Antithrombotic Therapy in Cerebral Cavernous Malformations: A Systematic Review, Meta-Analysis, and Network Meta-Analysis.

BACKGROUND: Cerebral cavernous malformations are complex vascular anomalies in the central nervous system associated with a risk of intracranial hemorrhage. Traditional guidelines have been cautious about the use of antithrombotic therapy in this patient group, citing concerns about potential bleeding risk. However, recent research posits that antithrombotic therapy may actually be beneficial. This study aims to clarify the association between antithrombotic therapy, including antiplatelet and anticoagulant medications, and the risk of intracranial hemorrhage in patients with cerebral cavernous malformations. METHODS AND RESULTS: A comprehensive literature search was conducted in PubMed, Web of Science, and Scopus databases, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Nine single-center, nonrandomized cohort studies involving 2709 patients were included. Outcomes were analyzed using random-effects model, and a network meta-analysis was conducted for further insight. Of the 2709 patients studied, 388 were on antithrombotic therapy. Patients on antithrombotic therapy had a lower risk of presenting with intracranial hemorrhage (odds ratio [OR], 0.56 [95% CI, 0.45-0.7]; P<0.0001). In addition, the use of antithrombotic therapy was associated with lower risk of intracranial hemorrhage from a cerebral cavernous malformation on follow-up (OR, 0.21 [95% CI, 0.13-0.35]; P<0.0001). A network meta-analysis revealed a nonsignificant OR of 0.73 (95% CI, 0.23-2.56) when antiplatelet therapy was compared with anticoagulant therapy. CONCLUSIONS: Our study explores the potential benefits of antithrombotic therapy in cerebral cavernous malformations. Although the analysis suggests a possible role for antithrombotic agents, it is critical to note that the evidence remains preliminary. Fundamental biases in study design, such as ascertainment and assignment bias, limit the weight of our conclusions. Therefore, our findings should be considered hypothesis-generating and not definitive for clinical practice change.

Cognitive outcomes following aneurysmal subarachnoid hemorrhage: Rehabilitation strategies.

Despite decreases in mortality rate, the treatment of cognitive deficits following aneurysmal subarachnoid hemorrhage (aSAH) remains a serious challenge for clinicians and survivors alike. Deficits in executive function, language, and memory prevent more than half of survivors from returning to their previous level of work and put a tremendous amount of stress on the individual and their family. New therapies are needed for survivors of aSAH in order to improve cognitive outcomes and quality of life. The aim of this review is to discuss the prevalence and contributing factors of cognitive deficits following aSAH, as well as areas for therapeutic intervention. Due to the limited research on cognitive rehabilitative strategies for aSAH, a literature search of traumatic brain injury (TBI) was used to explore therapies with the potential to improve cognitive outcomes in aSAH. Across cognitive domains, existing rehabilitative and pharmacotherapeutic strategies for TBI show promise to be useful for survivors of aSAH. However, further study of these therapies in addition to consistent assessment of cognitive deficits are required to determine their efficacy in survivors of aSAH.

The safety and accuracy of intratumoral catheter placement to infuse viral immunotherapies in children with malignant brain tumors: a multi-institutional study.

OBJECTIVE: Relatively little is known about the safety and accuracy of catheter placement for oncolytic viral therapy in children with malignant brain tumors. Accordingly, this study combines data from two phase I clinical trials that employed viral immunotherapy across two institutions to describe the adverse event profile, safety, and accuracy associated with the stereotactic placement and subsequent removal of intratumoral catheters. METHODS: Children with progressive/recurrent supratentorial malignant tumors were enrolled in two clinical trials (NCT03043391 and NCT02457845) and treated with either the recombinant polio:rhinovirus (lerapolturev) or the genetically modified oncolytic herpesvirus (G207). Age, sex, race, tumor diagnosis, and tumor location were analyzed. Events related to the catheter placement or removal were categorized. A catheter that was either pulled back or could not be used was defined as "misplaced." Neuronavigation software was used to analyze the accuracy of catheter placement for NCT03043391. Descriptive statistics were performed. RESULTS: Nineteen patients were treated across the two completed trials with a total of 49 catheters. The mean ± SD (range) age was 14.1 ± 3.6 (7-19) years. All tumors were grade 3 or 4 gliomas. Nonlobar catheter tip placement included the corpus callosum, thalamus, insula, and cingulate gyrus. Six of 19 patients (31.6%) had minor hemorrhage noted on CT; however, no patients were symptomatic and/or required intervention related to these findings. One of 19 patients had a delayed CSF leak after catheter removal that required oversewing of the surgical site. No patients developed infection or a neurological deficit. In 7 patients with accuracy data, the mean ± SD distance of the planned trajectory (PT) to the catheter tip was 1.57 ± 1.6 mm, the mean angle of the PT to the catheter was 2.43° ± 2.1°, and the greatest distance of PT to the catheter in the parallel plane was 1.54 ± 1.5 mm. Three of 49 (6.1%) catheters were considered misplaced. CONCLUSIONS: Although instances of minor hemorrhage were encountered, they were clinically asymptomatic. One of 49 catheters required intervention for a CSF leak. Congruent with previous studies in the literature, the stereotactic placement of catheters in these pediatric tumor patients was accurate with approximately 95% of catheters having been adequately placed.

High-resolution neural recordings improve the accuracy of speech decoding.

Patients suffering from debilitating neurodegenerative diseases often lose the ability to communicate, detrimentally affecting their quality of life. One solution to restore communication is to decode signals directly from the brain to enable neural speech prostheses. However, decoding has been limited by coarse neural recordings which inadequately capture the rich spatio-temporal structure of human brain signals. To resolve this limitation, we performed high-resolution, micro-electrocorticographic (µECoG) neural recordings during intra-operative speech production. We obtained neural signals with 57× higher spatial resolution and 48% higher signal-to-noise ratio compared to macro-ECoG and SEEG. This increased signal quality improved decoding by 35% compared to standard intracranial signals. Accurate decoding was dependent on the high-spatial resolution of the neural interface. Non-linear decoding models designed to utilize enhanced spatio-temporal neural information produced better results than linear techniques. We show that high-density µECoG can enable high-quality speech decoding for future neural speech prostheses.

Recombinant polio-rhinovirus immunotherapy for recurrent paediatric high-grade glioma: a phase 1b trial.

BACKGROUND: Outcomes of recurrent paediatric high-grade glioma are poor, with a median overall survival of less than 6 months. Viral immunotherapy, such as the polio-rhinovirus chimera lerapolturev, is a novel approach for treatment of recurrent paediatric high-grade glioma and has shown promise in adults with recurrent glioblastoma. The poliovirus receptor CD155 is ubiquitously expressed in malignant paediatric brain tumours and is a treatment target in paediatric high-grade glioma. We aimed to assess the safety of lerapolturev when administered as a single dose intracerebrally by convection enhanced delivery in children and young people with recurrent WHO grade 3 or grade 4 glioma, and to assess overall survival in these patients. METHODS: This phase 1b trial was done at the Duke University Medical Center (Durham, NC, USA). Patients aged 4-21 years with recurrent high-grade malignant glioma (anaplastic astrocytoma, glioblastoma, anaplastic oligoastrocytoma, anaplastic oligodendroglioma, or anaplastic pleomorphic xanthoastrocytoma) or anaplastic ependymoma, atypical teratoid rhabdoid tumour, or medulloblastoma with infusible disease were eligible for this study. A catheter was tunnelled beneath the scalp for a distance of at least 5 cm to aid in prevention of infection. The next day, lerapolturev at a dose of 5 × 107 median tissue culture infectious dose in 3 mL infusate loaded in a syringe was administered via a pump at a rate of 0·5 mL per h as a one-time dose. The infusion time was approximately 6·5 h to compensate for volume of the tubing. The primary endpoint was the proportion of patients with unacceptable toxic effects during the 14-day period after lerapolturev treatment. The study is registered with ClinicalTrials.gov, NCT03043391. FINDINGS: Between Dec 5, 2017, and May 12, 2021, 12 patients (11 unique patients) were enrolled in the trial. Eight patients were treated with lerapolturev. The median patient age was 16·5 years (IQR 11·0-18·0), five (63%) of eight patients were male and three (38%) were female, and six (75%) of eight patients were White and two (25%) were Black or African American. The median number of previous chemotherapeutic regimens was 3·50 (IQR 1·25-5·00). Six of eight patients had 26 treatment-related adverse events attributable to lerapolturev. There were no irreversible (ie, persisted longer than 2 weeks) treatment-related grade 4 adverse events or deaths. Treatment-related grade 3 adverse events included headaches in two patients and seizure in one patient. Four patients received low-dose bevacizumab on-study for treatment-related peritumoural inflammation or oedema, diagnosed by both clinical symptoms plus fluid-attenuated inversion recovery MRI. The median overall survival was 4·1 months (95% CI 1·2-10·1). One patient remains alive after 22 months. INTERPRETATION: Convection enhanced delivery of lerapolturev is safe enough in the treatment of recurrent paediatric high-grade glioma to proceed to the next phase of trial. FUNDING: Solving Kids Cancer, B+ Foundation, Musella Foundation, and National Institutes of Health.

Indication for a skull base approach in microvascular decompression for hemifacial spasm.

BACKGROUND: A thorough observation of the root exit zone (REZ) and secure transposition of the offending arteries is crucial for a successful microvascular decompression (MVD) for hemifacial spasm (HFS). Decompression procedures are not always feasible in a narrow operative field through a retrosigmoid approach. In such instances, extending the craniectomy laterally is useful in accomplishing the procedure safely. This study aims to introduce the benefits of a skull base approach in MVD for HFS. METHODS: The skull base approach was performed in twenty-eight patients among 335 consecutive MVDs for HFS. The site of the neurovascular compression (NVC), the size of the flocculus, and the location of the sigmoid sinus are measured factors in the imaging studies. The indication for a skull base approach is evaluated and verified retrospectively in comparison with the conventional retrosigmoid approach. Operative outcomes and long-term results were analyzed retrospectively. RESULTS: The extended retrosigmoid approach was used for 27 patients and the retrolabyrinthine presigmoid approach was used in one patient. The measurement value including the site of NVC, the size of the flocculus, and the location of the sigmoid sinus represents well the indication of the skull base approach, which is significantly different from the conventional retrosigmoid approach. The skull base approach is useful for patients with medially located NVC, a large flocculus, or repeat MVD cases. The long-term result demonstrated favorable outcomes in patients with the skull base approach applied. CONCLUSIONS: Preoperative evaluation for lateral expansion of the craniectomy contributes to a safe and secure MVD.

Second Case of Tumors Associated With Heterozygous NTHL1 Variant.

Homozygous mutations to NTHL1 are known to increase cancer risk, particularly in the colon and breast. NTHL1 tumor syndrome (NTS) is an autosomal recessive genetic condition. Little is known about the cancer risk in patients who have heterozygous NTHL1 mutations. We previously published a case of benign tumors associated with a heterozygous NTHL1 mutation. In this second case, we present a patient with a heterozygous NTHL1 mutation who developed a gastrointestinal stromal tumor, pilocytic astrocytoma, tall cell papillary thyroid cancer, invasive ductal papilloma, spinal nerve sheath tumors, and spinal hemangiomas. Here, we show that heterozygous NTHL1 mutations may increase cancer risk and may even manifest similarly to NTS.

Intraoperative microseizure detection using a high-density micro-electrocorticography electrode array.

One-third of epilepsy patients suffer from medication-resistant seizures. While surgery to remove epileptogenic tissue helps some patients, 30-70% of patients continue to experience seizures following resection. Surgical outcomes may be improved with more accurate localization of epileptogenic tissue. We have previously developed novel thin-film, subdural electrode arrays with hundreds of microelectrodes over a 100-1000 mm2 area to enable high-resolution mapping of neural activity. Here, we used these high-density arrays to study microscale properties of human epileptiform activity. We performed intraoperative micro-electrocorticographic recordings in nine patients with epilepsy. In addition, we recorded from four patients with movement disorders undergoing deep brain stimulator implantation as non-epileptic controls. A board-certified epileptologist identified microseizures, which resembled electrographic seizures normally observed with clinical macroelectrodes. Recordings in epileptic patients had a significantly higher microseizure rate (2.01 events/min) than recordings in non-epileptic subjects (0.01 events/min; permutation test, P = 0.0068). Using spatial averaging to simulate recordings from larger electrode contacts, we found that the number of detected microseizures decreased rapidly with increasing contact diameter and decreasing contact density. In cases in which microseizures were spatially distributed across multiple channels, the approximate onset region was identified. Our results suggest that micro-electrocorticographic electrode arrays with a high density of contacts and large coverage are essential for capturing microseizures in epilepsy patients and may be beneficial for localizing epileptogenic tissue to plan surgery or target brain stimulation.

Long-Term Outcomes for Patients With Atypical or Malignant Meningiomas Treated With or Without Radiation Therapy: A 25-Year Retrospective Analysis of a Single-Institution Experience.

Purpose: Atypical (World Health Organization [WHO] grade 2) and malignant (WHO grade 3) meningiomas have high rates of local recurrence, and questions remain about the role of adjuvant radiation therapy (RT) for patients with WHO grade 2 disease. These patients frequently require salvage therapy, and optimal management is uncertain given limited prospective data. We report on the long-term outcomes for patients with atypical and malignant meningiomas treated with surgery and/or RT at our institution. Methods and Materials: Data were collected through a retrospective chart review for all patients with WHO grade 2 or 3 meningiomas treated with surgery and/or RT at our institution between January 1992 and March 2017. Progression-free survival (PFS) and overall survival (OS) were described using the KaplanMeier estimator. The outcomes in the subgroups were compared with a log-rank test. A Cox proportional hazards model was used for the univariable and multivariable analyses of predictors of PFS. Results: A total of 66 patients were included in this analysis. The median follow-up was 12.4 years overall and 8.6 years among surviving patients. Fifty-two patients (78.8%) had WHO grade 2 meningiomas, and 14 patients (21.2%) had WHO grade 3 disease. Thirty-six patients (54.5%) were treated with surgery alone, 28 patients (42.4%) with surgery and adjuvant RT, and 2 patients (3%) with RT alone. Median PFS and OS were 3.2 years and 8.8 years, respectively. PFS was significantly improved with adjuvant RT compared with surgery alone (hazard ratio, 0.36; 95% confidence interval, 0.18-0.70). Patients with Ki-67 index >10% showed a trend toward worse PFS compared with patients with Ki-67 ≤10% (hazard ratio, 0.51; 95% confidence interval, 0.25-1.04). No significant differences in PFS or OS were observed with respect to Simpson or WHO grade. Conclusions: For patients with atypical or malignant meningiomas, adjuvant RT was associated with significantly improved PFS, and Ki-67 index >10% was associated with a trend toward worse PFS. Given the long-term survival, high recurrence rates, and efficacy of salvage therapy, patients with atypical and malignant meningiomas should be monitored systematically long after initial treatment.

Neurosurgery residency and fellowship education in the United States: 2 decades of system development by the One Neurosurgery Summit organizations.

The purpose of this report is to chronicle a 2-decade period of educational innovation and improvement, as well as governance reform, across the specialty of neurological surgery. Neurological surgery educational and professional governance systems have evolved substantially over the past 2 decades with the goal of improving training outcomes, patient safety, and the quality of US neurosurgical care. Innovations during this period have included the following: creating a consensus national curriculum; standardizing the length and structure of neurosurgical training; introducing educational outcomes milestones and required case minimums; establishing national skills, safety, and professionalism courses; systematically accrediting subspecialty fellowships; expanding professional development for educators; promoting training in research; and coordinating policy and strategy through the cooperation of national stakeholder organizations. A series of education summits held between 2007 and 2009 restructured some aspects of neurosurgical residency training. Since 2010, ongoing meetings of the One Neurosurgery Summit have provided strategic coordination for specialty definition, neurosurgical education, public policy, and governance. The Summit now includes leadership representatives from the Society of Neurological Surgeons, the American Association of Neurological Surgeons, the Congress of Neurological Surgeons, the American Board of Neurological Surgery, the Review Committee for Neurological Surgery of the Accreditation Council for Graduate Medical Education, the American Academy of Neurological Surgery, and the AANS/CNS Joint Washington Committee. Together, these organizations have increased the effectiveness and efficiency of the specialty of neurosurgery in advancing educational best practices, aligning policymaking, and coordinating strategic planning in order to meet the highest standards of professionalism and promote public health.

Retrolabyrinthine transsigmoid approach to complex parabrainstem tumors in the posterior fossa.

OBJECTIVE: The surgical management of large and complex tumors of the posterior fossa poses a formidable challenge in neurosurgery. The standard retrosigmoid craniotomy approach has been performed at most neurosurgical centers; however, the retrosigmoid approach may not provide enough working space without significant retraction of the cerebellum. The transsigmoid approach provides wider and shallower surgical fields; however, there have been few clinical and no cadaveric studies on its usefulness. In the present study, the authors describe the transsigmoid approach in clinical cases and cadaveric specimens. METHODS: For the clinical study, the authors retrospectively reviewed the medical records and operative charts of patients who had been surgically treated for parabrainstem tumors using the transsigmoid approach between 1997 and 2019. They analyzed patient demographic and clinical data, as well as surgical and clinical outcomes. In the cadaveric study, they compared the surgical views obtained in different approaches (retrosigmoid, presigmoid, retrolabyrinthine, and transsigmoid) and measured the sigmoid sinus width at the level of the endolymphatic sac and the distance between the anterior edge of the sigmoid sinus and the endolymphatic sac on 35 sides in 19 cadaveric specimens. RESULTS: A total of 21 patients (6 males and 15 females) with a mean age of 42.2 (range 15-67) years were included in the clinical study. Eleven patients had meningioma, 7 had vestibular schwannoma, 2 had hemangioblastoma, and 1 had epidermoid cyst. Gross-total, near-total, and subtotal removal were achieved in 7 (33.3%), 3 (14.3%), and 11 (52.4%) patients, respectively. In the cadaveric study, 19 cadaveric specimens were used. The sigmoid sinus was cut in the middle, and the incision was extended from the retrosigmoid to the presigmoid dura. The dura was then retracted upward and downward like opening a door. The results indicated that this technique can widen the operative field anteriorly by approximately 2 cm as compared to the retrosigmoid approach and provides a better view anterior to the brainstem. CONCLUSIONS: The transsigmoid approach is useful for complex parabrainstem tumors in the posterior fossa because it provides a wider and shallower operative view with less retraction of the cerebellum. This enables safer tumor removal with less damage to important structures in the posterior fossa, resulting in better operative and clinical outcomes.

Petrous bone lesions: surgical implementation and outcomes of extradural subtemporal approach.

BACKGROUND: Petrous bone lesions (PBLs) are rare with few reports in the neurosurgical literature. In this study, the authors describe our current technique of extradural subtemporal approach (ESTA). The objective of this study was to evaluate the role and efficacy of ESTA for treatment of the PBLs. To our knowledge, this is the largest reported clinical series of using an ESTA-treated PBLs in which the clinical outcomes were evaluated. METHODS: Between 1994 and 2019, 67 patients with PBLs treated by ESTA were retrospectively reviewed. Extent of resection, neurological outcomes, recurrence rate, and surgical complications were evaluated and compared with previous studies. The indications, advantages, limitations, and outcomes of ESTA were analyzed according to pathology. RESULTS: This series included 7 facial nerve schwannomas (10.4%), 16 cholesterol granulomas (23.9%), 16 chordomas (23.9%), 6 chondrosarcomas (9%), 5 trigeminal schwannomas (7.5%), 9 epidermoids/dermoids (13.4%), and 8 other pathologies (11.9%). The most common location of PBLs operated with ESTA was at the petrous apex and rhomboid areas (68.7%). Gross total resection was achieved in 35 (55.6%). Symptomatic improvement occurred in 56 patients (83.6%). Complications occurred in 7 (10.4%) of cases including one mortality. Nine patients (17%) had recurrence within the mean follow-up 71 months. Compared to previous literature, our results demonstrated comparable outcomes but with higher rates of hearing and facial nerve preservation as well as minimal morbidity. From our results, ESTA is an effective therapeutic option for lesions located at the rhomboid and petrous apex, particularly when patients presented with intact facial and hearing function. CONCLUSION: Our series demonstrated that ESTA provided satisfactory outcomes with excellent benefits of hearing and facial function preservation for patients with petrous bone lesions. ESTA should be considered as a safe and effective therapeutic option for selected patients with PBLs.

Neurosurgical management of petrous bone lesions: classification system and selection of surgical approaches.

BACKGROUND: Surgery of petrous bone lesions (PBLs) is challenging for neurosurgeons. Selection of the surgical approach is an important key for success. In this study, the authors present an anatomical classification for PBLs that has been used by our group for over the past 26 years. The objective of this study is to investigate the benefits and applicability of this classification. METHODS: Between 1994 and 2019, 117 patients treated for PBLs were retrospectively reviewed. Using the V3 and arcuate eminence as reference points, the petrous bone is segmented into 3 parts: petrous apex, rhomboid, and posterior. The pathological diagnoses, selection of the operative approach, and the extent of resection (EOR) were analyzed and correlated using this classification. RESULTS: This series included 22 facial nerve schwannomas (18.8%), 22 cholesterol granulomas (18.8%), 39 chordomas/chondrosarcomas (33.3%), 6 trigeminal schwannomas (5.1%), 13 epidermoids/dermoids (11.1%), and 15 other pathologies (12.8%). PBLs were most often involved with the petrous apex and rhomboid areas (46.2%). The extradural subtemporal approach (ESTA) was most frequently used (57.3%). Gross total resection was achieved in 58.4%. Symptomatic improvement occurred in 92 patients (78.6%). Our results demonstrated a correlation between this classification with each type of pathology (p < .001), selection of surgical approaches (p < 0.001), and EOR (p = 0.008). Chordoma/chondrosarcoma, redo operations, and lesions located medially were less likely to have total resection. Temporary complications occurred in 8 cases (6.8%), persistent morbidity in 5 cases (4.3%), and mortality in 1 case. CONCLUSION: In this study, we proposed a simple classification of PBLs. Using landmarks on the superior petrosal surface, the petrous bone is divided into 3 parts, apex, rhomboid, and posterior. Our results demonstrated that chordoma/chondrosarcoma, redo operations, and lesions involving the tip of the petrous apex or far medial locations were more difficult to achieve total resection. This classification could help surgeons understand surgical anatomy framework, predict possible structures at risk, and select the most appropriate approach for each patient.

How I do it: total resection of a giant sphenoclinoidal meningioma with normalization of near blind vision.

BACKGROUND: Resection of giant sphenoclinoidal meningiomas (SCLM) remains difficult. We discuss a patient presenting with right eye near blindness who underwent total removal of a giant SCLM, resulting in normal vision and no recurrence. METHOD: Utilizing frontotemporal craniotomy, devascularization, debulking, and detachment was achieved. Microdissection of tumor off the optic nerve and carotid perforators was accomplished, resulting in total resection, visual normalization, and no deficits using efficient face-to-face microscope set-up, 2-surgeon 4-hand technique, and double bipolar-suction arrangement. CONCLUSION: Frontotemporal craniotomy was adequate. Preservation of the optic nerve and carotid artery is key. Meticulous microsurgical techniques and refined instruments are important for success.

Flexible, high-resolution thin-film electrodes for human and animal neural research.

Objective.Brain functions such as perception, motor control, learning, and memory arise from the coordinated activity of neuronal assemblies distributed across multiple brain regions. While major progress has been made in understanding the function of individual neurons, circuit interactions remain poorly understood. A fundamental obstacle to deciphering circuit interactions is the limited availability of research tools to observe and manipulate the activity of large, distributed neuronal populations in humans. Here we describe the development, validation, and dissemination of flexible, high-resolution, thin-film (TF) electrodes for recording neural activity in animals and humans.Approach.We leveraged standard flexible printed-circuit manufacturing processes to build high-resolution TF electrode arrays. We used biocompatible materials to form the substrate (liquid crystal polymer; LCP), metals (Au, PtIr, and Pd), molding (medical-grade silicone), and 3D-printed housing (nylon). We designed a custom, miniaturized, digitizing headstage to reduce the number of cables required to connect to the acquisition system and reduce the distance between the electrodes and the amplifiers. A custom mechanical system enabled the electrodes and headstages to be pre-assembled prior to sterilization, minimizing the setup time required in the operating room. PtIr electrode coatings lowered impedance and enabled stimulation. High-volume, commercial manufacturing enables cost-effective production of LCP-TF electrodes in large quantities.Main Results. Our LCP-TF arrays achieve 25× higher electrode density, 20× higher channel count, and 11× reduced stiffness than conventional clinical electrodes. We validated our LCP-TF electrodes in multiple human intraoperative recording sessions and have disseminated this technology to >10 research groups. Using these arrays, we have observed high-frequency neural activity with sub-millimeter resolution.Significance.Our LCP-TF electrodes will advance human neuroscience research and improve clinical care by enabling broad access to transformative, high-resolution electrode arrays.

Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy.

Several immunotherapy clinical trials in recurrent glioblastoma have reported long-term survival benefits in 10-20% of patients. Here we perform genomic analysis of tumor tissue from recurrent WHO grade IV glioblastoma patients acquired prior to immunotherapy intervention. We report that very low tumor mutation burden is associated with longer survival after recombinant polio virotherapy or after immune checkpoint blockade in recurrent glioblastoma patients. A relationship between tumor mutation burden and survival is not observed in cohorts of immunotherapy naïve newly diagnosed or recurrent glioblastoma patients. Transcriptomic analyses reveal an inverse relationship between tumor mutation burden and enrichment of inflammatory gene signatures in cohorts of recurrent, but not newly diagnosed glioblastoma tumors, implying that a relationship between tumor mutation burden and tumor-intrinsic inflammation evolves upon recurrence.

Eosinophilic globules in a classic ependymoma: evidence of a possible secretory role.

A number of neoplasms of the central nervous system can demonstrate diffuse eosinophilic globules, known to be secretory products of the corresponding cell type, but they have not been a salient feature in descriptions of classic ependymoma. Here, we present a case of a posterior fossa ependymoma demonstrating glassy PAS-positive, diastase-resistant, eosinophilic globules with light microscopic and ultrastructural features resembling Reissner fiber, the secretory product of the subcommissural organ. While there has been a single published description of an ependymoma with intra- and extracellular granulofibrillary material suggested to be evidence of secretory differentiation, ours is the first case to demonstrate diffuse eosinophilic globules in an ependymoma. The extent of globules allowed full study by electron microscopy to provide new insight into the secretory material and the surrounding structures. Our findings suggest that neoplastic ependymal cells can recapitulate the secretory capacity of the subcommissural organ.

Autograft-derived spinal cord mass in the cervical spine following transplantation with olfactory mucosa cells for traumatic spinal cord injury: case report.

This study describes a patient with an autograft-derived spinal cord mass following transplantation of olfactory mucosa for treatment of cervical spine injury. The authors report the case of a 35-year-old man who suffered a complete spinal cord injury (SCI) at C5-6 in 2001. The patient underwent an olfactory mucosal cell implantation at the location of injury 4 years following initial trauma. Twelve years later, the patient presented with rapidly progressive decline in upper-extremity function as well as neuropathic pain. Imaging revealed a heterogeneously enhancing intramedullary mass from C3 to C7. At surgery, the patient was found to have a posttransplant mucinous mass. Each mucinous cyst was drained and a portion of the cyst wall was removed. Histological examination demonstrated ciliated epithelium-lined fibrous tissue, submucosal glands, and mucoid material, consistent with a transplant-derived tumor. This case report both documents a rare long-term complication of olfactory mucosal cell transplantation and serves as a cautionary tale encouraging prudent use of novel treatments in a vulnerable population of patients with severe SCI.

Perioperative Assessment of Cerebellar Masses and the Potential for Cerebellar Cognitive Affective Syndrome.

The cerebellum was long perceived to be a region of limited importance with primary functions in the regulation of motor control. A degree of its functional topography in motor modulation has been traditionally appreciated. However, an evolving body of evidence supports its role in a range of cognitive processes, including executive decision making, language, emotional processing, and working memory. To this end, numerous studies of cerebellar stroke syndromes as well as investigations with functional magnetic resonance imaging and diffusion tensor imaging have given clinicians a better model of the functional topography within the cerebellum and the essential lanes of communication with the cerebrum. With this deeper understanding, neurosurgeons should integrate these domains into the perioperative evaluation and postoperative rehabilitation of patients with cerebellar tumors. This review aims to discuss these understandings and identify valuable tools for implementation into clinical practice.