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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.

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.

Improved knowledge of the electrode-tissue impedance will be useful in optimizing the clinical protocols and resulting efficacy of the existing and emerging approaches to spinal cord stimulation. Toward that end, the complex impedance (amplitude and phase) of in vivo ovine spinal cord tissue was measured at the electrode-pial subdural surface interface from 5 Hz to 1 MHz, and with the bi-polar electrodes oriented both parallel and perpendicular to the rostral-caudal axis of the spinal cord. At stimulation frequencies above 10 kHz, most of the impedance then becomes resistive in nature and the phase diference between the stimulation signal and the resulting current drops to ≈ 10˚, thus maximizing power transfer to the tissues. Also, at these higher frequencies, the current pulse maintains significantly greater fidelity to the shape of the stimulation signal applied across the electrodes. Lastly, there were lower impedances associated with parallel as opposed to perpendicular orientation of the electrodes, thus reflecting the effects of fiber orientation within the spinal cord. Impedance differences of this kind have not been reported with epidural stimulation because of the electrical shunting effects of the intervening layer of relatively high conductivity cerebrospinal fluid. These observations provide a quantitative basis for improved models of spinal cord stimulation and suggest certain advantages for direct intradural stimulation relative to the standard epidural approaches. (Some figures in this article are in colour only in the electronic version)

The authors are developing a novel type of spinal cord stimulator, designed to be placed directly on the pial surface of the spinal cord, for more selective activation of target tissues within the dorsal columns. For pre-clinical testing of the device components, an ovine model has been implemented which utilizes the agility and flexibility of a sheep's cervical and upper thoracic regions, thus providing an optimal environment of accelerated stress-cycling on small gauge lead wires implanted along the dorsal spinal columns. The results are presented of representative biomechanical measurements of the angles of rotation and the angular velocities and accelerations associated with the relevant head, neck and upper back motions, and these findings are interpreted in terms of their impact on assessing the robustness of the stimulator implant systems.

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.

This study develops a means of delivering electrical stimuli directly to the pial surface of the spinal cord for treatment of intractable pain. This intradural implant must remain in direct contact with the cord as it moves within the spinal canal. Therefore, magnetic resonance imaging was used to measure the movement of the spinal cord between neutral and flexed-back positions in a series of volunteers (n = 16). Following flexion of the back, the mean change in the pedicle-to-spinal cord dorsal root entry zone distance at the T10-11 level was (8.5 ± 6.0) mm, i.e. a 71% variation in the range of rostral-caudal movement of the spinal cord across all patients. There will be a large spectrum of spinal cord strains associated with this observed range of rostral-caudal motions, thus calling for suitable axial compliance within the electrode bearing portion of the intradural implant.

We describe a novel spinal cord (SC) stimulator that is designed to overcome a major shortcoming of existing stimulator devices: their restricted capacity to selectively activate targeted axons within the dorsal columns. This device overcomes that limitation by delivering electrical stimuli directly to the pial surface of the SC. Our goal in testing this device was to measure its ability to physiologically activate the SC and examine its capacity to modulate somatosensory evoked potentials (SSEPs) triggered by peripheral stimulation. In this acute study on adult sheep (n = 7), local field potentials were recorded from a grid placed in the subdural space of the right hemisphere during electrical stimulation of the left tibial nerve and the spinal cord. Large amplitude SSEPs (>200 µV) in response to SC stimulation were consistently obtained at stimulation strengths well below the thresholds inducing neural injury. Moreover, stimulation of the dorsal columns with signals employed routinely by devices in standard clinical use, e.g., 50 Hz, 0.2 ms pulse width, produced long-lasting changes (>4.5 h) in the SSEP patterns produced by subsequent tibial nerve stimulation. The results of these acute experiments demonstrate that this device can be safely secured to the SC surface and effectively activate somatosensory pathways.

Our laboratories are developing treadmill-based gait analysis employing sheep to investigate potential efficacy of intra-dural spinal cord stimulation in the treatment of spinal cord injury and neuropathic pain. As part of efforts to establish the performance characteristics of the experimental arrangement, this study measured the treadmill speed via a tachometer, video belt-marker timing and ambulation-rate observations of the sheep. The data reveal a 0.1-0.3% residual drift in the baseline (unloaded) treadmill speed which increases with loading, but all three approaches agree on final speed to within 1.7%, at belt speeds of ≈ 4 km/h. Using the tachometer as the standard, the estimated upper limit on uncertainty in the video belt-marker approach is ± 0.18 km h(-1) and the measured uncertainty is ± 0.15 km h(-1). Employment of the latter method in determining timing differences between contralateral hoof strikes by the sheep suggests its utility in assessing severity of SCI and responses to therapeutic interventions.

We have designed, built and tested a novel device for placing intradural neurmodulator implants directly on the pial surface of the spinal cord. This applier tool is designed for ergonomic handling of delicate electro-mechanical devices such as the Iowa-Patch™ spinal cord stimulator implant, which is aimed at overcoming certain shortcomings in the performance of standard epidural stimulator devices. The applier is approximately 14 cm long, 6 mm in diameter, made of stainless steel components, and has simple and reliable mechanisms for the attachment and release of the implant from it. We describe the design of the device, details of its construction, and its performance during in vivo testing of somatosensory evoked potentials in an ovine model of intradural spinal cord stimulation.

We have used finite-element (FE) modeling to investigate the mechanical compliance, positional stability and contact pressures associated with a novel type of spinal cord stimulator that is placed directly on the pial surface of the spinal cord in order to more selectively activate neural structures for relief of intractable pain. The properties used in the model are those of the actual prototype devices employed in recent in vitro and chronic in vivo tests. The agreement between predictions and experimental observations serves to validate our FE approach, which can now be used to further optimize the device's design and performance.

Spinal cord stimulation has been in use for decades and is growing as a therapeutic treatment option. A significant problem arising from the epidural location of the lead is electrical shunting through the cerebrospinal fluid, providing sub-optimal delivery of the electrical current specifically to the Aβ fibers of the dorsal column.Our goal is to design a safe and effective intradural spinal cord stimulator (SCS) that places the stimulating electrodes directly against the pia similar to what is currently employed with the auditory brainstem implant.We have reviewed the literature on the early original intradural SCSs and designed, built, and tested an improved device that seeks to overcome the limitations the existing epidural stimulators.In particular, we have shown that the present design of our device allows for motion of the spinal cord without the device being displaced itself, exerts a surface pressure on the spinal cord surface that is below what would cause ischemia or vessel injury, activates somato-sensory evoked potentials at a lower threshold than epidural stimulation, and (iv) does not cause deleterious neurological deficits in a chronic ovine model of intradural stimulator implantation.While further studies to prove long-term safety and durability of the device are underway, we believe that revisiting an intradural approach to spinal cord stimulation may continue to improve our ability to treat certain chronic pain states and possibly the spasticity associated with spinal cord injuries.

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.

We have designed, built, and tested an apparatus used for investigating the biomechanical response of a novel intradural spinal cord stimulator to the simulated physiological movement of the spinal cord within the thecal sac. In this apparatus, the rostral-caudal displacements of an anthropomorphic spinal cord surrogate can be controlled with a resolution of approximately 0.1% of a target value for up to 10(7) lateral movement cycles occurring at a repetition rate of 2 Hz. Using this system, we have been able to determine that the restoring force of the stimulator's suspension system works in concert with the frictional coupling between the electrode array and the surrogate to overcome the 0.42 μN inertial force associated with the lateral motion of the array. The result is a positional stability of the array on the surrogate (in air) of better than 0.2 mm over ~500,000 movement cycles. Design modifications that might lead to improved physiological performance are discussed.

We have characterized the mechanical compliance of an improved version of the suspension system used to position the electrode-bearing membrane of an intradural neuromodulator on the dorsal pial surface of the spinal cord. Over the compression span of 5 mm, it exhibited a restoring force of 2.4 μN μm−1 and a mean pressure of 0.5 mm Hg (=66 Pa) on the surface below it, well within the range of normal intrathecal pressures. We have implanted prototype devices employing this suspension and a novel device fixation technique in a chronic ovine model of spinal cord stimulation and found that it maintains stable contact at the electrode-pia interface without lead fracture, as determined by measurement of the inter-contact impedances.

We have measured the forces that act on the electrode-bearing surface of an intradural neuromodulator designed to be in direct contact with the pial surface of the spinal cord, as part of our effort to develop a new method for treating intractable pain. The goal was to investigate the pressures produced by this device on the spinal cord and compare them with normal intrathecal pressure. For this purpose, we employed a dual-sensor arrangement that allowed us to measure the response of a custom-designed silicone spinal cord surrogate to the forces applied by the device. We found that the device had a mean compliance of ≈63 μN μm−1, and that over a 3 mm range of compression, the mid-span pressure it exerted on the spinal cord was ≈1.88 × 103 Pa = 14.1 mm Hg, which lies within the range of normal intrathecal pressure in humans.

Axial magnetic resonance images of the thoracic spinal cord of 50 patients are analyzed in order to measure the length of the dorsal arc span between the dorsal root entry zones for the purpose of optimizing the mechanical design dimensions of the Human Spinal Cord Modulation System (HSCMS), which delivers electrical stimuli directly to the spinal cord. Two mathematical approaches are used to assess the data, with validation of the results conducted via a direct physical measurement using a magnified image. Results show that the nominal value of the arc length is 6.7 ± 1.0 mm (1 σ), with high and low values of 8.8 and 5.1 mm, respectively. The mean radius of the spinal cord was found to be 3.6 ± 0.5 mm. Taking into account previously reported measurements, it is suggested that values at the high end of this range be used for further morphometric studies of the cord in the thoracic region. The implications of these findings on the design of the HSCMS are discussed.