Restoration of reaching and grasping movements through brain-controlled muscle stimulation in a person with tetraplegia: a proof-of-concept demonstration.

BACKGROUND: People with chronic tetraplegia, due to high-cervical spinal cord injury, 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 unrelated and limited in number, volitional movements (eg, facial muscle activity, head movements, shoulder shrugs). We report the findings of an individual with traumatic high-cervical spinal cord injury who coordinated reaching and grasping movements using his own paralysed arm and hand, reanimated through implanted FES, and commanded using his own cortical signals through an intracortical brain-computer interface (iBCI). METHODS: We recruited a participant into the BrainGate2 clinical trial, an ongoing study that obtains safety information regarding an intracortical neural interface device, and investigates the feasibility of people with tetraplegia controlling assistive devices using their cortical signals. Surgical procedures were performed at University Hospitals Cleveland Medical Center (Cleveland, OH, USA). Study procedures and data analyses were performed at Case Western Reserve University (Cleveland, OH, USA) and the US Department of Veterans Affairs, Louis Stokes Cleveland Veterans Affairs Medical Center (Cleveland, OH, USA). The study participant was a 53-year-old man with a spinal cord injury (cervical level 4, American Spinal Injury Association Impairment Scale category A). He received two intracortical microelectrode arrays in the hand area of his motor cortex, and 4 months and 9 months later received a total of 36 implanted percutaneous electrodes in his right upper and lower arm to electrically stimulate his hand, elbow, and shoulder muscles. The participant used a motorised mobile arm support for gravitational assistance and to provide humeral abduction and adduction under cortical control. We assessed the participant's ability to cortically command his paralysed arm to perform simple single-joint arm and hand movements and functionally meaningful multi-joint movements. We compared iBCI control of his paralysed arm with that of a virtual three-dimensional arm. This study is registered with ClinicalTrials.gov, number NCT00912041. FINDINGS: The intracortical implant occurred on Dec 1, 2014, and we are continuing to study the participant. The last session included in this report was Nov 7, 2016. The point-to-point target acquisition sessions began on Oct 8, 2015 (311 days after implant). The 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 paralysed arm, the participant volitionally performed self-paced reaches to drink a mug of coffee (successfully completing 11 of 12 attempts within a single session 463 days after implant) and feed himself (717 days after implant). INTERPRETATION: To our knowledge, this is the first report of a combined implanted FES+iBCI neuroprosthesis for restoring both reaching and grasping movements to people with chronic tetraplegia due to spinal cord injury, and represents a major advance, with a clear translational path, for clinically viable neuroprostheses for restoration of reaching and grasping after paralysis. FUNDING: National Institutes of Health, Department of Veterans Affairs.

Upper Extremity Assessment in Tetraplegia: The Importance of Differentiating Between Upper and Lower Motor Neuron Paralysis.

Scientific advances are increasing the options for improved upper limb function in people with cervical level spinal cord injury (SCI). Some of these interventions rely on identifying an aspect of paralysis that is not uniformly assessed in SCI: the integrity of the lower motor neuron (LMN). SCI can damage both the upper motor neuron and LMN causing muscle paralysis. Differentiation between these causes of paralysis is not typically believed to be important during SCI rehabilitation because, regardless of the cause, the muscles are no longer under voluntary control by the patient. Emerging treatments designed to restore upper extremity function (eg, rescue microsurgical nerve transfers, motor learning-based interventions, functional electrical stimulation) all require knowledge of LMN status. The LMN is easily evaluated using surface electrical stimulation and does not add significant time to the standard clinical assessment of SCI. This noninvasive evaluation yields information that contributes to the development of a lifetime upper extremity care plan for maximizing function and quality of life. Given the relative simplicity of this assessment and the far-reaching implications for treatment and function, we propose that this assessment should be adopted as standard practice for acute cervical SCI.

Implanted neuroprosthesis for restoring arm and hand function in people with high level tetraplegia.

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: Individuals with spinal cord injuries (N=2) at or above the C4 motor level. INTERVENTIONS: The 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 MEASURES: Successful installation and operation of the neuroprosthesis and 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 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. 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.

Clinical Outcomes of "Paralyzed" Nerve Transfer for Treating Spinal Cord Injury: A Proof of Concept in a Human Model.

Functional electrical stimulation (FES) is an option to restore function in individuals after high cervical spinal cord injury (SCI) who have limited available options for tendon or nerve transfer. To be considered for FES implantation, patients must possess upper motor neuron (UMN) type denervation in potential recipient muscles, which can be confirmed by response to surface electrical stimulation during clinical evaluation. Lower motor neuron (LMN) denervated muscles will not respond to electrical stimulation and, therefore, are unavailable for use in an FES system. Previous animal studies have demonstrated that a "paralyzed" nerve transfer of a UMN-denervated motor branch to an LMN-denervated motor branch can restore electrical excitability in the recipient. In this study, we report the indications, surgical technique, and successful outcome (restoration of M3 elbow flexion) after the first "paralyzed" nerve transfer in a human patient.

Surgical restoration of arm and hand function in people with tetraplegia.

Improved hand and arm function is the most sought after function for people living with a cervical spinal cord injury (SCI). Surgical techniques have been established to increase upper extremity function for tetraplegics, focusing on restoring elbow extension, wrist movement, and hand opening and closing. Additionally, more innovative treatments that have been developed (implanted neuroprostheses and nerve transfers) provide more options for improving function and quality of life. One of the most important steps in the process of restoring upper extremity function in people with tetraplegia is identifying appropriate candidates - typically those with American Spinal Injury Association (ASIA) motor level C5 or greater. Secondary complications of SCI can pose barriers to restoring function, particularly upper extremity spasticity. A novel approach to managing spasticity through high-frequency alternating currents designed to block unwanted spasticity is being researched at the Cleveland FES Center and may improve the impact of reconstructive surgery for these individuals. The impact of these surgeries is best measured within the framework of the World Health Organization's International Classification of Function, Disability and Health. Outcome measures should be chosen to reflect changes within the domains of body functions and structures, activity, and participation. There is a need to strengthen the evidence in the area of reconstructive procedures for people with tetraplegia. Research continues to advance, providing more options for improved function in this population than ever before. The contribution of well-designed outcome studies to this evidence base will ultimately help to address the complications surrounding access to the procedures.

Diagnosis and treatment of osteochondritis dissecans.

This clinical practice guideline is based on a series of systematic reviews of published studies in the available literature on the diagnosis and treatment of osteochondritis dissecans of the knee. None of the 16 recommendations made by the work group is graded as strong; most are graded inconclusive; two are graded weak; and four are consensus statements. Both of the weak recommendations are related to imaging evaluation. For patients with knee symptoms, radiographs of the joint may be obtained to identify the lesion. For patients with radiographically apparent lesions, MRI may be used to further characterize the osteochondritis dissecans lesion or identify other knee pathology.

A Rare Case of Cervical Charcot After Spinal Cord Injury: A Case Report.

CASE: We present a rare case of cervical Charcot disease that was diagnosed in a paraplegic patient by loss of function caudal to the original level of spinal cord injury. Clinical imaging, diagnosis, differentials, and operative management are discussed. CONCLUSIONS: Charcot disease of the cervical spine is rare and very difficult to diagnose in the paraplegic patient population. High clinical suspicion should be maintained in these patients who demonstrate any form of neurologic deterioration, mechanical instability, or change in spinal alignment. It is often necessary to rule out infection. Spinal decompression and surgical stabilization is the treatment of choice.

Evolution of Neuroprosthetic Approaches to Restoration of Upper Extremity Function in Spinal Cord Injury.

Background: Spinal cord injury (SCI) occurring at the cervical levels can result in significantly impaired arm and hand function. People with cervical-level SCI desire improved use of their arms and hands, anticipating that regained function will result in improved independence and ultimately improved quality of life. Neuroprostheses provide the most promising method for significant gain in hand and arm function for persons with cervical-level SCI. Neuroprostheses utilize small electrical currents to activate peripheral motor nerves, resulting in controlled contraction of paralyzed muscles. Methods: A myoelectrically-controlled neuroprosthesis was evaluated in 15 arms in 13 individuals with cervical-level SCI. All individuals had motor level C5 or C6 tetraplegia. Results: This study demonstrates that an implanted neuroprosthesis utilizing myoelectric signal (MES)-controlled stimulation allows considerable flexibility in the control algorithms that can be utilized for a variety of arm and hand functions. Improved active range of motion, grip strength, and the ability to pick up and release objects were improved in all arms tested. Adverse events were few and were consistent with the experience with similar active implantable devices. Conclusion: For individuals with cervical SCI who are highly motivated, implanted neuroprostheses provide the opportunity to gain arm and hand function that cannot be gained through the use of orthotics or surgical intervention alone. Upper extremity neuroprostheses have been shown to provide increased function and independence for persons with cervical-level SCI.

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.

Voluntary activation of biceps-to-triceps and deltoid-to-triceps transfers in quadriplegia.

The biceps or the posterior deltoid can be transferred to improve elbow extension function for many individuals with C5 or C6 quadriplegia. Maximum strength after elbow reconstruction is variable; the patient's ability to voluntarily activate the transferred muscle to extend the elbow may contribute to the variability. We compared voluntary activation during maximum isometric elbow extension following biceps transfer (n = 5) and deltoid transfer (n = 6) in three functional postures. Voluntary activation was computed as the elbow extension moment generated during maximum voluntary effort divided by the moment generated with full activation, which was estimated via electrical stimulation. Voluntary activation was on average 96% after biceps transfer and not affected by posture. Individuals with deltoid transfer demonstrated deficits in voluntary activation, which differed by posture (80% in horizontal plane, 69% in overhead reach, and 70% in weight-relief), suggesting inadequate motor re-education after deltoid transfer. Overall, individuals with a biceps transfer better activated their transferred muscle than those with a deltoid transfer. This difference in neural control augmented the greater force-generating capacity of the biceps leading to increased elbow extension strength after biceps transfer (average 9.37 N-m across postures) relative to deltoid transfer (average 2.76 N-m across postures) in our study cohort.

Posture-Dependent Corticomotor Excitability Differs Between the Transferred Biceps in Individuals With Tetraplegia and the Biceps of Nonimpaired Individuals.

BACKGROUND: Following biceps transfer to enable elbow extension in individuals with tetraplegia, motor re-education may be facilitated by greater corticomotor excitability. Arm posture modulates corticomotor excitability of the nonimpaired biceps. If arm posture also modulates excitability of the transferred biceps, posture may aid in motor re-education. OBJECTIVE: Our objective was to determine whether multi-joint arm posture affects corticomotor excitability of the transferred biceps similar to the nonimpaired biceps. We also aimed to determine whether corticomotor excitability of the transferred biceps is related to elbow extension strength and muscle length. METHODS: Corticomotor excitability was assessed in 7 arms of individuals with tetraplegia and biceps transfer using transcranial magnetic stimulation and compared to biceps excitability of nonimpaired individuals. Single-pulse transcranial magnetic stimulation was delivered to the motor cortex with the arm in functional postures at rest. Motor-evoked potential amplitude was recorded via surface electromyography. Elbow moment was recorded during maximum isometric extension trials, and muscle length was estimated using a biomechanical model. RESULTS: Arm posture modulated corticomotor excitability of the transferred biceps differently than the nonimpaired biceps. Elbow extension strength was positively related and muscle length was unrelated, respectively, to motor-evoked potential amplitude across the arms with biceps transfer. CONCLUSIONS: Corticomotor excitability of the transferred biceps is modulated by arm posture and may contribute to strength outcomes after tendon transfer. Future work should determine whether modulating corticomotor excitability via posture promotes motor re-education during the rehabilitative period following surgery.

Stability and selectivity of a chronic, multi-contact cuff electrode for sensory stimulation in human amputees.

OBJECTIVE: Stability and selectivity are important when restoring long-term, functional sensory feedback in individuals with limb-loss. Our objective is to demonstrate a chronic, clinical neural stimulation system for providing selective sensory response in two upper-limb amputees. APPROACH: Multi-contact cuff electrodes were implanted in the median, ulnar, and radial nerves of the upper-limb. MAIN RESULTS: Nerve stimulation produced a selective sensory response on 19 of 20 contacts and 16 of 16 contacts in subjects 1 and 2, respectively. Stimulation elicited multiple, distinct percept areas on the phantom and residual limb. Consistent threshold, impedance, and percept areas have demonstrated that the neural interface is stable for the duration of this on-going, chronic study. SIGNIFICANCE: We have achieved selective nerve response from multi-contact cuff electrodes by demonstrating characteristic percept areas and thresholds for each contact. Selective sensory response remains consistent in two upper-limb amputees for 1 and 2 years, the longest multi-contact sensory feedback system to date. Our approach demonstrates selectivity and stability can be achieved through an extraneural interface, which can provide sensory feedback to amputees.

The influence of elbow position on the range of motion of the wrist following transfer of the brachioradialis to the extensor carpi radialis brevis tendon.

BACKGROUND: In patients who have an injury of the cervical spinal cord, the brachioradialis tendon may be transferred to the extensor carpi radialis brevis tendon to restore voluntary wrist extension. We hypothesized that the active range of motion of the wrist depends on the position of the elbow after this transfer because the brachioradialis changes length substantially during elbow flexion, which implies the maximum force that the muscle can produce varies with elbow position. The objectives of this study were to determine whether the position of the elbow influences the range of motion of the wrist following transfer of the brachioradialis to the extensor carpi radialis brevis tendon and to evaluate the effect of surgical tensioning. METHODS: The range of motion of eight wrists was assessed after brachioradialis transfer. Two positions of the elbow were tested, the passive limit of elbow extension and 120 degrees of flexion. The range of motion of the wrist was also simulated with use of a biomechanical model. Using the model, we compared the active range of motion of the wrist, with the elbow at 0 degrees and 120 degrees of flexion, following three different approaches to surgical tensioning. The simulations were also repeated to evaluate how muscle strength influences outcomes. RESULTS: Wrist extension decreased and passive flexion increased when the elbow was flexed. Maximum wrist extension was significantly correlated with passive flexion in all subjects (r = 0.95 and p < 0.001 when the elbow was extended and r = 0.82 and p < 0.03 when the elbow was flexed). The biomechanical model suggested that tensioning the tendon transfer so that the fibers of the brachioradialis do not become excessively short when the elbow is flexed may improve outcomes. The simulations also revealed that it is more difficult to maintain a consistent wrist position with the elbow in different postures when a weaker muscle is transferred. CONCLUSIONS: The model suggests that altering the surgical tension could improve wrist extension when the elbow is flexed. However, the ultimate result is sensitive to the strength of the brachioradialis.

Restoration of elbow extension via functional electrical stimulation in individuals with tetraplegia.

Functional electrical stimulation of the triceps is a method of restoring elbow extension to individuals with paralyzed triceps. Eleven arms of individuals with cervical-level spinal cord injuries (SCIs) received a triceps electrode as an addition to a hand-grasp neuroprosthesis. Stimulation was controlled either as part of a preprogrammed pattern or via a switch or an accelerometer that was connected to the neuroprosthesis external controller. The outcome measures were (1) elbow extension moments at different elbow positions, (2) performance in controllable workspace experiments, and (3) comparison to an alternative method of providing elbow extension in these individuals--a posterior deltoid (PD) to triceps tendon transfer. Stimulated elbow extension moments in 11 arms ranged from 0.8 to 13.3 N.m. The stimulated elbow extension moments varied with elbow angle in a manner consistent with the length-tension properties of the triceps. Triceps stimulation provided a significantly stronger elbow extension moment than the PD to triceps tendon transfer. The elbow extension moment generated by the tendon transfer and triceps electrode being activated together was always greater than either method used separately. Stimulation of the long head of the triceps should be avoided in persons with weak shoulder abduction, since the long head adducts the shoulder and limits shoulder function in these cases. Statistically, elbow extension neuroprostheses significantly increased the ability to successfully reach and move an object and significantly decreased the time required to acquire an object while reaching.

Electrode fracture rates and occurrences of infection and granuloma associated with percutaneous intramuscular electrodes in upper-limb functional electrical stimulation applications.

This study was performed to assess the rate of electrode fracture and to provide an account of the occurrences of infection and granuloma associated with percutaneous intramuscular electrodes implanted in upper-limb muscles. Data were reviewed on 858 electrodes implanted in 62 research participants between October 1978 and July 1998. Survival analyses showed that the probability of an electrode remaining intact within the body at 6 months after implantation is 95%, and at 1 year is 91%. The probability of the electrode surviving both the in situ period and extraction after 6 months is 78%, and after 1 year is 57%. Ten participants (16%) experienced at least one occurrence of infection or granuloma associated with in-dwelling electrodes. Five of the twenty-three total adverse medical incidents were associated with electrode fragments retained in the body; the others were associated with intact electrodes. All incidents were localized nonsystematic occurrences and were resolved by administering antibiotics, cleaning the implant site, removing electrodes, cauterizing with silver nitrate, or excising electrodes or granulomas.

Implementation of an implantable joint-angle transducer.

An implantable joint-angle transducer (IJAT) was implemented to provide command-control information from the wrist for functional neuromuscular stimulation (FNS) neuroprostheses. The IJAT uses the Hall effect to sense joint angle. The objectives of this study were to evaluate (1) chronic functionality, (2) safety and biocompatibility, (3) repeatability of the implantation procedure, and (4) clinical feasibility. Accelerated bench testing projected an operating period of over 50 years. In chronic animal experiments, stable output was obtained from three of four IJATs for periods of 10 to 19 months. Histology revealed acceptable osseointegration of the implant. The device has been implanted in human subjects for over 2 years and provides an excellent control signal for hand grasp. We conclude that this device is safe and effective for chronic human use as a control input for an implanted hand neuroprosthesis.

Durability of implanted electrodes and leads in an upper-limb neuroprosthesis.

Implanted neuroprosthetic systems have been successfully used to provide upper-limb function for over 16 years. A critical aspect of these implanted systems is the safety, stability, and-reliability of the stimulating electrodes and leads. These components are (1) the stimulating electrode itself, (2) the electrode lead, and (3) the lead-to-device connector. A failure in any of these components causes the direct loss of the capability to activate a muscle consistently, usually resulting in a decrement in the function provided by the neuroprosthesis. Our results indicate that the electrode, lead, and connector system are extremely durable. We analyzed 238 electrodes that have been implanted as part of an upper-limb neuroprosthesis. Each electrode had been implanted at least 3 years, with a maximum implantation time of over 16 years. Only three electrode-lead failures and one electrode infection occurred, for a survival rate of almost 99 percent. Electrode threshold measurements indicate that the electrode response is stable over time, with no evidence of electrode migration or continual encapsulation in any of the electrodes studied. These results have an impact on the design of implantable neuroprosthetic systems. The electrode-lead component of these systems should no longer be considered a weak technological link.

Clinical applications of electrical stimulation after spinal cord injury.

During the last one-half century, electrical stimulation has become clinically significant for improving health and restoring useful function after spinal cord injury. Short-term stimulation can be provided by electrodes on the skin or percutaneous fine wires, but implanted systems are preferable for long-term use. Electrical stimulation of intact lower motor neurons can exercise paralyzed muscles and reverse wasting; improve strength, endurance, and cardiovascular fitness; and may reduce the progression of osteoporosis. Other potential therapeutic uses being investigated include reduction of spasticity, prevention of deep vein thrombosis, and improvement of tissue health. Pacing of intact phrenic nerves in high tetraplegia can produce effective respiration without mechanical ventilation, allowing improved speech, increased mobility, and increased sense of well-being. Improvement of cough has also been demonstrated. Stimulation of intact sacral nerves can produce effective micturition and reduce urinary tract infection; it can also improve bowel function and erection. It is usually combined with posterior sacral rhizotomy to improve continence and bladder capacity, and the combination has been shown to reduce costs of care. Electroejaculation can now produce semen in most men with spinal cord injury. Significant achievements have also been made in restoring limb function. Useful hand grasp can be provided in C5 and C6 tetraplegia, reducing dependence on adapted equipment and assistants. Standing, assistance with transfers, and walking for short distances can be provided to selected persons with paraplegia, improving their access to objects, places, and opportunities that are inaccessible from a wheelchair. This review summarizes the current state of therapeutic and neuroprosthetic applications of electrical stimulation after spinal cord injury and identifies some future directions of research and clinical and commercial development.

Indications and future directions for upper limb neuroprostheses in tetraplegic patients: a review.

The development of the upper extremity neuroprosthesis has been a challenging and rewarding contribution to the management of the SCI patient. The authors' experience and that of their clinical trial teams has verified that this technology is a strong alternative to conventional reconstruction and conservative management. In the future, even more powerful tools will emerge from the laboratory as these devices and collaborative surgical procedures evolve.