A Review on the Surgical Management of Insular Gliomas.

The surgical treatment of insular gliomas requires specialized knowledge. Over the last three decades, increased momentum in surgical resection of insular gliomas shifted the focus from one of expectant management to maximal safe resection to establish a diagnosis, characterize tumor genetics, treat preoperative symptoms (i.e., seizures), and delay malignant transformation through tumor cytoreduction. A comprehensive review of the literature was performed regarding insular glioma classification/genetics, insular anatomy, surgical approaches, and patient outcomes. Modern large, published series of insular resections have reported a median 80% resection, 80% improvement in preoperative seizures, and postsurgical permanent neurologic deficits of less than 10%. Major complication avoidance includes recognition and preservation of eloquent cortex for language and respecting the lateral lenticulostriate arteries.

Salvage Radiosurgery for Recurrent Supratentorial Primitive Neuroectodermal Tumors: A Single Institutional Series and Review of the Literature.

INTRODUCTION: Supratentorial primitive neuroectodermal tumor is a rare, aggressive intrinsic brain tumor with limited treatment options for recurrent disease. SRS as a treatment modality in the recurrent setting was investigated. METHODS: A retrospective review of 8 patients treated with SRS for local or distant recurrence of supratentorial PNET from 1999 to 2014 was conducted. RESULTS: Thirty-six tumors were treated in 15 sessions in 8 patients. The median patient age was 22.5 (interquartile range [IQR], 14.75-43.5 years) with a median 21-month period from diagnosis until SRS (IQR, 16-23.75 months). The median prescription isodose volume was 1.85 cm3 (IQR, 1.85-7.02 cm3); median tumor margin dose was 18 Gy (IQR 14-20 Gy); and median isocenters was 2 (range 1-13). No patients experienced adverse radiation effects. All but 1 patient died, and the median overall survival was 32 months (IQR, 26.75-53.5 months) with median overall survival following SRS of 9.5 months (IQR, 5.25-30 months). Univariate analysis failed to demonstrate a statistically significant association between age, number of gamma knife treatments, interval to gamma knife, and margin radiation dose with overall survival. DISCUSSION/CONCLUSION: This series supports the use of SRS in patients with recurrent supratentorial PNET following multimodal therapy.

International trends in grant and fellowship funding awarded to women in neurosurgery.

OBJECTIVE: Metric tracking of grant funding over time for academic neurosurgeons sorted by gender informs the current climate of career development internationally for women in neurosurgery. METHODS: Multivariate linear trend analysis of grant funding awarded to neurosurgeons in the NIH and World Research Portfolio Online Reporting Tools Expenditures and Results (RePORTER) was performed. Traveling fellowships for international neurosurgery residents sponsored by the AANS and Congress of Neurological Surgeons (CNS) were also analyzed. RESULTS: Within the US, funding awarded to female neurosurgeons has remained static from 2009 to 2019 after adjusting for inflation and overall trends in NIH funding (ß = -$0.3 million per year, p = 0.16). Internationally, female neurosurgeons represented 21.7% (n = 5) of project leads for World RePORTER grants. Traveling fellowships are also an important building block for young international female neurosurgeons, of which 7.4% (n = 2) of AANS international traveling fellowships and 19.4% (n = 7) of AANS/CNS pediatrics international traveling fellowships are women. CONCLUSIONS: Over the past decade, funding has increased in neurosurgery without a concordant increase in funding awarded to women. Recognition of this trend is essential to focus efforts on research and career development opportunities for women in neurosurgery. Worldwide, female neurosurgeons head one-fifth of the funded project leads and constitute a minority of international traveling fellowships awarded by organized neurosurgery.

Attenuating hypoxia driven malignant behavior in glioblastoma with a novel hypoxia-inducible factor 2 alpha inhibitor.

Hypoxia inducible factor (HIFs) signaling contributes to malignant cell behavior in glioblastoma (GBM). We investigated a novel HIF2α inhibitor, PT2385, both in vitro, with low-passage patient-derived cell lines, and in vivo, using orthotopic models of glioblastoma. We focused on analysis of HIF2α expression in situ, cell survival/proliferation, and survival in brain tumor-bearing mice treated with PT2385 alone and in combination with standard of care chemoradiotherapy. HIF2α expression increased with glioma grade, with over half of GBM specimens HIF2α positive. Staining clustered in perivascular and perinecrotic tumor regions. Cellular phenotype including proliferation, viability, migration/invasion, and also gene expression were not altered after PT2385 treatment. In the animal model, PT2385 single-agent treatment did improve median overall survival compared to placebo (p = 0.04, n = 21) without a bioluminescence correlate (t = 0.67, p = 0.52). No difference in animal survival was seen in combination treatment with radiation (RT)/temozolomide (TMZ)/PT2385 (p = 0.44, n = 10) or mean tumor bioluminescence (t 1.13, p = 0.32). We conclude that HIF2α is a reasonable novel therapeutic target as expressed in the majority of glioblastomas in our cohort. PT2385 as a single-agent was efficacious in vivo, however, an increase in animal survival was not seen with PT2385 in combination with RT/TMZ. Further study for targeting HIF2α as a therapeutic approach in GBM is warranted.

Craniocervical Osteoradionecrosis Treated with Neoadjuvant and Adjuvant Hyperbaric Oxygen in Combination with Posterior Spinal Fusion.

BACKGROUND: Radiation therapy for malignant head and neck cancers includes a risk for off-target effects to bony structures, posing a risk for osteoradionecrosis (ORN). Patients in whom ORN develops can also harbor concomitant osteomyelitis and reduced healing capacity, making for a particularly challenging entity to treat. Hyperbaric oxygen therapy (HBO) has been shown to be effective in the treatment of mandibular ORN in the otolaryngology literature; yet, few reports exist detailing its utility when treating ORN of the craniocervical junction. Herein, we report 2 cases of ORN of the craniocervical junction who received both neoadjuvant and adjuvant HBO in combination with posterior spinal fusion. CASE DESCRIPTION: Two patients with craniocervical junction ORN were treated with HBO delivered over 20 sessions before and after surgery in 90-minute treatments to 2.5 atmospheres of pressure. The patients underwent posterior occipital-cervical fusions with an average operative time of 301 (±21.5) minutes with 250 (±150) mL of blood loss. Both patients stayed in the hospital for 5 days, with no periprocedural complications. Outcomes included a 30% improvement of global assessment of function on follow-up EuroQol 5-Dimension Questionnaire. Postoperative imaging demonstrated solid bony fusion, and both patients returned to full work duty. CONCLUSIONS: ORN is a difficult-to-treat radiation complication in head and neck cancers. Few reports exist detailing treatment options for ORN of the craniocervical junction in conjunction with surgical stabilization. We report 2 successful cases of HBO-assisted treatment of ORN and highlight the important role HBO can play in promoting bony fusion in these at-risk patients.

Successful application of stereotactic radiosurgery for multiply recurrent Rathke's cleft cysts.

OBJECTIVE: Rathke's cleft cysts (RCCs) are benign lesions of the sella turcica that usually come to neurosurgical attention due to compression of the optic apparatus (OA) and headaches. Treatment options for these lesions include observation, aspiration of cyst contents, or open resection of the cyst with the cyst wall. All of these options involve the potential for cyst recurrence or enlargement. In this study the authors report on a potential new therapeutic option for RCCs, i.e., stereotactic radiosurgery (SRS). METHODS: A retrospective review was conducted of 5 patients with histologically confirmed, multiply recurrent RCCs who were treated with single-fraction SRS at a tertiary referral academic medical center. RESULTS: The total cohort consisted of 5 female patients with an average age of 31.8 years. The most common presenting symptom was headache followed by blurry vision. The symptoms were present on average for 7 months before intervention. The median number of surgeries prior to radiosurgery was 2. The average volume of lesion treated was 0.34 cm3. The median SRS dose was 12.5 Gy prescribed to the 50% isodose line with an average prescription coverage of 96.6%. The median dose to the OA was 5 Gy. At last follow-up, 3 of 5 cysts had completely regressed, 1 had regressed by more than 50% but was still present, and 1 was stable, with an overall mean follow-up duration of 34.2 months. There were no neurological, endocrinological, or visual complications attributable to SRS during the follow-up period. CONCLUSIONS: RCCs can be a challenging clinical entity to treat, especially when they are multiply recurrent. In patients with an average of 2 previous surgeries for resection, a single SRS session prevented recurrence universally, with an average follow-up of almost 3 years. These results indicate that further investigation of the treatment of RCCs with SRS is indicated.

Utility of cerebrospinal fluid lactate in aneurysmal subarachnoid hemorrhage.

BACKGROUND: An external ventricular drain (EVD) treats hydrocephalus in patients with aneurysmal subarachnoid hemorrhage (aSAH). This study examines the utility of cerebrospinal fluid (CSF) lactate collected from an EVD as a proposed biomarker to predict patient outcome and vasospasm/delayed cerebral ischemia. METHODS: Consecutive adults admitted to Wake Forest Baptist Medical Center from 2010 to 2015 with aSAH were identified through the electronic medical record, and clinical variables were collected and analyzed for correlation with incidence of vasospasm and discharge outcome. RESULTS: In all, 51 patients with aSAH and an EVD had CSF lactate measured which ranged from 1.9 to 6.2 mmol/L, with a median value of 3.2 mmol/L. Vasospasm based on transcranial Doppler assessment occurred in 29 patients (57%), of which 20 (45%) were clinically symptomatic. Good outcome (discharge to home/acute rehab) occurred in 35 patients (69%). Sixteen patients (31%) had an unfavorable outcome (died/discharged to nursing homes/long-term acute care facility). In multivariate regression analysis, unfavorable outcome at discharge (P = 0.02), elevated CSF protein (P = 0.04), and admission Hunt and Hess score 3-5 (P = 0.05) were significantly associated with higher CSF lactate. The risk of symptomatic vasospasm increased with lactate in univariate analysis, but did not reach statistical significance (P = 0.077). CONCLUSION: The measurement of the CSF biochemical markers using an EVD is feasible and safe. We found that elevated CSF lactate correlates with patient outcome. Larger prospective studies are needed to test the validity of this finding and for understanding the underlying pathophysiologic mechanisms.

Hypoxia-inducible factor 2α: a novel target in gliomas.

Hypoxia is an important contributor to aggressive behavior and resistance mechanisms in glioblastoma. Upregulation of hypoxia inducible transcription factors (HIFs) is the primary adaptive cellular response to a hypoxic environment. While HIF1α has been widely studied in cancer, HIF2α offers a potentially more specific and appealing target in glioblastoma given expression in glioma stem cells and not normal neural progenitors, activation in states of chronic hypoxia and expression that correlates with glioma patient survival. A first-in-class HIF2α inhibitor, PT2385, is in clinical trials for renal cell carcinoma, and provides the first opportunity to therapeutically target this important pathway in glioma biology.

Intraventricular recurrence of a craniopharyngioma: case report.

Craniopharyngiomas frequently recur locally or less commonly along the path of prior resection. Ectopic recurrence is rare, although cases are reported along the neuraxis spanning from the subgaleal space down to the S1 nerve root. This case reports on a girl with a history of craniopharyngioma first resected at 23 months of age with two local suprasellar recurrences managed with repeat craniotomy and external beam radiation therapy. At age 14 she complained of worsening headaches and brain MRI demonstrated an enhancing 1.2-cm cystic lesion in the posterior body of the left lateral ventricle. Pathology following endoscopic resection of the lesion was consistent with an adamantinomatous craniopharyngioma. This case report serves to describe the first reported recurrence of a craniopharyngioma in the lateral ventricle and emphasizes the need for a high index of suspicion along with long-term follow-up of patients with a history of craniopharyngioma.

Combined interventional and surgical treatment of tandem middle cerebral artery embolus and internal carotid artery occlusion: case report.

Tandem internal carotid artery (ICA) origin occlusion and middle cerebral artery (MCA) thromboembolism is a life-threatening condition with poor neurological outcome. The authors report on a patient presenting with acute ischemic stroke from a tandem ICA and MCA occlusion with penumbra. Emergency MCA mechanical thrombectomy was performed through percutaneous cervical ICA access due to the inability to cross the cervical carotid occlusion. Emergency carotid endarterectomy to reperfuse the poorly collateralized hemisphere and repair the ICA access site was performed 2 hours after completion of tissue plasminogen activator (tPA) infusion. This case illustrates the shortest reported interval between tPA infusion and open surgical intervention for carotid revascularization, as well as the role of direct carotid artery access for mechanical thrombectomy. The authors also describe the use of a temporizing femoral artery-to-ICA shunt to maintain cerebral perfusion in the setting of ICA occlusion.

Tracking Career Paths of Women in Neurosurgery.

BACKGROUND: Women represent a growing cohort of US neurosurgeons. OBJECTIVE: To describe postresidency fellowship, practice environment, and updated academic rank among female neurosurgeons. METHODS: Databases from the American Association of Neurological Surgeons (AANS) and the American Board of Neurological Surgery (ABNS) from 1964 to 2013 were reviewed for female neurosurgery residency graduates. Data on postresidency fellowships, practice environment (private vs academic), academic rank, board certification, and AANS/CNS (Congress of Neurological Surgeons) Joint Section on Women in Neurosurgery (WINS) membership were collected in 2016. Academic rank was verified from program websites and electronic correspondence. Faculty members were asked to report directorships and tenure. The AANS/CNS Joint Section on Women in Neurosurgery verified WINS membership. RESULTS: A total of 379 female neurosurgery residency graduates were identified in this 50-yr span. Of these, 70% became ABNS certified, and 2.1% left neurosurgery. Twenty-seven percent of women (n = 103) pursued fellowships, with pediatric neurosurgery (33%) the most common. Regarding practice environment, 26% entered academic medicine (n = 91), with 42 at the rank of assistant professor, 33 at the rank of associate professor, and 16 reaching the rank of full professor. CONCLUSION: Upon completion of training, 27% of women pursue fellowships. The distribution of women in private vs academic practice environments is proportionate to male neurosurgeons; however, the number women in academic leadership positions remains exceedingly low, with disproportionate representation in higher academic ranks. Women in national organized neurosurgery are increasing. Tracking the career paths of women in neurosurgery is a necessary step to identifying current achievements and opportunities for future progress.

Surgical Considerations in the Optimal Management of Patients with Malignant Brain Tumors.

OPINION STATEMENT: Advances in technology are revolutionizing medicine and the limits of what we can offer to our patients. In neurosurgery, technology continues to reduce morbidity, increase surgical accuracy, facilitate tissue acquisition, and promote novel techniques for prolonging survival in patients with neuro-oncologic disease. Surgery has been the backbone of glioma diagnosis and treatment by providing adequate, high quality material for precise histologic diagnosis, and genomic characterization in the setting of significant intratumoral heterogeneity, thus allowing personalized treatment selection in the clinic. The ability to obtain and accurately measure the maximal extent of resection in glioma surgery also remains a central role of the neurosurgeon in managing this cancer. To meet these goals, today's operating room has transformed from the traditional operating table and anesthesia machine to include neuronavigation instrumentation, intraoperative computed tomography, and magnetic resonance imaging scanners, advanced surgical microscopes fitted with fluorescent light filters, and electrocorticography machines. While surgeons, oncologists, and radiation oncologists all play unique critical roles in the care of patients with malignant gliomas, familiarity with developing techniques in complimentary subspecialties can enhance coordination of patient care, research productivity, professional interactions, and patient confidence and comfort with the physician team. Herein, we provide a summary of the advances in the field of neurosurgical oncology which allow more precise and optimal surgical resection for patients with malignant gliomas.

Evaluation of a Traumatic Vertebral Artery Occlusion.

BACKGROUND: Penetrating neck injury occurs in 5%-10% of all trauma cases and carries a significant burden of morbidity and mortality (15%). We describe the evaluation and management of a 25-year-old man shot in the neck with occlusion of the left vertebral artery from its origin to C6. This is a case report in which medical data were analyzed retrospectively with institutional review board approval. CASE DESCRIPTION: Neurologic examination revealed paresthesias and dysesthesias in a left C8 dermatomal distribution. Computed tomography angiography of the neck demonstrated no opacification of the left vertebral artery from its origin to C6. Magnetic resonance imaging of the cervical spine revealed an acute infarct in the left cerebellum. A cerebral angiogram highlighted hemodynamic compromise, and the patient was felt to be at significant risk of further cerebral infarction. Augmenting flow to the posterior circulation would mitigate that risk. The patient was taken to the operating room for a transposition of the vertebral artery to the common carotid artery. CONCLUSIONS: The patient presented with silent cerebellar infarction due to a vertebral artery injury and impending vertebrobasilar insufficiency. This case demonstrates clinical evaluation of the posterior circulation and treatment with a bypass technique through mobilization of the vertebral artery from the boney vertebral foramen with anastomosis to the common carotid.

Fungal Contamination of Methylprednisolone Causing Recurrent Lumbosacral Intradural Abscess.

Fungal meningitis transmitted through injections of methylprednisolone contaminated with Exserohilum rostratum affected 753 persons and caused 61 deaths in the United States in 2012. We report a case of infection recurrence after 24-months with the unique manifestation of an intradural fungal abscess. Fungal disease should remain on the differential diagnosis list for previously exposed patients.

Positive trends in neurosurgery enrollment and attrition: analysis of the 2000-2009 female neurosurgery resident cohort.

OBJECTIVE: Women compose a minority of neurosurgery residents, averaging just over 10% of matched applicants per year during this decade. A recent review by Lynch et al. raises the concern that women may be at a higher risk than men for attrition, based on analysis of a cohort matched between 1990 and 1999. This manuscript aims to characterize the trends in enrollment, attrition, and postattrition careers for women who matched in neurosurgery between 2000 and 2009. METHODS: Databases from the American Association of Neurological Surgeons (AANS) and the American Board of Neurological Surgery (ABNS) were analyzed for all residents who matched into neurosurgery during the years 2000-2009. Residents were sorted by female gender, matched against graduation records, and if graduation was not reported from neurosurgery residency programs, an Internet search was used to determine the residents' alternative path. The primary outcome was to determine the number of women residents who did not complete neurosurgery training programs during 2000-2009. Secondary outcomes included the total number of women who matched into neurosurgery per year, year in training in which attrition occurred, and alternative career paths that these women chose to pursue. RESULTS: Women comprised 240 of 1992 (12%) matched neurosurgery residents during 2000-2009. Among female residents there was a 17% attrition rate, compared with a 5.3% male attrition rate, with an overall attrition rate of 6.7%. The majority who left the field did so within the first 3 years of neurosurgical training and stayed in medicine--pursuing anesthesia, neurology, and radiology. CONCLUSIONS: Although the percentage of women entering neurosurgical residency has continued to increase, this number is still disproportionate to the overall number of women in medicine. The female attrition rate in neurosurgery in the 2000-2009 cohort is comparable to that of the other surgical specialties, but for neurosurgery, there is disparity between the male and female attrition rates. Women who left the field tended to stay within medicine and usually pursued a neuroscience-related career. Given the need for talented women to pursue neurosurgery and the increasing numbers of women matching annually, the recruitment and retention of women in neurosurgery should be benchmarked and assessed.

Relapsing intracranial plasma cell granuloma: A case report.

Plasma cell granuloma is a pathological entity reported in nearly every organ system; however, intracranial cases remain rare. In the current case report, we present a case of intracranial plasma cell granuloma with the longest known follow-up period in the literature. Medical follow-up over 14 years, detailing four recurrences following the patient's initial presentation and management, is presented. The patient's treatment course consisted of three craniotomies, 3,600-cGy fractionated radiation and two courses of glucocorticoid therapy. In addition to disease surveillance using clinical examination and imaging, this case represents the first description of the clinical utility of analyzing changes in an inflammatory blood marker, the erythrocyte sedimentation rate, which coincided with recurrence and response to therapy.