Effects of non-invasive vagus nerve stimulation on clinical symptoms and molecular biomarkers in Parkinson's disease.

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 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 neurotrophins, inflammatory markers and markers of oxidative stress in serum. Thirty-three PD patients with freezing of gait (FOG) were randomized to either active nVNS or sham nVNS. After baseline assessments, patients were instructed to deliver six 2 min stimulations (12 min/day) of the active nVNS/sham nVNS device for 1 month at home. Patients were then re-assessed. After a one-month washout period, they were allocated to the alternate treatment arm and the same process was followed. Significant improvements in key gait parameters (speed, stance time and step length) were observed with active nVNS. While serum tumor necrosis factor- α decreased, glutathione and brain-derived neurotrophic factor levels increased significantly (p < 0.05) after active nVNS treatment. Here we present the first evidence of the efficacy and safety of nVNS in the treatment of gait in PD patients, and propose that nVNS can be used as an adjunctive therapy in the management of PD patients, especially those suffering from FOG. Clinical trial registration: identifier ISRCTN14797144.

Non-invasive vagus nerve stimulation improves clinical and molecular biomarkers of Parkinson's disease in patients with freezing of gait.

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.

Dance movement therapy in rehabilitation of Parkinson's disease - A feasibility study.

INTRODUCTION: Environmental enrichment during physical exercise was found beneficial in neurological disorders. Application of dance in a structured way could effectively enhance the environment of physical rehabilitation. Therefore, dance therapy can be an alternative exercise program with potential benefit in affect, cognition and social integration in various neurological disorders. OBJECTIVE: This pre-post experimental study without control was designed to assess the impact of dance movement therapy on cognition, quality of life and motor symptoms in PD patients. METHODS: A group of 10 mild-moderate PD patients from Movement Disorders Clinic; I-NK, participated in group sessions for a period of 2 months (twice a week). Each session involved verbal communication followed by warming up movements and concluded with target oriented physical activities, focused on physical symptoms, emotional and cognitive aspects. All the patients were assessed before and after the intervention using Unified Parkinson's Disease Rating Scale part III (UPDRS part III), Hoehn and Yahr Scale (H and Y), Parkinson's Disease Questionnaire 39 (PDQ-39) and Montreal Cognitive Assessment (MOCA). RESULTS: We observed a change in median MOCA score from 19.00 to 22.00 (p .027). PDQ 39 also showed change in median score from 59.50 to 30.00 (p .027). The change in UPDRS III (0.08) and H and Y (0.157) failed to reach significant limit. CONCLUSION: Dance Movement Therapy was found beneficial in overall cognition and quality of life in patients with mild-moderate PD. Studies with larger sample size will assess the long-term safety and effectiveness of this alternative therapy in future.

Inflammasome and α-synuclein in Parkinson's disease: A cross-sectional study.

BACKGROUND: Alpha-synuclein and inflammatory pathology are evident in Parkinson's disease (PD) but, their link to disease pathogenesis needs further elucidation. OBJECTIVES: To explore α-synuclein-mediated inflammation in the serum of PD patients and its link with disease severity. METHODS: Serum levels of IL-1ß, NLRP3, total and phosphorylated α-synuclein were compared. RESULTS: IL-1ß, NLRP3 levels were significantly increased in PD. We also observed a linear correlation of NLRP3 with α-synuclein. Phosphorylated α-synuclein levels were significantly elevated in later stages of PD. CONCLUSIONS: The α-synuclein-NLRP3 mediated inflammation may underline the pathophysiology of PD and might serve as a novel therapeutic target in PD.

Slowed Movement Stopping in Parkinson's Disease and Focal Dystonia is Improved by Standard Treatment.

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.