Left Frontal Meningioangiomatosis Associated with Type IIIc Focal Cortical Dysplasia Causing Refractory Epilepsy and Literature Review.

BACKGROUND: We report the surgical management of a lesional drug-resistant epilepsy caused by a meningioangiomatosis associated with a type IIIc focal cortical dysplasia located in the left supplementary motor area in a young male patient. CASE DESCRIPTION: A first anatomically based partial surgical resection was performed on an 11-year-old under general anesthesia without intraoperative mapping, which allowed for postoperative seizure control (Engel IA) for 6 years. The patient then exhibited intractable right sensatory and aphasic focal onset seizures despite 2 appropriate antiepileptic drugs. A second functional-based surgical resection was performed using intraoperative corticosubcortical functional mapping with direct electrical stimulation under awake conditions. A complete surgical resection was performed, and a left partial supplementary motor area syndrome was observed. At 6 months postoperatively, the patient is seizure free (Engel IA) with an ongoing decrease in antiepileptic drug therapy. CONCLUSIONS: Intraoperative functional brain mapping can be applied to preserve the brain function and networks around a meningioangiomatosis to facilitate the resection of potentially epileptogenic perilesional dysplastic cortex and to tailor the extent of resection to functional boundaries.

Prognostic factors for survival in adult patients with recurrent glioblastoma: a decision-tree-based model.

We assessed prognostic factors in relation to OS from progression in recurrent glioblastomas. Retrospective multicentric study enrolling 407 (training set) and 370 (external validation set) adult patients with a recurrent supratentorial glioblastoma treated by surgical resection and standard combined chemoradiotherapy as first-line treatment. Four complementary multivariate prognostic models were evaluated: Cox proportional hazards regression modeling, single-tree recursive partitioning, random survival forest, conditional random forest. Median overall survival from progression was 7.6 months (mean, 10.1; range, 0-86) and 8.0 months (mean, 8.5; range, 0-56) in the training and validation sets, respectively (p = 0.900). Using the Cox model in the training set, independent predictors of poorer overall survival from progression included increasing age at histopathological diagnosis (aHR, 1.47; 95% CI [1.03-2.08]; p = 0.032), RTOG-RPA V-VI classes (aHR, 1.38; 95% CI [1.11-1.73]; p = 0.004), decreasing KPS at progression (aHR, 3.46; 95% CI [2.10-5.72]; p < 0.001), while independent predictors of longer overall survival from progression included surgical resection (aHR, 0.57; 95% CI [0.44-0.73]; p < 0.001) and chemotherapy (aHR, 0.41; 95% CI [0.31-0.55]; p < 0.001). Single-tree recursive partitioning identified KPS at progression, surgical resection at progression, chemotherapy at progression, and RTOG-RPA class at histopathological diagnosis, as main survival predictors in the training set, yielding four risk categories highly predictive of overall survival from progression both in training (p < 0.0001) and validation (p < 0.0001) sets. Both random forest approaches identified KPS at progression as the most important survival predictor. Age, KPS at progression, RTOG-RPA classes, surgical resection at progression and chemotherapy at progression are prognostic for survival in recurrent glioblastomas and should inform the treatment decisions.

The forgotten foramina: a study of the anterior cribriform plate.

PURPOSE: The olfactory cleft has garnered interest since the advent of endoscopic skull base surgery. Its precise anatomy, however, is still partially unknown. According to Rouvière, an "ethmoidal foramen" is located in its antero-medial part and contains a process of the dura mater. In a more lateral and anterior location, a second foramen, the "cribroethmoidal foramen", contains the anterior ethmoidal nerve. The aim of this study was to verify the existence of these elements and to establish landmarks for surgery. METHODS: We performed an anatomical and histological study of eight olfactory clefts in four cadavers using both endonasal endoscopic and endocranial dissection. RESULTS: An ethmoidal and a cribroethmoidal foramen were found in, respectively, 100 and 75% of cases. Their mean length was, respectively, 4.1 and 1.8 mm. They were located, respectively, in mean at 5.3 and 5.8 mm from the anterior ethmoidal artery. CONCLUSION: Our anatomical study demonstrates the existence of both foramina. The ethmoidal foramen clearly represents an area of least resistance in the anterior part of the olfactory cleft, which could predispose to anterior skull base cerebrospinal fluid leaks and meningoceles.

Prognostic Relevance of Histomolecular Classification of Diffuse Adult High-Grade Gliomas with Necrosis.

Diffuse adult high-grade gliomas (HGGs) with necrosis encompass anaplastic oligodendrogliomas (AOs) with necrosis (grade III), glioblastomas (GBM, grade IV) and glioblastomas with an oligodendroglial component (GBMO, grade IV). Here, we aimed to search for prognostic relevance of histological classification and molecular alterations of these tumors. About 210 patients were included (63 AO, 56 GBM and 91 GBMO). GBMO group was split into "anaplastic oligoastrocytoma (AOA) with necrosis grade IV/GBMO," restricted to tumors showing intermingled astrocytic and oligodendroglial component, and "GBM/GBMO" based on tumors presenting oligodendroglial foci and features of GBM. Genomic arrays, IDH1 R132H expression analyses and IDH direct sequencing were performed. 1p/19q co-deletion characterized AO, whereas no IDH1 R132H expression and intact 1p/19q characterized both GBM and GBM/GBMO. AOA with necrosis/GBMO mainly demonstrated IDH1 R132H expression and intact 1p/19q. Other IDH1 or IDH2 mutations were extremely rare. Both histological and molecular classifications were predictive of progression free survival (PFS) and overall survival (OS) (P < 10(-4) ). Diffuse adult HGGs with necrosis can be split into three histomolecular groups of prognostic relevance: 1p/19q co-deleted AO, IDH1 R132H-GBM and 1p/19q intact IDH1 R132H+ gliomas that might be classified as IDH1 R132H+ GBM. Because of histomolecular heterogeneity, we suggest to remove the name GBMO.

Mitotic index, microvascular proliferation, and necrosis define 3 groups of 1p/19q codeleted anaplastic oligodendrogliomas associated with different genomic alterations.

BACKGROUND: The aim of this study was to correlate histological features and molecular characteristics in anaplastic oligodendrogliomas (AOs). METHODS: The histological characteristics of 203 AO patients, enrolled in the French national network POLA, were analyzed. The genomic profiles of 191 cases were studied using genomic arrays. IDH mutational status was assessed by immunohistochemistry and direct sequencing. RESULTS: 1p/19q codeletion was present in 79% of cases and was associated with alpha-internexin expression (P < 10(-4)), IDH1/2 mutation (P < 10(-4)), chromosome 4 loss (P < 10(-3)), and better overall survival (P < 10(-4)). Based on mitotic index, microvascular proliferation (MVP), and necrosis, 3 groups of 1p/19q codeleted AOs were identified: (group 1) AO with more than 5 mitoses per 10-HPF, no MVP, and no necrosis; (group 2) AO with MVP and no necrosis; and (group 3) AO with MVP and necrosis. Compared with group 1, groups 2 and 3 AOs had a higher mean Ki-67 proliferation index and a higher rate of 9p and 9q losses. Compared with group 2, group 3 AOs had a higher number of chromosomal alterations including chromosome 4 loss. In the subgroup of 157 1p/19q codeleted AOs, chromosomal instability was associated with shorter progression-free survival (P = .024) and shorter overall survival (P = .023). CONCLUSIONS: The present study shows that oligodendrogliomas with classic histological features remain a molecularly heterogeneous entity and should be stratified according to 1p/19q status because of its major prognostic relevance. Moreover, 1p/19q codeleted AOs are also heterogeneous. Interestingly, mitotic index, MVP, and necrosis help to classify them into 3 groups associated with distinct genomic alterations.

SNP array analysis reveals novel genomic abnormalities including copy neutral loss of heterozygosity in anaplastic oligodendrogliomas.

Anaplastic oligodendrogliomas (AOD) are rare glial tumors in adults with relative homogeneous clinical, radiological and histological features at the time of diagnosis but dramatically various clinical courses. Studies have identified several molecular abnormalities with clinical or biological relevance to AOD (e.g. t(1;19)(q10;p10), IDH1, IDH2, CIC and FUBP1 mutations).To better characterize the clinical and biological behavior of this tumor type, the creation of a national multicentric network, named "Prise en charge des OLigodendrogliomes Anaplasiques (POLA)," has been supported by the Institut National du Cancer (InCA). Newly diagnosed and centrally validated AOD patients and their related biological material (tumor and blood samples) were prospectively included in the POLA clinical database and tissue bank, respectively.At the molecular level, we have conducted a high-resolution single nucleotide polymorphism array analysis, which included 83 patients. Despite a careful central pathological review, AOD have been found to exhibit heterogeneous genomic features. A total of 82% of the tumors exhibited a 1p/19q-co-deletion, while 18% harbor a distinct chromosome pattern. Novel focal abnormalities, including homozygously deleted, amplified and disrupted regions, have been identified. Recurring copy neutral losses of heterozygosity (CNLOH) inducing the modulation of gene expression have also been discovered. CNLOH in the CDKN2A locus was associated with protein silencing in 1/3 of the cases. In addition, FUBP1 homozygous deletion was detected in one case suggesting a putative tumor suppressor role of FUBP1 in AOD.Our study showed that the genomic and pathological analyses of AOD are synergistic in detecting relevant clinical and biological subgroups of AOD.