No abstract

Non-invasive vagus nerve stimulation (nVNS) is an established neurostimulation therapy used in the treatment of epilepsy, migraine and cluster headache. In this randomized, double-blind, sham-controlled crossover trial we explored the role of nVNS in the treatment of gait and other motor symptoms in Parkinson’s disease (PD) patients. In a subgroup of patients, we measured selected neurotrophin levels and markers of inflammation and oxidative stress in serum, before and after the experimental intervention. Thirty-three PD patients with associated freezing of gait were randomised to either nVNS or sham. After baseline assessments, patients were instructed to deliver 6 two-minute stimulations (total 12 min/day) of the nVNS/sham device (electroCore, Inc. USA) for one month at home. Patients were then re-assessed. After a washout period of one month, the same patients were allocated to the alternate treatment arm and the same process was followed. Significant improvements in key gait parameters were observed with nVNS, including walking speed, stance time and step length, compared to sham. Similarly, overall motor function (MDS-UPDRS III) also improved significantly following nVNS stimulation. Serum Tumor Necrosis Factor (TNF)-α and glutathione levels decreased and brain-derived neurotrophic factor (BDNF) levels increased significantly (p < 0.05) after treatment with nVNS. Here we present the first double-blind sham-controlled trial evidence of the efficacy and safety of nVNS in the treatment of gait and motor function in patients with PD.

Patients with Parkinson’s disease and focal dystonia have difficulty in generating and preventing movement. Reaction time (RT) and stop signal reaction time (SSRT) measure the speed to initiate and stop a movement respectively. We developed a portable device to assess RT and SSRT. This incorporated a novel analysis to measure SSRT more efficiently (optimal combination SSRT, ocSSRT). After validation ocSSRT was measured in Parkinson’s disease patients without dyskinesia (PD), cervical dystonia (CD) and writer’s cramp. We also assessed how ocSSRT responded to L-dopa in PD patients and botulinum toxin injections in CD patients. Participants were instructed to release a button following a green LED flash on the device. On 25% of trials, a red LED flashed 5–195 ms after the green LED; participations were instructed to abort the button release on these trials. ocSSRT and RT were significantly prolonged in patients with Parkinson’s disease and focal dystonia (one-way ANOVA p < 0.001). Administration of L-dopa significantly improved ocSSRT and RT in PD patients (p < 0.001). Administration of botulinum toxin significantly improved ocSSRT, but not RT, in CD patients (p < 0.05). ocSSRT is an easily-administered bedside neuro-physiological tool; significantly prolonged ocSSRT is associated with PD and focal dystonia.