Search

Adamantinomatous craniopharyngiomas (ACP) are characterized by alterations in the CTNNB1 gene while almost all papillary craniopharyngiomas (PCP) harbor a canonical V600E mutation in the BRAF gene. Although other recurrent driver genes have not been described to date in craniopharyngiomas, the heterogeneous clinical course of these tumors might be associated with the acquisition of further genomic alterations. It is well known that telomerase reverse transcriptase (TERT) promoter (TERTp) alterations, including mutations or methylation, upregulate the expression of TERT and increase telomerase activity, promoting tumorigenesis. We investigated whether TERTp mutations or methylation are associated with tumor relapse in a subset of craniopharyngiomas. Samples from 42 patients with histologically confirmed craniopharyngioma were retrieved. We determined TERTp, BRAF, and CTNNB1 hotspot mutations in all samples using targeted sequencing and the TERTp methylation status by methylation-specific polymerase chain reaction (PCR) in 30 samples. While BRAF V600E mutations and CTNNB1 mutations were detected in 12 (28.6%) and 21 patients (50%) in the initial tumors and subsequent recurrences, respectively, none of the patients in our cohort, including those with multiple relapses, harbored a TERTp mutation. Furthermore, TERTp methylation was detected in 14 out of 24 cases (58.3%) with available primary samples; however, no correlation between TERTp methylation with the pathological subtype, genotype, or tumor aggressiveness was detected. These data suggest that elevated telomerase activity via acquisition of TERTp mutations is an infrequent pathway in the tumorigenesis of craniopharyngiomas, regardless of their clinical course.

Objective To address variance in clinical care surrounding sporadic vestibular schwannoma, a modified Delphi study was performed to establish a general framework to approach vestibular schwannoma care. A multidisciplinary panel of experts was established with deliberate representation from key stakeholder societies. External validity of the final statements was assessed through an online survey of registered attendees of the 8th Quadrennial International Conference on Vestibular Schwannoma. Study design Modified Delphi method. Methods The panel consisted of 16 vestibular schwannoma experts (8 neurotology and 8 neurosurgery) and included delegates representing the AAOHNSF, AANS/CNS tumor section, ISRS, and NASBS. The modified Delphi method encompassed a four-step process, comprised of one prevoting round to establish a list of focus areas and three subsequent voting rounds to successively refine individual statements and establish levels of consensus. Thresholds for achieving moderate consensus, at ≥67% agreement, and strong consensus, at ≥80% agreement, were determined a priori. All voting was performed anonymously via the Qualtrics online survey tool and full participation from all panel members was required before procession to the next voting round. Results Through the Delphi process, 103 items were developed encompassing hearing preservation (N = 49), tumor control and imaging surveillance (N = 20), preferred treatment (N = 24), operative considerations (N = 4), and complications (N = 6). As a result of item refinement, moderate (4%) or strong (96%) consensus was achieved in all 103 final statements. Seventy-nine conference registrants participated in the online survey to assess external validity. Among these survey respondents, moderate (N = 21, 20%) or strong (N = 73, 71%) consensus was achieved in 94 of 103 (91%) statements, and no consensus was reached in 9 (9%). Of the four items with moderate consensus by the expert panel, one had moderate consensus by the conference participants and three had no consensus. Conclusion This modified Delphi study on sporadic vestibular schwannoma codifies 100% consensus within a multidisciplinary expert panel and is further supported by 91% consensus among an external group of clinicians who regularly provide care for patients with vestibular schwannoma. These final 103 statements address clinically pragmatic items that have direct application to everyday patient care. This document is not intended to define standard of care or drive insurance reimbursement, but rather to provide a general framework to approach vestibular schwannoma care for providers and patients.

This combined American Neurotology Society, American Otological Society, and American Academy of Otolaryngology - Head and Neck Surgery Foundation document aims to provide guidance during the coronavirus disease of 2019 (COVID-19) on 1) "priority" of care for otologic and neurotologic patients in the office and operating room, and 2) optimal utilization of personal protective equipment. Given the paucity of evidence to inform otologic and neurotologic best practices during COVID-19, the recommendations herein are based on relevant peer-reviewed articles, the Centers for Disease Control and Prevention COVID-19 guidelines, United States and international hospital policies, and expert opinion. The suggestions presented here are not meant to be definitive, and best practices will undoubtedly change with increasing knowledge and high-quality data related to COVID-19. Interpretation of this guidance document is dependent on local factors including prevalence of COVID-19 in the surgeons' local community. This is not intended to set a standard of care, and should not supersede the clinician's best judgement when managing specific clinical concerns and/or regional conditions.Access to otologic and neurotologic care during and after the COVID-19 pandemic is dependent upon adequate protection of physicians, audiologists, and ancillary support staff. Otolaryngologists and associated staff are at high risk for COVID-19 disease transmission based on close contact with mucosal surfaces of the upper aerodigestive tract during diagnostic evaluation and therapeutic procedures. While many otologic and neurotologic conditions are not imminently life threatening, they have a major impact on communication, daily functioning, and quality of life. In addition, progression of disease and delay in treatment can result in cranial nerve deficits, intracranial and life-threatening complications, and/or irreversible consequences. In this regard, many otologic and neurotologic conditions should rightfully be considered "urgent," and almost all require timely attention to permit optimal outcomes. It is reasonable to proceed with otologic and neurotologic clinic visits and operative cases based on input from expert opinion of otologic care providers, clinic/hospital administration, infection prevention and control specialists, and local and state public health leaders. Significant regional variations in COVID-19 prevalence exist; therefore, physicians working with local municipalities are best suited to make determinations on the appropriateness and timing of otologic and neurotologic care.

Clinical trials are performed to determine the safety, efficacy, or effectiveness of a medical or surgical intervention. A clinical trial is, by definition, prospective in nature with a uniform treatment of a defined patient cohort. The outcomes assessment should also be uniform. Often a control group is included. At present, the number of neurosurgical clinical trials is increasing, and the study designs have become more sophisticated. Historically, the standard of neurosurgical care has evolved from the findings from many case series and retrospective comparative studies. However, in the present report, we have focused exclusively on prospective clinical trials. An urgent need exists to understand how clinical trials have been performed in the past and how they can be improved to advance our neurosurgical practice. In the present review, we have discussed the barriers, successes, and failures regarding prospective clinical trials in neurosurgery with an outlook to the future.

Histopathological grading of meningiomas is insufficient for optimal risk stratification. The purpose of the present study was to determine the prognostic value of atypical histopathological features across all nonmalignant meningiomas (World Health Organization [WHO] grade I-II).The data from 334 patients with WHO grade I (n = 275) and grade II (n = 59) meningiomas who had undergone surgical resection from 2001 to 2015 at 2 academic centers were pooled. Progression/recurrence (P/R) was determined radiographically and measured from the date of surgery.The median follow-up was 52 months. The patients were stratified by the number of atypical features: 0 (n = 151), 1 (n = 71), 2 (n = 66), 3 (n = 22), and 4 or 5 (n = 24). The risk of P/R increased with an increasing number of atypical features (log-rank test, P = 0.001). The 5-year actuarial rates of P/R stratified by the number of atypical features were as follows: 0, 16.3% (95% confidence interval [CI], 10.7-24.4); 1, 21.7% (95% CI, 12.8-35.2); 2, 28.2% (95% CI, 18.4-41.7); 3, 30.4% (95% CI, 13.8-58.7); and 4 or 5, 51.4% (95% CI, 31.7-74.5). On univariate analysis, the presence of high nuclear/cytoplasmic ratio (P = 0.007), prominent nucleoli (P = 0.007), and necrosis (P0.00005) were associated with an increased risk of P/R. On multivariate analysis, the number of atypical features (hazard ratio [HR], 1.30; 95% CI, 1.03-1.63; P = 0.03), ≥4 mitoses per high-power fields (HR, 2.45; 95% CI, 1.17-5.15; P = 0.02), subtotal resection (HR, 3.9; 95% CI, 2.5-6.3; P0.0005), and the lack of adjuvant radiotherapy (HR, 2.40; 95% CI, 1.19-4.80; P = 0.01) were associated with an increased risk of P/R.An increased number of atypical features, ≥4 mitoses per 10 high-power fields, subtotal resection, and the lack of adjuvant radiotherapy were independently associated with P/R of WHO grade I-II meningiomas. Patients with these features might benefit from intensified therapy.

BACKGROUND: Recurrent atypical and malignant meningiomas have poor outcomes with surgical therapy alone. Neither adjuvant chemotherapy nor postoperative radiation therapy remedies this problem. OBJECTIVE: To evaluate our experience with the treatment of 15 patients treated with I-125 or Cs-131 brachytherapy radiation seeds as an adjuvant in these difficult cases. METHODS: Patients with high-grade recurrent meningioma who underwent resection and intraoperative placement of brachytherapy seeds at our institution from 2002 to 2014 were identified and studied by retrospective chart review. RESULTS: Fifteen patients with median age of 68.8 yr were treated with I-125 (n = 13) or Cs-131 (n = 2) brachytherapy seeds for cases of recurrent, grade II (n = 8), or grade III (n = 7) meningioma at our institution from 2002 to 2014. These lesions originated from a variety of locations including, convexity (3), falcine (3), frontal (2), occipital (1), parietal (2), 2 sphenoid wing (2), and temporal (2), based recurrent meningiomas. Patients had a median of 2 prior open surgical interventions and received local radiation therapy with a median dose of 55 Gy prior to brachytherapy. Survival at 2.5 yr was 56% for grade II and 17% for grade III lesions. Survival was significantly associated with patient age but not tumoral pathology. Forty percent of patients required reoperations for wound complications following brachytherapy. CONCLUSION: Brachytherapy with implantation of permanent radiation seeds provides a viable alternative treatment for recurrent meningioma while carrying a significant clinical risk of wound infection and need for reoperation.

PURPOSE: By incorporating major developments in genetics, ophthalmology, dermatology, and neuroimaging, to revise the diagnostic criteria for neurofibromatosis type 1 (NF1) and to establish diagnostic criteria for Legius syndrome (LGSS). METHODS: We used a multistep process, beginning with a Delphi method involving global experts and subsequently involving non-NF experts, patients, and foundations/patient advocacy groups. RESULTS: We reached consensus on the minimal clinical and genetic criteria for diagnosing and differentiating NF1 and LGSS, which have phenotypic overlap in young patients with pigmentary findings. Criteria for the mosaic forms of these conditions are also recommended. CONCLUSION: The revised criteria for NF1 incorporate new clinical features and genetic testing, whereas the criteria for LGSS were created to differentiate the two conditions. It is likely that continued refinement of these new criteria will be necessary as investigators (1) study the diagnostic properties of the revised criteria, (2) reconsider criteria not included in this process, and (3) identify new clinical and other features of these conditions. For this reason, we propose an initiative to update periodically the diagnostic criteria for NF1 and LGSS. ispartof: GENETICS IN MEDICINE vol:23 issue:8 pages:1506-1513 ispartof: location:United States status: published

High-grade meningiomas are associated with neuro-cognitive morbidity and have limited treatments. High-grade meningiomas harbor an immunosuppressive tumor microenvironment (TME) and programmed death-ligand 1 (PD-L1) expression may contribute to their aggressive phenotype. Here, we present the results of a single-arm, open-label phase 2 trial (NCT03279692) evaluating the efficacy of pembrolizumab, a PD-1 inhibitor, in a cohort of 25 evaluable patients with recurrent and progressive grade 2 and 3 meningiomas. The primary endpoint is the proportion of patients alive and progression-free at 6 months (PFS-6). Secondary endpoints include progression-free and overall survival, best intracranial response, and toxicity. Our study has met its primary endpoint and achieved a PFS-6 rate of 0.48 (90% exact CI: 0.31–0.66) and a median PFS of 7.6 months (90% CI: 3.4–12.9 months). Twenty percent of patients have experienced one (or more) grade-3 or higher treatment-related adverse events. These results suggest that pembrolizumab exerts promising efficacy on a subset of these tumors. Further studies are needed to identify the biological facets within the meningioma TME that may drive response to immune-based therapies.

Importance Cervical spondylotic myelopathy is the most common cause of spinal cord dysfunction worldwide. It remains unknown whether a ventral or dorsal surgical approach provides the best results. Objective To determine whether a ventral surgical approach compared with a dorsal surgical approach for treatment of cervical spondylotic myelopathy improves patient-reported physical functioning at 1 year. Design, Setting, and Participants Randomized clinical trial of patients aged 45 to 80 years with multilevel cervical spondylotic myelopathy enrolled at 15 large North American hospitals from April 1, 2014, to March 30, 2018; final follow-up was April 15, 2020. Interventions Patients were randomized to undergo ventral surgery (n = 63) or dorsal surgery (n = 100). Ventral surgery involved anterior cervical disk removal and instrumented fusion. Dorsal surgery involved laminectomy with instrumented fusion or open-door laminoplasty. Type of dorsal surgery (fusion or laminoplasty) was at surgeon’s discretion. Main Outcomes and Measures The primary outcome was 1-year change in the Short Form 36 physical component summary (SF-36 PCS) score (range, 0 [worst] to 100 [best]; minimum clinically important difference = 5). Secondary outcomes included 1-year change in modified Japanese Orthopaedic Association scale score, complications, work status, sagittal vertical axis, health resource utilization, and 1- and 2-year changes in the Neck Disability Index and the EuroQol 5 Dimensions score. Results Among 163 patients who were randomized (mean age, 62 years; 80 [49%] women), 155 (95%) completed the trial at 1 year (80% at 2 years). All patients had surgery, but 5 patients did not receive their allocated surgery (ventral: n = 1; dorsal: n = 4). One-year SF-36 PCS mean improvement was not significantly different between ventral surgery (5.9 points) and dorsal surgery (6.2 points) (estimated mean difference, 0.3; 95% CI, −2.6 to 3.1;P = .86). Of 7 prespecified secondary outcomes, 6 showed no significant difference. Rates of complications in the ventral and dorsal surgery groups, respectively, were 48% vs 24% (difference, 24%; 95% CI, 8.7%-38.5%;P = .002) and included dysphagia (41% vs 0%), new neurological deficit (2% vs 9%), reoperations (6% vs 4%), and readmissions within 30 days (0% vs 7%). Conclusions and Relevance Among patients with cervical spondylotic myelopathy undergoing cervical spinal surgery, a ventral surgical approach did not significantly improve patient-reported physical functioning at 1 year compared with outcomes after a dorsal surgical approach. Trial Registration ClinicalTrials.gov Identifier:NCT02076113

Objectives: Predicting the course of cranial nerve (CN) VII in the cerebellopontine angle (CPA) on preoperative imaging for vestibular schwannoma (VS) may help guide surgical resection and reduce complications. Diffusion MRI based tractography has been used to identify cranial nerve trajectory, but intraoperative validation of this novel approach is challenging. Currently, validation is based on operative report descriptions of the course of cranial nerves, but yields a simplified picture of the three-dimensional (3D) course of CN VII. In this study, we investigate the accuracy of tractography with detailed patient-specific 3D-printed VS tumors. Design: Retrospective case review. Setting: Tertiary referral center. Participants: Twenty adult VS surgical candidates. Main Outcome Measures: We compared tractography with intraoperative 3D course of CN VII. The surgeons were blinded to tractography and drew the intraoperative course of the CN VII on a patient specific 3D-printed tumor model for detailed comparison with tractography. Results: Of 20 patients, one was excluded due to subtotal removal and inability to assess CN VII course. In the remaining 19 patients, 84% (16/19) tractography was successful. In 94% of tumors with tractography (15/16), the intraoperative description of CN VII course matched the tractography finding. The maximum distance, however, between tractography and intraoperative course of CN VII was 3.7 mm ± 4.2 mm. Conclusion: This study presents a novel approach to CN VII tractography validation in VS. Although descriptions of CN VII intraoperatively match tractography, caution is warranted as quantitative measures suggest a clinically significant distance between tractography and CN VII course.

Author(s): Grossman, Stuart A; Romo, Carlos G; Rudek, Michelle A; Supko, Jeffrey; Fisher, Joy; Nabors, L Burt; Wen, Patrick Y; Peereboom, David M; Ellingson, Benjamin M; Elmquist, William; Barker, Fred G; Kamson, David; Sarkaria, Jann N; Timmer, William; Bindra, Ranjit S; Ye, Xiaobu

BACKGROUND Older age has been associated with worse outcomes in low-grade gliomas (LGGs). Given their rarity in the older population, determining optimal treatment plans and patient outcomes remains difficult. OBJECTIVE To retrospectively study LGG survival outcomes in an older population stratified by molecular genetic profiles. METHODS We included patients age ≥40 yr with pathologically confirmed World Health Organization grade II gliomas treated at a single institution between 1995 and 2015. We collected tumor genomic information when available. RESULTS Median overall survival for the entire group (n = 111, median age 51 yr, range 40-77 yr) was 15.75 yr with 5- and 10-yr survival rates of 84.3% and 67.7%, respectively. On univariate analysis, patients with isocitrate dehydrogenase (IDH) mutation had significantly increased survival compared to IDH wildtype (hazard ratio [HR] 0.17 [0.07-0.45], P

OBJECTIVE To analyze the role of industry sponsorship of randomized controlled trials (RCTs) published exclusively in 3 major North American neurosurgical journals. METHODS Our primary objective was to determine whether an association exists between study conclusion(s) in favor of industry sponsored drugs, devices/implants, or surgical techniques and industry sponsorship. The secondary objective was to describe the quality/quantity of these neurosurgical RCTs. RESULTS A total of 110 RCTs were analyzed, the majority were published in the Journal of Neurosurgery (85%) and were international in origin (55%). The most common subspecialty was spine (n = 29) and drug study was the most common type (n = 49). Overall quality was good with median Jadad and Detsky scores of 4 (range, 1-5) and 18 (range, 8-21), respectively. There was a statistically significant difference in RCTs with industry funding (31/40, 78%) versus those without (9/70, 13%) that published a favorable conclusion of the new drug, device/implant, or surgical technique (odds ratio [OR], 23.35; P < .0001). Multiple binomial logistic regression analysis identified "number of authors" as mildly protective (OR, 0.79; 95% confidence interval, 0.69-0.91; P = .001) and "industry funding" strongly predictive (OR, 12.34; 95% confidence interval, 2.97-51.29; P = .001) of a positive trial. CONCLUSION Industry funding was associated with a much greater chance of positive findings in RCTs published in neurosurgical journals. Further efforts are needed to define the relationship between the authors and financial sponsors of neurosurgical research and explore the reasons for this finding.

OBJECTIVEIn clinical routines, neuroprotective strategies in neurosurgical interventions are still missing. A pilot study (n = 30) and an analogously performed Phase III trial (n = 112) pointed to a beneficial effect of prophylactic nimodipine and hydroxyethyl starch (HES) in vestibular schwannoma (VS) surgery. Considering the small sample size, the data from both studies were pooled.METHODSThe patients in both investigator-initiated studies were assigned to 2 groups. The treatment group (n = 70) received parenteral nimodipine (1–2 mg/hour) and HES (hematocrit 30%–35%) from the day before surgery until the 7th postoperative day. The control group (n = 72) was not treated prophylactically. Facial and cochlear nerve functions were documented preoperatively, during the inpatient care, and 1 year after surgery.RESULTSPooled raw data were analyzed retrospectively. Intent-to-treat analysis revealed a significantly lower risk for hearing loss (Class D) 12 months after surgery in the treatment group compared with the control group (OR 0.46, 95% CI 0.22–0.97; p = 0.04). After exclusion of patients with preoperative Class D hearing, this effect was more pronounced (OR 0.38, 95% CI 0.17–0.83; p = 0.016). Logistic regression analysis adjusted for tumor size showed a 4 times lower risk for hearing loss in the treatment group compared with the control group (OR 0.25, 95% CI 0.09–0.63; p = 0.003). Facial nerve function was not significantly improved with treatment. Apart from dose-dependent hypotension (p < 0.001), the study medication was well tolerated.CONCLUSIONSProphylactic nimodipine is safe and may be recommended in VS surgery to preserve hearing. Prophylactic neuroprotective treatment in surgeries in which nerves are at risk seems to be a novel and promising concept.Clinical trial registration no.: DRKS 00000328 (https://drks-neu.uniklinik-freiburg.de/drks_web/)

To determine whether whole-brain radiation therapy (WBRT) is associated with improved overall survival among non-small cell lung cancer (NSCLC) patients with favorable prognoses at diagnosis.In the N0574 trial, patients with 1 to 3 brain metastases were randomized to receive stereotactic radiosurgery (SRS) or SRS plus WBRT (SRS + WBRT), with a primary endpoint of cognitive deterioration. We calculated diagnosis-specific graded prognostic assessment (DS-GPA) scores for NSCLC patients and evaluated overall survival according to receipt of WBRT and DS-GPA score using 2 separate cut-points (≥2.0 vs2.0 and ≥2.5 vs2.5).A total of 126 NSCLC patients were included for analysis, with median follow-up of 14.2 months. Data for DS-GPA calculation were available for 86.3% of all enrolled NSCLC patients. Overall, 50.0% of patients had DS-GPA score ≥2.0, and 23.0% of patients had DS-GPA scores ≥2.5. The SRS and SRS + WBRT groups were well balanced with regard to prognostic factors. The median survival according to receipt of WBRT was 11.3 months (+WBRT) and 17.9 months (-WBRT) for patients with DS-GPA ≥2.0 (favorable prognoses, P=.63; hazard ratio 0.86; 95% confidence interval 0.47-1.59). Median survival was 3.7 months (+WBRT) and 6.6 months (-WBRT) for patients with DS-GPA2.0 patients (unfavorable prognoses, P=.85; hazard ratio 0.95; 95% confidence interval 0.56-1.62). Outcomes according to the receipt of WBRT and DS-GPA remained similar utilizing DS-GPA ≥2.5 as a cutoff for favorable prognoses. There was no interaction between the continuum of the DS-GPA groups and WBRT on overall survival (P=.53).We observed no significant differences in survival according to receipt of WBRT in favorable-prognosis NSCLC patients. This study further supports the approach of SRS alone in the majority of patients with limited brain metastases.

Purpose Whole brain radiation therapy (WBRT) remains a commonly used cancer treatment, although controversy exists regarding the optimal dose/fractionation to optimize intracranial tumor control and minimize resultant cognitive deficits. Methods and Materials NCCTG N107C [Alliance]/CEC.3 randomized 194 patients with brain metastases to either stereotactic radiosurgery alone or WBRT after surgical resection. Among the 92 patients receiving WBRT, sites predetermined the dose/fractionation that would be used for all patients treated at that site (either 30 Gy in 10 fractions or 37.5 Gy in 15 fractions). Analyses were performed using Kaplan-Meier estimates, log rank tests, and Fisher’s exact tests. Results Among 92 patients treated with surgical resection and adjuvant WBRT, 49 were treated with 30 Gy in 10 fractions (53%), and 43 were treated with 37.5 Gy in 15 fractions (47%). Baseline characteristics, including cognitive testing, were well balanced between groups with the exception of primary tumor type (lung cancer histology was more frequent with protracted WBRT: 72% vs 45%, P = .01), and 93% of patients completed the full course of WBRT. A more protracted WBRT dose regimen (37.5 Gy in 15 fractions) did not significantly affect time to cognitive failure (hazard ratio [HR], 0.9; 95% confidence interval [CI], 0.6-1.39; P = .66), surgical bed control (HR, 0.52 [95% CI, 0.22-1.25], P = .14), intracranial tumor control (HR, 0.56 [95% CI, 0.28-1.12], P = .09), or overall survival (HR, 0.72 [95% CI, 0.45-1.16], P = .18). Although there was no reported radionecrosis, there is a statistically significant increase in the risk of at least 1 grade ≥3 adverse event with 37.5 Gy in 15 fractions versus 30 Gy in 10 fractions (54% vs 31%, respectively, P = .03). Conclusions This post hoc analysis does not demonstrate that protracted WBRT courses reduce the risk of cognitive deficit, improve tumor control in the hypoxic surgical cavity, or otherwise improve the therapeutic ratio. Adverse events were significantly higher with the lengthened course of WBRT. For patients with brain metastases where WBRT is recommended, shorter course hypofractionated regimens remain the current standard of care.

Evidence of a high interobserver variability of the subjective House-Brackmann facial nerve grading system (HBGS) would justify cost- and time-consuming technological enhancements of objective classifications for facial nerve paresis. A total of 112 patients were recruited for a randomized multi-center trial to investigate the efficacy of prophylactic nimodipine treatment in vestibular schwannoma (VS) surgery. For the present investigation both treatment groups were pooled for the assessment of facial nerve function preoperatively, in the early postoperative course and 1 year after the surgery. Facial nerve function was documented photographically at rest and in motion and classified according to the HBGS by three independent observers (neurosurgeon, neurologist, ENT) and by the investigator of each center. Interobserver variability was considerably different with respect to the three time points depending upon the severity of facial nerve paresis. Preoperative facial nerve function was normal or only mildly impaired (HB grade I or II) and was assessed consistently in 97%. Facial nerve function deteriorated during the early postoperative course and was subsequently documented without dissent in only 36%, with one grade difference in 45%, two grade difference in 17% and three grade difference in 2%. One year after surgery, facial nerve function predominantly improved resulting in a consistent assessment in 66%. Differing ratings were observed in 34% with one grade deviation in 88% and of two grades in 12%. Patients with differing ratings of two or more grades exhibited considerably worse facial nerve function (p

Background Posttraumatic seizure (PTS) is a significant complication of traumatic brain injury (TBI). Objective To perform a systematic review and meta-analysis to compare levetiracetam with phenytoin for seizure prophylaxis in patients diagnosed with severe TBI. Methods An inclusive search of several electronic databases and bibliographies was conducted to identify scientific studies that compared the effect of levetiracetam and phenytoin on PTS. Independent reviewers obtained data and classified the quality of each article that met inclusion criteria. A random effects meta-analysis was then completed. Results During June and July 2015, a systematic literature search was performed that identified 6097 articles. Of these, 7 met inclusion criteria. A random-effects meta-analysis was performed. A total of 1186 patients were included. The rate of seizure was 35 of 654 (5.4%) in the levetiracetam cohort and 18 of 532 (3.4%) in the phenytoin cohort. Our meta-analysis revealed no change in the rate of early PTS with levetiracetam compared with phenytoin (relative risk, 1.02; 95% confidence interval, 0.53-1.95; P = .96). Conclusion The lack of evidence on which antiepileptic drug to use in PTS is surprising given the number of patients prescribed an antiepileptic drug therapy for TBI. On the basis of currently available Level III evidence, patients treated with either levetiracetam or phenytoin have similar incidences of early seizures after TBI. Abbreviations ADE, adverse drug eventAED, antiepileptic drugCI, confidence intervalOR, odds ratioPTS, posttraumatic seizureTBI, traumatic brain injury.

OBJECTIVE To determine whether patients who learned the views of an expert surgeons' panel's assessment of equipoise between 2 alternative operative treatments had increased likelihood of consenting to randomization. BACKGROUND Difficulty obtaining patient consent to randomization is an important barrier to conducting surgical randomized clinical trials, the gold standard for generating clinical evidence. METHODS Observational study of the rate of patient acceptance of randomization within a 5-center randomized clinical trial comparing lumbar spinal decompression versus lumbar spinal decompression plus instrumented fusion for patients with symptomatic grade I degenerative lumbar spondylolisthesis with spinal stenosis. Eligible patients were enrolled in the trial and then asked to accept randomization. A panel of 10 expert spine surgeons was formed to review clinical information and images for individual patients to provide an assessment of suitability for randomization. The expert panel vote was disclosed to the patient by the patient's surgeon before the patient decided whether to accept randomization or not. RESULTS Randomization acceptance among eligible patients without expert panel review was 40% (19/48) compared with 81% (47/58) among patients undergoing expert panel review (P

We pooled the results of studies on natural history of cavernous malformations (CM) to calculate point estimates and investigate main sources of heterogeneity.We searched MEDLINE, EMBASE, and ISI Web of Science for relevant studies published before May 2015. We used fixed or random effects models and meta-regression to pool the data.Twenty-five studies were entered into the meta-analysis (90-1,295 patients depending on the analysis). Bleeding was defined as symptomatic hemorrhage plus radiologic evidence of hemorrhage. Sources of heterogeneity were identified as mixture of hemorrhage and rehemorrhage, mixture of rehemorrhage before and after 2 years of first bleeding, brainstem vs other locations, and calculation method. The rehemorrhage rate was higher than the hemorrhage rate (incidence rate ratio 16.5, p0.001, 95% confidence interval [CI] 9.7-28.0). Rehemorrhage within 2 years of the first hemorrhage was higher than after that (incidence rate ratio 1.8, p = 0.042, 95% CI 1.5-2.0). In two metaregression models, rough estimate of the annual incidence rate of hemorrhage was 0.3% (95% CI 0.1%-0.5%) and 2.8% (2.5%-3.3%) per person year in nonbrainstem and brainstem lesions and rough estimate of annual rehemorrhage rate per person year was 6.3% (3%-13.2%) and 32.3% (19.8%-52.7%) in nonbrainstem and brainstem lesions. Median time to rehemorrhage was 10.5 months. Posthemorrhage full recovery was 38.8%/person-year (28.7%-48.8%). Posthemorrhage full recovery or minimal disability was 79.5%/person-year (74.3%-84.8%). Mortality after bleeding was 2.2%.The incidence of symptomatic hemorrhage or rehemorrhage is higher in brainstem lesions. First symptomatic hemorrhage increases the chance of symptomatic rehemorrhage, which decreases after 2 years.

There are no approved Food and Drug Administration indications for pediatric auditory brainstem implant (ABI) surgery in the United States. Our prospective case series aims to determine the safety and feasibility of ABI surgery in pediatric patients

OBJECT A pilot study of prophylactic nimodipine and hydroxyethyl starch treatment showed a beneficial effect on facial and cochlear nerve preservation following vestibular schwannoma (VS) surgery. A prospective Phase III trial was undertaken to confirm these results. METHODS An open-label, 2-arm, randomized parallel group and multicenter Phase III trial with blinded expert review was performed and included 112 patients who underwent VS surgery between January 2010 and February 2013 at 7 departments of neurosurgery to investigate the efficacy and safety of the prophylaxis. The surgery was performed after the patients were randomly assigned to one of 2 groups using online randomization. The treatment group (n = 56) received parenteral nimodipine (1–2 mg/hr) and hydroxyethyl starch (hematocrit 30%–35%) from the day before surgery until the 7th postoperative day. The control group (n = 56) was not treated prophylactically. RESULTS Intent-to-treat analysis showed no statistically significant effects of the treatment on either preservation of facial nerve function (35 [67.3%] of 52 [treatment group] compared with 34 [72.3%] of 47 [control group]) (p = 0.745) or hearing preservation (11 [23.4%] of 47 [treatment group] compared with 15 [31.2%] of 48 [control group]) (p = 0.530) 12 months after surgery. Since tumor sizes were significantly larger in the treatment group than in the control group, logistic regression analysis was required. The risk for deterioration of facial nerve function was adjusted nearly the same in both groups (OR 1.07 [95% CI 0.34–3.43], p = 0.91). In contrast, the risk for postoperative hearing loss was adjusted 2 times lower in the treatment group compared with the control group (OR 0.49 [95% CI 0.18–1.30], p = 0.15). Apart from dose-dependent hypotension (p < 0.001), no clinically relevant adverse reactions were observed. CONCLUSIONS There were no statistically significant effects of the treatment. Despite the width of the confidence intervals, the odds ratios may suggest but do not prove a clinically relevant effect of the safe study medication on the preservation of cochlear nerve function after VS surgery. Further study is needed before prophylactic nimodipine can be recommended in VS surgery.

Progressive meningiomas that have failed surgery and radiation have a poor prognosis and no standard therapy. While meningiomas are more common in females overall, progressive meningiomas are enriched in males. We performed a comprehensive molecular characterization of 169 meningiomas from 53 patients with progressive/high-grade tumors, including matched primary and recurrent samples. Exome sequencing in an initial cohort (n = 24) detected frequent alterations in genes residing on the X chromosome, with somatic intragenic deletions of the dystrophin-encoding and muscular dystrophy-associated DMD gene as the most common alteration (n = 5, 20.8%), along with alterations of other known X-linked cancer-related genes KDM6A (n =2, 8.3%), DDX3X, RBM10 and STAG2 (n = 1, 4.1% each). DMD inactivation (by genomic deletion or loss of protein expression) was ultimately detected in 17/53 progressive meningioma patients (32%). Importantly, patients with tumors harboring DMD inactivation had a shorter overall survival (OS) than their wild-type counterparts [5.1 years (95% CI 1.3–9.0) vs. median not reached (95% CI 2.9–not reached, p = 0.006)]. Given the known poor prognostic association of TERT alterations in these tumors, we also assessed for these events, and found seven patients with TERT promoter mutations and three with TERT rearrangements in this cohort (n = 10, 18.8%), including a recurrent novel RETREG1–TERT rearrangement that was present in two patients. In a multivariate model, DMD inactivation (p = 0.033, HR = 2.6, 95% CI 1.0–6.6) and TERT alterations (p = 0.005, HR = 3.8, 95% CI 1.5–9.9) were mutually independent in predicting unfavorable outcomes. Thus, DMD alterations identify a subset of progressive/high-grade meningiomas with worse outcomes.

Risk stratification of meningiomas by histopathological grade alone is insufficient because it does not reliably predict which patients will progress/recur after definitive treatment. We sought to determine whether preoperative imaging and clinical characteristics could predict histopathological grade and/or improve prognostication of progression/recurrence (P/R). We retrospectively reviewed 144 patients divided into low-grade (2007 WHO grade I; n = 118) and high-grade (2007 WHO grades II/III; n = 26) groups that underwent surgery between 2002-2013 (median follow-up 49 months) and had preoperative MR imaging with diffusion-weighted imaging and/or head CT. Multivariate logistic regression analysis yielded an optimized model based on associations between high-grade histopathology and male gender, low apparent diffusion coefficient (ADC), absent calcification, and high peritumoral edema. Of these parameters, the logarithm of ADC had the strongest association with histopathological grade (OR 0.001 [0.0002-0.07]; P = 0.001). Interestingly, high-grade histopathology only demonstrated a borderline significant association with P/R (HR 2.01 [0.9-4.3]; P = 0.08). Remarkably, a multivariate Cox proportional-hazards model based on extent of resection and ADC outperformed the current standard, WHO histopathological grade, in predicting which patients will suffer P/R after initial treatment. Stratification of patients into four risk groups based on Simpson resection grade (I vs. other) and dichotomized ADC (high vs. low) significantly correlated with risk of P/R (P = 0.003). The high-risk group (non-Simpson grade I, low ADC; n = 31) had a 45% cumulative incidence of P/R whereas the low-risk group (Simpson grade I, high ADC; n = 31) had no P/R events at five years after treatment. Independent of histopathological grade, high-risk patients treated with adjuvant radiotherapy had a lower five-year crude rate of P/R compared with those who did not receive adjuvant radiotherapy (17% vs. 59%). Hence, patients with non-Simpson grade I resection and low ADC meningiomas are at significantly increased risk of P/R and may benefit from more aggressive treatment involving radiotherapy and/or additional surgery.

Objective To determine the safety and feasibility of auditory brainstem implantation in children younger than 5 years. Patient(s) Patients younger than 5 years who were not candidates for cochlear implantation because of anatomic considerations were included in the analyses. Intervention(s) Auditory brainstem implantation via retrosigmoid craniotomy. Main outcome measure(s) Audiologic, speech, quality of life, and safety outcomes were assessed. Results Auditory brainstem implantation was performed in a 16-month-old male infant with bilateral cochlear hypoplasia and cochlear nerve hypoplasia after a prior aborted attempt at cochlear implantation. Intraoperatively, multiphasic evoked auditory brainstem responses (EABRs) characteristic of synchronized responses of central auditory pathways were obtained on multiple electrodes. There were no complications in the immediate postoperative period, and the child was discharged home on Postoperative Day 4. Audiologic testing 2 and 4 months after activation indicated sound detection between 45 and 70 dB HL for warble tones, improvements in Infant Meaningful Auditory Integration Scale scores, and subjective gains in sound awareness, as well as quality of life measures. There were no major or minor complications of the procedure. Conclusion Based on our experience in combination with the work of others internationally, auditory brainstem implantation is feasible and safe in children younger than 5 years.

Cavernous malformations (CMs), also known as cavernous angiomas or cavernomas, are low-flow vascular malformations of the brain and spinal cord that consist of clusters of dilated sinusoidal channels lined with endothelial cells that do not exhibit intervening tight junctions. The involved blood vessels lack muscular and elastic layers, and blood at various stages of thrombosis and organization often fills the thin-walled vascular caverns. CMs are grossly distinct from adjacent brain and have a lobulated appearance sometimes likened to a mulberry, with a characteristic dark red or purple color. Hemosiderin and gliosis often surround CMs of the brain and spinal cord; no neural tissue is present inside the lesion. Except for developmental venous anomalies (DVAs) present in ≈33% of CMs,1 no abnormal vascularity is typically seen on digital subtraction angiography, leading CMs to be termed cryptic or occult vascular malformations (Figure 1). Multiple small hemorrhage events lead to a pathognomonic popcorn appearance on magnetic resonance (MR) imaging because of hemosiderin staining from blood products of various ages. Calcifications may be present on computed tomographic imaging (Figure 2). Figure 1. A 48-year-old woman presented with headaches. A , Magnetic resonance imaging of the brain with T2-weighted imaging demonstrated a 1.1-cm lesion in the cerebellar vermis with mixed signal intensity. B – D , Susceptibility-weighted imaging demonstrated hemosiderin within the lesion’s core and a developmental venous anomaly associated with the cavernous malformation (arrowheads). Figure 2. A 28-year-old woman presented with partial seizures without secondary generalization. A , Noncontrast computed tomography of the head demonstrated a 1.4-cm right posterior cingulate hyperdensity, with evidence of mild hemorrhage and calcification. Magnetic resonance imaging of the brain demonstrated the cavernous malformation to have a core of mixed signal intensity, heterogeneous enhancement, and a rim of hemosiderin consistent with a cavernous malformation, as evidenced on ( B ) susceptibility-weighted imaging, ( C ) T2-weighted …

Background. Patients with meningiomas have widely divergent clinical courses. Some entirely recover following surgery alone, while others have relentless tumor recurrences. This clinical conundrum is exemplified by rhabdoid meningiomas, which are designated in the World Health Organization Classification of Tumours as high grade, despite only a subset following an aggressive clinical course. Patient management decisions are further exacerbated by high rates of interobserver variability, biased against missing possibly aggressive tumors. Objective molecular determinants are needed to guide classification and clinical decision making. Methods. To define genomic aberrations of rhabdoid meningiomas, we performed sequencing of cancer-related genes in 27 meningiomas from 18 patients with rhabdoid features and evaluated breast cancer [BRCA]1-associated protein 1 (BAP1) expression by immunohistochemistry in 336 meningiomas. We assessed outcomes, germline status, and family history in patients with BAP1-negative rhabdoid meningiomas. Results. The tumor suppressor gene BAP1, a ubiquitin carboxy-terminal hydrolase, is inactivated in a subset of high-grade rhabdoid meningiomas. Patients with BAP1-negative rhabdoid meningiomas had reduced time to recurrence compared with patients with BAP1-retained rhabdoid meningiomas (Kaplan-Meier analysis, 26 mo vs 116 mo, P < .001; hazard ratio 12.89). A subset of patients with BAP1-deficient rhabdoid meningiomas harbored germline BAP1 mutations, indicating that rhabdoid meningiomas can be a harbinger of the BAP1 cancer predisposition syndrome. Conclusion. We define a subset of aggressive rhabdoid meningiomas that can be recognized using routine laboratory tests. We implicate ubiquitin deregulation in the pathogenesis of these high-grade malignancies. In addition, we show that familial and sporadic BAP1-mutated rhabdoid meningiomas are clinically aggressive, requiring intensive clinical management.

Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord dysfunction in the world. There are significant practice variation and uncertainty as to the optimal surgical approach for treating CSM.To determine whether ventral surgery is associated with superior Short Form-36 Physical Component Summary outcome at the 1-year follow-up compared with dorsal (laminectomy/fusion or laminoplasty) surgery for the treatment of CSM, to investigate whether postoperative sagittal balance is an independent predictor of overall outcome, and to compare health resource use for ventral and dorsal procedures.The study is a randomized, controlled trial with a nonrandomized arm for patients who are eligible but decline randomization. Two hundred fifty patients (159 randomized) with CSM from 11 sites will be recruited over 18 months. The primary outcome is the Short Form-36 Physical Component Summary score. Secondary outcomes include disease-specific outcomes, overall health-related quality of life (EuroQOL 5-dimension questionnaire), and health resource use.This will be the first randomized, controlled trial to compare directly the health-related quality-of-life outcomes for ventral vs dorsal surgery for treating CSM.A National Institutes of Health-funded (1R13AR065834-01) investigator meeting was held before the initiation of the trial to bring multiple stakeholders together to finalize the study protocol. Study investigators, coordinators, and major stakeholders were able to attend and discuss strengths of, limitations of, and concerns about the study. The final protocol was approved for funding by the Patient-Centered Outcomes Research Institute (CE-1304-6173). The trial began enrollment on April 1, 2014.

This study aims to demonstrate survival rates and treatment patterns among patients with chordomas of the skull base using a large population database. Patients with cranial chordomas between 1973 and 2009 were identified from the USA Surveillance, Epidemiology, and End Results (SEER) public use database. Kaplan-Meier analysis was used to examine the effect of surgery and radiation on overall survival. We identified 394 patients with histologically-confirmed cranial chordomas. Median survival was 151 months. Most patients (89.09%) underwent surgery. Less than half (44.92%) received radiation after diagnosis. Patients who underwent surgical resection survived significantly longer than those who did not undergo resection, regardless of other treatments (151 versus 81 months, p0.001). Ten year survival was lower among patients receiving radiation (44.8% versus 61.4%, p=0.66). Surgery predicted better overall survival by univariate analysis (hazard ratio [HR] 0.603, p=0.0293); younger age at diagnosis (HR 1.028, p0.001), and later year of diagnosis (HR 0.971, p=0.0027) were prognostic of improved survival in a multivariate model. In subgroup analysis of patients with documented tumor size, smaller tumor size (HR 1.021, p=0.0067), younger age (HR 1.031, p=0.001), and treatment within a higher volume registry (HR 0.490, p=0.0129) predicted improved survival. Surgical intervention offers survival benefit for cranial chordomas. Findings of decreased survival in patients receiving radiation may be associated with selection. Studies examining surgical extent of resection data and radiation details are needed to determine the impact of radiotherapy.

A major goal of the Section on Tumors of the American Association of Neurological Surgery (AANS) and Congress of Neurological Surgeons (CNS) since it was founded in 1984 has been to foster both education and research in the field of brain tumor treatment and development. In support of this goal, the Section sponsors a number of awards, named lectures, and fellowships at the annual meetings of the AANS and CNS. In this article, we describe the awards given by the AANS/CNS Section on Tumors since its foundation, the recipients of the awards, and their philanthropic donors. The subsequent history of awardees and their work is briefly examined. Specifically for the Preuss and Mahaley Awards, this article also examines the rates of publication among the award-winning abstracts and achievement of grant funding by awardees.

Objective: Neurofibromatosis (NF)-related benign tumors such as plexiform neurofibromas (PN) and vestibular schwannomas (VS) can cause substantial morbidity. Clinical trials directed at these tumors have become available. Due to differences in disease manifestations and the natural history of NF-related tumors, response criteria used for solid cancers (1-dimensional/RECIST [Response Evaluation Criteria in Solid Tumors] and bidimensional/World Health Organization) have limited applicability. No standardized response criteria for benign NF tumors exist. The goal of the Tumor Measurement Working Group of the REiNS (Response Evaluation in Neurofibromatosis and Schwannomatosis) committee is to propose consensus guidelines for the evaluation of imaging response in clinical trials for NF tumors. Methods: Currently used imaging endpoints, designs of NF clinical trials, and knowledge of the natural history of NF-related tumors, in particular PN and VS, were reviewed. Consensus recommendations for response evaluation for future studies were developed based on this review and the expertise of group members. Results: MRI with volumetric analysis is recommended to sensitively and reproducibly evaluate changes in tumor size in clinical trials. Volumetric analysis requires adherence to specific imaging recommendations. A 20% volume change was chosen to indicate a decrease or increase in tumor size. Use of these criteria in future trials will enable meaningful comparison of results across studies. Conclusions: The proposed imaging response evaluation guidelines, along with validated clinical outcome measures, will maximize the ability to identify potentially active agents for patients with NF and benign tumors.

HYPOTHESIS We hypothesize that the severity of hearing loss (HL) associated with sporadic vestibular schwannomas (VS) is correlated with tumor secretion of proteins with ototoxic or otoprotective potential. BACKGROUND Because the recognition that HL associated with VS is not solely due to compression of the auditory nerve, elucidating the mechanism by which VS cause HL has been an important task. We previously showed that VS stratified by hearing have differential gene expression. We now focus on identifying differentially expressed proteins in tumor secretions. METHODS Fresh surgical specimens of VS were incubated in sterile PBS at 37°C to collect secretions. The specimens were divided into a group associated with good hearing (GH, word recognition ≥ 70% and pure-tone average ≤ 30 dB, n = 11) or poor hearing (PH, n = 10). The groups were compared using a customized cytokine array. Statistically significant results were verified with an enzyme-linked immunosorbent assay on a different set of secretions (n = 8 for GH and n = 10 for PH group). RESULTS Of the 37 molecules we studied, 9 were significantly expressed in secretions from VS compared with secretions from control nerves. Secretion of fibroblast growth factor 2 (FGF2) was 3.5-fold higher in VS associated with GH versus PH based on cytokine array analysis (p = 0.02), which was validated with enzyme-linked immunosorbent assay. CONCLUSION This study highlights FGF2, a mitogen known to protect the auditory nerve, as a potential tumor-secreted mediator of hearing protection in VS. If FGF2's significant role in hearing protection in patients with VS is validated, then FGF2 could be used as a biomarker for HL in VS, and therapeutic targeting of the FGF2 signaling pathway may reduce HL due to VS.

Whole brain radiotherapy (WBRT) significantly improves tumor control in the brain after stereotactic radiosurgery (SRS), yet because of its association with cognitive decline, its role in the treatment of patients with brain metastases remains controversial.To determine whether there is less cognitive deterioration at 3 months after SRS alone vs SRS plus WBRT.At 34 institutions in North America, patients with 1 to 3 brain metastases were randomized to receive SRS or SRS plus WBRT between February 2002 and December 2013.The WBRT dose schedule was 30 Gy in 12 fractions; the SRS dose was 18 to 22 Gy in the SRS plus WBRT group and 20 to 24 Gy for SRS alone.The primary end point was cognitive deterioration (decline1 SD from baseline on at least 1 cognitive test at 3 months) in participants who completed the baseline and 3-month assessments. Secondary end points included time to intracranial failure, quality of life, functional independence, long-term cognitive status, and overall survival.There were 213 randomized participants (SRS alone, n = 111; SRS plus WBRT, n = 102) with a mean age of 60.6 years (SD, 10.5 years); 103 (48%) were women. There was less cognitive deterioration at 3 months after SRS alone (40/63 patients [63.5%]) than when combined with WBRT (44/48 patients [91.7%]; difference, -28.2%; 90% CI, -41.9% to -14.4%; P .001). Quality of life was higher at 3 months with SRS alone, including overall quality of life (mean change from baseline, -0.1 vs -12.0 points; mean difference, 11.9; 95% CI, 4.8-19.0 points; P = .001). Time to intracranial failure was significantly shorter for SRS alone compared with SRS plus WBRT (hazard ratio, 3.6; 95% CI, 2.2-5.9; P .001). There was no significant difference in functional independence at 3 months between the treatment groups (mean change from baseline, -1.5 points for SRS alone vs -4.2 points for SRS plus WBRT; mean difference, 2.7 points; 95% CI, -2.0 to 7.4 points; P = .26). Median overall survival was 10.4 months for SRS alone and 7.4 months for SRS plus WBRT (hazard ratio, 1.02; 95% CI, 0.75-1.38; P = .92). For long-term survivors, the incidence of cognitive deterioration was less after SRS alone at 3 months (5/11 [45.5%] vs 16/17 [94.1%]; difference, -48.7%; 95% CI, -87.6% to -9.7%; P = .007) and at 12 months (6/10 [60%] vs 17/18 [94.4%]; difference, -34.4%; 95% CI, -74.4% to 5.5%; P = .04).Among patients with 1 to 3 brain metastases, the use of SRS alone, compared with SRS combined with WBRT, resulted in less cognitive deterioration at 3 months. In the absence of a difference in overall survival, these findings suggest that for patients with 1 to 3 brain metastases amenable to radiosurgery, SRS alone may be a preferred strategy.clinicaltrials.gov Identifier: NCT00377156.

OBJECTIVEAntiepileptic drugs (AEDs) are often administered prophylactically following brain tumor resection. With conflicting evidence and unestablished guidelines, however, the nature of this practice among tumor surgeons is unknown.METHODSOn November 24, 2015, a REDCap (Research Electronic Database Capture) survey was sent to members of the AANS/CNS Section on Tumors to query practice patterns.RESULTSResponses were received from 144 individuals, including 18.8% of board-certified neurosurgeons surveyed (across 86 institutions, 16 countries, and 5 continents). The majority reported practicing in an academic setting (85%) as a tumor specialist (71%). Sixty-three percent reported always or almost always prescribing AED prophylaxis postoperatively in patients with a supratentorial brain tumor without a prior seizure history. Meanwhile, 9% prescribed occasionally and 28% rarely prescribed AED prophylaxis. The most common agent was levetiracetam (85%). The duration of seizure prophylaxis varied widely: 25% of surgeons administered prophylaxis for 7 days, 16% for 2 weeks, 21% for 2 to 6 weeks, and 13% for longer than 6 weeks. Most surgeons (61%) believed that tumor pathology influences epileptogenicity, with high-grade glioma (39%), low-grade glioma (31%), and metastases (24%) carrying the greatest seizure risk. While the majority used prophylaxis, 62% did not believe or were unsure if prophylactic AEDs reduced seizures postoperatively. The vast majority (82%) stated that a well-designed randomized trial would help guide their future clinical decision making.CONCLUSIONSWide knowledge and practice gaps exist regarding the frequency, duration, and setting of AED prophylaxis for seizure-naive patients undergoing brain tumor resection. Acceptance of universal practice guidelines on this topic is unlikely until higher-level evidence supporting or refuting the value of modern seizure prophylaxis is demonstrated.

BACKGROUND The evidence of or against the presence of a 'July phenomenon' in resident teaching hospitals has been inconsistent. Moreover, there are limited data on the "July phenomenon" in the field of neurosurgery. OBJECTIVE To determine whether a "July phenomenon" exists for neurosurgical mortality or complications. METHODS A search of the National Inpatient Sample database from 1998 to 2008 was performed for all admissions for International Classification of Diseases, 9th Revision codes corresponding to nontraumatic hemorrhage, central nervous system (CNS) trauma, CNS tumor, and hydrocephalus. Generalized linear mixed-model analysis was performed, adjusted for patient demographics and hospital characteristics, for the outcomes of mortality and complications for the month of July compared with all other months in teaching hospitals. RESULTS Generalized linear mixed-model analysis demonstrated that the risk of dying in the month of July vs any other month in a teaching hospital was not statistically different for any of the 4 diagnoses: nontraumatic hemorrhage (P = .071), CNS trauma category (P = .485), CNS tumor category (P = .578), hydrocephalus category (P = .1505). Moreover, the risk of any complication in the month of July vs any other month in a teaching hospital was not statistically different for any of the 4 diagnoses: nontraumatic hemorrhage (P = .529), CNS trauma category (P = .378), CNS tumor category (P = .461), and hydrocephalus category (P = .441). The same findings were true in an analysis of nonteaching hospitals performed as a control. CONCLUSION No "July phenomenon" was found for neurosurgical mortality or complications in patients with nontraumatic hemorrhage, CNS trauma, CNS tumor, or hydrocephalus.

Early studies suggest that bevacizumab treatment can result in tumor shrinkage and hearing improvement for some patients with neurofibromatosis type 2 (NF2). The aim of this study was to report extended follow-up in a larger cohort of similarly treated patients.Retrospective study.Tertiary referral centerThirty-one consecutive NF2 patients who received bevacizumab for progressive vestibular schwannomas.Hearing improvement, defined as an improvement in word recognition score above the 95% critical difference compared with baseline, and radiographic response, defined as a 20% or greater decrease in tumor volume compared with baseline.The median age was 26 years (range, 12-73 yr). The median volumetric tumor growth rate before treatment was 64% per year. At the time of analysis, the median duration of treatment was 14 months (range, 6-41 mo) with a total of 47 patient-years of follow-up. A hearing response occurred in 57% (13/23) of evaluable patients and a radiographic response in 55% (17/31) of target vestibular schwannomas. The median time to response was 3 months for both end points. The only clinical or radiographic feature at baseline that correlated with change in tumor volume at 3 months was the mean apparent diffusion coefficient value, a radiologic marker of edema (p = 0.036). Ninety percent of patients had stable or improved hearing after 1 year of treatment and 61% at 3 years; 88% of patients had stable or decreased tumor size after 1 year of treatment and 54% at 3 years. Overall, treatment was well tolerated.Bevacizumab treatment was followed by hearing improvement and tumor shrinkage in more than 50% of progressive vestibular schwannomas in NF2 patients. Stable or improved hearing was retained in the majority of patients.

BACKGROUND The Accreditation Council for Graduate Medical Education resident duty-hour restrictions were implemented in July 2003 based on the supposition that resident fatigue contributes to medical errors. OBJECTIVE To examine the effect of duty-hour restrictions on outcome in neurotrauma patients. METHODS The Nationwide Inpatient Sample database was analyzed for a time period with no restrictions (years 1999-2002) compared with a period with restrictions (years 2005-2008) for (1) mortality and (2) complications. We analyzed both teaching and nonteaching hospitals to account for potential differences attributed to non-resident-related factors. RESULTS There were 107,006 teaching hospital and 115,604 nonteaching hospital admissions for neurotrauma. Multivariate logistic regression demonstrated significantly more complications in the time period with restrictions in teaching hospitals. In nonteaching hospitals, there was no difference in complications. In both teaching and nonteaching hospitals, there was no difference in mortality between the 2 time periods. For teaching and nonteaching hospitals, there was no difference in hospital length of stay, but hospital charges were significantly higher in the period with restrictions. The occurrence of a complication was significantly associated with longer hospital length of stay and higher hospital charges in both time periods in both teaching and nonteaching hospitals. CONCLUSION The implementation of the Accreditation Council for Graduate Medical Education resident duty-hour restrictions was associated with increased complications and no change in mortality for neurotrauma patients in teaching hospitals. In nonteaching hospitals, there was no change in complications and mortality. The occurrence of a complication was associated with longer length of stay and higher hospital charges in both time periods in both teaching and nonteaching hospitals.

Managing a CNS neoplasm during pregnancy presents complex challenges, and population-based studies are lacking. We designed a retrospective cohort study using the Nationwide Inpatient Sample (NIS) to investigate pregnancy outcomes in women with CNS neoplasms. We constructed a logistic regression model for maternal mortality, preterm labor, intrauterine growth restriction (IUGR), and Caesarean delivery, controlling for age, comorbidities, and demographic characteristics. We identified 379 malignant brain tumors, 437 benign brain tumors, and 44 spine tumors among 19 million pregnancy-related admissions from 1988 through 2009. Malignant brain tumors were associated with maternal mortality (odds ratio [OR], 143), preterm labor (OR, 3.4), and IUGR (OR, 2.9). Benign brain tumors were associated with preterm labor (OR, 2.3). A diagnosis of hyperemesis gravidarum was more common in malignant (OR, 2.2) and benign (OR, 2.8) brain tumors. Compared with the general population, Caesarean delivery was more frequent for malignant (OR, 6.4) and benign (OR, 2.8) brain tumors and spine tumors (OR, 3.9). Admission without delivery was more common for malignant (OR, 8.6) and benign (OR, 4.3) brain tumors and spine tumors (OR, 3.8; P < .05 for all outcomes). Thirty-three percent of all hospitalizations involved neurosurgical procedures, but pregnancy complications were not significantly more likely to occur in surgical patients. In conclusion, malignant brain tumors were associated with adverse pregnancy outcomes, and CNS neoplasms were associated with higher rates of Caesarean delivery. Additional research is needed to improve understanding of obstetric risk in these patients and to assist with treatment, counseling, and monitoring during delivery.

BACKGROUND It is not clear whether treatment modality (clipping or coiling) affects the risk of seizures after treatment for cerebral aneurysms. OBJECTIVE To determine whether there is an increased risk of seizures after clipping vs coiling. METHODS Hospitalizations for clipping or coiling of ruptured and unruptured aneurysms were identified in the Nationwide Inpatient Sample Database for 2002 to 2007 by International Classification of Diseases 9th Revision codes for subarachnoid hemorrhage or unruptured cerebral aneurysm and codes for clipping or coiling. Clipping and coiling were compared for the combined primary endpoint of seizures or epilepsy. The analysis was adjusted for patient-specific and hospital-specific factors using generalized linear models with generalized estimated equations. RESULTS There were 10 899 hospitalizations for ruptured aneurysms (6593 clipping, 4306 coiling), and 9686 hospitalizations for unruptured aneurysms (4483 clipping, 5203 coiling). For ruptured aneurysm patients, clipping had a similar incidence of seizures or epilepsy compared with coiling (10.7% vs 11.1%, respectively, adjusted odds ratio: 0.596; 95% confidence interval: 0.158-2.248; P = .445 after adjustment for patient-specific and hospital-specific factors). For unruptured aneurysm patients, clipping was associated with a significantly higher risk of seizures or epilepsy (9.2%) compared with coiling (6.2%) (adjusted odds ratio: 1.362; 95% confidence interval: 0.155-1.606; P < .001 after adjustment for patient-specific and hospital-specific factors). Seizures or epilepsy were significantly associated with longer hospitalizations (P < .01) and higher hospital charges (P < .0001), except in coiled unruptured aneurysm patients, in which seizures or epilepsy were not significantly associated with hospital charges (P = .31). CONCLUSION In unruptured cerebral aneurysm patients, clipping is associated with a higher risk of seizures or epilepsy.

Background and Purpose— A stroke “weekend effect” on mortality has been demonstrated in other countries with a possible slight effect in the United States. We studied patients with stroke in the Nationwide Inpatient Sample database for a weekend effect on thrombolytic use, in-hospital mortality, discharge disposition, hospital charges, and length of stay. Methods— The Nationwide Inpatient Sample 2002 to 2007 was searched for all emergency room admissions for International Classification of Diseases, 9th Revision codes corresponding to ischemic stroke. Generalized estimated equations for generalized linear models were performed, adjusting for gender, age, race, season, median income level, payer, comorbidity score, hospital region, hospital location, teaching status, bed size, and hospital annual stroke case volume to compare weekend versus weekday stroke admission incidence of thrombolytic use, in-hospital mortality, discharge disposition, hospital charges, and length of stay. The same analysis was performed using the International Classification of Diseases, 9th Revision codes for ischemic stroke AND transient cerebral ischemia to check internal validity for coding irregularities that may occur in differentiating stroke from transient ischemic attack. Results— There were 599 087 emergency room admissions for ischemic stroke: 159 906 weekend admissions and 439 181 weekday admissions. Generalized estimated equation for generalized linear model analysis was performed and demonstrated weekend compared with weekday patients with stroke were slightly more likely to receive thrombolytics (OR=1.114; 95% CI=1.039 to 1.194; P =0.003); incur slightly higher total hospital charges (effect ratio=1.011; 95% CI=1.006 to 1.017; P P Conclusions— There is a slight stroke weekend effect on thrombolytic use, total hospital charges, and length of stay, but no difference in in-hospital mortality or discharge disposition.

OBJECTIVE: Racial disparities in American health care outcomes are well documented. We investigated racial disparities in hospital mortality and adverse discharge disposition after brain tumor craniotomies performed in the United States from 1988 to 2004. We explored potential explanations for the disparities. METHODS: The data source was the Nationwide Inpatient Sample. We used multivariate ordinal logistic regression corrected for clustering by hospital and adjusted for age, sex, primary payer for care, income in postal code of residence, geographic region, admission type and source, medical comorbidity, treatment year, hospital case volume, and disease-specific factors. Random-effects pooling was also used. RESULTS: A total of 99 665 craniotomies were studied. Hospital mortality and adverse discharge disposition (any discharge other than directly home) were more likely in black patients than others for all tumor types. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for blacks were: hospital craniotomy mortality (OR, 1.64; 95% CI, 1.32-2.03; P < .001), and adverse discharge disposition (OR, 1.43; 95% CI, 1.31-1.56; P < .001). Medicaid patients had higher mortality, while private-pay patients had lower mortality. Hospital annual case volume was lower for black and Hispanic patients and for those with Medicaid as the primary payer in pooled analyses, whereas patients with private insurance received care at higher-volume hospitals. Black patients generally presented with higher disease severity, including more emergency or urgent admissions (OR,1.71; 95% CI, 1.54-1.89; P < .001); more hemiparesis and hemiplegia for primary tumors, meningiomas, and metastases (P < .04 for all); and more hydrocephalus for acoustic neuromas (P= .1). CONCLUSION: Black patients died more often or had an adverse discharge disposition after tumor craniotomies in the United States in the period studied (1988-2004). Blacks had more severe disease at presentation and were treated at lower-volume hospitals for surgery. Other socially defined patient groups also showed disparities in access and outcomes of care.

Background and Purpose— We have previously reported the difference in length of stay and hospital charges for patients with cerebral aneurysms treated with either clipping or coiling at our institution. We now report an analysis of the same comparison at a national level conducted using the Nationwide Inpatient Sample database. Methods— We obtained the Nationwide Inpatient Sample from the Healthcare Cost and Utilization Project, Agency for Healthcare Quality and Research. The Nationwide Inpatient Sample is the largest all-payer inpatient care database in the US and represents ≈20% of all inpatient admissions to US nonfederal hospitals. Hospitalizations for clipping or coiling of ruptured and unruptured cerebral aneurysms from 2002 to 2006 were identified by cross-matching International Classification of Diseases-9 codes for diagnoses of subarachnoid hemorrhage (430) or unruptured cerebral aneurysm (437.3) with procedure codes for clipping (39.51) or coiling (39.79, 39.72, or 39.52) of cerebral aneurysms. Length of hospital stay and total hospital charges for clipping and coiling were compared using linear mixed models adjusted for the following patient and hospital-specific factors: gender, age, race/ethnicity, admission source and type, median income level in patient’s postal code of residence, payer for care, comorbidities, and hospital cerebral aneurysm case volume, bed size, teaching status, rural/urban location, and geographic region. Results— There were 9635 hospitalizations for ruptured aneurysm treatments (6019 clipping, 3616 coiling) and 9399 hospitalizations for unruptured aneurysm treatments (4700 clipping, 4699 coiling). For ruptured aneurysm patients, after adjusting for the effects of patient-specific and hospital-specific factors, clipping compared to coiling was associated with significantly longer length of stay ( P P P P Conclusions— The results of this nationwide analysis differed from the findings of our single institution study. Clipping compared to coiling was associated with significantly longer lengths of stay and significantly higher total hospital charges for both ruptured and unruptured aneurysm patients.

OBJECTIVE: Patients with intracranial aneurysms, both ruptured and unruptured, are frequently eligible for both open surgery ("clipping") and endovascular repair ("coiling"). Although results of randomized trials have informed this decision, the actual choice of clipping or coiling for individual patients remains complex. At the 2007 Congress of Neurological Surgeons (CNS) Annual Meeting, a novel active learning process called Integrated Medical Learning (IML) was applied to education about this critical treatment choice. METHODS: CNS members received an electronically distributed premeeting survey and educational materials about the clipping versus coiling decision and related topics. At the Annual Meeting, participants used handheld devices to choose clipping or coiling for treatment of individual aneurysms, both before and after expert opinion presentations. After the meeting, members who had answered premeeting surveys received a follow-up questionnaire. RESULTS: In the premeeting poll, respondents with self-described specialties of "vascular," Cerebrovascular Section members, surgeons with active cerebrovascular practices, and surgeons in practice for less than 20 years had higher levels of baseline knowledge of cerebrovascular literature (P < .03). Surgeons' clinical volumes of clipping and coiling strongly influenced their vote for clipping or coiling for a hypothetical patient (P

Background The purpose of this study was to determine treatment outcome and prognostic factors in patients with locally advanced primary sphenoid sinus malignancy treated with proton radiation therapy. Methods Between 1991 and 2005, 20 patients with primary sphenoid sinus malignancy received proton beam to a median dose of 76 Gray equivalent. Results With a median follow-up of 27 months, the 2-year local, regional, and freedom from distant metastasis rates were 86%, 86%, and 50%, respectively. The disease-free and overall-survival rates at 2 years were 31% and 53%, respectively. In multivariate analysis, oropharyngeal involvement (p = .005) and anterior cranial fossa invasion (p = .02) were predictive for poor disease-free survival rate. Brain invasion was predictive for decreased overall-survival rate (p = .05). Conclusions Proton radiation therapy results in excellent local control in patients with advanced primary sphenoid sinus malignancy. Brain invasion, involvement of the oropharynx and anterior cranial fossa are important prognostic factors. © 2009 Wiley Periodicals, Inc. Head Neck, 2009

Profound hearing loss is a serious complication of neurofibromatosis type 2, a genetic condition associated with bilateral vestibular schwannomas, benign tumors that arise from the eighth cranial nerve. There is no medical treatment for such tumors.We determined the expression pattern of vascular endothelial growth factor (VEGF) and three of its receptors, VEGFR-2, neuropilin-1, and neuropilin-2, in paraffin-embedded samples from 21 vestibular schwannomas associated with neurofibromatosis type 2 and from 22 sporadic schwannomas. Ten consecutive patients with neurofibromatosis type 2 and progressive vestibular schwannomas who were not candidates for standard treatment were treated with bevacizumab, an anti-VEGF monoclonal antibody. An imaging response was defined as a decrease of at least 20% in tumor volume, as compared with baseline. A hearing response was defined as a significant increase in the word-recognition score, as compared with baseline.VEGF was expressed in 100% of vestibular schwannomas and VEGFR-2 in 32% of tumor vessels on immunohistochemical analysis. Before treatment, the median annual volumetric growth rate for 10 index tumors was 62%. After bevacizumab treatment in the 10 patients, tumors shrank in 9 patients, and 6 patients had an imaging response, which was maintained in 4 patients during 11 to 16 months of follow-up. The median best response to treatment was a volumetric reduction of 26%. Three patients were not eligible for a hearing response; of the remaining seven patients, four had a hearing response, two had stable hearing, and one had progressive hearing loss. There were 21 adverse events of grade 1 or 2.VEGF blockade with bevacizumab improved hearing in some, but not all, patients with neurofibromatosis type 2 and was associated with a reduction in the volume of most growing vestibular schwannomas.