Objective: To investigate molecular mechanisms underlying non-invasive vagus nerve stimulation (nVNS) in Parkinson’s disease (PD) patients with freezing of gait (FOG).

Background: FOG remains one of the dopamine-resistant disabling gait abnormalities in PD. Neuromodulation with VNS may offer therapeutic benefit in FOG refractory to conventional treatment. In a cross-over trial, we observed that nVNS significantly improved motor symptoms in FOG patients. A key player in PD pathogenesis is neuroinflammation and there is growing evidence of involvement of peripheral inflammation. Since, VNS modulates inflammation, cervical nVNS might be useful in FOG treatment.

Method: Thirty-three PD patients with associated FOG were randomised to either nVNS or sham treatment. In this double-blind, sham-controlled trial, patients received six 2 min stimulations (total 12 min/day) of the nVNS/sham device (electroCore, Inc. USA) for one month. We measured selected neurotrophins, inflammatory markers and oxidative stress in serum, before and after stimulation. Inflammatory markers (TNF-α, IL-6, IL-10 and BDNF) were measured in serum by ELISA. Serum markers of oxidative stress, namely reduced glutathione and superoxide dismutase, were analysed by spectrophotometry.

Results: TNF-α levels were significantly reduced from baseline in patients receiving nVNS (28.1 to 23.5 pg/ml; p=0.028) but not in sham (23.2 to 24.7 pg/ml; p=0.499). The reduced glutathione concentration increased after nVNS (6.1 to 6.8 pg/ml; p=0.02) but did not change significantly after sham stimulation (6.7 to 6.1 pg/ml; p=0.05). BDNF levels significantly increased with the nVNS intervention (1946.7 to 2204.1 pg/ml; p=0.028) but decreased with sham stimulation (1943.7 to 1682.7 pg/ml; p=0.028). We did not find any significant differences in IL-6 (p=0.128), IL-10 (p=0.108) levels and the specific activity of superoxide dismutase between groups (p=0.058).

Conclusion: We provide the first evidence for the ability of nVNS to significantly reduce pro-inflammatory cytokines in PD patients and thereby indicate its anti-inflammatory mechanism. Increased serum BDNF also implicates neuroplastic changes by nVNS. The effects on antioxidant levels adds to its disease-modifying potential.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/non-invasive-vagus-nerve-stimulation-alters-molecular-markers-in-parkinsons-disease-patients-with-freezing-of-gait/