Dual threshold neural closed loop deep brain stimulation in Parkinson disease patients

• Main Authors: A. Velisar, J. Syrkin-Nikolau, Z. Blumenfeld, M.H. Trager, M.F. Afzal, V. Prabhakar, H. Bronte-Stewart
• Format: Article
• Language: English
• Published: Elsevier 2019-07-01
• Series: Brain Stimulation
• Subjects: Closed loop; Deep brain stimulation; Bradykinesia; Tremor; Parkinson's disease; Human
• Online Access: http://www.sciencedirect.com/science/article/pii/S1935861X19300737

Background: Closed loop deep brain stimulation (clDBS) in Parkinson's disease (PD) using subthalamic (STN) neural feedback has been shown to be efficacious only in the acute post-operative setting, using externalized leads and stimulators. Objective: To determine feasibility of neural (N)clDBS using the clinical implanted neurostimulator (Activa™ PC + S, FDA IDE approved) and a novel beta dual threshold algorithm in tremor and bradykinesia dominant PD patients on chronic DBS. Methods: 13 PD subjects (20 STNs), on open loop (ol)DBS for 22 ± 7.8 months, consented to NclDBS driven by beta (13–30 Hz) power using a dual threshold algorithm, based on patient specific therapeutic voltage windows. Tremor was assessed continuously, and bradykinesia was evaluated after 20 min of NclDBS using a repetitive wrist flexion-extension task (rWFE). Total electrical energy delivered (TEED) on NclDBS was compared to olDBS using the same active electrode. Results: NclDBS was tolerated for 21.67 [21.10–26.15] minutes; no subject stopped early. Resting beta band power was measurable and similar between tremor and bradykinesia dominant patients. NclDBS improved bradykinesia and tremor while delivering only 56.86% of the TEED of olDBS; rWFE velocity (p = 0.003) and frequency (p < 0.001) increased; tremor was below 0.15 rad/sec for 95.4% of the trial and averaged 0.26 rad/sec when present. Conclusion: This is the first study to demonstrate that STN NclDBS is feasible, efficacious and more efficient than olDBS in tremor and bradykinesia dominant PD patients, on long-term DBS, using an implanted clinical neurostimulator and driven by beta power with a novel dual threshold algorithm, based on customized therapeutic voltage windows.