Spiral Nerve Cuff Electrode Research Articles

The Fifth Bioelectronic Medicine Summit Hosted by the Feinstein Institutes for Medical Research (Manhasset, NY) and Columbia Engineering (NY, NY) at The Garden City Hotel, Garden City, NY 11530 on October 11-12th, 2022- Bioelectronic Medicine: Today’s Tools, Tomorrow’s Therapies

The Fifth Bioelectronic Medicine Summit Hosted by the Feinstein Institutes for Medical Research (Manhasset, NY) and Columbia Engineering (NY, NY) at The Garden City Hotel, Garden City, NY 11530 on October 11-12th, 2022- Bioelectronic Medicine: Today’s Tools, Tomorrow’s Therapies

\u201cLong-term stability of stimulating spiral nerve cuff electrodes on human peripheral nerves\u201d

BackgroundElectrical 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.MethodsSince 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.ResultsIn 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.ConclusionsThe 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.

Implanted Neuroprosthesis for Restoring Arm and Hand Function in People With High Level Tetraplegia

ObjectiveTo develop and apply an implanted neuroprosthesis to restore arm and hand function to individuals with high level tetraplegia. DesignCase study. SettingClinical research laboratory. ParticipantsIndividuals with spinal cord injuries (N=2) at or above the C4 motor level. InterventionsThe individuals were each implanted with 2 stimulators (24 stimulation channels and 4 myoelectric recording channels total). Stimulating electrodes were placed in the shoulder and arm, being, to our knowledge, the first long-term application of spiral nerve cuff electrodes to activate a human limb. Myoelectric recording electrodes were placed in the head and neck areas. Main Outcome MeasuresSuccessful installation and operation of the neuroprosthesis and electrode performance, range of motion, grasp strength, joint moments, and performance in activities of daily living. ResultsThe neuroprosthesis system was successfully implanted in both individuals. Spiral nerve cuff electrodes were placed around upper extremity nerves and activated the intended muscles. In both individuals, the neuroprosthesis has functioned properly for at least 2.5 years postimplant. Hand, wrist, forearm, elbow, and shoulder movements were achieved. A mobile arm support was needed to support the mass of the arm during functional activities. One individual was able to perform several activities of daily living with some limitations as a result of spasticity. The second individual was able to partially complete 2 activities of daily living. ConclusionsFunctional electrical stimulation is a feasible intervention for restoring arm and hand functions to individuals with high tetraplegia. Forces and movements were generated at the hand, wrist, elbow, and shoulder that allowed the performance of activities of daily living, with some limitations requiring the use of a mobile arm support to assist the stimulated shoulder forces.

Intraoperative evaluation of the spiral nerve cuff electrode on the femoral nerve trunk

Evaluation of the Case Western Reserve University spiral nerve cuff electrode on the femoral nerve trunk was performed intraoperatively in four subjects undergoing femoral-popliteal bypass surgery. The threshold, nerve size and selective activation capabilities of the electrode were examined. The activation thresholds for the first muscle to be recruited were 6.3, 9, 10.6, and 37.4 nC with pulse amplitudes ranging from 0.3 to 1 mA. The femoral nerve was found to have an elliptical cross-section with a major axis average length of 9 mm (8–12 mm) and a minor axis length of 1.5 mm. In all four subjects selective activation of the sartorius was obtained. In two subjects, the rectus femoris could also be selectively activated and in one subject the vastus medialis was selectively activated. Each electrode had four independent contacts that were evaluated separately. Small air bubbles were formed in the space over some contacts, preventing stimulation. This occurred in one contact in each electrode, leaving three effective stimulation channels. This issue has been corrected for future studies.

Stimulation Stability and Selectivity of Chronically Implanted Multicontact Nerve Cuff Electrodes in the Human Upper Extremity

Nine spiral nerve cuff electrodes were implanted in two human subjects for up to three years with no adverse functional effects. The objective of this study was to look at the long term nerve and muscle response to stimulation through nerve cuff electrodes. The nerve conduction velocity remained within the clinically accepted range for the entire testing period. The stimulation thresholds stabilized after approximately 20 weeks. The variability in the activation over time was not different from muscle-based electrodes used in implanted functional electrical stimulation systems. Three electrodes had multiple, independent contacts to evaluate selective recruitment of muscles. A single muscle could be selectively activated from each electrode using single-contact stimulation and the selectivity was increased with the use of field steering techniques. The selectivity after three years was consistent with selectivity measured during the implant surgery. Nerve cuff electrodes are effective for chronic muscle activation and multichannel functional electrical stimulation in humans.

Human Nerve Stimulation Thresholds and Selectivity Using a Multi-contact Nerve Cuff Electrode

Testing of the recruitment properties and selective activation capabilities of a multi-contact spiral nerve cuff electrode was performed intraoperatively in 21 human subjects. The study was conducted in two phases. An exploratory phase with ten subjects gave a preliminary overview of the data and data collection process and a systematic phase with eleven subjects provided detailed recruitment properties. The mean stimulation threshold of 25 +/- 17 nC was not significantly different than previous studies in animal models but much lower than muscle electrodes. The selectivity, defined as the percent of total activation of the first muscle recruited before another muscle reached threshold, ranged from 27% to 97% with a mean of 55%. In each case, the muscle that was selectively activated was the first muscle to branch distal to the cuff location. This study serves as a preliminary evaluation of nerve cuff electrodes in humans prior to chronic implant in subjects with high tetraplegia.

Biocompatibility of platinum-metallized silicone rubber: in vivo and in vitro evaluation

Silicone rubber is commonly used for biomedical applications, including implanted cuff electrodes for both recording and stimulation of peripheral nerves. This study was undertaken to evaluate the consequences of a new platinum metallization method on the biocompatibility of silicone rubber cuff electrodes. This method was introduced in order to allow the manufacture of spiral nerve cuff electrodes with a large number of contacts. The metallization process, implying silicone coating with poly(methyl methacrylate) (PMMA), its activation by an excimer laser and subsequent electroless metal deposition, led to a new surface microtexture. The neutral red cytotoxicity assay procedure was first applied in vitro on BALB/c 3T3 fibroblasts in order to analyze the cellular response elicited by the studied material. An in vivo assay was then performed to investigate the tissue reaction after chronic subcutaneous implantation of the metallized material. Results demonstrate that silicone rubber biocompatibility is not altered by the new platinum metallization method.

Neural and connective tissue response to long-term implantation of multiple contact nerve cuff electrodes.

The objective of this study was to characterize the tissue response to multiple contact spiral nerve cuff electrodes implanted on the sciatic nerve of seven cats for 28-34 weeks. The cuffs were surrounded by fibrous tissue encapsulation consisting of foreign body cells, collagen, and fibroblasts. Focal areas of abnormal neural morphology including perineurial thickening, endoneurial fibrosis, thinly myelinated axons, and focal reduction in the density of myelinated axons were noted in five of seven nerves. In three implants, the percutaneous lead cable was destroyed by the animal pulling on the external leads. Morphological changes were observed in two of three nerves from implants sustaining no known animal induced trauma (group A), and in three of four nerves from implants damaged by the animal pulling at the leads (group B). All nerves appeared normal 2 cm proximal to the cuff. At the cuff level, small regions of one fascicle in each of two nerves (both group B) exhibited abnormalities, while the proximal and distal sections of both nerves were normal. Distal to the cuff, small regions of seven fascicles distributed among three nerves (two group A, one group B) exhibited abnormalities. These nerves were normal at the cuff level but exhibited abnormalities in individual nerve branches distal to the cuff. The incidence and characteristics of the morphological abnormalities at the cuff level are consistent with those observed in previous studies of nerve cuff electrodes, and support the hypothesis that spiral cuff electrodes can be implanted with an internal diameter less than that of the nerve and expand to accommodate the nerve without compression The pattern of morphological abnormalities indicated that mechanical trauma had occurred at some time in the past, and the distribution suggested animal intervention and the lead cable as possible causes.

Stability of the input-output properties of chronically implanted multiple contact nerve cuff stimulating electrodes.

The objective of this investigation was to measure the input-output (I-O) properties of chronically implanted nerve cuff electrodes. Silicone rubber spiral nerve cuff electrodes, containing 12 individual platinum electrode contacts, were implanted on the sciatic nerve of seven adult cats for 28-34 weeks. Measurements of the torque generated at the ankle joint by electrical stimulation of the sciatic nerve were made every 1-2 weeks for the first 6 weeks post-implant and every 3-5 weeks between 6 weeks and 32 weeks post-implant. In three implants the percutaneous lead cable was irreparably damaged by the animal within 4 weeks after implant and further testing was not possible. One additional lead cable was irreparably damaged by the animal at 17 weeks post-implant. The three remaining implants functioned for 28, 31, and 32 weeks. Input-output curves of ankle joint torque as a function of stimulus current amplitude were repeatable within an experimental session, but there were changes in I-O curves between sessions. The degree of variability in I-O properties differed between implants and between different contacts within the same implant. After 8 weeks, the session to session changes in the stimulus amplitude required to generate 50% of the maximum torque (I50) were smaller (15+/-19%, mean +/- s.d.) than the changes in I50 measured between 1 week and 8 weeks post-implant (34+/-42%). Furthermore, the I-O properties were more stable across changes in limb position in the late post-implant period than in acutely implanted cuff electrodes. These results suggest that tissue encapsulation acted to stabilize chronically implanted cuff electrodes. Electrode movement relative to the nerve, de- and regeneration of nerve fibers, and the inability to precisely reproduce limb position in the measurement apparatus all may have contributed to the variability in I-O properties.

Spiral nerve cuff electrode for recordings of respiratory output.

The feasibility of using the spiral nerve cuff electrode design for recordings of respiratory output from the hypoglossal (HG) and phrenic nerves is demonstrated in anesthetized, paralyzed, and artificially ventilated cats. Raw neural discharges of the HG nerve were analyzed in terms of signal-to-noise ratios and frequency spectra. The rectified and integrated moving average activity of the HG nerve had a peak value of 1.74 +/- 0.21 microV and a baseline value of 0.72 +/- 0.11 microV at elevated respiratory drive induced by increases in CO2 or oxygen deprivation when recorded with 10-mm-long cuffs. The frequency content of the HG electroneurogram extended from several hundred hertz to 6 kHz. Spiral nerve cuff recordings without desheathing of the nerve provided large enough signal-to-noise ratios that allowed them to be used as a measure of respiratory output and had much wider frequency bandwidths than the hook electrode preparations. A major advantage of the cuff electrode over the hook electrode was its mechanical stability, which significantly improved the reproducibility of the recordings both in terms of signal amplitudes and frequency contents.

Quantification of recruitment properties of multiple contact cuff electrodes.

Nerve-based stimulating electrodes provide the technology for advancing the function of motor system neural prostheses. The goal of this work was to measure and quantify the recruitment properties of a 12 contact spiral nerve cuff electrode. The cuff was implanted on the cat sciatic nerve trunk, which consists of at least four distinct motor fascicles, and the torque generated at the ankle joint by selective stimulation of the nerve was recorded in nine acute experiments. Comparisons of torques generated with the cuff to torques generated by selective stimulation of individual nerve branches indicated that the cuff allowed selective activation of individual nerve fascicles. Selectivity was dependent on the relative location of the electrode contacts and the nerve fascicles, as well as the size and relative spacing of neighboring fascicles. Selective stimulation of individual nerve fascicles allowed independent and graded control of dorsiflexion and plantarflexion torques in all nine experiments. Field steering currents improved selectivity as reflected by significant increases in the maximum torques that could be generated before spillover to other fascicles, significant increases in the difference between the current amplitude at spillover and the current amplitude at threshold, and significant increases in the slope of the current distance relationship.

A spiral nerve cuff electrode for peripheral nerve stimulation.

A novel type of nerve cuff electrode consisting of conductive segments embedded within a self-curling sheath of biocompatible insulation has been developed. This spiral nerve cuff is biased to self-wrap around peripheral nerves and possesses a 'self-sizing' property, presenting an alternative to present commercially available, fixed-size nerve cuffs that are manually wrapped around nerves and sutured shut ('split-cylinder' cuffs). Spiral cuff design and manufacture are described. The authors hypothesize that unlike traditional cuffs, the spiral cuff potentially can be implanted safely when sized to fit peripheral nerves snugly. Theoretical pressure analyzes of traditional and spiral cuffs that support this hypothesis are presented. These analyses are designed to predict the minimum CNR (cuff diameter/nerve diameter ratio) at which there is no interference with intraneural blood flow. Results of a preliminary experiment in which snug spiral cuffs were implanted on feline peripheral nerve support the prediction that they may be safe.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>