Epidural magnetic stimulation of the motor cortex using an implantable coil.

BACKGROUND: Magnetic stimulation, represented by transcranial magnetic stimulation (TMS), is used to treat neurological diseases. Various strategies have been explored to improve the spatial resolution of magnetic stimulation. While reducing the coil size is the most impactful approach for increasing the spatial resolution, it decreases the stimulation intensity and increases heat generation. OBJECTIVE: We aim to demonstrate the feasibility of magnetic stimulation using an epidurally implanted millimeter-sized coil and that it does not damage the cortical tissue via heating even when a repetitive stimulation protocol is used. METHODS: A coil with dimensions of 3.5 × 3.5 × 2.6 mm3 was epidurally implanted on the left motor cortex of rat, corresponding to the right hindlimb. Before and after epidural magnetic stimulation using a quadripulse stimulation (QPS) protocol, changes in the amplitude of motor evoked potentials (MEPs) elicited by a TMS coil were compared. RESULTS: The experimental group showed an average increase of 88 % in MEP amplitude in the right hindlimb after QPS, whereas the MEP amplitude in the left hindlimb increased by 18 % on average. The control group showed no significant change in MEP amplitude after QPS in either hindlimb. The temperature changes at the coil surface remained <2 °C during repetitive stimulation, meeting the thermal safety limit for implantable medical devices. CONCLUSION: These results demonstrate the feasibility of epidural magnetic stimulation using an implantable coil to induce neuromodulation effects. This novel method is expected to be a promising alternative for focal magnetic stimulation with an improved spatial resolution and lowered stimulus current than previous magnetic stimulation methods.

Prevalence of autonomic dysreflexia during spinal cord stimulation after spinal cord injury.

Over the past decade, clinical trials have shown that spinal cord stimulation can restore motor functions that were thought to be permanently impaired in persons with spinal cord injury. However, the off-target effects of delivering electrical impulses to intertwined spinal networks remain largely unknown. This generates safety concerns for this otherwise fast-progressing technology. Herein, we present the prevalence of autonomic dysreflexia (AD) that occurred during implanted spinal cord stimulation testing for motor activation of the lower extremities. Eleven participants with spinal cord injury underwent implantation of temporary percutaneous epidural and dorsal root ganglia stimulation leads. Participants completed two days of parameter testing at baseline, then six days of motor rehabilitation sessions, and two days of parameter testing at end of study. The goal of parameter testing was to determine electrode configuration(s), pulse amplitudes, and frequencies that activated lumbosacral spinal sensorimotor networks that generate lower extremity functions. During all parameter testing sessions, continuous blood pressure and heart rate monitoring recordings were collected. Evidence of autonomic dysreflexia was found in 22% of all parameter tests with participants at rest. Most of these episodes (97%) were asymptomatic. These episodes occurred more frequently when using epidural stimulation, at or near amplitudes that elicited whole leg muscle activation and using a wide-field electrode configuration. Although monitoring occurred during passive testing, motor rehabilitation sessions use stimulation for longer periods, at higher frequencies and amplitudes. These sessions may carry additional risks of autonomic dysreflexia. Investigation of these concerns should continue as spinal cord stimulation progresses toward clinical translation.NEW & NOTEWORTHY Spinal cord stimulation for motor recovery after spinal cord injury is a popular research intervention, though off-target effects are a concern. Using continual blood pressure and heart rate recordings during passive spinal cord stimulation parameter testing, we identified frequent episodes of autonomic dysreflexia that were rarely associated with symptoms. This presents a previously unrecognized risk of spinal cord stimulation and appropriate vigilance in targeted monitoring is urged to maintain participant safety.

Bladder Responses to Thoracolumbar Epidural Stimulation in Female Urethane-Anesthetized Rats with Graded Contusion Spinal Cord Injuries.

Spinal cord epidural stimulation (scES) is a therapeutic option that promotes functional improvements in sensory, motor, and autonomic functions following spinal cord injury (SCI). Previous scES mapping studies targeting the lower urinary tract (LUT) in rats demonstrated functional response variability based upon lumbosacral level, parameters used, extent of injury (spinally intact vs. chronic anatomically complete spinal transections), and sex. In the current study, female rats with clinically relevant graded incomplete T9 contusion injuries were mapped with scES at 60 days post-injury at three spinal levels (T13, L3, L6) with a novel miniature 15-electrode array designed to deliver optimal specificity. The results obtained during bladder fill and void cycles conducted under urethane anesthesia indicate frequency dependent sub-motor threshold effects on LUT function with a single row of electrodes positioned across the full medio-lateral extent of the dorsal cord. The findings of improved storage and emptying, represented by significantly longer inter-contractile intervals with T13 scES and L3 scES and by a significantly increased estimated void efficiency with L6 scES, respectively, are consistent with previous studies using intact and chronic complete transected male and female rats. The data support the efficacy of selective spinal network stimulation to drive functionally relevant networks for storage versus emptying phases of the urinary cycle. The current findings further demonstrate the translational promise of scES for SCI individuals with LUT dysfunctions, regardless of injury severity.

Effects of Robotic Postural Stand Training with Epidural Stimulation on Sitting Postural Control in Individuals with Spinal Cord Injury: A Pilot Study.

(1) Background. High-level spinal cord injury (SCI) disrupts trunk control, leading to an impaired performance of upright postural tasks in sitting and standing. We previously showed that a novel robotic postural stand training with spinal cord epidural stimulation targeted at facilitating standing (Stand-scES) largely improved standing trunk control in individuals with high-level motor complete SCI. Here, we aimed at assessing the effects of robotic postural stand training with Stand-scES on sitting postural control in the same population. (2) Methods. Individuals with cervical (n = 5) or high-thoracic (n = 1) motor complete SCI underwent approximately 80 sessions (1 h/day; 5 days/week) of robotic postural stand training with Stand-scES, which was performed with free hands (i.e., without using handlebars) and included periods of standing with steady trunk control, self-initiated trunk and arm movements, and trunk perturbations. Sitting postural control was assessed on a standard therapy mat, with and without scES targeted at facilitating sitting (Sit-scES), before and after robotic postural stand training. Independent sit time and trunk center of mass (CM) displacement were assessed during a 5 min time window to evaluate steady sitting control. Self-initiated antero-posterior and medial-lateral trunk movements were also attempted from a sitting position, with the goal of covering the largest distance in the respective cardinal directions. Finally, the four Neuromuscular Recovery Scale items focused on sitting trunk control (Sit, Sit-up, Trunk extension in sitting, Reverse sit-up) were assessed. (3) Results. In summary, neither statistically significant differences nor large Effect Size were promoted by robotic postural stand training for the sitting outcomes considered for analysis. (4) Conclusions. The findings of the present study, together with previous observations, may suggest that robotic postural stand training with Stand-scES promoted trunk motor learning that was posture- and/or task-specific and, by itself, was not sufficient to significantly impact sitting postural control.

Selective Activation of the Spinal Cord with Epidural Electrical Stimulation.

Spinal cord epidural electrical stimulation (EES) has been successfully employed to treat chronic pain and to restore lost functions after spinal cord injury. Yet, the efficacy of this approach is largely challenged by the suboptimal spatial distribution of the electrode contacts across anatomical targets, limiting the spatial selectivity of stimulation. In this study, we exploited different ESS paradigms, designed as either Spatial-Selective Stimulation (SSES) or Orientation-Selective Epidural Stimulation (OSES), and compared them to Conventional Monopolar Epidural Stimulation (CMES). SSES, OSES, and CMES were delivered with a 3- or 4-contact electrode array. Amplitudes and latencies of the Spinally Evoked Motor Potentials (SEMPs) were evaluated with different EES modalities. The results demonstrate that the amplitudes of SEMPs in hindlimb muscles depend on the orientation of the electrical field and vary between stimulation modalities. These findings show that the electric field applied with SSES or OSES provides more selective control of amplitudes of the SEMPs as compared to CMES. We demonstrate that spinal cord epidural stimulation applied with SSES or OSES paradigms in the rodent model could be tailored to the functional spinal cord neuroanatomy and can be tuned to specific target fibers and their orientation, optimizing the effect of neuromodulation.

Thoracic canal morphology on preoperative magnetic resonance imaging in spinal cord stimulation patients.

INTRODUCTION: In high-frequency spinal cord stimulation anatomic placement targeting of the T9-10 disc space is based on "empiric" results that are best replicated with coverage broadly from T8 to T10. This study contains the largest cohort of patients evaluating low thoracic morphology and seeks to address the lack of MRI morphological analysis in literature. METHODS: This study was a retrospective review of a database of 101 consecutive patients undergoing permanent implant of thoracic SCS for chronic pain. Measurements were carried out on preoperative MRI imaging. Anteroposterior (AP) and lateral dimensions of the spinal cord as well as dural sac were measured. In addition, dorsal cerebrospinal fluid thickness and paddle depression distance were also measured. RESULTS: When comparing morphological dimensions by level, dorsal CSF thickness was smaller at T9-10 than T7-8 (p = 0.018). In addition, lateral dural and spinal cord diameters were larger at T10-11 than T9-10, contributing to larger dural surface area at T10-11 (p = 0.028). While trends of dorsal CSF thickness tend to decrease with lower thoracic levels, the ratio of surface area of spinal cord to dural sac appeared to remain relatively constant. CONCLUSIONS: Dorsal CSF thickness is smaller at T9-10 than T7-8 in chronic pain patients in this cohort. More ellipsoid, cord, and spinal canal diameter measurements were noted at lower levels of the thoracic spinal cord, particularly at T10-11. This may correlate with anatomical SCS placement. Future studies should evaluate efficacy of SCS therapy for pain based on these anatomical considerations.

Peak Slope Ratio of the Recruitment Curves Compared to Muscle Evoked Potentials to Optimize Standing Configurations with Percutaneous Epidural Stimulation after Spinal Cord Injury.

Background: Percutaneous spinal cord epidural stimulation (pSCES) has effectively restored varying levels of motor control in persons with motor complete spinal cord injury (SCI). Studying and standardizing the pSCES configurations may yield specific motor improvements. Previously, reliance on the amplitude of the SCES-evoked potentials (EPs) was used to determine the correct stimulation configurations. Methods: We, hereby, retrospectively examined the effects of wide and narrow-field configurations on establishing the motor recruitment curves of motor units of three different agonist-antagonist muscle groups. Magnetic resonance imaging was also used to individualize SCI participants (n = 4) according to their lesion characteristics. The slope of the recruitment curves using a six-degree polynomial function was calculated to derive the slope ratio for the agonist-antagonist muscle groups responsible for standing. Results: Axial damage ratios of the spinal cord ranged from 0.80 to 0.92, indicating at least some level of supraspinal connectivity for all participants. Despite the close range of these ratios, standing motor performance was enhanced using different stimulation configurations in the four persons with SCI. A slope ratio of ≥1 was considered for the recommended configurations necessary to achieve standing. The retrospectively identified configurations using the supine slope ratio of the recruitment curves of the motor units agreed with that visually inspected muscle EPs amplitude of the extensor relative to the flexor muscles in two of the four participants. Two participants managed to advance the selected configurations into independent standing performance after using tonic stimulation. The other two participants required different levels of assistance to attain standing performance. Conclusions: The findings suggest that the peak slope ratio of the muscle agonists-antagonists recruitment curves may potentially identify the pSCES configurations necessary to achieve standing in persons with SCI.

Robotic Postural Training With Epidural Stimulation for the Recovery of Upright Postural Control in Individuals With Motor Complete Spinal Cord Injury: A Pilot Study.

Activity-based training and lumbosacral spinal cord epidural stimulation (scES) have the potential to restore standing and walking with self-balance assistance after motor complete spinal cord injury (SCI). However, improvements in upright postural control have not previously been addressed in this population. Here, we implemented a novel robotic postural training with scES, performed with free hands, to restore upright postural control in individuals with chronic, cervical (n = 5) or high-thoracic (n = 1) motor complete SCI, who had previously undergone stand training with scES using a walker or a standing frame for self-balance assistance. Robotic postural training re-enabled and/or largely improved the participants' ability to control steady standing, self-initiated trunk movements and upper limb reaching movements while standing with free hands, receiving only external assistance for pelvic control. These improvements were associated with neuromuscular activation pattern adaptations above and below the lesion. These findings suggest that the human spinal cord below the level of injury can generate meaningful postural responses when its excitability is modulated by scES, and can learn to improve these responses. Upright postural control improvements can enhance functional motor recovery promoted by scES after severe SCI.

Closed-loop cervical epidural stimulation partially restores ipsilesional diaphragm EMG after acute C2 hemisection.

Cervical spinal cord injury creates lasting respiratory deficits which can require mechanical ventilation long-term. We have shown that closed-loop epidural stimulation (CL-ES) elicits respiratory plasticity in the form of increased phrenic network excitability (Malone et. al., E Neuro, Vol 9, 0426-21.2021, 2022); however, the ability of this treatment to create functional benefits for breathing function per se after injury has not been demonstrated. Here, we demonstrate in C2 hemisected anesthetized rats, a 20-minute bout of CL-ES administered at current amplitudes below the motor threshold restores paralyzed hemidiaphragm activity in-phase with breathing while potentiating contralesional activity. While this acute bout of stimulation did not elicit the increased network excitability seen in our chronic model, a subset of stimulated animals continued spontaneous ipsilesional diaphragm activity for several seconds after stopping stimulation. These results support the use of CL-ES as a therapeutic to rescue breathing after high cervical spinal cord injury, with the potential to lead to lasting recovery and device independence.

Interleaved configurations of percutaneous epidural stimulation enhanced overground stepping in a person with chronic paraplegia.

Descending motor signals are disrupted after complete spinal cord injury (SCI) resulting in loss of standing and walking. We previously restored standing and trunk control in a person with a T3 complete SCI following implantation of percutaneous spinal cord epidural stimulation (SCES). We, hereby, present a step-by-step procedure on configuring the SCES leads to initiate rhythmic lower limb activation (rhythmic-SCES) resulting in independent overground stepping in parallel bars and using a standard walker. Initially, SCES was examined in supine lying at 2 Hz before initiating stepping-like activity in parallel bars using 20 or 30 Hz; however, single lead configuration (+2, -5) resulted in lower limb adduction and crossing of limbs, impairing the initiation of overground stepping. After 6 months, interleaving the original rhythmic-SCES with an additional configuration (-12, +15) on the opposite lead, resulted in a decrease of the extensive adduction tone and allowed the participant to initiate overground stepping up to 16 consecutive steps. The current paradigm suggests that interleaving two rhythmic-SCES configurations may improve the excitability of the spinal circuitry to better interpret the residual descending supraspinal signals with the ascending proprioceptive inputs, resulting in a stepping-like motor behavior after complete SCI.

Standing Reactive Postural Responses of Lower Limbs With and Without Self-Balance Assistance in Individuals With Spinal Cord Injury Receiving Epidural Stimulation.

Spinal cord epidural stimulation can promote the recovery of motor function in individuals with severe spinal cord injury (SCI) by enabling the spinal circuitry to interpret sensory information and generate related neuromuscular responses. This approach enables the spinal cord to generate lower limb extension patterns during weight bearing, allowing individuals with SCI to achieve upright standing. We have shown that the human spinal cord can generate some standing postural responses during self-initiated body weight shifting. In this study, we investigated the ability of individuals with motor complete SCI receiving epidural stimulation to generate standing reactive postural responses after external perturbations were applied at the trunk. A cable-driven robotic device was used to provide constant assistance for pelvic control and to deliver precise trunk perturbations while participants used their hands to grasp onto handlebars for self-balance support (hands-on) as well as when participants were without support (free-hands). Five individuals with motor complete SCI receiving lumbosacral spinal cord epidural stimulation parameters specific for standing (Stand-scES) participated in this study. Trunk perturbations (average magnitude: 17 ± 3% body weight) were delivered randomly in the four cardinal directions. Participants attempted to control each perturbation such that upright standing was maintained and no additional external assistance was needed. Lower limb postural responses were generally more frequent, larger in magnitude, and appropriately modulated during the free-hands condition. This was associated with trunk displacement and lower limb loading modulation that were larger in the free-hands condition. Further, we observed discernible lower limb muscle synergies that were similar between the two perturbed standing conditions. These findings suggest that the human spinal circuitry involved in postural control retains the ability to generate meaningful lower limb postural responses after SCI when its excitability is properly modulated. Moreover, lower limb postural responses appear enhanced by a standing environment without upper limb stabilization that promotes afferent inputs associated with a larger modulation of ground reaction forces and trunk kinematics. These findings should be considered when developing future experimental frameworks aimed at studying upright postural control and activity-based recovery training protocols aimed at promoting neural plasticity and sensory-motor recovery.

Spinal cord stimulation for spinal cord injury - Where do we stand? A narrative review.

Recovery of function following a complete spinal cord injury (SCI) or an incomplete SCI where recovery has plateaued still eludes us despite extensive research. Epidural spinal cord stimulation (SCS) was initially used for managing neuropathic pain. It has subsequently demonstrated improvement in motor function in otherwise non-recovering chronic spinal cord injury in animal and human trials. The mechanisms of how it is precisely effective in doing so will need further research, which would help refine the technology for broader application. Transcutaneous spinal cord stimulation (TSCS) is also emerging as a modality to improve the functional outcome in SCI individuals, especially when coupled with appropriate rehabilitation. Apart from motor recovery, ESCS and TSCS have also shown improvement in autonomic, metabolic, genitourinary, and pulmonary function. Since the literature on this is still in its infancy, with no large-scale randomised trials and different studies using different protocols in a wide range of patients, a review of the present literature is imperative to better understand the latest developments in this field. This article examines the existing literature on the use of SCS for SCI individuals with the purpose of enabling functional recovery. It also examines the voids in the present research, thus providing future directions.

Spinal Cord Epidural Stimulation Improves Lower Spine Sitting Posture Following Severe Cervical Spinal Cord Injury.

Cervical spinal cord injury (SCI) leads to impaired trunk motor control, negatively impacting the performance of activities of daily living in the affected individuals. Improved trunk control with better sitting posture has been previously observed due to neuromuscular electrical stimulation and transcutaneous spinal stimulation, while improved postural stability has been observed with spinal cord epidural stimulation (scES). Hence, we studied how trunk-specific scES impacts sitting independence and posture. Fourteen individuals with chronic, severe cervical SCI with an implanted neurostimulator performed a 5-min tall-sit task without and with trunk-specific scES. Spine posture was assessed by placing markers on five spine levels and evaluating vertical spine inclination angles. Duration of trunk manual assistance was used to assess independence along with the number of independence changes and average independence score across those changes. With scES, the sacrum-L1 inclination and number of independence changes tended to decrease by 1.64 ± 3.16° (p = 0.07; Cohen's d = 0.53) and 9.86 ± 16.8 (p = 0.047; Cohen's d = 0.59), respectively. Additionally, for the participants who had poor sitting independence without scES, level of independence tended to increase by 12.91% [0%, 31.52%] (p = 0.38; Cohen's d = 0.96) when scES was present. Hence, trunk-specific scES promoted improvements in lower spine posture and lower levels of trunk assistance.

Happy Birthday "One Flew Over the Cuckoo's Nest": A Momentous Tale in the Quest for an Effective and Ethical Approach to Psychosurgery.

The anniversary of the publication of 'One Flew Over the Cuckoo's Nest' by Ken Kesey offers an opportunity for reflection on the use of neurosurgery in psychiatry. We used a narrative, historical and dialectical method to deliver an account of the controversial subject. A balanced representation of the negative and positive aspects, acknowledging some of the questionable ethical practices while describing well-reasoned applications is provided. It includes neurosurgeons, psychiatrists who have embraced these procedures with unwarranted enthusiasm and those who have opposed. Neurosurgical techniques for the treatment of severe mental disorders have evolved from rudimentary procedures which were used to 'correct' unwanted behaviours associated with a wide range of severe mental disorders to more refined and selective approaches used as a last resort to treat specific mental health conditions. In the absence of specific aetiological models to guide ablative surgical targets, non-ablative, stimulatory techniques have more recently been developed to allow reversibility when surgical treatment fails to obtain a sizeable improvement in quality of life. The subject is concretely illustrated by two eloquent clinical images: one on a series of brain computed tomography scans carried out on a Canadian population of subjects, who underwent leukotomy decades ago, and the other more contemporary on an implantation surgery to epidural stimulation. Alongside technical advances in psychosurgery, a regulatory framework has gradually developed to ensure vigilance in the appropriateness of patients' selection. Nevertheless, harmonisation of protocols around the world is necessary to ensure consistency in obtaining and maintaining the highest possible ethical standards for the benefit of patients. If the neurosciences promise today, in their new, better framed, and reversible applications, to provide answers to unmet therapeutic needs, we still must remain attentive to drifts linked the introduction of intrusive technologies for purposes of domination or behaviour modification that would impede our individual freedom.

Advances in Spinal Cord Neuromodulation: The Integration of Neuroengineering, Computational Approaches, and Innovative Conceptual Frameworks.

Spinal cord stimulation (SCS) is an approved treatment for intractable pain and has recently emerged as a promising area of research for restoring function after spinal cord lesion. This review will focus on the historical evolution of this transition and the path that remains to be taken for these methods to be rigorously evaluated for application in clinical practice. New developments in SCS are being driven by advances in the understanding of spinal cord lesions at the molecular, cellular, and neuronal levels, as well as the understanding of compensatory mechanisms. Advances in neuroengineering and the computational neurosciences have enabled the development of new conceptual SCS strategies, such as spatiotemporal neuromodulation, which allows spatially selective stimulation at precise time points during anticipated movement. It has also become increasingly clear that these methods are only effective when combined with intensive rehabilitation techniques, such as new task-oriented methods and robotic aids. The emergence of innovative approaches to spinal cord neuromodulation has sparked significant enthusiasm among patients and in the media. Non-invasive methods are perceived to offer improved safety, patient acceptance, and cost-effectiveness. There is an immediate need for well-designed clinical trials involving consumer or advocacy groups to evaluate and compare the effectiveness of various treatment modalities, assess safety considerations, and establish outcome priorities.

Targeted Selection of Stimulation Parameters for Restoration of Motor and Autonomic Function in Individuals With Spinal Cord Injury.

STUDY DESIGN: This is a report of methods and tools for selection of task and individual configurations targeted for voluntary movement, standing, stepping, blood pressure stabilization, and facilitation of bladder storage and emptying using tonic-interleaved excitation of the lumbosacral spinal cord. OBJECTIVES: This study aimed to present strategies used for selection of stimulation parameters for various motor and autonomic functions. CONCLUSIONS: Tonic-interleaved functionally focused neuromodulation targets a myriad of consequences from spinal cord injury with surgical implantation of the epidural electrode at a single location. This approach indicates the sophistication of the human spinal cord circuitry and its important role in the regulation of motor and autonomic functions in humans.

Spinal Cord Stimulation Prevents Autonomic Dysreflexia in Individuals with Spinal Cord Injury: A Case Series.

Spinal cord injury (SCI) results in severe cardiovascular dysfunction due to the disruption of supraspinal control. Autonomic dysreflexia (AD), an uncontrolled rise in blood pressure in response to peripheral stimuli including common bowel routine, digital anorectal stimulation (DARS), reduces the quality of life, and increases morbidity and mortality. Recently, spinal cord stimulation (SCS) has emerged as a potential intervention to mitigate unstable blood pressure following SCI. The objective of this case series was to test the real-time effect of epidural SCS (eSCS) at the lumbosacral spinal cord, the most common implant location, on mitigating AD in individuals with SCI. We recruited three individuals with cervical and upper thoracic motor-complete SCI who have an implanted epidural stimulator. We demonstrated that eSCS can reduce the elevation in blood pressure and prevent DARS-induced AD. The blood pressure variability analysis indicated that eSCS potentially reduced vascular sympathetic nervous system activity during DARS, compared to without eSCS. This case series provides evidence to support the use of eSCS to prevent AD episodes during routine bowel procedures, improving the quality of life for individuals with SCI and potentially reducing cardiovascular risks.

Spinal cord epidural stimulation for motor and autonomic function recovery after chronic spinal cord injury: A case series and technical note.

Background: Traumatic spinal cord injury (tSCI) is a debilitating condition, leading to chronic morbidity and mortality. In recent peer-reviewed studies, spinal cord epidural stimulation (scES) enabled voluntary movement and return of over-ground walking in a small number of patients with motor complete SCI. Using the most extensive case series (n = 25) for chronic SCI, the present report describes our motor and cardiovascular and functional outcomes, surgical and training complication rates, quality of life (QOL) improvements, and patient satisfaction results after scES. Methods: This prospective study occurred at the University of Louisville from 2009 to 2020. scES interventions began 2-3 weeks after surgical implantation of the scES device. Perioperative complications were recorded as well as long-term complications during training and device related events. QOL outcomes and patient satisfaction were evaluated using the impairment domains model and a global patient satisfaction scale, respectively. Results: Twenty-five patients (80% male, mean age of 30.9 ± 9.4 years) with chronic motor complete tSCI underwent scES using an epidural paddle electrode and internal pulse generator. The interval from SCI to scES implantation was 5.9 ± 3.4 years. Two participants (8%) developed infections, and three additional patients required washouts (12%). All participants achieved voluntary movement after implantation. A total of 17 research participants (85%) reported that the procedure either met (n = 9) or exceeded (n = 8) their expectations, and 100% would undergo the operation again. Conclusion: scES in this series was safe and achieved numerous benefits on motor and cardiovascular regulation and improved patient-reported QOL in multiple domains, with a high degree of patient satisfaction. The multiple previously unreported benefits beyond improvements in motor function render scES a promising option for improving QOL after motor complete SCI. Further studies may quantify these other benefits and clarify scES's role in SCI patients.

Effects of percutaneously-implanted epidural stimulation on cardiovascular autonomic function and spasticity after complete spinal cord injury: A case report.

Importance: There is a revived interest to explore spinal cord epidural stimulation (SCES) to improve physical function after spinal cord injury (SCI). This case report highlights the potential of eliciting multiple functional improvements with a single SCES configuration, a strategy which could improve clinical translation. Objective: To determine whether SCES intended to facilitate walking also acutely yields benefits in cardiovascular autonomic regulation and spasticity. Design: Case report from data collected at two timepoints 15 weeks apart from March to June 2022 as part of a larger clinical trial. Setting: Research lab at Hunter Holmes McGuire VA Medical Center. Participant: 27-year-old male, 7 years post a C8 motor complete spinal cord injury. Intervention: A SCES configuration intended to enhance exoskeleton-assisted walking training applied for autonomic and spasticity management. Main outcomes and measures: The primary outcome was cardiovascular autonomic response to a 45-degree head-up-tilt test. Systolic blood pressure (SBP), heart rate (HR), and absolute power of the low-frequency (LF) and high-frequency (HF) components of a heart-rate variability analysis were collected in supine and tilt with and without the presence of SCES. Right knee flexor and knee extensor spasticity was assessed via isokinetic dynamometry with and without SCES. Results: At both assessments with SCES off, transitioning from supine to tilt decreased SBP (assessment one: 101.8 to 70 mmHg; assessment two: 98.9 to 66.4 mmHg). At assessment one, SCES on in supine (3 mA) increased SBP (average 117 mmHg); in tilt, 5 mA stabilized SBP near baseline values (average 111.5 mmHg). At assessment two, SCES on in supine (3 mA) increased SBP (average 140 mmHg in minute one); decreasing amplitude to 2 mA decreased SBP (average 119 mmHg in minute five). In tilt, 3 mA stabilized SBP near baseline values (average 93.2 mmHg). Torque-time integrals at the right knee were reduced at all angular velocities for knee flexors (range: -1.9 to -7.8%) and knee extensors (range: -1 to -11.4%). Conclusions and relevance: These results demonstrate that SCES intended to facilitate walking may also enhance cardiovascular autonomic control and attenuate spasticity. Using one configuration to enhance multiple functions after SCI may accelerate clinical translation. Clinical trial registration: https://clinicaltrials.gov/ct2/show/, identifier NCT04782947.

Combined cervical transcutaneous with lumbosacral epidural stimulation improves voluntary control of stepping movements in spinal cord injured individuals.

Introduction: Lumbosacral spinal cord neuromodulation has shown the ability to restore voluntary control and stepping in individuals with chronic spinal cord injury. Methods: We combined cervical transcutaneous and lumbar epidural stimulation to explore the brain-spinal connectomes and their influence in spinal excitability and interlimb coupling. Four individuals with a prior implanted lumbosacral spinal cord epidural stimulator participated in the study. We assessed lower extremity muscle activity and kinematics during intentional stepping in both non-weight bearing and weight-bearing environments. Results: Our results showed an inhibition of motor evoked potentials generated by spinal cord epidural stimulation when cervical transcutaneous stimulation is applied. In contrast, when intentional stepping is performed in a non-weight bearing setting, range of motion, motor output amplitude, and coordination are improved when cervical transcutaneous and lumbar epidural stimulations are combined. Similarly, with both stimulations applied, coordination is improved and motor output variability is decreased when intentional stepping is performed on a treadmill with body weight support. Discussion: Combined transcutaneous cervical and epidural lumbar stimulation demonstrated an improvement of voluntary control of stepping in individuals with chronic motor complete paralysis. The immediate functional improvement promoted by the combination of cervical and lumbar stimulation adds to the body of evidence for increasing spinal excitability and improvement of function that is possible in individuals with chronic paralysis.