Quantifying changes in local basal ganglia structural connectivity in the 6-hydroxydopamine model of Parkinson's Disease using correlational tractography.

In recent years, tractography based on diffusion magnetic resonance imaging (dMRI) has become a popular tool for studying microstructural changes resulting from brain diseases like Parkinson's Disease (PD). Quantitative anisotropy (QA) is a parameter that is used in deterministic fiber tracking as a measure of connection between brain regions. It remains unclear, however, if microstructural changes caused by lesioning the median forebrain bundle (MFB) to create a Parkinsonian rat model can be resolved using tractography based on ex-vivo diffusion MRI. This study aims to fill this gap and enable future mechanistic research on structural changes of the whole brain network rodent models of PD. Specifically, it evaluated the ability of correlational tractography to detect structural changes in the MFB of 6-hydroxydopamine (6-OHDA) lesioned rats. The findings reveal that correlational tractography can detect structural changes in lesioned MFB and differentiate between the 6-OHDA and control groups. Imaging results are supported by behavioral and histological evidence demonstrating that 6-OHDA lesioned rats were indeed Parkinsonian. The results suggest that QA and correlational tractography is appropriate to examine local structural changes in rodent models of neurodegenerative disease. More broadly, we expect that similar techniques may provide insight on how disease alters structure throughout the brain, and as a tool to optimize therapeutic interventions.

Intramedullary disseminated sporotrichosis in an immunocompetent patient: case report and review of the literature.

BACKGROUND: Disseminated sporotrichosis is a severe opportunistic infection that often affects immunocompromised patients after a cutaneous inoculation. Here we present a rare case of disseminated sporotrichosis discovered as a solitary intramedullary thoracic spinal cord lesion in an immunocompetent patient. CASE DESCRIPTION: A 37-year-old man presented with progressive lower limb weakness and sensory changes over 1 week. A spinal magnetic resonance imaging (MRI) revealed a contrast-enhancing intramedullary lesion centered at T10. The patient was afebrile and reported no history of trauma or cutaneous lesions. The lesion was unresponsive to a trial of corticosteroids. A thoracic laminectomy was performed and a biopsy obtained. A cutaneous lesion on the arm was concurrently discovered, which was also biopsied. Both the skin and spinal cord biopsies showed Sporothrix schenckii by macroscopic and microscopic morphology which were later confirmed by MALDI-TOF mass spectrometry. CONCLUSION: This is a rare case of intramedullary disseminated sporotrichosis affecting the central nervous system of an immunocompetent patient. This unusual presentation should be taken into consideration when such intramedullary lesions are encountered.

Vagus nerve stimulation in the non-human primate: implantation methodology, characterization of nerve anatomy, target engagement and experimental applications.

BACKGROUND: Vagus nerve stimulation (VNS) is a FDA approved therapy regularly used to treat a variety of neurological disorders that impact the central nervous system (CNS) including epilepsy and stroke. Putatively, the therapeutic efficacy of VNS results from its action on neuromodulatory centers via projections of the vagus nerve to the solitary tract nucleus. Currently, there is not an established large animal model that facilitates detailed mechanistic studies exploring how VNS impacts the function of the CNS, especially during complex behaviors requiring motor action and decision making. METHODS: We describe the anatomical organization, surgical methodology to implant VNS electrodes on the left gagus nerve and characterization of target engagement/neural interface properties in a non-human primate (NHP) model of VNS that permits chronic stimulation over long periods of time. Furthermore, we describe the results of pilot experiments in a small number of NHPs to demonstrate how this preparation might be used in an animal model capable of performing complex motor and decision making tasks. RESULTS: VNS electrode impedance remained constant over months suggesting a stable interface. VNS elicited robust activation of the vagus nerve which resulted in decreases of respiration rate and/or partial pressure of carbon dioxide in expired air, but not changes in heart rate in both awake and anesthetized NHPs. CONCLUSIONS: We anticipate that this preparation will be very useful to study the mechanisms underlying the effects of VNS for the treatment of conditions such as epilepsy and depression, for which VNS is extensively used, as well as for the study of the neurobiological basis underlying higher order functions such as learning and memory.

Outcomes following conservative treatment of extension fractures in the setting of diffuse idiopathic skeletal hyperostosis: is external orthosis alone a reasonable option?

OBJECTIVE: Extension fractures in the setting of diffuse idiopathic skeletal hyperostosis (DISH) represent highly unstable injuries. As a result, these fractures are most frequently treated with immediate surgical fixation to limit any potential risk of associated neurological injury. Although this represents the standard of care, patients with significant comorbidities, advanced age, or medical instability may not be surgical candidates. In this paper, the authors evaluated a series of patients with extension DISH fractures who were treated with orthosis alone and evaluated their outcomes. METHODS: A retrospective review from 2015 to 2022 was conducted at a large level 1 trauma center. Patients with extension-type DISH fractures without neurological deficits were identified. All patients were treated conservatively with orthosis alone. Baseline patient characteristics and adverse outcomes are reported. RESULTS: Twenty-seven patients were identified as presenting with extension fractures associated with DISH without neurological deficit. Of these, 22 patients had complete follow-up on final chart review. Of these 22 patients, 21 (95.5%) were treated successfully with external orthosis. One patient (4.5%) who was noncompliant with the brace had an acute spinal cord injury 1 month after presentation, requiring immediate surgical fixation and decompression. No other complications, including skin breakdown or pressure ulcers related to bracing, were reported. CONCLUSIONS: Treatment of extension-type DISH fractures may be a reasonable option for patients who are not candidates for safe surgical intervention; however, a risk of neurological injury secondary to delayed instability remains, particularly if patients are noncompliant with the bracing regimen. This risk should be balanced against the high complication rate and potential mortality associated with surgical intervention in this patient population.

Computed Tomography Guidance for Percutaneous Glycerol Rhizotomy for Trigeminal Neuralgia.

BACKGROUND: Percutaneous glycerol rhizotomy (PGR) is a well-described treatment for trigeminal neuralgia; however, the technique in using surface landmarks and fluoroscopy has not drastically changed since being first introduced. In this paper, we describe a protocol for PGR using computed tomography (CT) guidance based on an experience of over 7 yr and 200 patients. OBJECTIVE: To introduce an approach for PGR using CT guidance and, in doing so, demonstrate possible benefits over the traditional fluoroscopic technique. METHODS: Using a standard CT scanner, patients are placed supine with head in extension. Barium paste and a CT scout image are used to identify and plan a trajectory to the foramen ovale. A laser localization system built into the CT scanner helps to guide placement of the spinal needle into the foramen ovale. The needle position in the foramen is confirmed with a short-sequence CT scan. RESULTS: CT-guided PGR provides multiple benefits over standard fluoroscopy, including improved visualization of the skull base and significant reduction in radiation exposure to the surgeon and staff. Side benefits include improved procedure efficiency, definitive imaging evidence of correct needle placement, and potentially increased patient safety. We have had no significant complications in over 200 patients. CONCLUSION: CT-guided PGR is a useful technique for treating trigeminal neuralgia based on better imaging of the skull base, better efficiency of the procedure, and elimination of radiation exposure for the surgeon and staff compared to traditional fluoroscopic based techniques.

Flexible, multichannel cuff electrode for selective electrical stimulation of the mouse trigeminal nerve.

The trigeminal nerve (cranial nerve V), along with other cranial nerves, has in recent years become a popular target for bioelectric medicine due to its direct access to neuromodulatory centers. Trigeminal nerve stimulation is currently being evaluated as an adjunctive treatment for various neurodegenerative and neuropsychiatric diseases despite the mechanism of action being in question. In this work, we describe the development and validation of a novel neural interface for the infraorbital branch of the trigeminal nerve utilizing a thin film (TF) nerve cuff containing multiple electrode sites allowing for more selective stimulation of the nerve. We characterized the properties of the device using electrochemical impedance spectroscopy, cyclic voltammetry, voltage excursions, and in vivo testing. Electrochemical measurements demonstrate that the platinum-based electrodes possess a capacitive charge carrying mechanism suitable for stimulation of biological tissue with a safe charge injection limit of 73.13 µC/cm2. In vivo stimulation experiments show that the TF cuff can reliably stimulate nerve targets eliciting cortical responses similar to a silicone cuff electrode. Furthermore, selecting different pairs of stimulation electrodes on the TF cuff modulated the magnitude and/or spatial pattern of cortical responses suggesting that the device may be able to selectively stimulate different parts of the nerve. These results suggest that the TF cuff is a viable neural interface for stimulation of the infraorbital branch of the trigeminal nerve that enables future research examining the therapeutic mechanisms of trigeminal nerve stimulation.

Strategies for interfacing with the trigeminal nerves in rodents for bioelectric medicine.

BACKGROUND: Bioelectric medicine seeks to modulate neural activity via targeted electrical stimulation to treat disease. Recent clinical evidence supports trigeminal nerve stimulation as a bioelectric treatment for several neurological disorders; however, the mechanisms of trigeminal nerve stimulation and potential side effects remain largely unknown. The goal of this study is to optimize the methodology and reproducibility of neural interface implantation for mechanistic studies in rodents. NEW METHOD(S): This article describes a single incision surgical approach to the infraorbital nerve of rats and mice and the supraorbital nerve in rats for trigeminal nerve stimulation studies. This article also presents the use of cortical evoked potentials and electromyography as methods for demonstrating effective engagement between the implanted electrode and target nerve. COMPARISON WITH EXISTING METHOD(S): A number of surgical approaches to the infraorbital nerve in rats exist, many of which are technically difficult. A simple, standardized approach to infraorbital nerve in rats and mice, as well as the supraorbital nerve of rats is integral to reproducibility of future trigeminal nerve stimulation studies. CONCLUSION: The infraorbital nerve of rats and mice can be easily accessed from a single dorsal incision on the bridge of the nose that avoids major anatomical structures such as the facial nerve. The supraorbital nerve is also accessible in rats from a single dorsal incision, but not mice due to size. Successful interfacing and engagement of the infra- and supraorbital nerves using the described methodology is demonstrated by recording of evoked cortical potentials and electromyography.

Progress in the Field of Micro-Electrocorticography.

Since the 1940s electrocorticography (ECoG) devices and, more recently, in the last decade, micro-electrocorticography (µECoG) cortical electrode arrays were used for a wide set of experimental and clinical applications, such as epilepsy localization and brain⁻computer interface (BCI) technologies. Miniaturized implantable µECoG devices have the advantage of providing greater-density neural signal acquisition and stimulation capabilities in a minimally invasive fashion. An increased spatial resolution of the µECoG array will be useful for greater specificity diagnosis and treatment of neuronal diseases and the advancement of basic neuroscience and BCI research. In this review, recent achievements of ECoG and µECoG are discussed. The electrode configurations and varying material choices used to design µECoG arrays are discussed, including advantages and disadvantages of µECoG technology compared to electroencephalography (EEG), ECoG, and intracortical electrode arrays. Electrode materials that are the primary focus include platinum, iridium oxide, poly(3,4-ethylenedioxythiophene) (PEDOT), indium tin oxide (ITO), and graphene. We discuss the biological immune response to µECoG devices compared to other electrode array types, the role of µECoG in clinical pathology, and brain⁻computer interface technology. The information presented in this review will be helpful to understand the current status, organize available knowledge, and guide future clinical and research applications of µECoG technologies.

Characterizing cortical responses evoked by electrical stimulation of the mouse infraorbital nerve.

In recent years, the trigeminal nerve (CN V) has become a popular target for neuromodulation therapies to treat of a variety of diseases due to its access to neuromodulatory centers. Despite promising preclinical and clinical data, the mechanism of action of trigeminal nerve stimulation (TNS) remains in question. In this work, we describe the development and evaluation of a neural interface targeting the mouse trigeminal nerve with the goal of enabling future mechanistic research on TNS. We performed experiments designed to evaluate the ability of a peripheral nerve interface (i.e. cuff electrode) to stimulate the infraorbital branch of the trigeminal nerve. We found that both artificial and naturalistic stimulation of the trigeminal nerve elicited robust cortical responses in the somatosensory cortex that scaled with increases in stimulus amplitude. These results suggest that an infraorbital nerve interface is a suitable candidate for examining the neural mechanisms of TNS in the mouse.

Neurovascular Compression at the Root Entry Zone Correlates with Trigeminal Neuralgia and Early Microvascular Decompression Outcome.

BACKGROUND: Trigeminal neurovascular contact (NVC) is hypothesized to be the etiology of classical trigeminal neuralgia (TGN). We aimed to seek a correlation between types of NVCs and the presence of TGN as well as early surgical outcome in patients with TGN treated with trigeminal microvascular decompression (MVD). METHODS: We blindly analyzed preoperative high-resolution magnetic resonance images with respect to the degree (none, "touch," or compression) and location of bilateral NVC in 57 retrospectively identified Burchiel Type 1 TGN patients treated by MVD. Location of NVC was noted as either at the root entry zone or distal to it. Using a logistic regression model, we assessed the degree and location of trigeminal NVC for correlation with the symptomatic side. Furthermore, the NVC characteristics on the symptomatic side were correlated with early postoperative pain relief. RESULTS: Although the degree and location of NVC were not statistically correlative independently, a combined interaction analysis of both statistically correlated with the symptomatic side and with early postoperative pain relief. CONCLUSIONS: We conclude that in TGN patients treated with MVD, magnetic resonance imaging identified neurovascular compression at the root entry zone (correlates with the affected side and early postoperative pain relief.

Awake Neurophysiologically Guided versus Asleep MRI-Guided STN DBS for Parkinson Disease: A Comparison of Outcomes Using Levodopa Equivalents.

BACKGROUND: Deep brain stimulation (DBS) for Parkinson's disease (PD) has traditionally been performed in awake patients. Some patients are unable to tolerate awake surgery or extensive time off their medication to allow for neurophysiological testing during traditional DBS implantation, which has previously limited surgical options for these patients. Recently, asleep image-guided lead placement using intraoperative MRI or CT for verification has been proposed as an alternative for patients unable or unwilling to undergo awake DBS surgery. METHODS: We conducted a retrospective chart review comparing PD patients who underwent asleep MRI-guided subthalamic nucleus (STN) DBS lead placement (n = 14) and awake neurophysiologically guided STN DBS lead placement (n = 23) at our institution. Both groups' levodopa equivalent daily doses (LEDDs) and complications at approximately 6 months of follow-up were compared, along with operative times. RESULTS: Both groups showed statistically similar reductions in LEDD at 6 months of therapy (38.27% for awake, 49.27% for asleep; p = 0.4447), and similar complications. Operative times were initially longer for MRI-guided DBS but improved with surgical experience. CONCLUSION: Asleep MRI-guided DBS is a viable option for PD patients unable or unwilling to undergo awake placement, with similar results in terms of LEDD reduction and complications.

Comparative effectiveness research in spine surgery.

Degenerative spine disorders are a significant cause of patient morbidity and are a prominent factor in healthcare costs in many countries. Pressure for healthcare cost control and the desire for improved outcomes have led to an expanding emphasis on evidence-based medicine methodologies in spine research. Determination of the optimal treatment paradigm for many common degenerative spinal disorders has proven difficult and comparative effectiveness research is increasingly being employed to examine these clinical dilemmas. The Swedish Spine Registry and the Registry of the Scoliosis Research Society are two of the long-standing databases compiling data for spine patients. Spine surgery professional organizations have recently taken a prominent role in assembling procedural- and diagnosis-based registries, specifically addressing therapeutic outcomes for spine patients. As healthcare systems continue to evolve, comparative effectiveness research driven by spine registries may better elucidate the appropriate clinical choices for patients with these challenging illnesses.

Progressive severe kyphosis as a complication of multilevel cervical percutaneous facet neurotomy: a case report.

BACKGROUND CONTEXT: Percutaneous facet neurotomy is a procedure commonly used for the treatment of pain thought to originate from zygoapophyseal joint dysfunction. Some practitioners have also used this technique to treat cervicogenic headache. Previously reported complications for this procedure have been minimal and have included dysthesias and local pain. STUDY DESIGN: Case report. METHODS: Bilateral multilevel cervical percutaneous facet neurotomies were used to treat a patient suffering from a chronic headache and neck pain that had failed to respond to extensive medical management. RESULTS: Within days of completing the bilateral facet neurotomies, the patient developed head drop. Subsequent electromyography revealed denervation of the patient's paraspinous muscles. Initially the patient was managed conservatively in a cervical collar with the hope that he would recover some function. After few years, the patient developed fixed kyphotic deformity. Correction of the patient's deformity required multilevel anterior cervical discectomy and fusion followed by posterior instrumented fusion. CONCLUSIONS: When performing multilevel percutaneous cervical facet neurotomies, there is a risk of paraspinous muscle denervation, and subsequent kyphotic deformity may occur. The likelihood of this rare and previously unreported complication can probably be reduced by proper needle positioning and by minimizing the number of levels at which the procedure is performed.