 13.61, I 2 = 88%, and p=0.05)], especially combined with conventional rehabilitation (FMA: MD = 5.91, 95% CI: 1.37-10.45, I 2 = 90%, p=0.01). However, data from 3-month follow-up showed the similar therapeutic effects of rehabilitation with or without taVNS (FMA: MD = 4.66, 95% CI: -1.22 to 10.54, I 2 = 93%, and p=0.12; WMFT: MD = 6.86, 95% CI: -5.91 to 19.62, I 2 = 96%, and p=0.29). No obvious side effects were reported. CONCLUSION: This meta-analysis showed augmented effect of taVNS on rehabilitation therapy in paretic upper limb motor function poststroke, especially combined with conventional rehabilitation. However, the high heterogeneity of aggregated results indicates more rigorously designed studies are needed.