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.

The Effective Use of Laser Ablation to Treat Mesial Temporal Lobe Epilepsy in the Setting of Implanted Responsive Neurostimulation.

BACKGROUND: Up to 16% of patients with responsive neurostimulation (RNS) implants for bilateral temporal epilepsy are found to have seizures originating mainly from just 1 lobe. OBJECTIVE: To describe the first use of laser interstitial thermal therapy (LITT) in a patient with a bilateral RNS implant to ablate the predominant temporal lobe and help control seizures. METHODS: A 55-year-old woman treated for temporal lobe epilepsy with conflicting information regarding lateralization underwent RNS implantation. She was then discovered to have seizures with electrographic onset nearly all from the right amygdala and hippocampus. She was offered LITT to ablate the affected region in the right temporal lobe, followed by reimplantation of the RNS lead in the remnant of the right hippocampal tail. RESULTS: Despite the positioning of the RNS ferrule on the operative side and the depth electrode in the contralateral lobe, we observed no significant artifact and obtained stable LITT temperature mapping using magnetic resonance. Laser ablation and RNS device replacement proceeded without complications. The patient has remained seizure-free for 6 months since the ablation in the setting of weaning antiseizure medications and regaining ambulation. CONCLUSION: LITT ablation can safely and effectively be performed in a patient with a concurrent RNS implant. Maintenance of the RNS device after ablation allows for continual detection and management of seizures.

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.

Dexmedetomidine depresses neuronal activity in the subthalamic nucleus during deep brain stimulation electrode implantation surgery.

Background: Micro-electrode recordings are often necessary during electrode implantation for deep brain stimulation of the subthalamic nucleus. Dexmedetomidine may be a useful sedative for these procedures, but there is limited information regarding its effect on neural activity in the subthalamic nucleus and on micro-electrode recording quality. Methods: We recorded neural activity in five patients undergoing deep brain stimulation implantation to the subthalamic nucleus. Activity was recorded after subthalamic nucleus identification while patients received dexmedetomidine sedation (loading - 1 µg kg-1 over 10-15 min, maintenance - 0.7 µg kg-1 h-1). We compared the root-mean square (RMS) and beta band (13-30 Hz) oscillation power of multi-unit activity recorded by microelectrode before, during and after recovery from dexmedetomidine sedation. RMS was normalised to values recorded in the white matter. Results: Multi-unit activity decreased during sedation in all five patients. Mean normalised RMS decreased from 2.8 (1.5) to 1.6 (1.1) during sedation (43% drop, p = 0.056). Beta band power dropped by 48.4%, but this was not significant (p = 0.15). Normalised RMS values failed to return to baseline levels during the time allocated for the study (30 min). Conclusions: In this small sample, we demonstrate that dexmedetomidine decreases neuronal firing in the subthalamic nucleus as expressed in the RMS of the multi-unit activity. As multi-unit activity is a factor in determining the subthalamic nucleus borders during micro-electrode recordings, dexmedetomidine should be used with caution for sedation during these procedures. Clinical trial number: NCT01721460.

Correction to: Ancestral Folate Promotes Neuronal Regeneration in Serial Generations of Progeny.

The original version of this article unfortunately contained error in Figure 4a to where some of the text was overlapping.

Ancestral Folate Promotes Neuronal Regeneration in Serial Generations of Progeny.

Folate supplementation in F0 mating rodents increases regeneration of injured spinal axons in vivo in 4 or more generations of progeny (F1-F4) in the absence of interval folate administration to the progeny. Transmission of the enhanced regeneration phenotype to untreated progeny parallels axonal growth in neuron culture after in vivo folate administration to the F0 ancestors alone, in correlation with differential patterns of genomic DNA methylation and RNA transcription in treated lineages. Enhanced axonal regeneration phenotypes are observed with diverse folate preparations and routes of administration, in outbred and inbred rodent strains, and in two rodent genera comprising rats and mice, and are reversed in F4-F5 progeny by pretreatment with DNA demethylating agents prior to phenotyping. Uniform transmission of the enhanced regeneration phenotype to progeny together with differential patterns of DNA methylation and RNA expression is consistent with a non-Mendelian mechanism. The capacity of an essential nutritional co-factor to induce a beneficial transgenerational phenotype in untreated offspring carries broad implications for the diagnosis, prevention, and treatment of inborn and acquired disorders.

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.

Use of a Laryngeal Mask Airway Decreases Radiation Exposure During Computed Tomography-Guided Percutaneous Glycerol Rhizotomy for Trigeminal Neuralgia.

BACKGROUND: We have been using computed tomography (CT) guidance for percutaneous glycerol rhizotomy (PGR) for the last 7 years. As a quality improvement exercise, we recently began using general anesthesia (GA) with the use of a laryngeal mask airway (LMA) because of our perception that the procedure went faster and that there was less radiation exposure because of less patient movement. We aim to compare PGR radiation exposure and procedural time between patients receiving local anesthetic with sedation and those receiving GA/LMA. METHODS: A single-center historical cohort study was performed using patients treated with PGR between 2017 and 2019. Ninety-two surgeries were conducted during the study period: 64 surgeries had local anesthetic with intravenous sedation, and 28 surgeries had deeper anesthetic with LMA. Data analyzed included the number of CT sequences obtained, needle placement time, and total radiation dose. RESULTS: Use of GA/LMA resulted in a 23% decrease in mean radiation dose (565.5 vs. 436.1 µGy × cm, P = 0.014), number of CT sequences required (7.4 vs. 5.7, P = 0.003), and needle placement time (12.8 vs. 9.8 minutes, P = 0.006). Additionally, 10 patients underwent multiple glycerol rhizotomies during the collection period with both anesthetic types being used at least once. Seven of 10 patients (70.0%) had a reduction in total radiation dose, number of CT sequences obtained, and needle placement time when GA/LMA was used. There were no procedure- or anesthetic-related complications in this patient cohort. CONCLUSIONS: The use of GA/LMA during PGR is associated with decreased radiation exposure without increased anesthetic complications.

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.

Deep Brain Stimulation for Treatment of Tremor.

Deep brain stimulation is now the most common surgical treatment of tremor. Tremor can be classified as action or resting tremor and is one of the most common movement disorders. Initial treatment of tremor should focus on medical treatment but, if patients fail medical therapy, deep brain stimulation should be considered with likely success. The usual target is the ventral intermediate nucleus of the thalamus. Common side effects of treatment include paresthesias, dysarthria, and less often ataxia. Future directions of research and development, including directional leads and closed-loop stimulation, may eventually lead to additional improvement in patient outcomes.

Intrathecal Baclofen Infusion for the Treatment of Movement Disorders.

Intrathecal baclofen infusion is an accepted treatment for spasticity. Evidence also exists for the treatment of secondary generalized dystonia with intrathecal baclofen infusion. Benefits include decreased tone, improved positioning, and decreased decubitus ulcers. Despite these benefits, there are significant complications that can occur with this therapy, including drug withdrawal, catheter infection, drug overdose, failure, and pump failure. In some cases, practitioners encourage a trial dose of intrathecal baclofen by injection or catheter infusion before pump implantation. To improve patient selection and outcomes many centers offering intrathecal baclofen therapy use a multidisciplinary team composed of physicians, surgeons, and physical therapists.

Nerve Stimulation for Pain.

Nerve stimulation is a reversible technique that is used successfully for the treatment of traumatic neuropathic pain, complex regional pain syndrome, and craniofacial neuropathic pain. Nerve field stimulation targets painful regions rather than a single nerve and has expanded indications, including axial low back pain. Appropriate patient education and motivation are crucial prior to surgery. Ongoing research is necessary to provide high-level evidence for the use of nerve stimulation. Most electrodes are primarily designed for spinal cord stimulation, hence the need to develop nerve electrodes dedicated for nerve stimulation.

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.

Subpectoral Implantation of Internal Pulse Generators for Deep Brain Stimulation: Technical Note for Improved Cosmetic Outcomes.

BACKGROUND: Deep brain stimulation is increasingly used to treat a variety of disorders. As the prevalence of this technology increases, greater demands are placed on neurosurgical practitioners to improve cosmetic results, maximize patient comfort, and minimize complication rates. We have increasingly employed subpectoral implantation of internal pulse generators (IPGs) to improve patient satisfaction. OBJECTIVE: To determine the complication rates of subpectorally placed IPGs as compared to those placed in a subcutaneous location. METHODS: We reviewed a series of 301 patients from a single institution. Complication rates including infection, hematoma, and lead fracture were recorded. Rates were compared for subcutaneously and subpectorally located devices. RESULTS: Of the records reviewed, we found 301 patients who underwent 308 procedures for initial IPG implantation. Of these, 275 were subpectoral IPG implantation, 19 were infraclavicular subcutaneous implantation, and 14 were subcutaneous implantation in the abdomen. A total of 6 IPG pocket infections occurred, 2 subpectoral and 4 infraclavicular subcutaneous. Of the IPG infections, 2 of the infraclavicular subcutaneous devices had associated erosions. Two patients had their devices relocated from a subpectoral pocket to a subcutaneous pocket in the abdomen due to discomfort. Two patients in the subpectoral group suffered from hematoma requiring evacuation. Two patients in the infraclavicular subcutaneous group had lead fracture occur. CONCLUSIONS: Subpectoral implantation of deep brain stimulation IPGs is a viable alternative with a low complication rate. This technique may offer a lower rate of infection and wound erosion.

Fabrication and utility of a transparent graphene neural electrode array for electrophysiology, in vivo imaging, and optogenetics.

Transparent graphene-based neural electrode arrays provide unique opportunities for simultaneous investigation of electrophysiology, various neural imaging modalities, and optogenetics. Graphene electrodes have previously demonstrated greater broad-wavelength transmittance (∼90%) than other transparent materials such as indium tin oxide (∼80%) and ultrathin metals (∼60%). This protocol describes how to fabricate and implant a graphene-based microelectrocorticography (µECoG) electrode array and subsequently use this alongside electrophysiology, fluorescence microscopy, optical coherence tomography (OCT), and optogenetics. Further applications, such as transparent penetrating electrode arrays, multi-electrode electroretinography, and electromyography, are also viable with this technology. The procedures described herein, from the material characterization methods to the optogenetic experiments, can be completed within 3-4 weeks by an experienced graduate student. These protocols should help to expand the boundaries of neurophysiological experimentation, enabling analytical methods that were previously unachievable using opaque metal-based electrode arrays.