Transcutaneous Auricular Vagus Nerve Stimulation Shows Effectiveness as Parkinson Disease Gait Modulator

Massimo Marano, MD, PhD

Data from a small-scale study of patients with mild-to-moderate Parkinson disease (PD) showed that the use of transcutaneous auricular vagus nerve stimulation (taVNS) as an add-on to levodopa therapy improved several objective gait parameters and thus may be considered a valuable tool in the neuromodulation landscape of PD.¹

In the study, 12 patients with idiopathic PD were randomly assigned to either taVNS or control groups, and after 1 week all individuals were crossed over to the other. Despite direct data on duration not being collected, the putative effect of taVNS persisted for the time duration of the Unified Parkinson’s Disease Rating Scale (UPDRS) motor assessment, the flanker test (mean completion time, 52 seconds [±13.7]), and on the single 10-m timed up and go (10mTUG) test, a gait assessment (mean completion time, 28 seconds [±7.3]).

Lead investigator Massimo Marano, MD, PhD, Department of Neurology, Universita Campus Bio-Medico di Roma, and colleagues concluded that "even though its mechanism of action is still debated, VNS can entrain the ascending cholinergic and noradrenergic pathways, which are involved in cognitive processing and in locomotor abilities," adding that, "Moreover, the study should be replicated on a larger sample, allowing a more robust statistical methodology, eventually exploring VNS dosage and duration."

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Patients included in the study were on chronic levodopa therapy without a history of levodopa-induced dyskinesias, had UPDRS Part II item 15 scores of at least 1 or 2, indicating walking difficulties, and modified Hoehn and Yahr score of less than 3 while on medication. taVNS was delivered either on the left internal tragus (active) or the earlobe (control) in trains lasting 30 seconds each, composed of 600 pulses repeated every 4.5 minutes for 30 minutes (6 cycles). In addition to UPDRS Part III, patients were evaluated on a flanker test for reaction time, a digital 10mTUG test performed in duplicate, and a Visual Analogue Scale (VAS).

The approach was proven to be safe, as all 12 subjects completed both the real and control stimulation. Stride length (0.61 m; ±0.11; P = .005), swing amplitude (0.59 m; ±0.21; P = .018), gait speed (1.26 m/s; ±0.31; P = .029), and gait time showed significant changes only after patients were treated with taVNS. Between the active and control groups, there was no significant variation on rotation time, stand time, and sit time. Additionally, the flanker reaction time improved after taVNS (1.50 s; ±0.47; P = .005).

"In this study, taVNS improved some dopamine-dependent gait parameters (eg, stride length),” Marano et al wrote. “If proven true, this would add information to the growing literature on the association between the vagus nerve and the dopaminergic system. However, despite our results being in line with recent noninvasive cervical VNS experiments, it is still not possible to draw a firm conclusion."

REFERENCES
1. Marano M, Anzini G, Musumeci G, et al. Transcutaneous auricular vagus stimulation improves gait and reaction time in Parkinson’s disease. Mov Disord. Published July 21, 2022. doi:10.1002/mds.29166