Electrophysiological Guidance of Epidural Electrode Array Implantation over the Human Lumbosacral Spinal Cord to Enable Motor Function after Chronic Paralysis.

Jonathan S Calvert,Jeffrey A Strommen,Kendall H Lee,Kristin D Zhao,Megan L Gill,Desmond A Brown,Dimitry G Sayenko,Daniel D Veith,Igor A Lavrov,Margaux B Linde,V Reggie Edgerton,Yury P Gerasimenko,Cesar Lopez,Lisa A Beck,Peter J Grahn,Meegan G Van Straaten

doi:10.1089/neu.2018.5921

Abstract

Epidural electrical stimulation (EES) of the spinal cord has been shown to restore function after spinal cord injury (SCI). Characterization of EES-evoked motor responses has provided a basic understanding of spinal sensorimotor network activity related to EES-enabled motor activity of the lower extremities. However, the use of EES-evoked motor responses to guide EES system implantation over the spinal cord and their relation to post-operative EES-enabled function in humans with chronic paralysis attributed to SCI has yet to be described. Herein, we describe the surgical and intraoperative electrophysiological approach used, followed by initial EES-enabled results observed in 2 human subjects with motor complete paralysis who were enrolled in a clinical trial investigating the use of EES to enable motor functions after SCI. The 16-contact electrode array was initially positioned under fluoroscopic guidance. Then, EES-evoked motor responses were recorded from select leg muscles and displayed in real time to determine electrode array proximity to spinal cord regions associated with motor activity of the lower extremities. Acceptable array positioning was determined based on achievement of selective proximal or distal leg muscle activity, as well as bilateral muscle activation. Motor response latencies were not significantly different between intraoperative recordings and post-operative recordings, indicating that array positioning remained stable. Additionally, EES enabled intentional control of step-like activity in both subjects within the first 5 days of testing. These results suggest that the use of EES-evoked motor responses may guide intraoperative positioning of epidural electrodes to target spinal cord circuitry to enable motor functions after SCI.

Highlights

Severe spinal trauma may result in spinal cord injury (SCI) with permanent, devastating loss of motor, sensory, and autonomic functions.[1,2] Scientific evidence from animal models of SCI and from early-phase clinical studies have reported positive outcomes such as decreased initial injury severity by pharmacological interventions,[3] repair of damaged spinal cord tissues by implantation of biomaterials and engineered cells at the injury site,[4,5,6] or direct signal transmission through or around the injury using state-Ó Jonathan S
While attempting to replicate the results reported by Harkema and colleagues,[11,22] we reported that electrical stimulation (EES) enabled intentional control of lower extremity movements and standing within the first 2 weeks of EES in a subject diagnosed with motor complete paraplegia,[12] and over the course of 43 weeks of multimodal rehabilitation, he achieved independent stepping in the presence of EES.[23]
Two males diagnosed with a sensorimotor complete, American Spinal Injury Association Impairment Scale Grade A (AIS-A) SCI38 were enrolled in this clinical trial (NCT02592668), and both provided written, informed consent to experimental procedures

Summary

Introduction

Severe spinal trauma may result in spinal cord injury (SCI) with permanent, devastating loss of motor, sensory, and autonomic functions.[1,2] Scientific evidence from animal models of SCI and from early-phase clinical studies have reported positive outcomes such as decreased initial injury severity by pharmacological interventions,[3] repair of damaged spinal cord tissues by implantation of biomaterials and engineered cells at the injury site,[4,5,6] or direct signal transmission through or around the injury using state-Ó Jonathan S. We provide a detailed description of the surgical approach with results from intraoperative electrophysiology of EES-evoked motor responses from leg muscles indicating appropriate positioning of the EES electrode array to enable motor functions, such as step-like lower extremity movement, after recovery from EES implantation.

Results

Conclusion