Glioma-Induced Alterations in Excitatory Neurons are Reversed by mTOR Inhibition.

Gliomas are highly aggressive brain tumors characterized by poor prognosis and composed of diffusely infiltrating tumor cells that intermingle with non-neoplastic cells in the tumor microenvironment, including neurons. Neurons are increasingly appreciated as important reactive components of the glioma microenvironment, due to their role in causing hallmark glioma symptoms, such as cognitive deficits and seizures, as well as their potential ability to drive glioma progression. Separately, mTOR signaling has been shown to have pleiotropic effects in the brain tumor microenvironment, including regulation of neuronal hyperexcitability. However, the local cellular-level effects of mTOR inhibition on glioma-induced neuronal alterations are not well understood. Here we employed neuron-specific profiling of ribosome-bound mRNA via 'RiboTag,' morphometric analysis of dendritic spines, and in vivo calcium imaging, along with pharmacological mTOR inhibition to investigate the impact of glioma burden and mTOR inhibition on these neuronal alterations. The RiboTag analysis of tumor-associated excitatory neurons showed a downregulation of transcripts encoding excitatory and inhibitory postsynaptic proteins and dendritic spine development, and an upregulation of transcripts encoding cytoskeletal proteins involved in dendritic spine turnover. Light and electron microscopy of tumor-associated excitatory neurons demonstrated marked decreases in dendritic spine density. In vivo two-photon calcium imaging in tumor-associated excitatory neurons revealed progressive alterations in neuronal activity, both at the population and single-neuron level, throughout tumor growth. This in vivo calcium imaging also revealed altered stimulus-evoked somatic calcium events, with changes in event rate, size, and temporal alignment to stimulus, which was most pronounced in neurons with high-tumor burden. A single acute dose of AZD8055, a combined mTORC1/2 inhibitor, reversed the glioma-induced alterations on the excitatory neurons, including the alterations in ribosome-bound transcripts, dendritic spine density, and stimulus evoked responses seen by calcium imaging. These results point to mTOR-driven pathological plasticity in neurons at the infiltrative margin of glioma - manifested by alterations in ribosome-bound mRNA, dendritic spine density, and stimulus-evoked neuronal activity. Collectively, our work identifies the pathological changes that tumor-associated excitatory neurons experience as both hyperlocal and reversible under the influence of mTOR inhibition, providing a foundation for developing therapies targeting neuronal signaling in glioma.

Case report: MR-guided laser induced thermal therapy for palliative cingulotomy.

In end-stage cancer, oncologic pain refractory to medical management significantly reduces patients' quality of life. In recent years, ablative surgery has seen a resurgence in treating diffuse and focal cancer pain in terminal patients. The anterior cingulate gyrus has been a key focus as it plays a role in the cognitive and emotional processing of pain. While radiofrequency ablation of the dorsal anterior cingulate is well described for treating cancer pain, MRI-guided laser-induced thermal therapy (LITT) is novel. Our paper describes a patient treated with an MRI-guided LITT therapy of the anterior cingulate gyrus for intractable debilitating pain secondary to terminal metastatic cancer.

Neuroablative central lateral thalamotomy for chronic neuropathic pain.

Chronic neuropathic pain refractory to medical management can be debilitating and can seriously affect one's quality of life. The interest of ablative surgery for the treatment or palliation of chronic neuropathic pain, cancer-related or chemotherapy-induced, has grown. Numerous regions along the nociceptive pathways have been prominent targets including the various nuclei of the thalamus. Traditional targets include the medial pulvinar, central median, and posterior complex thalamic nuclei. However, there has been little research regarding the role of the central lateral nucleus. In this paper, we aim to summarize the anatomy, pathophysiology, and patient experiences of the central lateral thalamotomy.

Recurrent liponeurocytoma: A case report and systematic review of the literature.

Background: Liponeurocytomas are rare neurocytic neoplasms that most often arise in the posterior fossa and affect individuals in the third and fifth decades of life. Most reported cases of this unique tumor in the literature have described a favorable clinical prognosis without recurrence. However, increasing reports of recurrent cases prompted the World Health Organization, in 2016, to recategorize the tumor from Grade I to the less favorable Grade II classification. We conducted a systematic review to identify recurrent cases of this unique tumor and to summarize differences between the primary and recurrent cases of liponeurocytoma. Methods: A systematic review exploring recurrent liponeurocytoma cases was conducted by searching the PubMed, Google Scholar, and Scopus databases for articles in English. Abstracts from articles were read and selected for full-text review according to a priori criteria. Relevant full-text articles were analyzed for symptoms, imaging, location, histological, pathological, treatment, and recurrence-free time between the primary and recurrent cases. Results: Of 4392 articles, 15 articles accounting for 18 patients were included (level of evidence: IV) in the study. Recurrence-free time decreased from an average of 82 months between the primary tumor resection to first recurrence to 31.3 months between the first and second recurrence. Recurrent tumors demonstrated increased pleomorphic neural cells, necrosis, vascular proliferation, and MIB-1 index when compared to the primary tumor. Several cases also demonstrated decreased lipidizing components when compared to the primary tumor, further indicating increased dedifferentiation. The primary treatment for this tumor was surgical resection with occasional adjunctive radiotherapy. Conclusion: Recurrent cases of liponeurocytoma have features of increased malignant proliferation compared to the primary cases. The standard treatment for these primary and recurrent tumors is gross total resection. The role of adjunctive radiotherapy remains a matter of debate.

Ablation Procedures.

Although ablation has a limited role in the management of chronic noncancer pain, ablation continues to help patients with treatment of refractory cancer-related pain. Interdisciplinary treatment involving supportive care, pain medicine, oncology, and neurosurgery is critical to optimizing the timing and outcome of neurosurgical ablative options for pain management. In this review, 3 targets for ablative surgery-the spinothalamic tract, the dorsal column's visceral pain pathway, and the anterior cingulate cortex-are discussed with a focus on patient selection and key aspects of surgical technique.

Intraoperative valence testing to adjudicate between ventral capsule/ventral striatum and bed nucleus of the stria terminalis target selection in deep brain stimulation for obsessive-compulsive disorder.

OBJECTIVE: Deep brain stimulation (DBS) is an accepted therapy for severe, treatment-refractory obsessive-compulsive disorder (trOCD). The optimal DBS target location within the anterior limb of the internal capsule, particularly along the anterior-posterior axis, remains elusive. Empirical evidence from several studies in the past decade has suggested that the ideal target lies in the vicinity of the anterior commissure (AC), either just anterior to the AC, above the ventral striatum (VS), or just posterior to the AC, above the bed nucleus of the stria terminalis (BNST). Various methods have been utilized to optimize target selection for trOCD DBS. The authors describe their practice of planning trajectories to both the VS and BNST and adjudicating between them with awake intraoperative valence testing to individualize permanent target selection. METHODS: Eight patients with trOCD underwent awake DBS with trajectories planned for both VS and BNST targets bilaterally. The authors intraoperatively assessed the acute effects of stimulation on mood, energy, and anxiety and implanted the trajectory with the most reliable positive valence responses and least stimulation-induced side effects. The method of intraoperative target adjudication is described, and the OCD outcome at last follow-up is reported. RESULTS: The mean patient age at surgery was 41.25 ± 15.1 years, and the mean disease duration was 22.75 ± 10.2 years. The median preoperative Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score was 39 (range 34-40). Two patients had previously undergone capsulotomy, with insufficient response. Seven (44%) of 16 leads were moved to the second target based on intraoperative stimulation findings, 4 of them to avoid strong negative valence effects. Three patients had an asymmetric implant (1 lead in each target). All 8 patients (100%) met full response criteria, and the mean Y-BOCS score reduction across the full cohort was 51.2% ± 12.8%. CONCLUSIONS: Planning and intraoperatively testing trajectories flanking the AC-superjacent to the VS anteriorly and to the BNST posteriorly-allowed identification of positive valence responses and acute adverse effects. Awake testing helped to select between possible trajectories and identify individually optimized targets in DBS for trOCD.

Electroceutically induced subthalamic high-frequency oscillations and evoked compound activity may explain the mechanism of therapeutic stimulation in Parkinson's disease.

Despite having remarkable utility in treating movement disorders, the lack of understanding of the underlying mechanisms of high-frequency deep brain stimulation (DBS) is a main challenge in choosing personalized stimulation parameters. Here we investigate the modulations in local field potentials induced by electrical stimulation of the subthalamic nucleus (STN) at therapeutic and non-therapeutic frequencies in Parkinson's disease patients undergoing DBS surgery. We find that therapeutic high-frequency stimulation (130-180 Hz) induces high-frequency oscillations (~300 Hz, HFO) similar to those observed with pharmacological treatment. Along with HFOs, we also observed evoked compound activity (ECA) after each stimulation pulse. While ECA was observed in both therapeutic and non-therapeutic (20 Hz) stimulation, the HFOs were induced only with therapeutic frequencies, and the associated ECA were significantly more resonant. The relative degree of enhancement in the HFO power was related to the interaction of stimulation pulse with the phase of ECA. We propose that high-frequency STN-DBS tunes the neural oscillations to their healthy/treated state, similar to pharmacological treatment, and the stimulation frequency to maximize these oscillations can be inferred from the phase of ECA waveforms of individual subjects. The induced HFOs can, therefore, be utilized as a marker of successful re-calibration of the dysfunctional circuit generating PD symptoms.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Neuroablative Procedures for Patients With Cancer Pain.

BACKGROUND: Managing cancer pain once it is refractory to conventional treatment continues to challenge caregivers committed to serving those who are suffering from a malignancy. Although neuromodulation has a role in the treatment of cancer pain for some patients, these therapies may not be suitable for all patients. Therefore, neuroablative procedures, which were once a mainstay in treating intractable cancer pain, are again on the rise. This guideline serves as a systematic review of the literature of the outcomes following neuroablative procedures. OBJECTIVE: To establish clinical practice guidelines for the use of neuroablative procedures to treat patients with cancer pain. METHODS: A systematic review of neuroablative procedures used to treat patients with cancer pain from 1980 to April 2019 was performed using the United States National Library of Medicine PubMed database, EMBASE, and Cochrane CENTRAL. After inclusion criteria were established, full text articles that met the inclusion criteria were reviewed by 2 members of the task force and the quality of the evidence was graded. RESULTS: In total, 14 646 relevant abstracts were identified by the literature search, from which 189 met initial screening criteria. After full text review, 58 of the 189 articles were included and subdivided into 4 different clinical scenarios. These include unilateral somatic nociceptive/neuropathic body cancer pain, craniofacial cancer pain, midline subdiaphragmatic visceral cancer pain, and disseminated cancer pain. Class II and III evidence was available for these 4 clinical scenarios. Level III recommendations were developed for the use of neuroablative procedures to treat patients with cancer pain. CONCLUSION: Neuroablative procedures may be an option for treating patients with refractory cancer pain. Serious adverse events were reported in some studies, but were relatively uncommon. Improved imaging, refinements in technique and the availability of new lesioning modalities may minimize the risks of neuroablation even further.The full guidelines can be accessed at https://www.cns.org/guidelines/browse-guidelines-detail/guidelines-on-neuroablative-procedures-patients-wi.

Ambulatory neurosurgery in the COVID-19 era: patient and provider satisfaction with telemedicine.

OBJECTIVE: Telemedicine has rapidly expanded in the recent years as technologies have afforded healthcare practitioners the ability to diagnose and treat patients remotely. Due to the COVID-19 pandemic, nonessential clinical visits were greatly limited, and much of the outpatient neurosurgical practice at the authors' institution was shifted quickly to telehealth. Although there are prior data suggesting that the use of telemedicine is satisfactory in other surgical fields, data in neurosurgery are limited. This study aimed to investigate both patient and provider satisfaction with telemedicine and its strengths and limitations in outpatient neurosurgery visits. METHODS: This quality improvement study was designed to analyze provider and patient satisfaction with telemedicine consultations in an outpatient neurosurgery clinic setting at a tertiary care, large-volume, academic center. The authors designed an 11-question survey for neurosurgical providers and a 13-question survey for patients using both closed 5-point Likert scale responses and multiple choice responses. The questionnaires were administered to patients and providers during the period when the clinic restricted in-person visits. At the conclusion of the study, the overall data were analyzed qualitatively and quantitatively. RESULTS: During the study period, 607 surveys were sent out to patients seen by telehealth at the authors' academic center, and 122 responses were received. For the provider survey, 85 surveys were sent out to providers at the authors' center and other academic centers, and 40 surveys were received. Ninety-two percent of patients agreed or strongly agreed that they were satisfied with that particular telehealth visit. Eighty-eight percent of patients agreed that their telehealth visit was more convenient for them than an in-person visit, but only 36% of patients stated they would like their future visits to be telehealth. Sixty-three percent of providers agreed that telehealth visits were more convenient for them than in-person visits, and 85% of responding providers stated that they wished to incorporate telehealth into their future practice. CONCLUSIONS: Although the authors' transition to telehealth was both rapid and unexpected, most providers and patients reported positive experiences with their telemedicine visits and found telemedicine to be an effective form of ambulatory neurosurgical care. Not all patients preferred telemedicine visits over in-person visits, but the high satisfaction with telemedicine by both providers and patients is promising to the future expansion of telehealth in ambulatory neurosurgery.

Percutaneous Computed Tomography-Guided Radiofrequency Ablation of Spinal Trigeminal Tract and Nucleus Caudalis for Refractory Trigeminal Neuropathic Pain: 2-Dimensional Operative Video.

This is a surgical video of a computed tomography (CT)-guided percutaneous radiofrequency ablation of the spinal trigeminal tract and nucleus caudalis for refractory trigeminal neuropathic pain.1,2 Many have contributed historically, among them, Sjoqvist3 in 1938 first described destruction of the descending medullary trigeminal tractus via open craniotomy.3-6 In 1967 and 1968, Crue7 and Hitchcock8 independently developed a percutaneous tractotomy technique. Although Kanpolat9,10 first described the use of CT imaging for percutaneous creation of a single tractotomy/nucleotomy lesion resulting in satisfactory pain relief for 85% of patients. The spinal trigeminal tract is a descending fiber pathway containing central processes of first-order afferent neurons from cranial nerves V, VII, IX, and X. The spinal trigeminal nucleus is the terminal projection of the spinal trigeminal tract comprised of 3 subnuclei: oralis, interpolaris, and caudalis. The nucleus caudalis is the most caudal of the 3 subdivisions of the spinal trigeminal nucleus and houses the cell bodies of second-order afferent neurons critical in nociception of the face. Lesioning of the spinal trigeminal tract and nucleus caudalis can provide pain relief without affecting facial sensation or trigeminal motor function.9,11-13 Percutaneous radiofrequency ablation is performed using anatomical landmarks, serial CT scans, impedance monitoring, and functional confirmation to ensure appropriate insertion of the probe to the target of interest prior to lesioning. This procedure remains uncommon in current practices even among functional neurosurgery pain specialists but offers a low-risk, minimally invasive treatment option for refractory facial pain.14 This procedure was done under Institutional Review Board guidance (H-41228: retrospective chart review of patients undergoing spine surgery for pain). The risks and benefits were explained, and the patient consented to videography/procedure. Images in the video used with permission from the following: Carter HV. Anatomy of the Human Body. Wikimedia Commons [Public Domain]. https://commons.wikimedia.org/wiki/File:Gray698.png. Published 1918. Accessed June 30, 2019; Carter HV. Anatomy of the Human Body. Wikimedia Commons [Public Domain]. https://commons.wikimedia.org/wiki/File:Gray784.png. Published 1918. Accessed June 30, 2019; Reprinted from Kanpolat Y, Kahilogullari G, Ugur HC, Elhan AH, CT-guided percutaneous trigeminal tractotomy-nucleotomy, Neurosurgery, 2008, 63(1 Suppl 1), ONS147-53; discussion ONS153-5, by permission of the Congress of Neurological Surgeons; Madhero88. Onion Distribution of Pain and Temperature Sense by Trigeminal Nerve. Wikimedia Commons [Creative Commons BY 3.0 license]. https://en.wikipedia.org/wiki/File:Onionskinddistribution.svg#/media/File:Onionskinddistribution.svg. Accessed June 30, 2019.

Cordotomy for Intractable Cancer Pain: A Narrative Review.

BACKGROUND: Cordotomy is an invasive procedure for the management of intractable pain not controlled by conventional therapies, such as analgesics or nerve block. This procedure involves mechanical disruption of nociceptive pathways in the anterolateral column, specifically the spinothalamic and spinoreticular pathways to relieve pain while preserving fine touch and proprioceptive tracts. OBJECTIVES: The purpose of this review article is to refresh our knowledge of cordotomy and support its continued use in managing intractable pain due to malignant disease. STUDY DESIGN: This is a review article with the goal of reviewing and summarizing the pertinent case reports, case series, retrospective studies, prospective studies, and review articles published from 2010 onward on spinal cordotomy. SETTING: The University of Texas, MD Anderson Cancer Center. METHODS: PubMed search of keywords "spinal cordotomy," "percutaneous cordotomy," or "open cordotomy" was undertaken. Search results were organized by year of publication. RESULTS: Cordotomy can be performed via percutaneous, open, endoscopic, or transdiscal approach. Percutaneous image-guided approach is the most well-studied and reported technique compared with others, with relatively good pain improvement both in the postoperative and short-term period. The use of open cordotomy has diminished significantly in recent years because of the advent of other less invasive approaches. Cordotomy in children, although rare, has been described in some case reports and case series with reported pain improvement postprocedure. Although complications can vary broadly, some reported side effects include ataxia and paresis due to lesion in the spinocerebellar/corticospinal tract; respiratory failure due to lesion in the reticulospinal tract; or sympathetic dysfunction, bladder dysfunctions, or Horner syndrome due to unintentional lesions in the spinothalamic tract. LIMITATIONS: Review article included literature published only in English. For the studies reviewed, the sample size was relatively small and the patient population was heterogeneous (in terms of underlying disease process, duration of symptoms, previous treatment attempted and length of follow-up). CONCLUSIONS: Cordotomy results in selective loss of pain and temperature perception on the contralateral side, up to several segments below the level of the disruption. The plethora of analgesics available and advanced technologies have reduced the demand for cordotomy in the management of intractable pain. However, some patients with pain unresponsive to medical and procedural management, particularly malignant pain, may benefit from this procedure, and it is a viable treatment option especially for patients with a limited life expectancy whose severe, unilateral pain is unresponsive to analgesic medications. KEY WORDS: Cancer pain, cordotomy complications, cordotomy indications, intractable pain, open cordotomy, percutaneous cordotomy.

Subthalamic Single Cell and Oscillatory Neural Dynamics of a Dyskinetic Medicated Patient With Parkinson's Disease.

Single cell neuronal activity (SUA) and local field potentials (LFP) in the subthalamic nucleus (STN) of unmedicated Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) surgery have been well-characterized during microelectrode recordings (MER). However, there is limited knowledge about the changes in the firing patterns and oscillations above and within the territories of STN after the intake of dopaminergic medication. Here, for the first time, we report the STN single cell and oscillatory neural dynamics in a medicated patient with idiopathic PD using intraoperative MER. We recorded LFP and SUA with microelectrodes at various depths during bilateral STN-DBS electrode implantation. We isolated 26 neurons in total and observed that tonic and irregular firing patterns of individual neurons predominated throughout the territories of STN. While burst-type firings have been well-characterized in the dorsal territories of STN in unmedicated patients, interestingly, this activity was not observed in our medicated subject. LFP recordings lacked the excessive beta (8-30 Hz) activity, characteristic of the unmedicated state and signal energy was mainly dominated by slow oscillations below 8 Hz. We observed sharp gamma oscillations between 70 and 90 Hz within and above the STN. Despite the presence of a broadband high frequency activity in 200-400 Hz range, no cross-frequency interaction in the form of phase-amplitude coupling was noted between low and high frequency oscillations of LFPs. While our results are in agreement with the previously reported LFP recordings from the DBS lead in medicated PD patients, the sharp gamma peak present throughout the depth recordings and the lack of bursting firings after levodopa intake have not been reported before. The lack of bursting in SUA, the lack of excessive beta activity and cross frequency coupling between HFOs and lower rhythms further validate the link between bursting firing regime of neurons and pathological oscillatory neural activity in PD-STN. Overall, these observations not only validate the existing literature on the PD electrophysiology in healthy/medicated animal models but also provide insights regarding the underlying electro-pathophysiology of levodopa-induced dyskinesias in PD patients through demonstration of multiscale relationships between single cell firings and field potentials.

Percutaneous Cordotomy for Pain Palliation in Advanced Cancer: A Randomized Clinical Trial Study Protocol.

BACKGROUND: Cancer pain, one of the most common symptoms for patients with advanced cancer, is often refractory to maximal medical therapy. A controlled clinical trial is needed to provide definitive evidence to support the use of ablative procedures such as cordotomy for patients with medically refractory cancer pain. OBJECTIVE: To assess the efficacy of cordotomy for patients with unilateral advanced cancer pain using a controlled clinical trial study design. The secondary objectives are to define the patient experience of cordotomy for medically refractory cancer pain as well as to determine the utility of magnetic resonance imaging as a non-invasive biomarker for successful cordotomy. METHODS: We will undertake a single-institution, double-blind, sham-controlled clinical trial of cordotomy in patients with refractory cancer pain. Patients in the cordotomy arm will undergo a percutaneous computed tomography-guided cordotomy at C1-C2, while patients in the control arm will undergo a similar procedure where the needle will not penetrate the thecal sac. The primary endpoint will be the reduction in pain intensity, as measured by the Edmonton Symptoms Assessment Scale. EXPECTED OUTCOMES: We expect that patients randomized to cordotomy will have a significantly greater reduction in pain intensity than those patients randomized to the control surgical intervention. DISCUSSION: This randomized clinical trial comparing cordotomy with a control intervention will provide the level of evidence necessary to determine whether cordotomy should be the standard of care intervention for patients with advanced cancer pain.

Magnetic Resonance-Based Radiomic Analysis of Radiofrequency Lesion Predicts Outcomes After Percutaneous Cordotomy: A Feasibility Study.

BACKGROUND: To date, there is limited data on evaluation of the cordotomy lesion and predicting clinical outcome. OBJECTIVE: To evaluate the utility of magnetic resonance (MR)-based radiomic analysis to quantify microstructural changes created by the cordotomy lesion and predict outcome in patients undergoing percutaneous cordotomy for medically refractory cancer pain. METHODS: This is a retrospective interpretation of prospectively acquired data in 10 patients (5 males, age range 43-76 yr) who underwent percutaneous computed tomography-guided high cervical cordotomy for medically refractory cancer pain between 2015 and 2016. All patients underwent magnetic resonance imaging (MRI) of the cordotomy lesion on postoperative day 1. After segmentation of T2-weighted images, 310 radiomic features were extracted. Pain outcomes were recorded on postoperative day 1 and day 7 using the visual analog scale. R software was used to build statistical models based on MRI radiomic features for prediction of pain outcomes. RESULTS: A total of 20 relevant radiomic features were identified using the maximum relevance minimum redundanc method. Radiomics predicted postoperative day 1 pain scores with an accuracy of 90% (P = .046), 100% sensitivity, 75% specificity, 85.7% positive predictive value, and 100% negative predictive value. The radiomics model also predicted if the postoperative day 1 pain score was sustained on postoperative day 7 with an accuracy of 100% (P = .028), 100% sensitivity, 100% specificity, and 100% positive and negative predictive value. CONCLUSION: MR-based radiomic analysis of the cordotomy lesion was predictive of pain outcomes at 1 wk after percutaneous cordotomy for intractable cancer pain.

Stereotactic Radiosurgery Hypophysectomy for Palliative Treatment of Refractory Cancer Pain: A Historical Review and Update.

Medically refractory pain in those with advanced cancer significantly reduces one's quality of life. Therefore, palliative interventions to mitigate cancer pain and reduce opioid requirements are necessary to reduce patient suffering and opioid-induced side effects. Hypophysectomy, a largely forgotten pain procedure with several technical variations, has been repeatedly studied in small series with encouraging results, though historically has been fraught with complications. As a result, the minimally invasive and more tolerable stereotactic radiosurgery (SRS) hypophysectomy has resurfaced as a possible treatment for cancer-related pain. While the mechanism of pain relief is not entirely understood, the hypothalamohypophyseal axis appears to play an essential role in pain perception and transmission and involves C fiber signal processing and downstream modulation of the brainstem and spinal cord via the hypothalamus. This review highlights the role of hypophysectomy in alleviating advanced cancer pain, both in hormonal and nonhormonal malignancy and the current mechanistic understanding of pain relief for the three primary hypophysectomy modalities used historically: surgical and chemical adenolysis, as well as the more recent, SRS hypophysectomy. Given the lack of high-quality evidence for stereotactic radiosurgery hypophysectomy, there is a need for further rigorous and prospective clinical studies despite its ideal and noninvasive approach.

Percutaneous CT-guided cordotomy for pain.

Cordotomy has evolved since the first open procedure by Spiller and the first percutaneous radiofrequency cordotomy by Mullan in 1965. Today, the minimally invasive, CT-guided percutaneous radiofrequency cordotomy is mostly used for the palliative management of medically intractable somatic pain related to malignancy in well-selected patients. The risk of adverse events is minimized with the use of intraoperative stimulation monitoring. This video highlights the spinal cord anatomy at the level of C1-2, the approach to patient selection, the associated risks and benefits, and, finally, the procedural setup and key steps involved in this unique neurosurgical procedure. The video can be found here: https://youtu.be/a-0ORqy0W2o.

Limited midline myelotomy for visceral pain.

The traditional commissural myelotomy consists of a sagittal cut in the midline and was originally described by Greenfield and performed by Armour in 1926. Today, myelotomy refers to the selective disruption of the ascending visceral pain pathway. The success of the procedure is incumbent on the correct identification of the midline. Limited midline open myelotomy for the treatment of medically intractable abdominal or pelvic visceral cancer pain, with the aid of somatosensory evoked potentials to identify midline, offers patients superior pain relief over similar percutaneous techniques. Multicenter registries are needed to better elucidate the best surgical technique for this procedure. The video can be found here: https://youtu.be/0unlmwp08po.

Unsupervised clustering reveals spatially varying single neuronal firing patterns in the subthalamic nucleus of patients with Parkinson's disease.

INTRODUCTION: Subthalamic nucleus (STN) is an effective target for deep brain stimulation (DBS) to reduce the motor symptoms of Parkinson's disease (PD). It is important to identify firing patterns within the structure for a better understanding of the electro-pathophysiology of the disease. Using recently established metrics, our study aims to autonomously identify the discharge patterns of individual cells and examine their spatial distribution within the STN. METHODS: We recorded single unit activity (SUA) from 12 awake PD patients undergoing a standard clinical DBS surgery. Three extracted features from raw SUA (local variation, bursting index and prominence of peak) were used with k-means clustering to achieve the aforementioned unsupervised grouping of firing patterns. RESULTS: 279 neurons were isolated and four distinct firing patterns were identified across patients: tonic (11%), irregular (55%), periodic (9%) and non-periodic bursts (25%). The mean firing rates for irregular discharges were significantly lower (p < 0.05) than the rest. Tonic firings were significantly ventral (p < 0.05) while periodic (p < 0.05) and non-periodic (p < 0.01) bursts were dorsal. The percentage of periodically bursting neurons in dorsal region and entire STN were significantly correlated with off state UPDRS tremor scores (r = 0.51, p = 0.04) and improvement in bradykinesia and rigidity (r = 0.57, p = 0.02) respectively. CONCLUSION: Strengthening the application of unsupervised clustering for firing patterns of individual cells, this study shows a unique spatial affinity of tonic activity towards the ventral and bursting activity towards the dorsal region of STN in PD patients. This spatial preference, together with the correlation of clinical scores, can provide a clue towards understanding Parkinsonian symptom generation.

Gastrointestinal stromal tumor with intracranial metastasis: case presentation and systematic review of literature.

BACKGROUND: Intracranial metastasis of Gastrointestinal Stromal Tumors (GISTs) is rare but presents unique treatment challenges. We present a case of intracranial metastasis of GIST with a systematic review of the literature. A literature search using key terms "'gastrointestinal stromal tumor' AND brain AND metastasis"" was conducted through May 2019 via Embase and Pubmed according to PRISMA guidelines. Only cases describing intradural metastases rather than calvarial or intraorbital metastases were included. CASE PRESENTATION: A 57-year-old woman with history of GIST metastatic to the liver presented with a six-week history of left facial weakness, left hearing loss, and left facial numbness, and a one-week history of headaches, gait disturbance, and dizziness. MRI revealed a contrast-enhancing dural-based left middle cranial fossa mass measuring 2.9 cm × 3.1 cm × 3.4 cm with extension into the internal auditory canal and cerebral edema. A left temporal craniotomy was performed to excise the lesion, and the patient was discharged to a rehabilitation facility at her preoperative baseline. Intraoperative pathology revealed a spindle cell neoplasm, postoperative MRI demonstrated gross total resection of the lesion, and microscopic analysis demonstrated sheets of spindled tumor cells with short ovoid, irregular, hyperchromatic nuclei and scattered large atypical nuclei without extensive necrosis. Immunohistochemical staining was positive for KIT proto-oncogene (CD117, c-KIT), and the patient was put on imatinib (400 mg/day). CONCLUSIONS: Of the 18 cases analyzed and our present case, metastasis typically involved the cerebrum with only one in infratentorial elements. The tumors in seven of the cases involved the dura, and one case metastasized to the pituitary. Eight patients died following treatment. Surgery remains the mainstay of intracranial metastatic GIST, however there are many reports of good responses to radiation or chemotherapy alone. More investigation is required to determine the best treatment course for these patients.