Efficacy and safety of vagus nerve stimulation on upper extremity motor function in patients with stroke: A meta-analysis of randomized controlled trials¹

Article type: Review Article

Authors: Wei, Tianqi^{a; 2} | Ge, Xiangyang^{b; 2} | Lu, Lingfeng^c | Li, Jing^d | Xu, Panpan^a | Wu, Qinfeng^{a; *}

Affiliations: [a] Department of Rehabilitation Medicine, The Affiliated Suzhou Hospital of Nanjing University Medical School, Jiangsu, China | [b] Department of Rehabilitation Medicine, Affiliated Maternity and Child Health Care Hospital of Nantong University, Jiangsu, China | [c] Department of Orthopedics, The Affiliated Suzhou Hospital of Nanjing Medical University, Jiangsu, China | [d] Department of Neurology, The Affiliated Suzhou Hospital of Nanjing University Medical School, Jiangsu, China

Correspondence: [*] Address for correspondence: Qinfeng Wu, Department of Rehabilitation Medicine, The Affiliated Suzhou Hospital of Nanjing University Medical School, Jiangsu, China. E-mail: [email protected].

Note: [1] This article received a correction notice (Erratum) with the reference 10.3233/NRE-236008, available at http://doi.org/10.3233/NRE-236008.

Note: [2] Equal contribution as first authors.

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, upper-limb function, stroke, rehabilitation, meta-analysis

DOI: 10.3233/NRE-230106

Journal: NeuroRehabilitation, vol. 53, no. 3, pp. 253-267, 2023