Efficacy of non-invasive Vagus nerve stimulation on Parkinson’s disease: A systematic review and meta-analysis

Purpose: Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms. Current treatments, primarily dopaminergic drugs, improve motor symptoms but have limitations and side effects. Non-pharmacological interventions like deep brain stimulation (DBS) and vagus nerve stimulation (VNS) are being explored for their potential to address both motor and non-motor symptoms, with VNS showing promise in preclinical models.Methods: A systematic review was conducted in September 2024 by searching PubMed, Scopus, and Web of Science, following the PRISMA guideline. The selection process involved a two-phase screening by independent researchers, with a third reviewer resolving discrepancies. Data extraction was performed using a standardized Excel sheet. Statistical analysis was performed using a random-effects model, while bias was evaluated with the ROBINS-I tool for non-randomized studies.Results: A total of 14 studies involving 321 patients undergoing non-invasive VNS were included in the analysis. Compared to control groups, no statistically significant effects were observed for MDS-UPDRS I (p=0.37) and III (p=0.48), postural sway (p=0.34), stride velocity variability (p=0.61), stride length (p=1.39), step length (p=1.71), stand time (p=0.35), rotation time (p=0.50), or freezing of gait (FOG; p=0.91). However, VNS did show a significant positive effect on step length variability (SMD=-1.09, p<0.0001).Conclusion: VNS shows potential as a non-pharmacological treatment for PD, particularly for step length variability. While broader effects on motor and non-motor symptoms require further investigation, the therapy appears safe and may modulate brain function and neuroinflammation.