Prognostic Factors and Nomogram for Choroid Plexus Tumors: A Population-Based Retrospective Surveillance, Epidemiology, and End Results Database Analysis.

Background: Choroid plexus tumors (CPTs) are rare neoplasms found in the central nervous system, comprising 1% of all brain tumors. These tumors include choroid plexus papilloma (CPP), atypical choroid plexus papilloma (aCPP), and choroid plexus carcinoma (CPC). Although gross total resection for choroid plexus papillomas (CPPs) is associated with long-term survival, there is a scarcity of prospective data concerning the role and sequence of neoadjuvant therapy in treating aCPP and CPC. Methods: From the years 2000 to 2019, 679 patients with CPT were identified from the Surveillance, Epidemiology, and End Result (SEER) database. Among these patients, 456 patients had CPP, 75 patients had aCPP, and 142 patients had CPC. Univariate and multivariable Cox proportional hazard models were run to identify variables that had a significant impact on the primary endpoint of overall survival (OS). A predictive nomogram was built for patients with CPC to predict 5-year and 10-year survival probability. Results: Histology was a significant predictor of OS, with 5-year OS rates of 90, 79, and 61% for CPP, aCPP, and CPC, respectively. Older age and African American race were prognostic for worse OS for patients with CPP. Older age was also associated with reduced OS for patients with aCPP. American Indian/Alaskan Native race was linked to poorer OS for patients with CPC. Overall, treatment with gross total resection or subtotal resection had no difference in OS in patients with CPP or aCPP. Meanwhile, in patients with CPC, gross total resection (GTR) was associated with significantly better OS than subtotal resection (STR) only. However, there is no difference in OS between patients that receive GTR and patients that receive STR with adjuvant therapy. The nomogram for CPC considers types of treatments received. It demonstrates acceptable accuracy in estimating survival probability at 5-year and 10-year intervals, with a C-index of 0.608 (95% CI of 0.446 to 0.77). Conclusions: This is the largest study on CPT to date and highlights the optimal treatment strategies for these rare tumors. Overall, there is no difference in OS with GTR vs. STR in CPP or aCPP. Furthermore, OS is equivalent for CPC with GTR and STR plus adjuvant therapy.

Survival Benefit from Multimodal Treatment for Patients with Atypical Teratoid Rhabdoid Tumor in a Surveillance, Epidemiology, and End Results Database Analysis.

INTRODUCTION: Atypical teratoid rhabdoid tumor (ATRT) is among the most aggressive central nervous system malignancies. Although rare, this tumor typically afflicts young children and results in mortality within months. Here, we aim to determine key clinical features and treatment options that impact the survival of patients with ATRT. METHODS: From the year 2000 to 2019, 363 patients with ATRT were identified from the Surveillance, Epidemiology, and End Results database. Univariate analysis was used to identify variables that had a significant impact on the primary endpoint of overall survival (OS). Multivariable analysis was then used to identify independent predictors of survival. RESULTS: The median OS of the entire cohort was 13 months. Univariate analysis identified ages between 1 and 3 years, ages between 4 and 17 years, years of diagnosis between 2010 and 2019, and the receipt of treatment to have a significant impact on survival. In multivariable analysis, ages between 1 and 3 years and receipt of treatment were the only significant independent predictors of survival. The median OS was significantly greater in patients who received surgical treatment, chemotherapy, or radiation when compared to those who did not receive any treatment. In general, the receipt of any combination of therapies improved the median OS significantly. The receipt of triple therapy had the greatest impact on survival. DISCUSSION: This study highlights the survival benefit of a multimodal approach in the treatment of ATRT. The use of triple therapy, including surgery, radiation, and chemotherapy, was found to have the greatest survival benefit for patients. Overall, these findings may guide future care for patients with ATRT.

Prognostic Indicators for Intracranial Metastases from Pancreatic Cancer: A Population-Based Retrospective Surveillance, Epidemiology, and End Results Database Analysis.

OBJECTIVE: The natural history, treatment options, and clinical outcomes of pancreatic metastases to the brain remain largely unknown. Here, we seek to investigate characteristics that influence OS in pancreatic metastases to the brain. METHODS: This is a population-based retrospective study of OS in 508 patients with pancreatic metastases to the brain using the SEER database. Univariate and multivariate Cox regression analyses were utilized, and a predictive nomogram was developed. RESULTS: There were 508 patients identified for this study, with a median OS of 2 months. In the univariate analysis, patients older than 65 years had significantly reduced OS (P < 0.001). Patients with liver metastases (P < 0.001) and liver and lung metastases (P < 0.001) exhibited significantly reduced OS. Treatment of the primary tumor with chemotherapy only (P < 0.001), radiation only (P = 0.01), radiation and chemotherapy (P < 0.001), and surgery only (P = 0.01) were associated with increased OS. Resection of a distant metastasis site (P = 0.009) and of a brain metastasis (P = 0.03) were associated with increased OS. In the multivariable analysis, factors that remained significant included patient age (P = 0.01), liver metastases (P < 0.001), liver and lung metastases (P < 0.001), treatment with chemotherapy (P < 0.001), treatment with radiation and chemotherapy (P < 0.001), and treatment with surgery and chemotherapy (P < 0.001). The nomogram had a C-index of 0.766, suggesting congruence between the findings on the nomogram and the results in the internal verification. CONCLUSIONS: Median OS is influenced by age, multiorgan metastases, and treatment of the primary tumor. These data highlight the marginal benefit of treatment, yet improved quality of life (QOL) remains to be elucidated.

Prognostic Factors of Survival for Grade 3 Solitary Fibrous Tumor/Hemangiopericytoma: A Population-Based Retrospective Surveillance, Epidemiology, and End Results Database Analysis.

INTRODUCTION: Grade 3 solitary fibrous tumor, previously known as anaplastic hemangiopericytoma, is a rare and highly malignant intracranial tumor with a limited understanding of its natural history and treatment outcomes. METHODS: We conducted a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database spanning 2000-2019 to evaluate the clinical characteristics and treatment modalities that influence overall survival in this tumor entity. A cohort of 249 patients with intracranial grade 3 solitary fibrous tumors was identified. Univariate and multivariable Cox proportional hazard models were employed to determine significant prognostic factors for overall survival. Kaplan-Meier models were used to visualize survival curves, and a nomogram was constructed to predict survival probabilities at 6- and 12-month following diagnosis. RESULTS: Our findings indicated that patient age (<65 years), localized or regional disease burden, surgical resection, and radiation therapy were significant predictors of better overall survival. Combination therapies showed improved survival, with surgery and radiation therapy having the most significant impact. However, chemotherapy alone or in combination did not demonstrate a significant survival benefit, likely due to the limited sample size. The nomogram provided personalized prognostic predictions based on significant clinical factors. CONCLUSIONS: These data emphasize the importance of surgical resection and radiation therapy in the management of grade 3 solitary fibrous tumors, supporting the use of combination therapies to improve overall survival in this rare and aggressive intracranial neoplasm.

Endothelial deletion of EPH receptor A4 alters single-cell profile and Tie2/Akap12 signaling to preserve blood-brain barrier integrity.

Neurobiological consequences of traumatic brain injury (TBI) result from a complex interplay of secondary injury responses and sequela that mediates chronic disability. Endothelial cells are important regulators of the cerebrovascular response to TBI. Our work demonstrates that genetic deletion of endothelial cell (EC)-specific EPH receptor A4 (EphA4) using conditional EphA4f/f/Tie2-Cre and EphA4f/f/VE-Cadherin-CreERT2 knockout (KO) mice promotes blood-brain barrier (BBB) integrity and tissue protection, which correlates with improved motor function and cerebral blood flow recovery following controlled cortical impact (CCI) injury. scRNAseq of capillary-derived KO ECs showed increased differential gene expression of BBB-related junctional and actin cytoskeletal regulators, namely, A-kinase anchor protein 12, Akap12, whose presence at Tie2 clustering domains is enhanced in KO microvessels. Transcript and protein analysis of CCI-injured whole cortical tissue or cortical-derived ECs suggests that EphA4 limits the expression of Cldn5, Akt, and Akap12 and promotes Ang2. Blocking Tie2 using sTie2-Fc attenuated protection and reversed Akap12 mRNA and protein levels cortical-derived ECs. Direct stimulation of Tie2 using Vasculotide, angiopoietin-1 memetic peptide, phenocopied the neuroprotection. Finally, we report a noteworthy rise in soluble Ang2 in the sera of individuals with acute TBI, highlighting its promising role as a vascular biomarker for early detection of BBB disruption. These findings describe a contribution of the axon guidance molecule, EphA4, in mediating TBI microvascular dysfunction through negative regulation of Tie2/Akap12 signaling.

Prognostic Indicators for H3K27M-Mutant Diffuse Midline Glioma: A Population-Based Retrospective Surveillance, Epidemiology, and End Results Database Analysis.

BACKGROUND: Diffuse midline glioma with histone H3K27M mutation (H3K27M DMG) is a recently recognized World Health Organization grade IV glioma with a dismal prognosis. Despite maximal treatment, this high-grade glioma exhibits an estimated median survival of 9-12 months. However, little is known with regards to prognostic risk factors for overall survival (OS) for patients with this malignant tumor. The aim of the present study is to characterize risk factors influencing survival in H3K27M DMG. METHODS: This is a population-based retrospective study of survival in patients with H3K27M DMG. The Surveillance, Epidemiology, and End Results database was examined from the years 2018 to 2019 and data from 137 patients were collected. Basic demographics, tumor site, and treatments regimens were retrieved. Univariate and multivariable analyses were conducted to assess for factors associated with OS. Nomograms were built based on the results of the multivariable analyses. RESULTS: Median OS of the entire cohort was 13 months. Patients with infratentorial H3K27M DMG exhibited worse OS compared to their supratentorial counterparts. Any form of radiation treatment resulted in a significantly improved OS. Most combination treatments significantly improved OS with the exception of the surgery plus chemotherapy group. The combination of surgery and radiation had the greatest impact on OS. CONCLUSIONS: Overall, the infratentorial location of H3K27M DMG portends a worse prognosis compared to their supratentorial counterparts. The combination of surgery and radiation had the greatest impact on OS. These data highlight the survival benefit in utilizing a multimodal treatment approach for H3K27M DMG.

Systemic Immune-Inflammation Index Predicts Acute Symptomatic Hydrocephalus After Spontaneous Nonaneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: The authors sought to investigate the association between white blood cell counts and acute hydrocephalus in spontaneous nonaneurysmal subarachnoid hemorrhage (nSAH). METHODS: We conducted a retrospective analysis of 105 consecutive patients with spontaneous nSAH. Univariate and multivariable logistic regression analyses were performed to investigate factors associated with hydrocephalus. Receiver operating characteristic curve analysis determined the optimal cutoff to differentiate between patients with and without hydrocephalus. The admission characteristics of hydrocephalic patients with aneurysmal and nSAH were compared. RESULTS: A total of 70 patients met inclusion criteria, of which 21 (30%) presented with hydrocephalus. In univariate logistic regression, leukocytes, neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, neutrophil-monocyte-to-lymphocyte ratio, and the systemic immune-inflammation (SII) index ([neutrophils × platelets/lymphocytes]/1000) were associated with hydrocephalus. After adjustments, the SII index independently predicted acute hydrocephalus with the highest odds among laboratory values (odds ratio 2.184, P = 0.006). Receiver operating characteristic curve analysis revealed the SII index differentiated between patients with and without hydrocephalus (area under the curve = 0.799, 95% CI: 0.688-0.909, P < 0.001) with an optimal cutoff of 1.385 103/µL. SII indices did not differ between aneurysmal and nSAH patients with hydrocephalus (3.5 vs. 3.6 103/µL, P = 0.795). CONCLUSIONS: A SII index ≥1.385 103/µL on admission predicts acute hydrocephalus in spontaneous nSAH. Hydrocephalic patients with aneurysmal and nSAH exhibit similar SII indices, and thus, an exaggerated inflammatory and thrombotic response follows spontaneous subarachnoid hemorrhage irrespective of hemorrhage etiology.

Natural History of Traumatic Encephaloceles: A Systematic Literature Review.

Encephaloceles rarely develop following traumatic skull fractures. Given their low incidence, the clinical presentations and management strategies of these lesions are confined to case reports and limited case series. A systematic literature review was performed using PubMed, Ovid, and Web of Science databases to identify relevant articles using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 37 articles met inclusion criteria, including the case presented herein. These articles reported 52 traumatic encephaloceles. Mean patient age was 25.3 years (range 6 mo-66 y) with a male predominance (63%, 33/52). The most common bony defects resulting in encephalocele formation were the orbital roof (52%, 27/52), ethmoid (35%, 18/52), and sphenoid (10%, 5/52). Mean time from traumatic injury to initial presentation was 21.3 months (range 0 d-36 y) with a bimodal distribution split between immediately following the traumatic injury (57%, 26/46) or in a delayed manner (43%, 20/46). Common presentations of orbital roof, frontonasal, and temporal bone encephaloceles were exophthalmos (85%, 23/27), cerebrospinal fluid rhinorrhea (71%, 17/24), and hearing loss (100%, 4/4), respectively. Operative approach, repair technique, and materials used for encephalocele reduction were highly variable. Surgical intervention afforded definitive symptomatic improvement or resolution in the majority of cases (89%, 42/47). Clinical outcomes did not differ between orbital, frontonasal, or temporal bone encephaloceles ( P =0.438). Traumatic encephaloceles are a rare entity with diverse presenting symptomatology dependent upon the location of fracture dehiscence. Surgical intervention affords symptomatic improvement in the majority of cases irrespective of encephalocele location, time to presentation, or operative approach.

Monocyte Count on Admission Is Predictive of Shunt-Dependent Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage.

The authors sought to evaluate whether immunologic counts on admission were associated with shunt-dependent hydrocephalus following aneurysmal subarachnoid hemorrhage. A retrospective analysis of 143 consecutive patients with aneurysmal subarachnoid hemorrhage over a 9-year period was performed. A stepwise algorithm was followed for external ventricular drain weaning and determining the necessity of shunt placement. Data were compared between patients with and without shunt-dependent hydrocephalus. Overall, 11.19% of the cohort developed shunt-dependent hydrocephalus. On multivariate logistic regression analysis, acute hydrocephalus (OR: 61.027, 95% CI: 3.890-957.327; p = 0.003) and monocyte count on admission (OR: 3.362, 95% CI: 1.024-11.037; p = 0.046) were found to be independent predictors for shunt dependence. Receiver operating characteristic curve analysis for the prediction of shunt-dependent hydrocephalus confirmed that monocyte count exhibited an acceptable area under the curve (AUC = 0.737, 95% CI: 0.601-0.872; p < 0.001). The best predictive cutoff value to discriminate between successful external ventricular drain weaning and shunt-dependent hydrocephalus was identified as a monocyte count ≥0.80 × 103/uL at initial presentation. These preliminary data demonstrate that a monocyte count ≥0.80 × 103/uL at admission predicts shunt-dependent hydrocephalus in patients with aneurysmal subarachnoid hemorrhage; however, further large-scale prospective trials and validation are necessary to confirm these findings.

Iatrogenic Leptomeningeal Carcinomatosis Following Craniotomy for Resection of Metastatic Serous Ovarian Carcinoma: A Systematic Literature Review and Case Report.

Metastasis of ovarian carcinoma to the central nervous system occurs in <2% of cases and classically localizes within the brain parenchyma. Moreover, leptomeningeal spread of these tumors is an exceedingly rare phenomenon. Here, we conduct a systematic review of the current literature on the natural history, treatment options, and proposed pathogenic mechanisms of leptomeningeal carcinomatosis in ovarian carcinoma. We also report a case of a 67-year-old female with stage IV metastatic ovarian serous carcinoma initially confined to the peritoneal cavity with a stable disease burden over the course of three years. Follow-up imaging demonstrated an intracranial lesion, which was resected via craniotomy, and pathology was consistent with the original diagnosis. Three months after surgery, she developed rapidly progressive dizziness, generalized weakness, fatigue, and ataxia. Repeat MRI demonstrated interval development of extensive and diffusely enhancing dural nodularity, numerous avidly enhancing supratentorial and infratentorial lesions, enhancement of the bilateral trigeminal nerves, internal auditory canals, and exit wound from the surgical site into the posterior aspect of the right-sided neck musculature consistent with diffuse leptomeningeal dissemination. The present case highlights that leptomeningeal dissemination of ovarian carcinoma is a potential yet rare consequence following surgical resection of an ovarian parenchymal metastasis. Progressive clinical symptomatology that develops postoperatively in this patient population should prompt urgent workup to rule out leptomeningeal disease and an expedited radiation oncology consultation if identified.

Perimesencephalic Subarachnoid Hemorrhage Has a Unique Peripheral Blood Leukocyte Profile Compared To Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: The authors sought to investigate if peripheral blood leukocyte profiles on admission differed between perimesencephalic, angio-occult, and aneurysmal subarachnoid hemorrhage cohorts. METHODS: We performed a retrospective analysis of 202 consecutive patients with spontaneous subarachnoid hemorrhage. We classified spontaneous subarachnoid hemorrhage as either aneurysmal or nonaneurysmal origin. Nonaneurysmal subarachnoid hemorrhage was subclassified as either perimesencephalic or angio-occult according to the distribution of hemorrhage on the initial imaging. Patient demographics, clinical parameters, radiographic metrics, and laboratory values were obtained on admission. In-hospital data including acute hydrocephalus, shunt dependence, vasospasm, and delayed cerebral ischemia were collected. Comparative analyses were conducted between cohorts. RESULTS: The perimesencephalic subarachnoid hemorrhage cohort exhibited significantly lower neutrophil (7.76 vs. 10.06; P = 0.004), lymphocyte (1.40 vs. 1.90; P = 0.024), and monocyte counts (0.52 vs. 0.73; P = 0.031) than the aneurysmal subarachnoid hemorrhage cohort. There were no significant differences in peripheral blood leukocyte profiles between the angio-occult and aneurysmal subarachnoid hemorrhage cohorts. The nonaneurysmal cohort exhibited significantly lower neutrophil (8.33 vs. 10.06; P = 0.005) and lymphocyte counts (1.47 vs. 1.90; P = 0.011) as well as a lower lymphocyte-to-monocyte ratio (2.80 vs. 4.51; P = 0.018) than the aneurysmal subarachnoid hemorrhage cohort. CONCLUSIONS: Perimesencephalic subarachnoid hemorrhage exhibits a unique peripheral blood leukocyte profile compared to aneurysmal subarachnoid hemorrhage. Moreover, these preliminary data demonstrate that blood leukocytes may be affected by the burden of cisternal subarachnoid hemorrhage or the presence of a ruptured aneurysm. Further large-scale prospective studies and validation are required to confirm these preliminary findings.

Initial intracranial pressure is an independent predictor of unfavorable functional outcomes after aneurysmal subarachnoid hemorrhage.

The authors sought to evaluate whether initial intracranial pressure was associated with functional outcomes following aneurysmal subarachnoid hemorrhage. This retrospective analysis consisted of 54 consecutive patients with aneurysmal subarachnoid hemorrhage and acute symptomatic hydrocephalus requiring emergent placement of an external ventricular drain. Patient demographics, clinical data, intracranial pressure parameters, and radiographic imaging were collected. Functional outcomes were evaluated at 3 months using the modified Rankin Scale and dichotomized as favorable (modified Rankin Scale 0-2) or unfavorable (modified Rankin Scale 3-6). Univariate and multivariate logistic regression analyses were performed to investigate parameters independently associated with functional outcomes. In an adjusted multivariate logistic regression model, initial intracranial pressure (OR: 1.371, 95% CI: 1.119-1.679; p = 0.002) was found to be an independent predictor of unfavorable functional outcomes at 3 months. Receiver operating characteristic curve analysis for the prediction of unfavorable functional outcomes demonstrated that initial intracranial pressure exhibited an acceptable area under the curve (AUC = 0.901, 95% CI: 0.818-0.985; p < 0.001). The optimal predictive threshold to distinguish between favorable and unfavorable functional outcomes was identified at an initial intracranial pressure of 25 mmHg.

Neutrophil Count on Admission Predicts Acute Symptomatic Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: To investigate the association between immunologic counts on admission and acute symptomatic hydrocephalus after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We conducted a retrospective analysis of 143 consecutive patients with aSAH. Patient demographics, clinical parameters, laboratory values, and radiographic imaging were obtained. Univariate and multivariate logistic regression analyses were performed to investigate parameters independently associated with acute symptomatic hydrocephalus. Receiver operating characteristic (ROC) curve analysis determined the best threshold value of neutrophil count to differentiate patients with and without hydrocephalus. RESULTS: Overall, acute symptomatic hydrocephalus developed in 39.16% of patients. In an adjusted multivariate logistic regression model, Hunt and Hess grade 4-5 (odds ratio [OR]: 16.052, 95% confidence interval [CI]: 1.188-216.983; P = 0.037), modified Fisher score 3-4 (OR: 10.107, 95% CI: 1.715-59.572; P = 0.011), intraventricular hemorrhage (OR: 4.578, 95% CI: 1.417-14.788; P = 0.011), neutrophil count (OR: 1.183, 95% CI: 1.033-1.354; P = 0.015), and prior ischemic stroke (OR: 7.003, 95% CI: 1.293-37.929; P = 0.024) were significantly associated with hydrocephalus. ROC analysis for neutrophil count confirmed an acceptable area under the curve (AUC 0.780, 95% CI: 0.701-0.859; P < 0.001). The best threshold value of neutrophil count to predict hydrocephalus was ≥9.80 × 103/mL. Overall, 81.25% of patients who developed shunt dependence had a neutrophil count ≥9.80 × 103/mL on admission (P = 0.003). CONCLUSIONS: Neutrophil count ≥9.80 × 103/mL on admission predicts acute symptomatic hydrocephalus after aSAH in an adjusted multivariate logistic regression model. Moreover, shunt dependence was associated with higher neutrophil counts.

Pineal Gland Metastasis From Poorly Differentiated Carcinoma of Unknown Primary Origin.

Pineal metastasis is an exceedingly rare finding in patients with systemic malignancies. Such lesions are typically the manifestation of a primary lung cancer; nonetheless, a variety of malignancies have been reported to disseminate to the pineal gland including gastrointestinal, endocrine, and skin cancers, among others. However, to our knowledge, pineal gland metastasis without a primary origin has yet to be described. Carcinoma of unknown primary origin is a heterogeneous group of cancers characterized by the presence of metastatic disease without an identifiable primary tumor on metastatic workup. Here, we present a case of a 65-year-old male found to have a heterogeneously enhancing lesion of the pineal gland as well as an enhancing lesion of the left cerebellar hemisphere. Comprehensive metastatic workup demonstrated multifocal metastatic adenopathy without an identifiable primary lesion. Stereotactic biopsy of the pineal lesion revealed poorly differentiated carcinoma with an immunophenotype most consistent with gastrointestinal origin. To our knowledge, this is the first case to describe a pineal gland metastasis without a primary origin. We discuss the relevant literature on pineal gland metastases as well as carcinoma of unknown primary origin.

Response of Pembrolizumab Alone for Non-small Cell Lung Cancer With Brain Metastasis: A Case Report and Literature Review.

Treatment of brain metastases often includes surgical resection, chemotherapeutics and radiotherapy. Given the difficulty in obtaining therapeutic levels of medications within the immune-privileged central nervous system, chemotherapy as a stand-alone treatment modality for brain metastases is an uncommon option. However, there is a growing body of evidence to suggest that immunomodulatory agents can induce a robust immune response in the central nervous system. Here, we describe a 68-year old male who presented with radiographic evidence of new and enlarging lung nodules with mediastinal adenopathy. Lung biopsy was consistent with adenocarcinoma. Immunohistochemical staining demonstrated high expression of programmed cell death protein 1 with a tumor proportion score of 100%. Surveillance magnetic resonance imaging of the brain demonstrated a single enhancing 11 × 7 × 12 mm lesion along the mesial surface of the right frontal lobe. The patient deferred surgical resection as well as stereotactic radiosurgery but agreed to treatment with pembrolizumab. Repeat magnetic resonance imaging at 3-months after initiation of treatment demonstrated complete radiographic resolution of the brain lesion. To our knowledge, this is one of only a few reports in the current literature to document complete resolution of non-small cell lung cancer brain metastasis with pembrolizumab alone. We discuss the emerging literature regarding the efficacy of pembrolizumab in the treatment of brain metastases, central nervous system penetration, and emerging new treatment paradigms involving novel immunotherapy agents.

Delayed cerebral ischemia causing cortical blindness due to repeat cocaine use weeks subsequent to aneurysmal subarachnoid hemorrhage.

Cocaine is a known vasoactive drug associated with poor clinical outcomes and high in-hospital mortality related to aneurysmal subarachnoid hemorrhage; however, the association of prior cocaine use with the incidence of vasospasm and delayed cerebral ischemia remains controversial. We report a case of a 42-year-old male with a history of active cocaine use who presented with a severe headache. Imaging demonstrated diffuse cisternal subarachnoid hemorrhage due to a ruptured basilar apex aneurysm, which was successfully treated with endovascular coil embolization. Despite expedited endovascular treatment and an initially benign clinical course, he suffered from delayed cerebral ischemia resulting in cortical blindness due to bilateral posterior cerebral artery vasospasm secondary to repeat cocaine use weeks after his initial ictus. To our knowledge, the present case is the first to describe delayed cerebral ischemia resulting in a severe neurologic deficit due to repeat cocaine use weeks subsequent to aneurysm rupture. We review the current literature on the association of cocaine use with the incidence of vasospasm and delayed cerebral ischemia as well as the effects of cocaine on the cerebrovasculature.

Recurrent Cerebral Vasospasm and Delayed Cerebral Ischemia Weeks Subsequent to Elective Clipping of an Unruptured Middle Cerebral Artery Aneurysm.

BACKGROUND: Cerebral vasospasm and delayed ischemic neurologic deficits are well-known clinical aftereffects of subarachnoid hemorrhage due to rupture of an intracranial aneurysm. However, vasospasm with consequential ischemia after clipping of an unruptured aneurysm is an exceedingly rare sequela encountered in the reported neurosurgical literature. CASE DESCRIPTION: A 53-year-old woman had presented for elective craniotomy with microsurgical clipping of an unruptured left middle cerebral artery bifurcation saccular aneurysm, which was successfully treated without complications. Despite an initially benign clinical course, she experienced diffuse vasospasm with profound ischemic neurologic deficits on postoperative day 13 with a left middle cerebral artery distribution ischemic infarct. Moreover, she developed recurrent delayed spasm of the right posterior cerebral artery on postoperative day 26 and, consequentially, a left homonymous hemianopsia despite treatment with intra-arterial verapamil infusion. CONCLUSIONS: To the best of our knowledge, we have reported the first case of recurrent cerebral vasospasm and delayed ischemia neurologic deficits weeks subsequent to clipping of an unruptured aneurysm. The findings from the present case highlight the importance of considering delayed vasospasm as a cause of acute onset neurologic symptoms for patients who have recently undergone elective aneurysm surgery. We also reviewed the current data regarding the epidemiology, surgical factors, and proposed pathophysiologic mechanisms related to vasospasm after elective cases.

Factors affecting R01 grant funding among academic neurosurgeons over the last decade.

BACKGROUND: Recent studies have reported a gender and medical degree disparity for those receiving Research Project Grants in surgical specialties. The aim of the present study is to analyze factors among academics neurosurgeons that correlate to higher amounts of R01 grant monies awarded. MATERIALS AND METHODS: The National Institutes of Health Research Portfolio Online Reporting Tools Expenditures and Results database was queried for neurosurgery funding between 2008 and 2018. Grant recipients were categorized among type of degree, secondary degree(s), professorship, gender, and h - index. Statistical analysis was performed. RESULTS: The National Institutes of Health awarded 480 R01 grants totaling $182,482,644 to 81 allopathic neurosurgeons between 2008 and 2018. No osteopathic neurosurgeons were awarded an R01 grant during this timeframe. There was a significant difference for type of professorship on the total awarded amount at the p < 0.05 level for the three types of professorship [F (2,78) = 4.85, p < 0.01)]. There was a significant difference for magnitude of h - index on total R01 monies (p < 0.00001). Males accounted for the majority of R01 monies (93.99%); however, no significant difference between average amount awarded and gender was identified (p = 0.86). A secondary degree was without significant difference for R01 amount awarded (p = 0.75). CONCLUSIONS: The present study establishes a medical degree disparity for academic neurosurgeons who receive an R01 grant. Statistically significant factors found to affect amount of R01 grant monies awarded were limited to type of professorship and magnitude of h - index.