Objective: We used wearable inertion motion sensors (WMS) to compare the acute effects of transcutaneous auricular vagal stimulation (taVNS) at 100Hz (taVNS100), 25Hz (taVNS25), and sham (sVNS) on levodopa (LD) responsive and non-responsive gait features in Parkinson’s disease(PD).

Background: Animal and clinical studies suggest that noninvasive VNS (nVNS) has a potential to modulate both LD responsive and non-responsive features of PD^1-5. However, the evidence for taVNS effect on gait in PD patients is lacking and the optimal stimulation parameters remain unknown. We assessed the effect of taVNS on gait features considered most responsive to LD, including range of motion of arm swing (RomAS), gait speed (GS), arm peak velocity (pvA), and step length (SL); and gait features considered least responsive to levodopa, including range of motion of the first step (RomFS), duration of first step (dFS), anticipatory postural adjustments duration (APAd) and asymmetry in the range of motion of arm swing (RomA) (Curtze et al., 2016⁶). We also assessed the cadence (CDN) and cycle duration (CD).

Method: 9 advanced PD (Hoehn-Yahr>2) patients were included in a within-subject, double-blind, sham-controlled study. Two instrumented stand and walk tests were recorded with WMS in the ON state at baseline, and during 3 types of stimulation: taVNS100, taVNS25, and sVNS (randomized).  taVNS was applied at left cymba conchae with parameters: square-shaped pseudobiphasic 300μs wide pulse, interpulse duration 80μs, pulse intensity 0,1mA above the perceptual threshold. For sVNS the earlobe was stimulated. We performed a rmANOVA (within subject factors VNS and left_right if applicable) and a generalized mixed model for all measures with missing values.

Results: VNS effect was significant for RomAS (p=0,04), GS (p=0,001), SL (p=0,026), RomFS (p=0,037), dFS (p=0,04), CDN (p=0,001) and CD (p=0,018). Compared to baseline (corrected for multiple comparisons), taVNS25 significantly improved RomFS, CND, GS, SL and CD, while taVNS100 improved GS. None of the measures were improved on sVNS.

Conclusion: Our pilot study indicates that in PD, taVNS has a potential to modulate LD nonresponsive and LD responsive (over and above the LD effect) gait features (RomFS, dFS and CDN, CD, GS, SL), with an overall superior effect of taVNS at 25 Hz compared to taVNS at 100 Hz. We are further recruiting participants.

References: 1. Jiang Y, Cao Z, Ma H, et al. Auricular Vagus Nerve Stimulation Exerts Antiinflammatory Effects and Immune Regulatory Function in a 6-OHDA Model of Parkinson’s Disease. Neurochem Res. 2018;43(11):2155-2164. doi:10.1007/s11064-018-2639-z
2. Mondal B, Choudhury S, Banerjee R, et al. Non-invasive vagus nerve stimulation improves clinical and molecular biomarkers of Parkinson’s disease in patients with freezing of gait. NPJ Park Dis. 2021;7(1). doi:10.1038/S41531-021-00190-X
3. Mondal B, Choudhury S, Chatterjee K, et al. Therapeutic effect of non-invasive vagus nerve stimulation in gait disturbance and freezing in Parkinson’s disease patients. Parkinsonism Relat Disord. 2018;46:e21. doi:10.1016/j.parkreldis.2017.11.070
4. Cakmak YO, Apaydin H, Kiziltan G, et al. Rapid Alleviation of Parkinson’s Disease Symptoms via Electrostimulation of Intrinsic Auricular Muscle Zones. Front Hum Neurosci. 2017;11:338. doi:10.3389/fnhum.2017.00338
5. Morris R, Yarnall AJ, Hunter H, Taylor JP, Baker MR, Rochester L. Noninvasive vagus nerve stimulation to target gait impairment in Parkinson’s disease. Mov Disord. 2019;34(6):918-919. doi:10.1002/mds.27664
6. Curtze C, Nutt JG, Carlson-Kuhta P, Mancini M, Horak FB. Objective Gait and Balance Impairments Relate to Balance Confidence and Perceived Mobility in People With Parkinson Disease. Phys Ther. 2016;96(11):1734-1743. doi:10.2522/ptj.20150662

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MDS Abstracts - https://www.mdsabstracts.org/abstract/transcutaneous-auricular-vagal-nerve-stimulation-has-frequency-depended-propensity-to-improve-gait-in-parkinsons-disease-a-pilot-study/