Immunotherapy is a promising new therapeutic field that has demonstrated significant benefits in many solid-tumor malignancies, such as metastatic melanoma and non-small cell lung cancer. However, only a subset of these patients responds to treatment. Glioblastoma (GBM) is the most common malignant primary brain tumor with a poor prognosis of 14.6 months and few treatment advancements over the last 10 years. There are many clinical trials testing immune therapies in GBM, but patient responses in these studies have been highly variable and a definitive benefit has yet to be identified. Biomarkers are used to quantify normal physiology and physiological response to therapies. When extensively characterized and vigorously validated, they have the potential to delineate responders from non-responders for patients treated with immunotherapy in malignancies outside of the central nervous system (CNS) as well as GBM. Due to the challenges of current modalities of radiographic diagnosis and disease monitoring, identification of new predictive and prognostic biomarkers to gauge response to immune therapy for patients with GBM will be critical in the precise treatment of this highly heterogenous disease. This review will explore the current and future strategies for the identification of potential biomarkers in the field of immunotherapy for GBM, as well as highlight major challenges of adapting immune therapy for CNS malignancies.

Objective The true incidence of perioperative coronavirus disease 2019 (COVID-19) has not been well elucidated in neurosurgical studies. We reviewed the effects of the pandemic on the neurosurgical case volume to study the incidence of COVID-19 in patients undergoing these procedures during the perioperative period and compared the characteristics and outcomes of this group to those of patients without COVID-19. Methods The neurosurgical and neurointerventional procedures at 2 tertiary care centers during the pandemic were reviewed. The case volume, type, and acuity were compared to those during the same period in 2019. The perioperative COVID-19 tests and results were evaluated to obtain the incidence. The baseline characteristics, including a modified Medically Necessary Time Sensitive (mMeNTS) score, and outcome measures were compared between those with and without COVID-19. Results A total of 405 cases were reviewed, and a significant decrease was found in total spine, cervical spine, lumbar spine, and functional/pain cases. No significant differences were found in the number of cranial or neurointerventional cases. Of the 334 patients tested, 18 (5.4%) had tested positive for COVID-19. Five of these patients were diagnosed postoperatively. The mMeNTS score, complications, and case acuity were significantly different between the patients with and without COVID-19. Conclusion A small, but real, risk exists of perioperative COVID-19 in neurosurgical patients, and those patients have tended to have a greater complication rate. Use of the mMeNTS score might play a role in decision making for scheduling elective cases. Further studies are warranted to develop risk stratification and validate the incidence.

Background: Worldwide, neurological disorders are the leading cause of disability-adjusted life years lost and the second leading cause of death. Despite global health capacity-building efforts, each year, 22.6 million individuals worldwide require neurosurgeon's care due to diseases such as traumatic brain injury and hydrocephalus, and 13.8 million of these individuals require surgery. It is clear that neurosurgical care is indispensable in both national and international public health discussions. This study highlights the role neurosurgeons can play in supporting the global health agenda, national surgical plans, and health strengthening systems (HSS) interventions.Methods: Guided by a literature review, the authors discuss key topics such as the global burden of neurosurgical diseases, the current state of neurosurgical care around the world and the inherent benefits of strong neurosurgical capability for health systems.Results: Neurosurgical diseases make up an important part of the global burden of diseases. Many neurosurgeons possess the sustained passion, resilience, and leadership needed to advocate for improved neurosurgical care worldwide. Neurosurgical care has been linked to 14 of the 17 Sustainable Development Goals (SDGs), thus highlighting the tremendous impact neurosurgeons can have upon HSS initiatives.Conclusion: We recommend policymakers and global health actors to: (i) increase the involvement of neurosurgeons within the global health dialogue; (ii) involve neurosurgeons in the national surgical system strengthening process; (iii) integrate neurosurgical care within the global surgery movement; and (iv) promote the training and education of neurosurgeons, especially those residing in Low-and middle-income countries, in the field of global public health.

The pathophysiology of epilepsy underlies a complex network dysfunction between neurons and glia, the molecular cell type-specific contributions of which remain poorly defined in the human disease. In this study, we validated a method that simultaneously isolates neuronal (NEUN +), astrocyte (PAX6 + NEUN–), and oligodendroglial progenitor (OPC) (OLIG2 + NEUN–) enriched nuclei populations from non-diseased, fresh-frozen human neocortex and then applied it to characterize the distinct transcriptomes of such populations isolated from electrode-mapped temporal lobe epilepsy (TLE) surgical samples. Nuclear RNA-seq confirmed cell type specificity and informed both common and distinct pathways associated with TLE in astrocytes, OPCs, and neurons. Compared to postmortem control, the transcriptome of epilepsy astrocytes showed downregulation of mature astrocyte functions and upregulation of development-related genes. To gain further insight into glial heterogeneity in TLE, we performed single cell transcriptomics (scRNA-seq) on four additional human TLE samples. Analysis of the integrated TLE dataset uncovered a prominent subpopulation of glia that express a hybrid signature of both reactive astrocyte and OPC markers, including many cells with a mixed GFAP + OLIG2 + phenotype. A further integrated analysis of this TLE scRNA-seq dataset and a previously published normal human temporal lobe scRNA-seq dataset confirmed the unique presence of hybrid glia only in TLE. Pseudotime analysis revealed cell transition trajectories stemming from this hybrid population towards both OPCs and reactive astrocytes. Immunofluorescence studies in human TLE samples confirmed the rare presence of GFAP + OLIG2 + glia, including some cells with proliferative activity, and functional analysis of cells isolated directly from these samples disclosed abnormal neurosphere formation in vitro. Overall, cell type-specific isolation of glia from surgical epilepsy samples combined with transcriptomic analyses uncovered abnormal glial subpopulations with de-differentiated phenotype, motivating further studies into the dysfunctional role of reactive glia in temporal lobe epilepsy.

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Objective Coronavirus disease 2019 (COVID-19) continues to affect all aspects of healthcare delivery and neurosurgical practices are not immune to its impact. We aim to evaluate neurosurgical practice patterns as well as perioperative incidence of COVID-19 in neurosurgical patients and their outcomes. Methods A retrospective review of neurosurgical and neurointerventional cases at two tertiary centers during the first three months of the first peak of COVID-19 pandemic (March 8-June 8) as well as following three months (post-peak pandemic; June 9-September 9) was performed. Baseline characteristics, perioperative COVID-19 test results, modified Medically Necessary Time Sensitive (mMeNTS) score, and outcome measures were compared between COVID-19 positive and negative patients through bivariate and multivariate analysis. Results 652 neurosurgical and 217 neurointerventional cases were performed during post-peak pandemic period. Cervical spine, lumbar spine, functional/pain, cranioplasty, and cerebral angiogram cases were significantly increased in the post-pandemic period. There was a 2.9% (35/1,197) positivity rate for COVID-19 testing overall and 3.6% (13/363) positivity rate postoperatively. Age, mMeNTS score, complications, length of stay, case acuity, ASA status, length of stay, and disposition were significantly different between COVID-19 positive and negative patients. Conclusion A significant increase in elective case volume during the post-peak pandemic period is feasible with low and acceptable incidence of COVID-19 in neurosurgical patients. COVID-19 positive patients were younger, less likely to undergo elective procedures, had increased length of stay, had more complications, and were discharged to a location other than home. The mMeNTS score plays a role in decision making for scheduling elective cases.

Background and objectives Malignant cerebral edema (MCE) is a feared complication in patients suffering from large vessel occlusion. Variables associated with the development of MCE have not been clearly elucidated. Use of pupillometry and the neurological pupil index (NPi) as an objective measure in patients undergoing mechanical thrombectomy (MT) has not been explored. We aim to evaluate variables significantly associated with MCE in patients that undergo MT and hypothesize that abnormal NPi is associated with MCE in this population. Methods A retrospective analysis of patients with acute ischemic stroke who had undergone MT at our institution between 2017 and 2020 was performed. Baseline and outcome variables were collected, including NPi values from pupillometry readings of patients within 72 h after the MT. Patients were divided into two groups: MCE versus non-MCE group. A univariate and multivariate analysis was performed. Results Of 284 acute ischemic stroke patients, 64 (22.5%) developed MCE. Mean admission glucose (137 vs. 173; p < 0.0001), NIHSS on admission (17 vs. 24; p < 0.01), infarct core volume (27.9 vs. 17.9 mL; p = 0.0036), TICI score (p = 0.001), and number of passes (2.9 vs. 1.8; p < 0.0001) were significantly different between the groups. Pupillometry data was present for 64 patients (22.5%). Upon multivariate analysis, abnormal ipsilateral NPi ; p = 0.007) and hemorrhagic conversion were independently associated with MCE. Conclusion Abnormal NPi and hemorrhagic conversion are significantly associated with MCE in patients following MT. Further investigation is warranted to better define an association between NPi and patient outcomes in this patient population.

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