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Barth Syndrome is an X-linked disorder of mitochondrial cardiolipin metabolism caused by pathogenic variants in TAFAZZIN with pleiotropic effects including cardiomyopathy, neutropenia, growth delay, and skeletal myopathy. Management requires a multidisciplinary approach to the organ-specific manifestations including specialists from cardiology, hematology, nutrition, physical therapy, genetics, and metabolism. Currently, treatment is centered on management of specific clinical features, and is not targeted towards remediating the underlying biochemical defect. However, two clinical trials have been recently undertaken which target the mitochondrial pathology of this disease: a study to examine the effects of elamipretide, a cardiolipin targeted agent, and a study to examine the effects of bezafibrate, a peroxisome proliferator-activated receptor (PPAR) agonist. Treatments to directly target the defective TAFAZZIN pathway are under development, including enzyme and gene therapies. This article is protected by copyright. All rights reserved.

OBJECTIVE To determine the influence extent of resection and tumor characteristics on facial nerve (FN) outcomes following microsurgical resection of vestibular schwannoma (VS). STUDY DESIGN Retrospective chart review. SETTING Tertiary referral center. PATIENTS Three hundred eighty-five patients who underwent VS microsurgical resection. INTERVENTIONS Microsurgical VS resection. MAIN OUTCOME MEASURES House-Brackmann (HB) scores postoperatively. Good FN function was defined as HB grade I and II and poor FN function was defined as HB grade III and VI. Gross total resection (GTR) versus subtotal resection (STR). Propensity-score matching was used in subset analysis to balance tumor volume between the surgical cohorts, followed by multivariable analysis. RESULTS Seventy-one patients (18%) underwent STR and 314 patients (82%) underwent GTR. Two hundred fourteen patients (63%) had good FN function at 2 to 3 weeks postoperatively, and 80% had good FN function at 1 year. In single predictor analysis, STR did not influence FN function at 2 to 3 weeks (p = 0.65). In propensity-score matched subset analysis (N = 178), patients with STR were less likely to have poor FN function at 2 to 3 weeks (p = 0.02) independent of tumor volume (p = 0.004), but there was no correlation between STR and FN function at 1 year (p = 0.09). Ventral extension of tumor relative to the internal auditory canal plane was associated with poor FN outcomes at 2 to 3 weeks (p = 0.0001) and 1-year postop (p = 0.002). CONCLUSIONS When accounting for tumor volume, STR is protective in immediate postoperative FN function compared to GTR. Ventral extension of the tumor is a clinical predictor of long-term FN outcomes.

OBJECTIVE The number of unsolicited patient complaints (UPCs) about surgeons correlates with surgical complications and malpractice claims. Using a large, national patient complaint database, the authors sought to do the following: 1) compare the rates of UPCs for neurosurgeons to those for other physicians, 2) analyze the risk of UPCs with individual neurosurgeon characteristics, and 3) describe the types of UPCs made about neurosurgeons. METHODS Patient and family complaint reports among 36,265 physicians, including 423 neurosurgeons, 8292 other surgeons, and 27,550 nonsurgeons who practiced at 33 medical centers (22 academic and 11 regional) from January 1, 2014, to December 31, 2017, were coded with a previously validated Patient Advocacy Reporting System (PARS) algorithm. RESULTS Among 423 neurosurgeons, 93% were male, and most (71%) practiced in academic medical centers. Neurosurgical subspecialties included general practice (25%), spine (25%), tumor (16%), vascular (13%), functional (10%), and pediatrics (10%). Neurosurgeons had more average total UPCs per physician (8.68; 95% CI 7.68–9.67) than nonsurgeons (3.40; 95% CI 3.33–3.47) and other surgeons (5.01; 95% CI 4.85–5.17; p < 0.001). In addition, a significantly higher percentage of neurosurgeons received at least one UPC (71.6%; 95% CI 67.3%–75.9%) than did nonsurgeons (50.2%; 95% CI 49.6%–50.8%) and other surgeons (58.2%; 95% CI 57.1%–59.3%; p < 0.001). Factors most associated with increased average UPCs were younger age, measured as median medical school graduation year (1990.5 in the 0-UPC group vs 1993 in the 14+-UPC group, p = 0.009) and spine subspecialty (13.4 mean UPCs in spine vs 7.9 mean UPCs in other specialties, 95% CI 2.3–8.5, p < 0.001). No difference in complaints was seen in those who graduated from non-US versus US medical schools (p = 0.605). The most common complaint types were related to issues surrounding care and treatment, communication, and accessibility, each of which was significantly more common for neurosurgeons than other surgical specialties (p < 0.001). CONCLUSIONS Neurosurgeons were more likely to generate UPCs than other surgical specialties, and almost 3 out of 4 neurosurgeons (71.6%) had at least one UPC during the study period. Prior studies have shown that feedback to physicians about behavior can result in fewer UPCs. These results suggest that neurosurgeons have opportunities to reduce complaints and potentially improve the overall quality of care delivered.

BACKGROUND: Cerebral vasospasm is a major contributor to disability and mortality after aneurysmal subarachnoid hemorrhage. Oxidation of cell-free hemoglobin plays an integral role in neuroinflammation and is a suggested source of tissue injury after aneurysm rupture. This study sought to determine if patients with subarachnoid hemorrhage and cerebral vasospasm were more likely to have been exposed to early hyperoxemia than those without vasospasm. METHODS: This single-center retrospective cohort study included adult patients presenting with aneurysmal subarachnoid hemorrhage to Vanderbilt University Medical Center between January 2007 and December 2017. Patients with an ICD-9/10 diagnosis of aneurysmal subarachnoid hemorrhage were initially identified (N=441) and subsequently excluded if they did not have intracranial imaging, arterial PaO(2) values, or died within 96 hours post-rupture (N=96). The final cohort was 345 subjects. The degree of hyperoxemia was defined by the highest PaO(2) measured within 72 hours after aneurysmal rupture. The primary outcome was development of cerebral vasospasm, which included asymptomatic vasospasm and delayed cerebral ischemia (DCI). Secondary outcomes were mortality and modified Rankin Scale. RESULTS: 345 patients met inclusion criteria; 218 patients (63%) developed vasospasm. Of those that developed vasospasm, 85 were diagnosed with delayed cerebral ischemia (DCI, 39%). The average patient age of the cohort was 55±13 years, and 68% were female. Ninety percent presented with Fisher Grade 3 or 4 hemorrhage (N=310) while 42% presented as Hunt-Hess Grade 4 or 5 (N=146). In univariable analysis, patients exposed to higher levels of PaO(2) by quintile of exposure had a higher mortality rate and were more likely to develop vasospasm in a dose-dependent fashion (P=0.015 and P=0.019, respectively). There were no statistically significant predictors that differentiated asymptomatic vasospasm from DCI and no significant difference in maximum PaO(2) between these two groups. In multivariable analysis, early hyperoxemia was independently associated with vasospasm (OR=1.15 per 50 mmHg increase in PaO2 [1.03, 1.28]; P=0.013), but not mortality (OR=1.10 [0.97, 1.25]; P=0.147) following subarachnoid hemorrhage. CONCLUSIONS: Hyperoxemia within 72 hours post-aneurysmal rupture is an independent predictor of cerebral vasospasm, but not mortality in subarachnoid hemorrhage. Hyperoxemia is a variable that can be readily controlled by adjusting the delivered FiO(2) and may represent a modifiable risk factor for vasospasm.

Tumor-induced osteomalacia (TIO) is a rare disease in which patients suffer from fractures and progressive disabling bone pain and muscle weakness. TIO is caused by the hypersecretion of Fibroblast Growth Factor 23 (FGF23) from rare neoplasms of mesenchymal origin. This case report describes a 29-year-old male with 2 years of low back/hip pain, gait changes, proximal muscle weakness, and multiple stress fractures. Bone densitometry was remarkable for severe osteoporosis, hypophosphatemia was seen on routine labs, and advanced labs demonstrated an “inappropriately normal” FGF23 level. A 68Ga-DOTATATE scan and MRI showed a 1.3 × 1.1 × 1.0 cm intracranial mass. The patient underwent tumor resection by Neurosurgery. Shortly after, laboratory levels normalized, and the patient's symptoms improved drastically. This case exemplifies the notion that TIO can be caused by FGF23 levels within normal limits, the role of 68-Ga DOTATATE imaging for establishing a diagnosis, and that these tumors can arise anywhere—even intracranially. We also review current surgical and nonsurgical treatment options, as well as emerging novel therapeutics. Keywords: TIO, Paraneoplastic syndrome, Tumor-induced osteomalacia, Fibroblast growth factor 23, 68Ga-DOTATATE, MRI, DXA, Burosumab

Background Preclinical neurosurgery electives have been shown to increase student familiarity with neurosurgery, yet the impact on students without a home neurosurgery program is unknown. We conducted a preclinical neurosurgery elective in a mixed cohort of students with and without home neurosurgery programs to 1) evaluate changes in neurosurgery perceptions, 2) discern differences between cohorts, and 3) identify important factors in those considering neurosurgery. Methods A yearly elective was offered to students at Vanderbilt University School of Medicine (VUSM; home program) or Meharry Medical College (MMC; no home program) from 2017 to 2018. Each class included a student-led presentation, faculty academic lecture, and faculty round-table discussion. Precourse and postcourse surveys were completed. Results Thirty-two students completed the course. VUSM students (n = 15) showed no changes in initial perceptions, whereas MMC students (n = 17) had multiple improved perceptions, including collegiality (P = 0.001) and family achievability (P = 0.010), and believed residency to be less rigorous than their initial perceptions (P = 0.046). Fourteen students (44%) showed an increase in the likelihood of considering a neurosurgical career; eight (57%) were MMC students. These 14 students had improved perceptions of neurosurgery as less emotionally draining (P = 0.042), with favorable collegiality (P = 0.003) and work/life balance (P = 0.001) but did not believe residency to be less difficult (P = 0.102) or have added financial security (P = 0.380). Conclusions Early exposure to neurosurgery at medical schools without home programs through preclinical electives may improve students' perceptions of neurosurgery, provide valuable information about the benefits and rigors of neurosurgery, and allow students to make informed decisions about further pursuit of neurosurgery.

Background/Purpose: A pathologic murmur may be the first sign of heart disease in children and is an appropriate indication for echocardiography, while an innocent murmur is not. However, stethoscope skills are in decline among primary providers making distinction of innocent from pathologic murmurs increasingly difficult. This may lead to over-referral to the cardiologist and overuse of echocardiography, resulting in unnecessary emotional and financial burdens on families. The use of telemedicine and an artificial intelligence (AI)-enabled electronic stethoscope may aid decision-making regarding referral of children with …

Background We conducted a segmental volumetric analysis of pre-operative brain magnetic resonance images (MRIs) of glioblastoma patients to identify brain- and tumor-related features that are prognostic of survival. Methods Using a dataset of 210 single-institutional adult glioblastoma patients, total volumes of the following tumor- and brain-related features were quantified on pre-operative MRIs using a fully automated segmentation tool: tumor enhancement, tumor non-enhancement, tumor necrosis, peri-tumoral edema, grey matter, white matter, and cerebrospinal fluid (CSF). Their association with survival using Cox regression models, adjusting for the well-known predictors of glioblastoma survival. The findings were verified in a second dataset consisting of 96 glioblastoma patients from The Cancer Imaging Archive and The Cancer Genome Atlas (TCIA/TCGA). Results CSF volume and edema were independently and consistently associated with overall survival of glioblastoma patients in both datasets. Greater edema was associated with increased hazard or decreased survival [adjusted hazard ratio (aHR) with 95% confidence interval (CI): 1.34 [1.08–1.67], p = 0.008 (institutional dataset); and, 1.44 [1.08–1.93], p = 0.013 (TCIA/TCGA dataset)]. Greater CSF volume also correlated with increased hazard or decreased survival [aHR 1.27 [1.02–1.59], p = 0.035 (institutional dataset), and 1.42 [1.03–1.95], p = 0.032 (TCIA/TCGA dataset)]. Conclusions Higher brain CSF volume and higher edema levels at diagnosis are independently associated with decreased survival in glioblastoma patients. These results highlight the importance of a broader, quantitative brain-wide radiological analyses and invite investigations to understand tumor-related causes of increased edema and possibly increased CSF volume.

BackgroundBrain tumors can present as focal neurologic deficits (reflecting the tumor location) or generalized symptoms due to increased intracranial pressure. Occasionally, brain tumors can be found incidentally in asymptomatic patients or in patients with unrelated symptoms who undergo brain imaging. The term incidentaloma is used to refer to these imaging abnormalities.ObjectiveThe object of this study was to examine the prevalence and correlates of asymptomatic glioma in a large epidemiological study of brain tumors.MethodsThe analysis was based on a large series of patients with glioma (N = 1989) enrolled in a multicenter clinic-based epidemiologic study between 2005 and 2017. Patients were considered asymptomatic from the tumor, and thus as having an incidentally detected glioma (IDG), if the tumor was diagnosed during workup of injury or unrelated medical condition.ResultsA total of 32 of 1989 (1.6%) patients were asymptomatic at diagnosis. The leading indication for brain imaging in IDG was non-workplace injuries followed by medical workup for unrelated conditions. IDG was more prevalent in patients younger than 50 years of age (2.6% vs 1.0%). IDG was also more common in patients with low grade gliomas (4.7% for WHO grade II and 1.5% for WHO grade III) vs glioblastomas (0.6% in WHO grade IV).ConclusionThe present data suggest that gliomas may be found incidentally, especially among low grade gliomas. Studies of IDG may be useful as a proxy for early detection of tumor as a means to improve patient survival.

Purpose: For many patients with intracranial tumors, accurate surgical resection is a mainstay of their treatment paradigm. During surgical resection, image guidance is used to aid in localization and resection. Intraoperative brain shift can invalidate these guidance systems. One cause of intraoperative brain shift is cavity collapse due to tumor resection, which will be referred to as “debulking.” We developed an imaging-driven finite element model of debulking to create a comprehensive simulation data set to reflect possible intraoperative changes. The objective was to create a method to account for brain shift due to debulking for applications in image-guided neurosurgery. We hypothesized that accounting for tumor debulking in a deformation atlas data framework would improve brain shift predictions, which would enhance image-based surgical guidance. Approach: This was evaluated in a six-patient intracranial tumor resection intraoperative data set. The brain shift deformation atlas data framework consisted of [Formula: see text] simulated deformations to account for effects due to gravity-induced and hyperosmotic drug-induced brain shift, which reflects previous developments. An additional complement of [Formula: see text] deformations involving simulated tumor growth followed by debulking was created to capture observed intraoperative effects not previously included. Results: In five of six patient cases evaluated, inclusion of debulking mechanics improved brain shift correction by capturing global mass effects resulting from the resected tumor. Conclusions: These findings suggest imaging-driven brain shift models used to create a deformation simulation data framework of observed intraoperative events can be used to assist in more accurate image-guided surgical navigation in the brain.

Objective To describe the incidence and clinical course of patients who develop delayed facial nerve paralysis (DFNP) after surgical resection of vestibular schwannoma. Setting Tertiary skull base center. Methods Retrospective chart review. Results Two hundred and forty six consecutive patients, who underwent surgical resection for vestibular schwannoma at a single center between 2010 and 2015, were analyzed. Of these patients, 22 (8.9%) developed DFNP, defined here as deterioration of function by at least 2 House–Brackmann (HB) grades within 30 days in patients with immediate postoperative HB ≤ 3. The mean age of DFNP patients was 47.2 years (range: 17–67) and 16 (73%) were female. The mean tumor size in greatest dimension was 2.1 cm (range: 0.7–3.5 cm). At the conclusion of each case, the facial nerve stimulated at the brainstem. Mean immediate postoperative facial nerve function was HB 1.8 (range: 1–3). Average facial nerve function at the 3-week-postoperative visit was 4.4 (range: 2–6). In 1-year, 8 patients (36%) recovered HB 1 function, 10 patients (46%) recovered to HB 2, and 2 patients (9%) were HB 3. The remaining 2 patients did not recover function and were HB 6 at last follow-up. Initial postoperative facial nerve function (HB 1 or HB 2) was associated with improved recovery to normal (HB 1) function (p = 0.018). Conclusion A majority of patients that develop delayed paralysis will recover excellent facial nerve function. Patients should be counseled; however, a small percentage of patients will not recover function long-term, despite having a previously functioning and anatomically intact nerve.

Objective: Review the clinical presentation and management of meningeal hemangiopericytomas of the lateral skull base and cerebellopontine angle (CPA), and describe a case of anaplastic hemangiopericytoma of the CPA presenting as a middle ear mass. Study design: Case report and literature review. Case description: A 51-year-old male presented with a one year history of hearing loss, pulsatile tinnitus, and disequilibrium. Physical examination demonstrated a mass in the left middle ear. Magnetic resonance imaging revealed a 4 cm, T1-/T2-isointense, contrast-enhancing mass in the middle cranial fossa. The erosive mass extended into the middle ear and surrounding temporal lobe. A trans-zygomatic approach with a pterional craniotomy exposed a well-encapsulated, highly vascular mass. Manipulation of the tumor resulted in significant hemorrhage. Following removal from the temporal lobe and middle ear, an anterior petrosectomy was performed to remove tumor from the internal auditory canal (IAC) and carotid artery. The facial nerve near the IAC was encased in tumor, and all but a small amount of tumor adherent to the nerve was successfully removed. The final pathologic diagnosis was anaplastic hemangiopericytoma (WHO Grade III). Metastatic workup revealed no extracranial disease, and the patient underwent adjuvant radiation therapy. He continues to do well with only mild disequilibrium at one year follow-up. Conclusions: Hemangiopericytomas are rare, malignant neoplasms that are aggressive and highly vascular. Current management recommendations include excision followed by radiotherapy. Close surveillance is required for patients with anaplastic hemangiopericytoma due to the aggressive nature of this tumor and its propensity for recurrence or metastasis. Keywords: Hemangiopericytoma, Transzygomatic, Skull base, Middle ear mass, Middle cranial fossa, Tumor

Gliomas are the most common type of malignant primary brain tumor and few risk factors have been linked to their development. Handedness has been associated with several pathologic neurological conditions such as schizophrenia, autism, and epilepsy, but few studies have evaluated a connection between handedness and risk of glioma. In this study, we examined the relationship between handedness and glioma risk in a large case-control study (1,849 glioma cases and 1,354 healthy controls) and a prospective cohort study (326,475 subjects with 375 incident gliomas). In the case-control study, we found a significant inverse association between left handedness and glioma risk, with left-handed persons exhibiting a 35% reduction in the risk of developing glioma (Odds Ratio (OR)=0.65, 95% Confidence Interval (CI): 0.51, 0.83) after adjustment for age, gender, race, education, and state of residence; similar inverse associations were observed for GBM (OR=0.69, 95% CI: 0.52, 0.91), and non-GBM (OR=0.59, 95% CI: 0.42, 0.82) subgroups. The association was consistent in both males and females, and across age strata, and was observed in both glioblastoma and in lower grade tumors. In the prospective cohort study, we found no association between handedness and glioma risk (Hazards Ratio=0.92, 95% CI: 0.67, 1.28) adjusting for age, gender, and race. Further studies on this association may help to elucidate mechanisms of pathogenesis in glioma.

Background One study has investigated postoperative growth rates following subtotal resection of petroclival meningiomas utilizing linear measurements, which are insensitive to the multidimensional complex growth of meningiomas, to estimate tumor volume. Objective To describe petroclival meningioma growth patterns following less-than-complete resection utilizing volumetric analysis and to identify variables associated with tumor progression. Methods Patients with surgically resected WHO grade I petroclival meningiomas were retrospectively reviewed (1999-2015). Image analysis software was utilized to perform volumetric analyses of tumor size and growth on serial MRI studies. The impact of preoperative and postoperative variables on tumor growth after subtotal resection was analyzed. An increase in tumor volume of at least 20% was defined as "tumor growth." Results Twenty-three patients had immediate preoperative and serial postoperative MRI studies available for review. The mean preoperative tumor volume was 20.9 cm3 (range 0.4-54.6). The mean extent of resection was 75.5% (range 31.5%-100.0%). At a mean follow-up of 24.8 mo, 12 tumors (66.7%) exhibited radiological tumor growth, while 6 tumors did not change in size. The median annual volumetric growth rate was 2.82 cm3/yr (range -0.34 to 10.1). Extent of resection and immediate postoperative tumor volume were significantly correlated with the annual volumetric growth rate following resection. At last follow-up, 3 (13%) patients required further intervention. Conclusion The majority of petroclival meningiomas exhibit growth following subtotal resection. Extent of resection is strongly associated with risk for disease progression following surgery.

To examine the association of age when adult height was attained with glioma risk. We analyzed data from a US-based case–control study of glioma risk factors. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) associated between age at attainment of adult height and glioma risk. Multivariate models were adjusted for age, race, sex, education, and state of residence. We examined associations overall, and according to glioma grade, sex, and final adult height. The study set included n = 951 controls and n = 776 cases, with a median age of 56 (18–92); the majority was male (53.8%) and identified as Caucasian. Older age at height completion was associated with an increased risk of glioma. A significant positive trend was observed both for glioblastoma (OR 1.10; 95% CI 1.04–1.17 per 1-year increase in age) and lower grade non-glioblastoma subtypes combined (OR 1.18; 95% CI 1.10–1.28 per year increase in age). The association was observed in men and women, and in all categories of final adult height. We observed for the first time a positive association between glioma risk and a prolonged adolescent growth phase. Our results suggest a role for factors governing the timing and intensity of growth in adolescence as risk-determining exposures in adult glioma.

BACKGROUND: Antiepileptic drugs (AEDs) are frequently administered prophylactically to mitigate seizures following craniotomy for brain tumor resection. However, conflicting evidence exists regarding the efficacy of AEDs, and their influence on surgery-related outcomes is limited. OBJECTIVE: To evaluate the influence of perioperative AEDs on postoperative seizure rate and hospital-reported quality metrics. METHODS: A retrospective cohort study was conducted, incorporating all adult patients who underwent craniotomy for glioma resection at our institution between 1999 and 2014. Patients in 2 cohorts—those receiving and those not receiving prophylactic AEDs—were compared on the incidence of postoperative seizures and several hospital quality metrics including length of stay, discharge status, and use of hospital resources. RESULTS: Among 342 patients with glioma undergoing cytoreductive surgery, 301 (88%) received AED prophylaxis and 41 (12%) did not. Seventeen patients (5.6%) in the prophylaxis group developed a seizure within 14 days of surgery, compared with 1 (2.4%) in the standard group (OR = 2.2, 95% CI [0.3-17.4]). Median hospital and intensive care unit lengths of stay were similar between the cohorts. There was also no difference in the rate at which patients presented within 90 days postoperatively to the emergency department or required hospital readmission. In addition, the rate of hospital resource consumption, including electroencephalogram and computed tomography scan acquisition, and neurology consultation, was similar between both groups. CONCLUSION: The administration of prophylactic AEDs following glioma surgery did not influence the rate of perioperative seizures, nor did it reduce healthcare resource consumption. The role of perioperative seizure prophylaxis should be closely reexamined, and reconsideration given to this commonplace practice.

The clinical effect of radiographic contact of glioblastoma (GBM) with neurogenic zones (NZ)-the ventricular-subventricular (VSVZ) and subgranular (SGZ) zones-and the corpus callosum (CC) remains unclear and, in the case of the SGZ, unexplored. We investigated (1) if GBM contact with a NZ correlates with decreased survival; (2) if so, whether this effect is associated with a specific NZ; and (3) if radiographic contact with or invasion of the CC by GBM is associated with decreased survival. We retrospectively identified 207 adult patients who underwent cytoreductive surgery for GBM followed by chemotherapy and/or radiation. Age, preoperative Karnofsky performance status score (KPS), and extent of resection were recorded. Preoperative MRIs were blindly analyzed to calculate tumor volume and assess its contact with VSVZ, SGZ, CC, and cortex. Overall (OS) and progression free (PFS) survivals were calculated and analyzed with multivariate Cox analyses. Among the 207 patients, 111 had GBM contacting VSVZ (VSVZ+GBMs), 23 had SGZ+GBMs, 52 had CC+GBMs, and 164 had cortex+GBMs. VSVZ+, SGZ+, and CC+ GBMs were significantly larger in size relative to their respective non-contacting controls. Multivariate Cox survival analyses revealed GBM contact with the VSVZ, but not SGZ, CC, or cortex, as an independent predictor of lower OS, PFS, and early recurrence. We hypothesize that the VSVZ niche has unique properties that contribute to GBM pathobiology in adults.

Objectives This study characterizes primary petroclival meningioma growth rates, before intervention, using volumetric analysis. In addition, predictors of growth are analyzed. Methods Patients with previously untreated petroclival meningiomas were retrospectively reviewed (1999-2015). Image analysis software was used to perform volumetric analyses of tumor size and growth. Three-dimensional segmentation volumetric analyses were compared with volumes estimated utilizing three orthogonal dimensions. Tumor growth was defined as a 15% increase in volume. Results Thirty-four patients who underwent at least two magnetic resonance imaging (MRI) studies before intervention were included. The mean age was 55.2 years, and 65.7% were women. The mean tumor volume at presentation was 5.6 cm (range, 0.1-25.8 cm) as determined from segmentation volumetric analysis. At a mean follow-up of 44.5 months (range, 3.7-125.1 mo), 88.2% of tumors grew. The mean annual volumetric growth rate was 2.38 cm/yr (-0.63 to 25.9 cm/yr). Tumor volume, T2 hyperintensity within the tumor, peritumoral edema, and ataxia and/or cerebellar symptoms at presentation were all significantly associated with greater rates of tumor growth. Ultimately, 10 (29.4%) patients underwent treatment during the follow-up period. Conclusion Our experience demonstrates that the vast majority (88%) of untreated petroclival meningiomas grow; the mean volumetric growth rate was noted to be 2.38 cm/yr. We found a significant association between increased growth rate and larger tumor size at diagnosis, T2 hyperintensity within the tumor, peritumoral edema, and the presence of ataxia and/or cerebellar symptoms.

Objective This study aimed to evaluate surgical outcomes after transzygomatic middle cranial fossa (MCF) (TZ-MCF) approach for tumor control in patients with large skull base lesions involving the MCF and adjacent sites. Setting This study was done at the tertiary skull base center. Design This is a retrospective case series. Main Outcome Measures The main outcome measures were tumor control (recurrence), new-onset cranial neuropathies, facial nerve and audiometric outcomes, cerebrospinal fluid (CSF) leak, and wound complications. Results Sixteen patients were identified with a median age of 45 years (range: 20–72). The mean maximum tumor dimension was 5.49 cm (standard deviation [SD]: 1.2, range: 3.1–7.3) and the mean tumor volume was 28.5 cm3 (SD: 18.8, range: 2.9–63.8). Ten (62.5%) tumors were left sided. The most common pathology encountered was meningioma (n = 7) followed by chondrosarcoma (n = 4). Mean follow-up was 36.3 (SD: 26.9) months. Gross total resection or near total resection was achieved in nine (56.2%) and planned subtotal resection was used in seven (43.7%). Postoperative additional new cranial nerve (CN) deficits included CN V (n = 1), CN III (n = 2), CN VI (n = 1), and CN X (n = 1). Major neurological morbidity (hemiplegia) was encountered in two patients with resolution. There were no cases of CSF leak, meningitis, hemorrhage, seizures, aphasia, or death. There was no recurrence or regrowth of residual tumor. Facial nerve function was preserved in all but one patient (House–Brackmann grade 2). Conclusion Various skull base tumors involving MCF with extension to adjacent sites can be successfully resected using the TZ-MCF approach in a multidisciplinary fashion. This approach yields optimal exposure and permits excellent tumor control with acceptable CN and neurological morbidity.

Recent developments in machine learning implemented dimensionality reduction and clustering tools to classify the cellular composition of patient-derived tissue in multi-dimensional, single cell studies. Current approaches, however, require prior knowledge of either categorical clinical outcomes or cell type identities. These algorithms are not well suited for application in tumor biology, where clinical outcomes can be continuous and censored and cell identities may be novel and plastic. Risk Assessment Population IDentification (RAPID) is an unsupervised, machine learning algorithm that identifies single cell phenotypes and assesses clinical risk stratification as a continuous variable. Single cell mass cytometry evaluated 34 different phospho-proteins, transcription factors, and cell identity proteins in tumor tissue resected from patients bearingIDHwild-type glioblastomas. RAPID identified and characterized multiple biologically distinct tumor cell subsets that independently and continuously stratified patient outcome. RAPID is broadly applicable for single cell studies where atypical cancer and immune cells may drive disease biology and treatment responses.

Conventional optical tracking systems use cameras sensitive to near-infrared (NIR) light and NIR illuminated/active-illuminating markers to localize instrumentation and the patient in the operating room (OR) physical space. This technology is widely used within the neurosurgical theater and is a staple in the standard of care for craniotomy planning. To accomplish, planning is largely conducted at the time of the procedure in the OR with the patient in a fixed head orientation. We propose a framework to achieve this in the OR without conventional tracking technology, i.e., a "trackerless" approach. Briefly, we investigate an extension of the 3D Slicer which combines surgical planning and craniotomy designation. While taking advantage of the well-developed 3D Slicer platform, we implement advanced features to aid the neurosurgeon in planning the location of the anticipated craniotomy relative to the preoperatively imaged tumor in a physical-to-virtual setup, and then subsequently aid the true physical procedure by correlating that physical-to-virtual plan with an intraoperative magnetic resonance imaging-to-physical registered field-of-view display. These steps are done such that the craniotomy can be designated without the use of a conventional optical tracking technology. To test this approach, four experienced neurosurgeons performed experiments on five different surgical cases using our 3D Slicer module as well as the conventional procedure for comparison. The results suggest that our planning system provides a simple, cost-efficient, and reliable solution for surgical planning and delivery without the use of conventional tracking technologies. We hypothesize that the combination of this craniotomy planning approach and our past developments in cortical surface registration and deformation tracking using stereo-pair data from the surgical microscope may provide a fundamental realization of an integrated trackerless surgical guidance platform.

Brain shift during neurosurgery can compromise the fidelity of image guidance and potentially lead to surgical error. We have developed a finite element model-based brain shift compensation strategy to correct preoperative images for improved intraoperative navigation. This workflow-friendly approach precomputes potential intraoperative deformations (a ‘deformation atlas’) via a biphasic-biomechanical-model accounting for brain deformation associated with cerebrospinal fluid drainage, osmotic agents, resection, and swelling. Intraoperatively, an inverse problem approach is employed to provide a combinatory fit from the atlas that best matches sparse intraoperative measurements. Subsequently, preoperative image is deformed accordingly to better reflect patient’s intraoperative anatomy. While we have performed several retrospective studies examining model’s accuracy using post- or intra-operative magnetic resonance imaging, one challenging task is to examine model’s ability to recapture shift due to the aforementioned effects independently with clinical data and in a longitudinal manner under varying conditions. The work here is a case study where swelling was observed at the initial stage of surgery (after craniotomy and dura opening), subsequently sag was observed in a later stage of resection. Intraoperative tissue swelling and sag were captured via an optically tracked stylus by identifying cortical surface vessel features (n = 9), and model-based correction was performed for these two distinct types of brain shift at different stages of the procedure. Within the course of the entire surgery, we estimate the cortical surface experienced a deformation trajectory absolute path length of approximately 19.4 ± 2.1 mm reflecting swelling followed by sag. Overall, model reduced swelling-induced shift from 7.3 ± 1.1 to 1.8 ± 0.5 mm (~74.6% correction); for subsequent sag movement, model reduced shift from 6.4 ± 1.5 to 1.4 ± 0.5 mm (~76.6% correction).

OBJECTIVE Seizures are among the most common perioperative complications in patients undergoing craniotomy for brain tumor resection and have been associated with increased disease progression and decreased survival. Little evidence exists regarding the relationship between postoperative seizures and hospital quality measures, including length of stay (LOS), disposition, and readmission. The authors sought to address these questions by analyzing a glioma population over 15 years. METHODS A retrospective cohort study was used to evaluate the outcomes of patients who experienced a postoperative seizure. Patients with glioma who underwent craniotomy for resection between 1998 and 2013 were enrolled in the institutional tumor registry. Basic data, including demographics and comorbidities, were recorded in addition to hospitalization details and complications. Seizures were diagnosed by clinical examination, observation, and electroencephalography. The Student t-test and chi-square test were used to analyze differences in the means between continuous and categorical variables, respectively. Multivariate logistic and linear regression was used to compare multiple clinical variables against hospital quality metrics and survival figures, respectively. RESULTS In total, 342 patients with glioma underwent craniotomy for first-time resection. The mean age was 51.0 ± 17.3 years, 192 (56.1%) patients were male, and the median survival time for all grades was 15.4 months (range 6.2–24.0 months). High-grade glioma (Grade III or IV) was seen in 71.9% of patients. Perioperative antiepileptic drugs were administered to 88% of patients. Eighteen (5.3%) patients experienced a seizure within 14 days postoperatively, and 9 (50%) of these patients experienced first-time seizures. The mean time to the first postoperative seizure was 4.3 days (range 0–13 days). There was no significant association between tumor grade and the rate of perioperative seizure (Grade I, 0%; II, 7.0%; III, 6.1%; IV, 5.2%; p = 0.665). A single ictal episode occurred in 11 patients, while 3 patients experienced 2 seizures and 4 patients developed 3 or more seizures. Compared with their seizure-free counterparts, patients who experienced a perioperative seizure had an increased average hospital (6.8 vs 3.6 days, p = 0.032) and ICU LOS (5.4 vs 2.3 days; p < 0.041). Seventy-five percent of seizure-free patients were discharged home in comparison with 55.6% of seizure patients (p = 0.068). Patients with a postoperative seizure were significantly more likely to visit the emergency department within 90 days (44.4% vs 19.0%; OR 3.41 [95% CI 1.29–9.02], p = 0.009) and more likely to be readmitted within 90 days (50.0% vs 18.4%; OR 4.45 [95% CI 1.69–11.70], p = 0.001). In addition, seizure-free patients had a longer median overall survival (15.6 months [interquartile range 6.6–24.4 months] vs 3.0 months [interquartile range 1.0–25.0 months]; p = 0.013). CONCLUSIONS Patients with perioperative seizures following glioma resection required longer hospital and ICU LOS, were readmitted at higher rates than seizure-free patients, and experienced shorter overall survival. Biological and clinical factors that predispose to the development of seizures after glioma surgery portend a worse outcome. Efforts to identify these factors and reduce the risk of postoperative seizure should remain a priority among neurosurgical oncologists.

In recent years, there has been increased recognition of the relationship between type 2 diabetes mellitus (DM) and poor outcomes following a variety of surgical procedures. We sought to study the role of type 2 DM as a prognostic factor affecting the long-term survival of patients undergoing surgical resection of a WHO Grade I meningioma.We conducted a retrospective cohort study on 196 patients who had a WHO Grade I meningioma resected at our institution between 2001 and 2013. The medical record was reviewed to identify a pre-existing diagnosis of type 2 DM. Patient mortality was reviewed by medical record and Social Security Death Index (SSDI). Variables associated with survival in a univariate analysis were included in the multivariate Cox model if P0.10. Variables with probability values0.05 were then removed from the multivariate model in a step-wise fashion.33 (17%) patients had pre-existing diagnoses of type 2 DM prior to clinical presentation. Mean survival time in diabetic patients was 52.1 months compared to 160.9 months in non-diabetics. The decreased survival rate and time in patients with type 2 DM were found to be statistically significant (p=0.008 and p0.0001, respectively). In a multivariate Cox analysis, a pre-existing history of type 2 DM was independently associated with decreased survival following the resection of a WHO Grade I meningioma (HR=2.6, p=0.045).A pre-existing diagnosis of type 2 DM is an independent negative prognostic indicator following the resection of a WHO Grade I meningioma.

OBJECTIVE To analyze disease presentation, treatment, and clinical course of a consecutive series of patients with primary cerebellopontine angle (CPA) epidermoids. PATIENTS Forty-seven consecutive patients with previously untreated CPA epidermoids. INTERVENTION(S) Observation and microsurgery. MAIN OUTCOME MEASURES Disease- and treatment-associated morbidity, recurrence. RESULTS Forty-seven patients (mean age 39 years; 53% women) were analyzed and the average duration of follow-up was 42 months. The most common presenting symptom was headache (27; 57%); 13 (28%) exhibited preoperative asymmetric sensorineural hearing loss, 3 (6%) facial nerve paresis, and 3 (6%) hemifacial spasm. Thirteen patients (28%) were initially observed over a mean interval of 56 months; however, five experienced disease progression requiring operation. Thirty-nine patients (83%) underwent surgical resection; 18 (46%) received gross total, 5 (13%) near total, and 16 (41%) aggressive subtotal resection. Three patients (8%) recurred at a median of 53 months; two after subtotal and one after gross total resection. Ninety-three percent of patients with useful hearing maintained serviceable hearing following treatment and one patient (3%) experienced mild long-term postoperative facial nerve paresis (HB II/VI). All patients with preoperative facial nerve paresis recovered normal function postoperatively. There were no episodes of stroke or death. CONCLUSIONS Surgical intervention is effective in alleviating symptoms of cranial neuropathy and brainstem compression from CPA epidermoids. Gross total resection is preferred; however, aggressive subtotal removal should be considered with adherent or extensive disease as reoperation rates are low, even in the setting of aggressive subtotal resection. Conservative observation with serial imaging is a viable initial strategy in asymptomatic or minimally symptomatic patients.

Previous authors have identified a number of factors that predict morbidity, mortality, and recurrence in patients undergoing resection of a meningioma. We sought to study a novel potential prognostic indicator: early postoperative visit to the emergency department (ED). We conducted a retrospective cohort study on 239 patients who underwent a meningioma resection at our institution between 2001 and 2013 with over 3 months of follow-up postoperatively. All postoperative entries in the medical record were reviewed to identify any ED visit with a neurologic or wound-related complaint within a 90 day postoperative period. The relationships between ED presentation, tumor grade, and extent of surgical resection with future risk of operative recurrence and mortality were analyzed using Fisher's exact test. Variables associated with increased risks of mortality or operative recurrence in a univariate analysis were then included in the multivariate logistic regression model. Patients with a postoperative ED visit were found to be significantly more likely to die during the follow-up period (23.0% versus 4.85%, p

Methylmercury (MeHg) is an environmental neurotoxin with human exposure mainly from dietary intake of contaminated fish. Exposure to MeHg has been implicated in neurological damage, but research on its role in cancers, specifically glioma, is limited. In a glioma case-control study, we examined associations between toenail mercury (Hg) and glioma risk. We also examined genetic polymorphisms in 13 genes related to MeHg metabolism for association with glioma risk; genetic associations were also studied in the UK Biobank cohort. Median toenail Hg in cases and controls, respectively, was 0.066 μg/g and 0.069 μg/g (interquartile range (IQR): 0.032–0.161 and 0.031–0.150 μg/g). Toenail Hg was not found to be significantly associated with glioma risk (Odds Ratio: 1.02; 95% Confidence Interval: 0.91, 1.14; p = 0.70 in analysis for ordinal trend with increasing quartile of toenail MeHg). No genetic variant was statistically significant in both of the studies; one variant, rs11859163 (MMP2) had a combined p-value of 0.02 though it was no longer significant after adjustment for multiple testing (Bonferroni corrected p = 1). This study does not support the hypothesis that exposure to MeHg plays a role in the development of glioma at levels of exposure found in this study population.

The purpose of this investigation is to test whether a poroelastic model with enhanced structure can capture in vivo interstitial pressure dynamics in a brain undergoing mock surgical loads. Using interstitial pressure data from a porcine study, we use an inverse model to reconstruct material properties in an effort to capture these in vivo brain tissue dynamics. Four distinct models for the reconstruction of parameters are investigated (full anatomical condition description, condition without dural septa description, condition without ventricle boundary description, and the conventional fully saturated model). These models are systematic in their development to isolate the influence of three model characteristics: the dural septa, the treatment of the ventricles, and the treatment of the brain as a saturated media. This study demonstrates that to capture appropriate pressure compartmentalization, interstitial pressure gradients, pressure transient effects, and deformations within the brain, the proposed boundary conditions and structural enhancement coupled with a heterogeneous description invoking partial saturation are needed in a biphasic poroelastic model. These findings suggest that with enhanced anatomical modeling and appropriate model assumptions, poroelastic models can be used to capture quite complex brain deformations and interstitial pressure dynamics.

BACKGROUND: Ventricular entry during glioblastoma resection and tumor contact with the subventricular zone (SVZ) have both been shown to associate with development of hydrocephalus, leptomeningeal dissemination, distant parenchymal recurrence, and decreased survival. However, prior studies did not analyze these variables together in a single-patient population; therefore, it is unknown which is an independent predictor of these outcomes. OBJECTIVE: To conduct a comparative outcome analysis of surgical ventricular entry and SVZ contact by glioblastoma in a retrospective cohort of 232 patients. METHODS: Outcomes studied included hydrocephalus, leptomeningeal dissemination, distant tumor recurrences, and progression-free (PFS) and overall (OS) survival. The Cox proportional regression analyses were adjusted for age at diagnosis, preoperative Karnofsky performance status score, extent of resection, temozolomide and radiation treatments, and tumor molecular status (specifically, IDH1/2 mutation and MGMT promoter methylation). RESULTS: Surgical ventricular entry, SVZ-contacting glioblastoma, hydrocephalus, leptomeningeal dissemination, and distant recurrences were observed in 85 (36.6%), 114 (49.1%), 19 (8.2%), 78 (33.6%), and 59 (25.4%) patients, respectively. Multivariate, adjusted analysis revealed SVZ tumor contact—but not ventricular entry—associated with hydrocephalus (hazard ratio, HR, 4.20 [1.13-15.7], P = .03), leptomeningeal dissemination (HR 1.93 [1.14-3.28], P = .01), PFS (HR 2.10 [1.53-2.88], P

Background Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax®-L) to standard therapy for newly diagnosed glioblastoma. Methods After surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS). Results For the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months from surgery. Because of the cross-over trial design, nearly 90% of the ITT population received DCVax-L. For patients with methylated MGMT (n = 131), mOS was 34.7 months from surgery, with a 3-year survival of 46.4%. As of this analysis, 223 patients are ≥ 30 months past their surgery date; 67 of these (30.0%) have lived ≥ 30 months and have a Kaplan-Meier (KM)-derived mOS of 46.5 months. 182 patients are ≥ 36 months past surgery; 44 of these (24.2%) have lived ≥ 36 months and have a KM-derived mOS of 88.2 months. A population of extended survivors (n = 100) with mOS of 40.5 months, not explained by known prognostic factors, will be analyzed further. Only 2.1% of ITT patients (n = 7) had a grade 3 or 4 adverse event that was deemed at least possibly related to the vaccine. Overall adverse events with DCVax were comparable to standard therapy alone. Conclusions Addition of DCVax-L to standard therapy is feasible and safe in glioblastoma patients, and may extend survival. Trial registration Funded by Northwest Biotherapeutics; Clinicaltrials.gov number: NCT00045968; https://clinicaltrials.gov/ct2/show/NCT00045968?term=NCT00045968&rank=1; initially registered 19 September 2002

Background Selenium is an essential trace element obtained through diet that plays a critical role in DNA synthesis and protection from oxidative damage. Selenium intake and polymorphisms in selenoproteins have been linked to the risk of certain cancers though data for glioma are sparse. Methods In a case-control study of glioma, we examined the associations of selenium in toenails and genetic variants in the selenoenzyme pathway with the risk of glioma and patient survival. A total of 423 genetic variants in 29 candidate genes in the selenoenzyme pathway were studied in 1547 glioma cases and 1014 healthy controls. Genetic associations were also examined in the UK Biobank cohort comprised of 313,868 persons with 322 incident glioma cases. Toenail selenium was measured in a subcohort of 300 glioma cases and 300 age-matched controls from the case-control study. Results None of the 423 variants studied were consistently associated with glioma risk in the case-control and cohort studies. Moreover, toenail selenium in the case-control study had no significant association with glioma risk (p trend = 0.70) or patient survival among 254 patients with high grade tumors (p trend = 0.70). Conclusion The present study offers no support for the hypothesis that selenium plays a role in the onset of glioma or patient outcome.

Background Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax®-L) to standard therapy for newly diagnosed glioblastoma. Methods After surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS). Results For the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months from surgery. Because of the cross-over trial design, nearly 90% of the ITT population received DCVax-L. For patients with methylated MGMT (n = 131), mOS was 34.7 months from surgery, with a 3-year survival of 46.4%. As of this analysis, 223 patients are ≥ 30 months past their surgery date; 67 of these (30.0%) have lived ≥ 30 months and have a Kaplan-Meier (KM)-derived mOS of 46.5 months. 182 patients are ≥ 36 months past surgery; 44 of these (24.2%) have lived ≥ 36 months and have a KM-derived mOS of 88.2 months. A population of extended survivors (n = 100) with mOS of 40.5 months, not explained by known prognostic factors, will be analyzed further. Only 2.1% of ITT patients (n = 7) had a grade 3 or 4 adverse event that was deemed at least possibly related to the vaccine. Overall adverse events with DCVax were comparable to standard therapy alone. Conclusions Addition of DCVax-L to standard therapy is feasible and safe in glioblastoma patients, and may extend survival. Trial registration Funded by Northwest Biotherapeutics; Clinicaltrials.gov number: NCT00045968; https://clinicaltrials.gov/ct2/show/NCT00045968?term=NCT00045968&rank=1; initially registered 19 September 2002

Background Metabolic complications such as obesity, hyperglycemia, and type 2 diabetes are associated with poor outcomes in patients with glioblastoma. To control peritumoral edema, use of chronic high-dose steroids in glioblastoma patients is common, which can result in de novo diabetic symptoms. These metabolic complications may affect tumors via profound mechanisms, including activation of insulin receptor (InsR) and the related insulin-like growth factor 1 receptor (IGF1R) in malignant cells. Methods In the present study, we assessed expression of InsR in glioblastoma surgical specimens and glioblastoma response to insulin at physiologically relevant concentrations. We further determined whether genetic or pharmacological targeting of InsR affected oncogenic functions of glioblastoma in vitro and in vivo. Results We showed that InsR was commonly expressed in glioblastoma surgical specimens and xenograft tumor lines, with mitogenic isoform-A predominating. Insulin at physiologically relevant concentrations promoted glioblastoma cell growth and survival, potentially via Akt activation. Depletion of InsR impaired cellular functions and repressed orthotopic tumor growth. The absence of InsR compromised downstream Akt activity, but yet stimulated IGF1R expression. Targeting both InsR and IGF1R with dual kinase inhibitors resulted in effective blockade of downstream signaling, loss of cell viability, and repression of xenograft tumor growth. Conclusions Taken together, our work suggests that glioblastoma is sensitive to the mitogenic functions of insulin, thus significant insulin exposure imposes risks to glioblastoma patients. Additionally, dual inhibition of InsR and IGF1R exhibits promise for treating glioblastoma.

Background Complementary therapy (CAM) is common in cancer patients. We undertook this study to assess the association of complementary therapy usage with mortality in glioblastoma (GBM) patients. Methods The analysis was based on 470 patients. Information on current use of CAM was collected in structured interviews conducted a median of 6 weeks following GBM diagnosis. Proportional hazards regression was used to estimate hazard ratios (HRs) for GBM-related death according to the use of individual supplements with multivariate adjustment for known prognostic factors including age, KPS, and extent of tumor resection (ESR). Results Use of CAM agents was common, with 77% of the cohort reporting CAM usage. No mortality association was observed with the use of multivitamins (HR = 0.91; P = .40) or omega-3 fatty acids (HR = 1.07; P = .69). Patients taking vitamin D as an individual supplement (containing higher dosages than in a multivitamin) had reduced mortality when compared with nonusers (age-adjusted HR = 0.68; P = .02). However, the association was diminished after adjustment for KPS and ESR (HR = 0.74; P = .09). Use of herbal supplements was also associated with reduced mortality (HR = 0.58; P = .04). Vitamin E users had a nonsignificantly higher mortality when compared with nonusers (HR = 1.54; P = .09). Conclusions Use of CAM is common in GBM patients. These exploratory analyses suggest no mortality association with the use of multivitamins or omega-3 fatty acids. Associations observed with vitamins D and E merit further investigation.

One of the major challenges impeding advancement in image-guided surgical (IGS) systems is the soft-tissue deformation during surgical procedures. These deformations reduce the utility of the patient’s preoperative images and may produce inaccuracies in the application of preoperative surgical plans. Solutions to compensate for the tissue deformations include the acquisition of intraoperative tomographic images of the whole organ for direct displacement measurement and techniques that combines intraoperative organ surface measurements with computational biomechanical models to predict subsurface displacements. The later solution has the advantage of being less expensive and amenable to surgical workflow. Several modalities such as textured laser scanners, conoscopic holography, and stereo-pair cameras have been proposed for the intraoperative 3D estimation of organ surfaces to drive patient-specific biomechanical models for the intraoperative update of preoperative images. Though each modality has its respective advantages and disadvantages, stereo-pair camera approaches used within a standard operating microscope is the focus of this article. A new method that permits the automatic and near real-time estimation of 3D surfaces (at 1Hz) under varying magnifications of the operating microscope is proposed. This method has been evaluated on a CAD phantom object and on full-length neurosurgery video sequences (~1 hour) acquired intraoperatively by the proposed stereovision system. To the best of our knowledge, this type of validation study on full-length brain tumor surgery videos has not been done before. The method for estimating the unknown magnification factor of the operating microscope achieves accuracy within 0.02 of the theoretical value on a CAD phantom and within 0.06 on 4 clinical videos of the entire brain tumor surgery. When compared to a laser range scanner, the proposed method for reconstructing 3D surfaces intraoperatively achieves root mean square errors (surface-to-surface distance) in the 0.28-0.81mm range on the phantom object and in the 0.54-1.35mm range on 4 clinical cases. The digitization accuracy of the presented stereovision methods indicate that the operating microscope can be used to deliver the persistent intraoperative input required by computational biomechanical models to update the patient’s preoperative images and facilitate active surgical guidance.

BACKGROUND The consequences of ventricular entry during resection of high-grade gliomas (HGG) are uncertain and often not detectable clinically. OBJECTIVE To reveal odds of tumor dissemination, hydrocephalus, and mortality in adult patients who had ventricular entry during surgical resection of HGG. METHODS Titles and abstracts of published journals in the NCBI/NLM PubMed and OVID EMBASE databases were searched without language restriction and systematically screened. Outcomes extracted included the odds of leptomeningeal dissemination and hydrocephalus in patients with ventricular entry during HGG resection compared to without. They were analyzed using a random-effects model to calculate summary odds ratios (sORs). Overall survival data were also compared between patients with and without ventricular entry. RESULTS Twenty final studies with 2251 total patients were included from the 6910 retrieved. Patients with ventricular entry during HGG resection demonstrated higher odds of leptomeningeal dissemination (sOR: 3.91 [95% confidence interval (CI): 1.89-8.10]; P = .0002; 86/410 vs 57/847 patients in 9 studies) and hydrocephalus (sOR: 7.78 [95% CI: 3.77-16.05]; P < .00001; 58/431 vs 11/565 patients in 11 studies). They also had decreased survival (median survival: 16.8 vs 19.1 mo; 413 vs 322 patients in 10 studies; hazard ratio: 1.25 [95% CI: 1.05-1.48], P = .01). CONCLUSION The association between ventricular entry during HGG resection and tumor dissemination, hydrocephalus, and decreased survival invites investigations to understand this link. Neurosurgeons and neuro-oncologists must be aware of the consequences of ventricular entry during surgery for HGG.

Objective Machine learning (ML) algorithms are powerful tools for predicting patient outcomes. This study pilots a novel approach to algorithm selection and model creation using prediction of discharge disposition following meningioma resection as a proof of concept. Materials and Methods A diversity of ML algorithms were trained on a single-institution database of meningioma patients to predict discharge disposition. Algorithms were ranked by predictive power and top performers were combined to create an ensemble model. The final ensemble was internally validated on never-before-seen data to demonstrate generalizability. The predictive power of the ensemble was compared with a logistic regression. Further analyses were performed to identify how important variables impact the ensemble. Results Our ensemble model predicted disposition significantly better than a logistic regression (area under the curve of 0.78 and 0.71, respectively, p = 0.01). Tumor size, presentation at the emergency department, body mass index, convexity location, and preoperative motor deficit most strongly influence the model, though the independent impact of individual variables is nuanced. Conclusion Using a novel ML technique, we built a guided ML ensemble model that predicts discharge destination following meningioma resection with greater predictive power than a logistic regression, and that provides greater clinical insight than a univariate analysis. These techniques can be extended to predict many other patient outcomes of interest.

OBJECTIVE To investigate whether the use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) impact the growth of vestibular schwannoma (VS). STUDY DESIGN Retrospective case series. SETTING Single academic, tertiary care center. PATIENTS Patients with VS who underwent at least two magnetic resonance imaging (MRI) studies before intervention. INTERVENTION(S) Serial MRI studies. MAIN OUTCOME MEASURE(S) VS tumor growth, defined as more than or equal to 2 mm increase in the maximum tumor diameter between consecutive MRI studies, or between the first and last available study. Mean growth rate was also calculated, defined as the change in tumor size divided by length of follow-up. RESULTS A total of 564 VS patients met inclusion criteria, with 234 (41.2%) taking some type of NSAID. Aspirin use was not associated with VS tumor growth, presenting tumor diameter, or mean VS growth rate. Further, aspirin dosage did not impact growth outcomes or presenting tumor diameter. A total of 96 (17.0%) patients took an NSAID other than aspirin. Neither non-aspirin NSAID use nor degree of cyclooxygenase-2 (COX-2) selectivity, including aspirin, was significantly associated with VS tumor growth, presenting tumor diameter, or mean VS growth rate. CONCLUSIONS While previous studies have suggested a relationship between aspirin usage and VS growth, we found no significant association in our series of 564 observed VS. Furthermore, there was no apparent relationship between aspirin dosage, non-aspirin NSAID use, and COX-2 selectivity with VS growth, presenting tumor diameter at presentation, or mean VS growth rate.

Introduction Stereotactic radiosurgery (SRS) is increasingly used as an alternative to whole brain radiotherapy (WBRT) following surgical resection of brain metastases. We analyzed the outcomes of postoperative frameless fractionated stereotactic radiosurgery (fSRS) cases for surgically resected brain metastases at our institution. Materials and Methods We performed a retrospective review of 85 patients who underwent fSRS to 87 resection beds from 2006 - 2014 with a median follow-up of 6.4 months. Clinically relevant outcomes were assessed with analysis to determine predictors of these outcomes. Results The median target volume was 9.8 cm­3 (1.1 - 43.1 cm­3). The most frequently used fractionation scheme was 3,000 cGy in five fractions. The rates of local control (LC), distant brain failure (DBF), and overall survival (OS) at one-year were 87%, 52%, and 52%, respectively. Five patients (5.9%) experienced Grade >2 toxicity related to fSRS, including seizures (two), symptomatic radionecrosis (two), and potential treatment-related death (one). A multivariable analysis revealed that tumor volume (p < 0.001) and number of fractions (p < 0.001) were associated with LC, while recursive partitioning analysis (RPA) class (p < .0001), tumor volume (p = .0181), and the number of fractions (p = .0181) were associated with OS. Conclusions Postoperative fSRS for surgically resected brain metastases is well-tolerated and achieves durable LC. Further studies are needed to determine the optimal dose and fractionation for fSRS as well as to compare outcomes with WBRT.

Image-guided surgery (IGS)1 provides a standard of care platform for guiding surgeons during brain tumor resection. Unfortunately, commercial IGS navigation systems do not have mechanisms to account for nonrigid tissue deformations, which commonly arise from cerebrospinal fluid drainage, tissue swelling due to edema, tissue contraction due to hyperosmotic drugs, or tissue retraction/resection.2 Solutions like intraoperative magnetic resonance (iMR) imaging,3 intraoperative computed tomography (iCT),4 and intraoperative ultrasound (iUS)5 have been proposed to compensate for soft-tissue changes. However, deficiencies like ionizing radiation of iCT, high cost of iMR, and poor image contrast/quality of iUS have compelled researchers to look for alternatives. Another cost effective method is to use sparse data acquired intraoperatively to drive a biomechanical model to update and register preoperative images to the intraoperative field.6 Laser range scanners (LRS) and stereoscopic microscopes are two widely used surface data acquisition techniques.7,8 Both devices can be used in an operating room (OR) and generate three-dimensional (3-D) cortical surface cloud data as well as a texture map. Typically, the microscope is continuously used during the whole surgery. Thus, it can provide high-resolution, consistent intraoperative information in near real time with very limited interruption to the surgical workflow. Performing a single LRS acquisition is more disruptive because it takes about 15 to 30 s and requires the surgical microscope to be moved away from the surgical field of view (FOV). Standard stereomicroscopes allow surgeons to appreciate the 3-D nature of their domain when performing surgery. This facilitates the physical execution of surgery. With respect to tracked microscopes, once calibrated, these will typically track the focal point of the scope in 3-D space. This allows one to probe the tissue one point at a time to determine the associated imaging data. If one wanted to measure the optical field quickly, such as in measuring the distribution of deformations on the brain surface, the process of refocusing the focal point for each measurement would be highly impractical. The proposed work herein is focused at a tracked stereo-pair reconstruction; put more simply, the system herein is focused at measuring the whole visible brain surface dynamically throughout surgery capturing multidimensional displacements. These measurements may subsequently be used within nonrigid image-to-physical registration methodologies to account for soft-tissue brain shift, which can compromise neuronavigation systems. The proposed tracked stereo-scope solution allows for those measurements potentially to be continually captured throughout surgery without disrupting workflow and with optimal visibility of the tissue of interest. In the recent work, we demonstrated using position-fixed stereo-pair cameras for surface measurements. This work used two identical Grasshopper digital cameras produced by Point Grey Research, Inc. (Richmond, British Columbia, Canada) and served as an initial testing prototype for our mock cortical surface environment.9 Here, we have extended those approaches to a surgical microscope that is used clinically at our institution. We have developed an interactive environment that permits acquisition of stereo-image capture from the microscope, calibration of the cameras, and adjustment of parameters used for 3-D point cloud reconstruction. We have also equipped the microscope with a rigid body tracking star (Microscope Tracking Array, Brainlab Inc., Westchester, Illinois) to permit tracking of the microscope position within an IGS system. We show that with this device we can register 3-D point clouds that are acquired with the microscope in different positions thus permitting an intraopertaive calculation of cortical surface displacement. While the availability of microscope focal point tracking is possible with commercial IGS systems (although accuracy on these commercial systems is not widely reported), the implementation of a fully 3-D tracked approach necessary for measuring full cortical surface field displacements is lacking. The methods we are utilizing for stereovision reconstruction are well-referenced and our goal is to explore this within the scope environment and within the context of brain shift measurement.

Intra-operative soft tissue deformation, referred to as brain shift, compromises the application of current imageguided surgery (IGS) navigation systems in neurosurgery. A computational model driven by sparse data has been used as a cost effective method to compensate for cortical surface and volumetric displacements. Stereoscopic microscopes and laser range scanners (LRS) are the two most investigated sparse intra-operative imaging modalities for driving these systems. However, integrating these devices in the clinical workflow to facilitate development and evaluation requires developing systems that easily permit data acquisition and processing. In this work we present a mock environment developed to acquire stereo images from a tracked operating microscope and to reconstruct 3D point clouds from these images. A reconstruction error of 1 mm is estimated by using a phantom with a known geometry and independently measured deformation extent. The microscope is tracked via an attached tracking rigid body that facilitates the recording of the position of the microscope via a commercial optical tracking system as it moves during the procedure. Point clouds, reconstructed under different microscope positions, are registered into the same space in order to compute the feature displacements. Using our mock craniotomy device, realistic cortical deformations are generated. Our experimental results report approximately 2mm average displacement error compared with the optical tracking system. These results demonstrate the practicality of using tracked stereoscopic microscope as an alternative to LRS to collect sufficient intraoperative information for brain shift correction.