Effectiveness of non-invasive vagal nerve stimulation in Parkinson’s disease: A comprehensive systematic review and meta-analysis

•Non-invasive vagal nerve stimulation (nVNS) shows promise in addressing specific Parkinson’s disease symptoms.•The systematic review and meta-analysis evaluated 10 studies with 217 Parkinson’s patients.•Study findings indicate no significant changes in UPDRS scores, gait speed, or balance when comparing nVNS to controls.•Emphasizes the need for standardized protocols and larger trials to assess nVNS efficacy in Parkinson’s disease management. Parkinson’s disease (PD) is a debilitating neurodegenerative disorder characterized by movement impairments. Vagus nerve stimulation (VNS) is a non-invasive brain stimulation technique that has shown promise in treating various neurological conditions, including PD. This systematic review aimed to evaluate the existing evidence on the efficacy of nVNS in managing PD symptoms. A comprehensive literature search was conducted to identify relevant studies published up to July 2024. The included studies investigated the effect of nVNS on various PD motor symptoms. The quality of studies was assessed using the Cochrane Risk of Bias 2 (ROB-2) and NIH tool for RCTs, single-arm studies, and case series studies respectively. Statistical analysis was conducted using Review Manager version 5.4.1 with outcomes expressed as Mean differences (MD) with 95% confidence intervals (CI). The systematic review included eight randomized controlled trials (RCTs), one single-arm study, and one case series, encompassing a total of 217 patients with PD. The review revealed that nVNS in increasing Freezing of Gait (FOG) in PD (p = 0.04). However, no significant differences were found in UPDRS-III (p = 0.19 and p = 0.89 for on and off-medication conditions, respectively), UPDRS-II (p = 0.9), UPDRS-I (p = 0.46), Time Up and Go (p = 0.61), stand time (p = 0.87), walking speed (p = 0.22), or step length measured in meters (p = 0.8). Interestingly, a significant improvement was observed in step length measured in centimetres (p = 0.0005). No study reported serious adverse effects associated with nVNS treatment. Our finding suggests a potential benefit of nVNS in reducing FOG in PD, but did not demonstrate a significant improvement in other motor symptoms. Larger, longer follow-up studies are needed to confirm the effect nVNS on PD management. PROSPERO number: CRD42024574822.