Vagus Nerve Stimulation Shows Broad Promise Across Multiple Movement Disorders

The vagus nerve serves as a critical bidirectional communication highway between the brain and peripheral organs, making it an attractive therapeutic target in neurological conditions driven by circuit dysfunction, neuroinflammation, and neurotransmitter dysregulation — all hallmarks of movement disorders. This 2025 systematic review, published in Movement Disorders, synthesizes the most current preclinical and clinical evidence on vagus nerve stimulation (VNS) across Parkinson's disease (PD), atypical parkinsonisms, essential tremor (ET), cervical dystonia (CD), and Tourette's syndrome (TS).

The review identified 32 eligible studies from a search of PubMed, Web of Science, and Scopus covering 2020–2025. The majority focused on PD (14 clinical, 8 preclinical), with smaller bodies of work in tremor/ET (4 clinical, 2 preclinical), cervical dystonia (2 clinical), and Tourette's syndrome (1 clinical). One clinical study examined multisystem atrophy type C. VNS modalities included invasive cervical implants (iVNS), transcutaneous cervical VNS (tcVNS), and transcutaneous auricular VNS (taVNS).

Preclinical PD studies using rat models consistently showed that iVNS and taVNS preserved tyrosine hydroxylase-positive dopaminergic neurons in the substantia nigra, reduced alpha-synuclein aggregation, restored norepinephrine and dopamine levels, and suppressed neuroinflammatory markers (TNF-α, IL-1β, Iba-1, GFAP). A key mechanistic finding was that neuroprotective effects are primarily mediated by afferent vagal fibers projecting to the locus coeruleus and nucleus of the solitary tract, rather than efferent pathways. High-frequency microburst iVNS (300 Hz) outperformed standard and low-frequency protocols across multiple outcomes. The BDNF-TrkB signaling pathway was identified as a partial mediator of neuroprotection, though locomotor benefits persisted even when this pathway was pharmacologically blocked.

Clinically, VNS — particularly non-invasive taVNS — demonstrated improvements in both motor (gait, tremor, rigidity) and non-motor symptoms (cognition, autonomic function, mood) in PD patients. In essential tremor, studies reported tremor amplitude reduction during and after stimulation. Cervical dystonia and Tourette's syndrome studies were limited to small samples but suggested reductions in dystonic posturing and tic severity, respectively. Across all conditions, VNS appeared to modulate key neurotransmitters implicated in movement disorders: GABA, norepinephrine, dopamine, and acetylcholine.

The review highlights that non-invasive taVNS is an especially attractive approach given its favorable safety profile compared to surgical implantation, making long-term, high-frequency use feasible. However, the field lacks standardized stimulation protocols, and most clinical trials are small and heterogeneous. The authors call for large, well-powered randomized controlled trials with harmonized outcome measures to establish clinical efficacy and optimize parameters such as frequency, intensity, pulse width, and stimulation duration.