Brian D. Dalm

Intradural approach to selective stimulation in the spinal cord for treatment of intractable pain: design principles and wireless protocol

We introduce an intradural approach to spinal cord stimulation for the relief of intractable pain, and describe the biophysical rationale that underlies its design and performance requirements. The proposed device relies on wireless, inductive coupling between a pial surface implant and its epidural controller, and we present the results of benchtop experiments that demonstrate the ability to transmit and receive a frequency-modulated 1.6 MHz carrier signal between micro-coil antennae scaled to the ≈ 1 cm dimensions of the implant, at power levels of about 5 mW. Plans for materials selection, microfabrication, and other aspects of future development are presented and discussed.

Pulsatile spinal cord surrogate for intradural neuromodulation studies

We have designed, built and tested a novel spinal cord surrogate that mimics the low-amplitude cardiac-driven pulsations of the human spinal cord, for use in developing intradural implants to be used in a novel form of neuromodulation for the treatment of intractable pain and motor system dysfunction. The silicone surrogate has an oval cross section, 10 mm major axis × 6 mm minor axis, and incorporates a 3 mm diameter × 3 cm long angioplasty balloon that serves as the pulsation actuator. When pneumatically driven at 1 Hz and 1.5 atmospheres (≈ 1140 mm Hg), the surrogate’s diametric pulsation is ≈ 100 μm, which corresponds well to in vivo observations. The applications for this surrogate are presented and discussed.

Lateralized effect of pallidal stimulation on self-mutilation in Lesch-Nyhan disease

Lesch-Nyhan disease (LND) is an X-linked hereditary disorder caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase. This syndrome is characterized by hyperuricemia, self-mutilation, cognitive impairment, and movement disorders such as spasticity and dystonia. The authors describe the case of a 15-year-old boy who underwent bilateral placement of globus pallidus internus (GPi) deep brain stimulation (DBS) electrodes for the treatment of generalized dystonia. His self-mutilating behavior gradually disappeared several weeks after the start of GPi stimulation. The dystonia and self-mutilating behavior returned on the left side only after a right lead fracture. This case is the first reported instance of LND treated with DBS in which the stimulation was interrupted and the self-mutilation returned in a lateralized fashion. The findings indicate that the neurobehavioral aspect of LND is lateralized and that contralateral GPi stimulation is responsible for lateralized improvement in self-injurious behavior.

Biomechanical performance of an ovine model of intradural spinal cord stimulation

Abstract 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.

Conditioned place preference and spontaneous dorsal horn neuron activity in chronic constriction injury model in rats.

Abstract Patients with neuropathic pain commonly present with spontaneous pain, in addition to allodynia and hyperalgesia. Although evoked responses in neuropathic pain models are well characterized, determining the presence of spontaneous pain is more challenging. We determined whether the chronic constriction injury (CCI) model could be used to measure effects of treatment of spontaneous pain, by evaluating dorsal horn neuron (DHN) spontaneous activity and spontaneous pain-related behaviors. We measured conditioned place preference (CPP) to analgesia produced by sciatic nerve block with bupivacaine in rats with established CCI. We undertook another CPP experiment using hind paw incision. We also examined DHN spontaneous activity in CCI rats. Although CCI produced nocifensive responses to mechanical stimuli, CPP to analgesic nerve block was not evident 14 days after injury: Compared with baseline (314 ± 65 seconds), CCI rats did not show a preference for the bupivacaine-paired chamber after conditioning (330 ± 102 seconds). However, sciatic nerve block after hind paw incision produced CPP on postoperative day 1, serving as a positive control. The proportion of spontaneously active DHNs (33%) was not significantly increased in CCI rats compared with the sham (21%). The median rate of spontaneous activity in the CCI group (12.6 impulses per second) was not different from the sham group (9.2 impulses per second). Also, there was no change in DHN spontaneous activity after sciatic nerve block with bupivacaine. Our findings suggest that CCI as a neuropathic pain model should not be used to measure effects of treatment of spontaneous pain driven by the peripheral input.

Revisiting intradural spinal cord stimulation: an introduction to a novel intradural spinal cord stimulation device

Abstract Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusion: 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.

Biomechanical analysis of anterior versus posterior instrumentation following a thoracolumbar corpectomy: Laboratory investigation.

OBJECT The objective of this study was to evaluate the biomechanical properties of lateral instrumentation compared with short- and long-segment pedicle screw constructs following an L-1 corpectomy and reconstruction with an expandable cage. METHODS Eight human cadaveric T10-L4 spines underwent an L-1 corpectomy followed by placement of an expandable cage. The spines then underwent placement of lateral instrumentation consisting of 4 monoaxial screws and 2 rods with 2 cross-connectors, short-segment pedicle screw fixation involving 1 level above and below the corpectomy, and long-segment pedicle screw fixation (2 levels above and below). The order of instrumentation was randomized in the 8 specimens. Testing was conducted for each fixation technique. The spines were tested with a pure moment of 6 Nm in all 6 degrees of freedom (flexion, extension, right and left lateral bending, and right and left axial rotation). RESULTS In flexion, extension, and left/right lateral bending, posterior long-segment instrumentation had significantly less motion compared with the intact state. Additionally, posterior long-segment instrumentation was significantly more rigid than short-segment and lateral instrumentation in flexion, extension, and left/right lateral bending. In axial rotation, the posterior long-segment construct as well as lateral instrumentation were not significantly more rigid than the intact state. The posterior long-segment construct was the most rigid in all 6 degrees of freedom. CONCLUSIONS In the setting of highly unstable fractures requiring anterior reconstruction, and involving all 3 columns, long-segment posterior pedicle screw constructs are the most rigid.

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.

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.

A Novel Dural Reconstruction Method Following Spinal Tumor Resection

Objective:This report describes a new method for reducing the risk of postoperative obliteration of the subdural space and spinal cord tethering that frequently occurs following resection of intradural spinal tumors. Methods:A 66-year-old patient underwent resection of a T1 to T2 intradural meningioma. A duraplasty procedure was performed to reconstruct the thecal sac and create a capacious cerebrospinal fluid (CSF)-filled space around the spinal cord. To prevent subsequent inward compression of the thecal sac from dorsally located soft tissue, a titanium strap was fashioned to span the laminectomy defect. Dural tack-up stitches were secured to the titanium strap and the laminoplasty construct was secured in place using standard bone screws. Results:The combined duraplasty-titanium laminoplasty procedure was technically straightforward and there were no complications following surgery. Postoperative MR imaging 6 weeks following surgery demonstrated that the goal of creating a capacious CSF-filled space around the spinal cord, without inward compression of the thecal sac by scar tissue, was achieved. MR images of the spinal cord and dura were not degraded by the presence of the overlying titanium strap. Conclusions:This simple method that combines a duraplasty and titanium laminoplasty procedure seems to be a safe and effective approach to achieving the objective of maintaining a capacious CSF-filled space surrounding the spinal cord following intradural surgery.