TSC2 alterations in anaplastic ependymoma progression to ependymosarcoma.

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.

Detection of tumor-derived DNA in cerebrospinal fluid of patients with primary tumors of the brain and spinal cord.

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.

Risk of Subdural Hematoma Expansion in Patients With End-Stage Renal Disease: Continuous Venovenous Hemodialysis Versus Intermittent Hemodialysis.

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.

Impact of Antithrombotic Medications and Reversal Strategies on the Surgical Management and Outcomes of Traumatic Acute Subdural Hematoma.

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.

Craniotomy versus craniectomy for traumatic acute subdural hematoma-coarsened exact matched analysis of outcomes.

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.

Genomic Alterations in Molecularly Defined Oligodendrogliomas.

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.

Histopathological correlates with survival in reoperated glioblastomas.

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.

Supratentorial glioblastoma multiforme: the role of surgical resection versus biopsy among older patients.

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.

Skull Base Leiomyomas and Angioleiomyomas: A Systematic Literature Review and an Uncommon Case Report.

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.

A Crowdsourced Consensus on Supratotal Resection Versus Gross Total Resection for Anatomically Distinct Primary Glioblastoma.

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.

Impact of COVID-19 on an Academic Neurosurgery Department: The Johns Hopkins Experience.

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.

Independent association of extent of resection with survival in patients with malignant brain astrocytoma.

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.

Gliadel (BCNU) wafer plus concomitant temozolomide therapy after primary resection of glioblastoma multiforme.

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 (

Efficacy of intravenous patient-controlled analgesia after supratentorial intracranial surgery: a prospective randomized controlled trial. Clinical article.

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.

Association of preoperative depression and survival after resection of malignant brain astrocytoma.

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.

Incidence of symptomatic retethering after surgical management of pediatric tethered cord syndrome with or without duraplasty.

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.

Epilepsy and temporal lobe injury after skull base proton beam therapy.

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.

Surgical Resection for Primary Central Nervous System Lymphoma: A Systematic Review.

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.

Identifying Recurrent Malignant Glioma after Treatment Using Amide Proton Transfer-Weighted MR Imaging: A Validation Study with Image-Guided Stereotactic Biopsy.

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.

Use of Gliadel (BCNU) wafer in the surgical treatment of malignant glioma: a 10-year institutional experience.

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.