Association of Epidural Stimulation With Cardiovascular Function in an Individual With Spinal Cord Injury.
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SUBMITTER: West CR
PROVIDER: S-EPMC5885254 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC6583212 | biostudies-literature
Project description:Sexual dysfunction is a common consequence for women with spinal cord injury (SCI); however, current treatments are ineffective, especially in the under-prioritized population of women with SCI. This case-series, a secondary analysis of the Epidural Stimulation After Neurologic Damage (E-STAND) clinical trial aimed to investigate the effect of epidural spinal cord stimulation (ESCS) on sexual function and distress in women with SCI. Three females, with chronic, thoracic, sensorimotor complete SCI received daily (24 h/day) tonic ESCS for 13 months. Questionnaires, including the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale (FSDS) were collected monthly. There was a 3.2-point (13.2%) mean increase in total FSFI from baseline (24.5 ± 4.1) to post-intervention (27.8 ± 6.6), with a 4.8-50% improvement in the sub-domains of desire, arousal, orgasm and satisfaction. Sexual distress was reduced by 55%, with a mean decrease of 12 points (55.4%) from baseline (21.7 ± 17.2) to post-intervention (9.7 ± 10.8). There was a clinically meaningful change of 14 points in the International Standards for Neurological Classification of Spinal Cord Injury total sensory score from baseline (102 ± 10.5) to post-intervention (116 ± 17.4), without aggravating dyspareunia. ESCS is a promising treatment for sexual dysfunction and distress in women with severe SCI. Developing therapeutic interventions for sexual function is one of the most meaningful recovery targets for people with SCI. Additional large-scale investigations are needed to understand the long-term safety and feasibility of ESCS as a viable therapy for sexual dysfunction. Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT03026816, NCT03026816.
| S-EPMC10167769 | 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: Not available
| S-EPMC7666087 | 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: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.
| S-EPMC10525621 | 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
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:IntroductionSpinal cord injury (SCI) leads to significant changes in morbidity, mortality and quality of life (QOL). Currently, there are no effective therapies to restore function after chronic SCI. Preliminary studies have indicated that epidural spinal cord stimulation (eSCS) is a promising therapy to improve motor control and autonomic function for patients with chronic SCI. The aim of this study is to assess the effects of tonic eSCS after chronic SCI on quantitative outcomes of volitional movement and cardiovascular function. Our secondary objective is to optimise spinal cord stimulation parameters for volitional movement.Methods and analysisThe Epidural Stimulation After Neurologic Damage (ESTAND) trial is a phase II single-site self-controlled trial of epidural stimulation with the goal of restoring volitional movement and autonomic function after motor complete SCI. Participants undergo epidural stimulator implantation and are followed up over 15 months while completing at-home, mobile application-based movement testing. The primary outcome measure integrates quantity of volitional movement and similarity to normal controls using the volitional response index (VRI) and the modified Brain Motor Control Assessment. The mobile application is a custom-designed platform to support participant response and a kinematic task to optimise the settings for each participant. The application optimises stimulation settings by evaluating the parameter space using movement data collected from the tablet application and accelerometers. A subgroup of participants with cardiovascular dysautonomia are included for optimisation of blood pressure stabilisation. Indirect effects of stimulation on cardiovascular function, pain, sexual function, bowel/bladder, QOL and psychiatric measures are analysed to assess generalisability of this targeted intervention.Ethics and disseminationThis study has been approved after full review by the Minneapolis Medical Research Foundation Institutional Review Board and by the Minneapolis VA Health Care System. This project has received Food and Drug Administration investigational device exemption approval. Trial results will be disseminated through peer-reviewed publications, conference presentations and seminars.Trial registration numberNCT03026816.
| S-EPMC9297213 | biostudies-literature
Project description:In individuals with severe spinal cord injury (SCI), the autonomic nervous system (ANS) is affected leading to cardiovascular deficits, which include significant blood pressure instability, with the prevalence of systemic hypotension and orthostatic intolerance resulting in an increased risk of stroke. Additionally, persons with SCI rostral to thoracic vertebral level 5 (T5), where sympathetic nervous system fibers exit the spinal cord and innervate the immune system, have clinically significant systemic inflammation and increased infection risk. Our recent studies show that lumbosacral spinal cord epidural stimulation (scES), applied at the lumbosacral level using targeted configurations that promote cardiovascular stability (CV-scES), can safely and effectively normalize blood pressure in persons with chronic SCI. Herein we present a case report in a female (age 27 years) with chronic clinically motor complete cervical SCI demonstrating that 97-sessions of CV-scES, which increased systemic blood pressure, improved orthostatic tolerance in association with increased cerebral blood flow velocity in the middle cerebral artery, also promoted positive immunological changes in whole-blood gene expression. Specifically, there was evidence of the down-regulation of inflammatory pathways and the up-regulation of adaptative immune pathways. The findings of this case report suggest that the autonomic effects of epidural stimulation, targeted to promote cardiovascular homeostasis, also improves immune system function, which has a significant benefit to long-term cardiovascular and immunologic health in individuals with long-standing SCI. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02307565.
| S-EPMC7593242 | biostudies-literature