Glioneuronal Tumor With Features of Ganglioglioma and Neurocytoma Arising in the Fourth Ventricle: A Report of 2 Unusual Cases and a Review of Infratentorial Gangliogliomas.

Infratentorial glioneuronal neoplasms are overall quite rare and are more commonly low-grade with surgical excision usually being curative. Multiple distinct histologic entities have been described including rosette-forming glioneuronal tumor, papillary glioneuronal tumor, neurocytoma, dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease), cerebellar liponeurocytoma, and ganglioglioma. While each of these entities has distinct findings, in some instances a tumor may demonstrate overlapping histologic features with mixed components. Herein, we report 2 unusual adult cases of a fourth ventricular glioneuronal tumor with features of ganglioglioma and neurocytoma, with one coming from a surgical resection and one found incidentally at autopsy. To the best of our knowledge, this specific histologic combination has not previously been described. As such, the clinical significance is unknown although in both cases the neoplasms were circumscribed and appeared to be low grade. The presence of the gangliogliomatous component was of particular interest since these are extremely rare occurrences in the fourth ventricle and we provide a comprehensive review of infratentorial gangliogliomas.

Glioblastoma in the elderly: the effect of aggressive and modern therapies on survival.

OBJECTIVE: The prognosis of elderly patients with glioblastoma (GBM) is universally poor. Currently, few studies have examined postoperative outcomes and the effects of various modern therapies such as bevacizumab on survival in this patient population. In this study, the authors evaluated the effects of various factors on overall survival in a cohort of elderly patients with newly diagnosed GBM. METHODS: A retrospective review was performed of elderly patients (≥ 65 years old) with newly diagnosed GBM treated between 2004 and 2010. Various characteristics were evaluated in univariate and multivariate stepwise models to examine their effects on complication risk and overall survival. RESULTS: A total of 120 patients were included in the study. The median age was 71 years, and sex was distributed evenly. Patients had a median Karnofsky Performance Scale (KPS) score of 80 and a median of 2 neurological symptoms on presentation. The majority (53.3%) of the patients did not have any comorbidities. Tumors most frequently (43.3%) involved the temporal lobe, followed by the parietal (35.8%), frontal (32.5%), and occipital (15.8%) regions. The majority (57.5%) of the tumors involved eloquent structures. The median tumor size was 4.3 cm. Every patient underwent resection, and 63.3% underwent gross-total resection (GTR). The vast majority (97.3%) of the patients received the postoperative standard of care consisting of radiotherapy with concurrent temozolomide. The majority (59.3%) of patients received additional agents, most commonly consisting of bevacizumab (38.9%). The median survival for all patients was 12.0 months; 26.7% of patients experienced long-term (≥ 2-year) survival. The extent of resection was seen to significantly affect overall survival; patients who underwent GTR had a median survival of 14.1 months, whereas those who underwent subtotal resection had a survival of 9.6 months (p = 0.038). Examination of chemotherapeutic effects revealed that the use of bevacizumab compared with no bevacizumab (20.1 vs 7.9 months, respectively; p < 0.0001) and irinotecan compared with no irinotecan (18.0 vs 9.7 months, respectively; p = 0.027) significantly improved survival. Multivariate stepwise analysis revealed that older age (hazard ratio [HR] 1.06 [95% CI1.02-1.10]; p = 0.0077), a higher KPS score (HR 0.97 [95% CI 0.95-0.99]; p = 0.0082), and the use of bevacizumab (HR 0.51 [95% CI 0.31-0.83]; p = 0.0067) to be significantly associated with survival. CONCLUSION: This study has demonstrated that GTR confers a modest survival benefit on elderly patients with GBM, suggesting that safe maximal resection is warranted. In addition, bevacizumab significantly increased the overall survival of these elderly patients with GBM; older age and preoperative KPS score also were significant prognostic factors. Although elderly patients with GBM have a poor prognosis, they may experience enhanced survival after the administration of the standard of care and the use of additional chemotherapeutics such as bevacizumab.

Novel chemotherapeutics and other therapies for treating high-grade glioma.

INTRODUCTION: Despite extensive research, high-grade glioma (HGG) remains a dire diagnosis with no change in the standard of care in almost a decade. However, recent advancements uncovering molecular biomarkers of brain tumors and tumor-specific antigens targeted by immunotherapies provide opportunities for novel personalized treatment regimens to improve survival. AREAS COVERED: In this review, the authors provide a comprehensive overview of recent therapeutic advancements in HGG. Furthermore, they describe new molecular biomarkers and molecular classifications, in addition to updated research on bevacizumab, targeted molecular therapies, immunotherapy and alternative delivery methods that overcome the blood-brain barrier to reach the target tumor tissue. Challenges regarding each therapy are also outlined. The authors also provide some insight into a novel non-chemotherapeutic treatment for malignant glioma, NovoTTFA, as well as a summary of current treatment options for recurrence. EXPERT OPINION: Current research for treating malignant gliomas are paving the path to personalized therapy, including immunotherapy, that involve integrated genomic and histolopathologic data, as well as a multi-modal treatment regimen. Immunotherapy will potentially be the next addition to the current standard of care, specialized to the antigens presented on the tumors. The results of the current trials of multi-antigen vaccines are eagerly anticipated.

Worse outcomes for patients undergoing brain tumor and cerebrovascular procedures following the ACGME resident duty-hour restrictions.

OBJECT: On July 1, 2003, the Accreditation Council for Graduate Medical Education (ACGME) implemented duty-hour restrictions for resident physicians due to concerns for patient and resident safety. Though duty-hour restrictions have increased resident quality of life, studies have shown mixed results with respect to patient outcomes. In this study, the authors have evaluated the effect of duty-hour restrictions on morbidity, mortality, length of stay, and charges in patients who underwent brain tumor and cerebrovascular procedures. METHODS: The Nationwide Inpatient Sample was used to evaluate the effect of duty-hour restrictions on complications, mortality, length of stay, and charges by comparing the pre-reform (2000-2002) and post-reform (2005-2008) periods. Outcomes were compared between nonteaching and teaching hospitals using a difference-in-differences (DID) method. RESULTS: A total of 90,648 patients were included in the analysis. The overall complication rate was 11.7%, with the rates not significantly differing between the pre- and post-duty hour eras (p = 0.26). Examination of hospital teaching status revealed that complication rates decreased in nonteaching hospitals (12.1% vs 10.4%, p = 0.0004) and remained stable in teaching institutions (11.8% vs 11.9%, p = 0.73) in the post-reform era. Multivariate analysis demonstrated a significantly higher complication risk in teaching institutions (OR 1.33 [95% CI 1.11-1.59], p = 0.0022), with no significant change in nonteaching hospitals (OR 1.11 [95% CI 0.91-1.37], p = 0.31). A DID analysis to compare the magnitude in change between teaching and nonteaching institutions revealed that teaching hospitals had a significantly greater increase in complications during the post-reform era than nonteaching hospitals (p = 0.040). The overall mortality rate was 3.0%, with a significant decrease occurring in the post-reform era in both nonteaching (5.0% vs 3.2%, p < 0.0001) and teaching (3.2% vs 2.3%, p < 0.0001) hospitals. DID analysis to compare the changes in mortality between groups did not reveal a significant difference (p = 0.40). The mean length of stay for all patients was 8.7 days, with hospital stay decreasing from 9.2 days to 8.3 days in the post-reform era (p < 0.0001). The DID analysis revealed a greater length of stay decrease in nonteaching hospitals than teaching institutions, which approached significance (p = 0.055). Patient charges significantly increased in the post-reform era for all patients, increasing from $70,900 to $96,100 (p < 0.0001). The DID analysis did not reveal a significant difference between the changes in charges between teaching and nonteaching hospitals (p = 0.17). CONCLUSIONS: The implementation of duty-hour restrictions correlated with an increased risk of postoperative complications for patients undergoing brain tumor and cerebrovascular neurosurgical procedures. Duty-hour reform may therefore be associated with worse patient outcomes, contrary to its intended purpose. Due to the critical condition of many neurosurgical patients, this patient population is most sensitive and likely to be negatively affected by proposed future increased restrictions.

Malignant brainstem gliomas in adults: clinicopathological characteristics and prognostic factors.

Adult malignant brainstem gliomas (BSGs) are poorly characterized due to their relative rarity. We have examined histopathologically confirmed cases of adult malignant BSGs to better characterize the patient and tumor features and outcomes, including the natural history, presentation, imaging, molecular characteristics, prognostic factors, and appropriate treatments. A total of 34 patients were identified, consisting of 22 anaplastic astrocytomas (AAs) and 12 glioblastomas (GBMs). The overall median survival for all patients was 25.8 months, with patients having GBMs experiencing significantly worse survival (12.1 vs. 77.0 months, p = 0.0011). The majority of tumors revealed immunoreactivity for EGFR (93.3 %) and MGMT (64.7 %). Most tumors also exhibited chromosomal abnormalities affecting the loci of epidermal growth factor receptor (92.9 %), MET (100 %), PTEN (61.5 %), and 9p21 (80 %). AAs more commonly appeared diffusely enhancing (50.0 vs. 27.3 %) or diffusely nonenhancing (25.0 vs. 0.0 %), while GBMs were more likely to exhibit focal enhancement (54.6 vs. 10.0 %). Multivariate analysis revealed confirmed histopathology for GBM to significantly affect survival (HR 4.80; 95 % CI 1.86-12.4; p = 0.0012). In conclusion, adult malignant BSGs have an overall poor prognosis, with GBM tumors faring significantly worse than AAs. As AAs and GBMs have differing imaging characteristics, tissue diagnosis may be necessary to accurately determine patient prognosis and identify molecular characteristics which may aid in the treatment of these aggressive tumors.

Cerebellopontine angle meningiomas: postoperative outcomes in a modern cohort.

OBJECT: Tumors of the cerebellopontine angle (CPA) have always proven difficult for neurosurgeons to optimally manage. Studies investigating the natural history and treatment of vestibular schwannomas have dominated the literature in this regard. Distinguishing meningiomas from schwannomas in this location carries particular importance as each tumor type has certain prognostic and surgical considerations. In this study, the authors have characterized the outcomes of 34 patients surgically treated for CPA meningiomas and have investigated various factors that may affect postoperative neurological function. METHODS: The medical records of patients with CPA meningiomas who underwent surgery from 2005 to 2013 at the Duke University Health System were reviewed. Various patient, clinical, and tumor data were gathered from the medical records including patient demographics, pre- and postoperative neurological examinations, duration of symptoms, procedural details, tumor pathology and size, and treatment characteristics. Differences in continuous variables were then analyzed using the Student t-test while categorical variables were evaluated using the chi-square test. RESULTS: A total of 34 patients underwent surgical treatment for CPA meningiomas during the 8-year period. Jugular foramen invasion was seen in 17.6% of tumors, with nearly half (41.2%) extending into the internal acoustic canal. The most common presenting symptom was hearing loss (58.8%), followed by headache (52.9%) and facial numbness/pain (50.0%). The most common cranial nerve (CN) affected was CN X (11.8%), followed by CNs VI and VII (5.9%). Postoperatively, no patients experienced a decrease in hearing, with only 5.9% of patients experiencing facial nerve palsies. Patients with tumors larger than 3 cm had a significantly higher incidence of permanent CN deficits than those with smaller tumors (45.5% vs 5.9%, respectively; p = 0.011). Also, tumor extension into the jugular foramen was associated with the occurrence of lower CN deficits, none of which occurred in tumors without jugular foramen invasion. Internal acoustic canal tumor extension was not seen to be associated with postoperative complications or CN deficits. CONCLUSIONS: Meningiomas of the CPA are challenging lesions to treat surgically. However, the risk of facial palsy and hearing loss is significantly lower when compared with vestibular schwannomas. Novel methods for preoperative differentiation are needed to appropriately counsel patients on surgical risks. Also, due to the significant potential for neurological deficits, further studies are needed to investigate the utility of radiotherapy for these lesions.

Clinical characteristics and treatment of malignant brainstem gliomas in elderly patients.

Adult brainstem gliomas (BSG) are uncommon tumors that constitute only 2% of all brain tumors. Due to its rare occurrence in the elderly (60 years and older), there is no literature discussing the natural history, prognosis, and best treatment strategy for malignant BSG in this population to our knowledge. We report seven elderly patients with malignant BSG and propose treatment strategies to manage these aggressive tumors. The median age at onset in this cohort was 65 years, with the majority of patients being male (71.4%) and Caucasian (85.7%). The median duration of symptoms prior to presentation was 0.5 months, with the most common symptoms being facial weakness, blurry vision, headache, and extremity weakness. Tumors were most commonly located in the pons (85.7%), with one tumor being located in the tectal plate. Five of seven (71.4%) patients underwent biopsies, with two patients undergoing partial resections. Following tissue diagnosis, patients received radiation therapy and concurrent temozolomide, followed by additional chemotherapeutics upon progression. Side effects as a result of treatment were seen in three patients and all involved reversible hematological complications such as neutropenia and thrombopenia. The median time to progression was 6.7 months and the median overall survival was 13.5 months. While malignant BSG in elderly patients are aggressive gliomas with an overall poor prognosis, these patients are able to safely undergo aggressive chemoradiotherapy, resulting in improved survival. Resection may be considered for select patients in which the tumor is mostly exophytic, near the brainstem surface, and easily accessible.

Low-grade astrocytomas: the prognostic value of fibrillary, gemistocytic, and protoplasmic tumor histology.

OBJECT: Low-grade astrocytomas are slow-growing, infiltrative gliomas that over time may progress into more malignant tumors. Various factors have been shown to affect the time to progression and overall survival including age, performance status, tumor size, and the extent of resection. However, more recently it has been suggested that histological subtypes (fibrillary, protoplasmic, and gemistocytic) may impact patient outcome. In this study the authors have performed a large comparative population-based analysis to examine the characteristics and survival of patients with the various subtypes of WHO Grade II astrocytomas. METHODS: Patients diagnosed with fibrillary, protoplasmic, and gemistocytic astrocytomas were identified through the Surveillance, Epidemiology, and End Results (SEER) database. The chi-square test and Student t-test were used to evaluate differences in patient and treatment characteristics between astrocytoma subtypes. Kaplan-Meier analysis was used to assess overall survival, and the log-rank test was used to evaluate the differences between survival curves. Univariate and multivariate analyses were also performed to determine the effect of various patient, tumor, and treatment variables on overall survival. RESULTS: A total of 500 cases were included in the analysis, consisting of 326 fibrillary (65.2%), 29 protoplasmic (5.8%), and 145 gemistocytic (29%) variants. Gemistocytic astrocytomas presented at a significantly older age than the fibrillary variant (46.8 vs 37.7 years, p < 0.0001), with protoplasmic and fibrillary subtypes having a similar age. Although protoplasmic and fibrillary variants underwent radiotherapy at similar rates, gemistocytic tumors more frequently received radiotherapy (p = 0.0001). Univariate analysis revealed older age, larger tumor size, and the use of radiotherapy to be poor prognostic factors, with resection being associated with improved survival. The gemistocytic subtype (hazard ratio [HR] 1.62 [95% CI 1.27-2.07], p = 0.0001) also resulted in significantly worse survival than fibrillary tumors. Bivariate analyses demonstrated that older age, the use of radiotherapy, and resection significantly influenced median survival. Tumor subtype also affected median survival; patients who harbored gemistocytic tumors experienced less than half the median survival of fibrillary and protoplasmic tumors (38 vs 82 months, p = 0.0003). Multivariate analysis revealed increasing age (HR 1.05 [95% CI 1.04-1.05], p < 0.0001), larger tumor size (HR 1.02 [95% CI 1.01-1.03], p = 0.0002), and the use of resection (HR 0.70 [95% CI 0.52-0.94], p = 0.018) to be independent predictors of survival. Examination of tumor subtype revealed that the gemistocytic variant (HR 1.30 [95% CI 0.98-1.74], p = 0.074) was associated with worse patient survival than fibrillary tumors, although this only approached significance. The protoplasmic subtype did not affect overall survival (p = 0.33). CONCLUSIONS: Gemistocytic tumor histology was associated with worse survival than fibrillary and protoplasmic astrocytomas. As protoplasmic astrocytomas have a survival similar to fibrillary tumors, there may be limited utility to the identification of this rare variant. However, increased attention should be paid to the presence of gemistocytes in low-grade gliomas as this is associated with shorter time to progression, increased malignant transformation, and reduced overall survival.

Clinicopathological characteristics and treatment of rhabdoid glioblastoma.

OBJECT: Rhabdoid glioblastoma (GB) is an exceedingly rare tumor in which some of the tumor cells possess rhabdoid features such as eccentric nuclei, abundant eosinophilic cytoplasm, and pseudopapillary formations. These tumors are exceptionally aggressive, and leptomeningeal dissemination is common. In the 9 previously reported cases, the longest survival was only 9 months, with a median survival of 17.8 weeks. The authors report the clinicopathological characteristics of 4 cases of rhabdoid GB and demonstrate the utility of intensive temozolomide and adjuvant therapy in these tumors. The authors also review the literature to provide the most comprehensive understanding of these rare tumors to date. METHODS: A retrospective review was performed of patients treated for GB at the Duke University Medical Center between 2004 and 2012. One of two experienced neuropathologists identified 4 cases as being rhabdoid GBs. Immunohistochemistry and fluorescence in situ hybridization analyses were performed in all cases. Kaplan-Meier analysis was used to assess overall survival, with the log-rank test being used to evaluate differences between survival curves. An extensive review of the literature was also performed. RESULTS: The median age of patients with rhabdoid GB was 30 years. Clinical presentation varied with location, with headache being a presenting symptom in 90% of patients. All lesions were supratentorial, and 45.5% of the cases involved the temporal lobe. Leptomeningeal dissemination occurred in 63.6% of patients, with 1 patient having extracranial metastasis to the scalp and lungs. Fluorescence in situ hybridization revealed epidermal growth factor receptor gain or amplification in all study cases. The median survival in the authors' cohort was significantly higher than that of all previously reported cases (27.5 vs 4.5 months, p = 0.003). Postoperative treatment in the authors' cohort included radiotherapy with concurrent temozolomide, bevacizumab, interleukin 13, CCNU, and/or etoposide. CONCLUSIONS: Enhanced survival in the authors' 4 patients suggests that the current standard of care for the treatment of GB may be beneficial in rhabdoid GB cases, with postoperative radiotherapy and concomitant temozolomide treatment followed by adjuvant therapy. Due to the rapid tumor dissemination associated with these lesions, aggressive and timely therapy is warranted, with frequent surveillance and/or continued therapy despite stable disease. Additionally, patients should undergo full craniospinal imaging to monitor the development of distant metastatic disease.

Adult primitive neuroectodermal tumors: the prognostic value of supratentorial location.

Primitive neuroectodermal tumors (PNETs) are tumors which primarily consist of undifferentiated round neuroepithelial cells. Central nervous system PNETs can be divided into two genetically distinct groups: infratentorial PNET (iPNET)/medulloblastoma and supratentorial PNET (sPNET). Currently, the comparative outcome of adult patients with sPNETs and iPNETs is unknown. In this study we have utilized the Surveillance, Epidemiology, and End Results database to perform a comparative analysis of 103 cases of adult sPNET and 669 adult medulloblastoma cases. Additionally we have analyzed various factors to identify their prognostic significance and characterize the optimal treatment for these tumors. Patients with sPNETs were seen to have a significantly worse survival than those diagnosed with medulloblastomas (16 vs. 155 months, p < 0.0001). Elderly patients (15 vs. 114 months, p < 0.0001) and those over the age of 40 (68 vs. 147 months, p < 0.0001) experienced significantly worse survival than younger patients. In contrast, radiotherapy (143 vs. 26 months, p < 0.0001), surgical resection (116 vs. 22 months, p = 0.0010) and the extent of resection (EOR) (173 vs. 81 months, p = 0.0005) resulted in significantly improved patient survival. Multivariate analysis revealed age greater than 40 years (HR: 1.57; 95 % CI: 1.17-2.11; p = 0.0028) and sPNET pathology (HR: 3.41; 95 % CI: 2.47-4.72; p < 0.0001) to be poor prognostic factors for survival while radiotherapy (HR: 0.52; 95 % CI: 0.38-0.71; p < 0.0001) and the EOR (HR: 0.73; 95 % CI: 0.55-0.96; p = 0.023) were associated with significantly improved survival. The treatment of sPNETs should therefore include maximal surgical resection when feasible followed by radiotherapy as these treatments have been demonstrated to confer a survival benefit. Additional studies are needed to identify effective chemotherapeutics and specific treatment regimens for adults with sPNETs.

Outcome and prognostic factors in adult cerebellar glioblastoma.

Cerebellar glioblastoma multiforme (GBM) occurs rarely in adults, accounting for 0.4-3.4% of all GBM. Current studies have all involved small patient numbers, limiting the clear identification of prognostic factors. Additionally, while few studies have compared cerebellar GBM to their supratentorial counterparts, there is conflicting data regarding their relative prognosis. To better characterize outcome and identify patient and treatment factors which affect survival, the authors analyzed cases of adult cerebellar GBM from the Surveillance, Epidemiology, and End Results database. A total of 247 adult patients with cerebellar GBM were identified, accounting for 0.67% of all adult GBM. Patients with cerebellar GBM were significantly younger than those with supratentorial tumors (56.6 versus 61.8 years, p < 0.0001), but a larger percentage of patients with supratentorial GBM were Caucasian (91.7% versus 85.0%, p < 0.0001). Overall median survival did not differ between those with cerebellar and supratentorial GBM (7 versus 8 months, p = 0.24), with similar rates of long-term (greater than 2 years) survival (13.4% versus 10.6%, p = 0.21). Multivariate analysis revealed age greater than 40 years (hazard ratio [HR]: 2.20; 95% confidence interval [CI]: 1.47-3.28; p = 0.0001) to be associated with worse patient survival, while the use of radiotherapy (HR: 0.33; 95% CI: 0.24-0.47; p < 0.0001) and surgical resection (HR: 0.66; 95% CI: 0.45-0.96; p = 0.028) were seen to be independent favorable prognostic factors. In conclusion, patients with cerebellar GBM have an overall poor prognosis, with radiotherapy and surgical resection significantly improving survival. As with supratentorial GBM, older age is a poor prognostic factor. The lack of differences between supratentorial and cerebellar GBM with respect to overall survival and prognostic factors suggests these tumors to be biologically similar.

Intraaxial dermoid cyst of the medulla.

Intracranial dermoid cysts are rare congenital lesions that typically occur in the cisternal spaces. However, exceptionally rare cases of intraaxial involvement have been reported, with only 8 cases having been described in the literature. The authors report the first case of an intraaxial dermoid cyst located in the medulla and the first occurrence in an elderly patient. They also review the literature of the existing intraparenchymal cases and provide treatment guidelines. A 66-year-old man presented with slowly progressive dysphagia, left lower-extremity numbness, nausea, and hyperhidrosis. Neurological examination revealed decreased pinprick sensation of the left side of his face and body, and decreased vibratory sensation in his left lower extremity. Additionally, he had an unusual extraocular movement in which abduction of the eye resulted in closure of the contralateral eye. Magnetic resonance imaging revealed a nonenhancing cystic lesion centered in the medulla. The patient underwent a suboccipital craniotomy with laminectomy of C1-2 for excision of the cyst, with subtotal resection due to adherence of the cyst wall to the brainstem. At follow-up 7.5 years after surgery, the patient's neurological examination was stable. Magnetic resonance imaging did not reveal any progression or recurrence of the cyst. As the cyst wall is typically adherent to surrounding structures, resection is usually subtotal due to the risk of neurological deficits. As there have been no cases of progression after subtotal resection, gross-total resection is not warranted for the treatment of these lesions.

Improved survival in the largest national cohort of adults with cerebellar versus supratentorial low-grade astrocytomas.

OBJECT: Low-grade gliomas (LGGs) are indolent tumors that have the potential to dedifferentiate into malignant high-grade tumors. Recent studies have demonstrated that cerebellar low-grade tumors have a better prognosis than supratentorial tumors, although no study has focused on the risk factors for poor prognosis in cerebellar LGGs in adults. The authors of the current study aimed to address both of these concerns by using a large cohort derived from a national cancer registry and a smaller cohort derived from their institution's experience. METHODS: Adults with diagnosed Grade I and Grade II gliomas of the cerebellum were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate Cox proportional hazard models were used to predict rates of survival, and the log-rank test was applied to evaluate differences in Kaplan-Meier survival curves. An institutional cohort was created by isolating all patients whose surgical pathology revealed an LGG of the cerebellum. Excluded from analysis were patients in whom a glioma was first diagnosed under the age of 18 years and those whose tumors could not be definitively determined to arise from the cerebellum. Results Data from the local cohort (11 patients) demonstrated that the most common presenting symptom was headache, which occurred in more than 70% of the cohort. Approximately half of the patients in this cohort had symptomatic improvement after treatment. RESULTS: from the SEER cohort (166 patients) revealed that adults with Grade I gliomas were slightly younger than those with Grade II tumors (p < 0.01), but no other demographic differences were observed. Patients with Grade I tumors were twice as likely to undergo gross-total resection (54% vs 21%), and those with Grade II gliomas were much more likely to receive postoperative radiation (3% vs 48%). Five-year survival was greater in the patients with Grade I gliomas than in those with Grade II lesions (91% vs 70%). Multivariate analysis revealed that an age ≥ 40 years (HR 7.30, 95% CI 3.55-15.0, p < 0.0001) and Grade II tumors (HR 2.76, 95% CI 1.12-6.84, p = 0.028) were risk factors for death, whereas female sex was protective (HR 0.28, 95% CI 0.14-0.59, p < 0.001). Log-rank tests revealed that a cerebellar location was protective (p < 0.0001), but this relationship was only true for Grade II tumors (p < 0.0001). Survival in patients with Grade I gliomas was not different based on the various lesion locations (p = 0.21). CONCLUSIONS: Taken together, adults with cerebellar WHO Grade I and II astrocytomas have a much more favorable survival curve than those with similar supratentorial tumors. Research demonstrates that the primary driver of this phenomenon is the improved survival in patients with cerebellar Grade II gliomas.

A comprehensive analysis of 41 patients with rosette-forming glioneuronal tumors of the fourth ventricle.

The rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle is a recently described, rare, and distinct tumor of the glioneuronal family. The presentation, natural history, and treatment response of these tumors has been unclear as there are no significant series of a sizeable population with long-term follow-up. We report a comprehensive analysis of 41 patients with RGNT to provide the most current understanding of this rare tumor. Treatment of these patients has consisted of resection via the transvermian and telovelar approaches, with one patient requiring radiotherapy due to tumor recurrence. Various unique imaging characteristics may allow for the preoperative identification of these tumors. Resection via the telovelar approach should be considered for symptomatic tumors and those that pose a risk of obstructive hydrocephalus. Due to their benign nature and low propensity for recurrence, subtotal resection may be appropriate for those that are adherent to the brainstem. Radiotherapy may be considered for patients with tumor recurrence.

Vestibular schwannomas in the modern era: epidemiology, treatment trends, and disparities in management.

OBJECT: There are a variety of treatment options for the management of vestibular schwannomas (VSs), including microsurgical resection, radiotherapy, and observation. Although the choice of treatment is dependent on various patient factors, physician bias has been shown to significantly affect treatment choice for VS. In this study the authors describe the current epidemiology of VS and treatment trends in the US in the modern era. They also illustrate patient and tumor characteristics and elucidate their effect on tumor management. METHODS: Patients diagnosed with VS were identified through the Surveillance, Epidemiology, and End Results database, spanning the years 2004-2009. Age-adjusted incidence rates were calculated and adjusted using the 2000 US standard population. The chi-square and Student t-tests were used to evaluate differences between patient and tumor characteristics. Multivariate logistic regression was performed to determine the effects of various patient and tumor characteristics on the choice of tumor treatment. RESULTS: A total of 6225 patients with VSs treated between 2004 and 2009 were identified. The overall incidence rate was 1.2 per 100,000 population per year. The median age of patients with VS was 55 years, with the majority of patients being Caucasian (83.16%). Of all patients, 3053 (49.04%) received surgery only, with 1466 (23.55%) receiving radiotherapy alone. Both surgery and radiation were only used in 123 patients (1.98%), with 1504 patients not undergoing any treatment (24.16%). Increasing age correlated with decreased use of surgery (OR 0.95, 95% CI 0.95-0.96; p<0.0001), whereas increasing tumor size was associated with the increased use of surgery (OR 1.04, 95% CI 1.04-1.05; p<0.0001). Older age was associated with an increased likelihood of conservative management (OR 1.04, 95% CI 1.04-1.05; p<0.0001). Racial disparities were also seen, with African American patients being significantly less likely to receive surgical treatment compared with Caucasians (OR 0.50, 95% CI 0.35-0.70; p<0.0001), despite having larger tumors at diagnosis. CONCLUSIONS: The incidence of vestibular schwannomas in the US is 1.2 per 100,000 population per year. Although many studies have demonstrated improved outcomes with the use of radiotherapy for small- to medium-sized VSs, surgery is still the most commonly used treatment modality for these tumors. Racial disparities also exist in the treatment of VSs, with African American patients being half as likely to receive surgery and nearly twice as likely to have their VSs managed conservatively despite presenting with larger tumors. Further studies are needed to elucidate the reasons for treatment disparities and investigate the nationwide trend of resection for the treatment of small VSs.

Thrombin and hemin as central factors in the mechanisms of intracerebral hemorrhage-induced secondary brain injury and as potential targets for intervention.

Intracerebral hemorrhage (ICH) is a subtype of stoke that may cause significant morbidity and mortality. Brain injury due to ICH initially occurs within the first few hours as a result of mass effect due to hematoma formation. However, there is increasing interest in the mechanisms of secondary brain injury as many patients continue to deteriorate clinically despite no signs of rehemorrhage or hematoma expansion. This continued insult after primary hemorrhage is believed to be mediated by the cytotoxic, excitotoxic, oxidative, and inflammatory effects of intraparenchymal blood. The main factors responsible for this injury are thrombin and erythrocyte contents such as hemoglobin. Therapies including thrombin inhibitors, N-methyl-D-aspartate antagonists, chelators to bind free iron, and antiinflammatory drugs are currently under investigation for reducing this secondary brain injury. This review will discuss the molecular mechanisms of brain injury as a result of intraparenchymal blood, potential targets for therapeutic intervention, and treatment strategies currently in development.

Prophylactic correction of the international normalized ratio in neurosurgery: a brief review of a brief literature.

Prophylactic fresh-frozen plasma (FFP) transfusion is often undertaken in hemodynamically stable patients with a minimally elevated international normalized ratio (INR) prior to invasive procedures, despite little evidence in support of this practice. The authors review the current literature in an attempt to clarify best clinical practice with regard to this issue. Although the activated partial thromboplastin time and prothrombin time-INR are useful laboratory tests to measure specific clotting factors in the coagulation cascade, in the absence of active bleeding or a preexisting coagulopathy, their utility as predictors of overall bleeding risk is limited. Several studies have shown an imperfect correlation between mild elevations in the INR and subsequent bleeding tendency. Furthermore, FFP transfusion is not always sufficient to achieve normal INR values in patients who have mild elevations (< 2) to begin with. Finally, there are risks associated with FFP transfusion, including potential transfusion-associated [disease] exposures as well as the time delay imposed by laboratory testing and transfusion administration prior to initiation of procedures. The authors propose that the current concept of a "normal" INR value warrants redefinition to make it a more meaningful clinical tool. Based on their review of the literature, the authors suggest that in a hemodynamically stable patient population there is a range of mildly prolonged INR values for which FFP transfusion is not beneficial, and is potentially harmful.

Treatment recommendations for primary extradural meningiomas.

Primary extradural meningiomas (PEMs) represent about 2% of all meningiomas and are often encountered by non-neurosurgeons. These lesions typically present as enlarging, painless, benign masses that can be surgically cured. Imaging is critical for defining involvement of adjacent structures; however, diagnosis depends on classic histologic patterns. Treatment for benign PEMs (WHO I) consists of resection with wide margins, whereas adjuvant therapy after resection of atypical (WHO II) or malignant (WHO III) PEMs should be considered. By using the collective experience from our comprehensive cancer center, including neuro-oncologists, neuroradiologists, and neurosurgeons, in addition to a complete literature review, the authors have established treatment guidelines not previously reported. This manuscript describes key features of these challenging tumors to aid in diagnosis, presents the largest published review of all reported PEMs (n = 163), and provides salient treatment guidelines to surgeons unfamiliar with these challenging tumors.

Emerging therapeutic targets and agents for glioblastoma migrating cells.

Glioblastoma multiforme (GBM) is one of the most common and most aggressive types of primary brain tumors in humans. Even with aggressive surgical resections using state of the art preoperative and intraoperative neuroim-aging, along with the most recent techniques in radiotherapy and chemotherapy, the prognosis for GBM patients remains dismal. Survival after diagnosis is about 12-14 months. The tumor cells which already have migrated into normal brain tissue beyond the surgical resection margin account for the inability to effectively treat this tumor. Understanding how to control the migration of GBM cells is paramount to future therapies. In this review, we will focus on the emerging targets and agents which are being exploited to inhibit the migration of glioma cells in GBM.