Repeat resection for recurrent glioblastoma in the temozolomide era: a real-world multi-centre study.

INTRODUCTION: In contrast to standard-of-care treatment of newly diagnosed glioblastoma, there is limited consensus on therapy upon disease progression. The role of resection for recurrent glioblastoma remains unclear. This study aimed to identify factors for overall survival (OS) and post-progression survival (PPS) as well as to validate an existing prediction model. METHODS: This was a multi-centre retrospective study that reviewed consecutive adult patients from 2006 to 2019 that received a repeat resection for recurrent glioblastoma. The primary endpoint was PPS defined as from the date of second surgery until death. RESULTS: 1032 glioblastoma patients were identified and 190 (18%) underwent resection for recurrence. Patients that had second surgery were more likely to be younger (<70 years) (adjusted OR: 0.3; 95% CI: 0.1-0.6), to have non-eloquent region tumours (aOR: 1.7; 95% CI: 1.1-2.6) and received temozolomide chemoradiotherapy (aOR: 0.2; 95% CI: 0.1-0.4). Resection for recurrent tumour was an independent predictor for OS (aOR: 1.5; 95% CI: 1.3-1.7) (mOS: 16.9 months versus 9.8 months). For patients that previously received temozolomide chemoradiotherapy and subsequent repeat resection (137, 13%), the median PPS was 9.0 months (IQR: 5.0-17.5). Independent PPS predictors for this group were a recurrent tumour volume of >50cc (aOR: 0.6; 95% CI: 0.4-0.9), local recurrence (aOR: 1.7; 95% CI: 1.1-3.3) and 5-ALA fluorescence-guided resection during second surgery (aOR: 1.7; 95% CI: 1.1-2.8). A National Institutes of Health Recurrent Glioblastoma Multiforme Scale score of 0 conferred an mPPS of 10.0 months, a score of 1-2, 9.0 months and a score of 3, 4.0 months (log-rank test, p-value < 0.05). CONCLUSION: Surgery for recurrent glioblastoma can be beneficial in selected patients and carries an acceptable morbidity rate. The pattern of recurrence influenced PPS and the NIH Recurrent GBM Scale was a reliable prognostication tool.

Patterns of care and survival of Chinese glioblastoma patients in the temozolomide era: a Hong Kong population-level analysis over a 14-year period.

Background: The aim of this study is to address the paucity of epidemiological data regarding the characteristics, treatment patterns and survival outcomes of Chinese glioblastoma patients. Methods: This was a population-level study of Hong Kong adult (>18 years) Chinese patients with newly diagnosed histologically confirmed glioblastoma between 2006 and 2019. The age standardized incidence rate (ASIR), patient-, tumor- treatment-related characteristics, overall survival (OS) as well as its predictors were determined. Results: One thousand and ten patients with a median follow-up of 10.0 months were reviewed. The ASIR of glioblastoma was 1.0 per 100 000 population with no significant change during the study period. The mean age was 57 + 14 years. The median OS was 10.6 months (IQR: 5.2-18.4). Independent predictors for survival were: Karnofsky performance score >80 (adjusted OR: 0.8; 95% CI: 0.6-0.9), IDH-1 mutant (aOR: 0.7; 95% CI: 0.5-0.9) or MGMT methylated (aOR: 0.7; 95% CI: 0.5-0.8) glioblastomas, gross total resection (aOR: 0.8; 95% CI: 0.5-0.8) and temozolomide chemoradiotherapy (aOR 0.4; 95% CI: 0.3-0.6). Despite the significant increased administration of temozolomide chemoradiotherapy from 39% (127/326) of patients in 2006-2010 to 63% (227/356) in 2015-2019 (P-value < .001), median OS did not improve (2006-2010: 10.3 months vs 2015-2019: 11.8 months) (OR: 1.1; 95% CI: 0.9-1.3). Conclusions: The incidence of glioblastoma in the Chinese general population is low. We charted the development of neuro-oncological care of glioblastoma patients in Hong Kong during the temozolomide era. Although there was an increased adoption of temozolomide chemoradiotherapy, a corresponding improvement in survival was not observed.

Epidemiological characteristics and genetic alterations in adult diffuse glioma in East Asian populations.

Understanding the racial specificities of diseases-such as adult diffuse glioma, the most common primary malignant tumor of the central nervous system-is a critical step toward precision medicine. Here, we comprehensively review studies of gliomas in East Asian populations and other ancestry groups to clarify the racial differences in terms of epidemiology and genomic characteristics. Overall, we observed a lower glioma incidence in East Asians than in Whites; notably, patients with glioblastoma had significantly younger ages of onset and longer overall survival than the Whites. Multiple genome-wide association studies of various cohorts have revealed single nucleotide polymorphisms associated with overall and subtype-specific glioma susceptibility. Notably, only 3 risk loci-5p15.33, 11q23.3, and 20q13.33-were shared between patients with East Asian and White ancestry, whereas other loci predominated only in particular populations. For instance, risk loci 12p11.23, 15q15-21.1, and 19p13.12 were reported in East Asians, whereas risk loci 8q24.21, 1p31.3, and 1q32.1 were reported in studies in White patients. Although the somatic mutational profiles of gliomas between East Asians and non-East Asians were broadly consistent, a lower incidence of EGFR amplification in glioblastoma and a higher incidence of 1p19q-IDH-TERT triple-negative low-grade glioma were observed in East Asian cohorts. By summarizing large-scale disease surveillance, germline, and somatic genomic studies, this review reveals the unique characteristics of adult diffuse glioma among East Asians, to guide clinical management and policy design focused on patients with East Asian ancestry.

Machine learning algorithms identify demographics, dietary features, and blood biomarkers associated with stroke records.

OBJECTIVE: We conducted a comprehensive evaluation of features associated with stroke records. METHODS: We screened the dietary nutrients, blood biomarkers, and clinical information from the National Health and Nutrition Examination Survey (NHANES) 2015-16 database to assess a self-reported history of all strokes (136 strokes, n = 4381). We computed feature importance, built machine learning (ML) models, developed a nomogram, and validated the nomogram on NHANES 2007-08, 2017-18, and the baseline UK Biobank. We calculated the odds ratios with/without adjusting sampling weights (OR/ORw). RESULTS: The clinical features have the best predictive power compared to dietary nutrients and blood biomarkers, with 22.8% increased average area under the receiver operating characteristic curves (AUROC) in ML models. We further modeled with ten most important clinical features without compromising the predictive performance. The key features positively associated with stroke include age, cigarette smoking, tobacco smoking, Caucasian or African American race, hypertension, diabetes mellitus, asthma history; the negatively associated feature is the family income. The nomogram based on these key features achieved good performances (AUROC between 0.753 and 0.822) on the test set, the NHANES 2007-08, 2017-18, and the UK Biobank. Key features from the nomogram model include age (OR = 1.05, ORw = 1.06), Caucasian/African American (OR = 2.68, ORw = 2.67), diabetes mellitus (OR = 2.30, ORw = 1.99), asthma (OR = 2.10, ORw = 2.41), hypertension (OR = 1.86, ORw = 2.10), and income (OR = 0.83, ORw = 0.81). CONCLUSIONS: We identified clinical key features and built predictive models for assessing stroke records with high performance. A nomogram consisting of questionnaire-based variables would help identify stroke survivors and evaluate the potential risk of stroke.

D2-Net: Dual Disentanglement Network for Brain Tumor Segmentation With Missing Modalities.

Multi-modal Magnetic Resonance Imaging (MRI) can provide complementary information for automatic brain tumor segmentation, which is crucial for diagnosis and prognosis. While missing modality data is common in clinical practice and it can result in the collapse of most previous methods relying on complete modality data. Current state-of-the-art approaches cope with the situations of missing modalities by fusing multi-modal images and features to learn shared representations of tumor regions, which often ignore explicitly capturing the correlations among modalities and tumor regions. Inspired by the fact that modality information plays distinct roles to segment different tumor regions, we aim to explicitly exploit the correlations among various modality-specific information and tumor-specific knowledge for segmentation. To this end, we propose a Dual Disentanglement Network (D2-Net) for brain tumor segmentation with missing modalities, which consists of a modality disentanglement stage (MD-Stage) and a tumor-region disentanglement stage (TD-Stage). In the MD-Stage, a spatial-frequency joint modality contrastive learning scheme is designed to directly decouple the modality-specific information from MRI data. To decompose tumor-specific representations and extract discriminative holistic features, we propose an affinity-guided dense tumor-region knowledge distillation mechanism in the TD-Stage through aligning the features of a disentangled binary teacher network with a holistic student network. By explicitly discovering relations among modalities and tumor regions, our model can learn sufficient information for segmentation even if some modalities are missing. Extensive experiments on the public BraTS-2018 database demonstrate the superiority of our framework over state-of-the-art methods in missing modalities situations. Codes are available at https://github.com/CityU-AIM-Group/D2Net.

Reducing meningo-cerebral adhesions by implanting an interpositional subdural polyesterurethane graft after high-grade glioma resection.

BACKGROUND: Meningo-cerebral adhesions are frequently encountered during recurrent high-grade glioma resections. Adhesiolysis not only lengthens operation times, but can also induce focal cortical tissue injury that could affect overall survival. METHODS: Immediately after the primary resection of a high-grade glioma, a polyesterurethane interpositional graft was implanted in the subdural space covering the entire exposed cortex as well as beneath the dural suture line. No postoperative complications were documented. All patients received adjuvant radiotherapy. Upon repeat resection for focal tumor recurrence, the graft was shown to effectively reduce meningo-cerebral adhesion development. CONCLUSION: The implantation of a synthetic subdural graft is a safe and effective method for preventing meningo-cerebral adhesions.

Diagnostic radiation-induced regression of a metastatic primary intracranial germinoma: a case report.

Pineal region germinomas are sensitive to radiotherapy. Standard neurosurgical management involves obtaining a tissue biopsy and to relieve the often accompanying obstructive hydrocephalus. We present a patient with a suspected hyper-radiosensitive metastatic primary intracranial germinoma where computed tomography scanning resulted in tumor regression before radiotherapy could be administered.

The protean manifestations of central nervous system IgG4-related hypertrophic pachymeningitis: a report of two cases.

BACKGROUND: IgG4-related hypertrophic pachymeningitis is a relative newly recognized and rare manifestation of IgG4-related disease, an immune-mediated fibroinflammatory tumefactive disorder. Fewer than 80 patients have been reported in the literature, and it can mimic common neurosurgical conditions. We describe the clinical presentation of two patients that were initially considered to have a subdural collection, tuberculous meningitis, and a cervical spinal meningioma, but were eventually diagnosed with this disease. CASE PRESENTATION: Two ethnic Chinese men, 86 and 62 years old, experienced a 4-week history of headache. Both patients had a history of autoimmune disease, namely glomerulonephritis and Grave's disease, respectively. Magnetic resonance brain imaging revealed diffuse dural thickening with the latter patient exhibiting homogeneous and intense gadolinium-contrast enhancement. Since the 86-year-old patient also had progressive bilateral visual loss, giant cell arteritis was suspected and a 2-week course of glucocorticoid therapy was prescribed, but his symptoms failed to improve. The 62-year-old patient also had accompanying low-grade fever and was treated empirically as having tuberculous meningitis although there were no confirmatory microbiological findings. This patient further developed right hemiparesis, and additional imaging revealed a C4/5 intradural-extramedullary contrast-enhancing lesion resembling a meningioma causing cord compression. Both patients underwent neurosurgical intervention with the former undergoing a dural biopsy and the latter having the cervical lesion resected. The final diagnosis was IgG4-related hypertrophic pachymeningitis with the hallmark histological features of lymphoplasmacytic infiltration of IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. In addition, their serum IgG4 levels were elevated (i.e., > 135 mg/dL). Both patients received at least 6 months of glucocorticoid therapy while the latter also had azathioprine. Their symptoms improved significantly and recurrent lesions were not detected on follow-up imaging. CONCLUSIONS: A high index of suspicion for this condition is suggested when a male patient with a history of autoimmune disease and compatible radiological findings, experiences subacute headache that is disproportionate to the degree of dural involvement. Neurosurgeons should consider early meningeal biopsy to establish a definitive histological diagnosis in order for early effective immunosuppressive treatment to be initiated and to avoid unnecessary morbidity.

Radiotherapy-induced glioblastoma: distinct differences in overall survival, tumor location, pMGMT methylation and primary tumor epidemiology in Hong Kong chinese patients.

INTRODUCTION: Radiotherapy-induced glioblastomas (RIGB) are a well-known late and rare complication of brain irradiation. Yet the clinical, radiological and molecular characteristics of these tumors are not well characterized. METHODS: This was a retrospective multicentre study that analysed adult patients with newly diagnosed glioblastoma over a 10-year period. Patients with RIGB were identified according to Cahan's criteria for radiation-induced tumors. A case-control analysis was performed to compare known prognostic factors for overall survival (OS) with an independent cohort of IDH-1 wildtype de novo glioblastomas treated with standard temozolomide chemoradiotherapy. Survival analysis was performed by Cox proportional hazards regression. RESULTS: A total of 590 adult patients were diagnosed with glioblastoma. 19 patients (3%) had RIGB. The mean age of patients upon diagnosis was 48 years ± 15. The mean latency duration from radiotherapy to RIGB was 14 years ± 8. The mean total dose was 58Gy ± 10. One-third of patients (37%, 7/19) had nasopharyngeal cancer and a fifth (21%, 4/19) had primary intracranial germinoma. Compared to a cohort of 146 de novo glioblastoma patients, RIGB patients had a shorter median OS of 4.8 months versus 19.2 months (p-value: <.001). Over a third of RIGBs involved the cerebellum (37%, 7/19) and was higher than the control group (4%, 6/146; p-value: <.001). A fifth of RIGBs (21%, 3/19) were pMGMT methylated which was significantly fewer than the control group (49%, 71/146; p-value: .01). For RIGB patients (32%, 6/19) treated with re-irradiation, the one-year survival rate was 67% and only 8% for those without such treatment (p-value: .007). CONCLUSION: The propensity for RIGBs to develop in the cerebellum and to be pMGMT unmethylated may contribute to their poorer prognosis. When possible re-irradiation may offer a survival benefit. Nasopharyngeal cancer and germinomas accounted for the majority of original malignancies reflecting their prevalence among Southern Chinese.

The Relationship Between Stimulation Current and Functional Site Localization During Brain Mapping.

BACKGROUND: Gliomas are often in close proximity to functional regions of the brain; therefore, electrocortical stimulation (ECS) mapping is a common technique utilized during glioma resection to identify functional areas. Stimulation-induced seizure (SIS) remains the most common reason for aborted procedures. Few studies have focused on oncological factors impacting cortical stimulation thresholds. OBJECTIVE: To examine oncological factors thought to impact stimulation threshold in order to understand whether a linear relationship exists between stimulation current and number of functional cortical sites identified. METHODS: We retrospectively reviewed single-institution prospectively collected brain mapping data of patients with dominant hemisphere gliomas. Comparisons of stimulation threshold were made using t-tests and ANOVAs. Associations between oncologic factors and stimulation threshold were made using multivariate regressions. The association between stimulation current and number of positive sites was made using a Poisson model. RESULTS: Of the 586 patients included in the study, SIS occurred in 3.92% and the rate of SIS events differed by cortical location (frontal 8.5%, insular 1.6%, parietal 1.3%, and temporal 2.8%; P = .009). Stimulation current was lower when mapping frontal cortex (P = .002). Stimulation current was not associated with tumor plus peritumor edema volume, world health organization) (WHO grade, histology, or isocitrate dehydrogenase (IDH) mutation status but was associated with tumor volume within the frontal lobe (P = .018). Stimulation current was not associated with number of positive sites identified during ECS mapping (P = .118). CONCLUSION: SISs are rare but serious events during ECS mapping. SISs are most common when mapping the frontal lobe. Greater stimulation current is not associated with the identification of more cortical functional sites during glioma surgery.

Incidence, Presentation, and Risk Factors for Sodium Valproate-Associated Hyperammonemia in Neurosurgical Patients: A Prospective, Observational Study.

OBJECTIVE: Sodium valproate (VPA) is a commonly prescribed antiepileptic drug (AED) in daily neurosurgical practice. However, the incidence of VPA-associated hyperammonemia (VAH) and its life-threatening consequence, VPA-induced hyperammonemic encephalopathy (VHE), in neurosurgical patients is unknown. We determined the incidence, clinical presentation, and risk factors for VAH. METHODS: This prospective cohort study was performed on adult neurosurgical patients prescribed VPA for at least a week over a 22-month period. Blood tests for ammonia, VPA, and liver function were performed at the time of recruitment. The primary end point was VAH. Secondary end points were VHE and liver dysfunction. RESULTS: In total, 252 patients were recruited. The commonest disease etiology was brain tumors (27%, 69), followed by aneurysmal subarachnoid hemorrhage (SAH; 26%, 65). VPA was prescribed for primary seizure prophylaxis in 110 patients (44%). The mean daily dose was 1148 mg for a mean duration of 48 months. The mean serum VPA level was 417 µmol/L. In total, 92 patients (37%) were prescribed an additional AED, the most common being phenytoin (65%, 60/92). The mean serum ammonia level was 47 µmol/L. In total, 28% (71/252) of patients had VAH and only 0.7% had VHE. Independent factors were aneurysmal SAH (adjusted odds ratio [aOR] 2.1; 95% confidence interval [CI] 1.1-4.2), concomitant phenytoin (aOR 1.9; 95% CI 1.0-3.5), and phenobarbital (aOR 4.6; 95% CI 1.1-20.0). No associations with VPA dose, duration, serum levels, and liver function were observed. CONCLUSIONS: Although VAH is common among neurosurgical patients, VHE is rare. Patients with aneurysmal SAH or on concomitant enzyme-inducing AEDs are at risk. Clinicians should be vigilant for VHE symptoms in these patients.

Impact of metformin on immunological markers: Implication in its anti-tumor mechanism.

Metformin, an anti-hyperglycemic drug, has been known to have antitumor properties for around 15 years. Although there are a number of reports attributing the antitumor function of metformin to its impact on energy homeostasis and oxygen re-distribution in tumor microenvironment, detailed mechanisms remain largely unknown. In the past several years, there is an increasing number of publications indicating that metformin can affect various immunological components including lymphocytes, macrophages, cytokines and several key immunological molecules in both human and animal studies. These interesting results appear to be in line with emerging data that suggest associations between immune responses and energy homeostasis/oxygen re-distribution, which may explain effective impacts of metformin on immunotherapies against autoimmune diseases as well as cancers. This review article is to analyse and discuss recent development in the above areas with aim to justify metformin as a new adjuvant for immunotherapy against human cancers. We hope that our summary will help to optimize the application of metformin for various types of human cancers.

Novel Wavelength-Specific Blue Light-Emitting Headlamp for 5-Aminolevulinic Acid Fluorescence-Guided Resection of Glioblastoma.

OBJECTIVE: Extent of resection of glioblastoma is an important predictor for overall survival, and 5-aminolevulinic acid fluorescence-guided surgery can improve outcomes. However, the technique requires the installation of a blue light module on operative microscopes and may be cost prohibitive. A novel and economical blue light-emitting headlamp was designed, and its clinical utility was explored. METHODS: A remote-controlled dual light emitting diode headlamp system was constructed with 1 diode emitting white light and the other blue. Spectrographic analysis of the blue light emitted from a commercial operative microscope and the headlamp was performed. A comparative evaluation of the 2 illumination systems was conducted for 3 patients who underwent craniotomy for glioblastoma resection. Histologic examination of the fluorescing tissue detected by the headlamp was performed, and the extent of resection was assessed by postoperative day 1 magnetic resonance imaging. RESULTS: Spectrography of blue light emitted from the headlamp system was wavelength specific with a single emission peak at 416 nm and a linewidth of 35 nm. In contrast, blue light from the microscope (peak: 426 nm) had a wider linewidth of 54 nm and was not wavelength specific with additional infrared radiation detected. Gross or near-total resection of contrast-enhancing glioblastoma was performed for all 3 patients. Intraoperatively, comparable tumor fluorescence was observed under microscope and headlamp blue light illumination. Histologic examination of tissue fluorescing under headlamp blue light confirmed the presence of glioblastoma. CONCLUSIONS: This novel proof-of-concept blue light-emitting headlamp device may offer an opportunity for institutions with limited resources to implement 5-aminolevulinic acid fluorescence-guided glioblastoma resections.

The importance of aspirin, catheterization accuracy, and catheter design in external ventricular drainage-related hemorrhage: a multicenter study of 1002 procedures.

BACKGROUND: External ventricular drainage (EVD) is the commonest neurosurgical procedure performed in daily neurosurgical practice, but relatively few studies have investigated the incidence and risk factors of its related hemorrhagic complications. METHODS: This was a multicenter retrospective review of consecutive EVD procedures. Patients 18 years or older who underwent EVD and had a routine postoperative computed tomography (CT) scan performed within 24 hours were included. EVD-related hemorrhage was defined as new intracranial hemorrhage immediately adjacent or within the ventricular catheter trajectory. The volume of hemorrhage and the position of the catheter tip were assessed. A review of patient-, disease-, and surgery-related factors including the ventricular catheter design utilized was conducted. The Bonferroni correction was applied to the alpha level of significance (0.05) for multivariable analysis. RESULTS: Nine hundred sixty-two patients underwent 1002 EVD performed by neurosurgeons in the operating theater. Sixteen percent (154) of patients were on aspirin before the procedure. Thirty-four percent (333) of patients had intracerebral hemorrhage, 25% (251) had aneurysmal subarachnoid hemorrhage and 16% (158) had traumatic brain injury. The mean duration from EVD to the first postoperative CT scan was 20 ± 4 h. EVD-related hematomas were detected after 81 procedures with a per-catheter risk of 8.1%. Mean hematoma volume was 1.2 ± 3.3 ml. Most were less than 1 ml (grade I, 79%, 64), 1 to 15 ml (grade II) in 20% (16) and a single clot larger than 15 ml (grade III, 1%) were detected. Clinically significant hemorrhage that resulted in catheter occlusion occurred in 1.7% (17) of procedures. Most catheters (62%, 625) were optimally placed, i.e., its tip being within the ipsilateral frontal horn or third ventricle. Three non-antibiotic-impregnated ventricular catheter designs were used with 55% (550) being the 2.2-mm Integra™ catheter, 14% (137) being the 2.8-mm Medtronic™ catheter, and 31% (315) being the 3.1-mm Codman™ catheter. Independent significant predictors for EVD-related hemorrhage were the preoperative prescription of aspirin (adjusted OR 1.94; 95% CI 1.10-3.44), catheter malposition (aOR 1.99; 95% CI 1.22-3.23), and use of the 2.8-mm Medtronic™ catheter (aOR 4.22; 95% CI 2.39-7.41). CONCLUSIONS: The per-catheter risk of hemorrhage was 8.1%, but the incidence of symptomatic hemorrhage was low. The only patient risk factor was aspirin intake. This is the first study to evaluate and establish an association between catheter malposition and catheter design with EVD-related hemorrhage.

Regression of BRAF V600E mutant adult glioblastoma after primary combined BRAF-MEK inhibitor targeted therapy: a report of two cases.

BACKGROUND: Up to 15% of young adults with glioblastoma have the activating oncogenic BRAF V600E mutation, an actionable target of the MAPK signal transduction pathway governing tumor cell proliferation. Small molecule inhibitors of BRAF and MEK, a downstream protein immediately following BRAF, have been shown to confer a survival advantage for patients with BRAF V600E mutant advanced melanoma. We describe our experience using this combined target therapy for two patients with BRAFV600E mutant glioblastoma (GBM) as primary treatment due to extenuating clinical circumstances that prohibited the prescription of standard treatment. CASE PRESENTATION: The two patients were both 22 years old on presentation. After the initial tumor resection, they both developed rapid deterioration in performance status within a few weeks due to leptomeningeal metastases. In view of the critical condition, BRAF and MEK inhibitors were prescribed as first line treatment. The two patients both achieved dramatic clinical response, which was parallel to the impressive radiological regression of the disease. Unfortunately, the duration of disease control was short as drug resistance developed rapidly. The two patients died 7 and 7.5 month after initial diagnosis of GBM. CONCLUSIONS: Primary treatment with inhibitors of BRAF and MEK can lead to tumor regression for patients with BRAF V600E mutant glioblastoma. We therefore recommend that all young GBM patients should undergo BRAFV600E mutation testing, especially for those with unusual aggressive clinical course.

Determining a cut-off residual tumor volume threshold for patients with newly diagnosed glioblastoma treated with temozolomide chemoradiotherapy: A multicenter cohort study.

Standard-of-care treatment of glioblastomas involves maximal safe resection and adjuvant temozolomide chemo-radiotherapy. Although extent of resection (EOR) is a well-known surgical predictor for overall survival most lesions cannot be completely resected. We hypothesize that in the event of incomplete resection, residual tumor volume (RTV) may be a more significant predictor than EOR. This was a multicenter retrospective review of 147 adult glioblastoma patients (mean age 53 years) that underwent standard treatment. Semiautomatic magnetic resonance imaging segmentation was performed for pre- and postoperative scans for volumetric analysis. Cox proportional hazards regression and Kaplan-Meier survival analyses were performed for prognostic factors including: age, Karnofsky performance score (KPS), O(6)-methylguanine methyltransferase (MGMT) promoter methylation status, EOR and RTV. EOR and RTV cut-off values for improved OS were determined and internally validated by receiver operator characteristic (ROC) analysis for 12-month overall survival. Half of the tumors had MGMT promoter methylation (77, 52%). The median tumor volume, EOR and RTV were 43.20 cc, 93.5%, and 3.80 cc respectively. Gross total resection was achieved in 52 patients (35%). Cox proportional hazards regression, ROC and maximum Youden index analyses for RTV and EOR showed that a cut-off value of <3.50 cc (HR 0.69; 95% CI 0.48-0.98) and ≥84% (HR 0.64; 95% CI 0.43-0.96) respectively conferred an overall survival advantage. Independent overall survival predictors were MGMT promoter methylation (adjusted HR 0.35; 95% CI 0.23-0.55) and a RTV of <3.50 cc (adjusted HR 0.53; 95% CI 0.29-0.95), but not EOR for incompletely resected glioblastomas.

A rare cause of sciatica discovered during digital rectal examination: case report of an intrapelvic sciatic notch schwannoma.

Intrapelvic sciatic nerve schwannomas are rare causes for non-discogenic sciatica. We describe a 44-year-old female who had a palpable mass on digital rectal examination that exhibited a positive Tinel's sign. The schwannoma was excised by a posterior transgluteal approach. Patients with negative spinal imaging should undergo pelvic scanning to rule out these tumors.

Intraventricular urokinase to treat a blocked ventriculoperitoneal shunt in a glioblastoma patient with leptomeningeal spread.

Leptomeningeal spread and hydrocephalus are increasingly recognized as late disease complications of glioblastoma with almost a quarter of patients requiring early cerebrospinal fluid shunting. The neurosurgeon is challenged with maintaining shunt patency when tumor disease progression is rapid and adjuvant oncologic therapy has yet to be initiated. We describe our experience in treating a young female with diffuse glioblastoma leptomeningeal spread and communicating hydrocephalus who had several episodes of shunt obstruction due to intraluminal tumor cell-fibrin deposits. Regular intraventricular instillations of urokinase fibrinolytic therapy not only re-established shunt patency but also contributed to the resolution of her hydrocephalus.

Computed tomography interobserver agreement in the assessment of aneurysmal subarachnoid hemorrhage and predictors for clinical outcome.

BACKGROUND: The severity of aneurysmal subarachnoid hemorrhage (SAH) is often assessed by the clinical state of the patient on presentation, but radiological evaluation of the extent of hemorrhage has rarely been examined in the literature. Several CT scan based grading systems exist yet only a few studies have investigated interobserver agreement. We evaluated five radiological grading systems and assessed their clinical value for early prognostication. METHODOLOGY: This was a retrospective study of patients diagnosed with aneurysmal SAH with a CT scan performed within 72 hours of symptom onset. Four independent observers, blinded to patient outcome, evaluated each scan using the five grading systems. A separate assessor determined 6 month outcome from clinical records. The primary outcome was interobserver agreement for each grading system using the Fleiss κ statistic. The secondary endpoint was the 6 month modified Rankin Scale score, with poor outcome defined as a score of 4-6. RESULTS: 165 patients with a mean age of 59 years were assessed. Interobserver agreement for the Fisher, modified Fisher, Claassen, Barrow Neurological Institute, and Hijdra grading systems were as follows: k=0.53 (moderate), k=0.42 (moderate), k=0.38 (mild), k=0.20 (poor), and k=0.66 (good), respectively. The only independent clinical risk factor for poor outcome was a World Federation of Neurological Surgeons (WFNS) grade of 4 or 5 (adjusted OR 6.55; p<0.05). After adjusting for confounders, Fisher grade 4 (adjusted OR 17.84), modified Fisher grade 4 (adjusted OR 5.65), and Hijdra grade 3 (adjusted OR 3.34) were associated with poor outcome. Receiver operator characteristic analysis revealed that the Hijdra grading system (area under the curve=0.76) was more predictive of outcome compared with the Fisher and modified Fisher systems. A Hijdra cut-off score of 22 was associated with poor outcome (adjusted OR 5.92). CONCLUSIONS: The Hijdra grading system had the best interobserver agreement and was a better independent early predictor for 6 month clinical outcome than the other systems. A Hijdra score ≥22 was associated with poor outcome.