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Neurosurgery is male dominated with women representing only 12% of residents and 5% of practicing neurosurgeons. The conflicting demands of training versus pregnancy and motherhood are significant deterrents to women entering the field. We examined pregnancy incidence and timing, perinatal complications, and the perceived career impact of motherhood on female neurosurgeons using an anonymous survey of 643 training, practicing, and retired female neurosurgeons from the United States. Among 260 respondents, 50.8% (132/260) reported pregnancies, with an average age at first pregnancy that was significantly higher than the national average (32.1 vs 26.3 yr). In all, 40.1% (53/132) of respondents reported perinatal complications in at least one of their pregnancies. Only 25% (33/132) of respondents noted designated program maternity allowances. The most significant challenges associated with being a mother and neurosurgeon reported were issues relating to work/life balance, "mommy guilt," and sleep deprivation. A majority of respondents, 70.1% (82/116), reported fear of backlash from co-residents, partners, and staff, as well as hindered career advancement related to childbearing. Female neurosurgeons face challenges surrounding family planning different from those faced by male practitioners. Higher perinatal and fetal complications, backlash from colleagues, and demanding workload are significant issues. Progress requires institutional support and mentorship for women to create a more diverse field of practitioners.

Neuro-Oncology research has dictated the need for animal models and since early 1970s rodent glioma models have been the choice model for investigators. These initial models were developed by exposing adult rodents to carcinogens to induce brain tumors. A panel of rodent tumor derived cells which form tumors upon reimplantation were then used to study tumor biology and response to therapeutics. The advent of immune compromised mouse models led to the expansion of these efforts to include human patient derived tumor cells. While these tumors captured the molecular background of GBM, they were poor models to understand immune micro-environment of brain tumors. Molecular biology advances further led to the development of murine models that generated spontaneous tumors. These models exquisitely recapitulate GBM molecular alterations in an immune competent environment. However the murine origin of these models often limits their utility for investigations of biological therapeutics that are inherently species specific. The advent of humanized mouse models heralds a new phase providing mice repopulated with human immune cells that bear human tumors. While these models are rarely isogenic, they are now considered the gold standard for research. However these models are cumbersome to use, and extremely expensive. Here we summarize the utility and challenges of the different rodent models frequently used in Neuro-Oncology research.

Previous studies have demonstrated possible differences in glioblastoma (GBM) survival attributable to ethnicity. The goal of this study was to quantify oncogenic differences and evaluate the overall survival (OS) and progression-free survival (PFS) differences in GBM patients across race/ethnicity using both population-based surveillance and institutional data sets from the United States (US) and Mexico.Retrospective cohort study comprising the Texas Cancer Registry (TCR, n = 4134) and referral institutions located in US (n = 254) and Mexico (n = 47) were evaluated. Primary outcomes include OS and PFS. Oncogenic differences attributable to ethnicity were assessed. IDH1/IDH2 status was evaluated by sequencing in US and Mexico samples. Kaplan-Meier and Cox proportional hazards regression for survival analysis.A total of 4134 GBM patients were identified from the TCR data set, ethnicity comparison demonstrated that Hispanic patients were diagnosed at a significantly younger age compared to non-Hispanic white patients (NHW) (median: 58 vs. 62, P0.001) and had improved OS (hazard ratio: 0.82, P0.001). In the oncogenic analysis, we observed a significant enrichment of IDH1/IDH2 mutations in Mexican Hispanic patients compared to US Hispanic patients (29.8% vs. 7.9%, P = 0.012); IDH2 mutations drove this difference. Post-progression survival was significantly shorter in patients from Mexico than US (3.0 vs. 11.4 months; P0.001), while OS remained similar.IDH2 mutations are more prevalent in Mexican Hispanic individuals compared to US individuals and may be a crucial contributor to the previously reported survival benefit of Hispanic individuals in large population databases. These findings are critical for both screening of IDH2 mutations and targeted interventions in GBM.

In recent years, oncolytic viruses (OVs) have emerged as a powerful, targeted immunotherapy with the identification of new viral vectors as well as genetically engineered viral payloads. Owing to t...

Background: Middle meningeal artery (MMA) pseudoaneurysms are rare but can occur secondary to trauma with an associated skull fracture and can present with a variety of hemorrhage patterns. Epidural, subdural, subarachnoid, and intraparenchymal hematomas have all been reported. Given the wide range of clinical presentations and radiographic findings, multiple treatment strategies have been employed, including surgical removal, endovascular intervention, and conservative treatment. MMA pseudoaneurysms typically range from 2 to 5 mm in size and have been shown to have unpredictable growth patterns. Case Description: A 54-year-old male identifying as a Jehovah’s Witness presented after a fall and was found to have an epidural hematoma with an accompanying temporal bone fracture. Imaging demonstrated a traumatic pseudoaneurysm of the MMA. Given the patient’s religious preferences, the emphasis was made during surgical planning for the minimization of blood loss. The epidural hematoma was evacuated, and the MMA pseudoaneurysm was directly visualized and surgically excised after ligation of its tributaries. The patient tolerated the procedure well without significant blood loss and made a complete neurological recovery. Conclusion: A well-circumscribed hypodensity on CT within a surrounding hyperintense collection should raise suspicion of MMA pseudoaneurysm in the setting of overlying temporal bone fracture as supported by previous imaging findings of large MMA pseudoaneurysms. The early detection of MMA pseudoaneurysm is imperative, as the presence may dictate more urgent intervention and changes in operative technique. Although not much is known about the nature and progression of these lesions, surgical excision has remained a safe, reliable method of treatment.

Oncolytic viruses (OVs) are designed to ablate cancerous cells while sparing non-malignant cells and tissues. In the wake of an active tumor infection, OVs can activate an anti-tumor immune response. Currently, an oncolytic Herpes simplex 1 (HSV-1) derived virus encoding for granulocyte-macrophage colony stimulating factor (GM-CSF) is approved in the US and Europe as a treatment for metastatic melanoma, and an oncolytic adenovirus (oAd) is approved in China for head and neck cancer therapy. Despite the approved use for these indications, this promising biological therapy is currently under-used. However, a multitude of viruses are actively being explored in preclinical animal models and clinically in patients with different malignancies for safety and efficacy. Several ongoing clinical trials evaluate OV utility in combination with other therapies, such as chemotherapeutics and immune checkpoint inhibitors. In this chapter, we highlight some of the barriers faced by OVs and discuss methods used to convert these challenges into opportunities for improvement. Major advancements in this field include engineering OVs to deliver payloads with anti-angiogenic, immune modulatory, or extracellular matrix degrading proteins, as well as in combination with immunotherapies, DNA damaging agents, and stem cells to enhance the therapeutic efficacy of OVs. Despite facing some challenges, there is continued enthusiasm for this innovative and promising biological arsenal in treating cancer.

Glioblastoma (GBM) is the most common primary malignant brain tumor of the central nervous system with a 5-year survival of < 5%. Population studies have demonstrated that among all ethnicities, non-Hispanic whites (NHW) have the worst prognosis; however, differences within the oncogenome based on ethnicity have not been assessed. We utilized the Texas Cancer Registry (TCR) for population-based analysis including 4,134 GBM patients between the years of 1995 to 2013 with 75.6% NHW and 16.5% Hispanics. In accordance with previously published findings, within the TCR we detected a 12% relative survival improvement in Hispanics compared to NHW when controlling for known survival mediators including age, resection, chemotherapy, and radiation. In order to assess for oncogenic differences, we utilized a prospectively maintained database of 257 GBM patients within the city of Houston, TX (14.9% Hispanic) and 48 GBM patients from the National Institute of Neurology and Neurosurgery in Mexico City, Mexico (100% Hispanic) to assess for oncogenomic differences attributable to ethnicity. Next generation sequencing of GBM within the Houston cohort, for 315 tumor-related genes, identified no significant differences in genomic alterations owing to ethnicity. However, when we compared the multigenerational, mixed-heritage Hispanics present in the Houston cohort to the Mexico cohort (Sanger sequencing), a significant difference was found in the frequency of IDH1and IDH2mutations (29.8 % Mexico Hispanics, 7.9% Houston Hispanics; p=0.014). In particular, the rate of IDH2mutations is significantly enriched in the Mexico population (19%) when compared to the Houston population (0%) or to previously published rates of IDH2 mutations in GBM (~3%). Ultimately, these findings highlight the need for multiethnic trial enrollment as well as the need for improved testing of IDH2 mutations in patients of distinct ethnicities. Future studies are needed to identify the mechanisms promoting the increased frequency of IDH2 mutations in Mexican Hispanics.