Effect of Combined Vagus Nerve Stimulation on Recovery of Upper Extremity Function in Patients with Stroke: A Systematic Review and Meta-Analysis

Objective: To evaluate the effectiveness of vagus nerve stimulation (VNS) combined with rehabilitation therapies in restoring upper extremity (UE) function following stroke. Data Sources A search was implemented in key databases along with hand searches of relevant papers and performed on 31 July 2021. Materials and Methods: Only randomized controlled trials (RCTs) assessing the effect of VNS focusing on UE dysfunction in patients post-stroke were identified in this systematic review. Data were extracted independently by two authors. The study was conducted by the Preferred Reporting Items for Meta-Analyses (PRISMA) guidelines. Meta-analyses were performed when deemed feasible. Results: Five RCTs involving 178 patients (VNS/C 87/91) were included. The primary outcome was the function assessment by upper UE Fugl-Meyer assessment (FMA-U). As secondary outcomes, strength was assessed with the Wolf motor function test (WMFT), the Stroke Impact Scale (SIS) and the Motor Activity Log (MAL). Meta-analysis showed a significant immediate favoring VNS-based rehabilitation (five studies) for improving upper extremity function after stroke (mean difference [MD] 3.31; 95% confidence interval [CI], 2.33-4.29; p < 0.0001,fixed-effects model), along the lines of the long-term effect (three studies) (MD = 3.13; 95% CI, 1.47--4.79; p < 0.0001,fixed-effects model). No effect was observed when compared with control groups in adverse outcomes (Risk Ratio [RR] 1.61; 95% CI, 0.65-3.99; P = 0.30). Conclusions: VNS combined with rehabilitation training may be considered as a promising intervention in UE recovery in stroke patients.