Investigation of deep brain stimulation mechanisms during implantable pulse generator replacement surgery

Abstract

Background: Direct testing of deep brain stimulation (DBS) mechanisms in humans is needed to assess therapy and to understand stimulation effects.

Objective: We developed an innovative paradigm for investigation of DBS on human movement disorders. Temporary connection to the DBS electrode during implantable pulse generator (IPG) replacement permitted analysis of novel patterns of stimulation on motor symptoms, which could enhance efficacy and improve battery life.

Materials and methods: Patients enrolled in this prospective, Institutional Review Board-approved study underwent IPG replacement using local (monitored) anesthesia. Following device explant, the DBS electrode was connected to an external, isolated electrical stimulator using a sterile adapter cable. Different temporal patterns of stimulation were delivered while quantifying upper-extremity tremor (tri-axial accelerometry) or bradykinesia (finger-tapping). Upon experiment completion, the new IPG was implanted.

Results: Among 159 IPG replacements from 2005 to 2011, 56 patients agreed to the research study (16 essential tremor [ET], 31 Parkinson's disease [PD], 5 mixed ET/PD tremor, 3 multiple sclerosis, 1 tremor/myoclonus). Surgical procedures were extended by 42 ± 8.2 min in 37 patients completing the study. Motor symptoms varied with stimulation pattern, with some patterns showing improved tremor or bradykinesia control. No postoperative infections or complications were observed in the 159 patients.

Conclusion: IPG replacement occurs when the DBS/brain interface is stable and patients demonstrate symptom reduction with known stimulation parameters. Conducting research at this time point avoids DBS implant issues, including temporary microlesion effects, fluctuating electrode impedances, and technical limitations of contemporary IPGs, providing advantageous conditions to conduct translational DBS research with minimal additional risk to research subjects.

Keywords: Deep brain stimulation; movement disorders; subthalamic nucleus; thalamus.

© 2013 International Neuromodulation Society.

Figures

Figure 1. Intraoperative Setup and Instrumentation

During the IPG replacement procedure it is important to maintain the sterile field (since an implant is involved), to allow ready access to the patient by the anesthesiologist for monitoring and assessment of the clinical condition, to allow easy and full control of the extremity being tested by the experimenters, and to maintain a visual path from the patient to the experimenters for instruction and to view the extremity being controlled. The diagram shows how these various goals are achieved, with a partial drape across the patient and complete separation of the sterile surgical field and the non-sterile experimentation and monitoring region.

Figure 2. Research Equipment

Custom stimulation trains are generated by (A) a laptop-controlled, (B) isolated multifunction data acquisition (DAQ) device. Unilateral stimulation is applied through (C) an optical stimulus isolator using stimulation contacts selected by (D) a custom passive switch box connected to the stimulation electrode via a sterile cable (E) and adaptor (F). Bradykinesia (G) and tremor (H) quantification signals are digitized by the DAQ unit and stored on the laptop.

Figure 3. Experimental Trial Design

Protocols for measuring tremor (above) and bradykinesia (below) include control trials with DBS off (Pre) to establish baseline symptom severity, which may vary with time, followed by trials with DBS on (DBS) to determine the effect of the stimulation treatment. Motor symptoms were quantified during 20 sec trials every 60 sec (tremor) or 120 sec (bradykinesia), and this pattern was repeated for each stimulation treatment.

Figure 4. Typical Results

Tremor amplitude (A) measured by accelerometric recordings show modulation by DBS. The power spectral density (B) of the recordings was integrated from 1-20 Hz to yield tremor power (C), which decreased with DBS ON. Parkinsonian finger-tapping durations (D) were regularized with DBS ON, decreasing the log-transformed coefficient of variation (CV) of tap duration (E).