Search

Background: Meningioangiomatosis is a poorly studied, rare, benign, and epileptogenic brain lesion., Objective: To demonstrate that surgical resection and a short-time interval to surgery improves epileptic seizure control, we performed a systematic review and meta-analysis of meningioangiomatosis cases., Methods: Using PRISMA-IPD guidelines, the authors performed a systematic review and meta-analysis of histopathologically-proven meningioangiomatosis cases. Literature search in French and English languages (PubMed, Embase, the Cochrane Library, and the Science Citation Index) including all studies (January 1981 to June 2020) dealing with histopathologically-proven meningioangiomatosis, without age restriction. We assessed clinical, imaging, histomolecular, management, and outcome findings of patients with meningioangiomatosis., Results: Two-hundred and seven cases of meningioangiomatosis from 78 studies were included. Most meningioangiomatosis was sporadic, preferentially concerned male patients, younger than 20 years old, and allowed a functionally independent status. Epileptic seizure was the main symptom, with 81.4% of patients having uncontrolled seizures at the time of surgery. Meningioangiomatosis mainly had frontal (32.3%) or temporal (30.7%) locations. Imaging presentation was heterogeneous, and the diagnosis was often missed preoperatively. The histopathologic pattern was similar whatever the clinical presentation, and immunohistochemistry had limited diagnostic value. On molecular analysis, allelic loss at 22q12 was more frequent in samples of meningioangiomatosis-associated meningioma (37.5%) than in isolated meningioangiomatosis (23.1%). Time interval from diagnosis to surgery ( p = 0.011) and lack of surgical resection of the meningioangiomatosis ( p = 0.009) were independent predictors of postoperative seizure control., Conclusions: Owing to low scientific evidence, a multicentric prospective study should help refining the management of meningioangiomatosis., (© 2020 American Academy of Neurology.)

Background: The function-based resection using trans-cortical approach for removing insular diffuse glioma shares a positive benefit-to-risk ratio with a low rate of permanent morbidity., Method: The technique requires intraoperative functional brain mapping to be performed under awake condition using direct electrical stimulations at both cortical and subcortical levels to identify brain connectivity supporting neurocognition., Conclusion: The trans-cortical approach is a safe and efficient technique to remove insular diffuse glioma. Intraoperative functional brain mapping under awake condition allows preserving brain connectivity and tailoring the resection. Great care must be taken in preventing vascular damages, and particularly the lenticulostriate arteries.

Background: Considering that pediatric high-grade gliomas (HGGs) are biologically distinct from their adult counterparts, the objective of this study was to define the landscape of HGGs in adolescents and young adults (AYAs)., Methods: We performed a multicentric retrospective study of 112 AYAs from adult and pediatric Ile-de-France neurosurgical units, treated between 1998 and 2013 to analyze their clinicoradiological and histomolecular profiles. The inclusion criteria were age between 15 and 25 years, histopathological HGG diagnosis, available clinical data, and preoperative and follow-up MRI. MRI and tumoral samples were centrally reviewed. Immunohistochemistry and complementary molecular techniques such as targeted/next-generation sequencing, whole exome sequencing, and DNA-methylation analyses were performed to achieve an integrated diagnosis according to the 2016 World Health Organization (WHO) classification., Results: Based on 80 documented AYA patients, HGGs constitute heterogeneous clinicopathological and molecular groups, with a predominant representation of pediatric subtypes (histone H3-mutants, 40%) but also adult subtypes (isocitrate dehydrogenase [IDH] mutants, 28%) characterized by the rarity of oligodendrogliomas, IDH mutants, and 1p/19q codeletion and the relative high frequency of "rare adult IDH mutations" (20%). H3G34-mutants (14%) represent the most specific subgroup in AYAs. In the H3K27-mutant subgroup, non-brainstem diffuse midline gliomas are more frequent (66.7%) than diffuse intrinsic pontine gliomas (23.8%), contrary to what is observed in children. We found that WHO grade has no prognostic value, but molecular subgrouping has major prognostic importance., Conclusions: HGGs in AYAs could benefit from a specific classification, driven by molecular subtyping rather than age group. Collaborative efforts are needed from pediatric and adult neuro-oncology teams to improve the management of HGGs in AYAs., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Neuroimaging and especially MRI has emerged as a necessary imaging modality to detect, measure, characterize and monitor brain tumours. Advanced MRI sequences such as perfusion MRI, diffusion MRI and spectroscopy as well as new post-processing techniques such as automatic segmentation of tumours and radiomics play a crucial role in characterization and follow up of brain tumours. The purpose of this review is to provide an overview on anatomical and functional MRI use for brain tumours boundaries determination and tumour characterization in the specific context of radiotherapy. The usefulness of anatomical and functional MRI on particular challenges posed by radiotherapy such as pseudo progression and pseudo esponse and new treatment strategies such as dose painting is also described., (Copyright © 2020 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Radiomics relies on the extraction of a wide variety of quantitative image-based features to provide decision support. Magnetic resonance imaging (MRI) contributes to the personalization of patient care but suffers from being highly dependent on acquisition and reconstruction parameters. Today, there are no guidelines regarding the optimal pre-processing of MR images in the context of radiomics, which is crucial for the generalization of published image-based signatures. This study aims to assess the impact of three different intensity normalization methods (Nyul, WhiteStripe, Z-Score) typically used in MRI together with two methods for intensity discretization (fixed bin size and fixed bin number). The impact of these methods was evaluated on first- and second-order radiomics features extracted from brain MRI, establishing a unified methodology for future radiomics studies. Two independent MRI datasets were used. The first one (DATASET1) included 20 institutional patients with WHO grade II and III gliomas who underwent post-contrast 3D axial T1-weighted (T1w-gd) and axial T2-weighted fluid attenuation inversion recovery (T2w-flair) sequences on two different MR devices (1.5 T and 3.0 T) with a 1-month delay. Jensen-Shannon divergence was used to compare pairs of intensity histograms before and after normalization. The stability of first-order and second-order features across the two acquisitions was analysed using the concordance correlation coefficient and the intra-class correlation coefficient. The second dataset (DATASET2) was extracted from the public TCIA database and included 108 patients with WHO grade II and III gliomas and 135 patients with WHO grade IV glioblastomas. The impact of normalization and discretization methods was evaluated based on a tumour grade classification task (balanced accuracy measurement) using five well-established machine learning algorithms. Intensity normalization highly improved the robustness of first-order features and the performances of subsequent classification models. For the T1w-gd sequence, the mean balanced accuracy for tumour grade classification was increased from 0.67 (95% CI 0.61-0.73) to 0.82 (95% CI 0.79-0.84, P = .006), 0.79 (95% CI 0.76-0.82, P = .021) and 0.82 (95% CI 0.80-0.85, P = .005), respectively, using the Nyul, WhiteStripe and Z-Score normalization methods compared to no normalization. The relative discretization makes unnecessary the use of intensity normalization for the second-order radiomics features. Even if the bin number for the discretization had a small impact on classification performances, a good compromise was obtained using the 32 bins considering both T1w-gd and T2w-flair sequences. No significant improvements in classification performances were observed using feature selection. A standardized pre-processing pipeline is proposed for the use of radiomics in MRI of brain tumours. For models based on first- and second-order features, we recommend normalizing images with the Z-Score method and adopting an absolute discretization approach. For second-order feature-based signatures, relative discretization can be used without prior normalization. In both cases, 32 bins for discretization are recommended. This study may pave the way for the multicentric development and validation of MR-based radiomics biomarkers.

Brain tumors, such as low grade gliomas (LGG), are molecularly classified which require the surgical collection of tissue samples. The pre-surgical or non-operative identification of LGG molecular type could improve patient counseling and treatment decisions. However, radiographic approaches to LGG molecular classification are currently lacking, as clinicians are unable to reliably predict LGG molecular type using magnetic resonance imaging (MRI) studies. Machine learning approaches may improve the prediction of LGG molecular classification through MRI, however, the development of these techniques requires large annotated data sets. Merging clinical data from different hospitals to increase case numbers is needed, but the use of different scanners and settings can affect the results and simply combining them into a large dataset often have a significant negative impact on performance. This calls for efficient domain adaption methods. Despite some previous studies on domain adaptations, mapping MR images from different datasets to a common domain without affecting subtitle molecular-biomarker information has not been reported yet. In this paper, we propose an effective domain adaptation method based on Cycle Generative Adversarial Network (CycleGAN). The dataset is further enlarged by augmenting more MRIs using another GAN approach. Further, to tackle the issue of brain tumor segmentation that requires time and anatomical expertise to put exact boundary around the tumor, we have used a tight bounding box as a strategy. Finally, an efficient deep feature learning method, multi-stream convolutional autoencoder (CAE) and feature fusion, is proposed for the prediction of molecular subtypes (1p/19q-codeletion and IDH mutation). The experiments were conducted on a total of 161 patients consisting of FLAIR and T1 weighted with contrast enhanced (T1ce) MRIs from two different institutions in the USA and France. The proposed scheme is shown to achieve the test accuracy of 74 . 81 % on 1p/19q codeletion and 81 . 19 % on IDH mutation, with marked improvement over the results obtained without domain mapping. This approach is also shown to have comparable performance to several state-of-the-art methods.

Background: We quantified the spontaneous imaging growth rate of oligodendrogliomas. We assessed whether (i) it discriminates between World Health Organization (WHO) grade II and grade III oligodendrogliomas, and (ii) grade III oligodendrogliomas with neo-angiogenesis are associated with more fast growth rates (≥8 mm/y)., Methods: This work employed a retrospective bicentric cohort study (2010-2016) of adult patients harboring a newly diagnosed supratentorial oligodendroglioma, isocitrate dehydrogenase (IDH) mutant and 1p/19q codeleted (WHO 2016 classification), with a minimum of 2 available MRIs before any treatment (minimum 6-week interval) to measure the spontaneous tumor growth rate., Results: We included 108 patients (age 44.7 ± 14.1 y, 60 males). The tumor growth rate was higher in grade III oligodendrogliomas with neo-angiogenesis (n = 37, median 10.4 mm/y, mean 10.0 ± 6.9) than in grade III oligodendrogliomas with increased mitosis count only (cutoff ≥6 mitoses, n = 18, median 3.9 mm/y, mean 4.5 ± 3.2; P = 0.004), and higher than in grade II oligodendrogliomas (n = 53, median 2.3 mm/y, mean 2.8 ± 2.2; P < 0.001). There was increased prevalence of fast tumor growth rates in grade III oligodendrogliomas with neo-angiogenesis (54.1%) compared with grade III oligodendrogliomas with increased mitosis count only (11.1%; P < 0.001), and in grade II oligodendrogliomas (0.0%; P < 0.001). The tumor growth rate trends did not differ between centers (P = 0.121). Neo-angiogenesis (P < 0.001) and mitosis count at ≥9 (P = 0.013) were independently associated with tumor growth rates ≥8 mm/year. A tumor growth rate ≥8 mm/year was the only predictor independently associated with shorter progression-free survival (P = 0.041)., Conclusions: The spontaneous tumor growth rate recapitulates oligodendroglioma aggressiveness, permits identification of grade III oligodendrogliomas preoperatively when ≥8 mm/year, and questions the grading by mitosis count., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Primary central nervous system tumors (PCNST) among adolescents and young adults (AYA, 15-39 y) have rarely been reported. We present a nationwide report of PCNST histologically confirmed in the French AYA population between 2008 and 2013., Methods: Patients were identified through the French Brain Tumor Database (FBTDB), a national dataset that includes prospectively all histologically confirmed cases of PCNST in France. Patients aged 15 to 39 years with histologically confirmed PCNST diagnosed between 2008 and 2013 were included. For each of the 143 histological subtypes of PCNST, crude rates, sex, surgery, and age distribution were provided. To enable international comparisons, age-standardized incidence rates were adjusted to the world-standard, European, and USA populations., Results: For 6 years, 9661 PCNST (males/females: 4701/4960) were histologically confirmed in the French AYA population. The overall crude rate was 8.15 per 100 000 person-years. Overall, age-standardized incidence rates were (per 100 000 person-years, population of reference: world/Europe/USA): 7.64/8.07/8.21, respectively. Among patients aged 15-24 years, the crude rate was 5.13 per 100 000. Among patients aged 25-39 years, the crude rate was 10.10 per 100 000. Age-standardized incidence rates were reported for each of the 143 histological subtypes. Moreover, for each histological subtype, data were detailed by sex, age, type of surgery (surgical resection or biopsy), and cryopreserved samples., Conclusion: These data represent an exhaustive report of all histologically confirmed cases of PCNST with their frequency and distribution in the French AYA population in 2008-2013. For the first time in this age group, complete histological subtypes and rare tumor identification are detailed., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Long-term use of high-dose progestin is known to promote the development of meningioma. Atypical meningioma in a patient under progestin has not previously been reported., Case Report: A 53-year-old right-handed woman presented with focal onset seizures, without impaired consciousness. Medical history featured endometriosis, treated successively by cyproterone acetate 25mg/day for 2 months then 50mg/day for 101 months, and chlormadinone acetate 5mg/day for 68 months then 10mg/day for 83 months. Brain MRI revealed multiple extra-axial lesions suggestive of left central meningioma associated with anterior skull base meningiomatosis. Surgical resection of the left central meningioma was achieved and progestin was withdrawn. Neuropathology diagnosed grade II atypical meningioma. Close clinical and imaging monitoring was implemented without adjuvant oncological treatment. At 25 months, imaging follow-up showed no recurrence of the left central meningioma and a significant regression of all other lesions, except for the right frontal lesion., Conclusions: Neurosurgeons should be aware of the possible aggressiveness of meningioma in patients under progestin, and particularly those treated by different types of progestin over a long period of time without interruption. This may require systematic close monitoring, to adapt neurosurgical management., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: No link has been demonstrated between diffuse intrinsic pontine glioma and developmental venous anomaly in pediatric patients., Objective: To determine the prevalence of developmental venous anomaly in a pediatric cohort of diffuse intrinsic pontine glioma., Methods: We performed a retrospective cohort study (1998-2017) of consecutive pediatric patients harboring a diffuse intrinsic pontine glioma (experimental set, n = 162) or a craniopharyngioma (control set, n = 142) in a tertiary pediatric neurosurgical center. The inclusion criteria were the following: age <18 yr at diagnosis; histopathological diagnosis of diffuse intrinsic pontine glioma or craniopharyngioma according to the 2016 World Health Organization classification of tumors of the central nervous system; no previous oncological treatment; and available preoperative magnetic resonance imaging performed with similar acquisition protocol., Results: We found a significantly higher prevalence of developmental venous anomaly in the experimental set of 162 diffuse intrinsic pontine gliomas (24.1%) than in the control set of 142 craniopharyngiomas (10.6%; P = .001). The prevalence of developmental venous anomalies was not significantly impacted by demographic data (sex, age at diagnosis, and underlying pathological condition), biomolecular analysis (H3-K27M-mutant subgroup, H3.1-K27M-mutant subgroup, and H3.3-K27M-mutant subgroup), or imaging findings (anatomic location, anatomic extension, side, and obstructive hydrocephalus) of the studied diffuse intrinsic pontine gliomas., Conclusion: We report a higher prevalence of developmental venous anomaly in pediatric diffuse intrinsic pontine glioma patients than in control patients, which suggests a potential underlying common predisposition or a causal relationship that will require deeper investigations., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Organic cation transporters (OCTs) participate in the handling of compounds in kidneys and at the synaptic cleft. Their role at the blood-brain barrier (BBB) in brain drug delivery is still unclear. The presence of OCT1,2,3 (SLC22A1-3) in mouse, rat and human isolated brain microvessels was investigated by either qRT-PCR, quantitative proteomics and/or functional studies. BBB transport of the prototypical substrate [ 3 H]-1-methyl-4-phenylpyridinium ([ 3 H]-MPP + ) was measured by in situ brain perfusion in six mouse strains and in Sprague Dawley rats, in primary human brain microvascular endothelial cells seeded on inserts, in the presence or absence of OCTs and a MATE1 (SLC49A1) inhibitor. The results show negligible OCT1 (SLC22A1) and OCT2 (SLC22A2) expression in either mice, rat or human brain microvessels, while OCT3 expression was identified in rat microvessels by qRT-PCR. The in vitro human cellular uptake of [ 3 H]-MPP + was not modified by OCTs/MATE-inhibitor. Brain transport of [ 3 H]-MPP + remains unchanged between 2- and 6-month old mice, and no alteration was observed in mice and rats with inhibitors. In conclusion, the evidenced lack of expression and/or functional OCTs and MATE at the BBB allows the maintenance of the brain homeostasis and function as it prevents an easy access of their neurotoxicant substrates to the brain parenchyma.

Objective: Functional-based resection under awake conditions had been associated with a nonnegligible rate of intraoperative and postoperative epileptic seizures. The authors assessed the incidence of intraoperative and early postoperative epileptic seizures after functional-based resection under awake conditions., Methods: The authors prospectively assessed intraoperative and postoperative seizures (within 1 month) together with clinical, imaging, surgical, histopathological, and follow-up data for 202 consecutive diffuse glioma adult patients who underwent a functional-based resection under awake conditions., Results: Intraoperative seizures occurred in 3.5% of patients during cortical stimulation; all resolved without any procedure being discontinued. No predictor of intraoperative seizures was identified. Early postoperative seizures occurred in 7.9% of patients at a mean of 5.1 ± 2.9 days. They increased the duration of hospital stay (p = 0.018), did not impact the 6-month (median 95 vs 100, p = 0.740) or the 2-year (median 100 vs 100, p = 0.243) postoperative Karnofsky Performance Status score and did not impact the 6-month (100% vs 91.4%, p = 0.252) or the 2-year (91.7 vs 89.4%, p = 0.857) postoperative seizure control. The time to treatment of at least 3 months (adjusted OR [aOR] 4.76 [95% CI 1.38-16.36], p = 0.013), frontal lobe involvement (aOR 4.88 [95% CI 1.25-19.03], p = 0.023), current intensity for intraoperative mapping of at least 3 mA (aOR 4.11 [95% CI 1.17-14.49], p = 0.028), and supratotal resection (aOR 6.24 [95% CI 1.43-27.29], p = 0.015) were independently associated with early postoperative seizures., Conclusions: Functional-based resection under awake conditions can be safely performed with a very low rate of intraoperative and early postoperative seizures and good 6-month and 2-year postoperative seizure outcomes. Intraoperatively, the use of the lowest current threshold producing reproducible responses is mandatory to reduce seizure occurrence intraoperatively and in the early postoperative period.

Microglia exhibit multiple, phenotype-dependent motility patterns often triggered by purinergic stimuli. However, little data exist on motility of human microglia in pathological situations. Here we examine motility of microglia stained with a fluorescent lectin in tissue slices from female and male epileptic patients diagnosed with mesial temporal lobe epilepsy or cortical glioma (peritumoral cortex). Microglial shape varied from ramified to amoeboid cells predominantly in regions of high neuronal loss or closer to a tumor. Live imaging revealed unstimulated or purine-induced microglial motilities, including surveillance movements, membrane ruffling, and process extension or retraction. At different concentrations, ADP triggered opposing motilities. Low doses triggered process extension. It was suppressed by P2Y12 receptor antagonists, which also reduced process length and surveillance movements. Higher purine doses caused process retraction and membrane ruffling, which were blocked by joint application of P2Y1 and P2Y13 receptor antagonists. Purinergic effects on motility were similar for all microglia tested. Both amoeboid and ramified cells from mesial temporal lobe epilepsy or peritumoral cortex tissue expressed P2Y12 receptors. A minority of microglia expressed the adenosine A2A receptor, which has been linked with process withdrawal of rodent cells. Laser-mediated tissue damage let us test the functional significance of these effects. Moderate damage induced microglial process extension, which was blocked by P2Y12 receptor antagonists. Overall, the purine-induced motility of human microglia in epileptic tissue is similar to that of rodent microglia in that the P2Y12 receptor initiates process extension. It differs in that retraction is triggered by joint activation of P2Y1/P2Y13 receptors. SIGNIFICANCE STATEMENT Microglial cells are brain-resident immune cells with multiple functions in healthy or diseased brains. These diverse functions are associated with distinct phenotypes, including different microglial shapes. In the rodent, purinergic signaling is associated with changes in cell shape, such as process extension toward tissue damage. However, there are little data on living human microglia, especially in diseased states. We developed a reliable technique to stain microglia from epileptic and glioma patients to examine responses to purines. Low-intensity purinergic stimuli induced process extension, as in rodents. In contrast, high-intensity stimuli triggered a process withdrawal mediated by both P2Y1 and P2Y13 receptors. P2Y1/P2Y13 receptor activation has not previously been linked to microglial morphological changes., (Copyright © 2020 the authors.)

Awake surgery is a well-defined procedure with a very low morbidity. In particular, stimulation-related intraoperative seizure (IOS) is a commonly discussed and serious complication associated with awake surgery. Here, we reviewed the literature on awake surgery and IOS and sought to obtain evidences on the predictive factors of IOS and on the effect of IOS on postoperative outcomes. We conducted a comprehensive search of the Embase, MEDLINE, and Cochrane Central Register of Controlled Trials databases to identify potentially relevant articles from 2000 to 2019. We used combinations of the following search terms: "intraoperative seizure awake craniotomy," "awake surgery seizures," and pertinent associations; the search was restricted to publications in English and only to papers published in the last 20 years. The search returned 141 articles, including 39 papers that reported the IOS rate during awake craniotomy. The reported IOS rates ranged between 0 and 24% (mean, 7.7%). Only few studies have assessed the relationships between awake surgery and IOS, and hence, drawing clear conclusions is difficult. Nevertheless, IOS does not cause permanent and severe postoperative deficits, but can affect the patient's status perioperatively and the hospitalization duration. Anterior tumor location is an important perioperative factor associated with high IOS risk, whereas having seizures at tumor diagnosis does not seem to influence. However, the role of antiepileptic drug administration and prophylaxis remains unclear. In conclusion, given the difficulty in identifying predictors of IOS, we believe that prompt action at onset and awareness of appropriate management methods are vital.

Background: The pharmacokinetics of temozolomide (TMZ) in patients with severe renal impairments (creatinine clearance, <36 mL/min/m 2 ) or in hemodialysis (HD) patients has not been investigated. TMZ and its metabolic products are mainly excreted in urine, as retention of these in the body may result in increased adverse events in HD patients., Methods: Seven HD patients with high-grade gliomas from 6 institutions were included in the study. Patient characteristics, treatment schedule, clinical course, pathological/molecular findings, and adverse events were evaluated., Results: The histopathological diagnoses were isocitrate dehydrogenase ( IDH ) wild-type glioblastoma in 4 cases, not other specified (NOS) glioblastoma in 2 cases, and IDH -mutant anaplastic astrocytoma in 1 case. Five of the 7 patients completed radiotherapy (48-60 Gy) with concomitant TMZ (75 mg/m 2 ) followed by adjuvant 5-day TMZ (150 mg/m 2 ) every 28 days. During the entire course of treatment with TMZ, severe (Common Terminology Criteria for Adverse Events [CTCAE] ≥ Grade 3) lymphocytopenia occurred in 57%, neutropenia in 0%, and thrombocytopenia in 14% of the patients. Generally, the frequency and degree of myelosuppression do not increase in HD patients with high-grade gliomas. Two of the 7 (28.5%) patients died of infectious disease despite having no direct correlation to myelosuppression; that is similar to the death rate of 21.9% resulting from infection in HD patients in Japan., Conclusions: Decreasing the dose of TMZ might not be required in HD patients with high-grade gliomas during concomitant radiochemotherapy and maintenance therapy. However, careful clinical and hematological observation is required to avoid critical hematotoxicity and infection., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Brain metastases occur in 15-30% of cancer patients and their frequency has increased over time. They can cause intracranial hypertension, even in the absence of hydrocephalus. Emergency surgical management of brain metastasis-related intracranial hypertension is not guided by specific recommendations., Objective: We aimed to make a French national survey of emergency management of intracranial hypertension without hydrocephalus in the context of cerebral metastasis., Methods: A national online survey of French neurosurgeons from 16 centers was conducted, consisting of three clinical files, with multiple-choice questions on diagnostic and therapeutic management in different emergency situations., Results: In young patients without any previously known primary cancer, acute intracranial hypertension due to a seemingly metastatic single brain tumor indicated emergency surgery for all those interviewed; 61% aimed at complete resection; brain MRI was mandatory for 74%. When a primary cancer was known, 74% of respondents were more likely to propose surgery if an oncologist confirmed the possibility of adjuvant treatment; 27% were more likely to operate on an emergency basis when resection was scheduled after multi-disciplinary discussion, prior to acute degradation., Conclusion: Currently, there is no consensus on the emergency management of intracranial hypertension in metastatic brain tumor patients. In case of previously known primary cancer, a discussion with the oncology team seems necessary, even in emergency. Decision criteria emerge from our literature review, but require analysis in further studies., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

During functional-based resection under awake conditions of a left frontal isocitrate dehydrogenase-wildtype glioblastoma, the initial intralesional debulking performed to alleviate mass effect unmasked the right hemibody negative motor networks that were identified on the neocortex by direct electric stimulation. As compared with preoperative evaluation, the 3-month postoperative functional magnetic resonance imaging (MRI) confirmed unmasked cortical clusters for the right hemibody that were absent preoperatively using the same functional MRI parameters; language clusters were also better seen. The glioma-induced mass effect can mask eloquent brain areas, and surgical decompression can unmask intraoperatively eloquent brain areas., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background Tumor location is a main prognostic parameter in patients with glioblastoma. Probabilistic MRI-based brain atlases specifying the probability of tumor location associated with important demographic, clinical, histomolecular, and management data are lacking for isocitrate dehydrogenase (IDH) wild-type glioblastomas. Purpose To correlate glioblastoma location with clinical phenotype, surgical management, and outcomes by using a probabilistic analysis in a three-dimensional (3D) MRI-based atlas. Materials and Methods This retrospective study included all adults surgically treated for newly diagnosed IDH wild-type supratentorial glioblastoma in a tertiary adult surgical neuro-oncology center (2006-2016). Semiautomated tumor segmentation and spatial normalization procedures to build a 3D MRI-based atlas were validated. The authors performed probabilistic analyses by using voxel-based lesion symptom mapping technology. The Liebermeister test was used for binary data, and the generalized linear model was used for continuous data. Results A total of 392 patients (mean age, 61 years ± 13; 233 men) were evaluated. The authors identified the preferential location of glioblastomas according to subventricular zone, age, sex, clinical presentation, revised Radiation Therapy Oncology Group-Recursive Partitioning Analysis class, Karnofsky performance status, O 6 -methylguanine DNA methyltransferase promoter methylation status, surgical management, and survival. The superficial location distant from the eloquent area was more likely associated with a preserved functional status at diagnosis (348 of 392 patients [89%], P < .05), a large surgical resection (173 of 392 patients [44%], P < .05), and prolonged overall survival (163 of 334 patients [49%], P < .05). In contrast, deep location and location within eloquent brain areas were more likely associated with an impaired functional status at diagnosis (44 of 392 patients [11%], P < .05), a neurologic deficit (282 of 392 patients [72%], P < .05), treatment with biopsy only (183 of 392 patients [47%], P < .05), and shortened overall survival (171 of 334 patients [51%], P < .05). Conclusion The authors identified the preferential location of isocitrate dehydrogenase wild-type glioblastomas according to parameters of interest and provided an image-based integration of multimodal information impacting survival results. This suggests the role of glioblastoma location as a surrogate and multimodal parameter integrating several known prognostic factors. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Huang in this issue.

Background: The postoperative outcomes and the predictors of seizure control are poorly studied for supratentorial cavernous angiomas (CA) within or close to the eloquent brain area., Objective: To assess the predictors of preoperative seizure control, postoperative seizure control, and postoperative ability to work, and the safety of the surgery., Methods: Multicenter international retrospective cohort analysis of adult patients benefitting from a functional-based surgical resection with intraoperative functional brain mapping for a supratentorial CA within or close to eloquent brain areas., Results: A total of 109 patients (66.1% women; mean age 38.4 ± 12.5 yr), were studied. Age >38 yr (odds ratio [OR], 7.33; 95% confidence interval [CI], 1.53-35.19; P = .013) and time to surgery > 12 mo (OR, 18.21; 95% CI, 1.11-296.55; P = .042) are independent predictors of uncontrolled seizures at the time of surgery. Focal deficit (OR, 10.25; 95% CI, 3.16-33.28; P < .001) is an independent predictor of inability to work at the time of surgery. History of epileptic seizures at the time of surgery (OR, 7.61; 95% CI, 1.67-85.42; P = .003) and partial resection of the CA and/or of the hemosiderin rim (OR, 12.02; 95% CI, 3.01-48.13; P < .001) are independent predictors of uncontrolled seizures postoperatively. Inability to work at the time of surgery (OR, 19.54; 95% CI, 1.90-425.48; P = .050), Karnofsky Performance Status ≤ 70 (OR, 51.20; 95% CI, 1.20-2175.37; P = .039), uncontrolled seizures postoperatively (OR, 105.33; 95% CI, 4.32-2566.27; P = .004), and worsening of cognitive functions postoperatively (OR, 13.71; 95% CI, 1.06-176.66; P = .045) are independent predictors of inability to work postoperatively., Conclusion: The functional-based resection using intraoperative functional brain mapping allows safe resection of CA and the peripheral hemosiderin rim located within or close to eloquent brain areas., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Prophylaxis or treatment of tumor-associated seizures is adaily concern in neurosurgical practice but is often guided by the surgeon's habits rather than evidence from clinical trials, which is lacking. The present study reviews the literature on the incidence, clinical aspects and treatment of epilepsy and epileptic seizures in patients undergoing surgery for meningioma. Based on the published data, we then performed a French nationwide survey of neurosurgeons' practices regarding perioperative management of meningioma-related epilepsy and epileptic seizures., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: When feasible, the surgical resection is the standard first step of the management of high-grade gliomas. 5-ALA fluorescence-guided-surgery (5-ALA-FGS) was developed to ease the intra-operative delineation of tumor borders in order to maximize the extent of resection., Methods: A Medline electronic database search was conducted. English language studies from January 1998 until July 2018 were included, following the PRISMA guidelines., Results: 5-ALA can be considered as a specific tool for the detection of tumor remnant but has a weaker sensibility (level 2). 5-ALA-FGS is associated with a significant increase in the rate of gross total resection reaching more than 90% in some series (level 1). Consistently, 5-ALAFGS improves progression-free survival (level 1). However, the gain in overall survival is more debated. The use of 5-ALA-FGS in eloquent areas is feasible but requires simultaneous intraoperative electrophysiologic functional brain monitoring to precisely locate and preserve eloquent areas (level 2). 5-ALA is usable during the first resection of a glioma but also at recurrence (level 2). From a practical standpoint, 5-ALA is orally administered 3 hours before the induction of anesthesia, the recommended dose being 20 mg/kg. Intra-operatively, the procedure is performed as usually with a central debulking and a peripheral dissection during which the surgeon switches from white to blue light. Provided that some precautions are observed, the technique does not expose the patient to particular complications., Conclusion: Although 5-ALA-FGS contributes to improve gliomas management, there are still some limitations. Future methods will be developed to improve the sensibility of 5-ALA-FGS., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: Epileptic seizures impair quality of life in diffuse low-grade glioma (DLGG) patients. Tumor resection significantly impacts postoperative seizure control, but the precise extent of resection (EOR) required for optimal seizure control is not clear yet., Objective: To identify the EOR and residual tumor volume that correlated to postoperative seizure control, defined as a total seizure freedom (Class 1A in reference to Engel classification system) with and without antiepileptic drugs in patients undergoing surgical resection of supratentorial DLGG., Methods: A retrospective review was conducted of all patients who underwent first-line surgical resection of supratentorial DLGG who presented with preoperative seizures without adjuvant oncological treatment. EOR and residual tumor volume were quantified from pre- and post-operative magnetic resonance imagings. Receiver operating characteristic curves were plotted to determine the EOR and residual tumor volume that corresponded to optimal postoperative seizure control., Results: Of the 346 included patients, 65.5% had controlled seizures postoperatively, with higher age at resection (adjusted OR per unit, 1.03 [95% confidence interval:1.01-1.06], P = .043) and higher percentage of resection (adjusted OR per unit, 1.02 [95% confidence interval:1.00-1.03], P < .001) found as independent predictors of postoperative seizure control. Optimal EOR was ≥91% and optimal residual tumor volume was ≤19 cc to improve postoperative seizure control., Conclusion: Postoperative seizure control is more likely when EOR is ≥91% and/or when residual tumor volume is ≤19 cc in supratentorial DLGG gliomas who present with seizures. Resected peritumoral cortex should, however, be taken into account in future studies., (Copyright © 2018 by the Congress of Neurological Surgeons.)

Background: Diffuse low-grade gliomas (DLGGs) are rare and incurable tumors. Whereas maximal safe, functional-based surgical resection is the first-line treatment, the timing and choice of further treatments (chemotherapy, radiation therapy, or combined treatments) remain controversial., Methods: An online survey on the management of DLGG patients was sent to 28 expert centers from the European Low-Grade Glioma Network (ELGGN) in May 2015. It contained 40 specific questions addressing the modalities of use of chemotherapy in these patients., Results: The survey demonstrated a significant heterogeneity in practice regarding the initial management of DLGG patients and the use of chemotherapy. Interestingly, radiation therapy combined with the procarbazine, CCNU (lomustine), and vincristine regimen has not imposed itself as the gold-standard treatment after surgery, despite the results of the Radiation Therapy Oncology Group 9802 study. Temozolomide is largely used as first-line treatment after surgical resection for high-risk DLGG patients, or at progression., Conclusions: The heterogeneity in the management of patients with DLGG demonstrates that many questions regarding the postoperative strategy and the use of chemotherapy remain unanswered. Our survey reveals a high recruitment potential within the ELGGN for retrospective or prospective studies to generate new data regarding these issues.

Competing Interests: There are no conflicts of interest.

Background: Glioblastoma multiforme (GBM) inevitably recurs, but no standard regimen has been established for recurrent patients. Reoperation at recurrence alleviates mass effects, and the survival benefit has been reported in many studies. However, in most studies, the effect of reoperation timing on survival benefit was ignored. The aim of this meta-analysis was to investigate whether reoperation provided similar survival benefits in recurrent GBM patients when it was analyzed as a fixed or time-dependent covariate. Methods: A systematic literature search of PubMed, EMBASE, and Cochrane databases was performed to identify original articles that evaluated the associations between reoperation and prognosis in recurrent GBM patients. Results: Twenty-one articles involving 8,630 patients were included. When reoperation was considered as a fixed covariate, it was associated with better overall survival (OS) and post-progression survival (PPS) (OS: HR = 0.66, 95% CI 0.61-0.71, p < 0.001, I 2 = 0%; PPS: HR = 0.70, 95% CI 0.57-0.88, p < 0.01, I 2 = 70.2%). However, such a survival benefit was not observed when reoperation was considered as a time-dependent covariate (OS: HR = 2.19, 95% CI 1.47-3.27, p < 0.001; PPS: HR = 0.95, 95% CI 0.82-1.10, p = 0.51, I 2 = 0%). The estimate bias caused by ignoring the time-dependent nature of reoperation was further demonstrated by the re-analysis of survival data in three included studies. Conclusions: The timing of reoperation may have an impact on the survival outcome in recurrent GBM patients, and survival benefits of reoperation in recurrent GBM may be overestimated when analyzed as fixed covariates. Proper analysis methodology should be used in future work to confirm the clinical benefits of reoperation.

To complement a project toward label-free optical biopsy and enhanced resection which the overall goal is to develop a multimodal nonlinear endomicroscope, this multimodal approach aims to enhance the accuracy in classifying brain tissue into solid tumor, infiltration and normal tissue intraoperatively. Multiple optical measurements based on one- and two-photon spectral and lifetime autofluorescence, including second harmonic generation imaging, were acquired. As a prerequisite, studying the effect of the time of measurement postexcision on tissue's spectral/lifetime fluorescence properties was warranted, so spectral and lifetime fluorescences of fresh brain tissues were measured using a point-based linear endoscope. Additionally, a comparative study on tissue's optical properties obtained by multimodal nonlinear optical imaging microscope from fresh and fixed tissue was necessary to test whether clinical validation of the nonlinear endomicroscope is feasible by extracting optical signatures from fixed tissue rather than from freshly excised samples. The former is generally chosen for convenience. Results of this study suggest that an hour is necessary postexcision to have consistent fluorescence intensities\lifetimes. The fresh (a,b,c) vs fixed (d,e,f) tissue study indicates that while all optical signals differ after fixation. The characteristic features extracted from one- and two-photon excitation still discriminate normal brain (a,d) cortical tissue, glioblastoma (GBM) (b,e) and metastases (c,f)., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Glioblastoma is the most frequent primary malignant brain tumor. In daily practice and at whole country level, oncological care management for glioblastoma patients is not completely known., Objectives: To describe oncological patterns of care, prognostic factors, and survival for all patients in France with newly-diagnosed and histologically confirmed glioblastoma, and evaluate the impact of extended temozolomide use at the population level., Methods: Nationwide population-based cohort study including all patients with newly-diagnosed and histologically confirmed glioblastoma in France in 2008 and followed until 2015., Results: Data from 2053 glioblastoma patients were analyzed (male/female ratio 1.5, median age 64 years). Median overall survival (OS) was 11.2 [95% confidence interval (CI) 10.7-11.9] months. The first-line therapy and corresponding median survival (MS, in months) were: 13% did not receive any oncological treatment (biopsy only) (MS = 1.8, 95% CI 1.6-2.1), 27% received treatment without the combination of radiotherapy (RT)-temozolomide (MS = 5.9, 95% CI 5.5-6.6), 60% received treatment including the initiation of the concomitant phase of RT-temozolomide (MS = 16.4, 95% CI 15.2-17.4) whom 44% of patients initiated the temozolomide adjuvant phase (MS = 18.9, 95% CI 18.0-19.8). Only 22% patients received 6 cycles or more of adjuvant temozolomide (MS = 25.5, 95% CI 24.0-28.3). The multivariate analysis showed that the risk of mortality was significantly higher for the non-progressive patients who stopped at 6 cycles (standard protocol) than those who continued the treatment, hazard ratio = 1.5 (95% CI 1.2-1.9)., Conclusion: In non-progressive patients, prolonging the adjuvant temozolomide beyond 6 cycles may improve OS.

The World Health Organization classifies diffuse low-grade gliomas (DLGGs) are highly epileptogenic primary brain tumors; epileptic seizures occur in more than 90% of cases. Epileptic seizures and drug resistance progress during the course of DLGGs. The glioma-related epileptogenic mechanisms are multifactorial; epileptogenic foci lie within the infiltrated peritumoral neocortex. A short seizure duration before surgery and a large extent of resection are the main predictors of postoperative seizure control in DLGGs. A supratotal resection of a DLGG can improve postoperative seizure control. Epileptic seizure at diagnosis positively affects DLGGs malignant transformation and overall survival., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To determine the prevalence of developmental venous anomaly in adult patients with diffuse glioma., Methods: We performed a retrospective cohort study (2010-2016) of consecutive adult patients harboring a supratentorial diffuse glioma in 2 centers: Sainte-Anne Hospital (experimental and control sets) and Pitié-Salpêtrière Hospital (external validation set). We included 219 patients with diffuse glioma (experimental set), 252 patients with brain metastasis (control set), and 200 patients with diffuse glioma (validation set). The inclusion criteria were age ≥18 years at diagnosis, histopathologic diagnosis of diffuse glioma according to the 2016 World Health Organization classification of tumors of the CNS, surgery as first-line treatment without previous oncologic treatment, available presurgical MRI performed with similar acquisition protocol, and absence of a nodular-like or a ring-like pattern of contrast enhancement on MRI that may preclude the identification of a possible developmental venous anomaly within the glioma., Results: We found more developmental venous anomaly in the experimental set (21.5%) than in the control set (5.2%, p < 0.001). Similarly, we found more developmental venous anomaly in the validation set (23.5%) than in the control set (5.2%, p < 0.001). There was no difference in the developmental venous anomaly prevalence between the experimental and validation sets. The developmental venous anomaly distribution was not significantly associated with histopathologic, molecular, or imaging findings of the diffuse gliomas., Conclusions: We report and replicate in an external cohort a high prevalence of developmental venous anomaly in adult patients with diffuse glioma, which suggests a potential underlying common predisposition or a causal relationship that requires deeper investigations., (© 2018 American Academy of Neurology.)

The primary line of therapy for high-grade brain tumor is surgical resection, however, identifying tumor margins in vivo remains a major challenge. Despite the progress in computer-assisted imaging techniques, biopsy analysis remains the standard diagnostic tool when it comes to delineating tumor margins. Our group aims to answer this challenge by exploiting optical imaging of endogenous fluorescence in order to provide a reliable and reproducible diagnosis close to neuropathology. In this study, we first establish the ability of two-photon microscopy (TPM) to discriminate normal brain tissue from glioblastomas and brain metastasis using the endogenous fluorescence response of fresh human brain sample. Two-photon fluorescence images were compared to gold standard neuropathology. "Blind" diagnosis realized by a neuropathologist on a group of TPM images show a good sensitivity, 100%, and specificity, 50% to discriminate non tumoral brain tissue versus glioblastoma or brain metastasis. Quantitative analysis on spectral and fluorescence lifetime measurements resulted in building a scoring system to discriminate brain tissue samples.

Background: There is no consensus concerning the management of adult patients with posterior fossa metastasis-associated obstructive hydrocephalus, especially regarding surgical procedures. A literature review was performed to assess the surgical strategy in the management of patients with metastatic brain tumor., Methods: A literature search was conducted of PubMed in November 2017 to identify all studies concerning brain metastases and obstructive hydrocephalus in English. All studies (except case reports and pediatric studies) between December 1953 and November 2017 that were about posterior fossa metastasis-associated obstructive hydrocephalus in adult patients were eligible. Eligible studies were classified by level of evidence. We assessed epidemiology, clinical and imaging findings, neurosurgical management, and prognosis of adult patients with posterior fossa metastasis-associated obstructive hydrocephalus. We suggest some practical considerations and a management decision tree on behalf of the Neuro-oncology Club of the French Society of Neurosurgery, with evidence-based analysis., Results: Direct surgical resection could be considered for patients with asymptomatic obstructive hydrocephalus, and endoscopic third ventriculostomy seems to be a reasonable procedure for patients with symptomatic obstructive hydrocephalus. A ventriculoperitoneal or atrial shunt seems to be a valid alternative when patients have a history of central nervous system infection or ventricular hemorrhage, leptomeningeal carcinomatosis, or unfavorable anatomy for an endoscopic third ventriculostomy to be performed., Conclusions: The Neuro-oncology Club of the French Society of Neurosurgery suggests a prospective assessment of these neurosurgical procedures to compare their safety and efficacy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Numerous molecular alterations have been described in supratentorial high-grade gliomas (1p19q co-deletion, IDH1/2, histone H3, hTERT promotor mutations, loss of ATRX) which have led to a new histomolecular classification of diffuse gliomas. We aimed at describing these alterations in a series of 19 adults with pure cerebellar high-grade gliomas. Systematic immunohistochemical analyses, including that of IDH1R132H, ATRX, p53, PTEN, EGFR, p16, FGFR3, BRAFV600E, mismatch repair proteins, H3K27me3, H3K36me3, and H3K27M; molecular analyses of IDH1/2, hTERT, BRAF, H3F3A, and HIST1H3B mutation hotspots; and EGFR, PTEN FISH were retrospectively performed in a multicentric study. We histopathologically identified 14 glioblastomas, 4 grade III astrocytomas and 1 gliosarcoma. Two cases showed a H3F3A K27M mutation. Only one case harbored a classical profile of glioblastoma with hTERT mutation, EGFR gain and 10q loss. The most frequent alteration was the absence of p16 immunoexpression. We report a histomolecular analysis of pure cerebellar high grade gliomas. The histomolecular profile appears to be different from that of supratentorial gliomas, with no IDH1/2 gene mutations and only 1 case with a classic profile of de novo glioblastoma. In 2 cases, we identified H3F3A K27M mutation, classically described in pediatric midline gliomas.
.

Objective: Imaging studies in diffuse low-grade gliomas (DLGG) vary across centers. In order to establish a minimal core of imaging necessary for further investigations and clinical trials in the field of DLGG, we aimed to establish the status quo within specialized European centers., Methods: An online survey composed of 46 items was sent out to members of the European Low-Grade Glioma Network, the European Association of Neurosurgical Societies, the German Society of Neurosurgery and the Austrian Society of Neurosurgery., Results: A total of 128 fully completed surveys were received and analyzed. Most centers (n = 96, 75%) were academic and half of the centers (n = 64, 50%) adhered to a dedicated treatment program for DLGG. There were national differences regarding the sequences enclosed in MRI imaging and use of PET, however most included T1 (without and with contrast, 100%), T2 (100%) and TIRM or FLAIR (20, 98%). DWI is performed by 80% of centers and 61% of centers regularly performed PWI., Conclusion: A minimal core of imaging composed of T1 (w/wo contrast), T2, TIRM/FLAIR, PWI and DWI could be identified. All morphologic images should be obtained in a slice thickness of ≤ 3 mm. No common standard could be obtained regarding advanced MRI protocols and PET., Importance of the Study: We believe that our study makes a significant contribution to the literature because we were able to determine similarities in numerous aspects of LGG imaging. Using the proposed "minimal core of imaging" in clinical routine will facilitate future cooperative studies.

Accurate intraoperative tumour margin assessment is a major challenge in neurooncology, where sparse tumours beyond the bulk tumour are left undetected under conventional resection. Non-linear optical imaging can diagnose tissue at the sub-micron level and provide functional label-free histopathology in vivo. For this reason, a non-linear endomicroscope is being developed to characterize brain tissue intraoperatively based on multiple endogenous optical contrasts such as spectrally- and temporally-resolved fluorescence. To produce highly sensitive optical signatures that are specific to a given tissue type, short femtosecond pulsed lasers are required for efficient two-photon excitation. Yet, the potential of causing bio-damage has not been studied on neuronal tissue. Therefore, as a prerequisite to clinically testing the non-linear endomicroscope in vivo, the effect of short laser pulse durations (40-340 fs) on ex vivo brain tissue was investigated by monitoring the intensity, the spectral, and the lifetime properties of endogenous fluorophores under 800 and 890 nm two-photon excitation using a bi-modal non-linear endoscope. These properties were also validated by imaging samples on a benchtop multiphoton microscope. Our results show that under a constant mean laser power, excitation pulses as short as 40 fs do not negatively alter the biochemical/ biophysical properties of tissue even for prolonged irradiation.

Background: Following recent studies underlining the differences between de novo and secondary anaplastic meningiomas and the prognostic value of telomerase reverse transcriptase (TERT) promoter mutation, we decided to conduct a multicenter retrospective study to address these questions and determine specific prognostic factors in each of these 2 anaplastic meningioma subgroups., Methods: Among the 68 meningioma cases initially selected, only 57 were confirmed as anaplastic meningiomas after centralized pathological review. TERT promoter mutation analysis was performed in all cases., Results: Median overall survival was 2.6 years and 5-year survival rate was 10%. This study confirmed the better prognosis of de novo anaplastic meningiomas (28 tumors) compared with secondary anaplastic meningiomas (29 tumors) (P = 0.02). In the "de novo" group, meningiomas diagnosed on histological anaplasia alone had a better prognosis than those in patients with a high number of mitoses with or without anaplasia (P = 0.01). In the "secondary" group, tumors demonstrate very heterogeneous clinical courses leading to malignant transformation, and time to first relapse as a low-grade tumor was a strong predictor of overall survival (P = 0.0007). TERT promoter mutation in anaplastic meningiomas was rare (14%) and did not influence overall survival but was associated with a shorter recurrence-free survival in the secondary anaplastic meningioma subgroup (P = 0.02). The absence of TERT promoter methylation, although rare (3/33 cases), may be associated with prolonged overall survival (P = 0.02)., Conclusion: This study highlights the different prognoses of de novo and secondary anaplastic meningiomas with specific prognostic factors in each subgroup. The analysis of TERT mutation and methylation could provide additional prognostic insights.

Clear cell meningioma (CCM) is a rare grade II histopathological subtype that usually occurs in young patients and displays high recurrence rate. Germline SMARCE1 mutations have been described in hereditary forms of this disease and more recently in small syndromic and sporadic CCM series. The diagnostic value of SMARCE1 in distinguishing between CCM and other meningioma variants has not been yet established. The aim of our study was to investigate the status of SMARCE1 in a series of CCMs and its morphological mimickers. We compared the performance of an anti-SMARCE1 antibody and the molecular analysis of the SMARCE1 gene in a retrospective multicenter series of CCMs. All CCMs lossed SMARCE1 immunoexpression. Bi-allelic inactivating events were found by NGS-based sequencing in all of these cases, except for one, which was incompletely explored, but had a wild-type sequence. We then validated the anti-SMARCE1 antibody specificity by analyzing additional 305 pediatric and adult meningiomas of various subtypes and 15 non-meningioma clear cell tumors by SMARCE1 immunohistochemistry. A nuclear immunostaining was preserved in all other meningioma variants, as well as non-meningioma clear cell tumors. In conclusion, our series showed, for the first time, that SMARCE1 immunostaining is a highly sensitive biomarker for CCM, useful as a routine diagnostic biomarker., (© 2017 International Society of Neuropathology.)

Gene fusions of EWSR1 with members of the CREB family of transcription factors (CREB1, ATF1, and CREM) have recently been described in exceptional intracranial myxoid mesenchymal tumors. Although this is a known gene fusion found in various mesenchymal tumors, EWSR1 fusion with CREM has only been observed in 3 intracranial myxoid tumors. In this paper, we present 1 such tumor with in-depth histopathological description and long-term follow-up. There is controversy regarding whether these tumors represent a novel entity or simply an intracranial localization of the myxoid variant of angiomatoid fibrous histiocytoma, a rare soft tissue tumor of the extremities. Out of 11 cases mentioned in the literature, the 3 isolated case reports by Dunham et al, Ochalski et al, and Alshareef et al are designated as angiomatoid fibrous histiocytoma, whereas the others are defined as a novel tumoral entity called intracranial myxoid mesenchymal tumor with EWSR1-CREB fusion. We believe the vast morphological and immunohistochemical spectrum of angiomatoid fibrous histiocytoma makes it difficult to dismiss this diagnosis.

Background: Cranioplasties are an important neurosurgical procedure not only for improved cosmesis but also for improved functional recovery after craniectomy with a large cranial defect. The aim of this study was to identify predictive factors of postcranioplasty complications using custom-made porous hydroxyapatite cranioplasty., Methods: Retrospective review was performed of all patients who underwent a reconstructive cranioplasty using custom-made hydroxyapatite at our institution between February 2008 and September 2017. Postoperative complications considered included bacterial infection, seizures, hydrocephalus requiring ventricular shunt placement, and cranioplasty-to-bone shift. Variables associated at P < 0.1 level in unadjusted analysis were entered into backward stepwise logistic regression models., Results: Of 109 patients included, 15 (13.8%) experienced postoperative infection, with craniectomy performed at an outside institution (adjusted odds ratio [OR] 10.37 [95% confidence interval [CI], 2.03-75.27], P = 0.012) and a previous infection at the surgical site (adjusted OR 6.15 [95%CI, 1.90-19.92], P = 0.003) identified as independent predictors. Six patients (5.5%) experienced postoperative seizures, with stroke (ischemic and hemorrhagic) as a reason for craniectomy (adjusted OR 11.68 [95% CI, 2.56-24.13], P < 0.001) and the presence of seizures in the month before cranioplasty (adjusted OR 9.39 [95% CI, 2.04-127.67], P = 0.002) identified as independent predictors. Four patients (3.7%) experienced postcranioplasty hydrocephalus necessitating shunt placement, and 5 patients (4.6%) experienced cranioplasty-to-bone shift ≥5 mm, but no significant predictive factors were identified for either complication., Conclusions: This study identified possible predictive factors for postcranioplasty complications to help identify at-risk patients, guide prophylactic care, and improve morbidity of this important surgical procedure., (Copyright © 2018 Elsevier Inc. All rights reserved.)