Surgical management of anterior clinoidal meningiomas: consensus statement on behalf of the EANS skull base section.

BACKGROUND: The optimal management of clinoidal meningiomas (CMs) continues to be debated. METHODS: We constituted a task force comprising the members of the EANS skull base committee along with international experts to derive recommendations for the management of these tumors. The data from the literature along with contemporary practice patterns were discussed within the task force to generate consensual recommendations. RESULTS AND CONCLUSION: This article represents the consensus opinion of the task force regarding pre-operative evaluations, patient's counselling, surgical classification, and optimal surgical strategy. Although this analysis yielded only Class B evidence and expert opinions, it should guide practitioners in the management of patients with clinoidal meningiomas and might form the basis for future clinical trials.

Petroclival meningiomas: update of current treatment and consensus by the EANS skull base section.

BACKGROUND: The optimal management of petroclival meningiomas (PCMs) continues to be debated along with several controversies that persist. METHODS: A task force was created by the EANS skull base section along with its members and other renowned experts in the field to generate recommendations for the management of these tumors. To achieve this, the task force reviewed in detail the literature in this field and had formal discussions within the group. RESULTS: The constituted task force dealt with the existing definitions and classifications, pre-operative radiological investigations, management of small and asymptomatic PCMs, radiosurgery, optimal surgical strategies, multimodal treatment, decision-making, and patient's counselling. CONCLUSION: This article represents the consensually derived opinion of the task force with respect to the management of PCMs.

Combined analysis of MGMT methylation and dynamic-susceptibility-contrast MRI for the distinction between early and pseudo-progression in glioblastoma patients.

INTRODUCTION: Currently, no single diagnostic modality allows the distinction between early progression (EP) and pseudo-progression (Psp) in glioblastoma patients. Herein we aimed to identify the characteristics associated with EP and Psp, and to analyze their diagnostic value alone and in combination. MATERIAL AND METHODS: We reviewed the clinical, conventional magnetic resonance imaging (MRI), and molecular characteristics (MGMT promoter methylation, IDH mutation, and EGFR amplification) of glioblastoma patients who presented an EP (n=59) or a Psp (n=24) within six months after temozolomide radiochemotherapy. We analyzed relative cerebral blood volume (rCBV) and relative vessel permeability on K2 maps (rK2) in a subset of 33 patients using dynamic-susceptibility-contrast MRI. RESULTS: In univariate analysis, EP was associated with neurological deterioration, higher doses of dexamethasone, appearance of a new enhanced lesion, subependymal enhancement, higher rCBV and rK2 values. Psp occurred earlier after radiotherapy completion and was associated with IDH1 R132H mutation, and MGMT methylation. In multivariate analysis, rCBV, rK2, and MGMT methylation status were independently associated with EP and Psp. All patients with a methylated MGMT promoter and a low rCBV (<1.75) were classified as Psp while all patients with an unmethylated MGMT promoter and a high rCBV (≥1.75) were classified as EP. Among patients with discordant MGMT methylation and rCBV characteristics, higher rK2 values tended to be associated with EP. CONCLUSION: Combined analysis of MGMT methylation, rCBV and vessel permeability on K2 maps seems helpful to distinguish EP from Psp. A prospective study is warranted to confirm these results.

The minimally invasive endoscopic management of septated chronic subdural hematomas: surgical technique.

BACKGROUND: Fibrin membranes and compartmentalization within the subdural space are a frequent cause of failure in the treatment of chronic subdural hematomas (CSH). This specific subtype of CSH classically requires craniotomy, which carries significant morbidity and mortality rates, particularly in elderly patients. In this work, we describe a minimally invasive endoscopic alternative. METHODS: Under local scalp anesthesia, a rigid endoscope is inserted through a parietal burr hole in the subdural space to collapse fibrin septa and cut the internal membrane. It also allows cauterization of active bleedings and the placement of a drain under direct visualization. CONCLUSIONS: The endoscopic treatment of septated CSH represents a minimally invasive alternative to craniotomy especially for the internal membranectomy.

Patterns of care and survival of glioblastoma patients: a comparative study between 2004 and 2008 in Lyon, France.

INTRODUCTION: The treatment of glioblastomas (GBMs) has changed significantly since 2005. However, the extent to which this change has improved overall survival (OS) of patients treated outside clinical trials remains to be determined. METHODS: We compared the patterns of care and OS of all GBM patients diagnosed in 2004 (n=105) and in 2008 (n=130) in our center. RESULTS: Younger patients (aged<70 years) diagnosed in 2008 received temozolomide radiochemotherapy as the initial treatment and bevacizumab at recurrence more frequently than those diagnosed in 2004 (69% vs 26% P<10(-4) and 41% vs 3%, P<10(-4), respectively). Elderly patients (aged≥70 years) diagnosed in 2008 received an oncological treatment (radiotherapy and/or chemotherapy) more frequently than those diagnosed in 2004 (67% vs 38%, P=0.006). The patients diagnosed in 2008 had longer OS than those diagnosed in 2004 (10.5 months vs 5.3 months, P=0.001). This finding was true for both younger and elderly patients (15.3 months vs 8.9 months, P=0.02 and 6.4 months vs 3.2 months, P=0.0002, respectively) and when considering only IDH1 wild-type patients (8.9 months vs 5.3 months, P=0.004). CONCLUSION: In our center, the change in the patterns of care for GBMs between 2004 and 2008 has been associated with a significant improvement in OS.

Management of brain metastases from germ cell tumors: a single center experience.

BACKGROUND: Brain metastases from germ cell tumors (GCT) are rare and treatment has not yet been standardized. METHODS: The clinical data of men with brain metastases from GCT treated in a single cancer hospital from January 1993 to September 2007 were reviewed. Patients with primary central nervous system GCT were excluded. RESULTS: Thirteen patients had brain metastases at initial diagnosis. All patients received cisplatin-based chemotherapy. Three also received radiotherapy and 1 underwent surgery. Eight of the patients died. Median survival was 19 months (95% CI 0.84-not reached). Twenty-two patients developed brain metastases at recurrence. Median time from initial diagnosis to brain metastases was 8.25 months (3-17.5 months). Five patients received radiotherapy alone, 3 received chemotherapy alone and 3 received supportive care only. Nine patients were operated on: 6 received postoperative chemotherapy and 1 received postoperative radiotherapy. Only 1 patient is still alive. Median survival was 5.1 months (95% CI: 2.2-10.5 months). CONCLUSIONS: Patients with GCT who present with brain metastases at diagnosis tend to do better than patients who develop them at relapse. Chemotherapy can be adequate treatment for initial brain metastases. Treatment for patients with brain metastases at relapse is still not optimal.

Through the orbit and beyond: Current state and future perspectives in endoscopic orbital surgery on behalf of the EANS frontiers committee in orbital tumors and the EANS skull base section.

Introduction: Orbital surgery has always been disputed among specialists, mainly neurosurgeons, otorhinolaryngologists, maxillofacial surgeons and ophthalmologists. The orbit is a borderland between intra- and extracranial compartments; Krönlein's lateral orbitotomy and the orbitozygomatic infratemporal approach are the historical milestones of modern orbital-cranial surgery. Research question: Since its first implementation, endoscopy has significantly impacted neurosurgery, changing perspectives and approaches to the skull base. Since its first application in 2009, transorbital endoscopic surgery opened the way for new surgical scenario, previously feasible only with extensive tissue dissection. Material and methods: A PRISMA based literature search was performed to select the most relevant papers on the topic. Results: Here, we provide a narrative review on the current state and future trends in endoscopic orbital surgery. Discussion and conclusion: This manuscript is a joint effort of the EANS frontiers committee in orbital tumors and the EANS skull base section.

[Shifting paradigm in skull base surgery: Roots, current state of the art and future trends of endonasal endoscopic approaches]. / Chirurgie endoscopique endonasale des tumeurs de la base du crane : historique, état de l'art et perspectives d'avenir.

During the last two decades, endoscopic endonasal approach has completed the minimally invasive skull base surgery armamentarium. Endoscopic endonasal skull base surgery (EESBS) was initially developed in the field of pituitary adenomas, and gained an increasing place for the treatment of a wide variety of skull base pathologies, extending on the midline from crista galli process to the occipitocervical junction and laterally to the parasellar areas and petroclival apex. Until now, most studies are retrospective and lack sufficient methodological quality to confirm whether the endoscopic endonasal pituitary surgery has better results than the microsurgical trans-sphenoidal classical approach. The impressions of the expert teams show a trend toward better results for some pituitary adenomas with the endoscopic endonasal route, in terms of gross total resection rate and probably more comfortable postoperative course for the patient. Excepting intra- and suprasellar pituitary adenomas, EESBS seems useful for selected lesions extending onto the cavernous sinus and Meckel's cave but also for clival pathologies. Nevertheless, this infatuation toward endoscopic endonasal approaches has to be balanced with the critical issue of cerebrospinal fluid leaks, which constitutes actually the main limit of this approach. Through their experience and a review of the literature, the authors aim to present the state of the art of this approach as well as its limits.

Prognostic factors for progression-free survival of the filum terminale ependymomas in adults.

OBJECTIVE: To define the prognostic factors for progression and to determine the impact of the histological grading (according to the World Health Organization) on the progression-free survival (PFS) of filum terminale ependymomas. METHODS: A retrospective chart review of 38 patients with ependymoma of the filum terminale was performed, focusing on demographic data, preoperative symptoms, tumor size, quality of resection, presence of a tumor capsule, and histological grade. RESULTS: Gross total resection (GTR) was achieved in 30 patients (78.9%). Histopathological analysis found 21 (55.3%) myxopapillary grade I ependymoma (MPE), 16 (42.1%) ependymoma grade II (EGII), and 1 (2.6%) ependymoma grade III. There was no significant difference between the mean±SD volume of MPE (5840.5±5244.2mm3) and the one of EGII (7220.3±6305.9mm3, p=0.5). The mean±SD follow-up was 54.1±38.4 months. At last follow-up, 30 (78.9%) patients were free of progression. In multivariate analysis, subtotal resection (p=0.015) and infiltrative tumor (p=0.03) were significantly associated with progression. The PFS was significantly higher in patients with encapsulated tumor than in patients with infiltrative tumor (log-rank p=0.01) and in patients who had a GTR in comparison with those who had an incomplete resection (log-rank p=0.05). There was no difference in PFS between patient with MPE and EGII (p=0.1). CONCLUSION: The progression of ependymoma of the filum terminale highly depends on the quality of resection, and whether the tumor is encapsulated. Except for anaplastic grade, histopathological type does not influence progression.

Cerebral empyema and abscesses due to Cutibacterium acnes.

INTRODUCTION: Cutibacterium acnes is a commensal bacterium of the skin, frequently reported in prosthetic shoulder or spinal implant infections, but rarely in cranial and intracranial infections. METHODS: We retrospectively reviewed patients with intracranial samples positive to Cutibacterium acnes managed in the neurosurgical units of our hospital of Lyon, France, between 2008-2016. RESULTS: We included 29 patients, of whom 23 had empyema (with or without abscess), 17 had cranial osteomyelitis, and six only had abscess. Prior neurosurgery was reported in 28 patients, and the remaining patient had four spontaneous abscesses. Twelve patients had polymicrobial infections, including methicillin-susceptible Staphylococcus in 11 cases. The clinical diagnosis was difficult because of indolent and delayed symptoms: a CT scan or MRI was required. Thirteen patients (52%) had material at the infection site. All patients with bone flap implant or bones from biological banks had a bone flap-associated infection. Drainage was surgically performed in 25 cases or by CT scan-guided aspiration in four cases. All patients received an adapted antibiotic therapy (from three weeks to six months). The outcome was favorable in 28 patients. Three patients relapsed during the antibiotic therapy, requiring further surgery. CONCLUSION: Cutibacterium acnes can be responsible for postoperative empyema and cerebral abscesses, with particular indolent forms, which make their diagnosis difficult. They are often polymicrobial and associated with bone flap osteomyelitis. Their outcome is favorable after drainage and adapted antibiotic therapy.

[Supervision of low-grade gliomas with multiparametric MR imaging: research of radiologic indicators of malignancy transformation]. / Intérêt de l'IRM, avec séquences de diffusion, de perfusion et de la spectrométrie dans le diagnostic et la surveillance de gliomes d'aspect initial de grade 2 : recherche de marqueurs radiologiques orientant vers une aggravation tumorale de grade.

We assessed the contribution of diffusion, perfusion and spectroscopy imaging for the diagnosis and follow-up of intraaxial tumors, suspected to be grade II gliomas. Twenty-four patients were included from April 2005 to July 2006, 17 initially and seven during their follow-up. The diagnosis was reconsidered in a first group of six patients: a high-grade tumor was suspected and confirmed in five. These patients presented a lipid peak; the perfusion results and the CHO/Cr and CHO/NAA ratios were not pathological. The second group included patients with grade II gliomas: these 18 patients had a radiographic work-up, initially, then at three months and every six months. For this group, no evidence of a change of grade were observed. Abnormal findings were noted in seven patients: among these patients, one developed radiographic progression, one other had radiographic progression associated with a spectroscopy lipid peak; only spectroscopy changes were noted in the third patient; the last patient had radiographic progression with perfusion and spectroscopy abnormalities; these four patients were treated. These observations suggest that diffusion, perfusion and spectroscopy can provide supplementary information for diagnosis and follow-up of glial tumors. The presence of a lipid peak is of particular value. The limitations of this work must also be taken into consideration: the follow-up was too short for slow-growing gliomas; the population was small and patients may have undergone surgery during the study, leading to structural modifications which may have compromised comparisons. This work should be continued with new examinations every six months and inclusion of new patients.

ALK7 expression in prolactinoma is associated with reduced prolactin and increased proliferation.

Prolactinoma represents the most frequent hormone-secreting pituitary tumours. These tumours appear in a benign form, but some of them can reach an invasive and aggressive stage through an unknown mechanism. Discovering markers to identify prolactinoma proliferative and invading character is therefore crucial to develop new diagnostic/prognostic strategies. Interestingly, members of the TGFß-Activin/BMP signalling pathways have emerged as important actors of pituitary development and adult function, but their role in prolactinomas remains to be precisely determined. Here, using a heterotopic allograft model derived from a rat prolactinoma, we report that the Activins orphan type I receptor ALK7 is ectopically expressed in prolactinomas-cells. Through immunohistological approaches, we further confirm that normal prolactin-producing cells lack ALK7-expression. Using a series of human tumour samples, we show that ALK7 expression in prolactinomas cells is evolutionary conserved between rat and human. More interestingly, our results highlight that tumours showing a robust expression of ALK7 present an increased proliferation as address by Ki67 expression and retrospective analysis of clinical data from 38 patients, presenting ALK7 as an appealing marker of prolactinoma aggressiveness. Beside this observation, our work pinpoints that the expression of prolactin is highly heterogeneous in prolactinoma cells. We further confirm the contribution of ALK7 in these observations and the existence of highly immunoreactive prolactin cells lacking ALK7 expression. Taken together, our observations suggest that Activin signalling mediated through ALK7 could therefore contribute to the hormonal heterogeneity and increased proliferation of prolactinomas.

[Nelson's syndrome: course of aggressive pituitary corticotroph adenoma]. / Syndrome de Nelson: évolution d'un adénome hypophysaire corticotrope agressif.

Nelson's syndrome was defined in 1958 as the association of an expanding pituitary tumor with high ACTH secretion after bilateral adrenalectomy for Cushing's disease. Pituitary MRI and ACTH measurements led to the definition of Nelson's syndrome as the proliferation of a corticotrophic microadenoma or an aggressive and highly proliferative tumor residue induced by the decreased glucocorticoid inhibition after bilateral adrenalectomy. Now, the problem is not the definition of Nelson's syndrome but rather the identification of markers predictive of tumor growth. Based on a typical case and a review of the literature, we point out some predictive markers of tumor growth after bilateral adrenalectomy: young age at diagnosis, presence of tumor residue on pituitary MRI before adrenalectomy, markers of tumor aggressiveness (Ki-67>3%, mitoses, nuclear PTTG) and increase of ACTH levels during the first months following adrenalectomy.

[Diffusion and perfusion MR imaging in cerebral lymphomas]. / IRM de diffusion-perfusion dans l'évaluation des lymphomes cérébraux.

Because of the increasing incidence of cerebral lymphoma, it is critical for patient management to recognize the MR features of this disease. We present the characteristic morphological and functional MRI features of this tumor. The findings on MRI studies, including morphological, diffusion and perfusion imaging, performed in 9 biopsy-proven cases of cerebral lymphoma with 13 lesions are presented and analyzed, and are discussed in comparison with published literature data. All patients underwent diffusion-weighted imaging with a single shot echo-planar pulse sequence. Dynamic susceptibility-contrast MRI was performed using a T2*-weighted gradient-echo echo-planar sequence after intravenous injection of chelates of gadolinium at the rate of 6 ml/s and a temporal resolution of 1 second. All cases of cerebral lymphoma appeared hypointense or isointense on T1-weighted images and in 75% of cases iso- or hypointense on T2-weighted images. All lesions enhanced except one in a patient receiving steroid therapy. On diffusion-weighted images, tumours were hyperintense with normal or decreased ADC values (0.717+/-0.152.10-3 mm2/sec, range: 0.550-1.014) and an ADC ratio tumour/normal white matter of 0.974+/-0.190 (range: 0.768-1.410). On perfusion, the signal intensity-time curve of each tumour showed a characteristic type of curve with a significant increase of the signal intensity above the baseline and a low maximum relative cerebral blood volume ratio (rCVBmax) of 1.43+/-0.64 (0.55-2.62). Due to their higher cellularity, the lack of neoangiogenesis, and the increased permeability of the blood-brain barrier related to the infiltration of blood vessels wall by lymphomatous cells, cerebral lymphoma presents characteristic diffusion and perfusion MRI features that should be useful for diagnosis and patient follow-up.

[Dendritic cells and gliomas: a hope in immunotherapy?]. / Cellules dendritiques et gliomes: un espoir en immunothérapie?

Immunotherapy has been explored for several decades to try to improve the prognosis of gliomas, but until recently no therapeutic benefit has been achieved. The discovery of dendritic cells, the most potent professional antigen presenting cells to initiate specific immune response, and the possibility of producing them ex vivo gave rise to new protocols of active immunotherapy. In oncology, promising experimental and clinical therapeutic results were obtained using these dendritic cells loaded with tumor antigen. Patients bearing gliomas have deficit antigen presentation making this approach rational. In several experimental glioma models, independent research teams have showed specific antitumor responses using these dendritic cells. Phase I/II clinical trials have demonstrated the feasibility and the tolerance of this immunotherapeutic approach. In neuro-oncology, the efficiency of such an approach remains to be established, similarly in oncology where positive phase III studies are missing. Nevertheless, dendritic cells comprise a complex network which is only partially understood and capable of generating either immunotolerance or immune response. Numerous parameters remain to be explored before any definitive conclusion about their utility as an anticancer weapon can be drawn. It seems however logical that immunotherapy with dendritic cells could prevent or delay tumor recurrence in patients with minor active disease. A review on glioma and dendritic cells is presented.

Headholders' - complications in neurosurgery: A review of the literature and recommendations for its use.

Several types of headholders are routinely used in neurosurgical practice to secure the head in a precise position, providing better security during surgical dissection as well as an absence of eye compression during prone positions. Nevertheless, potentially lethal complications might occur. We performed a review of the literature via PubMed and Google Scholar using the terms "Mayfield skull clamp", "Sugita headholders", "headholder complications" and "skull clamp complications". Twenty-six complications directly related to the use of headholders were identified through 19 papers published from 1981 to 2014: mainly skull fractures with or without a dural laceration (50%), epidural hematomas (23.8%), skull fractures with or without a dural laceration (50%), and air embolism (9.5%). The authors propose recommendations for the safe use of headholders.

[Surgical approaches of tumors of the posterior cone of the orbit]. / Voies d'abords des tumeurs du cône postérieur de l'orbite.

The surgical management of posterior orbital tumors is complex because it is an anatomical area located at the borders between the face and the skull base. The goal of the procedures carried-out in this area is to resect the tumor while preserving vision by using the safest possible approach. The aim of our work was to determine, in the light of our experience and of a review of the literature, the advantages and drawbacks of the numerous approaches described.