Chronic nerve health following implantation of femoral nerve cuff electrodes.

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.

Sum of phase-shifted sinusoids stimulation prolongs paralyzed muscle output.

Neuroprostheses that activate musculature of the lower extremities can enable standing and movement after paralysis. Current systems are functionally limited by rapid muscle fatigue induced by conventional, non-varying stimulus waveforms. Previous work has shown that sum of phase-shifted sinusoids (SOPS) stimulation, which selectively modulates activation of individual motor unit pools (MUPs) to lower the duty cycle of each while maintaining a high net muscle output, improves joint moment maintenance but introduces greater instability over conventional stimulation. In this case study, implementation of SOPS stimulation with a real-time feedback controller successfully decreased joint moment instability and further prolonged joint moment output with increased stimulation efficiency over open-loop approaches in one participant with spinal cord injury. These findings demonstrate the potential for closed-loop SOPS to improve functionality of neuroprosthetic systems.

Intraoperative Responses May Predict Chronic Performance of Composite Flat Interface Nerve Electrodes on Human Femoral Nerves.

Peripheral nerve cuff electrodes (NCEs) in motor system neuroprostheses can generate strong muscle contractions and enhance surgical efficiency by accessing multiple muscles from a single proximal location. Predicting chronic performance of high contact density NCEs based on intraoperative observations would facilitate implantation at locations that maximize selective recruitment, immediate connection of optimal contacts to implanted pulse generators (IPGs) with limited output channels, and initiation of postoperative rehabilitation as soon as possible after surgery. However, the stability of NCE intraoperative recruitment to predict chronic performance has not been documented. Here we report the first-in-human application of a specific NCE, the composite flat interface nerve electrode (C-FINE), at a new and anatomically challenging location on the femoral nerve close to the inguinal ligaments. EMG and moment recruitment curves were recorded for each of the 8 contacts in 2 C-FINE intraoperatively, perioperatively, and chronically for 6 months. Intraoperative measurements predicted chronic outcomes for 87.5% of contacts with 14/16 recruiting the same muscles at 6 months as intraoperatively. In both 8-contact C-FINEs, 3 contacts elicited hip flexion and 5 selectively generated knee extension, 3 of which activated independent motor unit populations each sufficient to support standing. Recruitment order stabilized in less than 3 weeks and did not change thereafter. While confirmation of these results will be required with future studies and implant locations, this suggests that remobilization and stimulated exercise may be initiated 3 weeks after surgery with little risk of altering performance.

"Long-term stability of stimulating spiral nerve cuff electrodes on human peripheral nerves".

BACKGROUND: Electrical stimulation of the peripheral nerves has been shown to be effective in restoring sensory and motor functions in the lower and upper extremities. This neural stimulation can be applied via non-penetrating spiral nerve cuff electrodes, though minimal information has been published regarding their long-term performance for multiple years after implantation. METHODS: Since 2005, 14 human volunteers with cervical or thoracic spinal cord injuries, or upper limb amputation, were chronically implanted with a total of 50 spiral nerve cuff electrodes on 10 different nerves (mean time post-implant 6.7 ± 3.1 years). The primary outcome measures utilized in this study were muscle recruitment curves, charge thresholds, and percent overlap of recruited motor unit populations. RESULTS: In the eight recipients still actively involved in research studies, 44/45 of the spiral contacts were still functional. In four participants regularly studied over the course of 1 month to 10.4 years, the charge thresholds of the majority of individual contacts remained stable over time. The four participants with spiral cuffs on their femoral nerves were all able to generate sufficient moment to keep the knees locked during standing after 2-4.5 years. The dorsiflexion moment produced by all four fibular nerve cuffs in the active participants exceeded the value required to prevent foot drop, but no tibial nerve cuffs were able to meet the plantarflexion moment that occurs during push-off at a normal walking speed. The selectivity of two multi-contact spiral cuffs was examined and both were still highly selective for different motor unit populations for up to 6.3 years after implantation. CONCLUSIONS: The spiral nerve cuffs examined remain functional in motor and sensory neuroprostheses for 2-11 years after implantation. They exhibit stable charge thresholds, clinically relevant recruitment properties, and functional muscle selectivity. Non-penetrating spiral nerve cuff electrodes appear to be a suitable option for long-term clinical use on human peripheral nerves in implanted neuroprostheses.

Efficient search and fit methods to find nerve stimulation parameters for multi-contact electrodes.

This paper describes a method to efficiently sample EMG recruitment space over a wide range of pulse amplitude (PA) and pulse width (PW). A gradient based search method is developed to find high information areas of a recruitment surface. This search method is first examined in the context of simulated EMG recruitment data and its ability to sample and subsequently fit Gompertz-Function-inspired surfaces to it. The search method is then used to determine parameters when stimulating through an 8 contact flat interface nerve electrode (FINE). The recorded EMG recruitment data are then used to validate the Gompertz surface fitting method as well as the search method.