Investigation of Deep Brain Stimulation Mechanisms During Implantable Pulse Generator Replacement Surgery

Abstract

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