Spinal sensorimotor networks that are functionally disconnected from the brain because of spinal cord injury (SCI) can be facilitated via epidural electrical stimulation (EES) to restore robust, coordinated motor activity in humans with paralysis. Previously, we reported a clinical case of complete sensorimotor paralysis of the lower extremities in which EES restored the ability to stand and the ability to control step-like activity while side-lying or suspended vertically in a body-weight support system (BWS). Since then, dynamic task-specific training in the presence of EES, termed multimodal rehabilitation (MMR), was performed for 43 weeks and resulted in bilateral stepping on a treadmill, independent from trainer assistance or BWS. Additionally, MMR enabled independent stepping over ground while using a front-wheeled walker with trainer assistance at the hips to maintain balance. Furthermore, MMR engaged sensorimotor networks to achieve dynamic performance of standing and stepping. To our knowledge, this is the first report of independent stepping enabled by task-specific training in the presence of EES by a human with complete loss of lower extremity sensorimotor function due to SCI.

Epidural electrical stimulation (EES) of the spinal cord has been shown to restore function after spinal cord injury (SCI). Characterization of EES-evoked motor responses has provided a basic understanding of spinal sensorimotor network activity related to EES-enabled motor activity of the lower extremities. However, the use of EES-evoked motor responses to guide EES system implantation over the spinal cord and their relation to post-operative EES-enabled function in humans with chronic paralysis attributed to SCI has yet to be described. Herein, we describe the surgical and intraoperative electrophysiological approach used, followed by initial EES-enabled results observed in 2 human subjects with motor complete paralysis who were enrolled in a clinical trial investigating the use of EES to enable motor functions after SCI. The 16-contact electrode array was initially positioned under fluoroscopic guidance. Then, EES-evoked motor responses were recorded from select leg muscles and displayed in real time to determine electrode array proximity to spinal cord regions associated with motor activity of the lower extremities. Acceptable array positioning was determined based on achievement of selective proximal or distal leg muscle activity, as well as bilateral muscle activation. Motor response latencies were not significantly different between intraoperative recordings and post-operative recordings, indicating that array positioning remained stable. Additionally, EES enabled intentional control of step-like activity in both subjects within the first 5 days of testing. These results suggest that the use of EES-evoked motor responses may guide intraoperative positioning of epidural electrodes to target spinal cord circuitry to enable motor functions after SCI.

Background: Quality of life measurements indicate that independent performance of activities of daily living, such as reaching to manipulate objects, is a high priority of individuals living with motor impairments due to spinal cord injury (SCI). In a small number of research participants with SCI, electrical stimulation applied to the dorsal epidural surface of the spinal cord, termed epidural spinal electrical stimulation (ES), has been shown to improve motor functions, such as standing and stepping. However, the impact of ES on seated reaching performance, as well as the approach to identifying stimulation parameters that improve reaching ability, have yet to be described. Objective: Herein, we characterize the effects of ES on seated reaching performance in two participants with chronic, complete loss of motor and sensory functions below thoracic-level SCI. Additionally, we report the effects of delivering stimulation to discrete cathode/anode locations on a 16-contact electrode array spanning the lumbosacral spinal segments on reach distance while participants were seated on a mat and/or in their wheelchair. Methods: Two males with mid-thoracic SCI due to trauma, each of which occurred more than 3 years prior to study participation, were enrolled in a clinical trial at Mayo Clinic, Rochester, MN, USA. Reaching performance was assessed, with and without ES, at several time points throughout the study using the modified functional reach test (mFRT). Altogether, participant 1 performed 1,164 reach tests over 26-time points. Participant 2 performed 480 reach tests over 17-time points.

Introduction: Spinal cord injury (SCI) often results in chronic secondary health conditions related to autonomic and metabolic dysfunction. Epidural electrical stimulation (EES) combined with task-specific training has been shown to enable motor function in individuals with chronic paralysis. The reported effects of EES on secondary health conditions, such as bladder function and body composition, are limited. We report the impact of EES on SCI-related secondary health changes in bladder function and body composition. Methods: Two participants with motor and sensory complete SCI performed 6 months of rehabilitation without EES followed by 12 months of task-specific training with EES after implantation of a 16-electrode array on the surface of the lumbosacral spinal cord. Participants performed three days of training per week in the laboratory, and additionally performed task-specific activities with EES at home during this time frame. Changes in bladder and body composition were recorded via clinically-available testing of neurogenic bladder functionality and dual-energy X-ray absorptiometry, respectively. Results: In one participant, we observed an increase in episodes of urinary incontinence with worsening bladder compliance and pressures at the end of the study. Bone mineral density changes were insignificant in both participants; however, one participant showed a substantial increase in lean mass (+9.1 kg; 6 months of training) via redistribution of body fat through an android/gynoid ratio reduction (−0.15; 6 months of training). Conclusion: EES optimized for standing and stepping may negatively impact neurogenic bladder functionality. Close monitoring of bladder health is imperative to prevent undesirable bladder compliance, which can lead to upper urinary tract deteriorations. Conversely, EES may serve as an adjunct tool with regular exercise modalities to improve body composition through activation of musculature innervated by spinal segments that are below the SCI.

Background: Regaining control of movement following a spinal cord injury (SCI) requires utilization and/or functional reorganization of residual descending, and likely ascending, supraspinal sensorimotor pathways, which may be facilitated via task-specific training through body weight supported treadmill (BWST) training. Recently, epidural electrical stimulation (ES) combined with task-specific training demonstrated independence of standing and stepping functions in individuals with clinically complete SCI. The restoration of these functions may be dependent upon variables such as manipulation of proprioceptive input, ES parameter adjustments, and participant intent during step training. However, the impact of each variable on the degree of independence achieved during BWST stepping remains unknown.Objective: To describe the effects of descending intentional commands and proprioceptive inputs, specifically body weight support (BWS), on lower extremity motor activity and vertical ground reaction forces (vGRF) during ES-enabled BWST stepping in humans with chronic sensorimotor complete SCI. Furthermore, we describe perceived changes in the level of assistance provided by clinicians when intent and BWS are modified.Methods: Two individuals with chronic, mid thoracic, clinically complete SCI, enrolled in an IRB and FDA (IDE G150167) approved clinical trial. A 16-contact electrode array was implanted in the epidural space between the T11-L1 vertebral regions. Lower extremity motor output and vertical ground reaction forces were obtained during clinician-assisted ES-enabled treadmill stepping with BWS. Consecutive steps were achieved during various experimentally-controlled conditions, including intentional participation and varied BWS (60% and 20%) while ES parameters remain unchanged.Results: During ES-enabled BWST stepping, the knee extensors exhibited an increase in motor activation during trials in which stepping was passive compared to active or during trials in which 60% BWS was provided compared to 20% BWS. As a result of this increased motor activation, perceived clinician assistance increased during the transition from stance to swing. Intentional participation and 20% BWS resulted in timely and purposeful activation of the lower extremities muscles, which improved independence and decreased clinician assistance.Conclusion: Maximizing participant intention and optimizing proprioceptive inputs through BWS during ES-enabled BWST stepping may facilitate greater independence during BWST stepping for individuals with clinically complete SCI.Clinical Trial Registration:ClinicalTrials.gov identifier: NCT02592668.

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Transcutaneous (TSS) and epidural spinal stimulation (ESS) are electrophysiological techniques that have been used to investigate the interactions between exogenous electrical stimuli and spinal sensorimotor networks that integrate descending motor signals with afferent inputs from the periphery during motor tasks such as standing and stepping. Recently, pilot-phase clinical trials using ESS and TSS have demonstrated restoration of motor functions that were previously lost due to spinal cord injury (SCI). However, the spinal network interactions that occur in response to TSS or ESS pulses with spared descending connections across the site of SCI have yet to be characterized. Therefore, we examined the effects of delivering TSS or ESS pulses to the lumbosacral spinal cord in nine individuals with chronic SCI. During low-frequency stimulation, participants were instructed to relax or attempt maximum voluntary contraction to perform full leg flexion while supine. We observed similar lower-extremity neuromusculature activation during TSS and ESS when performed in the same participants while instructed to relax. Interestingly, when participants were instructed to attempt lower-extremity muscle contractions, both TSS- and ESS-evoked motor responses were significantly inhibited across all muscles. Participants with clinically complete SCI tested with ESS and participants with clinically incomplete SCI tested with TSS demonstrated greater ability to modulate evoked responses than participants with motor complete SCI tested with TSS, although this was not statistically significant due to a low number of subjects in each subgroup. These results suggest that descending commands combined with spinal stimulation may increase activity of inhibitory interneuronal circuitry within spinal sensorimotor networks in individuals with SCI, which may be relevant in the context of regaining functional motor outcomes.

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