SUMMARYBackgroundPeople with chronic tetraplegia due to high cervical spinal cord injury (SCI) can regain limb movements through coordinated electrical stimulation of peripheral muscles and nerves, known as Functional Electrical Stimulation (FES). Users typically command FES systems through other preserved, but limited and unrelated, volitional movements (e.g. facial muscle activity, head movements). We demonstrate an individual with traumatic high cervical SCI performing coordinated reaching and grasping movements using his own paralyzed arm and hand, reanimated through FES, and commanded using his own cortical signals through an intracortical brain-computer-interface (iBCI).MethodsThe study participant (53 years old, C4, ASIA A) received two intracortical microelectrode arrays in the hand area of motor cortex, and 36 percutaneous electrodes for electrically stimulating hand, elbow, and shoulder muscles. The participant used a motorized mobile arm support for gravitational assistance and to provide humeral ab/adduction under cortical control. We assessed the participant’s ability to cortically command his paralyzed arm to perform simple single-joint arm/hand movements and functionally meaningful multi-joint movements. We compared iBCI control of his paralyzed arm to that of a virtual 3D arm. This study is registered with ClinicalTrials.gov, NCT00912041.FindingsThe participant successfully cortically commanded single-joint and coordinated multi-joint arm movements for point-to-point target acquisitions (80% – 100% accuracy) using first a virtual arm, and second his own arm animated by FES. Using his paralyzed arm, the participant volitionally performed self-paced reaches to drink a mug of coffee (successfully completing 11 of 12 attempts within a single session) and feed himself.InterpretationThis is the first demonstration of a combined FES+iBCI neuroprosthesis for both reaching and grasping for people with SCI resulting in chronic tetraplegia, and represents a major advance, with a clear translational path, for clinically viable neuroprostheses for restoring reaching and grasping post-paralysis.

Purpose-The purpose of this study was evaluate the potential of a second-generation implantable neuroprosthesis that provides improved control of hand grasp and elbow extension for individuals with cervical level spinal cord injury. The key feature of this system is that users control their stimulated function through electromyographic (EMG) signals.Methods-The second-generation neuroprosthesis consists of 12 stimulating electrodes, 2 EMG signal recording electrodes, an implanted stimulator-telemeter device, an external control unit, and a transmit/receive coil. The system was implanted in a single surgical procedure. Functional outcomes for each subject were evaluated in the domains of body functions and structures, activity performance, and societal participation.Results-Three individuals with C5/C6 spinal cord injury received system implantation with subsequent prospective evaluation for a minimum of 2 years. All 3 subjects demonstrated that EMG signals can be recorded from voluntary muscles in the presence of electrical stimulation of nearby muscles. Significantly increased pinch force and grasp function was achieved for each subject. Functional evaluation demonstrated improvement in at least 5 activities of daily living using the Activities of Daily Living Abilities Test. Each subject was able to use the device at home. There were no system failures. Two of 6 EMG electrodes required surgical revision because of suboptimal location of the recording electrodes.Conclusions-These results indicate that a neuroprosthesis with implanted myoelectric control is an effective method for restoring hand function in midcervical level spinal cord injury. Type of study/level of evidence-Therapeutic IV.Keywords functional electrical stimulation; neuroprosthesis; spinal cord injury; electromyography; activities of daily livingThe Ability To Grasp And Manipulate objects is an important factor in determining if the tetraplegic individual can regain independence and return to a functional role in society. Implantable functional electrical stimulation systems, or neuroprostheses, provide hand and arm function that is both versatile and transparent. These systems have evolved from the feasibility stage through clinical evaluation in an outpatient population to a Food and DrugCorresponding author: Kevin L. Kilgore, PhD, MetroHealth Medical Center, Hamann 601, 2500 MetroHealth Dr., Cleveland, OH 44109; e-mail: klk4@case.edu. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptAdministration (FDA)-approved medical product. 1 Neuroprostheses provide the user with increased independence, thus improving the opportunity for a better quality of life.A first-generation upper-extremity neuroprosthesis (NP) for hand control 2 was first implanted in 1986 3 and became known as the Freehand System. [4][5][6][7][8][9][10][11][12] The Freehand NP (NeuroControl Corp., Valley View, OH) used an 8-channel implanted receiver-stimulator with 8 epimysial or intramuscular forearm and hand electrodes, leads...

Objective To develop and apply an implanted neuroprosthesis to restore arm and hand function to individuals with high level tetraplegia Design Case study. Setting Clinical research laboratory. Participants Two individuals with spinal cord injuries at or above the C4 motor level. Interventions The individuals were each implanted with two stimulators (24 stimulation channels and 4 myoelectric recording channels total). Stimulating electrodes were placed in the shoulder and arm, including the first chronic application of spiral nerve cuff electrodes to activate a human limb. Myoelectric recording electrodes were placed in the head and neck areas. Main Outcome Measures The successful installation and operation of the neuroprosthesis, along with the electrode performance, range of motion, grasp strength, joint moments, and performance in activities of daily living. Results The 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 post-implant. 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 due to spasticity. The second individual was able to partially complete two activities of daily living. Conclusions Functional 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.

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.

Background Peripheral nerve damage resulting in pain, loss of sensation, or motor function may necessitate a reconstruction with a bridging material. The RANGER® Registry was designed to evaluate outcomes following nerve repair with processed nerve allograft (Avance® Nerve Graft; Axogen; Alachua, FL). Here we report on the results from the largest peripheral nerve registry to‐date. Methods This multicenter IRB‐approved registry study collected data from patients repaired with processed nerve allograft (PNA). Sites followed their own standard of care for patient treatment and follow‐up. Data were assessed for meaningful recovery, defined as ≥S3/M3 to remain consistent with previously published results, and comparisons were made to reference literature. Results The study included 385 subjects and 624 nerve repairs. Overall, 82% meaningful recovery (MR) was achieved across sensory, mixed, and motor nerve repairs up to gaps of 70 mm. No related adverse events were reported. There were no significant differences in MR across the nerve type, age, time‐to‐repair, and smoking status subgroups in the upper extremity ( p > .05). Significant differences were noted by the mechanism of injury subgroups between complex injures (74%) as compared to lacerations (85%) or neuroma resections (94%) ( p = .03) and by gap length between the <15 mm and 50–70 mm gap subgroups, 91 and 69% MR, respectively ( p = .01). Results were comparable to historical literature for nerve autograft and exceed that of conduit. Conclusions These findings provide clinical evidence to support the continued use of PNA up to 70 mm in sensory, mixed and motor nerve repair throughout the body and across a broad patient population.

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.

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.

ForewordFragility fractures, low-energy injuries that occur from a fall from a standing or lower height, represent a serious public health problem. After age 50, the lifetime risk of having a fragility fracture is 33% for an American woman and 20% for a man. 1 In the United States, 2.1 million people will suffer a fragility fracture each year.1 The incidence of fragility fractures increases steeply after age 65.2 Osteoporosis is present in most patients with a fragility fracture.Hip fractures are the most serious in terms of cost and morbidity. The average cost of inpatient care for a hip fracture in 2005 was $33 962.3 The lifetime risk of having a hip fracture is 6% for men and 17.5% for women. Although the mortality risk after a hip fracture is much higher for a man, a woman's risk of dying from a hip fracture is high and exceeds the lifetime risk of death from breast cancer, uterine cancer, and ovarian cancer combined. For those who survive after a hip fracture, most do not regain their preinjury level of function, and 30% lose their independence. This loss of independence is greatly feared by patients and is very costly to patients and society.Although a hip fracture may have the most serious consequences, other bones, such as the wrist, shoulder, ankle, pelvis, and spine, frequently fracture in the osteoporotic patient. For example, the lifetime risk of a forearm or vertebral compression fracture is 16% and 15.6%, respectively, for a woman and 2.5% and 5%, respectively, for a man. 4 These statistics clearly show that fragility fractures are a major problem facing American society today, 5 and the care of such fractures presents an even greater challenge, in part because the quality of care delivered in the United States varies widely, even within one region. Many such fractures are treated in an outpatient setting, although some may be treated in the inpatient hospital setting. However, the quality of care for seniors with fragility fractures receives relatively little attention. In 2004, the United States Surgeon General issued a comprehensive report calling for health professionals to make significant improvements in our nation's bone health, and an improvement in the system and methods of care was suggested. 5There has been little written on the subject of improving the system of care delivery in the United States.The goals of this blue book are to review the methods used in inpatient and outpatient care, as well as rehabilitation of the patient with a fragility fracture. We discuss evidence-based best care models and, where evidence is lacking, present expert opinions in an effort to improve the standard and the quality of care for the patient with a fragility fracture. We hope that this monograph will provide guidance to physicians, nurses, rehabilitation therapists, other health care providers, and administrators.Stephen L. Kates, MD Editor-in-Chief Simon C. Mears, MD, PhD