Ergogenic effects of an epidural neuroprosthesis in one individual with spinal cord injury.
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ABSTRACT:
SUBMITTER: Nightingale TE
PROVIDER: S-EPMC6382359 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Spinal cord injury (SCI) leads to severe impairment in cardiovascular control, commonly manifested as a rapid, uncontrolled rise in blood pressure triggered by peripheral stimuli-a condition called autonomic dysreflexia. The objective was to demonstrate the translational potential of noninvasive transcutaneous stimulation (TCS) in mitigating autonomic dysreflexia following SCI, using pre-clinical evidence and a clinical case report. In rats with SCI, we show that TCS not only prevents the instigation of autonomic dysreflexia, but also mitigates its severity when delivered during an already-triggered episode. Furthermore, when TCS was delivered as a multisession therapy for 6 weeks post-SCI, the severity of autonomic dysreflexia was significantly reduced when tested in the absence of concurrent TCS. This treatment effect persisted for at least 1 week after the end of therapy. More importantly, we demonstrate the clinical applicability of TCS in treatment of autonomic dysreflexia in an individual with cervical, motor-complete, chronic SCI. We anticipate that TCS will offer significant therapeutic advantages, such as obviating the need for surgery resulting in reduced risk and medical expenses. Furthermore, this study provides a framework for testing the potential of TCS in improving recovery of other autonomic functions such lower urinary tract, bowel, and sexual dysfunction following SCI.
| S-EPMC8423970 | biostudies-literature
Project description: Not available
| S-EPMC5885254 | biostudies-literature
Project description:The translation of new therapies for spinal cord injury to clinical trials can be facilitated with large animal models close in morpho-physiological scale to humans. Here, we report functional restoration and morphological reorganization after spinal contusion in pigs, following a combined treatment of locomotor training facilitated with epidural electrical stimulation (EES) and cell-mediated triple gene therapy with umbilical cord blood mononuclear cells overexpressing recombinant vascular endothelial growth factor, glial-derived neurotrophic factor, and neural cell adhesion molecule. Preliminary results obtained on a small sample of pigs 2 months after spinal contusion revealed the difference in post-traumatic spinal cord outcomes in control and treated animals. In treated pigs, motor performance was enabled by EES and the corresponding morpho-functional changes in hind limb skeletal muscles were accompanied by the reorganization of the glial cell, the reaction of stress cell, and synaptic proteins. Our data demonstrate effects of combined EES-facilitated motor training and cell-mediated triple gene therapy after spinal contusion in large animals, informing a background for further animal studies and clinical translation.
| S-EPMC7734573 | biostudies-literature
Project description:Previous studies have shown that epidural stimulation of the lumbosacral spinal cord (scES) can re-enable lower limb volitional motor control in individuals with chronic, clinically motor complete spinal cord injury (SCI). This observation entails that residual supraspinal connectivity to the lumbosacral spinal circuitry still persisted after SCI, although it was non-detectable when scES was not provided. In the present study, we aimed at exploring further the mechanisms underlying scES-promoted recovery of volitional lower limb motor control by investigating neuroimaging markers at the spinal cord lesion site via magnetic resonance imaging (MRI). Spinal cord MRI was collected prior to epidural stimulator implantation in 13 individuals with chronic, clinically motor complete SCI, and the spared tissue of specific regions of the spinal cord (anterior, posterior, right, left, and total cord) was assessed. After epidural stimulator implantation, and prior to any training, volitional motor control was evaluated during left and right lower limb flexion and ankle dorsiflexion attempts. The ability to generate force exertion and movement was not correlated to any neuroimaging marker. On the other hand, spared tissue of specific cord regions significantly and importantly correlated with some aspects of motor control that include activation amplitude of antagonist (negative correlation) muscles during left ankle dorsiflexion, and electromyographic coordination patterns during right lower limb flexion. The fact that amount and location of spared spinal cord tissue at the lesion site were not related to the ability to generate volitional lower limb movements may suggest that supraspinal inputs through spared spinal cord regions that differ across individuals can result in the generation of lower limb volitional motor output prior to any training when epidural stimulation is provided.
| S-EPMC7654217 | biostudies-literature
Project description:Epidural spinal cord stimulation has a long history of application for improving motor control in spinal cord injury. This review focuses on its resurgence following the progress made in understanding the underlying neurophysiological mechanisms and on recent reports of its augmentative effects upon otherwise subfunctional volitional motor control. Early work revealed that the spinal circuitry involved in lower-limb motor control can be accessed by stimulating through electrodes placed epidurally over the posterior aspect of the lumbar spinal cord below a paralyzing injury. Current understanding is that such stimulation activates large-to-medium-diameter sensory fibers within the posterior roots. Those fibers then trans-synaptically activate various spinal reflex circuits and plurisegmentally organized interneuronal networks that control more complex contraction and relaxation patterns involving multiple muscles. The induced change in responsiveness of this spinal motor circuitry to any residual supraspinal input via clinically silent translesional neural connections that have survived the injury may be a likely explanation for rudimentary volitional control enabled by epidural stimulation in otherwise paralyzed muscles. Technological developments that allow dynamic control of stimulation parameters and the potential for activity-dependent beneficial plasticity may further unveil the remarkable capacity of spinal motor processing that remains even after severe spinal cord injuries.
| S-EPMC4824029 | biostudies-literature
Project description:Epidural Spinal Cord Stimulation (eSCS) in combination with extensive rehabilitation has been reported to restore volitional movement in a select group of subjects after motor-complete spinal cord injury (SCI). Numerous questions about the generalizability of these findings to patients with longer term SCI have arisen, especially regarding the possibility of restoring autonomic function. To better understand the effect of eSCS on volitional movement and autonomic function, two female participants five and 10 years after injury at ages 48 and 52, respectively, with minimal spinal cord preservation on magnetic resonance imaging were implanted with an eSCS system at the vertebral T12 level. We demonstrated that eSCS can restore volitional movement immediately in two female participants in their fifth and sixth decade of life with motor and sensory-complete SCI, five and 10 years after sustaining severe radiographic injuries, and without prescribed or significant pre-habilitation. Both patients experienced significant improvements in surface electromyography power during a volitional control task with eSCS on. Cardiovascular function was also restored with eSCS in one participant with cardiovascular dysautonomia using specific eSCS settings during tilt challenge while not affecting function in a participant with normal cardiovascular function. Orgasm was achieved for the first time since injury in one participant with and immediately after eSCS. Bowel-bladder synergy improved in both participants while restoring volitional urination in one with eSCS. While numerous questions remain, the ability to restore some supraspinal control over motor function below the level of injury, cardiovascular function, sexual function, and bowel and bladder function should promote intense efforts to investigate and develop optimization strategies to maximize recovery in all participants with chronic SCI.
| S-EPMC6648195 | biostudies-literature
Project description:Epidural electrical stimulation can restore limb motor function after spinal cord injury by reactivating the surviving neural circuits. In previous epidural electrical stimulation studies, single electrode sites and continuous tetanic stimulation have often been used. With this stimulation, the body is prone to declines in tolerance and locomotion coordination. In the present study, rat models of complete spinal cord injury were established by vertically cutting the spinal cord at the T8 level to eliminate disturbance from residual nerve fibers, and were then subjected to epidural electrical stimulation. The flexible extradural electrode had good anatomical topology and matched the shape of the spinal canal of the implanted segment. Simultaneously, the electrode stimulation site was able to be accurately applied to the L2-3 and S1 segments of the spinal cord. To evaluate the biocompatibility of the implanted epidural electrical stimulation electrodes, GFAP/Iba-1 double-labeled immunofluorescence staining was performed on the spinal cord below the electrodes at 7 days after the electrode implantation. Immunofluorescence results revealed no significant differences in the numbers or morphologies of microglia and astrocytes in the spinal cord after electrode implantation, and there was no activated Iba-1+ cell aggregation, indicating that the implant did not cause an inflammatory response in the spinal cord. Rat gait analysis showed that, at 3 days after surgery, gait became coordinated in rats with spinal cord injury under burst stimulation. The regained locomotion could clearly distinguish the support phase and the swing phase and dynamically adjust with the frequency of stimulus distribution. To evaluate the matching degree between the flexible epidural electrode (including three stimulation contacts), vertebral morphology, and the level of the epidural site of the stimulation electrode, micro-CT was used to scan the thoracolumbar vertebrae of rats before and after electrode implantation. Based on the experimental results of gait recovery using three-site stimulation electrodes at L2-3 and S1 combined with burst stimulation in a rat model of spinal cord injury, epidural electrical stimulation is a promising protocol that needs to be further explored. This study was approved by the Animal Ethics Committee of Chinese PLA General Hospital (approval No. 2019-X15-39) on April 19, 2019.
| S-EPMC7996032 | biostudies-literature
Project description:Objective: To determine if an implanted neuroprosthesis for restoration of an effective cough is less costly than conventional methods of respiratory management. Methods: Nonrandomized clinical trial of participants (N = 14) with spinal cord injury (SCI) using the Cough Stimulator device in the inpatient hospital setting for Cough Stimulator implantation and outpatient hospital or residence for follow-up. A neuroprosthesis was implanted for restoration of an effective cough. The annual costs associated with respiratory management, without (pre implantation) and with (post implantation) the neuroprosthesis, were examined over a 4-year period. Results: The total cost related to implantation of the Cough Stimulator was $59,891, with no maintenance costs over subsequent years. The incidence of respiratory tract infections and the need for caregiver support fell significantly following implantation. The costs associated with respiratory tract infections fell significantly from a mean of $36,406 ± 11,855/year to $13,284 ± 7,035/year (p < .05) pre and post implantation, respectively. Costs fell further to $8,817 ± 5,990 and $4,467 ± 4,404 following the 2nd and 3rd years post implantation (p < .05), respectively. The costs associated with caregiver support fell significantly from $25,312 ± 8,019/year to $2,630 ± 2,233/year (p < .05) pre and post implantation, respectively, and remained low in subsequent years (p < .05). Other costs related to secretion management fell significantly and remained low in subsequent years (p < .05). Break-even analysis demonstrated that this point was reached in the first year. Conclusion: The results of this investigation demonstrate that implantation and use of the Cough Stimulator resulted in significant reductions in the overall costs of respiratory management in this patient population.
| S-EPMC5562035 | biostudies-literature
Project description:Epidural stimulation of the spinal cord is a promising technique for the recovery of motor function after spinal cord injury. The key challenges within the reconstruction of motor function for paralyzed limbs are the precise control of sites and parameters of stimulation. To activate lower-limb muscles precisely by epidural spinal cord stimulation, we proposed a high-density, flexible electrode array. We determined the regions of motor function that were activated upon epidural stimulation of the spinal cord in a rat model with complete spinal cord, which was established by a transection method. For evaluating the effect of stimulation, the evoked potentials were recorded from bilateral lower-limb muscles, including the vastus lateralis, semitendinosus, tibialis anterior, and medial gastrocnemius. To determine the appropriate stimulation sites and parameters of the lower muscles, the stimulation characteristics were studied within the regions in which motor function was activated upon spinal cord stimulation. In the vastus lateralis and medial gastrocnemius, these regions were symmetrically located at the lateral site of L1 and the medial site of L2 vertebrae segment, respectively. The tibialis anterior and semitendinosus only responded to stimulation simultaneously with other muscles. The minimum and maximum stimulation threshold currents of the vastus lateralis were higher than those of the medial gastrocnemius. Our results demonstrate the ability to identify specific stimulation sites of lower muscles using a high-density and flexible array. They also provide a reference for selecting the appropriate conditions for implantable stimulation for animal models of spinal cord injury. This study was approved by the Animal Research Committee of Southeast University, China (approval No. 20190720001) on July 20, 2019.
| S-EPMC8504402 | biostudies-literature
