Oliver E. Flouty

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.

Ovine Tests of a Novel Spinal Cord Neuromodulator and Dentate Ligament Fixation Method

ABSTRACT Background: To improve methods for the treatment of intractable pain, we are developing a novel intradural spinal cord stimulator that could be either attached to the dentate ligaments of the human spinal cord or fitted around the dorsal arc of the cord itself. Purpose: Our goal was to carry out the first in vivo tests of these attachment methods in an ovine model using custom-built devices and instrumentation. For eventual translational studies, we also explored methods of mimicking a human dentate ligament attachment technique in this large animal model. Methods: As a starting point, we investigated details of the gross and histological anatomy of the ovine denticulate ligaments, and compared them with their human counterpart. The gap between the dura and the spinal cord in the sheep is small; hence, the denticulate ligaments are not long enough to accommodate human-scaled attachment clips. Therefore, lateral strips of the spinal-canal dura were fashioned to serve this same device attachment function. Results: This form of dural anchoring was implemented surgically for fixation of a silicone membrane implant that had 12 electrodes, and somatosensory evoked potentials were obtained successfully when stimuli were applied to it. The dorsal arc clamping technique was also implemented. Conclusions: We demonstrated that the dural attachment method is an effective surrogate model for testing the human dentate ligament device fixation technique, and that this mode of fixation was preferable to dorsal arc attachment. The relevant surgical innovations, anatomical findings, and the preliminary electrophysiological data from a pial surface stimulator attached in this way are presented.

A new device concept for directly modulating spinal cord pathways: initial in vivo experimental results

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.

A human prefrontal-subthalamic circuit for cognitive control

The subthalamic nucleus is a key site controlling motor function in humans. Deep brain stimulation of the subthalamic nucleus can improve movements in patients with Parkinsons disease; however, for unclear reasons, it can also have cognitive effects. Here, we show that the human subthalamic nucleus is monosynaptically connected with cognitive brain areas such as the prefrontal cortex. Single neurons and field potentials in the subthalamic nucleus are modulated during cognitive processing and are coherent with 4-Hz oscillations in medial prefrontal cortex. These data predict that low-frequency deep brain stimulation may alleviate cognitive deficits in Parkinsons disease patients. In line with this idea, we found that novel 4-Hz deep brain stimulation of the subthalamic nucleus improved cognitive performance. These data support a role for the human hyperdirect pathway in cognitive control, which could have relevance for brain-stimulation therapies aimed at cognitive symptoms of human brain disease.awx300media15660002226001.

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.

Intraventricular foramen of Monro cavernous malformation

We present a 64-year-old woman who was evaluated after being found unresponsive. Imaging revealed a foramen of Monro cavernoma resulting in hydrocephalus. Supratentorial cavernomas are most frequently found in the cerebral cortex, and although ventricular cavernomas do occur, they are rarely located in the foramen of Monro. Foramen of Monro cavernomas are extremely dangerous, requiring aggressive management when identified.

A Unique Case of Primary Ewing’s Sarcoma of the Cervical Spine in a 53-Year-Old Male: A Case Report and Review of the Literature

Extraskeletal Ewings sarcoma (EES) is a rare presentation, representing only 15% of all primary Ewings sarcoma cases. Even more uncommon is EES presenting as a primary focus in the spinal canal. These rapidly growing tumors often present with focal neurological symptoms of myelopathy or radiculopathy. There are no classic characteristic imaging findings and thus the physician must keep a high index of clinical suspicion. Diagnosis can only be definitively made by histopathological studies. In this report, we discuss a primary cervical spine EES in a 53-year-old man who presented with a two-month history of left upper extremity pain and acute onset of weakness. Imaging revealed a cervical spinal canal mass. After undergoing cervical decompression, histopathological examination confirmed a diagnosis of Ewings sarcoma. A literature search revealed fewer than 25 reported cases of primary cervical spine EES published in the past 15 years and only one report demonstrating this pathology in a patient older than 30 years of age (age = 38). Given the low incidence of this pathology presenting in this age group and the lack of treatment guidelines, each patients plan should be considered on a case-by-case basis until further studies are performed to determine optimal evidence based treatment.

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.

Risk factors associated with distal catheter migration following ventriculoperitoneal shunt placement

Ventriculoperitoneal (VP) shunt placement is used to treat hydrocephalus. Shunt migration following VP shunt placement has been reported. The risk factors related to this complication have not been previously evaluated to our knowledge. In this retrospective cohort study, we aimed to determine risk factors leading to distal catheter migration and review the literature on the current methods of management and prevention. Adult patients undergoing VP shunt placement from June 2011 to December 2013 at a single institution were identified using electronic health records. The records were reviewed for demographic and procedural information, and subsequent treatment characteristics. The parameters of patients with distal shunt migration were compared to those undergoing new VP shunt placement for the same time period. We identified 137 patients undergoing 157 new VP shunt procedures with an average age of 57.7 ± standard deviation of 18.4 years old. There were 16 distal shunt migrations. Body mass index >30 kg/m(2) and number of previous shunt procedures were found to be independent risk factors for distal catheter migration. Obesity and number of previous shunt procedures were factors for distal catheter migration. Providers and patients should be aware of these possible risk factors prior to VP shunt placement.