Efficacy and safety of vagus nerve stimulation on upper extremity motor function in patients with stroke: A meta-analysis of randomized controlled trials

Abstract

Background: In 2021, the U.S. Food and Drug Administration (FDA) approved paired vagus nerve stimulation (VNS) for patients with moderate-to-severe upper extremity motor impairments following chronic ischemic stroke.

Objective: Previous meta-analyses have shown that VNS may impact stroke rehabilitation, but each has some limitations.

Methods: PubMed, Ovid, Cochrane Library, ScienceDirect, Web of Science and WHO ICTRP databases were searched until July 14, 2022 for randomized controlled trials (RCTs). We defined primary outcomes as Fugl-Meyer Assessment for Upper Extremity (FMA-UE) and Wolf Motor Function Test (WMFT). Subgroup analyses included types of VNS, time since onset and long-term effects. Secondary outcomes included adverse events of VNS.

Results: Eight RCTs involving 266 patients were analyzed, of which five used direct VNS and three transcutaneous auricular VNS. The results revealed that VNS enhanced upper extremity function via FMA-UE (SMD = 0.73; 95% CI: 0.48 to 0.99; P < 0.00001) and WMFT (SMD = 0.82; 95% CI:0.52 to 1.13; P < 0.00001) in comparison to the control group, but showed no significant change on long-term effects of FMA-UE (SMD = 0.69; 95% CI: - 0.06 to 1.44; P = 0.07). There was no difference in adverse events between the VNS and control groups (RR = 1.16; 95% CI: 0.46 to 2.92; P = 0.74).

Conclusion: For stroke victims with upper limb disabilities, VNS paired with rehabilitation was significantly safe and effective. More high-quality multicentric RCTs are needed to validate this conclusion.

Keywords: Vagus nerve stimulation; meta-analysis; rehabilitation; stroke; upper-limb function.