Noninvasive vagus nerve stimulation (nVNS) may improve gait and other motor symptoms in patients with Parkinson disease, according to the results of biomarker research published in Nature.

Neurostimulation is already used to treat epilepsy, migraine, and cluster headache. The researchers hypothesized that nVNS may address neuroinflammation in Parkinson disease.

The randomized, double-blind, sham-controlled, crossover study included 36 participants with Parkinson disease, with 17 randomly assigned to receive nVNS group and 19 to receive sham stimulation initially. A total of 21 patients completed both arms of the crossover study. The researchers looked at nVNS as an adjunct to standard of care for 1 month, focusing on the impact of treatment on freezing of gait. The researchers measured serum biomarkers of inflammation and oxidative stress as well as brain-derived neurotrophic factor (BDNF).


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The researchers found that velocity increased by 16% (P =.018), step length increased by 11% (P =.021) and step time decreased by 16% (P =.003) in the active nVNS group. There were no significant changes in velocity (2.3%; P =1.0), step length (1%; P =1.0) or step time (1.7%; P =.708) in the sham group.

Clinical scores before and after treatment in the 2 groups separately showed improved clinical outcome measures in both groups. Unified Parkinson’s Disease Rating Scale Parts II and III (UPDRS II, III), falls efficacy scale score, and freezing of gait questionnaire scores all improved significantly in both groups.

Although the results are “promising” according to the researchers, they found no significant difference between the groups after correlation for multiple comparisons. The researchers also did not measure molecular biomarkers. The video-based estimation of freezing of gait is another limitation.

“Overall, our results provide the first evidence that nVNS downregulates major pro-inflammatory cytokines, upregulates BDNF and increases levels of the antioxidant (reduced glutathione) in [patients with Parkinson disease], and that nVNS might have disease-modifying effects in [Parkinson disease],” the researchers said. “Moreover, BDNF, [tumor necrosis factor]-α and reduced glutathione might serve as biomarkers, alongside improvement in motor symptoms” in patients with Parkinson disease.

Reference

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 Parkinsons Dis. 2021;7(1):46. doi:10.1038/s41531-021-00190-x