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Oligodendrogliomas are defined at the molecular level by the presence of an IDH mutation and codeletion of chromosomal arms 1p and 19q. In the past, case reports and small studies described gliomas with sarcomatous features arising from oligodendrogliomas, so called oligosarcomas. Here, we report a series of 24 IDH-mutant oligosarcomas from 23 patients forming a distinct methylation class. The tumors were recurrences from prior oligodendrogliomas or developed de novo. Precursor tumors of 12 oligosarcomas were histologically and molecularly indistinguishable from conventional oligodendrogliomas. Oligosarcoma tumor cells were embedded in a dense network of reticulin fibers, frequently showing p53 accumulation, positivity for SMA and CALD1, loss of OLIG2 and gain of H3K27 trimethylation (H3K27me3) as compared to primary lesions. In 5 oligosarcomas no 1p/19q codeletion was detectable, although it was present in the primary lesions. Copy number neutral LOH was determined as underlying mechanism. Oligosarcomas harbored an increased chromosomal copy number variation load with frequent CDKN2A/B deletions. Proteomic profiling demonstrated oligosarcomas to be highly distinct from conventional CNS WHO grade 3 oligodendrogliomas with consistent evidence for a smooth muscle differentiation. Expression of several tumor suppressors was reduced with NF1 being lost frequently. In contrast, oncogenic YAP1 was aberrantly overexpressed in oligosarcomas. Panel sequencing revealed mutations in NF1 and TP53 along with IDH1/2 and TERT promoter mutations. Survival of patients was significantly poorer for oligosarcomas as first recurrence than for grade 3 oligodendrogliomas as first recurrence. These results establish oligosarcomas as a distinct group of IDH-mutant gliomas differing from conventional oligodendrogliomas on the histologic, epigenetic, proteomic, molecular and clinical level. The diagnosis can be based on the combined presence of (a) sarcomatous histology, (b) IDH-mutation and (c) TERT promoter mutation and/or 1p/19q codeletion, or, in unresolved cases, on its characteristic DNA methylation profile.

Background The aim of this study is to share our experiences on a series of 21 patients with intraventricular meningiomas (IVMs). Histopathologic examinations are reviewed in detail and the cell of origin of IVMs is discussed. Methods We retrospectively reviewed 1372 patients with intracranial meningioma who were surgically treated between September 1986 and July 2018. From this cohort, 21 patients with IVM were identified. The clinical, radiologic, surgical, and follow-up records were analyzed. The archival pathologic specimens were reviewed. Tissue microarray blocks were performed from the formalin-fixed, paraffin-embedded samples of all IVM cases, 2 choroid plexus tissue adjacent to the tumors, and 10 extraventricular fibrous meningioma cases selected as control randomly. Immunohistochemical staining with the antibodies S-100, SOX10, NGFR, and OTX2 was performed according to the protocols indicated by the manufacturers. Results Surgical complications included hemiparesis in 1 patient (5%), postoperative seizure in 1 patient (5%), sensorial aphasia in 1 patient (5%), and preexisting headache in 1 patient (5%). Seventeen (81%) of the IVMs had grade I pathology and 4 (19%) had grade II pathology. The immunoprofile of IVMs is identical to the immunoprofile of normal choroid plexus epithelium. Conclusions Transcortical approaches using intraoperative ultrasonography and intraoperative monitoring with avoidance of eloquent cortical areas can achieve good outcomes. Resection of the choroidal attachments should be attempted. Our results indicate that IVMs do not show arachnoid cap cell phenotype and the findings support that IVMs originate from the choroid plexus epithelium or the progenitors of the choroid plexus epithelium.

Background Meningiomas are heterogeneous, with differences in anatomical, histopathological, and clinical characteristics. Such spatial variability in meningioma biology is thought to result from differences in the expression of critical developmental regulators. We hypothesized that the variability in meningioma biology would follow gradients such as in embryology and tested a cohort of 366 meningiomas for histopathological and immunohistochemical gradients. Methods The medical records from 366 patients treated for meningiomas from 2003 to 2016 were retrospectively analyzed for age, gender, anatomical localization, recurrence-free survival, overall survival, histopathological diagnosis, and immunohistochemistry findings for 6 markers: epithelial membrane antigen (EMA), progesterone receptor (PR), CD34, S100, p53, and Ki-67 labeling index. Results EMA, PR, S100, p53, and CD34 were expressed in 94%, 73%, 49%, 26%, and 23% of the tumors, respectively. p53 expression correlated positively with Ki-67 and World Health Organization (WHO) grade (rτ = 0.31 and rτ = 0.4, respectively). PR positivity correlated inversely with S100, p53, Ki-67, and WHO grade (rτ = −0.19, rτ = −0.14, rτ = −0.15, and rτ = −0.16, respectively). All secretory meningiomas were positive for EMA and PR and negative for S100, and this pattern exhibited a rostrocaudal gradient. The overall proportion of EMA+PR+S100− cases was significantly lower in the cranial vault (30.3%) than in the skull base (45.89%; P = 0.021). The proportion of WHO grade II-III tumors was greater in cranial vault than in skull base meningiomas. Conclusions Unsupervised methods detected an association between the anatomical location and tumor biology in meningiomas. Unlike the categorical associations that former studies had indicated, the present study revealed a rostrocaudal gradient in both the cranial vault and the skull base, correlating with human developmental biology.

Background We and others have identified mutually exclusive molecular subgroups of meningiomas; however, the implications of this classification for clinical prognostication remain unclear. Integrated genomic and epigenomic analyses implicate unique oncogenic processes associated with each subgroup, suggesting the potential for divergent clinical courses. The aim of this study was to understand the associated clinical outcomes of each subgroup, as this could optimize treatment for patients. Methods We analyzed outcome data for 469 meningiomas of known molecular subgroup, including extent of resection, postoperative radiation, surveillance imaging, and time to recurrence, when applicable. Statistical relationships between outcome variables and subgroup were assessed. Features previously associated with recurrence were further investigated after stratification by subgroup. We used Kaplan–Meier analyses to compare progression-free survival, and identified factors significantly associated with recurrence using Cox proportional hazards modeling. Results Meningioma molecular subgroups exhibited divergent clinical courses at 2 years of follow-up, with several aggressive subgroups (NF2, PI3K, HH, tumor necrosis factor receptor–associated factor 7 [TRAF7]) recurring at an average rate of 22 times higher than others (KLF4, POLR2A, SMARCB1). PI3K-activated tumors recurred earlier than other subgroups but had intermediate long-term outcome. Among low-grade tumors, HH and TRAF7 meningiomas exhibited elevated recurrence compared with other subgroups. Recurrence of NF2 tumors was associated with male sex, high grade, and elevated Ki-67. Multivariate analysis identified molecular subgroup as an independent predictor of recurrence, along with grade and previous recurrence. Conclusion We describe distinct clinical outcomes and recurrence rates associated with meningioma molecular subgroups. Our findings emphasize the importance of genomic characterization to guide postoperative management decisions for meningiomas.

Aim Role of extrachromosomal DNA in cancer and the consequences of mutations are unclear. However, mitochondrial DNA (mtDNA) variants in the D-loop region have been suggested to be associated with different clinical parameters and proposed as controversial prognostic markers. Impaired function of mitochondria cannot be tolerated by highly energy requiring brain cells. Therefore, we have focused on the regulatory region D-loop which is thought to cause no growth disadvantage for cells. Our aim is to investigate the effect of mtDNA variants mainly in D-loop on glioma biology. Material and methods Sanger sequencing of D-loop (15971 - 16451 bp) for 52 glioma patients was performed and the variations were statistically analyzed for gender, WHO classification, morphological grade, IDH / TERT status. Results Total of 122 variations (51 unique) was identified in 52 patients. C16223T, T16189C, T16311C and T16126C variants were frequently detected. Total variation number was statistically non-significant among the analyzed categories. When individual variants were considered, T16311C and T16224C were statistically significant for WHO classification (p=0.033), morphological grade (p=0.036) and gender (p=0.039), respectively. Conclusion Total variation number in D-loop was not found to be related with clinical variables. Our data suggests that individual variants may play critical role in glioma biology.

There is a growing interest in noninvasively defining molecular subsets of hemispheric diffuse gliomas based on the isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase gene promoter (TERTp) mutation status, which correspond to distinct tumor entities, and differ in demographics, natural history, treatment response, recurrence, and survival patterns.To investigate whether metabolite levels detected with short echo time (TE) proton MR spectroscopy (Retrospective.In all, 112 hemispheric diffuse gliomas (70 males/42 females, mean age: 42.1 ± 13.9 years).Short-TEMetabolic differences between IDH mutant and IDH wildtype gliomas were assessed by a Mann-Whitney U-test. A Kruskal-Wallis test followed by a Tukey-Kramer test was used to analyze metabolic differences between IDH and TERTp mutational molecular subsets of gliomas. A Spearman rank correlation coefficient was used to assess the correlations of metabolite intensities with the Ki-67 index. Furthermore, machine learning was employed to classify the IDH and TERTp mutational status of gliomas, and the accuracy, sensitivity, and specificity values were estimated.Short-TEShort-TE3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1799-1809.

Background Improved life expectancy and advanced diagnostic tools including computed tomography and magnetic resonance imaging have increased the awareness and diagnosis of intracranial meningiomas in the elderly population. The risk/benefit ratio of surgery in elderly patients with intracranial meningioma has not been clearly defined because of the lack of objective measurement tools. We aimed to understand the risk factors associated with postsurgical outcomes and how these risk factors affected postsurgical outcomes in elderly patients with intracranial meningioma. Methods We retrospectively evaluated 1372 patients, who were operated on for intracranial meningioma, using our prospectively collected database. The same senior author operated on all patients at 2 different tertiary clinics. Patients' clinical charts, presurgical postcontrast T1-weighted magnetic resonance images, operative reports, and pathology reports were reviewed. The relevant literature was also reviewed. Results Higher age, higher American Society of Anesthesiologists class, presence of comorbidities, tumor location, larger initial tumor size, and presence of peritumoral edema were all associated with postsurgical complications in elderly patients with intracranial meningioma. Age ≥50 years was the strongest predictor of postsurgical systemic complications, whereas higher American Society of Anesthesiologists class was the strongest predictor of postsurgical neurologic complications. A literature review showed higher morbidity and mortality of elderly patients with intracranial meningioma. Initial tumor size and postsurgical MIB-1 labeling index were higher in the elderly patients, both of which were predictors of tumor growth. Conclusions Even though elderly patients operated on for intracranial meningioma had higher morbidity and mortality compared with younger patients, surgery is still much more beneficial than wait-and-see strategy in elderly patients.

Objective Sphenoid wing meningiomas are the third most common group of intracranial meningiomas. Their management is a challenge because of their bone invasion potential and their proximity to neurovascular structures and the cavernous sinus. Methods A cohort of 141 patients with sphenoid wing meningioma who were operated on and followed up between 1986 and 2018 were retrospectively analyzed. Demographic data, clinical and radiologic features, surgical results, and follow-up data are presented. The effects of adjuvant treatments (radiosurgery, radiotherapy, and chemotherapy) are reviewed. The invasion pattern of tumors and other factors were noted to analyze the extent of resection. Recurrence/regrowth rates were also analyzed. Results There were 96 female and 45 male patients with a median age of 51 years (range, 17–87 years). The median follow-up was 62 months (range, 1–303 months). Tumors were grouped as spheno-orbital (31 patients), lateral (34 patients), middle (35 patients), and medial (41 patients). Gross total resection was achieved in 98 patients, and 43 tumors were resected subtotally. One hundred and twenty of these cases had World Health Organization grade I pathology, whereas the remainder had grade II. In the follow-up, there were 14 recurrences of totally resected tumors, and 24 regrowths were observed in the subtotally resected group. No invasion pattern was strongly predictive of extent of resection alone, and a scoring system was built up and proposed. Conclusions Sphenoid wing meningioma is a large group with characteristics associated with skull base meningiomas and convexity meningiomas. The results of surgery and other adjuvant treatments are heterogeneous.

OBJECTIVERecent studies have established that hemispheric diffuse gliomas may be grouped into subsets on the basis of molecular markers; these subsets are loosely correlated with the histopathological diagnosis but are strong predictors of clinical tumor behavior. Based on an analysis of molecular and clinical parameters, the authors hypothesized that mutations of the telomerase promoter (TERTp-mut) mark separate oncogenic programs among isocitrate dehydrogenase 1 and/or 2 (IDH) mutant (IDH-mut) and IDH wild-type (IDH-wt) diffuse gliomas independent of histopathology or WHO grade.METHODSFour molecular subsets of the combined statuses of IDH and TERT-promoter mutations (double mutant, IDH only, TERT only, and double negative) were defined. Differences in age, anatomical location, molecular genetics, and survival rates in a surgical cohort of 299 patients with a total of 356 hemispheric diffuse gliomas (WHO Grade II, III, or IV) were analyzed.RESULTSTERTp-mut were present in 38.8% of IDH-mut and 70.2% of IDH-wt gliomas. The mutational status was stable in each patient at 57 recurrence events over a 2645-month cumulative follow-up period. Among patients with IDH-mut gliomas, those in the double-mutant subset had better survival and a lower incidence of malignant degeneration than those in the IDH-only subset. Of patients in the double-mutant subset, 96.3% were also positive for 1p/19q codeletions. All patients with 1p/19q codeletions had TERTp-mut. In patients with IDH-mut glioma, epidermal growth factor receptor or phosphatase and tensin homolog mutations were not observed, and copy-number variations were uncommon. Among IDH-wt gliomas, the TERT-only subset was associated with significantly higher age, higher Ki-67 labeling index, primary glioblastoma-specific oncogenic changes, and poor survival. The double-negative subset was genetically and biologically heterogeneous. Survival analyses (Kaplan-Meier, multivariate, and regression-tree analyses) confirmed that patients in the 4 molecular subsets had distinct prognoses.CONCLUSIONSMolecular subsets result in different tumor biology and clinical behaviors in hemispheric diffuse gliomas.

Objective Clinical characteristics and management of hemangioblastomas of the spinal cord associated with von Hippel-Lindau syndrome have been extensively covered in the literature. This report aims to analyze the characteristics and surgical treatment results of sporadic spinal hemangioblastomas (SSHB). Methods This is a retrospective analysis of 14 patients with SSHB (8 men and 6 women) operated on during a span of 23 years. The median age was 41.5 years (24–70 years). von Hippel Lindau syndrome was excluded by imaging in all patients. The median follow-up was 4 years (1–23 years). We also conducted a meta-analysis of all 271 SSHB cases reported in the English-speaking language literature from 1967 to 2011. Results Nine (64.3%) lesions were cervical, 3 (28.5%) were thoracic, and 1 (7.1%) was lumbar. Eight (57.1%) tumors were dorsal intramedullary, 4 (28.6%) were exophytic, 1 (7.1%) was intradural extramedullary, and 1 (7.1%) was completely extradural. Diffuse segmental cord enlargement was present in 7 patients (50%) and a cyst/syrinx was present in 7 (50%). These 14 patients underwent 15 operations, and gross total resection was achieved in all operations. There was no mortality. Symptoms improved after 8 (53.3%) of 15 operations, remained the same after 5 (33.3%), and worsened after 2 (13.3%). The mean Karnofsky performance score improved from 79.3 (± 17.5) to 87.3 (± 12.2) after 6 months of follow-up. There was one recurrence 15 years after magnetic resonance imaging confirmed total resection. Conclusions The SSHBs occur most often in the upper spinal cord. Excellent surgical results and long-term outcome can be achieved using microsurgery alone with only rare recurrences.

The single nucleotide polymorphism rs55705857, located in a non-coding but evolutionarily conserved region at 8q24.21, is strongly associated with IDH-mutant glioma development and was suggested to be a causal variant. However, the molecular mechanism underlying this association has remained unknown. With a case control study in 285 gliomas, 316 healthy controls, 380 systemic cancers, 31 other CNS-tumors, and 120 IDH-mutant cartilaginous tumors, we identified that the association was specific to IDH-mutant gliomas. Odds-ratios were 9.25 (5.17–16.52; 95% CI) for IDH-mutated gliomas and 12.85 (5.94–27.83; 95% CI) for IDH-mutated, 1p/19q co-deleted gliomas. Decreasing strength with increasing anaplasia implied a modulatory effect. No somatic mutations were noted at this locus in 114 blood-tumor pairs, nor was there a copy number difference between risk-allele and only-ancestral allele carriers. CCDC26 RNA-expression was rare and not different between the two groups. There were only minor subtype-specific differences in common glioma driver genes. RNA sequencing and LC-MS/MS comparisons pointed to significantly altered MYC-signaling. Baseline enhancer activity of the conserved region specifically on the MYC promoter and its further positive modulation by the SNP risk-allele was shown in vitro. Our findings implicate MYC deregulation as the underlying cause of the observed association., Scientific Reports, 6, ISSN:2045-2322

AIM: Olfactory groove meningiomas make up 4 to 13\% of meningiomas. The first line treatment of meningiomas is surgery, but the extent and types of approaches advised for olfactory groove meningiomas are diverse, from aggressive skull base approaches to standard or minimally invasive craniotomies and endoscopic approaches. We retrospectively reviewed our series of olfactory groove meningiomas that were operated microsurgically by standard pterional or unifrontal approaches. MATERIAL and METHODS: Our series of 61 olfactory groove meningioma patients operated through pterional or unifrontal approaches between March 1987 and September 2015 was reviewed and the clinical data, radiological findings, surgical treatment and clinical outcomes of the patients were retrospectively analyzed. RESULTS: Sixty-three craniotomies were performed in total. Pterional and unifrontal approaches were used in 38 (60.3\%) and 25 (39.7\%) surgical procedures, respectively. Overall, gross total tumor resection was achieved in 59 (93.7\%) cases. Complications were seen in 8 cases, and 2 of these patients underwent reoperation. Three of the 4 patients where only subtotal resection could be achieved underwent gamma knife radiosurgery. CONCLUSION: Pterional and unifrontal approaches, which are familiar and standard for neurosurgeons, can accomplish high rates of total resection with acceptable complication and recurrence rates for the treatment of olfactory groove meningiomas.

Background. Current literature on tuberculum sellae meningiomas is very heterogenous due to wide variation in nomenclature, diagnostic and operative techniques. The aim of this study is specifically to analyze the results of pterional craniotomy for tuberculum sellae meningiomas. A homogenous cohort of 42 consecutively operated tuberculum sellae meningioma cases are reviewed with special emphasis on the effects of pterional microsurgery on visual outcome. Methods. This is a retrospective clinical analysis. 42 consecutive patients operated upon during the period of 15 years in a single institution using standard imaging protocols and pterional microsurgery are presented and effect of various variables on visual outcome analysed. Findings. 81% of the patients presented with visual symptoms. The mean duration of symptoms was 12 months. Tumour volumes ranged from 7.5 to 210 mm3. A right sided pterional microsurgery was used in all patients. Complete resection rate was 81%. Vision improved in 58%, worsened in 14%. Non-visual morbidity was 7.1% and mortality was 2.4%. The follow up period of patients ranged from 3 to 192 months (median: 30 months). The mean was 37.5 months (SD = ±36.7 months) and a recurrence rate of 2.4% was observed. Conclusions. A standard pterional craniotomy using microsurgical technique provides the necessary exposure enabling total removal while keeping the complications to a minimum. Upon analysis of our findings we found that patient age of more than 60, duration of visual symptoms longer than 1 year, severe visual symptomatology, predominantly vertical growth, presence of significant peri-tumoural oedema, absence of an intact arachnoid plane and subtotal removal were correlated with a dismal visual outcome.

BACKGROUND: DR-70 is an immunoassay for fibrin and FDP in plasma and it has been shown useful in detection of over 14 different cancers. This study investigated the validity of the DR-70 test in gliomas as well as meningiomas. METHODS: 77 brain tumor patients as well as 40 healthy individuals were prospectively included in the study and investigated using DR-70 kit. The glioma cohort of 33 patients consisted of 1, 11, 6 and 15 WHO grade 1, 2, 3 and 4 gliomas, respectively. The meningioma cohort of 44 patients contained 38, 5 and 1 WHO grade 1, 2 and 3 tumors. RESULTS: Test results were significantly higher than control values for both gliomas and meningiomas. The most balanced sensitivity and specificity values were obtained at cut-off level of 0.5 µg/ml FDP for both gliomas and meningiomas. Above this cutoff level the relative-risk for having a glioma was 5.1 times higher compared to controls with sensitivity and specificity of 76% and 85%, respectively. The relative-risk for meningioma was 5.8 with a sensitivity and specificity of 87% and 85%, respectively. CONCLUSION: FDP testing, which is a nonspecific cancer screening tool, is sensitive to the two most common primary brain malignancies, gliomas and meningiomas.

The goal of surgery in high-grade gliomas is to maximize the resection of contrast-enhancing tumor without causing additional neurological deficits. Intraoperative MRI improves surgical results. However, when using contrast material intraoperatively, it may be difficult to differentiate between surgically induced enhancement and residual tumor. The purpose of this study was to assess the usefulness of intraoperative dynamic contrast-enhanced T1-weighted MRI to guide this differential diagnosis and test it against tissue histopathology.Preoperative and intraoperative dynamic contrast-enhanced MRI was performed in 21 patients with histopathologically confirmed WHO Grade IV gliomas using intraoperative 3-T MRI. Standardized regions of interest (ROIs) were placed manually at 2 separate contrast-enhancing areas at the resection border for each patient. Time-intensity curves (TICs) were generated for each ROI. All ROIs were biopsied and the TIC types were compared with histopathological results. Pharmacokinetic modeling was performed in the last 10 patients to confirm nonparametric TIC analysis findings.Of the 42 manually selected ROIs in 21 patients, 25 (59.5%) contained solid tumor tissue and 17 (40.5%) retained the brain parenchymal architecture but contained infiltrating tumor cells. Time-intensity curves generated from residual contrast-enhancing tumor and their preoperative counterparts were comparable and showed a quick and persistently increasing slope ("climbing type"). All 17 TICs obtained from regions that did not contain solid tumor tissue were undulating and low in amplitude, compared with those obtained from residual tumors ("low-amplitude type"). Pharmacokinetic findings using the transfer constant, extravascular extracellular volume fraction, rate constant, and initial area under the curve parameters were significantly different for the tumor mass, nontumoral regions, and surgically induced contrast-enhancing areas.Intraoperative dynamic contrast-enhanced MRI provides quick, reproducible, high-quality, and simply interpreted dynamic MR images in the intraoperative setting and can aid in differentiating surgically induced enhancement from residual tumor.

Genetic Clues to Meningioma Meningiomas are the most common primary brain tumors in adults. Located within the layer of tissue covering the brain, these tumors are usually slow-growing and benign but can cause serious neurological complications. About half of these tumors have mutations in the neurofibromin 2 gene ( NF2 ). To identify other genes that contribute to meningioma pathogenesis, Clark et al. (p. 1077 , published online 24 January) performed genome sequence analysis on 300 tumors. Meningiomas fell into two general classes: benign tumors located at the skull base—which tend to harbor mutations in the TRAF7, KLF4, AKT1 , and SMO genes—and higher-grade tumors located in the cerebral and cerebellar hemispheres harbor mutations in NF2.

Object The authors had previously shown that 3-T intraoperative MRI (ioMRI) detects residual tumor tissue during low-grade glioma and that it helps to increase the extent of resection. In a proportion of their cases, however, the ioMRI disclosed T2-hyperintense areas at the tumor resection border after the initial resection attempt and prompted a differential diagnosis between residual tumor and nontumoral changes. To guide this differential diagnosis the authors used intraoperative long-TE single-voxel proton MR spectroscopy (ioMRS) and tested the correlation of these findings with findings from pathological examination of resected tissue. Methods Patients who were undergoing surgery for hemispheric or insular WHO Grade II gliomas and were found to have T2 changes around the resection cavity at the initial ioMRI were prospectively examined with ioMRS and biopsies were taken from corresponding localizations. In 14 consecutive patients, the ioMRS diagnosis in 20 voxels of interest was tested against the histopathological diagnosis. Intraoperative diffusion-weighted imaging (ioDWI) was also performed, as a part of the routine imaging, to rule out surgically induced changes, which could also appear as T2 hyperintensity. Results Presence of tumor was documented in 14 (70%) of the 20 T2-hyperintense areas by histopathological examination. The sensitivity of ioMRS for identifying residual tumor was 85.7%, the specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 75%. The specificity of ioDWI for surgically induced changes was high (100%), but the sensitivity was only 60%. Conclusions This is the first clinical series to indicate that ioMRS can be used to differentiate residual tumor from nontumoral changes around the resection cavity, with high sensitivity and specificity.

Anterior clinoidal meningiomas are considered different from meningiomas of the medial sphenoid wing, but there is still some confusion about identification. The current classification scheme only considers tumour origin and invasion pattern around the clinoid process as indicators of resectability. However, the size of the tumour has important effects on surgical outcome. The purpose of this study was to analyze our clinical experience with anterior clinoidal meningiomas and refine the current classification scheme.Forty-three consecutive cases of anterior clinoidal meningioma were retrospectively analyzed. All were surgically treated at the Marmara University Department of Neurosurgery, the Marmara University Institute for Neurological Sciences, and the Department of Neurosurgery at Acibadem Hospital between 1987 and 2006. A pterional approach was used in all cases.The mean tumour volume was 34.2 +/- 46.6 cc. Sixteen (37.2%) of the tumours were giant (largest diameter4 cm). Total surgical removal was achieved in 39 cases (90.7%) and subtotal removal in 4 cases (9.3%). Eight patients (18.6%) developed early postoperative complications. The median and range of follow-up time was 39, R = 99 (3, 102) months. Four (9.3%) of the 43 tumours recurred during follow-up and were treated with radiosurgery.Anterior clinoidal meningioma is a separate disease entity from other meningiomas of the medial third of the sphenoid wing. Relatively good outcomes can be stated in this specific subgroup if growth criteria competable with true diagnosis are fulfilled. Size should be incorporated into any classification scheme for determining clinical and surgical risk. The standard pterional approach is sufficient for removing anterior clinoidal meningiomas.

Chordomas and chondrosarcomas are malignant tumors that are reported to have similar clinical presentations and radiological features but different behaviors and outcomes. The aim of this retrospective study was to determine whether specific radiological features of skull-base chordomas or chondrosarcomas are correlated with histopathology, and thus allow preoperative diagnosis. The study involved 32 classic chordomas, 6 chondroid chordomas and 4 chondrosarcomas (42 tumors total). For each case, tumor size and extent, the detailed anatomy involved, and magnetic resonance imaging and computed tomography findings were analyzed. Tumor extent was assessed using a novel method that assessed presence/absence in 18 defined skull-base zones. The chondrosarcomas presented significantly earlier in life than the chordomas (means, 20.5 years versus 36 years, respectively). At time of diagnosis, the median tumor volume was 23 cm(3) (range, 1.2-78.8 cm(3)) and the mean tumor extent was 6.7+/-2.9 zones. There were no differences between chordomas and chondrosarcomas, or between the two chordoma subgroups, with respect to lesion volume or extent. Comparison of other imaging findings revealed no features that were diagnostic for either chordoma or chondrosarcoma. The data support previous claims that chondrosarcomas present earlier in life than chordomas, but this finding is not diagnostic. There is wide variation in the extent of skull-base chordomas and chondrosarcomas, and in the specific anatomical structures these tumors involve. None of the MRI or CT features of these tumors appear to be useful for differentiating chordomas from chondrosarcomas preoperatively. For surgical planning, specific, area-oriented definition of tumor extent might provide more useful information than tumor-type classification schemes.

The popularisation of cavernous sinus approaches and subsequent experience has shaped our treatment paradigms for cavernous sinus meningiomas. However, pathologies in this region are diverse and each one requires individual consideration. The purpose of this study was first to analyse, define and summarise the individual characteristics of different non-meningeal tumours of the cavernous sinus and, secondly, to stress that their surgery can be accomplished with acceptable morbidity and rewarding results when those characteristics are considered. A retrospective analysis of 42 cases of benign non-meningeal tumours of the cavernous sinus operated on at Marmara University between April 1992 and April 2003 is presented. The patients were 15 males and 27 females aged 24-72 years. The study cohort consisted of 13 pituitary adenomas, 11 trigeminal schwannomas, seven chordomas, three chondrosarcomas, two juvenile angiofibromas, two epidermoid tumours, one plasmacytoma, one cavernous haemangioma and one internal carotid plexus schwannoma. The 42 patients underwent 46 operations aimed at radical surgical excision. Total resection was achieved in 50% and subtotal resection in 50% of cases. The majority of incompletely resected tumours were pituitary adenomas and chordomas, and 95% required further treatment. Twenty-nine percent of patients developed complications, namely cerebrospinal fluid fistula, haematoma, hydrocephalus, diabetes insipidus, cerebral infarction and cranial nerve palsies. Recurrence was seen in 7.1% of patients. At final follow up at an average of 48.2 months after surgery, the mean Karnofsky performance scale had risen from 83.4 to 87.4. Non-meningeal tumours of the cavernous sinus can be surgically resected with acceptable morbidity and mortality. In selected tumours the results are better than those for cavernous sinus meningiomas. The best surgical results are achieved with interdural tumours of the lateral sinus wall and the worst surgical results are seen in invasive tumours such as chordomas and pituitary adenomas. Individual tumour characteristics are presented in the text.

Secondary hemifacial spasm due to vestibular schwannoma is very rare. This is the first reported case of hemifacial spasm responsive to gamma knife radiosurgery in a patient with an intracanalicular vestibular schwannoma. Both the resolution of the spasm as well as tumor growth control were achieved with a single session of gamma knife radiosurgery. We report a 49-year-old male patient with a 6-month history of right-sided hearing loss and hemifacial spasm. MR examination revealed an intracanalicular vestibular schwannoma. The patient was treated with radiosurgery and received 13 Gy to the 50 % isodose line. Tumor growth control was achieved and no change in the tumor volume was present at the last follow-up at 22 months. The hemifacial spasm completely resolved after one year. Surgical removal of the presumably causative mass lesion has been reported to be the sole treatment in secondary hemifacial spasm. This case report indicates that it may be responsive to gamma knife radiosurgery. Whether or not this might be a treatment option in selected refractory cases of hemifacial spasm remains to be defined.

Despite the introduction of skull base approaches, there is still controversy in the optimum surgical management of foramen magnum meningiomas. Between January 1990 and January 2003, 22 patients underwent 23 surgical procedures with a diagnosis of foramen magnum meningioma at Marmara University, Department of Neurosurgery. The suboccipital approach was used for 2 posteriorly located tumors with radiological total removal. The paramedian suboccipital approach was replaced by the far-lateral modification in the treatment of ventral meningiomas. 1 of the 20 ventral tumors was operated twice. The classical suboccipital approach was followed by the far-lateral modification. A gross-total removal was achieved in 21 patients. The overall morbidity was 32%. No specific and clinically significant complications attributable to the far-lateral modification were observed. The far-lateral approach has improved the success of surgery in ventrally located lesions. The posterior suboccipital approach is still indicated in the removal of lesions placed posterior to the dentate ligament.

The aim of this study is to determine the impact of surgery on tumor progression and malignant degeneration in hemispheric diffuse astrocytoma WHO grade II. Twenty-eight patients who were operated or underwent stereotactic biopsy for hemispheric diffuse astrocytoma WHO grade II at Marmara University between January 1987 and January 1996, were prospectively reviewed for the presence of recurrence and histopathological dedifferentiation at their fourth years after the initial treatment. Twenty-two patients underwent surgical resection. Of this group, 7 patients had a total, 11 had a subtotal and 4 patients had a partial resection. Six patients underwent stereotactic biopsy. All patients, except for the ones in whom a radiological total surgical removal could be achieved, received postoperative radiotherapy. In the total surgical-removal group only one patient had recurrence, while no upgrade was noted. All of the patients in the partial resection and stereotactic biopsy groups recurred at a higher grade. Our results indicate that both tumor progression and histopathological dedifferentiation were less commonly seen when a total or subtotal resection could be achieved. So, surgery, as radical as possible, should be the choice of treatment in low-grade hemispheric astrocytomas.

Schwannomas of the trochlear nerve are very rare. Only 25 cases without associated neurofibromatosis were reported in the literature, only 15 of which were surgically verified. We report an unusual case of a 31-year-old man who presented with isolated unilateral trochlear nerve palsy due to a left sided trochlear nerve schwannoma. The tumor was totally resected without additional morbidity using an infratentorial lateral supracerebellar approach.

Summary: Purpose: We have developed and characterized a novel model of epileptogenesis based on the convulsive actions of flurothyl in mice. The hallmark feature of this model is a reliable change in the type of seizure expressed in response to flurothyl from generalized clonic to generalized tonic seizures. The purpose of our study was to evaluate the effects of chronic administration of valproate (VPA), phenytoin (PHT), and MK-801 on the change in seizure phenotype observed in our model system. Methods: Male C57BL/6J mice received flurothyl seizures on 8 consecutive days. Two hours after the last generalized seizure, chronic drug or vehicle was administered twice daily at 12-h intervals for 28 days. The drugs evaluated were VPA (250 mg/kg), PHT (30 mg/kg), and MK-801 (0.5 mg/kg). After a 7-day drug washout period, mice were retested with flurothyl. Results: Among uninjected or vehicle-injected control mice, there was a significant increase in the proportion of animals expressing tonic seizures after the 28-day stimulation-free interval. Chronic administration of VPA or MK-801, but not PHT, blocked the characteristic change in seizure type from clonic to tonic. Conclusions: The change in seizure phenotype observed after exposure to our paradigm indicates a fundamental reorganization in the propagation of flurothyl-initiated seizures. As in electrical kindling, VPA and MK-801 are effective at blocking or retarding the reorganization, whereas PHT is not. The concordance in pharmacologic profiles between kindling and our model suggests that the processes underlying changes in seizure susceptibility in these two models share mechanisms in common.