Epidural Spinal Cord Stimulation Research Articles

Treatment Outcomes for Patients with Failed Back Surgery

Failed back surgery syndrome (FBSS) is a frequently encountered disease entity following lumbar spinal surgery. Although many plausible reasons have been investigated, the exact pathophysiology remains unknown. Various medications, reoperations, interventions such as spinal cord stimulation, epidural adhesiolysis or epidural injection, exercise therapy, and psychotherapy have been suggested treatment options. However, the evidence of the clinical outcome for each treatment has not been clearly determined. To evaluate the outcomes of each treatment modality and to present treatment guidelines for patients with FBSS. A systematic review of each treatment regimen in patients with FBSS. The available literature regarding each modality for the treatment of refractory back pain or radiating pain for FBSS was reviewed. The quality assessment and the level of evidence were analyzed using the "Methodology Checklist" of SIGN (Scottish Intercollegiate Guidelines Network). Data sources included relevant English language literature identified through searches of Pubmed, EMBASE, and Cochrane library from 1980 to Feb 2016. The primary outcome measure was pain relief of back pain or radiating pain for at least 3 months. Secondary outcome measures were improvement of the patient's functional status, health-related quality of life, return to work, and reduction of opioid use. Twenty-three articles were finally identified and reviewed. Based on our analysis, epidural adhesiolysis showed a short-term (6 to 24 months) effect (grade A) and spinal cord stimulation showed a mid-term (2 or 3 years) effect (grade B). Epidural injections showed a short-term (up to 2 years) effect (grade C). However, other treatments were recommended as grade D or inconclusive. The limitations of this systematic review included the rarity of relevant literature. Epidural adhesiolysis or spinal cord stimulation can be effective in order to control chronic back pain or leg pain due to FBSS, and its recommendation grades are A and B, respectively. Other treatments showed poor or inconclusive evidence.Key words: Failed back surgery syndrome, post spinal surgery syndrome, chronic low back pain, post lumbar surgery syndrome, epidural adhesiolysis, spinal cord stimulation, epidural injection, revision.

Epidural Stimulation of Rat Spinal Cord at Lumbosacral Segment Using a Surface Electrode: A Computer Simulation Study.

Clinical research indicates that the epidural spinal cord stimulation (ESCS) at lumbosacral segment has shown potential for promoting locomotor recovery in patients with incomplete spinal cord injury. However, the underlying neural mechanism needs to be determined by animal experiments. In order to refine experimental protocols, we used a finite element simulation to investigate the activation of nerve fibers in a rat spinal cord model. Our model is composed of a volume conductor model from L1 to S2 spinal segments and the McIntyre-Richard-Grill axon model, which is used to investigate the threshold of selected spinal fibers with different diameters at varied locations and predict the neural responses of any target fibers with bipolar electrode configuration. Mathematical modeling suggests that the electrode-fiber distance may play an important role in the recruitment of nerve fibers, whereas longer pulse width predicted greater activity of spinal root fibers and dorsal column fibers, as well as may exert an effective influence on the motor system by the ability to increase and even "steer" spatial selectivity with deeper penetration into the dorsal columns. The spikes were initiated at sites along the nerve fibers depending on which component was closest to the cathode among the longitudinal part of the fiber, its entrance into spinal cord, or strong bending at the entry. Our simulation results show good agreement with the previous findings from animal studies. It is concluded that the computational ESCS model is a valuable tool to obtain a better insight into the immediately evoked electrophysiological phenomena in animal models, and provides further guidelines for conducting animal experiments to enhance the exploration of basic neural mechanisms.

An ovine model of spinal cord injury

Objective: To develop a large animal model of spinal cord injury (SCI), for use in translational studies of spinal cord stimulation (SCS) in the treatment of spasticity. We seek to establish thresholds for the SCS parameters associated with reduction of post-SCI spasticity in the pelvic limbs, with implications for patients.Study Design: The weight-drop method was used to create a moderate SCI in adult sheep, leading to mild spasticity in the pelvic limbs. Electrodes for electromyography (EMG) and an epidural spinal cord stimulator were then implanted. Behavioral and electrophysiological data were taken during treadmill ambulation in six animals, and in one animal with and without SCS at 0.1, 0.3, 0.5, and 0.9 V.Setting: All surgical procedures were carried out at the University of Iowa. The gait measurements were made at Iowa State University.Material and Methods: Nine adult female sheep were used in these institutionally approved protocols. Six of them were trained in treadmill ambulation prior to SCI surgeries, and underwent gait analysis pre- and post-SCI. Stretch reflex and H-reflex measurements were also made in conscious animals.Results: Gait analysis revealed repeatable quantitative differences in 20% of the key kinematic parameters of the sheep, pre- and post-SCI. Hock joint angular velocity increased toward the normal pre-injury baseline in the animal with SCS at 0.9 V.Conclusion: The ovine model is workable as a large animal surrogate suitable for translational studies of novel SCS therapies aimed at relieving spasticity in patients with SCI.

Epidural spinal cord stimulation for recovery from spinal cord injury: its place in therapy

Epidural spinal cord stimulation for recovery from spinal cord injury: its place in therapy Line Jacques, Michael Safaee Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA Abstract: This paper is a review of some of the current research focused on using existing epidural spinal cord stimulation technologies in establishing the effectiveness in the recovery of independent standing, ambulation, or intentional movement of spinal cord injury patients. From a clinician’s perspective, the results have been intriguing, from a restorative perspective they are promising, and from a patient’s perspective they are hopeful. The outcomes, although still in the experimental phase, show some proof of theory and support further research. From a high volume university based clinician’s perspective, the resources needed to integrate this type of restorative care into a busy clinical practice are highly challenging without a well-structured and resource rich institutional restorative program. Patient selection is profoundly critical due to the extraordinary resources needed, and the level of motivation required to participate in such an intense and arduous rehabilitation process. Establishing an algorithmic approach to patient selection and treatment will be paramount to effectively utilize scarce resources and optimize outcomes. Further research is warranted, and the development of dedicated technological hardware and software for this therapeutic treatment versus using traditional spinal cord stimulation devices may yield more robust and efficacious outcomes. Keywords: independent standing, ambulation, intentional movement, recovery, rehabilitation, locomotion

Novel fractal planar electrode design for efficient neural stimulation.

Planar electrodes are used in epidural spinal cord stimulation and cortical stimulation. Stimulation efficiency of an electrode is characterized by its ability to activate a volume of neural tissue with lower voltage and power requirements. As current density tends to increase towards the sharp edges of an electrode, we hypothesize that electrode designs involving a greater amount of sharp edges will have higher variations of current density, and therefore increase stimulation efficiency, compared to electrodes with flat or rounded edges. This study uses three Koch snowflake fractal design iterations to compare each voltage and power requirements to those of the traditional square and circular electrode designs. Electrode geometries were constructed in COMSOL Multiphysics, each with an equal surface area. Voltages obtained from the finite element models were interpolated to determine the nodal voltages of 100 axons randomly positioned around the electrode. Threshold voltage and power for activating these model axons were simulated in NEURON. Current density variation was significantly higher on the surface of the 3rd iteration Koch snowflake electrode than the traditional square electrode. This novel electrode also activated a significantly greater number of axons with a lower threshold as compared to the traditional square electrode. The computational models used in this study demonstrated the feasibility of increasing stimulation efficiency through the design of novel planar electrodes with Koch snowflake fractal iterations. Future studies could explore and optimize efficiency when more fractal additions are taken, as well as exploiting other fractal shapes.

Activation of cannabinoid CB1 receptor contributes to suppression of spinal nociceptive transmission and inhibition of mechanical hypersensitivity by Aβ-fiber stimulation.

Activation of Aβ-fibers is an intrinsic feature of spinal cord stimulation (SCS) pain therapy. Cannabinoid receptor type 1 (CB1) is important to neuronal plasticity and pain modulation, but its role in SCS-induced pain inhibition remains unclear. In this study, we showed that CB1 receptors are expressed in both excitatory and inhibitory interneurons in substantia gelatinosa (SG). Patch-clamp recording of the evoked excitatory postsynaptic currents (eEPSCs) in mice after spinal nerve ligation (SNL) showed that electrical stimulation of Aβ-fibers (Aβ-ES) using clinical SCS-like parameters (50 Hz, 0.2 millisecond, 10 μA) induced prolonged depression of eEPSCs to C-fiber inputs in SG neurons. Pretreatment with CB1 receptor antagonist AM251 (2 μM) reduced the inhibition of C-eEPSCs by Aβ-ES in both excitatory and inhibitory SG neurons. We further determined the net effect of Aβ-ES on spinal nociceptive transmission in vivo by recording spinal local field potential in SNL rats. Epidural SCS (50 Hz, Aβ-plateau, 5 minutes) attenuated C-fiber-evoked local field potential. This effect of SCS was partially reduced by spinal topical application of AM251 (25 μg, 50 μL), but not CB2 receptor antagonist AM630 (100 μg). Finally, intrathecal pretreatment with AM251 (50 μg, 15 μL) in SNL rats blocked the inhibition of behavioral mechanical hypersensitivity by SCS (50 Hz, 0.2 millisecond; 80% of motor threshold, 60 minutes). Our findings suggest that activation of spinal CB1 receptors may contribute to synaptic depression to high-threshold afferent inputs in SG neurons after Aβ-ES and may be involved in SCS-induced inhibition of spinal nociceptive transmission after nerve injury.

Neuromodulation of the neural circuits controlling the lower urinary tract

The inability to control timely bladder emptying is one of the most serious challenges among the many functional deficits that occur after a spinal cord injury. We previously 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 and can be used to enable voiding in spinal rats. In the present study, we examined the neuromodulation of lower urinary tract function associated with acute epidural spinal cord stimulation, locomotion, and peripheral nerve stimulation in adult rats. Herein we demonstrate that electrically evoked potentials in the hindlimb muscles and external urethral sphincter are modulated uniquely when the rat is stepping bipedally and not voiding, immediately pre-voiding, or when voiding. We also show that spinal cord stimulation can effectively neuromodulate the lower urinary tract via frequency-dependent stimulation patterns and that neural peripheral nerve stimulation can activate the external urethral sphincter both directly and via relays in the spinal cord. The data demonstrate that the sensorimotor networks controlling bladder and locomotion are highly integrated neurophysiologically and behaviorally and demonstrate how these two functions are modulated by sensory input from the tibial and pudental nerves. A more detailed understanding of the high level of interaction between these networks could lead to the integration of multiple neurophysiological strategies to improve bladder function. These data suggest that the development of strategies to improve bladder function should simultaneously engage these highly integrated networks in an activity-dependent manner.

Epidural Spinal Cord Stimulation for the Restoration of Balance and Gait Following Spinal Cord Injury.

Epidural Spinal Cord Stimulation for the Restoration of Balance and Gait Following Spinal Cord Injury.

Unique Spatiotemporal Neuromodulation of the Lumbosacral Circuitry Shapes Locomotor Success after Spinal Cord Injury.

Spinal cord epidural stimulation has resulted in the initiation of voluntary leg movements and improvement in postural, bladder, and sexual function. However, one of the limitations in reaching the full potential of epidural stimulation for therapeutic purposes in humans has been the identification of optimal stimulation configurations that can neuromodulate the spinal cord for stepping. In the present work, we investigated the mechanisms underlying the specificity of interaction between the rostral and caudal spinal cord circuitries in enabling locomotion in spinal rats (n = 10) by epidural spinal cord stimulation. By using unique spatiotemporal epidural stimulation parameters of the lumbar and sacral spinal cords, a robust stepping pattern in spinal rats was observed with only six training sessions and as early as 3 weeks post-injury. Electrophysiological evidence reveals that in addition to frequency of stimulation pulses at the stimulation sites, the relative timing between stimulation pulses applied at the lumbar (L2) and sacral (S1) segments of the spinal cord heavily impacted stepping performance. Best stepping was established at a higher stimulation frequency (40 Hz vs. 5, 10, 15, and 20Hz) and at specific relative time-intervals between the stimulation pulses (L2 pulse applied at 18-25 msec after the onset of the S1 pulse; S1 pulse applied 0-7 msec after the L2 pulse). Our data suggest that controlling pulse-to-pulse timing at multiple stimulation sources provides a novel strategy to optimize spinal stepping by fine-tuning the physiological state of the locomotor networks. These findings hold direct relevance to the clinician who will incorporate electrical stimulation strategies for optimizing control of locomotion after complete paralysis.

Spinal Cord Stimulation and Augmentative Control Strategies for Leg Movement after Spinal Paralysis in Humans.

Severe spinal cord injury is a devastating condition, tearing apart long white matter tracts and causing paralysis and disability of body functions below the lesion. But caudal to most injuries, the majority of neurons forming the distributed propriospinal system, the localized gray matter spinal interneuronal circuitry, and spinal motoneuron populations are spared. Epidural spinal cord stimulation can gain access to this neural circuitry. This review focuses on the capability of the human lumbar spinal cord to generate stereotyped motor output underlying standing and stepping, as well as full weight-bearing standing and rhythmic muscle activation during assisted treadmill stepping in paralyzed individuals in response to spinal cord stimulation. By enhancing the excitability state of the spinal circuitry, the stimulation can have an enabling effect upon otherwise "silent" translesional volitional motor control. Strategies for achieving functional movement in patients with severe injuries based on minimal translesional intentional control, task-specific proprioceptive feedback, and next-generation spinal cord stimulation systems will be reviewed. The role of spinal cord stimulation can go well beyond the immediate generation of motor output. With recently developed training paradigms, it can become a major rehabilitation approach in spinal cord injury for augmenting and steering trans- and sublesional plasticity for lasting therapeutic benefits.

A Comparison of the Effects of Burst and Tonic Spinal Cord Stimulation on Hyperalgesia and Physical Activity in an Animal Model of Neuropathic Pain.

Parameters of spinal cord stimulation (SCS) play a role in its effectiveness and may impact SCS mechanisms and outcomes. For example, SCS applied in a bursting pattern may result in better pain relief than that for tonic SCS for neuropathic pain. We tested the effectiveness of different SCS pulse frequencies given at 2 different burst frequencies in an animal model of neuropathic pain. After Sprague-Dawley rats were anesthetized, neuropathic pain was induced using the spared nerve injury model, and an epidural SCS lead was implanted in the upper lumber spinal cord. One of the 8 different SCS parameters was delivered daily for 4 days at 90% motor threshold 2 weeks after nerve injury. Four burst patterns were administered at 4- or 40-Hz frequency with a train of 4 pulses at frequencies of 60, 500, and 1000 Hz. Sham and tonic patterns at 16, 60, and 160 Hz were chosen as controls. Paw withdrawal threshold was assessed before the surgery and 15 minutes before, during, and after SCS daily for 4 days. Physical activity (distance, crossing, rearing, and grooming) was assessed before surgery, before SCS on day 1, and after SCS on day 4. Animals showed a decrease in paw withdrawal threshold and physical activity levels 2 weeks after nerve injury. During stimulation, burst SCS with pulse frequencies of 60, 500, or 1000 Hz were more effective for improving paw withdrawal threshold than sham and tonic SCS at 16 Hz. Burst SCS with higher pulse frequencies (500 and 1000 Hz) than 60-Hz SCS and burst SCS with higher pulse frequencies (1000 Hz) than 160-Hz SCS were more effective. In addition, tonic SCS at 160 Hz and burst SCS with higher pulse frequencies (500 and 1000 Hz) significantly increased the distance traveled. Burst SCS at 4 Hz with pulse frequency of 1000 Hz also increased the number of crossings when compared with sham control and tonic SCS at 16 Hz. The current study shows that a variety of SCS pulse frequencies applied with a burst frequency result in greater improvement in hyperalgesia and activity levels than tonic SCS in a neuropathic pain model during stimulation.

Targeting Lumbar Spinal Neural Circuitry by Epidural Stimulation to Restore Motor Function After Spinal Cord Injury.

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.Electronic supplementary materialThe online version of this article (doi:10.1007/s13311-016-0421-y) contains supplementary material, which is available to authorized users.

Spinal cord stimulation in the treatment of chronic pain syndromes

The study objective was to estimate the efficacy of chronic epidural spinal cord stimulation in the treatment of patients with neuropathic pain syndrome. A system for chronic spinal cord stimulation (St. Jude) was implanted to 75 patients with neuropathic pain syndrome. Fifty three (70.7%) patients were diagnosed with failed back surgery syndrome (FBSS); 9 (12.0%) patients had complex regional pain syndrome type II; 4 (5.3%) patients had diabetic polyneuropathy of the lower limbs; 3 (4.0%) patients had idiopathic pelvic-perineal pain; 2 (2.7%) patients had spinal stroke pain; 2 (2.7%) patients had postherpetic intercostal neuralgia; 1 (1.3%) patient had stump pain; 1 (1.3%) patient had spinal cord injury pain. The treatment efficacy was evaluated using the visual analog scale (VAS) and DN4 questionnaire. The follow-up period ranged from 6 to 18 months. 136 patients underwent test stimulation at the Center in 2014. A significant reduction in pain was observed in 75 (55.1%) patients. These patients underwent the second stage of surgery that included implantation of permanent electrodes and a generator. The mean VAS score was 6.5 (maximum: 10; minimum: 5) before surgery, 3.2 at discharge, and 3.1 after 3 and 6 months. The VAS score amounted to 3.6 after 12 months. Complications in the form of pain at the generator implantation site and the need for removal of the system occurred in 2 patients (2.6%), electrode migration was observed in 4 (5.3%) cases. Chronic epidural spinal cord stimulation is an effective and safe technique for the treatment of drug-resistant chronic neurogenic pain syndromes.

SENSORIMOTOR REGULATION OF MOVEMENTS: NOVEL STRATEGIES FOR THE RECOVERY OF MOBILITY.

A series of observations have provided important insight into properties of the spinal as well as supraspinal circuitries that control posture and movement. We have demonstrated that spinal rats can regain full weight-bearing standing and stepping over a range of speeds and directions with the aid of electrically enabling motor control (eEmc), pharmacological modulation (fEmc), and training. Also, we have reported that voluntary control movements of individual joints and limbs can be regained after complete paralysis in humans. However, the ability to generate significant levels of voluntary weight-bearing stepping with or without epidural spinal cord stimulation remains limited. Herein we introduce a novel method of painless transcutaneous electrical enabling motor control (pcEmc) and sensory enabling motor control (sEmc) strategy to neuromodulate the physiological state of the spinal cord. We have found that a combination of a novel non-invasive transcutaneous spinal cord stimulation and sensory-motor stimulation of leg mechanoreceptors can modulate the spinal locomotor circuitry to that enables voluntary rhuthmic locomotor movements.

Epidural Spinal Cord Stimulation for Neuropathic Pain: Algology Unit in Bagcilar Training and Research Hospital Data Collection and Analysis

Spinal cord stimulation (SCS) is a technique used worldwide to treat several types of chronic neuropathic pain refractory to any conservative treatment.

Regulation of Peripheral Nerve Stimulation Technology.

The number of peripheral nerve stimulation (PNS) indications, targets, and devices is expanding, yet the development of the technology has been slow because many devices used for PNS do not have formal regulatory approval. Manufacturers have not sought Food and Drug Administration (FDA) approval for PNS devices because of a perceived lack of interest amongst practitioners and patients. Without FDA approval, companies cannot invest in marketing to educate the implanters and the patients about the benefits of PNS in the treatment of chronic pain. Violation of this has resulted in governmental investigation and prosecution. Most of the PNS devices currently used to treat chronic pain are FDA approved for epidural spinal cord stimulation. Many of the complications seen in PNS surgery can be attributed to the lack of purpose-built hardware with FDA approval. Despite the lack of regulatory approval, there are insurance companies that approve PNS procedures when deemed medically necessary. As the targets and indications for PNS continue to expand, there will be an even greater need for customized technological solutions. It is up to the medical device industry to invest in the design and marketing of PNS technology and seek out FDA approval. Market forces will continue to push PNS into the mainstream and physicians will increasingly have the choice to implant devices specifically designed and approved to treat chronic peripheral nerve pain.

Neuromodulation for Refractory Failed Back Surgery Syndrome Patients

doi: 10.17691/stm2015.7.3.13 Received February 23, 2015I.N. Morozov, Md, dSc, Senior Researcher, Advisory and Rehabilitation department;А.I. Ushakov, Neurosurgeon, department of NeurosurgeryPrivolzhsky Federal Research Medical Center, Ministry of Health of the Russian Federation, 18 Verkhne-Volzhskaya naberezhnaya St., Nizhny Novgorod, 603155, Russian FederationThe aim of the investigation was to assess the capabilities of spinal cord stimulation, and compare it with conventional nonsurgical treatment in failed back syndrome.Materials and Methods. The study involved the patients with at least one anatomically successful lumber disc hernia excision, post-traumatic spinal deformity in their past history, the patients keeping suffering from neuropathic pain.Group 1 patients (n=45) in addition to traditional therapy underwent spinal cord stimulation. Group 2 control patients (n=35) were given medicines, therapeutic blocks, physiotherapy, and psychotherapy.Results. Epidural spinal cord stimulation in chronic pain syndrome treatment enables to improve significantly the patients, condition: it lowers pain level, increases the functionality and improves the quality of life.Conclusion. Being minimally invasive and highly safe, neuromodulation enables to achieve good treatment results in failed back syndrome.Key words: neuromodulation; spinal cord stimulation; SCS; failed back surgery syndrome; FBSS.For contacts: Morozov ivan Nicolaevich, e-mail: ivanmorozov@list.ru

Effects of Lumbosacral Spinal Cord Epidural Stimulation for Standing after Chronic Complete Paralysis in Humans.

Sensory and motor complete spinal cord injury (SCI) has been considered functionally complete resulting in permanent paralysis with no recovery of voluntary movement, standing or walking. Previous findings demonstrated that lumbosacral spinal cord epidural stimulation can activate the spinal neural networks in one individual with motor complete, but sensory incomplete SCI, who achieved full body weight-bearing standing with independent knee extension, minimal self-assistance for balance and minimal external assistance for facilitating hip extension. In this study, we showed that two clinically sensory and motor complete participants were able to stand over-ground bearing full body-weight without any external assistance, using their hands to assist balance. The two clinically motor complete, but sensory incomplete participants also used minimal external assistance for hip extension. Standing with the least amount of assistance was achieved with individual-specific stimulation parameters, which promoted overall continuous EMG patterns in the lower limbs’ muscles. Stimulation parameters optimized for one individual resulted in poor standing and additional need of external assistance for hip and knee extension in the other participants. During sitting, little or negligible EMG activity of lower limb muscles was induced by epidural stimulation, showing that the weight-bearing related sensory information was needed to generate sufficient EMG patterns to effectively support full weight-bearing standing. In general, electrode configurations with cathodes selected in the caudal region of the array at relatively higher frequencies (25–60 Hz) resulted in the more effective EMG patterns for standing. These results show that human spinal circuitry can generate motor patterns effective for standing in the absence of functional supraspinal connections; however the appropriate selection of stimulation parameters is critical.

Transcutaneous electrical spinal-cord stimulation in humans

Locomotor behavior is controlled by specific neural circuits called central pattern generators primarily located at the lumbosacral spinal cord. These locomotor-related neuronal circuits have a high level of automaticity; that is, they can produce a “stepping” movement pattern also seen on electromyography (EMG) in the absence of supraspinal and/or peripheral afferent inputs. These circuits can be modulated by epidural spinal-cord stimulation and/or pharmacological intervention. Such interventions have been used to neuromodulate the neuronal circuits in patients with motor-complete spinal-cord injury (SCI) to facilitate postural and locomotor adjustments and to regain voluntary motor control. Here, we describe a novel non-invasive stimulation strategy of painless transcutaneous electrical enabling motor control (pcEmc) to neuromodulate the physiological state of the spinal cord. The technique can facilitate a stepping performance in non-injured subjects with legs placed in a gravity-neutral position. The stepping movements were induced more effectively with multi-site than single-site spinal-cord stimulation. From these results, a multielectrode surface array technology was developed. Our preliminary data indicate that use of the multielectrode surface array can fine-tune the control of the locomotor behavior. As well, the pcEmc strategy combined with exoskeleton technology is effective for improving motor function in paralyzed patients with SCI. The potential impact of using pcEmc to neuromodulate the spinal circuitry has significant implications for furthering our understanding of the mechanisms controlling locomotion and for rehabilitating sensorimotor function even after severe SCI.

Periodic modulation of repetitively elicited monosynaptic reflexes of the human lumbosacral spinal cord.

In individuals with motor-complete spinal cord injury, epidural stimulation of the lumbosacral spinal cord at 2 Hz evokes unmodulated reflexes in the lower limbs, while stimulation at 22-60 Hz can generate rhythmic burstlike activity. Here we elaborated on an output pattern emerging at transitional stimulation frequencies with consecutively elicited reflexes alternating between large and small. We analyzed responses concomitantly elicited in thigh and leg muscle groups bilaterally by epidural stimulation in eight motor-complete spinal cord-injured individuals. Periodic amplitude modulation of at least 20 successive responses occurred in 31.4% of all available data sets with stimulation frequency set at 5-26 Hz, with highest prevalence at 16 Hz. It could be evoked in a single muscle group only but was more strongly expressed and consistent when occurring in pairs of antagonists or in the same muscle group bilaterally. Latencies and waveforms of the modulated reflexes corresponded to those of the unmodulated, monosynaptic responses to 2-Hz stimulation. We suggest that the cyclical changes of reflex excitability resulted from the interaction of facilitatory and inhibitory mechanisms emerging after specific delays and with distinct durations, including postactivation depression, recurrent inhibition and facilitation, as well as reafferent feedback activation. The emergence of large responses within the patterns at a rate of 5.5/s or 8/s may further suggest the entrainment of spinal mechanisms as involved in clonus. The study demonstrates that the human lumbosacral spinal cord can organize a simple form of rhythmicity through the repetitive activation of spinal reflex circuits.