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Low-grade gliomas are a broad category of tumors that can manifest at different stages of life. As a group, their prognosis has historically been considered to be favorable, and surgery is a mainstay of treatment. Advances in the molecular characterization of individual lesions has led to newer classification systems, a better understanding of the biological behavior of different neoplasms, and the identification of previously unrecognized entities. New prospective genetic and molecular data will help delineate better treatment paradigms and will continue to change the taxonomy of central nervous system tumors in the coming years. Advances in the field of radiomics will help predict the molecular profile of a particular tumor through noninvasive testing. Similarly, more precise methods of intraoperative tumor tissue analysis will aid surgical planning. Improved surgical outcomes propelled by novel surgical techniques and intraoperative adjuncts and emerging forms of medical treatment in the field of immunotherapy have enriched the management of these lesions. We review the contemporary management and innovations in the treatment of low-grade gliomas.

Low-grade gliomas are clinically challenging entities. Patients with these tumors tend to be relatively young at presentation, and lesions are often incidental findings or are identified because the patient presents with a seizure. Rapidly emerging and evolving molecular classifications of gliomas have influenced treatment paradigms. Importantly, low-grade gliomas can be classified on the basis of IDH mutation status, whereby low-grade astrocytomas harbor the IDH mutation, while oligodendrogliomas are defined by both IDH mutant status and 1p/19q co-deletion. Given the importance of molecular classification for diagnosis, treatment planning, and prognostication, tissue samples are necessary for proper management. Literature supports improved overall survival and outcomes with increased extent of resection for low-grade glioma. Awake craniotomies and resection of insular low-grade gliomas both have been demonstrated as safe and improve outcomes for patients with lesions located in eloquent areas. Given the younger age at diagnosis of these lesions compared with higher-grade gliomas, fertility, fertility preservation, and potential malignant transformation should be discussed with patients of childbearing age.

BACKGROUND Craniosynostosis (CSS) is the premature fusion of calvarial sutures associated with identified genetic mutations or secondary to alterations in intracranial pressure, brain, or bone growth patterns. Of the metabolic etiologies implicated in CSS, X-linked hypophosphatemic rickets (XLHR) is the most common, with dysfunctional bone mineralization leading to progressive hyperostosis and delayed synostosis. There is a paucity of literature discussing the unique surgical considerations for XLHR-related CSS. OBSERVATIONS A 26-month-old male with XLHR-related sagittal CSS underwent cranial vault remodeling (CVR). Surgery was complicated by the presence of diploic hypertrophy with significant intraoperative estimated blood loss (EBL). EBL greatly exceeded reference ranges for CVR in all-cause CSS. As a result, the surgical goals were modified and the complete planned procedure aborted. Subsequent review of preoperative imaging revealed multiple fine vascular lacunae within the bone. A systematic literature review was conducted to identify reported complications relating to surgical intervention for rickets-associated CSS. LESSONS Future considerations for patients with XLHR-related CSS should emphasize awareness of metabolic risk factors with associated complications, and the need for selection of approach and operative management techniques to avoid EBL. Further research is required to elucidate underlying mechanisms and determine whether the encountered phenomenon is characteristic across this patient population and potentially minimized by preoperative medical therapy.

OBJECTIVE Aneurysmal bone cysts (ABCs) are benign cystic lesions most commonly occurring in the long bones of pediatric patients. Spinal ABCs may be difficult to resect given their invasive, locally destructive nature, proximity to critical structures such as the spinal cord, and their intrinsic hypervascularity, for which complete embolization is often constrained by radiculomedullary segmental feeders. Denosumab, a monoclonal antibody that binds the receptor activator of nuclear factor kappa B (NF-κB) ligand, has been utilized in the treatment of ABCs most often as a rescue therapy for recurrent disease. Here, the authors present 3 cases of neoadjuvant denosumab use in surgically unresectable tumors to calcify and devascularize the lesions, allowing for safer, more complete resection. METHODS This is a single-center, retrospective case series treated at a tertiary care cancer center. The authors present 3 cases of spinal ABC treated with neoadjuvant denosumab. RESULTS All 3 patients experienced calcification, size reduction, and a significant decrease in the vascularity of their ABCs on denosumab therapy. None of the patients developed new neurological deficits while on denosumab. Subsequently, all underwent resection. One patient continued denosumab during the immediate postoperative period because a subtotal resection had been performed, with stabilization of the residual disease. No complications were associated with denosumab administration. CONCLUSIONS The use of denosumab in unresectable ABCs can cause calcification and devascularization, making safe resection more likely.

Salvage of recurrent previously irradiated brain metastases (rBrM) is a significant challenge. Resection without adjuvant re-irradiation is associated with a high local failure rate, while reirradiation only partially reduces failure but is associated with greater radiation necrosis risk. Salvage resection plus Cs131 brachytherapy may offer dosimetric and biologic advantages including improved local control versus observation, with reduced normal brain dose versus re-irradiation, however data are limited.A prospective registry of consecutive patients with post-stereotactic radiosurgery (SRS) rBrM undergoing resection plus implantation of collagen-matrix embedded Cs131 seeds (GammaTile, GT Medical Technologies) prescribed to 60 Gy at 5 mm from the cavity was analyzed.Twenty patients underwent 24 operations with Cs131 implantation in 25 tumor cavities. Median maximum preoperative diameter was 3.0 cm (range 1.1-6.3). Gross- or near-total resection was achieved in 80% of lesions. A median of 16 Cs131 seeds (range 6-30), with a median air-kerma strength of 3.5 U/seed were implanted. There was one postoperative wound dehiscence. With median follow-up of 1.6 years for survivors, two tumors recurred (one in-field, one marginal) resulting in 8.4% 1-year progression incidence (95%CI = 0.0-19.9). Radiographic seed settling was identified in 7/25 cavities (28%) 1.9-11.7 months post-implantation, with 1 case of distant migration (4%), without clinical sequelae. There were 8 cases of radiation necrosis, of which 4 were symptomatic.With 1.5 years of follow-up, intraoperative brachytherapy with commercially available Cs131 implants was associated with favorable local control and toxicity profiles. Weak correlation between preoperative tumor geometry and implanted tiles highlights a need to optimize planning criteria.

OBJECTIVE Syringomyelia (syrinx) associated with Chiari malformation type I (CM-I) is commonly managed with posterior fossa decompression, which can lead to resolution in most cases. A persistent syrinx postdecompression is therefore uncommon and challenging to address. In the setting of radiographically adequate decompression with persistent syrinx, the authors prefer placing fourth ventricular subarachnoid stents that span the craniocervical junction particularly when intraoperative observation reveals arachnoid plane scarring. The objective of this study was to evaluate the safety and efficacy of a fourth ventricle stent for CM-I–associated persistent syringomyelia, assess dynamic changes in syrinx dimensions, and report stent-reduction durability, clinical outcomes, and procedure-associated complications. METHODS The authors performed a single-institution, retrospective review of patients who underwent fourth ventricular subarachnoid stent placement for persistent CM-I–associated syringomyelia following a prior posterior fossa decompression. The authors’ institutional Chiari database contains 600 cases with 149 decompressions for CM-I–associated syringomyelia, of which 13 met criteria for inclusion. Data on patient demographics, clinical presentation and outcomes, and MRI findings were collected. The maximal syrinx diameter was estimated by calculating the area of an elliptical cross-section in the largest axial plane from preoperative, immediately postoperative, and late postoperative T2-weighted MR images. RESULTS All 13 patients experienced a significant decrease in mean syrinx area from the preoperative to the late postoperative MRI (mean syrinx diameter 114.1 ± 81.8 mm2 vs 24.5 ± 23.8 mm2, p < 0.001). The mean time until late postoperative MRI was 19.7 months (range 2.0–70.7 months). The syrinx area reduced on average by 75.0% ± 23.9% at the time of the last postoperative scan. Syrinx resolution was variable, with 4 patients (30.8%) achieving near-complete resolution (> 90%, grade III reduction), 7 patients (50%) having 50%–90% reduction (grade II), and 2 patients (14.3%) having < 50% decrease (grade I). One patient experienced catheter migration into the left brachium pontis with an associated cyst at the tip of the catheter that decreased in size on follow-up imaging. CONCLUSIONS Placement of fourth ventricular subarachnoid stents spanning the craniocervical junction in patients with persistent CM-I–associated syringomyelia after posterior fossa decompression is a safe therapeutic option and significantly reduced the mean syrinx area, with a greater reductive effect seen over longer follow-up periods.

Pituitary tumors are the second most common primary brain tumors. Functional tumors demonstrate increased PD-L1 expression, but expression of other checkpoint regulators has not been characterized. We sought to characterize the immune microenvironment of human pituitary tumors to identify new treatment opportunities. 72 pituitary tumors were evaluated for expression of the immune regulatory markers programmed death ligand 1 (PD-L1), programmed death ligand 2 (PD-L2), V-domain Ig suppressor of T cell activation (VISTA), lymphocyte activation gene 3 (LAG3) and tumor necrosis factor receptor superfamily member 4 (OX40) by immunohistochemistry (IHC). Lymphocyte infiltration, macrophage infiltration, and angiogenesis were analyzed using IHC. Expression of pituitary tumor initiating cell marker CD15 and mismatch repair proteins MutS protein homolog 2 (MSH2) and MutS protein homolog 6 (MSH6) was also assessed. Pituitary tumors were infiltrated by macrophages and T cells, and they expressed varying levels of PD-L1, PD-L2, VISTA, LAG3, and OX40. Functional tumors and tumors with high expression of tumor stem cell markers had higher immune cell infiltration and greater expression of immunosuppressive checkpoint regulators. Increased PD-L1 and LAG3 and reduced VISTA were observed in primary tumors compared to recurrent tumors. Immune cell infiltration and checkpoint regulator expression vary depending on functional status and presence of pituitary tumor initiating cells. Functional tumors may have a particularly immunosuppressive microenvironment. Further studies of immune checkpoint blockade of pituitary tumors, particularly functional tumors, are warranted, though combination therapy may be required.

BACKGROUND Vestibular schwannomas exhibit a uniquely variable natural history of growth, stability, or even spontaneous regression. We hypothesized that a transitory population of immune cells, or immunomodulation of tumors cells, may influence the growth pattern of schwannomas. We therefore sought to characterize the impact of the immune microenvironment on schwannoma behavior. METHODS Forty-eight vestibular schwannomas with preoperative magnetic resonance imaging and 11 with serial imaging were evaluated for presence of immune infiltrates (including the pan-leukocyte marker Cluster of Differentiation (CD)45, CD4 and CD8 T-cell, and CD68 and CD163 macrophages) as well as expression of immunomodulatory regulators (Programmed Death Ligand 1 (PD-L1), Programmed Death Ligand 2 (PD-L2), LAG-3, TIM-3, V-domain Ig Suppressor of T cell Activation). Maximal diameter, volume, and recurrence were annotated. RESULTS Vestibular schwannomas were characterized by diverse signatures of tumor infiltrating leukocytes and immunomodulatory markers. The median tumor volume was 4.7 cm (Interquartile Range (IQR) 1.0-13.0) and maximum diameter was 2.3 cm (IQR 1.5-3.2). Among tumors with serial imaging, the median volumetric growth was 0.04 cm/mo (IQR 0.01-0.18). Tumor volume and maximum diameter demonstrated strong concordance (R = 0.90; p

Acromegaly results from excessive secretion of insulinlike growth factor-1 and growth hormone, which most commonly occurs because of pituitary somatotrophinoma. Diagnostic features of acromegaly include elevated insulinlike growth factor-1 and growth hormone; lesion on brain MRI; and clinically dysmorphic features, such as soft tissue swelling, jaw prognathism, and acral overgrowth. Transsphenoidal resection is the primary therapy for individuals with acromegaly, even in the cases where gross total resection is not possible because of parasellar extension and cavernous sinus involvement. For recurrent or persistent disease after resection, systemic medications and stereotactic radiosurgery are used.

The management of metastatic disease has been greatly influenced by molecular-based tumor classification and associated therapeutic targets, leading to a significant improvement in survival in many cases. This improvement, in both progression free survival and overall survival, has led to an increased incidence of brain metastases (BM) in a population with systemically well controlled disease or patients with promising therapeutic options available. Within this review, we discuss the paradigm of treatment for 5 to 15 BM, and how the treatment has evolved away from short-term palliation towards providing long term intracranial control.A review of literature pertaining to treatment of multiple BM was performed. We searched in PubMed to identify literature on treatment of multiple brain metastases. Only English literature published until February 1st, 2022 was reviewed.The management of 5-15 BM include multi-modality treatment pathways that are tailored towards each individual's primary cancer and burden of disease. Surgical resection of a dominant metastasis is still reserved for large symptomatic lesions, and is combined with post-operative local disease control. Overall, there is a shift away from whole brain radiation therapy (WBRT) due to side effect profile towards stereotactic radiosurgery (SRS). However, advances in WBRT continue to be studied, as well as the use of immunotherapy, targetable mutations, and synergistic effects between SRS and targeted therapies.The use of SRS to treat 5 to 15 BM is an increasingly acceptable and well-regarded practice, along with a combinatorial approach taking into account systemic options during all treatment timepoints.

Olfactory groove meningiomas (OGMs) are commonly treated with open craniotomy. Endonasal approaches have also been described. To present clinical and radiographic outcomes for the minimally invasive eyebrow incision supraorbital keyhole approach with endoscopic assistance for OGMs. We performed a retrospective single-center cohort study and a systematic literature review. Fifteen patients were identified, all with Grade I meningiomas. Radiographic gross total resection of enhancing tumor was achieved in all patients. Mean frontal lobe fluid-attenuated inversion recovery volume decreased from 11.1 ± 18.3 cm3 preoperatively to 9.9 ± 11.4 cm3 immediately postoperatively, and there was minimal new restricted diffusion (3.2 ± 2.2 cm3; max 7.5 cm3). Median length of stay was 3 days (range 2–8). Vision was improved in 4 (80%) and stable in 1 (20%) of 5 patients with a preoperative deficit. New postoperative anosmia occurred in 3 (23%) of 13 patients with any preoperative olfaction. All patients were satisfied with their cosmetic result at 3 months. After a median follow-up of 32.2 months, there were 2 (13.3%) asymptomatic radiographic recurrences, 1 treated with radiosurgery and the other with endoscopic endonasal approach (EEA). No patients required further craniotomy. Systematic review revealed the present series to be the largest to date reporting disaggregated outcomes for the eyebrow approach to OGM. The eyebrow incision supraorbital keyhole craniotomy with endoscopic assistance is a safe and effective approach to OGM with tumor control rates similar to more invasive open approaches and better than the endonasal approach. Rates of frontal lobe injury, CSF leak and anosmia are comparatively low.

The use of 5-aminolevulinic acid (5-ALA) for intraoperative protoporphyrin IX fluorescent imaging in the resection of malignant gliomas has been demonstrated to improve tumor visualization, increase the extent of resection, and extend progression-free survival. The current technique for visualization of 5-ALA consists of excitation and emission filters built into the operating microscope. However, there are notable limitations to this process, including low quantum yield, expense, and masking of surrounding anatomy.We present 3 cases in which 3 separate methods were employed for visualizing fluorescence. The devices reported are 1) a low-cost blue light flashlight, 2) a low-cost headlamp, and 3) the first reported case of the new Designs for Vision REVEAL Fluorescence-Guided Surgery (FGS) 5-ALA fluorescent headlight and loupes. The aim of the study is to provide confirmation that tumor fluorescence can be observed using commercially available products other than the microscope.We demonstrate through 3 intraoperative cases that a variety of devices can produce visible fluorescence of the high-grade tumor and allow for simultaneous real-time visualization of the adjacent brain parenchyma and vasculature. The REVEAL FGS system appears to offer increased fluorescence emission compared with all other methods, including the microscope.Our study demonstrates the feasibility of using blue/ultraviolet light supplied by a commercially available, inexpensive flashlight or headlamp to visualize 5-ALA fluorescence in high-grade gliomas. We also provide the first documentation of the intraoperative use of the new Designs for Vision REVEAL FGS 5-ALA fluorescent headlight and loupes and report on the experience. Lack of an operative microscope capable of fluorescent illumination should not be a limiting factor in performing fluorescent-guided glioma resection.

Introduction The Coronavirus disease 2019 (COVID-19) pandemic has uprooted healthcare systems worldwide, disrupting care and increasing dependence on alternative forms of health care delivery. It is yet to be determined how the pandemic affected neuro-oncology patient outcomes, given that the majority of even “elective” neurosurgical oncology procedures are time-sensitive. This study quantifies changes in neuro-oncological care during the height of the pandemic and investigates patient outcomes in 2020 compared to a historical control. Methods We performed a retrospective review of patients with malignant brain tumor diagnoses who were seen at our institution between March 13 and May 1 of 2020 and 2019. Alterations in care, including shift from in-person to telehealth, delays in evaluation and intervention, and treatment modifications were evaluated. These variables were analyzed with respect to brain tumor control and mortality. Results 112 patients from 2020 to 166 patients from 2019 were included. There was no significant difference in outcomes between the cohorts, despite significantly more treatment delays (p = 0.0160) and use of telehealth (p

Surgical interns who have completed medical school in the era of Covid-19 will not have the same experience gained through the traditional multi-month fourth-year surgical subinternships. During subinternships, medical students learn relevant anatomic and radiographic features of surgical pathologies, hone technical skills, and gain exposure to surgical consults and procedures. This lack of intensive exposure will have this cohort starting at a lower comfort and knowledge level compared to years prior. Residency programs, especially subspeciality programs, should review and utilize national resources to facilitate the transition to intern year, such as the American College of Surgeons Entering Resident Readiness Assessment and American College of Surgeons/ Association of Program Directors in Surgery/Association for Surgical Education Resident Prep Curriculum. We recommend the use of a specialty-tailored intern boot-camp and longitudinal curriculum that focuses on learning procedural skills and surgical conditions, anatomy, pathology, clinical examination, radiographic findings, surgical approach, and postoperative complications. These steps will help address knowledge gaps and promote intern readiness in this cohort of individuals.

IntroductionBrain metastases are the most common brain tumors in adults, whose management remains nuanced. Improved understanding of risk factors for surgical complications and mortality may guide treatment decisions.MethodsA nationwide, multicenter analysis was conducted with a retrospective cohort. Adult patients in the 2012-2015 American College of Surgeons National Surgical Quality Improvement Project (ACS NSQIP) databases who received a craniotomy for resection of brain metastasis were included.Results3500 cases were analyzed, of which 17% were considered frail and 24% were infratentorial. The most common 30-day medical complications were venous thromboembolism (3%, median time-to-event [TTE] 4.5 days), pneumonia (4%, median TTE 6 days), and urinary tract infections (2%, median TTE 5 days). Reoperation and unplanned readmission occurred in 5% and 12% of patients, respectively. Infratentorial approach and frailty were associated with reoperation before discharge (OR 2.0 for both; p=0.01 and p=0.03 respectively), but not after discharge. Infratentorial approaches conferred heightened risk for readmission for hydrocephalus (OR 5.1, p=0.02) and reoperation for cerebrospinal fluid diversion (OR 7.1, pConclusionsOptimization of metrics contributing to patient frailty and heightened surveillance in patients with infratentorial metastases may be considered in the peri-operative period.

OBJECTIVEThe authors report the diagnosis, management, and outcomes of 6 cases of spindle cell oncocytoma (SCO) in an effort to guide clinical diagnosis and management of these uncommon lesions.METHODSThis study is a retrospective review of cases involving adult patients who underwent resection of pituitary lesions at the authors’ institutions between January 2000 and October 2017. The authors identified patients with histopathological confirmation of SCO and collected clinical data, including preoperative, perioperative, and postoperative management, complications, and outcomes.RESULTSSix patients with SCO were identified. Clinical findings at initial presentation included visual disturbances, dizziness, and headache. All patients underwent resection. Four resections were initially performed by the transsphenoidal approach, and 2 resections were performed by craniotomy at an outside institution with subsequent transsphenoidal reoperations. Neither necrosis nor increased mitotic activity was seen in the tumor samples. All samples stained positive for S100 protein and thyroid transcription factor 1 and negative for glial fibrillary acidic protein and pituitary hormones. Five of the samples stained positive for epithelial membrane antigen. The average MIB-1 index was 8.3% (range 2–17). Postoperatively, 3 of the 6 patients received further treatment for progression of residual tumor or for recurrence, 2 have stable residual tumor, and 1 has had no recurrence after gross-total resection. Two patients developed postoperative complications of transient sixth cranial nerve palsy and diplopia. There were no other complications.CONCLUSIONSSCO poses both a diagnostic and therapeutic challenge. These tumors are often initially misdiagnosed as nonfunctional pituitary adenomas because of their sellar location and nonspecific symptomatology. Postoperatively, SCO must also be distinguished from other neoplasms of the posterior pituitary gland through histopathological examination. Resection of SCO can be challenging, given its highly vascular and adherent nature. Long-term follow-up is critical, as the tumor is associated with higher recurrence and progression rates compared to other benign neoplasms of the sella.

Olfactory groove meningiomas (OGMs) are commonly treated with open craniotomy. Endonasal approaches have also been described. To present clinical and radiographic outcomes for the minimally invasive eyebrow incision supraorbital keyhole approach with endoscopic assistance for OGMs. We performed a retrospective single-center cohort study and a systematic literature review. Fifteen patients were identified, all with Grade I meningiomas. Radiographic gross total resection of enhancing tumor was achieved in all patients. Mean frontal lobe fluid-attenuated inversion recovery volume decreased from 11.1 ± 18.3 cm3 preoperatively to 9.9 ± 11.4 cm3 immediately postoperatively, and there was minimal new restricted diffusion (3.2 ± 2.2 cm3; max 7.5 cm3). Median length of stay was 3 days (range 2–8). Vision was improved in 4 (80%) and stable in 1 (20%) of 5 patients with a preoperative deficit. New postoperative anosmia occurred in 3 (23%) of 13 patients with any preoperative olfaction. All patients were satisfied with their cosmetic result at 3 months. After a median follow-up of 32.2 months, there were 2 (13.3%) asymptomatic radiographic recurrences, 1 treated with radiosurgery and the other with endoscopic endonasal approach (EEA). No patients required further craniotomy. Systematic review revealed the present series to be the largest to date reporting disaggregated outcomes for the eyebrow approach to OGM. The eyebrow incision supraorbital keyhole craniotomy with endoscopic assistance is a safe and effective approach to OGM with tumor control rates similar to more invasive open approaches and better than the endonasal approach. Rates of frontal lobe injury, CSF leak and anosmia are comparatively low.

Pituitary tumors are the second most common primary brain tumors. Functional tumors demonstrate increased PD-L1 expression, but expression of other checkpoint regulators has not been characterized. We sought to characterize the immune microenvironment of human pituitary tumors to identify new treatment opportunities.72 pituitary tumors were evaluated for expression of the immune regulatory markers programmed death ligand 1 (PD-L1), programmed death ligand 2 (PD-L2), V-domain Ig suppressor of T cell activation (VISTA), lymphocyte activation gene 3 (LAG3) and tumor necrosis factor receptor superfamily member 4 (OX40) by immunohistochemistry (IHC). Lymphocyte infiltration, macrophage infiltration, and angiogenesis were analyzed using IHC. Expression of pituitary tumor initiating cell marker CD15 and mismatch repair proteins MutS protein homolog 2 (MSH2) and MutS protein homolog 6 (MSH6) was also assessed.Pituitary tumors were infiltrated by macrophages and T cells, and they expressed varying levels of PD-L1, PD-L2, VISTA, LAG3, and OX40. Functional tumors and tumors with high expression of tumor stem cell markers had higher immune cell infiltration and greater expression of immunosuppressive checkpoint regulators. Increased PD-L1 and LAG3 and reduced VISTA were observed in primary tumors compared to recurrent tumors.Immune cell infiltration and checkpoint regulator expression vary depending on functional status and presence of pituitary tumor initiating cells. Functional tumors may have a particularly immunosuppressive microenvironment. Further studies of immune checkpoint blockade of pituitary tumors, particularly functional tumors, are warranted, though combination therapy may be required.

Pineal region metastases are rare but often cause severe neurologic deficits. Surgical resection and chemoradiotherapy can provide therapeutic benefit. We investigated the literature to analyze clinical characteristics, management strategies, and survival of adult patients with pineal region metastases.PubMed, Embase, Scopus, and Cochrane were searched following the PRISMA guidelines, including studies reporting clinical outcomes of patients with pineal region metastases. Clinical presentation, management, and survival were reviewed.We included 31 studies comprising 47 patients. Lung cancer (29.8%) and carcinomas of unknown origin (14.9%) were the most frequent primary tumors. In 48.9% of patients, symptomatic pineal metastases preceded primary tumor diagnosis. Headache (67.4%) and confusion (46.5%) were the most common symptoms. Parinaud syndrome (46.5%) and hydrocephalus (87.2%) were noted. Biopsy (65.9%) was preferred over resection (34.1%), and shunting strategies used were endoscopic third ventriculostomy (43.9%) and ventriculoperitoneal (26.8%). Eleven patients (32.3%) received adjuvant chemotherapy and 32 (68%) received radiotherapy. Posttreatment improvement in symptoms (56.6%) and hydrocephalus (80.5%) were noted. In patients who received adjuvant chemotherapy/radiotherapy, significant improvement in posttreatment performance status occurred with both biopsy (P0.001) and resection (P = 0.007). No survival differences were reported between surgery and biopsy (P = 0.912) or between complete and partial resection (P = 0.220). Overall survival was neither influenced by surgical approach (P = 0.157) nor by shunting strategy (P = 0.822). Mean follow-up was 8 months and median overall survival 3 months. Only 2 cases (4.8%) of pineal metastasis showed recurrence.Pineal region metastases carry significant morbidity. Biopsy or surgical resection, combined with adjuvant chemotherapy/radiotherapy and/or shunting, may significantly improve performance status.

This article reviews emerging percutaneous ablative and radiosurgical techniques for the treatment of spinal metastases. The percutaneous ablative techniques discussed are laser interstitial thermal therapy, radiofrequency ablation, and cryoablation. Stereotactic radiosurgery also is reviewed as an adjuvant to surgical resection or separation surgery.

Background Quality improvement, value-based care delivery, and personalized patient care depend on robust clinical, financial, and demographic data streams of neurosurgical outcomes. The neurosurgical literature lacks a comprehensive review of large national databases. Objective To assess the strengths and limitations of various resources for outcomes research in neurosurgery. Methods A review of the literature was conducted to identify surgical outcomes studies using national data sets. The databases were assessed for the availability of patient demographics and clinical variables, longitudinal follow-up of patients, strengths, and limitations. Results The number of unique patients contained within each data set ranged from thousands (Quality Outcomes Database [QOD]) to hundreds of millions (MarketScan). Databases with both clinical and financial data included PearlDiver, Premier Healthcare Database, Vizient Clinical Data Base and Resource Manager, and the National Inpatient Sample. Outcomes collected by databases included patient-reported outcomes (QOD); 30-day morbidity, readmissions, and reoperations (National Surgical Quality Improvement Program); and disease incidence and disease-specific survival (Surveillance, Epidemiology, and End Results-Medicare). The strengths of large databases included large numbers of rare pathologies and multi-institutional nationally representative sampling; the limitations of these databases included variable data veracity, variable data completeness, and missing disease-specific variables. Conclusion The improvement of existing large national databases and the establishment of new registries will be crucial to the future of neurosurgical outcomes research.

Background The existing body of literature on postoperative neurosurgical infections lacks large multicenter reports on postoperative neurosurgical infections. This is the largest study to date of postoperative neurosurgical infections rates, time to event, and risk factors. Methods Demographics, medical history, and postoperative infections were assessed for all adult patients in the large, randomized, multicenter American College of Surgeons–National Surgical Quality Improvement Program (ACS-NSQIP) database undergoing an operation with a surgeon whose primary specialty was neurological surgery from 2006 to 2014. Results Of 3,723,797 cases from 517 institutions in the NSQIP from 2006 to 2014, 132,063 neurosurgery cases were identified. Within these patients, the 30-day rate of postoperative infections was 5.3%. Postoperatively, 1.8% of patients developed surgical site infections (SSI), and 3.9% developed other infections including pneumonia and urinary tract infections. Superficial SSI had a cumulative incidence of 0.8% at a median of 16 (interquartile range [IQR], 11–22) days. Pneumonia had a cumulative incidence of 1.4% at a median of 5 days (IQR, 2–10 days). Systemic inflammatory response syndrome had a cumulative incidence of 1.6% at a median of 3 days (IQR, 8–16 days). Predictors of postoperative infections on multivariable analysis included female sex, older age, obesity, functionally dependent status before surgery, ventilator dependence, preoperative steroid use, bleeding disorders, hyponatremia, lymphocytosis, anemia, thrombocytosis, emergent case status, wound class II–IV, American Society of Anesthesiologists class 3–5, and longer operative times. Conclusion The overall ACS-NSQIP reported rate of postoperative infections was 5.3% from 2006 to 2014. Multivariable analysis demonstrated several predictive factors for postoperative infections.

This study aimed to elucidate current medical student perceptions on barriers to a career in surgery, with a particular focus on gender-specific differences.Although gender parity in medical school composition has been reached, women continue to be underrepresented in the field of surgery.An anonymous, single-institution, internet-based survey conducted at Harvard Medical School.Approximately 720 medical students were surveyed and 261 completed the questionnaire (36.3%; 58.6% women, 41% men, 0.4% transgender). Overall, there was no significant gender difference in intention to pursue surgery (27% of men, 22% of women; P = 0.38). Sixty-nine percent of all students and 75% of those pursuing surgery reported verbal discouragement from pursuing a surgical career. Women were significantly more likely to perceive that the verbal discouragement was based on gender (P0.0001), age (P0.0001), and family aspirations (P = 0.043) compared to men. Surgical work hours and time for outside interests were the greatest deterrents for both genders. Significantly more women reported concerns about time to date or marry (P = 0.042), time to spend with family (P = 0.015), finding time during residency to have a child (P0.0001), taking maternity/paternity leave during residency (P0.0001), and being too old after residency to have a child (P0.0001).Both men and women reported high rates of verbal discouragement, but more women perceived that the discouragement was gender-based. Concerns about marriage and childbearing/rearing significantly deterred more women than men. Family aspirations were also a significant factor for men to choose an alternative career path. Additional support within the surgical field is needed to mitigate these concerns and support trainees in both their career and familial aspirations.

OBJECTIVE Conventional techniques for atlantoaxial fixation and fusion typically pass cables or wires underneath C1 lamina to secure the bone graft between the posterior elements of C1-2, which leads to complications such as cerebrospinal fluid (CSF) leak and neurological injury. With the evolution of fixation hardware, we propose a novel C1-2 fixation technique that avoids the morbidity and complications associated with sublaminar cables and wires. METHODS This technique entails wedging and anchoring a structural iliac crest graft between C1 and C2 for interlaminar arthrodesis and securing it using a 0-Prolene suture at the time of C1 lateral mass and C2 pars interarticularis screw fixation. RESULTS We identified 32 patients who underwent surgery for atlantoaxial with our technique. A 60% improvement in pain-related disability from preoperative baseline was demonstrated by Neck Disability Index (p < 0.001). There were no neurologic deficits. Complications included 2 patients CSF leaks related to presenting trauma, 1 patient with surgical site infection, and 1 patient with transient dysphagia. The rate of radiographic atlantoaxial fusion was 96.8% at 6 months, with no evidence of instrumentation failure, graft dislodgement, or graft related complications. CONCLUSION We demonstrate a novel technique for C1-2 arthrodesis that is a safe and effective option for atlantoaxial fusion.

Post-operative respiratory failure can occur after neurosurgical operations. Identification of risk factors for respiratory failure after neurosurgery may help guide clinical decision-making, decrease length of stay, improve patient outcomes, and lower costs. We performed a search of the ACS-NSQIP database for all patients undergoing operations with a neurosurgeon from 2006 to 2013. We analyzed demographics, past medical history, and post-operative respiratory failure, defined as unplanned intubation and/or ventilator dependence for more than 48 h post-operatively. Of 94,621 NSQIP-reported neurosurgical patients from 2006 to 2013, 2325 (2.5 %) developed post-operative respiratory failure. Of these patients, 1270 (54.6 %) were male, with an overall mean age of 60.59 years; 571 (24.56 %) were current smokers and 756 (32.52 %) were ventilator-dependent. Past medical history included dyspnea in 204 patients (8.8 %), COPD in 198 (8.5 %), and congestive heart failure in 66 (2.8 %). The rate of post-operative respiratory failure decreased from 4.1 % in 2006 to 2.1 % in 2013 (p

Tumor interferon signaling promotes PD-L1 expression to suppress T cell-mediated immunosurveillance. We identify the interferon- (IFN)-stimulated non-coding RNA 1 (INCR1) as a long noncoding RNA (lncRNA) transcribed from the PD-L1 locus and show that INCR1 controls IFNγ signaling in multiple tumor types. Silencing INCR1 decreases the expression of PD-L1, JAK2 and several other IFNγ-stimulated genes. INCR1 knockdown sensitizes tumor cells to cytotoxic T cell-mediated killing, improving CAR T cell therapy. We discover that PD-L1 and JAK2 transcripts are negatively regulated by binding to HNRNPH1, a nuclear ribonucleoprotein. INCR1’s primary transcript binds HNRNPH1 to block its inhibitory effects on the neighboring genes PD-L1 and JAK2 enabling their expression. Together, these findings introduce a mechanism of tumor IFNγ signaling regulation mediated by the lncRNA INCR1 and suggest a therapeutic target for cancer immunotherapy.

OBJECTIVECraniopharyngiomas are among the most challenging of intracranial tumors to manage because of their pattern of growth, associated morbidities, and high recurrence rate. Complete resection on initial encounter can be curative, but it may be impeded by the risks posed by the involved neurovascular structures. Recurrent craniopharyngiomas, in turn, are frequently refractory to additional surgery and adjuvant radiation or chemotherapy.METHODSThe authors conducted a review of primary literature.RESULTSRecent advances in the understanding of craniopharyngioma biology have illuminated potential oncogenic targets for pharmacotherapy. Specifically, distinct molecular profiles define two histological subtypes of craniopharyngioma: adamantinomatous and papillary. The discovery of overactive B-Raf signaling in the adult papillary subtype has led to reports of targeted inhibitors, with a growing acceptance for refractory cases. An expanding knowledge of the biological underpinnings of craniopharyngioma will continue to drive development of targeted therapies and immunotherapies that are personalized to the molecular signature of each individual tumor.CONCLUSIONSThe rapid translation of genomic findings to medical therapies for recurrent craniopharyngiomas serves as a roadmap for other challenging neurooncological diseases.

Tumor-to-tumor metastasis is an uncommon phenomenon, and a metastasis from an extracranial donor tumor to an intracranial recipient tumor is extremely rare. In particular, there are only 14 cases reported in the literature that describe a tumor-to-tumor metastasis involving a glioma. We present a rare case of an 83-year-old man with an 11-year history of lentigo maligna melanoma who presented with impaired balance and cognitive slowing and was found to have rapid progression of a previously known indolent right frontal brain mass. Pathologic examination of the tumor after resection revealed the presence of both malignant melanoma and an oligodendroglioma WHO grade II. To the best of our knowledge, this is the first reported case of malignant melanoma metastasizing to an oligodendroglioma that has been confirmed by immunohistochemistry and genetic analysis.

Pituitary tumors are undergoing a transformation in histopathologic and molecular classification, coincident with the continued refinement of increasingly powerful methods of genomic annotation and discovery. We highlight novel genomic alterations identified in pituitary adenomas and craniopharyngiomas and discuss their clinical implications. Sporadic pituitary adenomas are associated with relatively few recurrent somatic mutations. Recurrent mutations occur largely in subsets of hormone-producing tumors, including GNAS and GPR101 in somatotroph adenomas and USP8 in corticotroph adenomas. Additionally, they manifest with a dichotomous signature of copy number alterations, ranging from almost none to widespread genome instability, while microduplication of chromosome Xq26.3, containing the GNAS gene, defines X-linked acrogigantism. Papillary craniopharyngiomas are defined by BRAF V600E mutations while β-catenin alterations characterize adamantinomatous craniopharyngiomas. Genomic annotation of pituitary tumors is defining increasing subsets of neuroendocrine adenohypophyseal tumors and craniopharyngiomas, offering rationale-based pharmacologic targets and potential biomarkers for clinical outcome.

BACKGROUND CONTEXT Several surgical techniques for atlantoaxial fixation and arthrodesis have been proposed over the years to treat patients with atlantoaxial instability with the goal of achieving C1-2 fusion. PURPOSE We report a novel C1-2 fixation technique for treating patients with atlantoaxial instability using a loop-suture technique without the use of cables or wires. We propose a safer alternative to securing structural bone graft between C1-2. STUDY DESIGN/SETTING A retrospective review of a prospective database was performed using this technique from 2013-2018 for patients with atlantoaxial instability related to trauma, degeneration, and inflammatory arthropathy. Primary bone and metastatic cancer were excluded. The technique entails anchoring a structural iliac crest autograft or allograft between C1 and C2 for interlaminar arthrodesis in addition to C1 lateral mass and C2 pars/pedicle screw placement. The bone graft is secured using a 0-Prolene suture which is looped under the C1 lamina with the blunt end of the needle first. The needle is then passed through the graft, through the C2-3 interspinous ligaments, and then tied over the graft. We report the utility, safety, durability, and effectiveness of this approach in 32 consecutive patients METHODS A retrospective review of a prospective database was performed using this technique from 2013-2018 for patients with atlantoaxial instability related to trauma, degeneration, and inflammatory arthropathy. Primary bone and metastatic cancer were excluded. The technique entails anchoring a structural iliac crest autograft or allograft between C1 and C2 for interlaminar arthrodesis in addition to C1 lateral mass and C2 pars/pedicle screw placement. The bone graft is secured using a 0-Prolene suture which is looped under the C1 lamina with the blunt end of the needle first. The needle is then passed through the graft, through the C2-3 interspinous ligaments, and then tied over the graft. We report the utility, safety, durability, and effectiveness of this approach in 32 consecutive patients. RESULTS A total of 32 patients were identified who met criteria for atlantoaxial instability due to traumatic dislocation or ligamentous injury (60.0%), cervical spine degeneration (34.5%), deformity (5.25%) or combination of trauma and degeneration (5.25%). The follow-up period ranged from 6 to 24 months (mean 7.8 months). All patients had improvement in their pain by VAS and NDI (85% and 60% improvement respectively, p CONCLUSIONS We demonstrate a novel approach for C1-2 arthrodesis that utilizes a safe technique for securing bone graft without the use of wires or cables, allowing for less sublaminar dissection and potential dural and neurologic injury as well as improved clinical outcomes. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Background Atlantoaxial instability, which can arise in the setting of trauma, degenerative diseases, and neoplasm, is often managed surgically with C1-C2 arthrodesis. Classical C1-C2 fusion techniques require placement of instrumentation in close proximity to the vertebral artery and C2 nerve root. Objective To report a novel C1-C2 fusion technique that utilizes C2 translaminar screws and C1 sublaminar cables to decrease the risk of injury to the vertebral artery and C2 nerve root. Methods To facilitate fixation to the atlas, while minimizing the risk of injury to the vertebral artery and to the C2 nerve root, we sought to determine the feasibility of using a soft cable around the C1 arch and affixing it to a rod connected to C2 laminar screws. We reviewed our experience in 3 patients. Results We used this technique in patients in whom we anticipated difficult C1 screw placement. Three patients were identified through a review of the senior author's cases. Atlantoaxial instability was associated with trauma in 2 patients and chronic degenerative changes in 1 patient. Common symptoms on presentation included pain and limited range of motion. All patients underwent C1-C2 fusion with C2 translaminar screws with sublaminar cable harnessing of the posterior arch of C1. There were no reports of postoperative complications or hardware failure. Conclusion We demonstrate a novel, technically straightforward approach for C1-C2 fusion that minimizes risk to the vertebral artery and to the C2 nerve root, while still allowing for semirigid fixation in instances of both traumatic and chronic degenerative atlantoaxial instability.

BACKGROUND: Brain metastases are the most frequent brain tumors in adults, whose management remains nuanced. We aim to improve risk stratification for brain metastases patients who might be candidates for surgical resection. METHODS: We conducted a nationwide, retrospective cohort analysis of adult patients who received craniotomy for resection of brain metastasis using the 2012–2015 American College of Surgeons National Surgical Quality Improvement Project databases. Our primary outcomes of interest were post-operative medical complications, reoperation, readmission, and mortality. RESULTS: 3500 cases were included, of which 17% were considered frail and 24% were infratentorial. The most common 30-day medical complications were pneumonia (4%), venous thromboembolism (VTE;3%), and urinary tract infections (2%). Cardiac events and cerebrovascular accidents tended to occur in the early post-operative period, while VTEs and infections occurred in a more delayed fashion. Reoperation and unplanned readmission occurred in 5% and 12% of patients, respectively. Infratentorial approach and frailty were associated with reoperation before discharge (OR 2.0 for both; p=0.01 and p=0.03 respectively), but not after discharge. Frail patients were especially at risk for surgical evacuation of hematoma (OR 3.6). Infratentorial approaches conferred heightened risk for readmission for hydrocephalus (OR 5.1, p=0.02) and reoperation for cerebrospinal fluid diversion (OR 7.1, p< 0.001). Overall 30-day mortality was 4%, with nearly three-quarters occurring after discharge. Pre-frailty and frailty were associated with increased odds for post-discharge mortality (OR 1.7 and 2.7, p< 0.05), but not pre-discharge mortality. We developed a model to predictors of death, which identified frailty, thrombocytopenia, and high American Society of Anesthesiologists score as the strongest predictors of 30-day mortality (AUROC 0.75). CONCLUSION: Optimization of metrics contributing to patient frailty and heightened surveillance in patients with infratentorial metastases may be considered in the peri-operative period.

INTRODUCTION: Brain metastases are the most common type of brain tumor, though determining candidates for resection may be challenging. Patients’ unfavorable prognoses make pre-operative risk stratification critical in the selection of patients that are likely to benefit from resection. METHODS: Multivariable logistic regression was applied to 3,532 cases of secondary neoplasms of the brain in the American College of Surgeons National Surgical Quality Improvement Program database. The validated 5-criteria modified frailty index (mFI-5) score was utilized to quantify frailty, characterized as an mFI-5 score of 2 or higher. RESULTS: The median age in the cohort was 61 years, and the majority of patients were female (55%). Frailty was present in 17% of patients. The most frequent 30-day post-operative medical complications were venous thromboembolism (3.1%), pneumonia (2.7%), and urinary tract infections (2.2%). Unplanned readmissions and reoperations occurred in 12.2% of patients and 4.9% of patients, respectively. The incidence of death was 4.2% across the cohort, including 1.2% during index hospitalization. Frailty was associated with pneumonia (OR 2.7, p DISCUSSION: Frailty was associated with post-operative medical complications and death, in particular during the post-discharge phase. Frailty should be used in risk-stratifying patients.

The American College of Surgeons National Surgical Quality Improvement Program database aims to reduce 30-day postoperative complications. Reduction of postoperative stroke and coma can decrease length and cost of hospitalization, improve patient functional status, and decrease morbidity and mortality.We performed a search of the American College of Surgeons National Surgical Quality Improvement Program database for all patients from 2006 to 2013 undergoing an operation with a surgeon whose primary specialty was neurologic surgery.Of 94,546 neurosurgical patients reported, there were 687 (0.73%) cases of postoperative stroke and coma. The annual rate of coma longer than 24 hours decreased from 0.90% in 2006 to 0.002% in 2013 (P0.001), and the annual rate of stroke decreased from 1.2% in 2006 to 0.5% in 2013 (P = 0.013). Multivariate analysis showed that inpatient status (P = 0.001; odds ratio [OR], 30.3), age (P = 0.005; OR, 1.012), history of diabetes (P = 0.017; OR, 1.515), ventilator dependence (P0.001; OR, 4.379), impaired sensorium (P0.001; OR, 2.314), history of coma longer than 24 hours (P0.001; OR, 2.655), hemiparesis (P = 0.022; OR, 1.492), cerebrovascular accident/stroke with neurologic deficit (P0.001; OR, 2.091), cerebrovascular accident/stroke without neurologic deficit (P = 0.001; OR, 2.44), and tumor involving central nervous system (P0.001; OR, 2.928) are significant risk factors for developing postneurosurgical stroke and coma.The rate of postneurosurgical stroke decreased from 1.2% in 2006 to 0.5% in 2013 and the rate of postneurosurgical coma greater than 24 hours decreased from 0.9% in 2006 to 0.002% in 2013. Ten risk factors for developing postneurosurgical stroke and coma were identified using multivariable analysis. These risk factors should be assessed preoperatively and incorporated into clinical decision making so that individuals who are at higher risk for the development of stroke and coma can be appropriately monitored during the postoperative period.

We aimed to identify trends in the neurosurgical practice environment in the United States from 2006 to 2013 using the American College of Surgeons-National Surgical Quality Improvement Program (NSQIP) database, and to determine the complication rate for spinal and cranial procedures and identify risk factors for post-operative complications across this time period. We performed a search of the American College of Surgeons-NSQIP database for all patients undergoing an operation with a surgeon whose primary specialty was neurological surgery from 2006 to 2013. Analysis of patient demographics and pre-operative co-morbidities was performed, and multivariate analysis was used to determine predictors of surgical complications. From 2006 to 2013, the percentage of spinal operations performed by neurosurgeons relative to cranial and peripheral nerve cases increased from 68.0% to 76.8% (p

To compare the self-reported liability characteristics and defensive medicine practices of neurosurgeons in Texas with neurosurgeons in Illinois in an effort to describe the effect of medicolegal environment on defensive behavior.An online survey was sent to 3344 members of the American Board of Neurological Surgery. Respondents were asked questions in 8 domains, and responses were compared between Illinois, the state with the highest reported average malpractice insurance premium, and Texas, a state with a relatively low average malpractice insurance premium.In Illinois, 85 of 146 (58.2%) neurosurgeons surveyed responded to the survey. In Texas, 65 of 265 (24.5%) neurosurgeons surveyed responded. In Illinois, neurosurgeons were more likely to rate the overall burden of liability insurance premiums to be an extreme/major burden (odds ratio [OR] = 7.398, P0.001) and to have$2 million in total coverage (OR = 9.814, P0.001) than neurosurgeons from Texas. Annual malpractice insurance premiums in Illinois were more likely to be higher than $50,000 than in Texas (OR = 9.936, P0.001), and survey respondents from Illinois were more likely to believe that there is an ongoing medical liability crisis in the United States (OR = 9.505, P0.001). Neurosurgeons from Illinois were more likely to report that they very often/always order additional imaging (OR = 2.514, P = 0.011) or very often/always request additional consultations (OR = 2.385, P = 0.014) compared with neurosurgeons in Texas.Neurosurgeons in Illinois are more likely to believe that there is an ongoing medical liability crisis and more likely to practice defensively than neurosurgeons in Texas.