Molecular imaging studies have recently found inter- and intratumoral heterogeneity in World Health Organization (WHO) grade II gliomas. A correlative analysis with tumor histology, however, is still lacking. For elucidation we conducted the current prospective study. Fifty-five adult patients with an MRI-based suspicion of a WHO grade II glioma were included. [F-18]Fluoroethyltyrosine ((18)FET) uptake kinetic studies were combined with frame-based stereotactic localization techniques and used as a guide for stepwise (1-mm steps) histopathological evaluation throughout the tumor space. In tumors with heterogeneous PET findings, the O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and expression of mutated protein isocitrate dehydrogenase variant R132H (IDH1) were determined inside and outside of hot spot volumes. Metabolic imaging revealed 3 subgroups: the homogeneous WHO grade II glioma group (30 patients), the homogeneous malignant glioma group (10 patients), and the heterogeneous group exhibiting both low- and high-grade characteristics at different sites (15 patients). Stepwise evaluation of 373 biopsy samples indicated a strong correlation with analyses of uptake kinetics (p < 0.0001). A homogeneous pattern of uptake kinetics was linked to homogeneous histopathological findings, whereas a heterogeneous pattern was associated with histopathological heterogeneity; hot spots exhibiting malignant glioma characteristics covered 4-44% of the entire tumor volumes. Both MGMT and IDH1 status were identical at different tumor sites and not influenced by heterogeneity. Maps of (18)FET uptake kinetics strongly correlated with histopathology in suspected grade II gliomas. Anaplastic foci can be accurately identified, and this finding has implications for prognostic evaluation and treatment planning.

In suspected grade II gliomas, three distinct patterns of time-activity curves (TAC) on O-(2-[ positron emission tomography (PET) have been delineated (i) increasing TAC homogeneously throughout the tumor, and decreasing TAC, (ii) either homogeneously throughout the tumor or (iii) only focally within otherwise increasing TAC patterns.Increasing TAC was associated with low-grade histology and decreasing TAC with high-grade histology. This prospective study analyzed whether these patterns correlate with distinct biological tumor subtypes and differential outcome. 18 F-FET PET-guided biopsies were used for stepwise histopathological evaluation. Molecular-genetic evaluation included O 6 -methylguanine-DNA methyltransferase (MGMT) promoter methylation, isocitrate dehydrogenase (IDH1/2) mutational and 1p/19q codeletion status. Progression-free survival (PFS) was estimated with the Kaplan-Meier method. Prognostic factors were obtained from multivariate regression models. 98 adult patients were included. Homogeneous increasing, focal decreasing and homogeneous decreasing TAC were seen in 51, 19 and 28 patients. The corresponding 1-year (2-years) PFS were 92% (85%), 89% (51%) and 50% (28%; p 5 0.002). IDH1/2 mutations were more frequent in tumors with homogeneous increasing (90%) and focal decreasing (79%) TAC, but were rare in those exhibiting homogeneous decreasing TAC (25%; p < 0.001). Overall, TAC patterns, IDH1/2 mutational and 1p/19q codeletion status were powerful and independent prognostic factors. Dynamic 18 F-FET PET might be an important and independent imaging biomarker for patients with suspected WHO grade II gliomas and offers perspectives for stratified diagnostic and therapeutic strategies. Tumors with focal decreasing TAC need highly targeted surgical interventions to avoid undergrading and undertreatment.

IntracranIal dural arteriovenous fistulas (DAVFs) are pathological shunts between dural arteries and dural venous sinuses, meningeal veins, or cortical veins. DAVFs account for 10%-15% of intracranial arteriovenous malformations.9 The venous drainage pattern of a DAVF determines its severity and classification according to Borden et al. 1 and Cognard et al. 3 Both of these systems associate cortical venous drainage with increased risk of intracranial hemorrhage and neurological deficits. 2,4,6,7,13,15,16 During the past 2 decades, embolization has become the first-line treatment for DAVFs. In particular, the invention of highly compliant, inflatable occlusion balloons and the Onyx liquid embolic agent (ev3 Neurovascular) opened a new horizon in the endovascular treatment of DAVFs. By temporarily inflating a large-lumen compliant balloon in the diseased sinus compartment during the injection of Onyx into an arterial feeder, this combined sinus-preserving embolization (CSPE) approach is supposed to preserve the natural venous drainage pattern and allow a better penetration of the fistula network by the liquid embolic agent.Transvenous embolization (TVE) is performed by retrograde catheterization of the involved dural sinus or cortical vein, followed by deposition of coils and/or liquid abbreviations CCA = common carotid artery; CCF = carotid cavernous fistula; CSOE = combined sinus-occluding embolization; CSPE = combined sinus-preserving embolization; DAVF = dural arteriovenous fistula; DSA = digital subtraction angiography; ECA = external carotid artery; SO = sinus-occluding; SP = sinus-preserving; TAE = transarterial embolization; TVE = transvenous embolization. methods Clinical symptoms, complication rates, and Cognard grading prior to and after endovascular DAVF treatment using different technical approaches was retrospectively analyzed in 36 patients with lateral DAVF Cognard Types I-IIb. The long-term success rate was determined by a standardized questionnaire. results The SO approaches offered a higher rate of definitive fistula occlusion (93% SO vs 71% SP) but were accompanied by a significantly higher complication rate (33% or 20% SO vs 0% SP). The patients interviewed reported very high satisfaction with their health in long-term follow-up in both groups. conclusions A higher rate of definitive fistula occlusion in the SO group was attained at the price of a significantly higher complication rate. The SP approaches offered a good primary success rate in combination with a very low complication rate. Despite some limitations of the data (e.g., a small sample size) the authors thus recommend an SP variant as the primary therapeutic option for the endovascular treatment of low-and intermediate-grade DAVFs. The SO approaches should be restricted to cases in which SP treatment does not achieve a downgrading to no worse than Cognard Type IIa.http://thejns.org/doi/abs/10.3171/2016.2.JNS152081

TAC measurements constitute a powerful biomarker independent from tumor grade and IDH status.

The number of elderly patients with aneurysmal subarachnoid hemorrhage (SAH) is increasing with the aging of the population. However, management recommendations based on long-term outcome data and analyses of prognostic factors are scarce. Our study focused exclusively on elderly patients aged ≥ 60 years at the onset of SAH. Patients were selected from an in-house database and compared in cohorts of age 60-69, 70-79, and ≥ 80, regarding pre-existing medical conditions, treatment, clinical course including complications, and outcome. A multivariate analysis was conducted to identify prognostic factors for death and disability. A total of 256 patients (138 aged 60-69, 93 aged 70-79, 25 aged ≥ 80) with putative aneurysmal SAH who had been admitted to our hospital between January 1, 1996 and June 30, 2007 were extracted. The median follow-up of our total cohort was 35.5 months (range <1-154 months). Endovascular or conservative aneurysm treatment was applied more often with increasing age (p < 0.006). The 1-year survival rate was 78, 65, and 38 % in the three age groups, respectively (p = 0.0002); most of the patients died from the initial hemorrhage or from medical complications. Patients aged <70 with an initial World Federation of Neurosurgical Societies (WFNS) score of I-III showed the best clinical recovery. WFNS score, age, and clipping/coiling were extracted as prognostic factors from the Cox model. Elderly patients who get admitted with a good WFNS score (I-III) seem to benefit from aggressive treatment whereas caution seems to be warranted particularly in patients ≥ 70 years of age who get admitted in a WFNS score of IV and V because of their limited short- and long-term prognosis.

This study was conducted to determine the risk factors and the clinical impact of intraprocedural aneurysm rupture (IAR) and periprocedural ischemia in the treatment of symptomatic and asymptomatic unruptured intracranial aneurysms (UIAs). A single-center retrospective data analysis of 563 UIAs treated between 2000 and 2010 was conducted. Treatment assignment was made on the basis of individual aneurysmal criteria in an interdisciplinary neurovascular conference with attending neurosurgeons, neuroradiologists and neurologists. In 363 microsurgical and 200 endovascular procedures, the permanent morbidity rate was 4.9 and 6 %. The overall mortality rate was 0.7 %-no procedure-related death occurred in microsurgery, and four patients had fatal outcomes after endovascular treatment. IAR occurred in 34 (9.4 %) microsurgical and 8 (4 %) endovascular procedures (p = 0.03). Risk factors for IAR were age, aneurysm diameter, symptomatic aneurysms, hypertension and smoking in microsurgery. IAR was associated with significantly worse outcome at discharge after microsurgical and at discharge and follow-up after endovascular procedures and was followed by fatal outcome in four endovascular cases. Periprocedural ischemia (12.1 vs. 9 %) resulted in significantly worse outcome in both groups. Risk factors for periprocedural ischemia were IAR during microsurgery, aneurysm diameter, symptomatic aneurysms and smoking in either group. Treatment of UIAs can be conducted with an equivalent low rate of permanent morbidity for clipping and coiling-treatment of symptomatic aneurysms elevates the procedural risk. IAR was less frequent during coiling, but was associated with relevant mortality. IAR and periprocedural ischemia represent significant treatment-associated risks, which should be taken into account in interdisciplinary treatment planning and patient counseling.

Stereotactic bidirectional drainage of cystic craniopharyngiomas is effective and provides a better endocrinological outcome than conventional microsurgery.

Bradykinin (BK) was shown to stimulate the production of physiologically active metabolites, blood-brain barrier disruption, and brain edema. The aim of this prospective study was to measure BK concentrations in blood and cerebrospinal fluid (CSF) of patients with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), and ischemic stroke and to correlate BK levels with the extent of cerebral edema and intracranial pressure (ICP). Blood and CSF samples of 29 patients suffering from acute cerebral lesions (TBI, 7; SAH,: 10; ICH, 8; ischemic stroke, 4) were collected for up to 8 days after insult. Seven patients with lumbar drainage were used as controls. Edema (5-point scale), ICP, and the GCS (Glasgow Coma Score) at the time of sample withdrawal were correlated with BK concentrations. Though all plasma-BK samples were not significantly elevated, CSF-BK levels of all patients were significantly elevated in overall (n=73) and early (≤72 h) measurements (n=55; 4.3±6.9 and 5.6±8.9 fmol/mL), compared to 1.2±0.7 fmol/mL of controls (p=0.05 and 0.006). Within 72 h after ictus, patients suffering from TBI (p=0.01), ICH (p=0.001), and ischemic stroke (p=0.02) showed significant increases. CSF-BK concentrations correlated with extent of edema formation (r=0.53; p<0.001) and with ICP (r=0.49; p<0.001). Our results demonstrate that acute cerebral lesions are associated with increased CSF-BK levels. Especially after TBI, subarachnoid and intracerebral hemorrhage CSF-BK levels correlate with extent of edema evolution and ICP. BK-blocking agents may turn out to be effective remedies in brain injuries.