Vagus Nerve Stimulation in Movement Disorders, from Principles to a Systematic Review of Evidence

Background: The vagus nerve (VN), the principal component of the parasympathetic branch of the autonomic nervous system (ANS), mediates bidirec communication between the central nervous system (CNS) and peripheral organs. Vagus nerve stimulation (VNS), delivered through invasive (iVNS) or non-invasive (transcutaneous cervical [tcVNS] and transcutaneous auricular [taVNS]), exerts multimodal effects on multiple circuits and neurotransmitters, and is currently under investigation in movement disorders. Objectives: This systematic review evaluates the therapeutic potential of VNS in movement disorders (MDs), with a focus on Parkinson's disease (PD), parkinsonism, tremor and essential tremor (ET), cervical dystonia (CD), and Tourette's syndrome (TS). Methods: A systematic search of PubMed, Web of Science, and Scopus was conducted for studies published between 2020 and 2025, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Results: Thirty-two studies met the inclusion criteria: 22 on PD or parkinsonism (14 clinical and 8 preclinical on PD, 1 clinical on multisystem atrophy), 6 on tremor and ET (4 clinical, 2 preclinical), 2 clinical studies on CD, and 1 clinical study on TS. Across conditions, VNS was reported to improve motor and non-motor, enhance synaptic plasticity, modulate neurotransmitter activity relevant to MDs (GABA, norepinephrine, dopamine, and acetylcholine), and reduce neuroinflammation. Conclusions: Current evidence supports the multimodal effect of VNS in MDs, particularly in PD, where the most consistent benefits were observed. Non-invasive taVNS represents a promising, safer alternative to iVNS. Larger randomized controlled trials with standardized protocols are needed to validate efficacy, optimize stimulation parameters, and determine long-term clinical and biological impact. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.