Chronic nerve health following implantation of femoral nerve cuff electrodes

Abstract

Background: Peripheral nerve stimulation with implanted nerve cuff electrodes can restore standing, stepping and other functions to individuals with spinal cord injury (SCI). We performed the first study to evaluate the clinical electrodiagnostic changes due to electrode implantation acutely, chronic presence on the nerve peri- and post-operatively, and long-term delivery of electrical stimulation.

Methods: A man with bilateral lower extremity paralysis secondary to cervical SCI sustained 5 years prior to enrollment received an implanted standing neuroprosthesis including composite flat interface nerve electrodes (C-FINEs) electrodes implanted around the proximal femoral nerves near the inguinal ligaments. Electromyography quantified neurophysiology preoperatively, intraoperatively, and through 1 year postoperatively. Stimulation charge thresholds, evoked knee extension moments, and weight distribution during standing quantified neuroprosthesis function over the same interval.

Results: Femoral compound motor unit action potentials increased 31% in amplitude and 34% in area while evoked knee extension moments increased significantly (p < 0.01) by 79% over 1 year of rehabilitation with standing and quadriceps exercises. Charge thresholds were low and stable, averaging 19.7 nC ± 6.2 (SEM). Changes in saphenous nerve action potentials and needle electromyography suggested minor nerve irritation perioperatively.

Conclusions: This is the first human trial reporting acute and chronic neurophysiologic changes due to application of and stimulation through nerve cuff electrodes. Electrodiagnostics indicated preserved nerve health with strengthened responses following stimulated exercise. Temporary electrodiagnostic changes suggest minor nerve irritation only intra- and peri-operatively, not continuing chronically nor impacting function. These outcomes follow implantation of a neuroprosthesis enabling standing and demonstrate the ability to safely implant electrodes on the proximal femoral nerve close to the inguinal ligament. We demonstrate the electrodiagnostic findings that can be expected from implanting nerve cuff electrodes and their time-course for resolution, potentially applicable to prostheses modulating other peripheral nerves and functions.

Trial registration: ClinicalTrials.gov NCT01923662 , retrospectively registered August 15, 2013.

Keywords: Chronic nerve health; Electrical stimulation; Electrodiagnostics and neuromuscular diseases; Electromyography; Rehabilitation; Spinal cord injury; peripheral nerve cuff electrodes.

Conflict of interest statement

The authors declare that they have no competing interest.

Figures

Fig. 1

C-FINEs, implantation on femoral nerves, percutaneous leads, and intraoperative EMG. a Example 8-contact C-FINE in open (top) and closed (bottom) configurations. Asterisk indicates flexible edges of C-FINE. b Images of C-FINE placed around femoral nerve (top). c Percutaneous leads approximately 3 months after implantation (bottom). White arrow indicates an area of mild, occasional erythema at one of the indwelling leads. d Intraoperative EMG collection (light blue boxes) and implant location compared to previous implants [1] (light green boxes and inset at top right). Note proximity of NCE to inguinal ligament to be implanted proximal to the first branches off the femoral nerve

Fig. 2

Implant diagram and C-FINE recipient standing using implanted neuroprosthesis. a Lead routing showing C-FINEs (purple) plugged into connectors (green) which are either connected to percutaneous leads (percutaneous phase, orange wires) or an IPG (standing phase, blue wires). Red wires indicate IPG connections to intramuscular electrodes which are used to stimulate muscles not innervated by the femoral nerves and are required for standing. b and c Pictures show subject standing from his wheelchair taken from his front (b) and from his side (c). External control unit communicates with the IPG via a pair of radiofrequency coils. A physical therapist is spotting the C-FINE recipient but is not providing support, as later confirmed by force plate measurements

Fig. 3

Experimental timeline. “Nerve health testing,” including NCS and needle EMG, was performed at 1 time-point preoperatively and 7 time-points postoperatively. “Functional testing,” including charge threshold and moment measurements, was performed intraoperatively without moment measurements and at 7 time-points postoperatively. Moment was collected at all postoperative time-points but was restricted to twitch moments only until the third week postoperatively. The percutaneous phase ended when a 16-channel IPG, full standing neuroprosthesis system was implanted. This required a reduction in the number of contacts for knee extension from 16 to 6 across both C-FINEs to allow stimulus channels to be assigned to intramuscular electrodes for hip and trunk extension

Fig. 4

Example of typical CMAP and SNAP. CMAP (left) of RF after surface stimulation of femoral nerve. Blue arrows indicate duration (horizontal) and amplitude (vertical) of the CMAP which gave an amplitude of 8.8 mV, and area of 47.8 mV ms. SNAP of the saphenous nerve (right) was recorded after stimulation of sensory fibers. The stimulus artifact extended to roughly − 40 μV on this plot but was cropped for readability. Blue arrows again measure duration and amplitude and this SNAP had an amplitude of 4.2 μV

Fig. 5

Summary of femoral motor and saphenous sensory nerve conduction studies. Time axis is the same for all plots with preoperative period shaded. Measurements in this region are used as baseline values. Dashed lines indicate C-FINE-elicited CMAPs. Solid lines indicate surface-elicited CMAPs (the clinical standard). CMAP is measured at RF. a Femoral MNCV. Mean MNCV of quadriceps muscles compared to clinical minimum normal velocities. Error bars represent SEM between velocities to the heads of quadriceps muscles. b Femoral CMAP Amplitudes: C-FINE-elicited compared to baselines surface-elicited 2 weeks preoperatively and minimum normal values. C-FINE-Elicited CMAPs also compared with subject sitting (hips flexed 90°) and supine. Error bars represent standard deviations between 3 trials of supramaximal stimulation. c Femoral CMAP Areas collected and presented identically to CMAP amplitudes and at the same time points. d Saphenous SNAP Amplitudes. Postoperative amplitudes compared to baseline elicited 2 weeks preoperatively and minimum normal amplitudes

Fig. 6

Stimulation charge thresholds from implantation through 1 year postoperatively. Thresholds defined by charge when rectified, integrated, normalized EMG (solid lines) or moments (dashed lines) reach 10% of maximum recorded value for a given muscle. Error bars on median measure represent SEM. Reduction in data points after 6 months due to removal of percutaneous leads and 3 out of 8 contacts chosen per C-FINE and connected to the IPG

Fig. 7

Knee moments normalized by body mass over 1 year on each of the selected knee extensor selective C-FINE contacts at 0.8 mA, 255 μs. These contacts were chosen because they were able to achieve strong knee extension moments with insignificant hip flexion. Error bars indicate standard deviation between contacts. Dashed line represents linear best-fit to mean tetanic moments. Based on linear regression t-testing, an increase in moment over 1 year is significant (p < 0.01 on the left and p < 0.02 on the right)

Fig. 8

Histogram of summed and normalized vertical component of ground reaction forces measured during quiet standing with take-home “standing” pattern, indicating percentage of body weight supported through legs