Eight-hours adaptive deep brain stimulation in patients with Parkinson disease

Abstract

Objectives: To assess the feasibility and clinical efficacy of local field potentials (LFPs)-based adaptive deep brain stimulation (aDBS) in patients with advanced Parkinson disease (PD) during daily activities in an open-label, nonblinded study.

Methods: We monitored neurophysiologic and clinical fluctuations during 2 perioperative experimental sessions lasting for up to 8 hours. On the first day, the patient took his/her daily medication, while on the second, he/she additionally underwent subthalamic nucleus aDBS driven by LFPs beta band power.

Results: The beta band power correlated in both experimental sessions with the patient's clinical state (Pearson correlation coefficient r = 0.506, p < 0.001, and r = 0.477, p < 0.001). aDBS after LFP changes was effective (30% improvement without medication [3-way analysis of variance, interaction day × medication p = 0.036; 30.5 ± 3.4 vs 22.2 ± 3.3, p = 0.003]), safe, and well tolerated in patients performing regular daily activities and taking additional dopaminergic medication. aDBS was able to decrease DBS amplitude during motor "on" states compared to "off" states (paired t test p = 0.046), and this automatic adjustment of STN-DBS prevented dyskinesias.

Conclusions: The main findings of our study are that aDBS is technically feasible in everyday life and provides a safe, well-tolerated, and effective treatment method for the management of clinical fluctuations.

Classification of evidence: This study provides Class IV evidence that for patients with advanced PD, aDBS is safe, well tolerated, and effective in controlling PD motor symptoms.

Figure 1. Experimental protocol and aDBS functioning

(A) Top timeline shows the activities recorded during the 8 hours (10 am–6 pm) for a representative patient. Middle plot represents the activity index (i.e., a custom index based on accelerometer data in the band of 0.5–4 Hz representing the amount of motor activity) corresponding to each activity, and the bottom trace is beta power percentage change from baseline throughout the 8 hours. Bottom arrows show the times in which the patient was assessed (baseline, peak dose 1, end dose 1, peak dose 2, end dose 2) and received levodopa. (B) Beta power changes from baseline in day 1 (top trace) and day 2 (bottom trace) of a representative patient (patient 4). The x-axis represents time (hours) and y-axis represents percent beta power change from baseline. Gray rectangles highlight beta power during clinical assessments (baseline, peak dose 1, end dose 1, peak dose 2, end dose 2). (C) Average beta power changes from baseline in day 1 (top trace) and day 2 (bottom trace). Only the time windows of ±10 minutes around clinical assessments were represented to allow averaging among patients. The x-axis represents time (hours) and y-axis represents percent beta power change from baseline. Gray rectangles highlight beta power during clinical assessments (baseline, peak dose 1, end dose 1, peak dose 2, end dose 2). aDBS = adaptive deep brain stimulation; AU = arbitrary units; UPDRS = Unified Parkinson's Disease Rating Scale.

Figure 2. aDBS efficacy on day 2

(A) Graph represents average UPDRS III values on day 1 (green line) and day 2 (light gray line) at baseline, at end dose/medication “off,” and at peak dose/medication “on.” Error bars are SEMs. UPDRS III values at end dose/medication “off” on day 1 were significantly different from those on day 2 and from those on peak dose/medication “on” on the same day 1. (B) Graph represents average UDysRS, part III and IV values on day 1 (green line) and on day 2 (light gray line) at baseline, at end dose/medication “off,” and at peak dose/medication “on.” Error bars are SEMs. No significant differences were detected among conditions. (C) Details of the UPDRS III values on day 1 (green line) and on day 2 (light gray line) at baseline, at end dose/medication “off,” and at peak dose/medication “on” in the 2 sessions throughout the whole 8-hour experiment. On day 1, only values at peak dose/medication “on” were different from baseline values, whereas on day 2, the difference was significant at all time points after aDBS was turned on. (D) Histogram represents the average voltage change in the peak dose/medication “on” condition (green) and in the end dose/medication “off” (light gray) during day 2. Error bars are SEMs. aDBS = adaptive deep brain stimulation; HSD = highest significant difference; UPDRS = Unified Parkinson's Disease Rating Scale; UDysRS = Unified Dyskinesias Rating Scale.