Biomarker Optimization of Spinal Cord Stimulation Therapies.

OBJECTIVES: We are in the process of designing and testing an intradural stimulation device that will shorten the distance between the location of the electrode array and the targeted neural tissue, thus improving the efficacy of electrical current delivery. Identifying a biomarker that accurately reflects the response to this intervention is highly valued because of the potential to optimize interventional parameters or predict a response before it is clinically measurable. In this report, we summarize the findings pertaining to the study of biomarkers so that we and others will have an up-to-date reference that critically evaluates the current approaches and select one or several for testing during the development of our device. MATERIALS AND METHODS: We have conducted a broad survey of the existing literature to catalogue the biomarkers that could be coupled to intradural spinal cord stimulation. We describe in detail some of the most promising biomarkers, existing limitations, and suitability to managing chronic pain. RESULTS: Chronic, intractable pain is an all-encompassing condition that is incurable. Many treatments for managing chronic pain are nonspecific in action and intermittently administered; therefore, patients are particularly susceptible to large fluctuations in pain control over the course of a day. The absence of a reliable biomarker challenges assessment of therapeutic efficacy and contributes to either incomplete and inconsistent pain relief or, alternatively, intolerable side effects. Fluctuations in metabolites or inflammatory markers, signals captured during dynamic imaging, and genomics will likely have a role in governing how a device is modulated. CONCLUSIONS: Efforts to identify one or more biomarkers are well underway with some preliminary evidence supporting their efficacy. This has far-reaching implications, including improved outcomes, fewer adverse events, harmonization of treatment and individuals, performance gains, and cost savings. We anticipate that novel biomarkers will be used widely to manage chronic pain.

Risk Factors and Survival Analysis of Spinal Cord Stimulator Explantation.

OBJECTIVE: The treatment failure rate for spinal cord stimulators (SCS) remains unacceptably high, with reports of removal in up to 30% of patients. The purpose of this study is to perform survival and multivariate regression analyses of patients who have undergone SCS explantation in order to identify patient characteristics that may predict treatment failure. MATERIALS AND METHODS: We identified 253 patients who underwent SCS placement using current procedural terminology codes in a private health insurance data base spanning 2003-2016. Patient demographics, opioid use, surgical indications, as well as comorbidities were noted. At least 6 months of continuous claims data before and after implantation were required for inclusion. Patients who underwent explantation were defined as those who underwent removal without replacement within 90 days and had at least 90 days of continuous insurance eligibility following removal. Those who underwent removal for infectious reasons were identified with corresponding diagnosis codes. RESULTS: Of the 252 patients who met the inclusion criteria, 17 (6.7%) underwent SCS explantation. Median follow-up time was 2.0 years. Of those who had their system explanted, six patients (2.8%) had their systems removed for infection and 11 (4.3%) for noninfectious reasons. Bivariate analysis revealed that younger age and tobacco use were associated with an increased likelihood of explantation. The Cox proportional hazards analysis demonstrated that younger age, tobacco use, and the presence of "other" mental health disorders were predictive of explantation. CONCLUSIONS: In a cohort of SCS patients from multiple institutions, this study demonstrates that explantation for noninfectious reasons is more likely in younger patients, tobacco users, and those with certain psychiatric conditions. With an estimated 10% of patients opting to have their devices removed within 5 years of implantation, refining the ability of clinicians to predict who will see benefit from SCS treatment remains necessary.

Spinal Cord Stimulation for Visceral Pain: Present Approaches and Future Strategies.

INTRODUCTION: The introduction of successful neuromodulation strategies for managing chronic visceral pain lag behind what is now treatment of choice in refractory chronic back and extremity pain for many providers in the United States and Europe. Changes in public policy and monetary support to identify nonopioid treatments for chronic pain have sparked interest in alternative options. In this review, we discuss the scope of spinal cord stimulation (SCS) for visceral pain, its limitations, and the potential role for new intradural devices of the type that we are developing in our laboratories, which may be able to overcome existing challenges. METHODS: A review of the available literature relevant to this topic was performed, with particular focus on the pertinent neuroanatomy and uses of spinal cord stimulation systems in the treatment of malignant and nonmalignant gastrointestinal, genitourinary, and chronic pelvic pain. RESULTS: To date, there have been multiple off-label reports testing SCS for refractory gastrointestinal and genitourinary conditions. Though some findings have been favorable for these organs and systems, there is insufficient evidence to make this practice routine. The unique configuration and layout of the pelvic pain pathways may not be ideally treated using traditional SCS implantation techniques, and intradural stimulation may be a viable alternative. CONCLUSIONS: Despite the prevalence of visceral pain, the application of neuromodulation therapies, a standard approach for other painful conditions, has received far too little attention, despite promising outcomes from uncontrolled trials. Detailed descriptions of visceral pain pathways may offer several clues that could be used to implement devices tailored to this unique anatomy.

Intervertebral Displacement of the Thoracic Spine with and without Loading: Radiographic and in Vitro Measurements.

BACKGROUND: We are developing an intradural approach to spinal cord stimulation, where the thin electrode array is affixed stably to the underside of the thoracic spinal dura mater without leakage of cerebrospinal fluid. As part of the design and testing process, we sought to evaluate the potential risk of inadvertent contact of the array with the pial surface of the spinal cord during variations in spinal loading. METHODS: As part of the risk assessment process, a 2-part study was undertaken. First, a retrospective review of the imaging studies of 25 patients was done in the supine, 45- and 90-degree positions to measure the positional shift between the T9 and T10 vertebral bodies as a function of spinal angulation. Second, similar measurements were made on a cadaveric model, with and without a prototype intradural stimulator implanted at the T9-T10 position and with and without 13.8 kg (30 lb) of axial spinal loading at the 90-degree orientation. RESULTS: In all cases, the measured relative displacement of the dura mater towards the spinal cord in both the imaging and the cadaveric arms of the study was less than 1 mm. CONCLUSIONS: The implantation method for the thin intradural array of the prototype device will ensure that the anatomic separation between it and the pial surface of the spinal cord will be the same as that of the dura mater. Therefore the risk of inadvertent contact will be no greater than that due to the mass effects of standard epidural stimulator implants.

In Vivo Testing of a Prototype Intradural Spinal Cord Stimulator in a Porcine Model.

BACKGROUND: Chronic midline low back pain is the number one reason for disability in the United States despite the prolific use of medical and surgical interventions. Notwithstanding the widespread use of epidural spinal cord stimulators (SCSs), there remains a large portion of the population with inadequate pain control thought to be because of the limited volume of stimulated neural tissue. Intradural SCSs represent an underexplored alternative strategy with the potential to improve selectivity, power efficiency, and efficacy. We studied and carried out development of an intradural form of an SCS. Herein we present the findings of in vivo testing of a prototype intradural SCS in a porcine model. METHODS: Six female juvenile pigs underwent surgical investigation. One control animal underwent a laminectomy only, whereas the 5 other animals had implantation of an intradural SCS prototype. One of the prototypes was fully wired to enable acute stimulation and concurrent electromyographic recordings. All animals underwent terminal surgery 3 months postimplantation, with harvesting of the spinal column. Imaging (microcomputed tomography scan) and histopathologic examinations were subsequently performed. RESULTS: All animals survived implantation without evidence of neurologic deficits or infection. Postmortem imaging and histopathologic examination of the spinal column revealed no evidence of spinal cord damage, cerebrospinal fluid fistula formation, abnormal bony overgrowth, or dural defect. Viable dura was present between the intra- and extradural plates of the device. Electromyographic recordings revealed evoked motor units from the stimulator. CONCLUSIONS: Chronically implanted intradural device in the porcine model demonstrated safety and feasibility for translation into humans.

Predictors of Reduced Opioid Use With Spinal Cord Stimulation in Patients With Chronic Opioid Use.

OBJECTIVES: Spinal cord stimulation (SCS) has gained traction as an alternative to chronic opioid therapy in light of the opioid crisis. Prior reports vary widely in their estimates of its effect on opioid consumption. We therefore aimed to address the following questions: 1) Does chronic opioid use change after SCS? 2) Which patient characteristics predict reduced opioid consumption after SCS? MATERIALS AND METHODS: Claims from a private health insurance company were used to identify patients with SCS implantation from 2003 to 2014. We required 12 months of continuous data before and after surgery (i.e., a minimum total observation period of two years), and at least two opioid prescription fills in the six months before surgery. Daily morphine equivalent dose (MED) was calculated from prescription medication claims. Diagnosis codes identified common comorbidities. RESULTS: Hundred forty-five patients met inclusion criteria. MED of 65 was the most statistically meaningful preoperative dose threshold. Approximately half of patients decreased opioid use >20% after SCS implantation. Logistic regression analysis revealed age (p = 0.0362), gender (p = 0.0076), and preoperative daily MED < 65 (p = 0.0322) as predictors of meaningful reduction, which was defined as a 20% reduction in MED. CONCLUSIONS: With only half of chronic opioid users demonstrating meaningful opioid reduction after SCS implantation, we demonstrate that current SCS technology does not reliably help a larger number of patients reduce opioid usage. Women, older age, and preoperative MED < 65 are predictive of meaningful opioid reduction but only one of these is modifiable. As not all patients saw benefit from their therapies, there is still much room for improvement in the treatment of refractory chronic pain that is associated with failed back surgery syndrome and chronic regional pain syndrome.

Contemporary Approaches to Preventing and Treating Infections of Novel Intrathecal Neurostimulation Devices.

INTRODUCTION: Contemporary approaches to surgical site infections have evolved significantly over the last several decades in response to the economic pressures of soaring health care costs and increasing patient expectations of safety. Neurosurgeons face multiple unique challenges when striving to avoid as well as manage surgical implant infections. The tissue compartment, organ system, or joint is characterized by biological factors and physical forces that may not be universally relevant. Such implants, once rare, are now routine. Although the prevention, diagnosis, and treatment of surgical site infections involving neural implants has advanced, guidelines are ever changing, and the incidence still exceeds acceptable levels. We assess the impact of these factors on a new class of implantable neuromodulation devices. METHODS: The available evidence along with practice patterns were examined and organized to establish relevant groupings for continuing evaluation and to propose justifiable recommendations for the treatment of infections that might arise in the case of intradural spinal cord stimulators. RESULTS: Few studies in the modern era have systematically evaluated preventive behaviors that were applied to intradural neural implants alone. We anticipate that future efforts will focus even more on the investigation of modifiable factors along a continuum from bacterially repellant implants to weight management. Early diagnosis could offer the best hope for device salvage but to date has been largely understudied. CONCLUSIONS: Historically, prevention is the cornerstone to infection mitigation. However, immediate diagnosis and hardware salvage have not received the attention deserved, and that approach may be especially important for intradural devices.

Intradural Spinal Cord Stimulation: Performance Modeling of a New Modality.

Introduction: Intradural spinal cord stimulation (SCS) may offer significant therapeutic benefits for those with intractable axial and extremity pain, visceral pain, spasticity, autonomic dysfunction and related disorders. A novel intradural electrical stimulation device, limited by the boundaries of the thecal sac, CSF and spinal cord was developed to test this hypothesis. In order to optimize device function, we have explored finite element modeling (FEM). Methods: COMSOL®Multiphysics Electrical Currents was used to solve for fields and currents over a geometric model of a spinal cord segment. Cathodic and anodic currents are applied to the center and tips of the T-cross component of the electrode array to shape the stimulation field and constrain charge-balanced cathodic pulses to the target area. Results: Currents from the electrode sites can move the effective stimulation zone horizontally across the cord by a linear step method, which can be diversified considerably to gain greater depth of penetration relative to standard epidural SCS. It is also possible to prevent spread of the target area with no off-target action potential. Conclusion: Finite element modeling of a T-shaped intradural spinal cord stimulator predicts significant gains in field depth and current shaping that are beyond the reach of epidural stimulators. Future studies with in vivo models will investigate how this approach should first be tested in humans.

Durotomy Surrogate and Seals for Intradural Spinal Cord Stimulators: Apparatus and Review of Clinical Methods and Materials.

INTRODUCTION: We are developing a novel intradural spinal cord stimulator for treatment of neuropathic pain and spasticity. A key feature is the means by which it seals the dura mater to prevent leakage of cerebrospinal fluid (CSF). We have built and employed a test rig that enables evaluation of candidate seal materials. METHODS: To guide the design of the test rig, we reviewed the literature on neurosurgical durotomies. The test rig has a mock durotomy slot with a dural substitute serving as the surrogate dura mater and water as the CSF. The primary experimental goal was to evaluate the effectiveness of candidate gasket materials as seals against CSF leakage in an implanted prototype device, at both normal and super-physiologic pressures. A secondary goal was to measure the transmembrane flows in a representative dural substitute material, to establish its baseline aqueous transport properties. RESULTS: The seals prevented leakage of water at the implantation site over periods of ≈ ten days, long enough for the scar tissue to form in the clinical situation. The seals also held at water pressure transients approaching 250 mm Hg. The residual volumetric flux of water through the dura substitute membrane (Durepair®) was δVT /A ≈ 0.24 mm3 /min/cm2 , consistent with expectations for transport through the porous membrane prior to closure and equalization of internal/external pressures. CONCLUSIONS: We have demonstrated the workability of obtaining robust seal against leakage at the implantation site of a novel intradural stimulator using a custom-designed test rig. Extension of the method to in vivo testing in a large animal model will be the next step.

Ovine model of neuropathic pain for assessing mechanisms of spinal cord stimulation therapy via dorsal horn recordings, von Frey filaments, and gait analysis.

BACKGROUND: It is becoming increasingly important to understand the mechanisms of spinal cord stimulation (SCS) in alleviating neuropathic pain as novel stimulation paradigms arise. PURPOSE: Additionally, the small anatomic scale of current SCS animal models is a barrier to more translational research. METHODS: Using chronic constriction injury (CCI) of the common peroneal nerve (CPN) in sheep (ovine), we have created a chronic model of neuropathic pain that avoids motor deficits present in prior large animal models. This large animal model has allowed us to implant clinical grade SCS hardware, which enables both acute and chronic testing using von Frey filament thresholds and gait analysis. Furthermore, the larger anatomic scale of the sheep allows for simultaneous single-unit recordings from the dorsal horn and SCS with minimal electrical artifact. RESULTS: Detectable tactile hypersensitivity occurred 21 days after nerve injury, with preliminary indications that chronic SCS may reverse it in the painful limb. Gait analysis revealed no hoof drop in the CCI model. Single neurons were identified and discriminated in the dorsal horn, and their activity was modulated via SCS. Unlike previous large animal models that employed a complete transection of the nerve, no motor deficit was observed in the sheep with CCI. CONCLUSION: To our knowledge, this is the first reported large animal model of chronic neuropathic pain which facilitates the study of both acute and chronic SCS using complementary behavioral and electrophysiologic measures. As demonstrated by our successful establishment of these techniques, an ovine model of neuropathic pain is suitable for testing the mechanisms of SCS.

Spinal dura mater: biophysical characteristics relevant to medical device development.

Understanding the relevant biophysical properties of the spinal dura mater is essential to the design of medical devices that will directly interact with this membrane or influence the contents of the intradural space. We searched the literature and reviewed the pertinent characteristics for the design, construction, testing, and imaging of novel devices intended to perforate, integrate, adhere or reside within or outside of the spinal dura mater. The spinal dura mater is a thin tubular membrane composed of collagen and elastin fibres that varies in circumference along its length. Its mechanical properties have been well-described, with the longitudinal tensile strength exceeding the transverse strength. Data on the bioelectric, biomagnetic, optical and thermal characteristics of the spinal dura are limited and sometimes taken to be similar to those of water. While various modalities are available to visualise the spinal dura, magnetic resonance remains the best modality to segment its structure. The reaction of the spinal dura to imposition of a foreign body or other manipulations of it may compromise its biomechanical and immune-protective benefits. Therefore, dural sealants and replacements are of particular clinical, research and commercial interest. In conclusion, existing devices that are in clinical use for spinal cord stimulation, intrathecal access or intradural implantation largely adhere to traditional designs and their attendant limitations. However, if future devices are built with an understanding of the dura's properties incorporated more fully into the designs, there is potential for improved performance.

Intrathecal Therapeutics: Device Design, Access Methods, and Complication Mitigation.

INTRODUCTION: The intrathecal space remains underutilized for diagnostic testing, invasive monitoring or as a pipeline for the delivery of neurological therapeutic agents and devices. The latter including drug infusions, implants for electrical modulation, and a means for maintaining the physiologic pressure column. The reasons for this are many but include unfamiliarity with the central nervous system and the historical risks that continue to overshadow the low complication rates in modern clinical series. MATERIALS AND METHODS: Our intent in this review is to explore the access devices currently on the market, assess the risk associated with breaching the intrathecal space, and propose a research model for bringing to patients the next generation of intrathecal hardware. For this purpose, we reviewed both historical and contemporary literature that pertains to the access devices and catheters intended for both temporary and permanent implantation and the complications thereof. RESULTS: There are few devices that are currently marketed in the United States or Europe for intrathecal use. Most hew to a relatively fixed design pattern predicated on the dimensions and properties of the thecal sac. All are typically composed of soft silicone, and employ a Tuohy needle for access despite design limitations. In general, these catheters are engineered for durability, ease of use, and regional deployment. Devices on the market with steerability or targeted intrathecal fixation are not yet available. Complications, once a legitimate concern, are now quite rare when recommended techniques are followed. CONCLUSIONS: Over the next decade, advances in intrathecal catheter design, access techniques, imaging, and greater understanding of the spinal cord neurophysiology will usher in an era where the intrathecal space is recognized as a highly valued diagnostic and therapeutic target. We anticipate that this will occur in several concurrent phases, each with the potential to accelerate the growth of the others.

Spinal Cord Stimulation for Spasticity: Historical Approaches, Current Status, and Future Directions.

INTRODUCTION: Millions of people worldwide suffer with spasticity related to irreversible damage to the brain or spinal cord. Typical antecedent events include stroke, traumatic brain injury, and spinal cord injury, although insidious onset is also common. Regardless of the cause, the resulting spasticity leads to years of disability and reduced quality of life. Many treatments are available to manage spasticity; yet each is fraught with drawbacks including incomplete response, high cost, limited duration, dose-limiting side effects, and periodic maintenance. Spinal cord stimulation (SCS), a once promising therapy for spasticity, has largely been relegated to permanent experimental status. METHODS: In this review, our goal is to document and critique the history and assess the development of SCS as a treatment of lower limb spasticity. By incorporating recent discoveries with the insights gained from the early pioneers in this field, we intend to lay the groundwork needed to propose testable hypotheses for future studies. RESULTS: SCS has been tested in over 25 different conditions since a potentially beneficial effect was first reported in 1973. However, the lack of a fully formed understanding of the pathophysiology of spasticity, archaic study methodology, and the early technological limitations of implantable hardware limit the validity of many studies. SCS offers a measure of control for spasticity that cannot be duplicated with other interventions. CONCLUSIONS: With improved energy-source miniaturization, tailored control algorithms, novel implant design, and a clearer picture of the pathophysiology of spasticity, we are poised to reintroduce and test SCS in this population.

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.

Comparison of Conventional and Kilohertz Frequency Epidural Stimulation in Patients Undergoing Trialing for Spinal Cord Stimulation: Clinical Considerations.

OBJECTIVE: Compare therapeutic response of patients to conventional versus high-frequency spinal cord stimulation (SCS). METHODS: Twelve patients with back and leg pain who met standard clinical criteria for a trial of conventional SCS (low-frequency stimulation [LFS]) participated in a half-day session of high-frequency stimulation (HFS) during their weeklong conventional trial. HFS consisted of frequencies ranging from 50 Hz to 4 kHz, or 100 Hz to10 kHz, at constant voltage settings increasing from 0.5 V to 10 V. Visual Analog Scale scores from 0 to10 were recorded, along with notes of any clinical discomfort and open patient comments. RESULTS: Two of 12 patients had no benefit from either LFS or HFS. In the remaining 10 patients, paresthesias were significantly altered by HFS, and four experienced complete elimination of paresthesias. Five patients preferred HFS to LFS, with an additional three preferring both equally. Abrupt sensation to the onset of HFS was described in six patients, and in ten patients, HFS allowed maximum voltage stimulation of 10 V without discomfort. The four patients who did not have a successful trial of stimulation had significantly longer duration of pain compared to the eight patients who went on to permanent implant (11.2 vs. 4.3 years, P = 0.04). CONCLUSIONS: HFS significantly altered the feeling of paresthesias in the majority of patients (ten of 12), was preferred to LFS in five of 12 patients, and non-inferior to LFS in eight of 12 patients. Both 4 kHz and 10 kHz stimulation allowed patients to benefit from HFS. HFS allowed maximum voltage stimulation without discomfort.

Kinematic analysis of the gait of adult sheep during treadmill locomotion: Parameter values, allowable total error, and potential for use in evaluating spinal cord injury.

We are developing a novel intradural spinal cord (SC) stimulator designed to improve the treatment of intractable pain and the sequelae of SC injury. In-vivo ovine models of neuropathic pain and moderate SC injury are being implemented for pre-clinical evaluations of this device, to be carried out via gait analysis before and after induction of the relevant condition. We extend previous studies on other quadrupeds to extract the three-dimensional kinematics of the limbs over the gait cycle of sheep walking on a treadmill. Quantitative measures of thoracic and pelvic limb movements were obtained from 17 animals. We calculated the total-error values to define the analytical performance of our motion capture system for these kinematic variables. The post- vs. pre-injury time delay between contralateral thoracic and pelvic-limb steps for normal and SC-injured sheep increased by ~24s over 100 steps. The pelvic limb hoof velocity during swing phase decreased, while range of pelvic hoof elevation and distance between lateral pelvic hoof placements increased after SC injury. The kinematics measures in a single SC-injured sheep can be objectively defined as changed from the corresponding pre-injury values, implying utility of this method to assess new neuromodulation strategies for specific deficits exhibited by an individual.

Postsurgical pathologies associated with intradural electrical stimulation in the central nervous system: design implications for a new clinical device.

Spinal cord stimulation has been utilized for decades in the treatment of numerous conditions such as failed back surgery and phantom limb syndromes, arachnoiditis, cancer pain, and others. The placement of the stimulating electrode array was originally subdural but, to minimize surgical complexity and reduce the risk of certain postsurgical complications, it became exclusively epidural eventually. Here we review the relevant clinical and experimental pathologic findings, including spinal cord compression, infection, hematoma formation, cerebrospinal fluid leakage, chronic fibrosis, and stimulation-induced neurotoxicity, associated with the early approaches to subdural electrical stimulation of the central nervous system, and the spinal cord in particular. These findings may help optimize the safety and efficacy of a new approach to subdural spinal cord stimulation now under development.

Comparison of spinal cord stimulation profiles from intra- and extradural electrode arrangements by finite element modelling.

Spinal cord stimulation currently relies on extradural electrode arrays that are separated from the spinal cord surface by a highly conducting layer of cerebrospinal fluid. It has recently been suggested that intradural placement of the electrodes in direct contact with the pial surface could greatly enhance the specificity and efficiency of stimulation. The present computational study aims at quantifying and comparing the electrical current distributions as well as the spatial recruitment profiles resulting from extra- and intra-dural electrode arrangements. The electrical potential distribution is calculated using a 3D finite element model of the human thoracic spinal canal. The likely recruitment areas are then obtained using the potential as input to an equivalent circuit model of the pre-threshold axonal response. The results show that the current threshold to recruitment of axons in the dorsal column is more than an order of magnitude smaller for intradural than extradural stimulation. Intradural placement of the electrodes also leads to much higher contrast between the stimulation thresholds for the dorsal root entry zone and the dorsal column, allowing better focusing of the stimulus.

Intracranial somatosensory responses with direct spinal cord stimulation in anesthetized sheep.

The efficacy of spinal cord stimulators is dependent on the ability of the device to functionally activate targeted structures within the spinal cord, while avoiding activation of near-by non-targeted structures. In theory, these objectives can best be achieved by delivering electrical stimuli directly to the surface of the spinal cord. The current experiments were performed to study the influence of different stimulating electrode positions on patterns of spinal cord electrophysiological activation. A custom-designed spinal cord neurostimulator was used to investigate the effects of lead position and stimulus amplitude on cortical electrophysiological responses to spinal cord stimulation. Brain recordings were obtained from subdural grids placed in four adult sheep. We systematically varied the position of the stimulating lead relative to the spinal cord and the voltage delivered by the device at each position, and then examined how these variables influenced cortical responses. A clear relationship was observed between voltage and electrode position, and the magnitude of high gamma-band oscillations. Direct stimulation of the dorsal column contralateral to the grid required the lowest voltage to evoke brain responses to spinal cord stimulation. Given the lower voltage thresholds associated with direct stimulation of the dorsal column, and its possible impact on the therapeutic window, this intradural modality may have particular clinical advantages over standard epidural techniques now in routine use.

Power and signal transmission protocol for a contactless subdural spinal cord stimulation device.

Wireless signal transmission will play a critical role in developing reliable subdural spinal cord stimulation systems. We have developed an approach to inductively coupling signals across the epidural spacing between the pial and epidural surfaces. The major design constraints include tolerance of coil misalignments from spinal cord geometries in addition to reasonable power efficiencies within the expected range of movement. The design of the primary side as a driving circuit is simplified by several turns of commercial magnetic wire, whereas the implanted secondary side is implemented in a micro-planar spiral coil tuned to a resonant frequency of 1.6 MHz. We present the results of wireless inductive coupling experiments that demonstrate the ability to transmit and receive a frequency modulated 1.6 MHz carrier signal between primary and secondary coil antennae scaled to 10 mm. Power delivery is in the range of 400 mW at a link efficiency of 32 % for strong coupling (coil separations of 0.5 mm ) and in the range of 70 mW at 4 % efficiency for weak coupling (coil separations of 10 mm).