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Background and Objectives: Oligodendrogliomas are defined by IDH1/2 mutation and codeletion of chromosome arms 1p/19q. Although previous studies identified CIC, FUBP1, and TERTp as frequently altered in oligodendrogliomas, the clinical relevance of these molecular signatures is unclear. Moreover, previous studies predominantly used research panels that are not readily available to providers and patients. Accordingly, we explore genomic alterations in molecularly defined oligodendrogliomas using clinically standardized next-generation sequencing (NGS) panels., Methods: A retrospective single-center study evaluated adults with pathologically confirmed IDH-mutant, 1p/19q-codeleted oligodendrogliomas diagnosed between 2005 and 2021. Genetic data from formalin-fixed, paraffin-embedded specimens were analyzed with the NGS Solid Tumor Panel at the Johns Hopkins Medical Laboratories, which tests more than 400 cancer-related genes. Kaplan-Meier plots and log-rank tests compared progression-free survival (PFS) and overall survival by variant status. χ2 tests, t-tests, and Wilcoxon rank-sum tests were used to compare clinical characteristics between genomic variant status in the 10 most frequently altered genes., Results: Two hundred and seventy-seven patients with molecularly defined oligodendrogliomas were identified, of which 95 patients had available NGS reports. Ten genes had 9 or more patients with a genomic alteration, with CIC, FUBP1, and TERTp being the most frequently altered genes (n = 60, 23, and 22, respectively). Kaplan-Meier curves showed that most genes were not associated with differences in PFS or overall survival. At earlier time points (PFS <100 months), CIC alterations conferred a reduction in PFS in patients (P = .038)., Conclusion: Our study confirms the elevated frequency of CIC, FUBP1, and TERTp alterations in molecularly defined oligodendrogliomas and suggests a potential relationship of CIC alteration to PFS at earlier time points. Understanding these genomic variants may inform prognosis or therapeutic recommendations as NGS becomes routine., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background and Objectives: Subdural hematoma (SDH) patients with end-stage renal disease (ESRD) require renal replacement therapy in addition to neurological management. We sought to determine whether continuous venovenous hemodialysis (CVVHD) or intermittent hemodialysis (iHD) is associated with higher rates of SDH re-expansion as well as morbidity and mortality., Methods: Hemodialysis-dependent patients with ESRD who were discovered to have an SDH were retrospectively identified from 2016 to 2022. Rates of SDH expansion during CVVHD vs iHD were compared. Hemodialysis mode was included in a multivariate logistic regression model to test for independent association with SDH expansion and mortality., Results: A total of 123 hemodialysis-dependent patients with ESRD were discovered to have a concomitant SDH during the period of study. Patients who received CVVHD were on average 10.2 years younger ( P < .001), more likely to have traumatic SDH (47.7% vs 19.0%, P < .001), and more likely to have cirrhosis (25.0% vs 10.1%, P = .029). SDH expansion affecting neurological function occurred more frequently during iHD compared with CVVHD (29.7% vs 12.0%, P = .013). Multivariate logistic regression analysis found that CVVHD was independently associated with decreased risk of SDH affecting neurological function (odds ratio 0.25, 95% CI 0.08-0.65). Among patients who experienced in-hospital mortality or were discharged to hospice, 5% suffered a neurologically devastating SDH expansion while on CVVHD compared with 35% on iHD., Conclusion: CVVHD was independently associated with decreased risk of neurologically significant SDH expansion. Therefore, receiving renal replacement therapy through a course of CVVHD may increase SDH stability in patients with ESRD., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Objective: Careful hematologic management is required in surgical patients with traumatic acute subdural hematoma (aSDH) taking antithrombotic medications. We sought to compare outcomes between patients with aSDH taking antithrombotic medications at admission who received antithrombotic reversal with patients with aSDH not taking antithrombotics., Methods: Retrospective review identified patients with traumatic aSDH requiring surgical evacuation. The cohort was divided based on antithrombotic use and whether pharmacologic reversal agents or platelet transfusions were administered. A 3-way comparison of outcomes was performed between patients taking anticoagulants who received pharmacologic reversal, patients taking antiplatelets who received platelet transfusion, and patients not taking antithrombotics. Multivariable regressions, adjusted for injury severity, further investigated associations with outcomes., Results: Of 138 patients who met inclusion criteria, 13.0% (n = 18) reported taking anticoagulants, 16.7% (n = 23) reported taking antiplatelets, and 3.6% (n = 5) reported taking both. Patients taking antiplatelets who received platelet transfusion had longer intraoperative times (P = 0.040) and higher rates of palliative care consultations (P = 0.046) compared with patients taking anticoagulants who received pharmacologic reversal and patients not taking antithrombotics. Across groups, no significant differences were found in frequency of in-hospital intracranial hemorrhage and venous thromboembolism, length of hospital stay, rate of inpatient mortality, or follow-up health status. In multivariable analysis, intraoperative time remained longest for the antiplatelets with platelet transfusion group. Other outcomes were not associated with patient group., Conclusions: Among surgical patients with traumatic aSDH, those taking antiplatelet medications who receive platelet transfusions experience longer intraoperative procedure times and higher rates of palliative care consultation. Comparable outcomes were observed between patients receiving antithrombotic reversal and patients not taking antithrombotics., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Objectives: Acute subdural hematoma (aSDH) after traumatic brain injury frequently requires emergent craniotomy (CO) or decompressive craniectomy (DC). We sought to determine the variables associated with either surgical approach and to compare outcomes between matched patients., Methods: A multi-center retrospective review was used to identify traumatic aSDH patients who underwent CO or DC. Patient variables independently associated with surgical approach were used for coarsened exact matching.Multivariate logistic regression and multivariate Cox proportional-hazards regression wereconducted on matched patients to determine independent predictors of mortality., Results: Seventy-six patients underwent CO and sixty-two underwent DC for aSDH evacuation. DC patients were21.4 years younger (P < 0.001), more likely to be male (80.6 % vs 60.5 %,P = 0.011), and present with GCS ≤ 8 (64.5 % vs 36.8 %,P = 0.001). Age (P < 0.001), epidural hematoma (P = 0.01), skull fracture (P = 0.001), and cisternal effacement (P = 0.02) were independently associated with surgical approach. After coarsened exact matching, DC (P = 0.008), older age (P = 0.007), male sex (P = 0.04), and intraventricular hemorrhage (P = 0.02), were independently associated with inpatient mortality. Multivariate Cox proportional-hazards regression demonstrated that DC was independently associated with mortality at 90-days (P = 0.001) and 1-year post-operation (P = 0.003)., Conclusion: aSDH patients who receive surgical evacuation via DC as opposed to CO are younger, more likely to be male, and have worse clinical exam. After controlling for patient differences via coarsened exact matching, DC is independently associated with mortality., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Skull base leiomyomas (LMs) and angioleiomyomas (ALMs) are rare, and the understanding of this disease is limited. We present a systematic literature review of skull base LM and ALM and report a case of internal auditory canal (IAC) ALM., Methods: A systematic review was conducted following the PRISMA guidelines. PubMed and Embase were systematically queried for skull base LM and ALM, and Rayyan QCRI was used for the review. After applying exclusion criteria, individual articles were evaluated for quality control, data collection, and analysis. The presentation, management, and outcome of a 37-year-old man with a right-sided IAC ALM are described., Results: Of 68 unique entries, 27 studies were included. Thirty-four cases of skull base LM (n = 6) or ALM (n = 28) were identified. Average age at presentation was 45.1 ± 14.5 years, and 52.9% of patients were male. Tumor diameter was 2.75 ± 1.6 cm, with headaches being the most reported symptom. Commonly reported locations were the cavernous sinus and the external auditory canal. Only 3 cases of IAC ALM met the criteria for this review. All tumors were treated with surgery, and gross total resection was achieved in 27 patients. Radiation was given in 3 cases with subtotal resection., Conclusions: Skull base LM and ALM are rare. Given the need for pathology, surgery has been the standard treatment for symptomatic skull base LM and ALM. It is important to understand the available data about this disease and consider it in the differential of skull base lesions., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Gross total resection (GTR) of contrast-enhancing tumor is associated with increased survival in primary glioblastoma. Recently, there has been increasing interest in performing supratotal resections (SpTRs) for glioblastoma., Objective: To address the published results, which have varied in part due to lack of consensus on the definition and appropriate use of SpTR., Methods: A crowdsourcing approach was used to survey 21 neurosurgical oncologists representing 14 health systems nationwide. Participants were presented with 11 definitions of SpTR and asked to rate the appropriateness of each definition. Participants reviewed T1-weighed postcontrast and fluid-attenuated inversion-recovery magnetic resonance imaging for 22 anatomically distinct glioblastomas. Participants were asked to assess the tumor location's eloquence, the perceived equipoise of enrolling patients in a randomized trial comparing gross total to SpTR, and their personal treatment plans., Results: Most neurosurgeons surveyed (n = 18, 85.7%) agree that GTR plus resection of some noncontrast enhancement is an appropriate definition for SpTR. Overall, moderate inter-rater agreement existed regarding eloquence, equipoise, and personal treatment plans. The 4 neurosurgeons who had performed >10 SpTRs for glioblastomas in the past year were more likely to recommend it as their treatment plan (P < .005). Cases were divided into 3 anatomically distinct groups based upon perceived eloquence. Anterior temporal and right frontal glioblastomas were considered the best randomization candidates., Conclusion: We established a consensus definition for SpTR of glioblastoma and identified anatomically distinct locations deemed most amenable to SpTR. These results may be used to plan prospective trials investigating the potential clinical utility of SpTR for glioblastoma., (© Congress of Neurological Surgeons 2021.)

Objective: Coronavirus disease 2019 (COVID-19) is a disruptive pandemic that has continued to test the limits of health care system capacities. It is important to highlight the specific challenges facing US neurosurgery during these difficult circumstances. In the present study, we have described our neurosurgery department's unique experience during the COVID-19 pandemic., Methods: We analyzed the following data points both before and during the first months of the COVID-19 pandemic: the number of patients infected with COVID-19 at our institution, changes in neurosurgical operative workflow, changes in neurosurgical outpatient and inpatient clinic workflows, resident redeployment statistics and changes in call schedules, and changes in neurosurgical education., Results: At our institution, the adult surgery numbers decreased from 120 during the week of March 4-11, 2020 (before the World Health Organization had classified the COVID-19 outbreak as a pandemic) to 17 during the week of April 13-17, 2020. The number of pediatric surgeries decreased from 15 to 3 during the same period. Significantly more surgeries were cancelled than were delayed (P < 0.0001). A drastic decline occurred in the number of in-person neurosurgery clinic visits (97.12%) between March and April 2020 (P = 0.0020). The inpatient census declined from mid-March to mid-April 2020 by 44.68% compared with a 4.26% decline during the same period in 2019 (P < 0.0001). Finally, neurosurgery education has largely shifted toward video-conferencing sessions rather than in-person sessions., Conclusion: By detailing our experience during the COVID-19 pandemic, we hope to have provided a detailed picture of the challenges facing neurosurgery within an academic medical center., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Ependymosarcomas are rare, biphasic tumors composed of ependymal and sarcomatous components. Due to their rarity, their biologic basis is not well understood. We report the case of a 38-year-old male with anaplastic ependymoma (WHO grade III) that progressed to ependymosarcoma in less than 2 years after multiple resections, chemoradiotherapy, and anti-PD1 immunotherapy. Next-generation sequencing was performed on both high-grade anaplastic ependymoma and ependymosarcoma samples to detect small base changes, insertions, and deletions in exons and splice junctions from a panel of over 400 genes. We identify genetic variants in the tumor suppressors RB1 , TP53 , and TSC2 in these samples and discuss the potential significance of an additional TSC2 genetic variant in the progression to ependymosarcoma.

Background: Primary central nervous system lymphomas (PCNSLs) account for 1%-2% of primary central nervous system tumors. Until recently, treatment has centered on biopsy, radiotherapy, and high-dose methotrexate, without a clear role for cytoreductive surgery. The objective of this article is to compare the impact of biopsy versus cytoreductive surgery in outcomes of patients with PCNSL, including postoperative complications and survival., Methods: We performed a systematic review of literature published from January 1, 1968 to May 2, 2018 related to PCNSL treatment in patients undergoing biopsy or resection. Data on morbidity, progression-free survival, and overall survival were extracted and analyzed., Results: A total of 1291 nonduplicate citations were identified, with 244 articles selected for full-text review. Twenty-four articles were included for data abstraction including 2 level IIb studies, 4 level IIIb studies, and the remaining 18 articles representing level IVb studies. Of these articles, 15 failed to show benefit with cytoreductive surgery; most of these articles included relatively small sample sizes and predated standardization of high-dose systemic methotrexate treatment. Larger, more recent series included 9 articles providing evidence in support of cytoreductive surgery. Patient age, functional status, and treatment with chemotherapy and/or radiation were associated with improved survival across studies., Conclusions: The treatment of PCNSL is challenging and ever-evolving. Earlier, smaller studies failed to show the benefit of cytoreductive surgery over biopsy in patients with PCNSL. Larger, more recent series seem to show the possible benefit of cytoreductive surgery in PCNSL. Future well-designed prospective studies may help further elucidate the role of resection in the modern treatment of PCNSL., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To quantify the accuracy of amide proton transfer-weighted (APTw) MRI for identifying active glioma after treatment via radiographically guided stereotactic tissue validation. Experimental Design: Twenty-one patients who were referred for surgery for MRI features concerning for tumor progression versus treatment effect underwent preoperative APTw imaging. Stereotactic biopsy samples were taken from regions of interest with varying APTw signal intensities. The relationship between final clinical pathology and the histopathology of each of the 64 specimens was analyzed relative to APTw results. Analysis of confirmed recurrent tumor or treatment effect tissue was used to perform ROC analysis., Results: Eighteen of 21 patients had recurrent tumor, and 3 had treatment effect on clinical pathology. In 12 patients, there were multiple histopathologic assignments confirmed within the same tumor. Of the 64 total specimens, 20 specimens were active glioma, 27 mixed active and quiescent glioma, and 17 quiescent/no identifiable tumor. APTw signal intensity and histopathologic assignment, cellularity, and proliferation index had significant positive correlations ( R = 0.651, 0.580, and 0.458, respectively; all P < 0.001). ROC analysis with a 1.79% APTw intensity cutoff differentiated active from nonactive tumor (AUC of 0.881) with 85.1% sensitivity and 94.1% specificity. Analysis of clinical pathology showed the mean APTw intensity for each patient had 94.4% sensitivity and 100% positive predictive value for identifying recurrent glioma at this cutoff., Conclusions: APTw imaging hyperintensity may be a marker of active malignant glioma. It is able to distinguish between regions of heterogeneous abnormality on anatomic brain MRI with high sensitivity and specificity., (©2018 American Association for Cancer Research.)

Purpose: Pathological assessment using World Health Organization (WHO) criteria is the gold standard for diagnosis of gliomas. However, the accuracy of diagnosis is limited by tissue sampling, particularly for infiltrating, heterogeneous tumours. We assessed the accuracy of amide proton transfer-weighted (APTw) magnetic resonance imaging (MRI)-guided tissue sampling to identify regions of high-grade glioma via radiographic-histopathologic correlation in patients with newly suspected glioma., Patients and Methods: Twenty-four patients with previously undiagnosed gliomas underwent a volumetric APTw MRI prior to their first neurosurgical procedure. A total of 70 specimens were collected via APTw image-directed stereotactic biopsy. Cellularity, necrosis, proliferation and glioma WHO grade were analysed for all specimens and correlated with corresponding APTw signal intensities., Results: Thirty-three specimens displayed grade-II pathology, 14 grade-III, 15 grade-IV, and eight specimens revealed only peritumoural oedema. Multiple glioma grades were found within a single lesion in six patients. APTw signal intensities of the biopsied sites and the maximum APTw values across all biopsied sites in each patient were significantly higher for high-grade versus low-grade specimens. APTw signal intensities were significantly positively correlated with cellularity (R = 0.757) and proliferation (R = 0.538). Multiple linear regression analysis showed that tumour cellularity and proliferation index were the best predictors of APTw signal intensities., Conclusion: APTw imaging identified tumour areas of higher cellularity and proliferation, allowing identification of high-grade regions within heterogeneous gliomas. APTw imaging can be readily translated for more widespread use and can assist diagnostic neurosurgical procedures by increasing the accuracy of tumour sampling in patients with infiltrating gliomas., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: Metastatic brain tumors are the most common brain tumors in adults. Patients with metastatic brain tumors have poor prognoses with median survival of 6-12 months. Seizures are a major presenting symptom and cause of morbidity and mortality. In this article, risk factors for the onset of preoperative seizures and postoperative seizure control are examined., Methods: Adult patients who underwent resection of one or more brain metastases at a single institution between 1998 and 2011 were reviewed retrospectively., Results: Of 565 patients, 114 (20.2%) patients presented with seizures. Factors independently associated with preoperative seizures were preoperative headaches (P = 0.044), cognitive deficits (P = 0.031), more than 2 intracranial metastatic tumors (P = 0.013), temporal lobe location (P = 0.031), occipital lobe location (P = 0.010), and bone involvement by tumor (P = 0.029). Factors independently associated with loss of seizure control after surgical resection were preoperative seizures (P = 0.001), temporal lobe location (P = 0.037), lack of postoperative chemotherapy (P = 0.010), subtotal resection of tumor (P = 0.022), and local recurrence (P = 0.027). At last follow-up, the majority of patients (93.8%) were seizure-free. Thirty patients (5.30%) in total had loss of seizure control, and only 8 patients (1.41%) who did not have preoperative seizures presented with new-onset seizures after surgical resection of their metastases., Conclusions: The brain is a common site for metastases from numerous primary cancers, such as breast and lung. The identification of factors associated with onset of preoperative seizures as well as seizure control postoperatively could aid management strategies for patients with metastatic brain tumors. Patients with preoperative seizures who underwent resection tended to have good seizure control after surgery., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: In patients with progressive low-grade glioma (LGG), the presence of new magnetic resonance imaging (MRI) enhancement is commonly used as an indicator of malignant degeneration, but its accuracy in this setting is uncertain., Objective: We characterize the ability of new MRI enhancement to serve as a surrogate for histologic grade in patients with progressive LGG, and to explore the prognostic value of new MRI enhancement, pathologic grade, and extent of resection., Methods: Patients at our institution with World Health Organization grade II glioma diagnosed between 1994 and 2010 and who underwent repeat biopsy or resection at progression were retrospectively reviewed (n = 108). The positive predictive value, negative predictive value, sensitivity, and specificity of new MRI enhancement were characterized. A multivariable proportional hazards model was used to test associations with overall survival (OS), and Kaplan-Meier curves were constructed to compare OS between patient subsets., Results: The positive predictive value, negative predictive value, sensitivity, and specificity of new MRI enhancement were 82%, 77%, 92%, and 57%, respectively. In patients without malignant degeneration, new MRI enhancement was associated with inferior median OS (92.5 months vs. not reached; P = 0.03). In patients with malignant degeneration, gross or near total resection was associated with improved median OS (58.8 vs. 28.8 months; P = 0.02)., Conclusion: In patients with progressive LGG, new MRI enhancement and pathologic grade were discordant in greater than 20% of cases. Pathologic confirmation of grade should therefore be attempted, when safe, to dictate management. Beyond functioning as a surrogate for pathologic grade, new MRI enhancement may predict for worse outcomes, a concept that merits prospective investigation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Human tumor cell lines form the basis of the majority of present day laboratory cancer research. These models are vital to studying the molecular biology of tumors and preclinical testing of new therapies. When compared to traditional adherent cell lines, suspension cell lines recapitulate the genetic profiles and histologic features of glioblastoma multiforme (GBM) with higher fidelity. Using a modified neural stem cell culture technique, here we report the characterization of GBM cell lines including GBM variants., Methods: Tumor tissue samples were obtained intra-operatively and cultured in neural stem cell conditions containing growth factors. Tumor lines were characterized in vitro using differentiation assays followed by immunostaining for lineage-specific markers. In vivo tumor formation was assayed by orthotopic injection in nude mice. Genetic uniqueness was confirmed via short tandem repeat (STR) DNA profiling., Results: Thirteen oncosphere lines derived from GBM and GBM variants, including a GBM with PNET features and a GBM with oligodendroglioma component, were established. All unique lines showed distinct genetic profiles by STR profiling. The lines assayed demonstrated a range of in vitro growth rates. Multipotency was confirmed using in vitro differentiation. Tumor formation demonstrated histologic features consistent with high grade gliomas, including invasion, necrosis, abnormal vascularization, and high mitotic rate. Xenografts derived from the GBM variants maintained histopathological features of the primary tumors., Conclusions: We have generated and characterized GBM suspension lines derived from patients with GBMs and GBM variants. These oncosphere cell lines will expand the resources available for preclinical study.

OBJECT Chiari Type I malformation involves caudal displacement of the cerebellar tonsils below the foramen magnum, which obstructs normal cerebrospinal fluid flow and increases intracranial pressure. Certain aspects of its surgical treatment remain controversial. A retrospective study was conducted to assess the efficacy of tonsillar cautery on syrinx resolution among pediatric Chiari patients undergoing cervicomedullary decompression. METHODS A retrospective cohort study was performed for patients 0-18 years of age who underwent surgical correction for Chiari Type I malformation with syrinx between 1995 and 2013. Basic demographic information was collected as well as data for preoperative symptoms, prior surgical history, perioperative characteristics, and postsurgical outcomes. Descriptive statistics were performed in addition to bivariate analyses. Candidate predictor variables were identified based on an association with tonsillar cautery with p < 0.10. Forward stepwise likelihood ratio was used to select candidate predictors in a binary logistic regression model (P in = 0.05, P out = 0.10) most strongly associated with the outcome. RESULTS A total of 171 patients with Chiari Type I malformation with syrinx were identified, and 43 underwent tonsillar cautery. Patients who underwent tonsillar cautery had 6.11 times greater odds of improvement in their syrinx (95% CI 2.57-14.49, p < 0.001). There was no effect of tonsillar cautery on increased perioperative complications as well as the need for repeat decompressions. CONCLUSIONS Tonsillar cautery is safe and effective in the treatment of Chiari Type I malformation with syrinx and may decrease time to syrinx resolution after cervicomedullary decompression. Tonsillar cautery does not increase postoperative complications in pediatric Chiari Type I malformation patients.

Cell-free DNA shed by cancer cells has been shown to be a rich source of putative tumor-specific biomarkers. Because cell-free DNA from brain and spinal cord tumors cannot usually be detected in the blood, we studied whether the cerebrospinal fluid (CSF) that bathes the CNS is enriched for tumor DNA, here termed CSF-tDNA. We analyzed 35 primary CNS malignancies and found at least one mutation in each tumor using targeted or genome-wide sequencing. Using these patient-specific mutations as biomarkers, we identified detectable levels of CSF-tDNA in 74% [95% confidence interval (95% CI) = 57-88%] of cases. All medulloblastomas, ependymomas, and high-grade gliomas that abutted a CSF space were detectable (100% of 21 cases; 95% CI = 88-100%), whereas no CSF-tDNA was detected in patients whose tumors were not directly adjacent to a CSF reservoir (P < 0.0001, Fisher's exact test). These results suggest that CSF-tDNA could be useful for the management of patients with primary tumors of the brain or spinal cord.

Objectives: Patients with glioblastoma (GBM) have an inherently shortened survival because of their disease. It has been recently shown that carmustine wafers in addition to other therapies (surgery, temozolomide, and radiation) can further extend survival. There is concern, however, that these therapies may increase infection risk. The goals of this study were to calculate the incidence of postoperative infection, evaluate if carmustine wafers changes the risk of infection and identify factors independently associated with an infection following GBM surgery., Methods: All patients who underwent non-biopsy, surgical resection of an intracranial GBM from 2007 to 2011 at a single institution were retrospectively reviewed. Stepwise multivariate proportional hazards regression analysis was used to identify factors associated with infection, including the use of carmustine wafers. Variables with P < 0.05 were considered statistically significant., Results: Four hundred and one patients underwent resection of an intracranial GBM during the reviewed period, and 21 (5%) patients developed an infection at a median time of 40 [28-286] days following surgery. The incidence of infection was not higher in patients who had carmustine wafers, and this remained true in multivariate analyses to account for differences in treatment cohorts. The factors that remained significantly associated with an increased risk of infection were prior surgery [RR (95% CI); 2.026 (1.473-4.428), P = 0.01], diabetes mellitus [RR (95% CI); 6.090 (1.380-9.354)], P = 0.02], and increasing duration of hospital stay [RR (95% CI); 1.048 (1.006-1.078); P = 0.02], where the greatest risk occurred with hospital stays > 5 days [RR (95% CI); 3.904 (1.003-11.620), P = 0.05]., Discussion: These findings may help guide treatment regimens aimed at minimizing infection for patients with GBM.

Objective: The management of patients with brain metastases is typically dependent on their prognosis. Recursive partitioning analysis (RPA) is the most commonly used method for prognosticating survival, but has limitations for patients in the intermediate class. The aims of this study were to ascertain preoperative risk factors associated with survival, develop a preoperative prognostic grading system, and evaluate the utility of this system in predicting survival for RPA class 2 patients., Methods: Adult patient who underwent intracranial metastatic tumor surgery at an academic tertiary care institution from 1997 to 2011 were retrospectively reviewed. Multivariate proportional hazards regression analysis was used to identify preoperative factors associated with survival. The identified associations were then used to develop a grading system. Survival as a function of time was plotted using the Kaplan-Meier method, and survival rates were compared using log-rank analyses., Results: A total of 421 (59%) of 708 patients were RPA class 2. The preoperative factors found to be associated with poorer survival were: male gender (P < 0.0001), motor deficit (P = 0.0007), cognitive deficit (P = 0.0004), nonsolitary metastases (P = 0.002), and tumor size >2 cm (P = 0.003). Patients having 0-1, 2, and 3-5 of these variables were assigned a preoperative grade of A, B, and C, respectively. Patients with a preoperative grade of A, B, and C had a median survival of 17.0, 10.3, and 7.3 months, respectively. These grades had distinct survival times (P < 0.05)., Conclusions: The present study devised a preoperative grading system that may provide prognostic information for RPA class 2 patients, which may also guide medical and surgical therapies before any intervention is pursued., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The development of noninvasive methods to detect and monitor tumors continues to be a major challenge in oncology. We used digital polymerase chain reaction-based technologies to evaluate the ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types. We found that ctDNA was detectable in >75% of patients with advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocellular, and head and neck cancers, but in less than 50% of primary brain, renal, prostate, or thyroid cancers. In patients with localized tumors, ctDNA was detected in 73, 57, 48, and 50% of patients with colorectal cancer, gastroesophageal cancer, pancreatic cancer, and breast adenocarcinoma, respectively. ctDNA was often present in patients without detectable circulating tumor cells, suggesting that these two biomarkers are distinct entities. In a separate panel of 206 patients with metastatic colorectal cancers, we showed that the sensitivity of ctDNA for detection of clinically relevant KRAS gene mutations was 87.2% and its specificity was 99.2%. Finally, we assessed whether ctDNA could provide clues into the mechanisms underlying resistance to epidermal growth factor receptor blockade in 24 patients who objectively responded to therapy but subsequently relapsed. Twenty-three (96%) of these patients developed one or more mutations in genes involved in the mitogen-activated protein kinase pathway. Together, these data suggest that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes in patients with multiple different types of cancer.

Introduction: Surgery is first-line therapy for glioblastoma, and there is evidence that gross total resection is associated with improved survival. Gross total resection, however, is not always possible, and relationships among extent (percent) of resection (EOR), residual volume (RV), and survival are unknown. The goals were to evaluate whether there is an association between EOR and RV with survival and recurrence and to establish minimum EOR and maximum RV thresholds., Methods: Adult patients who underwent primary glioblastoma surgery from 2007 to 2011 were retrospectively reviewed. Three-dimensional volumetric tumor measurements were made. Multivariate proportional hazards regression analysis was used to evaluate the relationship between EOR and RV with survival and recurrence., Results: Of 259 patients, 203 (78%) died and 156 (60%) had tumor recurrence. The median survival and progression-free survival were 13.4 and 8.9 months, respectively. The median (interquartile range) pre- and postoperative tumor volumes were 32.2 (14.0-56.3) and 2.1 (0.0-7.9) cm(3), respectively. EOR was independently associated with survival (hazard ratio [HR], 0.995; 95% confidence interval [CI]: 0.990-0.998; P = .008) and recurrence (HR [95% CI], 0.992 [0.983-0.998], P = .005). The minimum EOR threshold for survival (P = .0006) and recurrence (P = .005) was 70%. RV was also associated with survival (HR [95% CI], 1.019 [1.006-1.030], P = .004) and recurrence (HR [95% CI], 1.024 [1.001-1.044], P = .03). The maximum RV threshold for survival (P = .01) and recurrence (P = .01) was 5 cm(3)., Conclusion: This study shows for the first time that both EOR and RV are significantly associated with survival and recurrence, where the thresholds are 70% and 5 cm(3), respectively. These findings may help guide surgical and adjuvant therapies aimed at optimizing outcomes for glioblastoma patients.

Glioblastoma multiforme (GBM) is the most common primary malignant adult brain tumor and is associated with poor survival. Recently, stem-like cell populations have been identified in numerous malignancies including GBM. To identify genes whose expression is changed with differentiation, we compared transcript profiles from a GBM oncosphere line before and after differentiation. Bioinformatic analysis of the gene expression profiles identified podocalyxin-like protein (PODXL), a protein highly expressed in human embryonic stem cells, as a potential marker of undifferentiated GBM stem-like cells. The loss of PODXL expression upon differentiation of GBM stem-like cell lines was confirmed by quantitative real-time PCR and flow cytometry. Analytical flow cytometry of numerous GBM oncosphere lines demonstrated PODXL expression in all lines examined. Knockdown studies and flow cytometric cell sorting experiments demonstrated that PODXL is involved in GBM stem-like cell proliferation and oncosphere formation. Compared to PODXL-negative cells, PODXL-positive cells had increased expression of the progenitor/stem cell markers Musashi1, SOX2, and BMI1. Finally, PODXL expression directly correlated with increasing glioma grade and was a marker for poor outcome in patients with GBM. In summary, we have demonstrated that PODXL is expressed in GBM stem-like cells and is involved in cell proliferation and oncosphere formation. Moreover, high PODXL expression correlates with increasing glioma grade and decreased overall survival in patients with GBM.

Somatic mutations in Isocitrate Dehydrogenase 1 (IDH1) are frequent in low grade and progressive gliomas and are characterized by the production of 2-hydroxyglutarate (2-HG) from α-ketoglutarate by the mutant enzyme. 2-HG is an "oncometabolite" that competitively inhibits α-KG dependent dioxygenases resulting in various widespread cellular changes including abnormal hypermethylation of genomic DNA and suppression of cellular differentiation. Despite the growing understanding of IDH mutant gliomas, the development of effective therapies has proved challenging in part due to the scarcity of endogenous mutant in vivo models. Here we report the generation of an endogenous IDH1 anaplastic astrocytoma model which rapidly grows in vivo, produces 2-HG and exhibits DNA hypermethylation. Using this model, we have demonstrated the preclinical efficacy and mechanism of action of the FDA approved demethylating drug 5-azacytidine in vivo. Long term administration of 5-azacytidine resulted in reduction of DNA methylation of promoter loci, induction of glial differentiation, reduction of cell proliferation and a significant reduction in tumor growth. Tumor regression was observed at 14 weeks and subsequently showed no signs of re-growth at 7 weeks despite discontinuation of therapy. These results have implications for clinical trials of demethylating agents for patients with IDH mutated gliomas.

Objective Skull base metastases (SBMs) are rare lesions in close proximity to critical neural and vasculature structures. This rarity and complexity have led many to only offer nonsurgical therapies. The surgical outcomes for patients with SBM therefore remain unknown. Design Retrospective, comparison analyses. Setting Johns Hopkins Hospital. Participants All patients who underwent intracranial metastatic tumor surgery. Main Outcome Measure Survival and recurrence. Results Of the 708 patients who underwent intracranial metastatic tumor surgery, 29 (4%) had SBM: 3 (10%) involved the anterior skull base, 7 (24%) the sella, 6 (21%) the orbit, 2 (7%) the sphenoid wing, 3 (10%) the clivus, 4 (14%) the petrous bone, and 4 (14%) the paranasal sinuses. Following surgery, 6 (50%) had improvements in vision and 14 (88%) had improvement and/or maintenance of their cranial nerve symptoms. Three (10%), 0(0%), and 1(3%) developed a new motor, language, and vision deficit, respectively. There were no differences in median survival (10.0 versus 9.2 months, p = 0.48) and local progression-free survival (PFS) (p = 0.52), but there was improved distal PFS (p = 0.04) between patients with and without SBM. Conclusions Patients with SBM are relatively rare. These patients can tolerate surgery with minimal morbidity and mortality, and they have similar prognoses to patients without SBM.

The addition of concomitant and adjuvant chemotherapy to radiation therapy after surgical resection has increased significantly the survival of patients with glioblastoma (GB). In conjunction, there has been an increasing fraction of patients who present with new enlarged areas of contrast enhancement and edema on post-treatment imaging that improve without further treatment. It remains to be established how this phenomenon, commonly termed pseudoprogression, can be distinguished from true tumor recurrence defined as the histological presence of active high-grade tumor, as well as its prognostic significance. Data for over 500 patients undergoing surgery for recurrent GB were reviewed. Pathological specimens were categorized as those that contained active high-grade glioma in any amount, and those that did not. Patient survival was compared between these two groups, and independent associations were assessed using Cox proportionate hazards regression analysis. 59 patients met the study criteria including complete pathological and follow-up data. Mean age was 53 ± 11 years. Median survival from suspected recurrence and initial diagnosis were 8 [5-14] and 20 [12-30] months. Seventeen patients (29 %) had no evidence of active high-grade tumor and 42 (71 %) had at least focal active high-grade glioma. Pathologic pseudoprogression at re-operation (p = 0.03) and gross total resection (p = 0.01) were independently associated with survival. The histopathological features defined here and used to assess the tumor at reoperation were independently associated with survival. These findings may be important in designing treatment strategies and clinical trial endpoints for patients with GB.

Patients with glioblastoma (GB) are known to have poor prognoses, and among these patients, those with poor neurological function have an even poorer prognosis. Consequently, aggressive surgeries and adjuvant therapies are often withheld because of this dismal outlook. The effects of aggressive therapies in this small subset of patients remain unknown. The goal of this study was to evaluate outcomes and factors associated with survival for poor functioning patients who underwent aggressive resection of their GB. Adult patients who underwent surgical resection of an intracranial primary GB at an academic tertiary-care institution between 1997 and 2007 were retrospectively reviewed. Patients with a Karnofsky Performance Scale (KPS) score of ≤60 were included. A total of 100 patients with primary GB met the inclusion criteria. The average age (± standard deviation) and KPS score of this cohort were 54 ± 15 years and 53 ± 12, respectively. No patient (0%) experienced perioperative mortality, and 0 (0%), 10 (10%), and 3 (3%) of patients incurred a new or increasing language, motor, and visual deficit, respectively. At last follow-up, 88 (88%) patients died with a median survival of 6.6 months. The factors associated with improved survival were age <65 year (p = 0.005), tumor size >2 cm (p = 0.01), radical tumor resection (p=0.01), and temozolomide (p = 0.001). This study identifies a subset of patients with poor functional status who may benefit from aggressive surgical resection., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Object: Glioblastoma is the most common and aggressive type of primary brain tumor in adults. These tumors recur regardless of intervention. This propensity to recur despite aggressive therapies has made many perceive that repeated resections have little utility. The goal of this study was to evaluate if patients who underwent repeat resections experienced improved survival as compared with patients with fewer numbers of resections, and whether the number of resections was an independent predictor of prolonged survival., Methods: The records of adult patients who underwent surgery for an intracranial primary glioblastoma at an academic tertiary-care institution between 1997 and 2007 were retrospectively reviewed. Multivariate proportionalhazards regression analysis was used to identify an association between glioblastoma resection number and survival after controlling for factors known to be associated with survival, such as age, functional status, periventricular location, extent of resection, and adjuvant therapy. Survival as a function of time was plotted using the Kaplan-Meier method, and survival rates were compared using log-rank analysis., Results: Five hundred seventy-eight patients with primary glioblastoma met the inclusion/exclusion criteria. At last follow-up, 354, 168, 41, and 15 patients underwent 1, 2, 3, or 4 resections, respectively. The median survival for patients who underwent 1, 2, 3, and 4 resections was 6.8, 15.5, 22.4, and 26.6 months (p < 0.05), respectively. In multivariate analysis, patients who underwent only 1 resection experienced shortened survival (relative risk [RR] 3.400, 95% CI 2.423-4.774; p < 0.0001) as compared with patients who underwent 2 (RR 0.688, 95% CI 0.525-0.898; p = 0.0006), 3 (RR 0.614, 95% CI 0.388-0.929; p = 0.02), or 4 (RR 0.600, 95% CI 0.238-0.853; p = 0.01) resections. These results were verified in a case-control evaluation, controlling for age, neurological function, periventricular tumor location, extent of resection, and adjuvant therapy. Patients who underwent 1, 2, or 3 resections had a median survival of 4.5, 16.2, and 24.4 months, respectively (p < 0.05). Additionally, the risk of infections or iatrogenic deficits did not increase with repeated resections in this patient population (p > 0.05)., Conclusions: Patients with glioblastoma will inevitably experience tumor recurrence. The present study shows that patients with recurrent glioblastoma can have improved survival with repeated resections. The findings of this study, however, may be limited by an intrinsic bias associated with patient selection. The authors attempted to minimize these biases by using strict inclusion criteria, multivariate analyses, and case-control evaluation.

Objective: Seizures are common among patients with meningiomas and are a significant cause of morbidity and poor quality of life. The factors associated with the onset of seizures as well as factors associated with seizure control remains poorly understood., Methods: Adult patients who underwent primary resection of a supratentorial World Health Organization grade I meningioma at a single institution between 1996 and 2006 were retrospectively reviewed. Multivariate logistical regression analyses were used to identify associations with preoperative seizures, and multivariate proportional hazards regression analyses were used to identify associations with prolonged seizure control after surgical resection., Results: Of the 626 patients in this series, 84 (13%) presented with seizures. The factors independently associated with preoperative seizures were Karnofsky performance score ≤ 80 (P< 0.0001), absence of headaches (P = 0.0006), and vasogenic edema (P = 0.007). At 48 months postoperatively, 90% were Engel class I, 3% were class II, 0 were class III, and 7% were class IV. The factors independently associated with decreased seizure control after surgical resection were uncontrolled preoperative seizures (P = 0.04), parasagittal tumors (P = 0.03), and tumors along the sphenoid wing (P = 0.05). The association between seizure recurrence and tumor recurrence trended toward but did not achieve statistical significance (P = 0.11)., Conclusions: With the widespread availability of various neuroimaging modalities, there will be increased detection of intracranial meningiomas. The identification and consideration of factors associated with seizure onset and prolonged seizure control may help guide treatment strategies aimed at improving the quality of life for patients with meningiomas., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The poor prognosis for patients with glioblastoma (GB) heightens the importance of maintaining function throughout treatment. Hyperglycemia has been linked to poor neurological outcomes following stroke, traumatic brain and spinal cord injury. We hypothesized this may also be true following the resection of GB. We assessed associations with post-operative function with the goal of identifying modifiable factors in the peri-operative period with a particular focus on blood glucose levels. Independent associations with worse post-operative function included: patient age, pre-operative motor deficit, deep tumor location, post-operative motor deficit, and elevated mean peri-operative glucose. Interestingly, controlling for associated factors including dexamethasone dosing, patients with elevated peri-operative glucose levels were nearly twice as likely to have new post-operative neurological deficits. These results suggest, together with the broad literature supporting a role for hyperglycemia in neurological injury, that this may represent a modifiable factor in the peri-operative care of these patients., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: Peak incidence of glioblastoma multiforme (GBM) occurs in individuals aged 65 years and older. The goal was to evaluate the efficacy of carmustine wafers in prolonging survival for older GBM patients., Methods: One hundred and thirty-three consecutive patients aged 65 years and older who underwent surgery for an intracranial primary (de novo) GBM from 1997-2007 were retrospectively reviewed. Among these 133 patients, 45 patients with carmustine wafer implantation were matched with 45 patients without implantation. These groups were matched for factors consistently shown to be associated with survival (age, Karnofsky performance scale, extent of resection, radiation therapy, and temozolomide). Survival was expressed as estimated Kaplan-Meier plots, and log-rank analysis was used to compare survival curves. Variables with P<0.05 were considered statistically significant., Results: The mean (±standard deviation) age of the cohort was 73±5 years, and the median survival of the entire cohort was 5.9 months. Among patients with and without carmustine wafers, there were no significant differences in pre- and peri-operative variables. However, patients with carmustine wafers demonstrated prolonged survival as compared to patients without wafers. The median survival for patients with carmustine wafers was 8.7 months, while median survival for patients without wafers was 5.5 months (P=0.007). Likewise, in subgroup analysis, patients older than 70 years (P=0.0003) and 75 years (P=0.04) who had carmustine wafers had significantly longer survival than matched patients without wafers., Discussion: Older patients with GBM may benefit from carmustine wafers. The survival for older patients who received carmustine wafers is significantly longer than matched patients who did not receive carmustine wafers.

Object: The median survival duration for patients with glioblastoma is approximately 12 months. Maximizing quality of life (QOL) for patients with glioblastoma is a priority. An important, yet understudied, QOL component is functional independence. The aims of this study were to evaluate functional outcomes over time for patients with glioblastoma, as well as identify factors associated with prolonged functional independence., Methods: All patients who underwent first-time resection of either a primary (de novo) or secondary (prior lower grade glioma) glioblastoma at a single institution from 1996 to 2006 were retrospectively reviewed. Patients with a Karnofsky Performance Scale (KPS) score ≥ 80 were included. Kaplan-Meier, log-rank, and multivariate proportional hazards regression analyses were used to identify associations (p < 0.05) with functional independence (KPS score ≥ 60) following glioblastoma resection., Results: The median follow-up duration time was 10 months (interquartile range [IQR] 5.6-17.0 months). A patient's preoperative (p = 0.02) and immediate postoperative (within 2 months) functional status was associated with prolonged survival (p < 0.0001). Of the 544 patients in this series, 302 (56%) lost their functional independence at a median of 10 months (IQR 6-16 months). Factors independently associated with prolonged functional independence were: preoperative KPS score ≥ 90 (p = 0.004), preoperative seizures (p = 0.002), primary glioblastoma (p < 0.0001), gross-total resection (p < 0.0001), and temozolomide chemotherapy (p < 0.0001). Factors independently associated with decreased functional independence were: older age (p < 0.0001), coexistent coronary artery disease (p = 0.009), and incurring a new postoperative motor deficit (p = 0.009). Furthermore, a decline in functional status was independently associated with tumor recurrence (p = 0.01)., Conclusions: The identification and consideration of these factors associated with prolonged functional outcome (preoperative KPS score ≥ 90, seizures, primary glioblastoma, gross-total resection, temozolomide) and decreased functional outcome (older age, coronary artery disease, new postoperative motor deficit) may help guide treatment strategies aimed at improving QOL for patients with glioblastoma.

Object: As the population ages, the incidence of glioblastoma multiforme (GBM) among older patients (age > 65 years) will increase. Older patients, unlike their younger counterparts, are not often offered aggressive surgery because of their age, comorbidities, and potential inability to tolerate surgery. The goal of this study was to identify preoperative factors associated with decreased survival for older patients who underwent resection of a GBM. The identification of these factors may provide insight into which patients would benefit most from aggressive surgery., Methods: All patients older than 65 years who underwent nonbiopsy resection of an intracranial GBM at a single institution between 1997 and 2007 were retrospectively reviewed. Factors associated with overall survival were assessed using multivariate proportional hazards regression analysis after controlling for peri- and postoperative factors known to be associated with outcome (extent of resection, carmustine wafer implantation, temozolomide chemotherapy, and radiation therapy). Variables with p < 0.05 were considered statistically significant., Results: A total of 129 patients with an average age of 73 ± 5 years met the inclusion/exclusion criteria. At last follow-up, all 129 patients had died, with a median survival of 7.9 months. The preoperative factors that were independently associated with decreased survival were Karnofsky Performance Scale (KPS) score less than 80 (p = 0.001), chronic obstructive pulmonary disease (p = 0.01), motor deficit (p = 0.01), language deficit (p = 0.005), cognitive deficit (p = 0.02), and tumor size larger than 4 cm (p = 0.002). Patients with 0-1 (Group 1), 2-3 (Group 2), and 4-6 (Group 3) of these factors had statistically different survival times, where the median survival was 9.2, 5.5, and 4.4 months, respectively. In log-rank analysis, the median survival for Group 1 was significantly longer than that for Group 2 (p = 0.004) and Group 3 (p < 0.0001), while Group 2 had longer survival than Group 3 (p = 0.02)., Conclusions: Older patients with an increasing number of these factors may not benefit as much from aggressive surgery as patients with fewer factors. This may provide insight into identifying which patients older than 65 years of age may benefit from aggressive surgery.

Background: The peak incidence of glioblastoma multiforme (GBM) occurs in those aged 65 years and older. However, studies on this patient group remain limited. The goal of this study is to evaluate the efficacy of surgery versus biopsy for older patients with these lesions., Methods: 133 and 72 consecutive patients aged 65 years and older who underwent surgery and needle biopsy for intracranial primary (de novo) GBM between 1997 and 2007 were retrospectively reviewed. Among these patients, 40 who underwent surgical resection were matched with 40 who underwent needle biopsy alone for factors consistently shown to be associated with survival [age, Karnofsky Performance Scale (KPS) indexing, eloquent involvement, radiation, temozolomide]. Survival was expressed as estimated Kaplan-Meier plots, and log-rank analysis was used to compare survival curves., Results: Mean ± standard deviation age was 73 ± 5 years, and median survival was 4.9 months. There were no significant differences in perioperative outcomes among patients who underwent surgical resection versus needle biopsy. Patients who underwent resection had median survival of 5.7 months as compared with 4.0 months for patients who underwent needle biopsy (P = 0.02). Likewise, for patients aged 70 years and older, median survival was 4.5 months for 26 patients who underwent surgical resection as compared with 3.0 months for 26 patients who underwent needle biopsy (P = 0.03)., Conclusion: This study demonstrates that older patients tolerate aggressive surgery without increased surgery-related morbidity and have prolonged survival as compared with similar patients undergoing needle biopsy. These findings may help guide treatment decisions for patients, their families, and their physicians.

Background: Parasagittal meningiomas invading the superior sagittal sinus (SSS) pose formidable obstacles to surgical management. Invasion is often considered a contraindication to surgery because of associated morbidity, such as cerebral venous thrombosis., Objective: We report our most recent experience with the resection of parasagittal meningiomas invading the SSS., Methods: Between 1992 and 2004, 110 patients with parasagittal meningiomas underwent surgery at the Johns Hopkins Medical Institutions. Clinical charts, radiological studies, pathological features, and operative notes were retrospectively analyzed; only those patients with minimum 24 months follow-up (n = 61) were further studied., Results: Tumor distribution by location along the SSS was: 21% anterior, 62% middle, and 17% posterior. All patients were managed with initial surgical resection with radiosurgery for residual/recurrent disease if indicated (19.6%). Pathological examination revealed 80% grade I meningiomas, 13% grade II meningiomas, and 7% grade III meningiomas. Simpson grade I/II resection was achieved in 81% of patients. Major complications included venous thrombosis/infarction (7%), intraoperative air embolism (1.5%), and death (1.5%); long-term outcomes assessed included recurrence (11%) and improvement in Karnofsky Performance Score (85%)., Conclusion: On the basis of our study, the incidence of postoperative venous sinus thrombosis is 7% in the setting of a recurrence rate of 11% with a mean follow-up of 41 months. In comparison with the published literature, the data corroborate the rationale for our treatment paradigm; lesions invading the sinus can initially be resected to the greatest extent possible without excessive manipulation of vascular structures, whereas residual/recurrent disease can be observed and managed with radiosurgery.

Object: Patients harboring anaplastic astrocytomas (AAs) typically have a poor prognosis, with median survival times of approximately 3 years following resection. However, a significant variability in individual outcomes remains, with some patients surviving for a few months and others for several years. The ability to predict patient outcomes based on preoperative variables would help prognosticate survival and may also guide treatment strategies. The prognostic implications of a preoperative contrast-enhancing AA remain poorly understood., Methods: The medical records of all patients who underwent a craniotomy for a hemispheric AA from 1996 to 2006 at a single institution were retrospectively reviewed. Multivariate proportional hazards regression analysis was used to identify independent associations with recurrence and survival. The Kaplan-Meier method and log-rank analysis were used to plot and compare outcomes for patients with and without preoperative contrast enhancement., Results: One hundred sixty-five patients were available for analysis. The AAs were contrast enhancing in 102 patients (62%), and nonenhancing in 63 patients (38%). There were no significant differences in clinical and treatment-related variables between patients with and without contrast enhancement. After multivariate analysis, contrast enhancement was independently associated with decreased survival (p = 0.02) and increased recurrence (p = 0.04). The 5-year overall survival rates for patients with contrast-enhancing versus nonenhancing tumors were 31 and 38.5%, respectively. The 3-year rates of progression-free survival for patients with contrast-enhancing versus nonenhancing tumors were 32 and 56%, respectively. Interestingly, heterogeneously enhancing tumors appear to result in poorer outcomes as compared with other types of enhancement (such as ring enhancing, nodular, and others). Among patients with contrast-enhancing AAs, gross-total resection significantly delayed recurrence (p = 0.05) but did not significantly prolong survival (p = 0.52)., Conclusions: This study may provide insights into risk-stratifying patients with AAs, and most specifically those with AAs that enhance with contrast administration.

Background: Low-grade gliomas have been documented to undergo transformation into high-grade astrocytomas, and the time interval of this transformation has been reported to generally occur within 5 years in about 50% of patients harboring these low-grade lesions. Several studies have investigated the evolution of low-grade gliomas into malignant gliomas by CT and MRI characteristics, but many have not documented the timing of these transformation processes., Case Description: The authors discuss the cases of 2 patients with histopathologically confirmed grade II astrocytomas after craniotomies that underwent rapid evolution into malignant gliomas within 13 weeks. Interestingly, both low-grade astrocytomas were positive with immunostaining for the epidermal growth factor receptor, in which its amplification has been implicated as a molecular marker of malignant gliomas. In addition, the grade II astrocytomas were negative for p53 in both patients but were found to be positive upon transformation into malignant gliomas., Conclusions: To our knowledge, this is the first report of rapid malignant transformation of low-grade gliomas, which were proven by histology, within 13 weeks. There may be patients with a subtype of low-grade astrocytomas that may warrant molecular characterization to determine if aggressive adjuvant therapy would be of benefit., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Purpose: In this study, we analyzed the magnetic resonance imaging (MRI) changes in patients after GliaSite treatment and characterized the prognostic MRI indicators in these patients., Methods and Materials: A total of 25 patients with recurrent glioblastoma multiforme were treated with the GliaSite Radiation Therapy System. Patients at the Johns Hopkins Hospital with recurrent glioblastoma multiforme underwent surgical resection followed by GliaSite balloon implantation. Available MRI scans for 20 patients were obtained throughout the post-GliaSite treatment course. These were reviewed and analyzed for prognostic significance., Results: After GliaSite treatment, all patients developed some degree of T(1)-weighted contrast and T(2)-weighted hyperintensity around the resection cavity. The development of enhancement on T(1)-weighted contrast-enhanced imaging and the size of these lesions, in the absence of increasing T(2)-weighted hyperintensity, before clinical progression was not associated with decreased survival. Patients with T(1)-weighted enhancement >1 cm had a median survival of 13.6 months and those with T(1)-weighted lesions

Objective: Balancing the benefits of extensive tumor resection with the consequence of potential postoperative deficits remains a challenge in malignant astrocytoma surgery. Although studies have suggested that increasing extent of resection may benefit survival, the effect of new postoperative deficits on survival remains unclear. We set out to determine whether new-onset postoperative motor or speech deficits were associated with survival in our institutional experience with glioblastoma multiforme (GBM)., Methods: We retrospectively reviewed records of all patients (age range, 18-70 years; Karnofsky Performance Scale score, 80-100) who had undergone GBM resection between 1996 and 2006 at a single institution. Survival was compared between patients who had experienced surgically acquired motor or language deficits versus those who did not experience these deficits., Results: Three hundred six consecutive patients (age, 54 +/- 11 years; median Karnofsky Performance Scale score, 80) underwent primary GBM resection. Nineteen patients (6%) developed surgically acquired motor deficits and 15 (5%) developed surgically acquired language deficits. Median survival was decreased in patients who acquired language deficits (9.6 months; P < 0.05) or motor deficits (9.0 months; P < 0.05) versus patients without surgically acquired deficits (12.8 months). Two-year survival was 8% and 0% for patients with surgically acquired motor or language deficits, respectively, versus 23% for patients without new-onset deficits., Conclusion: In our experience, the development of new perioperative motor or language deficits was associated with decreased overall survival despite similar extent of resection and adjuvant therapy. Although it is well known that surgically induced neurological deficits affect quality of life, our results suggest that these surgical morbidities may also affect survival. Care should be taken to avoid surgically induced deficits in the management of GBM.

Background: Cord retethering and other postoperative complications can occur after the surgical untethering of a first-time symptomatic tethered cord. It is unclear if using duraplasty vs. primary dural closure in the initial operation is associated with decreased incidence of either immediate postoperative complications or subsequent symptomatic retethering. It is also unclear if different etiologies are associated with different outcomes after each method of closure. We reviewed our pediatric experience in first-time surgical untethering of symptomatic tethered cord syndrome (TCS) to identify the incidence of postoperative complications and symptomatic retethering after duraplasty vs. primary closure., Materials and Methods: We retrospectively reviewed 110 consecutive pediatric (<18 years old) cases of first-time symptomatic spinal cord untethering at our institution over a 10-year period. Incidence of postoperative complications and symptomatic retethering were compared in cases with duraplasty vs. primary dural closure use., Results: Mean age was 5.7 +/- 4.8 years old. "Complex" etiologies included lipomyelomeningocele or prior lipomyelomeningocele repair in 22 (20%) patients, prior myelomeningocele repair in 35 (32%), and concurrent lumbosacral lipoma in 18 (16%). "Noncomplex etiologies" included fatty filum in 26 (24%) and split cord malformation in five (4%). Seventy-five (68%) cases underwent primary dural closure vs. 35 (32%) with duraplasty. Twenty-nine (26%) patients experienced symptomatic retethering at a median [interquartile range (IQR)] of 30.5 [20.75-41.75] months postoperatively. There was no difference in incidence of postoperative cerebrospinal fluid leak, surgical site infection, or median [IQR] length of stay in patients receiving primary dural closure [4 (5%), 7 (9%), and 5 (4-6) days, respectively] vs. duraplasty [3 (9%), 3 (9%), and 6 [5-8] days, respectively], p > 0.05. Complex etiologies were more likely to retether than noncomplex etiologies after primary closure (33.6% vs. 6.6%, p = 0.05) but not after duraplasty (13.7% vs. 5.4%, p = 0.33). Duraplasty graft type (polytetrafluoroethylene vs. bovine pericardium) was not associated with pseudomeningocele or retethering., Conclusion: In our experience, the increased rate of symptomatic retethering observed with complex pediatric TCS (pTCS) etiologies after primary dural closures was not observed when duraplasty was instituted. Expansile duraplasty may be valuable specifically in the management of patient subgroups with complex pTCS etiologies.

We present three patients who developed temporal lobe injury and epilepsy after proton beam therapy to the skull base. This particular form of treatment-related toxicity should be considered when treating skull base tumors.

Object: Opioid administration following major intracranial surgery is often limited by a presumed lack of need and a concern that opioids will adversely affect postoperative outcome and interfere with the neurological examination. Nevertheless, evidence is accumulating that these patients suffer moderate to severe postoperative pain and that this pain is often undertreated. The authors hypothesized that intravenous patient-controlled analgesia (PCA) would safely and more effectively treat postoperative supratentorial craniotomy pain than conventional as needed (PRN) therapy., Methods: Following a standardized course of general anesthesia, adult patients who underwent elective supratentorial intracranial surgery were randomized in the neurosciences intensive care unit to receive either PRN intravenous fentanyl 25-50 microg every 30 minutes or PCA intravenous fentanyl 0.5 microg/kg every 15 minutes (maximum 4 doses/hour). The authors measured pain (self-reported scale score [0-10]), sedation (Ramsay Sedation Scale score), Glasgow Coma Scale score, fentanyl use, and major adverse events (excessive sedation, respiratory depression, pruritus, nausea, or vomiting) hourly., Results: Sixty-four patients with a mean age of 48 years (range 22-77 years) were randomized to intravenous PCA (29 patients) or PRN fentanyl (35 patients) groups. There were no statistically significant demographic differences between the 2 groups. Patients receiving intravenous PCA had significantly lower pain scores than those receiving intravenous PRN fentanyl (2.53 +/- 1.96 vs 3.62 +/- 2.11 [p = 0.039]) and received significantly more fentanyl than the PRN group (44.1 +/- 34.5 vs 23.6 +/- 23.7 microg/hour [p = 0.007]). There were no differences between the 2 groups regarding the number of patients with adverse events., Conclusions: Intravenous PCA more effectively treats the pain of supratentorial intracranial surgery than PRN fentanyl, and patients in the former group did not experience any untoward events related to the self-administration of opioids.

Background: Clinical depression has been shown to negatively influence the morbidity and mortality of multiple disease states. It remains unclear if clinical depression affects survival after surgical management of malignant brain astrocytoma. We set out to determine whether patients with a diagnosis of clinical depression before surgery experienced decreased survival independent of treatment modality or degree of disability., Methods: One thousand fifty-two patients undergoing surgical management for malignant brain astrocytoma (WHO grade 3 or 4) performed at a single institution from 1995 to 2006 were retrospectively reviewed. The independent association of depression prior to surgery and subsequent survival was assessed via multivariate proportional hazards regression analysis., Results: Surgical management consisted of primary resection in 605 (58%) patients, secondary resection in 410 (39%), and biopsy in 37 patients (3.5%). Pathology was WHO grade IV in 829 (79%) and grade III in 223 (21%). Forty-nine patients (5%) carried the diagnosis of depression at the time of surgery. Mean age and KPS on admission was 51 +/- 16 and 80 +/- 10 years, respectively. Two hundred ninety patients (28%) received Gliadel (BCNU MGI Pharma, Inc., Bloomington, MN, USA) wafer implantation and 274 (26%) received postoperative temozolomide (concomitant in 102, delayed adjuvant in 172 patients). Subsequent resection was performed at the time of recurrence in 135 (13%) patients a mean of 10 +/- 6 months after surgery. Adjusting for all variables associated with survival in this model, age (P < .001), KPS (P < .001), WHO grade III vs IV (P < .001), primary versus secondary resection (P < .001), gross-total resection (P < .001), Gliadel wafer implantation (P = .048), postoperative temozolomide therapy (P < .001), and subsequent resection at time of recurrence (P < .001); preoperative depression was independently associated with decreased survival (relative risk [95% CI]: 1.41 [1.1-1.96], P < .05). The difference in percent survival between the depression and nondepression cohorts was most notable at 12 months (15% vs 41%) and 20 months (0% vs 21%) after surgery., Conclusion: In our experience, patients who are actively depressed at the time of surgery were associated with decreased survival after surgical management of malignant astrocytoma, independent of degree of disability, tumor grade, or subsequent treatment modalities. In our opinion, the presence of an association between preoperative depression and survival warrants further investigation.

Object: Gliadel (BCNU) wafer and concomitant temozolomide (TMZ) therapy, when used individually as adjuvant therapies, extend survival from that achieved by resection and radiation therapy (XRT) for glioblastoma multiforme (GBM). It remains unstudied whether combining Gliadel and TMZ therapy is safe or further improves survival in patients with newly diagnosed GBM. The authors reviewed their initial experience utilizing combined Gliadel, TMZ, and radiation therapy for the treatment of GBM., Methods: All cases involving patients undergoing primary resection of GBM with or without Gliadel wafer (3.85% BCNU) implantation and adjuvant XRT over a 10-year period (1997-2006) were retrospectively reviewed. Beginning in 2004, concomitant TMZ became the standard of care at the authors' institution and all patients with Gliadel implantation also received concomitant TMZ (Stupp protocol). Overall survival and treatment-related morbidity were assessed for all patients treated with Gliadel plus concomitant TMZ (XRT + Gliadel + TMZ). Age-matched (

Object: With recent advances in the adjuvant treatment of malignant brain astrocytomas, it is increasingly debated whether extent of resection affects survival. In this study, the authors investigate this issue after primary and revision resection of these lesions., Methods: The authors retrospectively reviewed the cases of 1215 patients who underwent surgery for malignant brain astrocytomas (World Health Organization [WHO] Grade III or IV) at a single institution from 1996 to 2006. Patients with deep-seated or unresectable lesions were excluded. Based on MR imaging results obtained < 48 hours after surgery, gross-total resection (GTR) was defined as no residual enhancement, near-total resection (NTR) as having thin rim enhancement of the resection cavity only, and subtotal resection (STR) as having residual nodular enhancement. The independent association of extent of resection and subsequent survival was assessed via a multivariate proportional hazards regression analysis., Results: Magnetic resonance imaging studies were available for review in 949 cases. The mean age and mean Karnofsky Performance Scale (KPS) score at time of surgery were 51 +/- 16 years and 80 +/- 10, respectively. Surgery consisted of primary resection in 549 patients (58%) and revision resection for tumor recurrence in 400 patients (42%). The lesion was WHO Grade IV in 700 patients (74%) and Grade III in 249 (26%); there were 167 astrocytomas and 82 mixed oligoastrocytoma. Among patients who underwent resection, GTR, NTR, and STR were achieved in 330 (35%), 388 (41%), and 231 cases (24%), respectively. Adjusting for factors associated with survival (for example, age, KPS score, Gliadel and/or temozolomide use, and subsequent resection), GTR versus NTR (p < 0.05) and NTR versus STR (p < 0.05) were independently associated with improved survival after both primary and revision resection of glioblastoma multiforme (GBM). For primary GBM resection, the median survival after GTR, NTR, and STR was 13, 11, and 8 months, respectively. After revision resection, the median survival after GTR, NTR, and STR was 11, 9, and 5 months, respectively. Adjusting for factors associated with survival for WHO Grade III astrocytoma (age, KPS score, and revision resection), GTR versus STR (p < 0.05) was associated with improved survival. Gross-total resection versus NTR was not associated with an independent survival benefit in patients with WHO Grade III astrocytomas. The median survival after primary resection of WHO Grade III (mixed oligoastrocytomas excluded) for GTR, NTR, and STR was 58, 46, and 34 months, respectively., Conclusions: In the authors' experience with both primary and secondary resection of malignant brain astrocytomas, increasing extent of resection was associated with improved survival independent of age, degree of disability, WHO grade, or subsequent treatment modalities used. The maximum extent of resection should be safely attempted while minimizing the risk of surgically induced neurological injury.

Objective: Symptom recurrence remains a problem for some patients after surgical decompression for Chiari I malformation. We set out to identify variables at presentation that could identify subgroups most likely to experience incomplete symptom relief after hindbrain decompression for Chiari I malformation., Materials and Methods: We retrospectively reviewed the records of all pediatric patients undergoing first-time suboccipital decompression for Chiari I malformation over a 10-year period. Measured outcomes included (1) persistence or recurrence of symptoms regardless of severity and (2) need for revision decompression., Results: Two hundred fifty-six children (10 5 years old) underwent surgery for Chiari I malformation and were followed up for a mean of 27 months. Presenting symptoms included headache in 192 (75%) patients and brainstem or cranial nerve symptoms in 68 (27%) patients. Fifty-seven (22%) patients experienced mild to moderate symptom recurrence. Nineteen (7%) patients required revision decompression for significant symptom recurrence. Headache was 70% more likely to persist or recur versus cranial nerve or brainstem symptoms (relative risk 1.70, p < 0.05). Vertigo and frontal headache independently increased the odds of symptom recurrence 2.9- and 1.5-fold, respectively. Each increasing year of preoperative headache duration was independently associated with 15% increase in likelihood of symptom persistence (p < 0.05). Severe tonsilar ectopia (caudal to C2 lamina) was twice as likely to require revision decompression (14% versus 6%)., Conclusion: In our experience, recurrence of mild symptomatology not severe enough to justify revision surgery may occur in nearly a fifth of patients after surgery. Headache was more likely to recur than objective cranial nerve or brainstem symptoms. Increasing duration of headaches, frontal headaches, and vertigo may be more refractory symptoms of Chiari I malformation.

Background: Gliadel (polifeprosan 20 with carmustine [BCNU] implant) is commonly used for local delivery of BCNU to high-grade gliomas after resection and is associated with increased survival. Various complications of Gliadel wafers have been reported but not consistently reproduced. We set out to characterize Gliadel-associated morbidity in our 10-year experience with Gliadel wafers for treatment of malignant glioma., Methods: We retrospectively reviewed records of 1013 patients undergoing craniotomy for resection of malignant brain astrocytoma (World Health Organization grade III/IV disease). Perioperative morbidity occurring within 3 months of surgery was assessed for patients and compared between patients receiving versus not receiving Gliadel wafer. Overall survival was assessed for all patients., Results: A total of 1013 craniotomies were performed for malignant brain astrocytoma. A total of 288 (28%) received Gliadel wafer (250 glioblastoma multiforme (GBM), 38 anaplastic astrocytoma/anaplastic oligodendroglioma (AA/AO), 166 primary resection, 122 revision resection). Compared with the non-Gliadel cohort, patients receiving Gliadel were older (55 +/- 14 vs. 50 +/- 17, P = .001) and more frequently underwent gross total resection (75% vs 36%, P < .01) but otherwise similar. Patients in Gliadel versus non-Gliadel cohorts had similar incidences of perioperative surgical site infection (2.8% vs. 1.8%, P = .33), cerebrospinal fluid leak (2.8% vs. 1.8%, P = .33), meninigitis (.3% vs. .3%, P = 1.00), incisional wound healing difficulty (.7% vs. .4%, P = .63), symptomatic malignant edema (2.1% vs. 2.3%, P = 1.00), 3-month seizure incidence (14.6% vs. 15.7%, P = .65), deep-vein thrombosis (6.3% vs. 5.2%, P = .53), and pulmonary embolism (PE) (4.9% vs. 3.7%, P = .41). For patients receiving Gliadel for GBM, median survival was 13.5 months after primary resection (20% alive at 2 years) and 11.3 months after revision resection (13% alive at 2 years). For patients receiving Gliadel for AA/AO, median survival was 57 months after primary resection (66% alive at 2 years) and 23.6 months after revision resection (47% alive at 2 years)., Conclusion: In our experience, use of Gliadel wafer was not associated with an increase in perioperative morbidity after surgical treatment of malignant astrocytoma.

Objective: It remains unknown whether the extent of surgical resection affects survival or disease progression in patients with supratentorial low-grade gliomas., Methods: We conducted a retrospective cohort study (n = 170) between 1996 and 2007 at a single institution to determine whether increasing extent of surgical resection was associated with improved progression-free survival (PFS) and overall survival (OS). Surgical resection of gliomas defined as gross total resection (GTR) (complete resection of the preoperative fluid-attenuated inversion recovery signal abnormality), near total resection (NTR) (<3-mm thin residual fluid-attenuated inversion recovery signal abnormality around the rim of the resection cavity only), or subtotal resection (STR) (residual nodular fluid-attenuated inversion recovery signal abnormality) based on magnetic resonance imaging performed less than 48 hours after surgery. Our main outcome measures were OS, PFS, and malignant degeneration-free survival (conversion to high-grade glioma)., Results: One hundred thirty-two primary and 38 revision resections were performed for low-grade astrocytomas (n = 93) or oligodendrogliomas (n = 77). GTR, NTR, and STR were achieved in 65 (38%), 39 (23%), and 66 (39%) cases, respectively. GTR versus STR was independently associated with increased OS (hazard ratio, 0.36; 95% confidence interval, 0.16-0.84; P = 0.017) and PFS (HR, 0.56; 95% confidence interval, 0.32-0.98; P = 0.043) and a trend of increased malignant degeneration-free survival (hazard ratio, 0.46; 95% confidence interval, 0.20-1.03; P = 0.060). NTR versus STR was not independently associated with improved OS, PFS, or malignant degeneration-free survival. Five-year OS after GTR, NTR, and STR was 95, 80, 70%, respectively, and 10-year OS was 76, 57, and 49%, respectively. After GTR, NTR, and STR, median time to tumor progression was 7.0, 4.0, and 3.5 years, respectively. Median time to malignant degeneration after GTR, NTR, and STR was 12.5, 5.8, and 7 years, respectively., Conclusion: GTR was associated with a delay in tumor progression and malignant degeneration as well as improved OS independent of age, degree of disability, histological subtype, or revision versus primary resection. GTR should be safely attempted when not limited by eloquent cortex.

Background: We aimed to determine the long-term natural history of low-grade astrocytomas (LGA) in children, with respect to pathology, and to evaluate influence of treatment on survival., Patients and Methods: A consecutive cohort of patients < or =21 years with surgically confirmed LGA from 1965 to 1996 was assembled. All available pathology specimens were reviewed, masked to original diagnosis, patient data, and neuroimaging., Results: Two hundred seventy-eight children (160 males; mean age 9.1 years; tumor location: 77 cerebrum, 62 cerebellum, 51 hypothalamic, 30 thalamus, 9 ventricle, 40 brainstem, and 9 spine) were assessed. Among 246 specimens reviewed, diagnoses were 135 pilocytic astrocytoma (PA), 27 diffuse astrocytoma (DA), 75 unclassifiable well-differentiated astrocytoma (NOS), and 9 subependymal giant cell astrocytoma. At 5 and 10 years from initial surgery, for all LGA overall survival (OS) was 87% and 83%, while progression-free survival (PFS) was 55% and 42%, respectively. Original pathology diagnoses did not predict PFS (P = 0.47), but reviewed diagnoses were significantly associated with PFS (P = 0.007). Reviewed diagnoses were highly associated with OS (P < 0.0001), with 5-year OS for PA 96%, DA 48%, and NOS 86%; these differences remained significant when stratified by location or extent of resection. Among patients with residual tumor after surgery, 5-year PFS was 48% with observation alone (n = 114), no different (P = 0.32) from that achieved with immediate irradiation (n = 86)., Conclusion: LGA, particularly PA, have excellent long-term OS. While tumor location and resection extent affect outcome, pathologic diagnosis when carefully interpreted significantly influences long-term survival. Immediate postoperative irradiation does not confer an advantage in delaying first progression in children with residual PA.

Object: Indications for duraplasty in treatment of Chiari malformation Type I (CM-I) remain unclear. In the present study, the authors evaluate their surgical experience to determine whether intraoperative ultrasonography is effective in the selection of patients with CM-I who can be adequately treated with craniectomy alone without duraplasty., Methods: The authors reviewed the records of 256 children who underwent first-time hindbrain decompression for CM-I. Craniectomy alone (without duraplasty) was performed when intraoperative ultrasonography suggested adequate decompression of the subarachnoid spaces ventral and dorsal to the tonsils after suboccipital craniectomy alone. Duraplasty was performed if intraoperative ultrasonography demonstrated persistent dural compression of the tonsils following craniectomy. Symptom recurrence as a function of time was compared between cases of duraplasty versus suboccipital decompression alone stratified by extent of tonsillar herniation., Results: Duraplasty was performed in 140 patients (55%), and suboccipital decompression alone was performed in 116 patients (45%). Patients underwent follow-up for 29 +/- 15 months. Symptoms included headache in 192 patients (75%) and lower cranial nerve and brainstem dysfunction in 68 (27%). In 38 patients (15%) there was tonsillar herniation rostral to the C-1 lamina, in 195 (76%) it extended between the C-1 and C-2 lamina, and in 23 patients (9%) there was herniation caudal to the lower border of the C-2 lamina. In children with tonsillar herniation caudal to C-1, ultrasonography-guided suboccipital decompression alone was associated with a 2-fold increase in the risk of symptom recurrence compared with those who also underwent duraplasty (p = 0.01). In children with tonsillar herniation rostral to C-1, outcome was equivalent between suboccipital decompression alone and duraplasty (p = 0.41)., Conclusions: In the setting of moderate-to-severe tonsillar CM-I, intraoperative ultrasonography demonstrating decompression of the subarachnoid spaces ventral and dorsal to the tonsils may not effectively select patients in whom bone decompression alone is sufficient. Duraplasty may be warranted in cases of tonsillar herniation that extends below the C-1 lamina regardless of intraoperative ultrasonography findings. More objective cerebrospinal fluid flow or volumetric measures may be needed intraoperatively to guide duraplasty in patients with more pronounced tonsillar herniation.