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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 1 – 3 . 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) 4 . 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. In a human subject with chronic paraplegia, a combination of epidural electrical stimulation and long-term rehabilitative training have culminated in the first report of unassisted, voluntary independent stepping in a paralyzed individual.

Neuromodulation of spinal networks can improve motor control after spinal cord injury (SCI). The objectives of this study were to (1) determine whether individuals with chronic paralysis can stand with the aid of non-invasive electrical spinal stimulation with their knees and hips extended without trainer assistance, and (2) investigate whether postural control can be further improved following repeated sessions of stand training. Using a double-blind, balanced, within-subject cross-over, and sham-controlled study design, 15 individuals with SCI of various severity received transcutaneous electrical spinal stimulation to regain self-assisted standing. The primary outcomes included qualitative comparison of need of external assistance for knee and hip extension provided by trainers during standing without and in the presence of stimulation in the same participants, as well as quantitative measures, such as the level of knee assistance and amount of time spent standing without trainer assistance. None of the participants could stand unassisted without stimulation or in the presence of sham stimulation. With stimulation all participants could maintain upright standing with minimum and some (n = 7) without external assistance applied to the knees or hips, using their hands for upper body balance as needed. Quality of balance control was practice-dependent, and improved with subsequent training. During self-initiated body-weight displacements in standing enabled by spinal stimulation, high levels of leg muscle activity emerged, and depended on the amount of muscle loading. Our findings indicate that the lumbosacral spinal networks can be modulated transcutaneously using electrical spinal stimulation to facilitate self-assisted standing after chronic motor and sensory complete paralysis.

The present prognosis for the recovery of voluntary control of movement in patients diagnosed as motor complete is generally poor. Herein we introduce a novel and noninvasive stimulation strategy of painless transcutaneous electrical enabling motor control and a pharmacological enabling motor control strategy to neuromodulate the physiological state of the spinal cord. This neuromodulation enabled the spinal locomotor networks of individuals with motor complete paralysis for 2–6 years American Spinal Cord Injury Association Impairment Scale (AIS) to be re-engaged and trained. We showed that locomotor-like stepping could be induced without voluntary effort within a single test session using electrical stimulation and training. We also observed significant facilitation of voluntary influence on the stepping movements in the presence of stimulation over a 4-week period in each subject. Using these strategies we transformed brain–spinal neuronal networks from a dormant to a functional state sufficiently to enable recovery of voluntary movement in five out of five subjects. Pharmacological intervention combined with stimulation and training resulted in further improvement in voluntary motor control of stepping-like movements in all subjects. We also observed on-command selective activation of the gastrocnemius and soleus muscles when attempting to plantarflex. At the end of 18 weeks of weekly interventions the mean changes in the amplitude of voluntarily controlled movement without stimulation was as high as occurred when combined with electrical stimulation. Additionally, spinally evoked motor potentials were readily modulated in the presence of voluntary effort, providing electrophysiological evidence of the re-establishment of functional connectivity among neural networks between the brain and the spinal cord.

In children with spinal cord injury (SCI), scoliosis due to trunk muscle paralysis frequently requires surgical treatment. Transcutaneous spinal stimulation enables trunk stability in adults with SCI and may pose a non-invasive preventative therapeutic alternative. This non-randomized, non-blinded pilot clinical trial (NCT03975634) determined the safety and efficacy of transcutaneous spinal stimulation to enable upright sitting posture in 8 children with trunk control impairment due to acquired SCI using within-subject repeated measures study design. Primary safety and efficacy outcomes (pain, hemodynamics stability, skin irritation, trunk kinematics) and secondary outcomes (center of pressure displacement, compliance rate) were assessed within the pre-specified endpoints. One participant did not complete the study due to pain with stimulation on the first day. One episode of autonomic dysreflexia during stimulation was recorded. Following hemodynamic normalization, the participant completed the study. Overall, spinal stimulation was well-tolerated and enabled upright sitting posture in 7 out of the 8 participants. Scoliosis due to trunk muscle paralysis frequently requires surgical treatment in children with spinal cord injury. The authors demonstrate the safety and efficacy of transcutaneous spinal stimulation to enable upright sitting posture in 7/8 children with trunk control impairment in a within-subjects, repeated measures pilot clinical trial.

Repeated periods of stimulation of the spinal cord and training increased the ability to control movement in animal models of spinal cord injury. We hypothesised that tonic epidural spinal cord stimulation can modulate spinal circuitry in human beings into a physiological state that enables sensory input from standing and stepping movements to serve as a source of neural control to undertake these tasks. A 23-year-old man who had paraplegia from a C7–T1 subluxation as a result of a motor vehicle accident in July 2006, presented with complete loss of clinically detectable voluntary motor function and partial preservation of sensation below the T1 cord segment. After 170 locomotor training sessions over 26 months, a 16-electrode array was surgically placed on the dura (L1–S1 cord segments) in December 2009, to allow for chronic electrical stimulation. Spinal cord stimulation was done during sessions that lasted up to 250 min. We did 29 experiments and tested several stimulation combinations and parameters with the aim of the patient achieving standing and stepping. Epidural stimulation enabled the man to achieve full weight-bearing standing with assistance provided only for balance for 4·25 min. The patient achieved this standing during stimulation using parameters identified as specific for standing while providing bilateral load-bearing proprioceptive input. We also noted locomotor-like patterns when stimulation parameters were optimised for stepping. Additionally, 7 months after implantation, the patient recovered supraspinal control of some leg movements, but only during epidural stimulation. Task-specific training with epidural stimulation might reactivate previously silent spared neural circuits or promote plasticity. These interventions could be a viable clinical approach for functional recovery after severe paralysis. National Institutes of Health and Christopher and Dana Reeve Foundation.

Paralysis of the upper extremities following cervical spinal cord injury (SCI) significantly impairs one's ability to live independently. While regaining hand function or grasping ability is considered one of the most desired functions in tetraplegics, limited therapeutic development in this direction has been demonstrated to date in humans with a high severe cervical injury. The underlying hypothesis is that after severe cervical SCI, nonfunctional sensory-motor networks within the cervical spinal cord can be transcutaneously neuromodulated to physiological states that enable and amplify voluntary control of the hand. Improved voluntary hand function occurred within a single session in every subject tested. After eight sessions of non-invasive transcutaneous stimulation, combined with training over 4 weeks, maximum voluntary hand grip forces increased by ∼325% (in the presence of stimulation) and ∼225% (when grip strength was tested without simultaneous stimulation) in chronic cervical SCI subjects (American Spinal Injury Association Impairment Scale [AIS] B, n = 3; AIS C, n = 5) 1-21 years post-injury). Maximum grip strength improved in both the left and right hands and the magnitude of increase was independent of hand dominance. We refer to the neuromodulatory method used as transcutaneous enabling motor control to emphasize that the stimulation parameters used are designed to avoid directly inducing muscular contractions, but to enable task performance according to the subject's voluntary intent. In some subjects, there were improvements in autonomic function, lower extremity motor function, and sensation below the level of the lesion. Although a neuromodulation-training effect was observed in every subject tested, further controlled and blinded studies are needed to determine the responsiveness of a larger and broader population of subjects varying in the type, severity, and years post-injury. It appears rather convincing, however, that a “central pattern generation” phenomenon as generally perceived in the lumbosacral networks in controlling stepping neuromodulator is not a critical element of spinal neuromodulation to regain function among spinal networks.

Electrical neuromodulation of spinal networks improves the control of movement of the paralyzed limbs after spinal cord injury (SCI). However, the potential of noninvasive spinal stimulation to facilitate postural trunk control during sitting in humans with SCI has not been investigated. We hypothesized that transcutaneous electrical stimulation of the lumbosacral enlargement can improve trunk posture. Eight participants with non-progressive SCI at C3-T9, American Spinal Injury Association Impairment Scale (AIS) A or C, performed different motor tasks during sitting. Electromyography of the trunk muscles, three-dimensional kinematics, and force plate data were acquired. Spinal stimulation improved trunk control during sitting in all tested individuals. Stimulation resulted in elevated activity of the erector spinae, rectus abdominis, and external obliques, contributing to improved trunk control, more natural anterior pelvic tilt and lordotic curve, and greater multi-directional seated stability. During spinal stimulation, the center of pressure (COP) displacements decreased to 1.36 ± 0.98 mm compared with 4.74 ± 5.41 mm without stimulation (p = 0.0156) in quiet sitting, and the limits of stable displacement increased by 46.92 ± 35.66% (p = 0.0156), 36.92 ± 30.48% (p = 0.0156), 54.67 ± 77.99% (p = 0.0234), and 22.70 ± 26.09% (p = 0.0391) in the forward, backward, right, and left directions, respectively. During self-initiated perturbations, the correlation between anteroposterior arm velocity and the COP displacement decreased from r = 0.5821 (p = 0.0007) without to r = 0.5115 (p = 0.0039) with stimulation, indicating improved trunk stability. These data demonstrate that the spinal networks can be modulated transcutaneously with tonic electrical spinal stimulation to physiological states sufficient to generate a more stable, erect sitting posture after chronic paralysis.

We report a case of chronic traumatic paraplegia in which epidural electrical stimulation (EES) of the lumbosacral spinal cord enabled (1) volitional control of task-specific muscle activity, (2) volitional control of rhythmic muscle activity to produce steplike movements while side-lying, (3) independent standing, and (4) while in a vertical position with body weight partially supported, voluntary control of steplike movements and rhythmic muscle activity. This is the first time that the application of EES enabled all of these tasks in the same patient within the first 2 weeks (8 stimulation sessions total) of EES therapy.

The inability to control timely bladder emptying is one of the most serious challenges among the several functional deficits that occur after a complete spinal cord injury. Having demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis, we hypothesized that a similar approach could be used to recover bladder function after paralysis. Also knowing that posture and locomotion can be initiated immediately with a specific frequency-dependent stimulation pattern and that with repeated stimulation-training sessions these functions can improve even further, we reasoned that the same two strategies could be used to regain bladder function. Recent evidence suggests that rats with severe paralysis can be rehabilitated with a multisystem neuroprosthetic training regime that counteracts the development of neurogenic bladder dysfunction. No data regarding the acute effects of locomotion on bladder function, however, were reported. In this study we show that enabling of locomotor-related spinal neuronal circuits by epidural stimulation also influences neural networks controlling bladder function and can play a vital role in recovering bladder function after complete paralysis. We have identified specific spinal cord stimulation parameters that initiate bladder emptying within seconds of the initiation of epidural stimulation. The clinical implications of these results are substantial in that this strategy could have a major impact in improving the quality of life and longevity of patients while simultaneously dramatically reducing ongoing health maintenance after a spinal cord injury.

(1) Background: Restoring arm and hand function is a priority for individuals with cervical spinal cord injury (cSCI) for independence and quality of life. Transcutaneous spinal cord stimulation (tSCS) promotes the upper extremity (UE) motor function when applied at the cervical region. The aim of the study was to determine the effects of cervical tSCS, combined with an exoskeleton, on motor strength and functionality of UE in subjects with cSCI. (2) Methods: twenty-two subjects participated in the randomized mix of parallel-group and crossover clinical trial, consisting of an intervention group (n = 15; tSCS exoskeleton) and a control group (n = 14; exoskeleton). The assessment was carried out at baseline, after the last session, and two weeks after the last session. We assessed graded redefined assessment of strength, sensibility, and prehension (GRASSP), box and block test (BBT), spinal cord independence measure III (SCIM-III), maximal voluntary contraction (MVC), ASIA impairment scale (AIS), and WhoQol-Bref; (3) Results: GRASSP, BBT, SCIM III, cylindrical grip force and AIS motor score showed significant improvement in both groups (p ≤ 0.05), however, it was significantly higher in the intervention group than the control group for GRASSP strength, and GRASSP prehension ability (p ≤ 0.05); (4) Conclusion: our findings show potential advantages of the combination of cervical tSCS with an exoskeleton to optimize the outcome for UE.