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PURPOSE: The reliability and reproducibility of T2-weighted imaging/fluid-attenuated inversion recovery (T2/FLAIR) mismatch were investigated in the diagnosis of isocitrate dehydrogenase (IDH) mutant astrocytoma between WHO grade II and III diffuse hemispheric gliomas. METHODS: WHO grade II and grade III diffuse hemispheric gliomas (n=133) treated in our institute were included in the study. Pathological findings and molecular markers of the cases were reviewed with the criteria of WHO 2016. The finding of mismatch between T2-weighted and FLAIR images in preoperative magnetic resonance imaging (MRI) of the cases was evaluated by two different radiologists. The readers reviewed MRIs independently, blinded to the histopathologic diagnosis or molecular subset of tumors. The cases were classified as IDH-mutant astrocytoma, oligodendroglioma and IDH-wildtype (IDH-wt) astrocytoma according to molecular and genetic features. RESULTS: T2/FLAIR mismatch positivity was observed in 46 patients (34.6%). T2/FLAIR mismatch positivity was observed in 42 of 75 IDH-mutant astrocytomas (56%) and 4 of 43 oligodendrogliomas (9.30%), while it was not seen among IDH-wt astrocytomas (0/15, 0%). The T2/FLAIR mismatch ratio was significantly different between IDH-mutant astrocytomas (WHO grade II and grade III) and oligodendrogliomas (chi-square, p

OBJECTIVE Gliomas frequently involve the insula both primarily and secondarily by invasion. Despite the high connectivity of the human insula, gliomas do not spread randomly to or from the insula but follow stereotypical anatomical involvement patterns. In the majority of cases, these patterns correspond to the intrinsic connectivity of the limbic system, except for tumors with aggressive biology. On the basis of these observations, the authors hypothesized that these different involvement patterns may be correlated with distinct outcomes and analyzed these correlations in an institutional cohort. METHODS Fifty-nine patients who had undergone surgery for insular diffuse gliomas and had complete demographic, pre- and postoperative imaging, pathology, molecular genetics, and clinical follow-up data were included in the analysis (median age 37 years, range 21–71 years, M/F ratio 1.68). Patients with gliomatosis and those with only minor involvement of the insula were excluded. The presence of T2-hyperintense tumor infiltration was evaluated in 12 anatomical structures. Hierarchical biclustering was used to identify co-involved structures, and the findings were correlated with established functional anatomy knowledge. Overall survival was evaluated using Kaplan-Meier and Cox proportional hazards regression analysis (17 parameters). RESULTS The tumors involved the anterior insula (98.3%), posterior insula (67.8%), temporal operculum (47.5%), amygdala (42.4%), frontal operculum (40.7%), temporal pole (39%), parolfactory area (35.6%), hypothalamus (23.7%), hippocampus (16.9%), thalamus (6.8%), striatum (5.1%), and cingulate gyrus (3.4%). A mean 4.2 ± 2.6 structures were involved. On the basis of hierarchical biclustering, 7 involvement patterns were identified and correlated with cortical functional anatomy (pure insular [11.9%], olfactocentric [15.3%], olfactoopercular [33.9%], operculoinsular [15.3%], striatoinsular [3.4%], translimbic [11.9%], and multifocal [8.5%] patterns). Cox regression identified hippocampal involvement (p = 0.006) and postoperative tumor volume (p = 0.027) as significant negative independent prognosticators of overall survival and extent of resection (p = 0.015) as a significant positive independent prognosticator. CONCLUSIONS The study findings indicate that insular gliomas primarily involve the olfactocentric limbic girdle and that involvement in the hippocampocentric limbic girdle is associated with a worse prognosis.

Background 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. Purpose To investigate whether metabolite levels detected with short echo time (TE) proton MR spectroscopy (1 H-MRS) at 3T can be used for noninvasive molecular classification of IDH and TERTp mutation-based subsets of gliomas. Study type Retrospective. Subjects In all, 112 hemispheric diffuse gliomas (70 males/42 females, mean age: 42.1 ± 13.9 years). Field strength/sequence Short-TE 1 H-MRS (repetition time (TR) = 2000 msec, TE = 30 msec, number of signal averages = 192) and routine clinical brain tumor MR protocols were acquired at 3T. Assessment 1 H-MRS data were quantified using LCModel software. TERTp and IDH1 or IDH2 (IDH1/2) mutations in the tissue were determined by either minisequencing or Sanger sequencing. Statistical tests Metabolic 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. Results Short-TE 1 H-MRS classified the presence of an IDH mutation with 88.39% accuracy, 76.92% sensitivity, and 94.52% specificity, and a TERTp mutation within primary IDH wildtype gliomas with 92.59% accuracy, 83.33% sensitivity, and 95.24% specificity. Data conclusion Short-TE 1 H-MRS could be used to identify molecular subsets of hemispheric diffuse gliomas corresponding to IDH and TERTp mutations. Level of evidence 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1799-1809.

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.

Background In the clinical setting, workflows for analyzing individual genomics data should be both comprehensive and convenient for clinical interpretation. In an effort for comprehensiveness and practicality, we attempted to create a clinical individual whole exome sequencing (WES) analysis workflow, allowing identification of genomic alterations and presentation of neurooncologically-relevant findings. Methods The analysis workflow detects germline and somatic variants and presents: (1) germline variants, (2) somatic short variants, (3) tumor mutational burden (TMB), (4) microsatellite instability (MSI), (5) somatic copy number alterations (SCNA), (6) SCNA burden, (7) loss of heterozygosity, (8) genes with double-hit, (9) mutational signatures, and (10) pathway enrichment analyses. Using the workflow, 58 WES analyses from matched blood and tumor samples of 52 patients were analyzed: 47 primary and 11 recurrent diffuse gliomas. Results The median mean read depths were 199.88 for tumor and 110.955 for normal samples. For germline variants, a median of 22 (14–33) variants per patient was reported. There was a median of 6 (0–590) reported somatic short variants per tumor. A median of 19 (0–94) broad SCNAs and a median of 6 (0–12) gene-level SCNAs were reported per tumor. The gene with the most frequent somatic short variants was TP53 (41.38%). The most frequent chromosome-/arm-level SCNA events were chr7 amplification, chr22q loss, and chr10 loss. TMB in primary gliomas were significantly lower than in recurrent tumors (p = 0.002). MSI incidence was low (6.9%). Conclusions We demonstrate that WES can be practically and efficiently utilized for clinical analysis of individual brain tumors. The results display that NOTATES produces clinically relevant results in a concise but exhaustive manner.

Gamma knife radiosurgery (GKRS) delivers an unevenly distributed radiation dose to a tumor, with a sharp falloff outside the target. Although the dose inhomogeneity within a tumor is strongly influenced by its shape, routine GKRS dose planning does not account for it. We hypothesized that shape irregularity measures were correlated with treatment planning indices, and might provide insight during treatment planning. The aims of this study were to quantify the shape irregularity measures in vestibular schwannomas, estimate their correlations with core radiosurgical planning measures, and define the most predictive shape feature for dose effectiveness. METHODS: Four dose plan indices, which were the selectivity index (SI), gradient index (GI), efficiency index (EI), and Paddick’s conformity index (PCI) were estimated from the GKRS plans of 234 vestibular schwannomas. All dose plans were prepared using Gamma Plan 10.0 and above and all treatments were delivered using a perfexion/ICON platform. Three-dimensional (3D) tumor models were rendered using 3D Slicer Software from segmented T1-weighted MR images. Sixteen irregularity measures were calculated for each tumor using Radiomics in MATLAB. Spearman correlation coefficients (r) were computed to find associations of the dose plan indices with the irregularity descriptors. The most predictive shape feature for dose efficiency was identified using the least absolute shrinkage and selection operator (Lasso). RESULTS: The shape irregularity measures were negatively correlated with SI, EI, and PCI, and positively correlated with GI. Volumetric index of sphericity (VioS) had the highest correlations with SI (r = 0.63, p= 3.27E-23), GI (r= -0.58, p= 1.10E-19), EI (r = 0.69, p= 0.00), and PCI(r= 0.68, p = 6.73E-28), and Lasso feature selection identified VioS as the most important feature for predicting all dose plan indices. CONCLUSION: VioS provides a numerical quantification of tumor shape irregularity, and it is highly correlated with the GKRS dose planning indices. *indicates co-senior authors

The incidence of meningiomas is rising and the number of incidental cases is increasing steadily. The efficiency and the safety of each treatment strategy are also improving over time. Therefore the indications to treat meningiomas are constantly changing. The aim of meningioma treatment is keeping the patient fully functional while achieving long-term relief or prevention from problems related to intracranial tumor growth. This chapter reviews the natural history and treatment results and aims to put together the information for the most objective decision-making in treating meningiomas. Factors acting on the treatment decision such as anatomical localization, symptomatology, variations in tumor biology, recurrence status, age and co-morbidities, operative gains, and patient preference are individually discussed.

Up to 80% of meningiomas are classified as clinically low-grade, however, a subset of these ‘benign’ cases will ultimately recur and require additional treatment. The role of molecular subgroup in meningioma recurrence has not been thoroughly investigated, despite correlations of this variable with other clinical features. Indeed, epigenetic and transcriptional evidence supports involvement of distinct oncogenic processes within each subgroup, and as shown in other brain tumors, this may result in divergent clinical courses. In the present study, we classified 429 meningiomas into six established molecular subgroups based on genomic driver, and investigated associations of each subgroup with tumor recurrence. At two years of follow-up, we observed differences in progression free survival curves among relatively aggressive (NF2-loss, PI3K-activated, Hedgehog-activated) and quiescent (KLF4-mutant, SMARCB1-mutant, POLR2A-mutant) subgroups (log rank p = 4.3 x 10-2), with the former group recurring at a rate 14x higher. We found PI3K-activated meningiomas recurred significantly earlier than other subgroups (average time to recurrence of 19.2 months; p = 2.2 x 10-2), though we observed an intermediate long-term outcome relative to the Hedgehog and NF2 lesions. Overall, Hedgehog tumors recurred significantly more frequently than other low-grade meningiomas (adj. p = 3.1 x 10-2), and this subgroup was found to be an independent predictor of progression free survival using cox proportional hazards modelling (HR = 3.1; p = 2.4 x 10-2). By contrast, the aggressiveness of NF2 meningiomas was found to depend upon gender, WHO grade, and elevated Ki-67 index, and this subgroup was not an independent prognostic predictor. Our results suggest molecular subgroup is predictive of recurrence in low-grade meningiomas, and thus is an important consideration in post-operative management decisions. Routine genotyping to detect Hedgehog and PI3K mutant lesions may identify patients that would benefit from closer follow-up and consideration of adjuvant therapies.

OBJECTIVERecent large-cohort sequencing studies have investigated the genomic landscape of meningiomas, identifying somatic coding alterations in NF2, SMARCB1, SMARCE1, TRAF7, KLF4, POLR2A, BAP1, and members of the PI3K and Hedgehog signaling pathways. Initial associations between clinical features and genomic subgroups have been described, including location, grade, and histology. However, further investigation using an expanded collection of samples is needed to confirm previous findings, as well as elucidate relationships not evident in smaller discovery cohorts.METHODSTargeted sequencing of established meningioma driver genes was performed on a multiinstitution cohort of 3016 meningiomas for classification into mutually exclusive subgroups. Relevant clinical information was collected for all available cases and correlated with genomic subgroup. Nominal variables were analyzed using Fisher’s exact tests, while ordinal and continuous variables were assessed using Kruskal-Wallis and 1-way ANOVA tests, respectively. Machine-learning approaches were used to predict genomic subgroup based on noninvasive clinical features.RESULTSGenomic subgroups were strongly associated with tumor locations, including correlation of HH tumors with midline location, and non-NF2 tumors in anterior skull base regions. NF2 meningiomas were significantly enriched in male patients, while KLF4 and POLR2A mutations were associated with female sex. Among histologies, the results confirmed previously identified relationships, and observed enrichment of microcystic features among “mutation unknown” samples. Additionally, KLF4-mutant meningiomas were associated with larger peritumoral brain edema, while SMARCB1 cases exhibited elevated Ki-67 index. Machine-learning methods revealed that observable, noninvasive patient features were largely predictive of each tumor’s underlying driver mutation.CONCLUSIONSUsing a rigorous and comprehensive approach, this study expands previously described correlations between genomic drivers and clinical features, enhancing our understanding of meningioma pathogenesis, and laying further groundwork for the use of targeted therapies. Importantly, the authors found that noninvasive patient variables exhibited a moderate predictive value of underlying genomic subgroup, which could improve with additional training data. With continued development, this framework may enable selection of appropriate precision medications without the need for invasive sampling procedures.

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.

BACKGROUND Meningiomas can be classified into six genomic subgroups based on mutations in NF2, SMARCB1, KLF4, POLR2A, or activating variants in the PI3K or Hedgehog signaling pathways. Previous work has identified specific associations of driver events with clinical and molecular features, such as tumor location. However, their utility in predicting post-operative patient outcomes is not well-explored. Similar to recently described epigenetic signatures, underlying genomic subgroup may provide prognostic value in meningioma management. METHODS Targeted sequencing data was used to classify over 500 meningiomas into established genomic subgroups, and available patient outcome data was assembled based on retrospective chart reviews. Collected data included recurrence (based on imaging), extent of resection (EOR), use of post-operative radiation, and radiologic follow-up period. Statistical associations between genomic subgroup and recurrence were assessed using Fisher’s exact, Kaplan-Meier, and Cox proportional hazards modeling, including stratification based on use of radiation, EOR, grade, and location. RESULTS Meningiomas in the PI3K subgroup exhibited higher rates of early recurrence during the first five post-operative years. This subgroup affiliation was found to be an independent predictor of recurrence free survival from Ki-67, grade, and other clinical features. By contrast, recurrence was rare in the POLR2A, SMARCB1, and KLF4 subgroups, and was typically associated with use of post-operative radiation in these cases. The longest average recurrence free survival was observed in POLR2A mutant meningiomas. CONCLUSIONS Our analysis identifies divergence in meningioma patient outcomes based on genomic subgroup and suggests patients with PI3K activating events may require closer surveillance. These tumors, which often occur near and encase critical neurovascular structures along the sphenoid wing, may further benefit from consideration of radiation and emerging precision therapies. Conversely, other subgroups rarely recur, suggesting caution be invoked with use of potentially morbid adjuvant treatment.

Background Glioblastoma multiforme (GBM) constitutes nearly half of all malignant brain tumors and has a median survival of 15 months. The standard treatment for these lesions includes maximal resection, radiotherapy, and chemotherapy; however, individual tumors display immense variability in their response to these approaches. Genomic techniques such as whole-exome sequencing (WES) provide an opportunity to understand the molecular basis of this variability. Methods Here, we report WES-guided treatment of a patient with a primary GBM and two subsequent recurrences, demonstrating the dynamic nature of treatment-induced molecular changes and their implications for clinical decision-making. We also analyze the Yale-Glioma cohort, composed of 110 whole exome- or whole genome-sequenced tumor-normal pairs, to assess the frequency of genomic events found in the presented case. Results Our longitudinal analysis revealed how the genomic profile evolved under the pressure of therapy. Specifically targeted approaches eradicated treatment-sensitive clones while enriching for resistant ones, generated due to chromothripsis, which we show to be a frequent event in GBMs based on our extended analysis of 110 gliomas in the Yale-Glioma cohort. Despite chromothripsis and the later acquired mismatch-repair deficiency, genomics-guided personalized treatment extended survival to over 5 years. Interestingly, the case displayed a favorable response to immune checkpoint inhibition after acquiring mismatch repair deficiency. Conclusions Our study demonstrates the importance of longitudinal genomic profiling to adjust to the dynamic nature of treatment-induced molecular changes to improve the outcomes of precision therapies. Electronic supplementary material The online version of this article (doi:10.1186/s13073-017-0401-9) contains supplementary material, which is available to authorized users.

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.

Object 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. Methods 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. Results 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. Conclusions 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.

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: Experimental models to study cerebrovascular malformations are limited therefore we used the neonatal rodent retina as a model to study cerebral angiogenesis. OBJECTIVE: We performed a gene expression analysis to define temporal changes in the expression of 96 angiogenesis-related genes during retinal vascularization. METHODS: A total of 72 retinas from 36 newborn C57BL/6 mice were used. Sets of neonatal mouse retinas were surgically isolated by 2-day intervals starting from postnatal day 0 to day 20 and at the 32nd day (representing adult retinas). For each of these 12 time points in the postnatal developmental period of mouse retinas, separate sets of 6 retinas from 3 mice were pooled, and their RNA was hybridized to an angiogenesis-specific gene array. Temporal expression patterns of each of the 96 angiogenesis-related genes were analyzed. For confirmation, vascular endothelial growth factor protein expression was also studied by immunohistochemistry. RESULTS: Twenty-two of the 96 genes analyzed displayed a significantly different temporal expression profile, and the rest exhibited a static expression, as compared to the human glyceraldehyde-3-phosphate dehydrogenase gene. Among these genes, the temporal pattern of expression was variable, but peaks were seen mostly on days 8, 10, 12, and 16. This timing corresponds well to morphologic changes that occur in the retina during different stages of angiogenesis. CONCLUSION: The neonatal rodent retina, which has a cellular architecture similar to that of the brain, has active and quantifiable angiogenic activity during the neonatal period and can be used as a simple and convenient model to study cerebral angiogenesis.

Metastatic tumors and malignant gliomas make up the majority of cancers in the brain. They are invariably fatal and there is currently no cure. Fromin vitrocomparisons of a number of viruses, we selected one that appeared the best in selectively killing glioblastoma cells. This replication-competent virus, the glioma-adapted vesicular stomatis virus strain VSVrp30a, was used forin vivotests with the underlying view that infection of tumor cells will lead to an increase in the number of viruses subsequently released to kill additional tumor cells. Intravenous injection of VSVrp30a expressing a green fluorescent protein reporter, rapidly targeted and destroyed multiple types of human and mouse tumors implanted in the mouse brain, including glioblastoma and mammary tumors. When tumors were implanted both in the brain and peripherally, emulating systemic cancer metastasis, tumors inside and outside the brain were simultaneously infected. Intranasal inoculation, leading to olfactory nerve transport of the virus into the brain, selectively infected and killed olfactory bulb tumors. Neither control cortical wounds nor transplanted normal mouse or human cells were targeted, indicating viral tumor selectivity. Control viruses, including pseudorabies, adeno-associated, or replication-deficient VSV, did not infect the brain tumor. Confocal laser time-lapse imaging through a cranial window showed that intravenous VSV infects the tumor at multiple sites and kills migrating tumor cells. Disrupted tumor vasculature, suggested by dye leakage, may be the port of entry for intravenously delivered VSV. Quantitative PCR analysis of how VSVrp30a selectively infected tumor cells suggested multiple mechanisms, including cell surface binding and internalization.

Chordoid glioma is a slowly growing and uncommon neoplasm which involves the third ventricle and is commonly seen in middle age woman. It is a novel entity which was just recently been incorporated to the World Health Organization (WHO) pathological central nervous system (CNS) tumor classification with chordoma like histologic features and glial fibrillary acidic protein immunoreactivity. Hereby we report a case of third ventricular chordoid glioma in a 32 year old man with history of headache and visual disturbances. Magnetic Resonance Imaging (MRI) imaging showed a homogeneously enhancing mass occupying in the third ventricle. The lesion underwent a subcapsular removal through craniotomy. Histologically the tumor had a uniform appearance consisting of clusters and cords of epithelioid cells embedded within a mucinous stroma, containing a lymphoplasmacytic infiltrate. Immunohistochemistry revealed diffuse expression of Glial Fibrillary Acidic Protein (GFAP), vimentin, cytokeratin and S-100 protein reactivity. An uncommonly high MIB-1 index of 10% was detected. There was no nuclear accumulation of p53 protein. Our patient, who rejected radiotherapy and chemotherapy options after surgery (at 52 months), is currently disease-free

Objective: This study aims at evaluating the adequacy of digital subtraction angiography and magnetic resonance venography in imaging of the galenic venous system for surgical planning of approaches to the pineal region. Anatomical dissections were carried out in 10 cadavers of several age groups and these were compared to imaging findings in 10 living subjects. Methods: The presence or absence of 10 predetermined veins or vein groupings belonging to the galenic venous system were prospectively analyzed in 10 cadaver dissections and imaging findings of 10 age matched human subjects. The studied vessels were the vein of galen, the internal cerebral veins, both basal vein of Rosenthals, internal occipital vein, occipitotemporal veins, precentral cerebellar veins, tectal veins, pineal veins, superior vermian veins (including superior cerebellar veins (SCVs)) and posterior pericallosal veins. Each of the subjects had both digital subtraction angiography and magnetic resonance venography studies performed. Diagnostic digital subtraction angiography was performed using the transfemoral route and the venous phase was used for the study. Magnetic resonance venography was performed in 1.5 T MRI equipment using the 2D-TOF sequence. All studies were reported to be normal. Results: There was wide variation in the anatomy of the galenic venous system. There were interpersonal, intrapersonal and age related variations. Both the digital subtraction angiography and the magnetic resonance venography were efficient at demonstrating large veins. However, smaller veins were less readily demonstrated in either study. The general sensitivities of the digital subtraction angiography and the magnetic resonance venography for the galenic venous system were 45.5% and 32.5%, respectively. Surgically important veins were missed in most studies. Conclusions: Anatomically, the galenic venous system is highly variable. This variability is caused by interpersonal, intrapersonal and age related differences and causes each individual galenic venous system to be unique. Therefore, modern neurosurgical procedures require anatomical information on individual differences. Current radiological methods of digital subtraction angiography and magnetic resonance venography fail short of providing the necessary information. New and more sophisticated MRI technology may fulfill this need.

BACKGROUND Although current guidelines for the management of unruptured intracranial aneurysms (IAs) suggest aneurysms larger than 7 mm should be considered for treatment, a significant number of subarachnoid hemorrhages are caused by IAs 7 mm or smaller. Thus, we sought to identify risk factors associated with the rupture of IAs 7 mm or smaller. METHODS We identified 100 patients with subarachnoid hemorrhage resulting from IAs 7 mm or smaller between January 2001 and 2004. Patients were compared with controls (n = 51) with unruptured IAs 7 mm or smaller, diagnosed by conventional angiography or three-dimensional computerized angiography, with respect to aneurysm characteristics (size, location, and age of presentation) and risk factors (hypertension, smoking, cocaine use, and family history). RESULTS Hypertensive patients with IAs 7 mm or smaller were 2.6 times more likely to experience rupture (P = 0.01; 95% confidence interval, 1.21-5.53) than patients with normal blood pressure. Posterior circulation aneurysms were 3.5 times more likely to rupture than anterior circulation aneurysms (P = 0.048; 95% confidence interval, 0.95-19.4). After adjustment for location and hypertension, the age of patient on presentation was associated with a trend toward inverse correlation with aneurysmal rupture risk (P = 0.07). Hypertension and posterior location remained significant independent predictors in the logistic regression model. CONCLUSION Among patients with small aneurysms (< or = 7 mm), hypertension, relatively young age, and posterior circulation were significant risk factors for rupture. Given the minimal long-term morbidity and mortality of treatment of unruptured aneurysms in large, tertiary medical centers, management of unruptured aneurysms 7 mm or smaller should be governed by factors other than size, specifically age, history of hypertension, and location.

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.

Summary: Primary hypophysitis is a rare but significant cause of sellar spaceoccupying lesions. Three forms have been described: granulomatous, lymphocytic, and xanthomatous hypophysitis. Current methods cannot diagnose or distinguish these entities before surgery with sufficient certainty. The disease most commonly presents with sellar space-occupying symptoms as a result of pituitary enlargement and hormonal abnormalities such as potentially lethal pituitary insufficiency or hyperprolactinemia. Pituitary insufficiency almost always ensues, with progressive inflammatory destruction of the pituitary tissue. All three disorders clinically and radiologically mimic pituitary adenomas, and the diagnosis is usually made after surgery. Idiopathic giant cell granulomatous hypophysitis is a cryptogenic inflammatory lesion. The diagnosis rests on eliminating secondary causes. Lymphocytic hypophysitis is a chronic autoimmune disorder of the anterior and, rarely, posterior pituitary. Although it is most commonly seen in peripartum women, it may be encountered in either sex and may be associated with other autoimmune diseases. Surgical removal, biopsy, and medical therapy are the three options of therapy. Response to medical therapy is unpredictable, but remissions are reported with steroids. A consensus regarding drug choice timing, duration, and dosage of therapy is lacking, but in preoperatively suspected cases, a therapeutic trial is justified. Surgery results in cure at the expense of potentially viable pituitary tissue. The natural course of these rare disorders is currently unknown, the prognosis is unpredictable, and the choice of effective therapy is yet to be established.

OBJECTIVE : Tenascin is an extracellular matrix glycoprotein that is expressed during embryogenesis, inflammation, angiogenesis, and carcinogenesis. The aim of this study was to investigate how tenascin expression relates to histological grade, angiogenesis, and radiological findings in meningiomas. Methods: Twenty typical, 20 atypical, and 5 malignant meningiomas were studied retrospectively. Tenascin expression and vascular endothelial growth factor (VEGF) expression in the tumor tissue were investigated by immunohistochemistry. Tenascin messenger ribonucleic acid expression was also studied by comparative reverse transciptase-polymerase chain reaction. Magnetic resonance images from each case were assessed for peritumoral edema and tumor border shape. Results: The atypical and malignant meningiomas showed higher levels of tenascin expression than the typical meningiomas. The more sensitive messenger ribonucleic acid-based methods confirmed this finding. Tenascin expression was correlated with peritumoral edema and VEGF expression byt not with tumor border shape. In the 13 tumors with marked tenascin expression, peritumoral edema was Grade 0 in one, Grade 1 in three, and Grade 2 in nine specimens. In the same 13 tumors, VEGF expression was Grade 1 in five and Grade 2 in eight specimens, and the findings for tumor border shape were Grade 0 in seven, Grade 1 in four, and Grade 2 in two speciemens. Conclusion: In meningiomas, tenascin expression is correlated with anaplasia, tumor-associated edema, and VEGF expression but not with tumor border shape. This protein may play a role in the neoplastic and/or angiogenic processes in atypical and malignant meningiomas and may thus be a potential target for meningioma therapy.

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.

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.

With a population of more than 70 million, Turkey has a large demand for neurosurgery. Neurosurgery is provided by a socialized health care system partly supported by private institutions. There are more than 1200 neurosurgeons practicing in Turkey, and sophisticated surgical procedures are performed in most large cities. Residency training is provided at universities and training hospitals, and the quality of care is supported by two neurosurgical societies.

Chordomas are rare, slow growing tumors of the axial skeleton, which derive from the remnants of the fetal notochord. They can be encountered anywhere along the axial skeleton, most commonly in the sacral area, skull base and less commonly in the spine. Chordomas have a benign histopathology but exhibit malignant clinical behavior with invasive, destructive and metastatic potential. Genetic and molecular pathology studies on oncogenesis of chordomas are very limited and there is little known on mechanisms governing the disease. Chordomas most commonly present with headaches and diplopia and can be readily diagnosed by current neuroradiological methods. There are 3 pathological subtypes of chordomas: classic, chondroid and dedifferentiated chordomas. Differential diagnosis from chondrosarcomas by radiology or pathology may at times be difficult.

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.

Study design: Review article on spinal involvement of hydatid disease. Objectives: A better understanding of this rare but clinically challenging disease is intended. An overview of the epidemiology, pathogenesis, presentation and diagnosis of spinal hydatid disease is provided. Management problems and frequent pitfalls are discussed as well as current therapeutic options, results and outcome. Methods: Thirty-seven reports of spinal hydatid disease published between 1964 and 2000 were reviewed. Results: Most of the reported cases of spinal hydatid disease presented with spinal cord compression syndrome. Due to the relative rarity of the problem the diagnosis was frequently made during surgery. Surgical intervention by decompressive laminectomy was the most frequent first management. Reports of anterior procedures as well as spinal stabilization exist. Intraoperative prophylaxis to reduce spillage as well as pharmacotherapy were usually instituted. Results of surgery were generally reported to be poor. Progressive neurological and mechanical deterioration over the years was the most frequently reported disease course. Anecdotal reports of alternative management strategies exist. Conclusion: Spinal hydatid disease should be considered in the differential diagnosis of spinal cord compression syndrome in endemic countries and sought after with imaging and serology. Treatment is based on surgical decompression. Despite therapy the disease frequently relapses with progressive destruction of the vertebral column and neurological deterioration. Retention of spinal stability is the major long term concern. Overall outcome is poor with few reports of disease-free long term survival.