Description of a Novel, Surgically Implanted Neuromodulatory Technique Known As Bilateral Epidural Prefrontal Cortical Stimulation (Epcs) for Treatment-Resistant Depression (TRD)

Summary

We describe the implantation of 4 epidural stimulation paddles directly above the dura mater over both the left and right frontopolar and dorsolateral prefrontal cortices. Placement was verified using postoperative computed tomography (CT) coregistered with presurgical magnetic resonance imaging (MRI).

Abstract

We describe the targeting, surgical technique, intraoperative testing, and postoperative programming strategy for the invasive neuromodulatory technique termed epidural prefrontal cortical stimulation (EpCS). While EpCS has been explored by several groups, the unique approach described here involves surgical placement of four epidural cortical stimulation paddles - two over the bilateral dorsolateral prefrontal cortex (DLPFC) and two over the frontopolar cortex (FPC). The safety and efficacy of this technique for treatment-resistant depression has been described previously by the authors. 5 subjects were implanted with EpCS (3 with major depression, 2 with bipolar affective disorder I, depressive type) and their depressive symptoms were followed for five years. Application of chronic electrical stimulation (10-15mA) across all four of these paddles produced a durable antidepressant response for 3 of 5 subjects at the five-year follow-up. This manuscript discusses the unique intraoperative testing strategy as well as the programming approaches employed in this study. We aim to give guidance into improving the effect size of this novel form of stimulation.

Introduction

Nonpharmacologic brain stimulation therapies have emerged as potentially promising treatments for a variety of illnesses, including depression¹. Depression is a disabling psychiatric disorder of melancholia that not only affects an individual's daily life and social functioning², but is a leading cause of premature mortality and disability worldwide³. Large clinical trials have shown that pharmacologic interventions have limited success in treating depression⁴. Roughly 41% of patients fail to respond to two adequate trials of pharmacologic treatment, which is the defini....

Protocol

These experiments were conducted at the Medical University of South Carolina (MUSC) in compliance with an Investigational Device Exemption issued to Ziad Nahas and later transferred to Edward Baron Short under US Food and Drug Administration (FDA) guidance. The MUSC Institutional Review Board approved the protocol.

1. Participants

1. For each subject, conduct comprehensive assessment including detailed neuropsychological testing at baseline and repeatedly after implantation. Fuse the .......

Discussion

In this manuscript, we describe the method of EpCS of the bilateral DLPFC and FPC for the treatment of TRD. This first iteration of bilateral EpCS of DLPFC and FPC resulted in a remission rate of 60% at five year follow-up, and 80% shortly thereafter, in a group of severely depressed patients³³. Despite years of chronic stimulation of the FPC and DLPFC, no changes were noted in neuropsychiatric measures of cognition and this method was generally well tolerated by all participants.

Materials

Name	Company	Catalog Number	Comments
3T MRI Scanner	Siemens
Computer workstation
Imaging software	University of South Caroline		MRIcro; http://www.sph.sc.edu/comd/rorden/mricro.html
Electrocardiography
Pulse oximetry
End-tidal CO2
Non-invasive blood pressure monitoring
Fentanyl (50-250 micrograms)
Propofol infusion (25-100 micrograms/kg/min
2% lidocaine with epinephrine (2ccs)
Equal mixture of 1% lidocaine with epinephrine 1:100,000 and bupivacaine 0.5% (5ccs)
Skull clamp with surgical pins	IntegraTM, Plainsboro, New Jersey		Mayfield
Neuronavigation system	BrainLab, Westchester, Illinois		VectorVision
Paddle leads with extensions	Medtronic Inc., Minneapolis, Minnesota		Resume
Pulse generater with 2 channels	Medtronic Inc., Minneapolis, Minnesota		Synergy
Neurostimulator	Medtronic Inc., Minneapolis, Minnesota		Activa PC/RC
Standard aesculap power-drill
Generic 4mm spherical diamond drill bit
Plates and microscrews	Stryker, Kalamazoo, Michigan		Leibinger "Dog-bone" style
Bacitracin solution
Vancomycin power
Gelfoam
2-0 vicryl sutures
3-0 nylon sutures
Sterile dressing materals
Endotracheal anesthesia			As dictated by patient's history and anesthesiologist's preference
3-0 vicryl sutures
4-0 nylon sutures
High resolution spiral CT scan without contrast
Opiate analgesics
Programmer wand	Medtronic Inc., Minneapolis, Minnesota		N'Vision Clinician Programmer