Human Cervical Epidural Spinal Electrogram Topographically Maps Distinct Volitional Movements.

Little is known about the electrophysiologic activity of the intact human spinal cord during volitional movement. We analyzed epidural spinal recordings from a total of five human subjects of both sexes during a variety of upper extremity movements and found that these spinal epidural electrograms contain spectral information distinguishing periods of movement, rest, and sensation. Cervical epidural electrograms also contained spectral changes time-locked with movement. We found that these changes were primarily associated with increased power in the theta (4-8 Hz) band and feature increased theta phase to gamma amplitude coupling, and this increase in theta power can be used to topographically map distinct upper extremity movements onto the cervical spinal cord in accordance with established myotome maps of the upper extremity. Our findings have implications for the development of neurostimulation protocols and devices focused on motor rehabilitation for the upper extremity, and the approach presented here may facilitate spatiotemporal mapping of naturalistic movements.

Predictors of Skip Laminotomy for Placement of Paddle Leads for Spinal Cord Stimulation.

OBJECTIVES: Placement of a standard paddle lead for spinal cord stimulation (SCS) requires a laminotomy for positioning of the lead within the epidural space. During initial placement, an additional laminotomy or laminectomy, termed a "skip" laminotomy, may be necessary at a higher level to pass the lead to the appropriate midline position. Patient and radiographic factors that predict the need for a skip laminotomy have yet to be identified. MATERIALS AND METHODS: Participants who underwent SCS paddle placement at Albany Medical Center between 2016 and 2017 were identified. Operative reports were reviewed to identify the paddle type, level of initial laminotomy, target level, and skip laminotomy level. Preoperative thoracic magnetic resonance images (MRIs) were reviewed, and spinal canal diameter, interpedicular distance, and dorsal cerebral spinal fluid thickness were measured for each participant when available. RESULTS: A total of 106 participants underwent thoracic SCS placement. Of these, 97 had thoracic MRIs available for review. Thirty-eight participants required a skip laminotomy for placement of the paddle compared with 68 participants who did not. There was no significant difference in demographic features including age, sex, body mass index, and surgical history. Univariate analyses that suggested trends were selected for further analysis using binary logistic regression. Level of initial laminotomy (odds ratio [OR] = 1.51, p = 0.028), spinal canal diameter (OR = 0.71, p = 0.015), and dorsal cerebrospinal fluid thickness (OR = 0.61, p = 0.011) were correlated with skip laminotomy. Target level (OR = 1.27, p = 0.138) and time from trial (1.01, p = 0.117) suggested potential association. The multivariate regression was statistically significant, X2(10) = 28.02, p = 0.002. The model explained 38.3% of the variance (Nagelkerke R2) and predicted skip laminectomy correctly in 73.3% of cases. However, for the multivariate regression, only a decrease in spinal canal diameter (OR = 0.59, p = 0.041) was associated with a greater odds of skip laminotomy. CONCLUSIONS: This study aims to characterize the patient and radiographic factors that may predict the need to perform a skip laminotomy during the initial placement of SCS paddles. Here, we show that radiographic and anatomic variables, primarily spinal canal diameter, play an important role in predicting the need for a skip laminotomy. Furthermore, we suggest that target level for placement and level of initial laminotomy also may contribute. Further investigation of the predictive factors for performing a skip laminotomy would help optimize surgical planning and preoperative patient selection and counseling.

Fast inference of spinal neuromodulation for motor control using amortized neural networks.

Objective.Epidural electrical stimulation (EES) has emerged as an approach to restore motor function following spinal cord injury (SCI). However, identifying optimal EES parameters presents a significant challenge due to the complex and stochastic nature of muscle control and the combinatorial explosion of possible parameter configurations. Here, we describe a machine-learning approach that leverages modern deep neural networks to learn bidirectional mappings between the space of permissible EES parameters and target motor outputs.Approach.We collected data from four sheep implanted with two 24-contact EES electrode arrays on the lumbosacral spinal cord. Muscle activity was recorded from four bilateral hindlimb electromyography (EMG) sensors. We introduce a general learning framework to identify EES parameters capable of generating desired patterns of EMG activity. Specifically, we first amortize spinal sensorimotor computations in a forward neural network model that learns to predict motor outputs based on EES parameters. Then, we employ a second neural network as an inverse model, which reuses the amortized knowledge learned by the forward model to guide the selection of EES parameters.Main results.We found that neural networks can functionally approximate spinal sensorimotor computations by accurately predicting EMG outputs based on EES parameters. The generalization capability of the forward model critically benefited our inverse model. We successfully identified novel EES parameters, in under 20 min, capable of producing desired target EMG recruitment duringin vivotesting. Furthermore, we discovered potential functional redundancies within the spinal sensorimotor networks by identifying unique EES parameters that result in similar motor outcomes. Together, these results suggest that our framework is well-suited to probe spinal circuitry and control muscle recruitment in a completely data-driven manner.Significance.We successfully identify novel EES parameters within minutes, capable of producing desired EMG recruitment. Our approach is data-driven, subject-agnostic, automated, and orders of magnitude faster than manual approaches.

Differences in backward and forward treadmill locomotion in decerebrated cats.

Locomotion in different directions is vital for animal life and requires fine-adjusted neural activity of spinal networks. To compare the levels of recruitability of the locomotor circuitry responsible for forward and backward stepping, several electromyographic and kinematic characteristics of the two locomotor modes were analysed in decerebrated cats. Electrical epidural spinal cord stimulation was used to evoke forward and backward locomotion on a treadmill belt. The functional state of the bilateral spinal networks was tuned by symmetrical and asymmetrical epidural stimulation. A significant deficit in the backward but not forward stepping was observed when laterally shifted epidural stimulation was used but was not observed with central stimulation: only half of the cats were able to perform bilateral stepping, but all the cats performed forward stepping. This difference was in accordance with the features of stepping during central epidural stimulation. Both the recruitability and stability of the EMG signals as well as inter-limb coordination during backward stepping were significantly decreased compared with those during forward stepping. The possible underlying neural mechanisms of the obtained functional differences of backward and forward locomotion (spinal network organisation, commissural communication and supraspinal influence) are discussed.

Revision and Replacement of Spinal Cord Stimulator Paddle Leads.

OBJECTIVES: Paddle leads for spinal cord stimulation (SCS) offer more efficient energy delivery and advantages in some patients. However, there is concern for how safely SCS paddles can be replaced once previously implanted because of scar tissue and the relative vulnerability of the thoracic cord. In this study, we share our experience on SCS paddle replacement. MATERIALS AND METHODS: Participants who underwent SCS replacement at Albany Medical Center between 2011 and 2020 were identified. The medical records were reviewed for demographic data and information regarding initial complications, reason for removal or revision, subsequent complications of replacement surgery and its timing, and whether the implant was ultimately removed. Percutaneous lead replacement cases performed over the same period were used as a comparison group. RESULTS: A total of 1265 patients were identified to have had an SCS-related procedure based on billing codes. Of these, 73 involved replacement of epidural leads (51 paddles, 22 percutaneous). Most paddles (48/51) were replaced at the time of removal. A total of 30 of the 51 paddle replacements required additional lamina removal. Re-operations that occurred more than one year after initial implant were significantly more likely to require additional bone removal (p < 0.001). Paddle re-operations lasted in general 1.7 ± 0.2 hours and had 35 ± 5 mL of blood loss, whereas percutaneous operations lasted 1.3 ± 0.2 hours and had 12.5 ± 2 mL of blood loss. Despite the invasive nature of paddle replacement, there was no difference in complications (p = 0.23) compared with that in percutaneous leads. CONCLUSIONS: This study characterizes the safety profile of SCS paddle replacement surgeries. Here, we demonstrate that the replacement of paddle leads at the time of removal, with additional lamina removal if needed because of scar, is associated with low rates of complications. This validates the feasibility and low-risk profile of replacing paddle leads when clinically indicated for experienced surgeons with specialization in SCS.

Activity of Spinal Interneurons during Forward and Backward Locomotion.

Higher vertebrates are capable not only of forward but also backward and sideways locomotion. Also, single steps in different directions are generated for postural corrections. While the networks responsible for the control of forward walking (FW) have been studied in considerable detail, the networks controlling steps in other directions are mostly unknown. Here, to characterize the operation of the spinal locomotor network during FW and backward walking (BW), we recorded the activity of individual spinal interneurons from L4 to L6 during both FW and BW evoked by epidural stimulation (ES) of the spinal cord at L5-L6 in decerebrate cats of either sex. Three groups of neurons were revealed. Group 1 (45%) had a similar phase of modulation during both FW and BW. Group 2 (27%) changed the phase of modulation in the locomotor cycle depending on the direction of locomotion. Group 3 neurons were modulated during FW only (Group 3a, 21%) or during BW only (Group 3b, 7%). We suggest that Group 1 neurons belong to the network generating the vertical component of steps (the limb elevation and lowering) because it should operate similarly during locomotion in any direction, while Groups 2 and 3 neurons belong to the networks controlling the direction of stepping. Results of this study provide new insights into the organization of the spinal locomotor circuits, advance our understanding of ES therapeutic effects, and can potentially be used for the development of novel strategies for recuperation of impaired balance control, which requires the generation of corrective steps in different directions.SIGNIFICANCE STATEMENT Animals and humans can perform locomotion in different directions in relation to the body axis (forward, backward, sideways). While the networks that control forward walking have been studied in considerable detail, the networks controlling steps in other directions are unknown. Here, by recording the activity of the same spinal neurons during forward and backward walking, we revealed three groups of neurons forming, respectively, the network operating similarly during stepping in different directions, the network changing its operation with a change in the direction of stepping, and the network operating only during locomotion in a specific direction. These networks presumably control different aspects of the step. The obtained results provide new insights into the organization of the spinal locomotor networks.

New Therapy for Spinal Cord Injury: Autologous Genetically-Enriched Leucoconcentrate Integrated with Epidural Electrical Stimulation.

The contemporary strategy for spinal cord injury (SCI) therapy aims to combine multiple approaches to control pathogenic mechanisms of neurodegeneration and stimulate neuroregeneration. In this study, a novel regenerative approach using an autologous leucoconcentrate enriched with transgenes encoding vascular endothelial growth factor (VEGF), glial cell line-derived neurotrophic factor (GDNF), and neural cell adhesion molecule (NCAM) combined with supra- and sub-lesional epidural electrical stimulation (EES) was tested on mini-pigs similar in morpho-physiological scale to humans. The complex analysis of the spinal cord recovery after a moderate contusion injury in treated mini-pigs compared to control animals revealed: better performance in behavioural and joint kinematics, restoration of electromyography characteristics, and improvement in selected immunohistology features related to cell survivability, synaptic protein expression, and glial reorganization above and below the injury. These results for the first time demonstrate the positive effect of intravenous infusion of autologous genetically-enriched leucoconcentrate producing recombinant molecules stimulating neuroregeneration combined with neuromodulation by translesional multisite EES on the restoration of the post-traumatic spinal cord in mini-pigs and suggest the high translational potential of this novel regenerative therapy for SCI patients.

The plasticity of nerve fibers: the prolonged effects of polarization of afferent fibers.

The review surveys various aspects of the plasticity of nerve fibers, in particular the prolonged increase in their excitability evoked by polarization, focusing on a long-lasting increase in the excitability of myelinated afferent fibers traversing the dorsal columns of the spinal cord. We review the evidence that increased axonal excitability 1) follows epidurally applied direct current (DC) as well as relatively short (5 or 10 ms) current pulses and synaptically evoked intrinsic field potentials; 2) critically depends on the polarization of branching regions of afferent fibers at the sites where they bifurcate and give off axon collaterals entering the spinal gray matter in conjunction with actions of extrasynaptic GABAA membrane receptors; and 3) shares the feature of being activity-independent with the short-lasting effects of polarization of peripheral nerve fibers. A comparison between the polarization evoked sustained increase in the excitability of dorsal column fibers and spinal motoneurons (plateau potentials) indicates the possibility that they are mediated by partly similar membrane channels (including noninactivating type L Cav++ 1.3 but not Na+ channels) and partly different mechanisms. We finally consider under which conditions transspinally applied DC (tsDCS) might reproduce the effects of epidural polarization on dorsal column fibers and the possible advantages of increased excitability of afferent fibers for the rehabilitation of motor and sensory functions after spinal cord injuries.NEW & NOTEWORTHY This review supplements previous reviews of properties of nerve fibers by surveying recent experimental evidence for their long-term plasticity. It also extends recent descriptions of spinal effects of DC by reviewing effects of polarization of afferent nerve fibers within the dorsal columns, the mechanisms most likely underlying the long-lasting increase in their excitability and possible clinical implications.

Complications of epidural spinal stimulation: lessons from the past and alternatives for the future.

STUDY DESIGN: Systematic review. OBJECTIVES: Over the past decade, an increasing number of studies have demonstrated that epidural spinal cord stimulation (SCS) can successfully assist with neurorehabilitation following spinal cord injury (SCI). This approach is quickly garnering the attention of clinicians. Therefore, the potential benefits of individuals undergoing epidural SCS therapy to regain sensorimotor and autonomic control, must be considered along with the lessons learned from other studies on the risks associated with implantable systems. METHODS: Systematic analysis of literature, as well as preclinical and clinical reports. RESULTS: The use of SCS for neuropathic pain management has revealed that epidural electrodes can lose their therapeutic effects over time and lead to complications, such as electrode migration, infection, foreign body reactions, and even SCI. Several authors have also described the formation of a mass composed of glia, collagen, and fibrosis around epidural electrodes. Clinically, this mass can cause myelopathy and spinal compression, and it is only treatable by surgically removing both the electrode and scar tissue. CONCLUSIONS: In order to reduce the risk of encapsulation, many innovative efforts focus on technological improvements of electrode biocompatibility; however, they require time and resources to develop and confirm safety and efficiency. Alternatively, some studies have demonstrated similar outcomes of non-invasive, transcutaneous SCS following SCI to those seen with epidural SCS, without the complications associated with implanted electrodes. Thus, transcutaneous SCS can be proposed as a promising candidate for a safer and more accessible SCS modality for some individuals with SCI.

Comparison of Epidural Pressure Decrease Pattern According to Different Lumbar Epidural Approaches.

BACKGROUND: During lumbar epidural injection (LEI) using a midline approach, we might encounter failure of identifying the epidural space owing to an equivocal or absent loss of resistance (LOR) sensation. The reason for such absence of LOR sensation has been suggested as paucity of midline ligamentum flavum, paravertebral muscle, and cyst in the interspinous ligament of the lumbar spine. Despite its low specificity, LOR is the most commonly used method to identify the epidural space. OBJECTIVES: The purpose of this study was to analyze lumbar epidural pressure decrease patterns and identify factors contributing to this pressure decrease. STUDY DESIGN: Prospective randomized trial. SETTING: An interventional pain management practice in South Korea. METHODS: This prospective study included 104 patients receiving LEI due to lumbar radiculopathy. A midline or paramedian approach of LEI was determined with randomization. Among various factors, gender, age, body mass index (BMI), and diagnosis were analyzed using a subgroup that included 60 cases of only a paramedian approach. RESULTS: Grades I, II (abrupt decrease), and III (gradual decrease) were found as patterns of epidural pressure decrease. Abrupt pressure decrease was more frequently observed in the paramedian group (P < 0.001). Age, gender, BMI, and diagnosis did not show any significant difference in frequencies between abrupt and gradual pressure decrease. LIMITATIONS: We could not match LOR sensation with epidural pressure decrease shown in the monitor. CONCLUSIONS: This study demonstrates that abrupt pressure decrease occurs more frequently with the paramedian approach. However, age, gender, BMI, or diagnosis did not affect the incidence of epidural pressure decrease. KEY WORDS: Epidural, paramedian, midline, pressure decrease.

Epidural recordings in cochlear implant users.

OBJECTIVE: In the long term it is desirable for CI users to control their device via brain signals. A possible strategy is the use of auditory evoked potentials (AEPs). Several studies have shown the suitability of auditory paradigms for such an approach. However, these investigations are based on non-invasive recordings. When thinking about everyday life applications, it would be more convenient to use implanted electrodes for signal acquisition. Ideally, the electrodes would be directly integrated into the CI. Further it is to be expected that invasively recorded signals have higher signal quality and are less affected by artifacts. APPROACH: In this project we investigated the feasibility of implanting epidural electrodes temporarily during CI surgery and the possibility to record AEPs in the course of several days after implantation. Intraoperatively, auditory brainstem responses were recorded, whereas various kinds of AEPs were recorded postoperatively. After a few days the epidural electrodes were removed. MAIN RESULTS: Data sets of ten subjects were obtained. Invasively recorded potentials were compared subjectively and objectively to clinical standard recordings using surface electrodes. Especially the cortical evoked response audiometry depicted clearer N1 waves for the epidural electrodes which were also visible at lower stimulation intensities compared to scalp electrodes. Furthermore the signal was less disturbed by artifacts. The objective quality measure (based on data sets of six patients) showed a significant better signal quality for the epidural compared to the scalp recordings. SIGNIFICANCE: Altogether the approach revealed to be feasible and well tolerated by the patients. The epidural recordings showed a clearly better signal quality than the scalp recordings with AEPs being clearer recognizable. The results of the present study suggest that including epidural recording electrodes in future CI systems will improve the everyday life applicability of auditory closed loop systems for CI subjects.

Emergence of Epidural Electrical Stimulation to Facilitate Sensorimotor Network Functionality After Spinal Cord Injury.

BACKGROUND: Traumatic spinal cord injury (SCI) disrupts signaling pathways between the brain and spinal networks below the level of injury. In cases of severe SCI, permanent loss of sensorimotor and autonomic function can occur. The standard of care for severe SCI uses compensation strategies to maximize independence during activities of daily living while living with chronic SCI-related dysfunctions. Over the past several years, the research field of spinal neuromodulation has generated promising results that hold potential to enable recovery of functions via epidural electrical stimulation (EES). METHODS: This review provides a historical account of the translational research efforts that led to the emergence of EES of the spinal cord to enable intentional control of motor functions that were lost after SCI. We also highlight the major limitations associated with EES after SCI and propose future directions of spinal neuromodulation research. RESULTS: Multiple, independent studies have demonstrated return of motor function via EES in individuals with chronic SCI. These enabled motor functions include intentional, controlled movement of previously paralyzed extremities, independent standing and stepping, and increased grip strength. In addition, improvements in cardiovascular health, respiratory function, body composition, and urologic function have been reported. CONCLUSIONS: EES holds promise to enable functions thought to be permanently lost due to SCI. However, EES is currently restricted to scientific investigation in humans with SCI and requires further validation of factors such as safety and efficacy before clinical translation.

Slow sinusoidal tilt movements demonstrate the contribution to orthostatic tolerance of cerebrospinal fluid movement to and from the spinal dural space.

Standing up elicits a host of cardiovascular changes which all affect the cerebral circulation. Lowered mean arterial blood pressure (ABP) at brain level, change in the cerebral venous outflow path, lowered end-tidal PCO2 (PET CO2 ), and intracranial pressure (ICP) modify cerebral blood flow (CBF). The question we undertook to answer is whether gravity-induced blood pressure (BP) changes are compensated in CBF with the same dynamics as are spontaneous or induced ABP changes in a stable position. Twenty-two healthy subjects (18/4 m/f, 40 ± 8 years) were subjected to 30° and 70° head-up tilt (HUT) and sinusoidal tilts (SinTilt, 0°â†¨60° around 30° at 2.5-10 tilts/min). Additionally, at those three tilt levels, they performed paced breathing at 6-15 breaths/min to induce larger than spontaneous cardiovascular oscillations. We measured continuous finger BP and cerebral blood flow velocity (CBFv) in the middle cerebral artery by transcranial Doppler to compute transfer functions (TFs) from ABP- to CBFv oscillations. SinTilt induces the largest ABP oscillations at brain level with CBFv gains strikingly lower than for paced breathing or spontaneous variations. This would imply better autoregulation for dynamic gravitational changes. We demonstrate in a mathematical model that this difference is explained by ICP changes due to movement of cerebrospinal fluid (CSF) into and out of the spinal dural sack. Dynamic cerebrovascular autoregulation seems insensitive to how BP oscillations originate if the effect of ICP is factored in. CSF-movement in-and-out of the spinal dural space contributes importantly to orthostatic tolerance by its effect on cerebral perfusion pressure.

Decoding neural activity to predict rat locomotion using intracortical and epidural arrays.

OBJECTIVE: Recovery of voluntary gait after spinal cord injury (SCI) requires the restoration of effective motor cortical commands, either by means of a mechanical connection to the limbs, or by restored functional connections to muscles. The latter approach might use functional electrical stimulation (FES), driven by cortical activity, to restore voluntary movements. Moreover, there is evidence that this peripheral stimulation, synchronized with patients' voluntary effort, can strengthen descending projections and recovery. As a step towards establishing such a cortically-controlled FES system for restoring function after SCI, we evaluate here the type and quantity of neural information needed to drive such a brain machine interface (BMI) in rats. We compared the accuracy of the predictions of hindlimb electromyograms (EMG) and kinematics using neural data from an intracortical array and a less-invasive epidural array. APPROACH: Seven rats were trained to walk on a treadmill with a stable pattern. One group of rats (n = 4) was implanted with intracortical arrays spanning the hindlimb sensorimotor cortex and EMG electrodes in the contralateral hindlimb. Another group (n = 3) was implanted with epidural arrays implanted on the dura overlying hindlimb sensorimotor cortex. EMG, kinematics and neural data were simultaneously recorded during locomotion. EMGs and kinematics were decoded using linear and nonlinear methods from multiunit activity and field potentials. MAIN RESULTS: Predictions of both kinematics and EMGs were effective when using either multiunit spiking or local field potentials (LFPs) recorded from intracortical arrays. Surprisingly, the signals from epidural arrays were essentially uninformative. Results from somatosensory evoked potentials (SSEPs) confirmed that these arrays recorded neural activity, corroborating our finding that this type of array is unlikely to provide useful information to guide an FES-BMI for rat walking. SIGNIFICANCE: We believe that the accuracy of our decoders in predicting EMGs from multiunit spiking activity is sufficient to drive an FES-BMI. Our future goal is to use this rat model to evaluate the potential for cortically-controlled FES to be used to restore locomotion after SCI, as well as its further potential as a rehabilitative technology for improving general motor function.

Transmission electron microscopy and histological analysis of the peridural membrane.

INTRODUCTION: While first described in 1904, the characterisation of the peridural membrane, which is frequently encountered, yet usually unnoticed, during lumbar decompression surgery, remains inconclusive. This relatively little known membrane is continuous with the posterior longitudinal ligament and lines the epidural space. In this study, we are comparing the membrane and ligamentum flavum from patients to analyse the variations of the histological and ultrastructural compositions. MATERIALS AND METHODS: We took samples of the membrane and ligamentum flavum from five separate patients who were undergoing lumbar spine decompression surgery for herniated discs which were then analysed with transmission electron microscopy and stained with H&E (morphology), trichrome (collagen content), and Verhoeff-Van Gieson (elastin content). RESULTS: Upon analysis of the peridural membrane, we observed tightly packed collagen fibres, interspaced with elastin fibres and very few fibroblasts. While the ligamentum flavum showed a significantly higher elastin to collagen ratio and looser arrangement of collagen fibres with a larger extracellular matrix. The peridural membrane was similar in appearance and constituent parts to the dura mater. CONCLUSION: The peridural membrane is a distinctive and important membrane in the spinal canal, and given its high collagen to elastin ratio and it tightly packed nature, we conclude that it forms a protective layer around the spinal cord which may help in minimising the compressive nature of intervertebral disc herniation.

In Vivo Impedance Characterization of Cortical Recording Electrodes Shows Dependence on Electrode Location and Size.

OBJECTIVE: Neural prostheses are improving the quality of life for those suffering from neurological impairments. Electrocorticography electrodes located in subdural, epidural, and intravascular positions show promise as long-term neural prostheses. However, chronic implantation affects the electrochemical environments of these arrays. METHODS: In the present work, the effect of electrode location on the electrochemical properties of the interface was compared. The impedances of the electrode arrays were measured using electrochemical impedance spectroscopy in vitro in saline and in vivo four-week postimplantation. RESULTS: There was not a significant effect of electrode location (subdural, intravascular, or epidural) on the impedance magnitude, and the effect of the electrode size on the impedance magnitude was frequency dependent. There was a frequency-dependent statistically significant effect of electrode location and electrode size on the phase angles of the three arrays. The subdural and epidural arrays showed phase shifts closer to -90° indicating the capacitive nature of the interface in these locations. The impact of placing electrodes within a blood vessel and adjacent to the blood vessel wall was most obvious when looking at the phase responses at frequencies below 10 kHz. CONCLUSION: Our results show that intravascular electrodes, like those in subdural and epidural positions, show electrical properties that are suitable for recording. These results provide support for the use of intravascular arrays in clinically relevant neural prostheses and diagnostic devices. SIGNIFICANCE: Comparison of electrochemical impedance of the epidural, intravascular, and subdural electrode array showed that all three locations are possible placement options, since impedances are in comparable ranges.

Transforaminal Epiduroscopic Basivertebral Nerve Laser Ablation for Chronic Low Back Pain Associated with Modic Changes: A Preliminary Open-Label Study.

Background: Chronic low back pain (CLBP) arising from degenerative disc disease continues to be a challenging clinical and diagnostic problem whether treated with nonsurgical, pain intervention, or motion-preserving stabilization and arthrodesis. Methods: Fourteen patients with CLBP, greater than 6 months, unresponsive to at least 4 months of conservative care were enrolled. All patients were treated successfully following screening using MRI findings of Modic type I or II changes and positive confirmatory provocative discography to determine the affected levels. All patients underwent ablation of the basivertebral nerve (BVN) using 1414 nm Nd:YAG laser-assisted energy guided in a transforaminal epiduroscopic approach. Macnab's criteria and visual analog scale (VAS) score were collected retrospectively at each follow-up interval. Results: The mean age was 46 ± 9.95 years. The mean symptoms duration was 21.21 ± 21.87 months. The mean follow-up was 15.3 ± 2.67 months. The preoperative VAS score of 7.79 ± 0.97 changed to 1.92 ± 1.38, postoperatively (P < 0.01). As per Macnab's criteria, seven patients (50%) had excellent, six patients (42.85%) had good, and one patient (7.14%) had fair outcomes. Conclusion: The transforaminal epiduroscopic basivertebral nerve laser ablation (TEBLA) appears to be a promising option in carefully selected patients with CLBP associated with the Modic changes.

Evidence of axon connectivity across a spinal cord transection in rats treated with epidural stimulation and motor training combined with olfactory ensheathing cell transplantation.

Olfactory ensheathing cells (OECs) are unique glia that support axon outgrowth in the olfactory system, and when used as cellular therapy after spinal cord injury, improve recovery and axon regeneration. Here we assessed the effects of combining OEC transplantation with another promising therapy, epidural electrical stimulation during a rehabilitative motor task. Sprague-Dawley rats received a mid-thoracic transection and transplantation of OECs or fibroblasts (FBs) followed by lumbar stimulation while climbing an inclined grid. We injected pseudorabies virus (PRV) into hindlimb muscles 7 months post-injury to assess connectivity across the transection. Analyses showed that the number of serotonergic (5-HT) axons that crossed the rostral scar border and the area of neurofilament-positive axons in the injury site were both greater in OEC- than FB-treated rats. We detected PRV-labeled cells rostral to the transection and remarkable evidence of 5-HT and PRV axons crossing the injury site in 1 OEC- and 1 FB-treated rat. The axons that crossed suggested either axon regeneration (OEC) or small areas of probable tissue sparing (FB). Most PRV-labeled thoracic neurons were detected in laminae VII or X, and ~25% expressed Chx10, a marker for V2a interneurons. These findings suggest potential regeneration or sparing of circuits that connect thoracic interneurons to lumbar somatic motor neurons. Despite evidence of axonal connectivity, no behavioral changes were detected in this small-scale study. Together these data suggest that when supplemented with epidural stimulation and climbing, OEC transplantation can increase axonal growth across the injury site and may promote recovery of propriospinal circuitry.

Distribution of Spinal Neuronal Networks Controlling Forward and Backward Locomotion.

Higher vertebrates, including humans, are capable not only of forward (FW) locomotion but also of walking in other directions relative to the body axis [backward (BW), sideways, etc.]. Although the neural mechanisms responsible for controlling FW locomotion have been studied in considerable detail, the mechanisms controlling steps in other directions are mostly unknown. The aim of the present study was to investigate the distribution of spinal neuronal networks controlling FW and BW locomotion. First, we applied electrical epidural stimulation (ES) to different segments of the spinal cord from L2 to S2 to reveal zones triggering FW and BW locomotion in decerebrate cats of either sex. Second, to determine the location of spinal neurons activated during FW and BW locomotion, we used c-Fos immunostaining. We found that the neuronal networks responsible for FW locomotion were distributed broadly in the lumbosacral spinal cord and could be activated by ES of any segment from L3 to S2. By contrast, networks generating BW locomotion were activated by ES of a limited zone from the caudal part of L5 to the caudal part of L7. In the intermediate part of the gray matter within this zone, a significantly higher number of c-Fos-positive interneurons was revealed in BW-stepping cats compared with FW-stepping cats. We suggest that this region of the spinal cord contains the network that determines the BW direction of locomotion.SIGNIFICANCE STATEMENT Sequential and single steps in various directions relative to the body axis [forward (FW), backward (BW), sideways, etc.] are used during locomotion and to correct for perturbations, respectively. The mechanisms controlling step direction are unknown. In the present study, for the first time we compared the distributions of spinal neuronal networks controlling FW and BW locomotion. Using a marker to visualize active neurons, we demonstrated that in the intermediate part of the gray matter within L6 and L7 spinal segments, significantly more neurons were activated during BW locomotion than during FW locomotion. We suggest that the network determining the BW direction of stepping is located in this area.

Femoral vascular conductance and peroneal muscle sympathetic nerve activity responses to acute epidural spinal cord stimulation in humans.

NEW FINDINGS: What is the central question of this research? Does acute spinal cord stimulation increase vascular conductance and decrease muscle sympathetic nerve activity in the lower limbs of humans? What is the main finding and its importance? Acute spinal cord stimulation led to a rapid rise in femoral vascular conductance, and peroneal muscle sympathetic nerve activity demonstrated a delayed reduction that was not associated with the initial increase in femoral vascular conductance. These findings suggest that neural mechanisms in addition to attenuated muscle sympathetic nerve activity might be involved in the initial increase in femoral vascular conductance during acute spinal cord stimulation. ABSTRACT: Clinical cases have indicated an increase in peripheral blood flow after continuous epidural spinal cord stimulation (SCS) and that reduced muscle sympathetic nerve activity (MSNA) might be a potential mechanism. However, no studies in humans have directly examined the effects of acute SCS (<60 min) on vascular conductance and MSNA. In study 1, we tested the hypothesis that acute SCS (<60 min) of the thoracic spine would lead to increased common femoral vascular conductance, but not brachial vascular conductance, in 11 patients who previously underwent surgical SCS implantation for management of neuropathic pain. Throughout 60 min of SCS, common femoral artery conductance was elevated and significantly different from brachial artery conductance [in millilitres per minute: 15 min, change (Δ) 26 ± 37 versus Δ-2 ± 19%; 30 min, Δ28 ± 45 versus Δ0 ± 26%; 45 min, Δ48 ± 43 versus Δ2 ± 21%; 60 min, Δ36 ± 61 versus Δ1 ± 24%; and 15 min post-SCS, Δ51 ± 64 versus Δ6 ± 33%; P = 0.013]. A similar examination in a patient with cervical SCS revealed minimal changes in vascular conductance. In study 2, we examined whether acute SCS reduces peroneal MSNA in a subset of SCS patients (n = 5). The MSNA burst incidence in response to acute SCS gradually declined and was significantly reduced at 45 and 60 min of SCS (in bursts per 100 heart beats: 15 min, Δ-1 ± 12%; 30 min, Δ-14 ± 12%; 45 min, Δ-19 ± 16%; 60 min, Δ-24 ± 18%; and 15 min post-SCS: Δ-11 ± 7%; P = 0.015). These data demonstrate that acute SCS rapidly increases femoral vascular conductance and reduces peroneal MSNA. The gradual reduction in peroneal MSNA observed during acute SCS suggests that neural mechanisms in addition to attenuated MSNA might be involved in the acute increase in femoral vascular conductance.