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OBJECTIVE Surgery for giant diffuse lower-grade gliomas (LGGs) is challenging, and very few data have been reported on this topic in the literature. In this article, the authors investigated surgical, functional, and oncological aspects in patients who underwent awake resection for large LGGs with a volume > 100 cm3. METHODS The authors retrospectively reviewed a consecutive cohort of patients who underwent surgery in an awake condition for an LGG (WHO grade 2 with possible foci of grade 3 transformation) with a volume > 100 cm3. RESULTS A total of 108 patients were included, with a mean age of 36.1 ± 8.5 years. The mean presurgical LGG volume was 136.7 ± 34.5 cm3. In all but 2 patients a disconnection resective surgery up to functional boundaries was possible thanks to active patient collaboration during the awake period. At 3 months of follow-up, all but 1 patient had a normal neurological examination, with a mean Karnofsky Performance Status (KPS) score of 89.8 ± 10.36. In all patients with preoperative epilepsy, there was postoperative control or significant reduction of seizure events. Moreover, 85.1% of patients returned to work. The mean extent of resection (EOR) was 88.9% ± 7.0%, with a mean residual tumor volume (RTV) of 16.3 ± 12.0 cm3 (median RTV 15 cm3). Pathological examination revealed 73 grade 2 gliomas (67.6%; 26 oligodendrogliomas and 47 astrocytomas) and 35 gliomas with foci of grade 3 (32.4%; 19 oligodendrogliomas and 16 astrocytomas). During the postoperative period, 93.6% of patients underwent adjuvant chemotherapy with a median interval between surgery and first chemotherapy of 14 months (IQR 2–26 months), and 55% of patients had radiotherapy with a median interval of 38.5 months (IQR 18–59.8 months). At the last follow-up, 69.7% of patients were still alive with a median follow-up of 62 months (IQR 36–99 months). Overall survival (OS) rates at 1, 5, and 10 years were 100% (95% CI 0.99–1), 80% (95% CI 0.72–0.9), and 58% (95% CI 0.45–0.73), respectively. The median OS was 138 months. In multivariable Cox regression analysis, RTV was established as the only independent prognostic factor for survival. CONCLUSIONS With the application of rigorous surgical methodology based on functional-guided resection, resection of giant LGGs (volume > 100 cm3) can be reproducibly achieved during surgery with patients under awake mapping with both favorable functional results (< 1% permanent neurological worsening) and favorable long-term oncological outcomes (median OS > 11 years, with a more significant benefit when the RTV is < 15 cm3).

Despite their rarity, PIK3CA mutations in meningiomas have raised interest as potentially targetable, ubiquitous mutations owing to their presence in sporadic benign and malignant tumors but also in hormone-related cases. Using new genetically engineered mouse models, we here demonstrate that Pik3ca mutations in post-natal meningeal cells are sufficient to promote meningioma formation but also tumor progression in mice. Conversely, hormone impregnation, wether alone or in association with Pik3ca and Nf2 mutations, fails to induce meningioma tumorigenesis while promoting breast tumor formation. We then confirm in vitro the effect of Pik3ca mutations but not hormone impregnation on the proliferation of primary cultures of mouse meningeal cells. Finally we show by exome analysis of breast tumors and meninges that hormone impregnation promotes breast tumor formation without additional somatic oncogenic mutation but is associated with an increased mutational burden on Pik3ca mutant background. Taken together, these results tend to suggest a prominent role of Pik3ca mutations over hormone impregnation in meningioma tumorigenesis, the exact effect of the latter still to be discovered.

A multicystic intraventricular tumour of the right ventricular atrium was incidentally diagnosed on follow-up imaging of a 61-year-old man with a history of prostatic adenocarcinoma. Surgical resection of the lesion was performed after a one-year radio-clinical follow-up due to progressive expansion of the lesion size and a rising prostate specific antigen blood-level. Morphological features with papillary pattern on pathological examination were compatible with malignant adenocarcinoma or choroid plexus carcinoma. The immunoprofile was conclusive for an exceptional choroid plexus metastasis (CPM) of a prostatic adenocarcinoma. To our knowledge, this is the first report of a proven prostatic origin of a CPM.

International audience; PURPOSE: Meningiomas represent the most frequent tumor of the central nervous system in adults. While most meningiomas are efficiently treated by surgery and radiotherapy/radiosurgery, there is a small portion of radiation- and surgery-refractory tumors for which there is no clear recommendation for optimal management. The French National Tumor Board Meeting on Meningiomas (NTBM) offers a glimpse on the current management of such patients. METHODS: We retrospectively reviewed the charts of patients presented to the multidisciplinary Meeting between 2016 and 2019. We selected patients with a progressive disease after at least two treatments, including surgery and radiotherapy. RESULTS: In this multicentric cohort of 86 cases, patients harbored 17 (19.8%) WHO Grade I, 48 (55.8%) WHO Grade II and 21 (24.4%) WHO Grade III tumors. The median number of treatments received before inclusion was 3 (range: 2 - 11). Following the Board Meeting, 32 patients (37.2%) received chemotherapy, 11 (12.8%) surgery, 17 (19.8%) radiotherapy, 14 (16.3%) watchful observation and 12 (13.9%) palliative care. After a mean follow-up of 13 months post-inclusion, 32 patients (37.2%) had died from their disease. The mean progression free survival was 27 months after radiotherapy, 10 months after surgery, 8.5 months after chemotherapy (Bevacizumab: 9 months - Octreotide/Everolimus: 8 months). CONCLUSIONS: Surgery- and radiation-refractory meningiomas represent a heterogeneous group of tumors with a majority of WHO Grade II cases. If re-irradiation and redo-surgery are not possible, bevacizumab and octreotide-everolimus appear as a valuable option in heavily pre-treated patients considering the current EANO guidelines.

International audience; Background: Incidentally discovered suspected diffuse low-grade gliomas (LGGs) on brain imaging pose a challenge to neurosurgeons. Modern surgical series of LGGs favor early prophylactic surgery with a maximal extent of resection. However, some nonevolutive lesions may mimic LGGs on magnetic resonance imaging (MRI).Objective: To determine objective criteria to advocate surgical resection of an incidentally discovered suspected LGG based upon MRI findings.Methods: The prospective cohort of patients referred to our institution for an incidental finding suggestive of LGG was retrospectively reviewed. Stable lesions underwent systematic serial MRI follow-up, while evolutive lesions underwent prophylactic surgery under awake conditions. Initial clinico-radiological features were compared between stable and evolutive lesions in order to determine predictive criteria of further evolution.Results: Among 101 patients referred for surgical resection of incidentally discovered suspected LGG in our center, 19 patients (18.8%) had nonevolutive MRI lesions after a mean follow-up of 46.9 ± 34.9 mo. Insular topography (P = .003), higher mean volume at discovery (19.2 vs 5.2 cm3, P < .001), and adjacent sulcal effacement (P = .001) were associated with evolutive lesions. Histopathological diagnosis of LGG was confirmed in all surgical cases.Conclusion: Increasing volume is an effective predictor of LGG diagnosis in incidental MRI findings, as all patients who subsequently underwent surgery had confirmed histopathological diagnosis of diffuse glioma. Approximately 18.8% of incidental findings were stable over time. Insular topography, adjacent sulcal effacement, and volume greater than 4.5 cm3 were predictive of further radiological progression. These significant elements will help neurosurgeons to define personalized strategies in this complex setting of incidental discovery.

Meningiomas are tumors arising from the meninges and represent the most frequent central nervous system tumors in adults. Recent large-scale genetic studies and preclinical meningioma mouse modelling led to a better comprehension of meningioma development and suggested evidences of close relationships between meningeal embryology and tumorigenesis. In this non-systematic review, we summarize the current knowledge on meningeal embryology and developmental biology, and illustrate how meningioma tumorigenesis is deeply related to meningeal embryology, concerning the potential cell of origin, the role of reactivation of embryonic stem cells, the influence of the embryonic tissue of origin, and the parallelism between topography-dependant molecular pathways involved in normal meninges and in meningioma development. Our study emphasizes why future studies on meningeal embryology are mandatory to affine our comprehension of mechanisms underlying meningioma initiation and development.

International audience; We report a case of malignant melanoma revealed by a metastasis to the pituitary gland. The tumor was misdiagnosed as a pituitary adenoma and aggressive transsphenoidal surgery was complicated by a cerebrospinal fluid fistula. Nine weeks later, the patient presented multiple leptomeningeal and brain metastases spreading from the sellar region. Regarding these observations, we conducted a systematic review of the literature in order to investigate clinicoradiological features that should lead clinicians to suspect pituitary metastasis and how it should impact the surgical management.

Background Cerebral cavernous malformations (CCMs) are common sporadic and inherited vascular malformations of the central nervous system. Although familial CCMs are linked to loss-of-function mutations in KRIT1 (CCM1), CCM2, or PDCD10 (CCM3), the genetic cause of sporadic CCMs, representing 80% of cases, remains incompletely understood. Methods We developed two mouse models harboring mutations identified in human meningiomas with the use of the prostaglandin D2 synthase (PGDS) promoter. We performed targeted DNA sequencing of surgically resected CCMs from patients and confirmed our findings by droplet digital polymerase-chain-reaction analysis. Results We found that in mice expressing one of two common genetic drivers of meningioma - Pik3ca H1047R or AKT1 E17K - in PGDS-positive cells, a spectrum of typical CCMs develops (in 22% and 11% of the mice, respectively) instead of meningiomas, which prompted us to analyze tissue samples from sporadic CCMs from 88 patients. We detected somatic activating PIK3CA and AKT1 mutations in 39% and 1%, respectively, of lesion tissue from the patients. Only 10% of lesions harbored mutations in the CCM genes. We analyzed lesions induced by the activating mutations Pik3ca H1074R and AKT1 E17K in mice and identified the PGDS-expressing pericyte as the probable cell of origin. Conclusions In tissue samples from sporadic CCMs, mutations in PIK3CA were represented to a greater extent than mutations in any other gene. The contribution of somatic mutations in the genes that cause familial CCMs was comparatively small. (Funded by the Fondation ARC pour la Recherche contre le Cancer and others.).

International audience; AimsMutations activating the Hedgehog (Hh) signalling pathway have been described in anterior skull base meningiomas, raising hope for the use of targeted therapies. However, identification of Hh-activated tumours is hampered by the lack of a reliable immunohistochemical marker. We report the evaluation of GAB1, an immunohistochemical marker used to detect Hh pathway activation in medulloblastoma, as a potential marker of Hh-activated meningiomas.MethodsGAB1 staining was compared to SMO mutation detection with Sanger and NGS techniques as well as Hh pathway activation study through mRNA expression level analyses in a discovery set of 110 anterior skull base meningiomas and in a prospective validation set of 21 meningiomas.ResultsUsing an expression score ranging from 0 to 400, we show that a cut-off score of 250 lead to excellent detection of Hh pathway mutations (sensitivity 100%, specificity 86%). The prospective validation set confirmed the excellent negative predictive value of GAB1 to exclude Hedgehog independent meningiomas. We describe a large series of 32 SMO-mutant meningiomas and define multiple ways of Hh activation, either through somatic mutations or associated with mutually co-exclusive SHH (Sonic Hedgehog) or IHH (Indian Hedgehog) overexpression independent of the mutations.ConclusionThe assessment of GAB1 expression by an immunohistochemical score is a fast and cost-efficient tool to screen anterior skull base meningiomas for activation of the Hedgehog pathway. It could facilitate the identification of selected cases amenable to sequencing for hedgehog pathway genes as predictive markers for targeted therapy.

Simple Summary Meningiomas are the most frequent primitive central nervous tumors in adults. Mouse models of cancer are used to study disease mechanisms and to establish preclinical drug testing. In this review, we describe all mouse models of meningiomas reported in the literature. This includes graft models wherein human meningioma cells are injected in nude mice, and genetically engineered mouse models. Taken together, these models have offered the possibility to study tumorigenesis mechanisms of initiation and progression and have provided useful tools for preclinical testing of a huge range of innovative drugs and therapeutic options. This review provides a systematic and comprehensive overview on how these different models can be used depending on the scientific questions to be answered. Abstract Meningiomas are the most frequent primitive central nervous system tumors found in adults. Mouse models of cancer have been instrumental in understanding disease mechanisms and establishing preclinical drug testing. Various mouse models of meningioma have been developed over time, evolving in light of new discoveries in our comprehension of meningioma biology and with improvements in genetic engineering techniques. We reviewed all mouse models of meningioma described in the literature, including xenograft models (orthotopic or heterotopic) with human cell lines or patient derived tumors, and genetically engineered mouse models (GEMMs). Xenograft models provided useful tools for preclinical testing of a huge range of innovative drugs and therapeutic options, which are summarized in this review. GEMMs offer the possibility of mimicking human meningiomas at the histological, anatomical, and genetic level and have been invaluable in enabling tumorigenesis mechanisms, including initiation and progression, to be dissected. Currently, researchers have a range of different mouse models that can be used depending on the scientific question to be answered.

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.

Cerebral venous sinus thrombosis (CVST) following brain surgery is a feared complication, commonly described after direct injury to the sinus. However, distant CVST occurring away from the operative area are unexpected. Yet, there is a strong physio-pathological rational supporting the role of intracranial hypotension as a risk factor of CVST. Here, we report the case of a frontal arachnoid cyst depletion followed by an extensive contralateral CVST. Given the major prognostic consequences observed in this clinical illustration, we further investigated the hypothesis of intracranial hypotension as an etiology of CVST by carrying out a systematic review of the literature.

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BackgroundChronic subdural hematoma (CSDH) is a common condition requiring surgical treatment; however, recurrence occurs in 15% of cases at 1 year. Middle meningeal artery (MMA) embolization has recently emerged as a promising treatment to prevent CSDH recurrence.ObjectiveTo investigate the effect of MMA embolization on hematoma volume resorption (HVR) after surgery in symptomatic patients.MethodsFrom April 2018 to October 2018, participants with CSDH requiring surgery were prospectively randomized in a pilot study, and received either surgical treatment alone (ST group) or surgery and adjuvant MMA embolization (ST+MMAE group). The primary outcome was HVR measured on the 3 month CT scan compared with the immediate pre-embolization CT scan. Secondary outcomes were clinical recurrence of CSDH and safety measures.Results46 patients were randomized and 41 of these achieved a 3 month follow-up . Twenty-one patients received MMA embolization. At 3 months, the HVR from postsurgical level was higher in the ST+MMAE group (mean difference 17.5 mL, 95% CI 3.87 to 31.16 mL; p=0.015). Two participants presented a CSDH recurrence (one in each group). One patient died (ST group). No MMA embolization-related adverse events were reported.ConclusionThe addition of MMA embolization to surgery led to an increase in CSDH resorption at 3 months. One recurrence of CSDH was reported in each group, and there were no treatment-related complications.

International audience; To report the results of a series of patients undergoing the endoscopic subperichondrial transseptal (STRAS) approach for pituitary surgery and to evaluate the efficiency and the safety of this approach. Methods: This is a single-centre retrospective study including all patients undergoing pituitary lesion resection through the STRAS approach from January 2002 to December 2017 by a multidisciplinary surgical team (ENT and neurosurgeon). Demographic data, tumour type, complication rate and pre- and post-operative visual, endocrine and tumour status were retrospectively analysed.Results: 119 patients were included in the study, 80 (67%) presenting macroadenoma, 24 (20%) microadenoma (20%) and 6 (5%) giant adenoma. 61 (51%) patients had secreting adenoma and 51 (42%) patient had non-functioning adenoma. The STRAS approach allowed a good visualization of intrasphenoidal and intrasellar anatomical landmarks in all cases and no patient needed turbinate resection. No patient died or had neurological deficit. Endocrine remission or control was achieved in 90.5% of hormone-secreting microadenomas and in 84.2% of hormone-secreting macroadenomas. Gross-total resection was achieved for 39 patients (48.8%) of the 80 macroadenomas. Nasal complication rate was very low, with no septal perforation and two epistaxis (1.7%) medically treated.Conclusion: The STRAS approach is an elegant approach to the sphenoid sinus that enables a good exposure of the intrasphenoidal anatomical landmarks with a maximal preservation of the nasal mucosa. This approach allows an intrasellar work with great comfort and safety for the surgeon using a two-hand or a four-hand technique.

International audience; BACKROUND:Increasing indications for endoscopic endonasal approaches have led neurosurgeons to develop new reconstruction techniques for larger skull base defects. Vascularized grafts have been a great adjunction to reduce the rate of cerebrospinal fluid leak and can also be used to cover exposed critical structures such as the internal carotid artery. The nasoseptal flap and the inferior or middle turbinate flap are thus widely used in endoscopic skull base surgery, but may be insufficient for very large defects.OBJECTIVE:To present a new mucosal flap used to cover large skull base defects in which the mucosa of the inferior turbinate, inferior meatus, nasal floor, and nasal septum is harvested in 1 piece keeping both vascular pedicles intact (inferior turbinate and septal arteries).METHODS:We describe a surgical technique to harvest a combined inferior turbinate-nasoseptal flap.RESULTS:Technical pearls and surgical pitfalls are described through 2 clinical cases in which the nasoseptal mucosa was partially damaged during a previous surgery, rendering the nasoseptal flap insufficient by itself. The flap is harvested thanks to 2 mucosal cuts: a first circular cut around the choanal arch and the junction between the hard and the soft palate, and a second one combining classical cuts of the nasoseptal flap and the inferior turbinate flap.CONCLUSION:The inferior turbinate-nasoseptal flap can be a useful alternative in patients whose septal mucosa was partially damaged and/or with very large postoperative skull base defects.

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.

International audience; OBJECTIVE:It is unknown whether spinal instrumentation is required to prevent deformity after partial vertebrectomy in the treatment of primary bronchogenic carcinomas invading the spine (PBCIS). In this study, we focus on the postoperative spine deformity in patients who underwent operation for partial vertebrectomies without instrumentation during en bloc PBCIS resection. Our objective was to determine whether deformity depends on the type of vertebral resection and if any vertebral resection threshold can be observed to justify additional spinal instrumentation.METHODS:This is a retrospective study, including all patients with PBCIS operated without spinal instrumentation from 2009 to 2018. Partial vertebrectomies were classified into categories A, B, and C depending on vertebral resection. Patients had long-term radiologic follow-up to assess the spine deformity evolution.RESULTS:Eighteen patients were included. The median follow-up was 27 months. Four patients underwent a secondary posterior instrumentation surgical procedure due to progressive spinal deformity. A low-risk group of deformation was characterized as type A resection and type B resection on less than 3 vertebrae.CONCLUSIONS:There are no validated criteria to justify a systematic spinal instrumentation when performing a partial vertebrectomy during en bloc resection of PBCIS. Performed alone without spine instrumentation, both type A and type B resections on less than 3 resected vertebrae were not subject to sagittal and coronal deformity even after a long follow-up, emphasizing that a systematic stabilization is not needed in this low-risk group. These results could help to reduce the perioperative morbidity of these procedures that are usually long and complex.

International audience; Background: Herpes simplex encephalitis (HSE) and glioblastoma multiforme (GBM) co-occurrence has been described in few cases presenting immunocompromised status related to chemotherapy or chemoradiotherapy. Focal encephalitis over surgical edge of resection occurring shortly after GBM resection is rarely reported, and such infection has never been reported in low-grade glioma with secondary malignant transformation (i.e., secondary GBM). Here, we report a case of HSE misdiagnosed in the early postoperative course following a secondary GBM resection. We also provide a review of the literature about HSE occurring after glioma surgery. Case description: We report a case of an acute HSE with a fatal outcome occurring shortly after surgery for a secondary GBM. The patient presented with hyperthermia 12 days after the surgery and was treated with empirical antibiotics. She later suffered from seizure and neurologic deterioration, leading to death despite delayed antiviral administration. Magnetic resonance imaging revealed considerable fluid-attenuated inversion-recovery signal progression at the edge of the surgical resection and polymerase chain reaction amplification of herpes simplex virus (HSV) 1 DNA was positive. Conclusions: Clinicians should be aware of the existing co-occurrence between HSV infections and GBM during the postoperative course. Cerebrospinal fluid analysis with HSV polymerase chain reaction testing should be promptly undertaken, and some keys clinical elements should justify early empirical treatment, including acyclovir administration. The significant prognostic implication of HSE complicating GBM must raise the attention of neurosurgeon and neuro-oncologist about this entity.

International audience; BACKGROUND: Bow hunter's syndrome is a symptomatic vertebrobasilar insufficiency resulting from a rotational stenosis or occlusion of a dominant vertebral artery (VA). The VA is dynamically compressed by cervical osteoarthritis (discovertebral structure or osteophytes) during head rotation or neck extension. Diagnosis is based on dynamic computed tomography angiography and confirmed with dynamic catheter angiography. Surgery tends to be the best treatment option in most cases. Dynamic intraoperative assessment of VA decompression seems to improve surgical results but remains poorly evaluated in the literature. CASE DESCRIPTION: A 70-year-old man with bow hunter's syndrome related to left VA compression by C3-4 osteophyte protrusion presented with syncopal episodes during left head rotation. Bow hunter's syndrome was successfully managed with an anterior transuncal surgical decompression of the left VA and C3-4 fusion. Surgical decompression was guided by dynamic intraoperative catheter angiography and secured with an intra-arterial remodeling balloon placed just before surgery. The patient was symptom-free after surgery. CONCLUSIONS: Surgical decompression guided by dynamic intraoperative catheter angiography leads to selective VA release and allows real-time assessment of the efficacy of the decompression. This multidisciplinary treatment involving neurosurgical and neuroradiologic teams is a simple and effective treatment. Dynamic intraoperative catheter angiography is an essential guide to perform selective decompression of the VA, and implementation of an intra-arterial remodeling balloon can improve the safety of surgery making this method valuable compared with other intraoperative assessment techniques, such as Doppler ultrasound and indocyanine green fluorescent videography.

International audience; Somatic activating mutations of smoothened (SMO), a component of the embryonic sonic hedgehog (SHH) signaling pathway, are found in 3-5% of grade I meningiomas, most of them corresponding to meningothelial meningiomas located at the anterior skull base. By generating different developmental stage-specific conditional activations in mice, we define a restricted developmental window during which conditional activation of Smo in Prostaglandin D2-synthase-positive mesoderm-derived meningeal layer of the skull base results in meningothelial meningioma formation. We show a selective vulnerability of the arachnoid from the skull base to Smo activation to initiate tumor development. This prenatal period and specific topography are correlated to the timing and location of SHH signaling involvement in the formation of craniofacial and meninges patterning, strongly corroborating the hypothesis of a developmental origin for Smo-activated meningiomas. Finally, we provide preclinical in vitro evidence of the efficacy of the SMO-inhibitor Sonidegib, supporting further preclinical and clinical evaluation of targeted treatment for refractory SMO-mutant meningiomas.

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.

International audience; OBJECTIVE:Awake craniotomy (AC) in brain lesions has allowed an improvement of both oncologic and functional results. However, intraoperative seizures (IOSs) were reported as a cause of failure of AC. Here, we analyze the incidence, risk factors, and consequences of IOSs in a prospective cohort of 374 ACs without electrocorticography (ECoG).METHODS:We performed a prospective study including all patients who underwent AC for an intra-axial supratentorial cerebral lesion from 2009-2014 in our department. Occurrence of IOS was analyzed with respect to medical and epilepsy history, tumor characteristics, operative technique, and postoperative outcomes.RESULTS:The study comprised 374 patients with a major incidence of low-grade glioma (86%). Most of the patients (83%) had epilepsy history before surgery (20% had intractable seizures). Preoperative mean Karnofsky performance scale (KPS) score was 91. IOSs occurred in 13 patients (3.4%). All IOSs were partial seizures, which quickly resolved by irrigation with cold Ringer lactate. No procedure failed because of IOS, and the rate of aborted AC whatever the cause was nil. Mean stimulation current intensity for cortical and subcortical mapping was 2.25 ± 0.6 mA. Presurgical refractory epilepsy was not associated with a higher incidence of IOS. Three months after surgery, no patients had severe or disabling permanent worsening, even within the IOS group (mean KPS score of 93.7).CONCLUSIONS:AC for intra-axial brain lesion can be safely and reproducibly achieved without ECoG, with a low rate of IOS and excellent functional results, even in patients with preoperative intractable epilepsy.

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Background Meningiomas are the most common primary intracranial tumors in adults. Identification of SMO and AKT1 mutations in meningiomas has raised the hope for targeted therapies. It would be useful to know the precise frequency of these mutations in anatomical subgroups and clarify their prognostic value. Methods We used the Sanger sequencing technique to characterize 79 samples of olfactory groove meningiomas for SMO (L412F and W535L) and AKT1E17K mutations. We reviewed clinical data to assess the prognostic value of these mutations in this anatomical subgroup. Results Out of the 79 patients with olfactory groove meningiomas, we identified targetable mutations in 34 patients (43%) (22 patients [28%] with SMO mutation-L412F almost exclusively-and 12 patients [15%] with AKT1 mutation). Meningiomas in the SMO-mutant group had an overall 36% recurrence rate, significantly higher than in the AKT1-mutant group (16%) and in the "SMO and AKT1 wildtype" group (11%) (χ2 test, P = .04). All late recurrences (after 5 y) occurred in the SMO-mutant group. Among grade I meningiomas, the SMO-mutant group was identified as having a significantly poorer prognosis. World Health Organization histological grade II (P = .006) and incomplete resection (P = .001) were independently associated with shorter recurrence-free survival. Conclusion Molecular diagnosis of SMOL412F/W535L and AKT1E17K mutations improves prognostic evaluation in olfactory groove meningiomas and opens new therapeutic perspectives with SMO or AKT inhibitors for recurrent cases.

Object Spinal instrumentation has a high rate of surgical site infection (SSI), but results greatly vary depending on surveillance methodology, surgical procedures, or quality of follow-up. Our aim was to study true incidence of SSI in spinal surgery by significant data collection, and to compare it with the results obtained through the hospital information system. Methods This work is a single center prospective cohort study that included all patients consecutively operated on for spinal instrumentation by posterior approach over a six-month period regardless the etiology. For all patients, a “high definition” prospective method of surveillance was performed by the infection control (IC) department during at least 12 months after surgery. Results were then compared with findings from automatic surveillance though the hospital information system (HIS). Results One hundred and fifty-four patients were included. We found no hardly difference between “high definition” and automatic surveillance through the HIS, even if HIS tended to under-estimate the infection rate: rate of surgical site infection was 2.60% and gross SSI incidence rate via the hospital information system was 1.95%. Smoking and alcohol consumption were significantly related to a SSI. Conclusion Our SSI rates to reflect the true incidence of infectious complications in posterior instrumented adult spinal surgery in our hospital and these results were consistent with the lower levels of published infection rate. In-house surveillance by surgeons only is insufficiently sensitive. Further studies with more patients and a longer inclusion time are needed to conclude if SSI case detection through the HIS could be a relevant and effective alternative method.

International audience; PURPOSE:While image guidance and neuronavigation have enabled a more accurate placement of pedicle implants, they can inconvenience the surgeon. Robot-assisted placement of pedicle screws appears to overcome these disadvantages. However, recent data concerning the superiority of currently available robots in assisting spinal surgeons are conflicting. The aim of our study was to evaluate the percentage of accurately placed pedicle screws, inserted using a new robotic-guidance system.METHOD:20 Patients were operated on successively by the same surgeon using robotic assistance (ROSA™, Medtech) (Rosa group 10 patients, n = 40 screws) or by the freehand conventional technique (Freehand group 10 patients, n = 50 screws). Patient characteristics as well as the duration of the operation and of exposure to X rays were recorded.RESULTS:The mean age of patients in each group (RG and FHG) was 63 years. Mean BMI and operating time among the RG and FHG were, respectively, 26 and 27 kg/m(2), and 187 and 119 min. Accurate placement of the implant (score A and B of the Gertzbein Robbins classification) was achieved in 97.3% of patients in the RG (n = 36) and in 92% of those in the FHG (n = 50). Four implants in the RG were placed manually following failed robotic assistance.CONCLUSION:We report a higher rate of precision with robotic as compared to the FH technique. Providing assistance by permanently monitoring the patient's movements, this image-guided tool helps more accurately pinpoint the pedicle entry point and control the trajectory. Limitations of the study include its small sized and non-randomized sample. Nevertheless, these preliminary results are encouraging for the development of new robotic techniques for spinal surgery.

Les méningiomes sont les tumeurs primitives les plus fréquentes du système nerveux central chez l’adulte. Bien que les évènements génétiques à l’origine de leur formation commencent à être bien caractérisés, la temporalité de leur apparition reste inconnue. Des hypothèses récentes suggèrent la possibilité d’une dérégulation dès la période prénatale. Il apparaît donc fondamental d’étudier plus précisément les liens entre l’embryologie des méninges et la tumorigénèse méningée.Méthodes : nous avons étudié une série rétrospective de 120 méningiomes de grades I (méningothéliaux, fibroblastiques et transitionnels) et II de l’OMS. Leurs caractéristiques phénotypiques (démographiques, radiologiques, anatomo-pathologiques et pronostiques) ont été revues et corrélées à leur origine embryologique. L’expression de trois marqueurs immunohistochimiques de la méninge embryonnaire (Prostaglandine D2 Synthase (PGDS), Aquaporine 1 (AQP-1) et Claudine 11 (Cl-11)) a été caractérisée sur la cohorte de méningiomes, afin de déterminer la fréquence d’expression et le lien éventuel avec des caractéristiques phénotypiques. Résultats : les méningiomes ont été classés en fonction de leur origine embryologique, à partir de leur topographie selon les données validées de la littérature. Le tissu embryologique d’origine (cellules des crêtes neurales ou cellules du mésoderme) détermine à la fois le sous-type histologique et la topographie des méningiomes. L’origine mésodermique était corrélée à la topographie base du crâne (OR=46.1 [13.5 ; 212], p