Spontaneous resolution of intracranial hypertension following radiotherapy for posterior parasagittal meningioma: About two cases and review of the literature.

We report the cases of two patients who underwent normofractionated radiotherapy for evolutive asymptomatic parasagittal meningiomas. After completion of radiotherapy, both patients presented severe headache and vomiting episodes without papillar edema. We then decided a "wait-and-scan" strategy because of the slit-ventricles, and symptoms regressed spontaneously. MRI showed significant tumor regression a year after radiotherapy with a newly developed collateral venous drainage system in the first patient and a left, unusually large, superior anastomotic vein in the second. These clinical presentation and radiological evolution are compatible with venous stenosis caused by radiation-induced symptomatic edema, fading after the development of a collateral venous drainage system. The relation between pressure-related headaches and venous anatomy remains unclear in parasagittal meningiomas. These observations underline the importance of the study of venous anatomy when pressure-related headaches are suspected. Further clinical descriptions might help the clinicians to treat these patients' symptoms.

Delayed cerebral ischemia after meningioma resection: Literature review and illustrative case.

BACKGROUND: Cerebral vasospasm results from arterial vasoconstriction, mainly following aneurysmal subarachnoid hemorrhage, and may cause delayed cerebral ischemia (DCI). DCI rarely occurs after tumor resection. We performed a systematic review of the literature together with a case report of DCI after meningioma resection. LITERATURE REVIEW: METHODS: A systematic literature review was performed following the PRISMA statement, searching the PubMed, Medline and Cochrane databases using keywords and MESH terms related to "vasospasm/DCI and meningioma resection". RESULTS: In the studies retrieved in the literature, 5 cases of DCI after meningioma surgery were identified. The average age of patients was 52 years. The average onset time of DCI was 9.7 days. Clinical presentation was highly variable: hemiparesis (60%), confusion (60%) and/or aphasia (40%). Meningioma location was most frequently sphenoidal (60%). Most patients had vasospasm in multiple cerebral vessels, involving only the anterior circulation. Various management strategies were used: endovascular treatment (33.3%), antiplatelet therapy (50%) and/or nimodipine (40%). In terms of outcome, there were no deaths, but most patients had variable neurological sequelae (80%): aphasia, visual impairment, hemiparesis. CONCLUSION: The systematic literature review and the present case of DCI following resection of an olfactory meningioma suggested that the main etiologic factors causing this rare pathology are: 1) intraoperative subarachnoid hemorrhagic contamination; 2) microvascular manipulation; 3) and possible dysregulation of hypothalamic function.

[Meningiomas: A review of current knowledge]. / Les méningiomes : mise au point sur les connaissances actuelles.

Meningiomas are the most frequent among intracranial tumors, and represent more than 30% of primitive central nervous system neoplasms. Arising from the meninges, they are generally benign lesions and can be treated by either radio-clinical follow-up or surgical resection with excellent outcome. However, more than 20% of meningiomas harbor atypical or malignant features and represent challenges for both prognostic evaluation and therapeutic strategy. The discovery of the genetic and epigenetic landscapes of meningiomas enabled the identification of new prognostic markers and potential therapeutic targets for refractory meningiomas. This review summarizes current epidemiology, histological and molecular characteristics, diagnosis and treatments for meningiomas, and highlights the close relationship between the development of meningiomas and hormonal intake, as illustrated by recent recommendations of the "Agence Nationale de Securité du Medicament", the French national drug safety agency.

[New indications of protontherapy for adults intracranial tumours]. / Nouvelles indications de protonthérapie et essais cliniques en cours : tumeurs intracrâniennes.

Considering intracranial tumours, only few indications of protontherapy, such as chordoma, chondrosarcoma or uveal melanoma, are uniformly approved in the world. Other indications, excluding paediatric pathologies, are still debated. The aim of this article is to describe the rationale for the use of protonbeam irradiation for meningioma, pituitary adenoma, craniopharyngioma, paraganglioma, glioma, and schwannoma, and to inform the radiation oncologists if prospective studies or randomized studies are opened for inclusions. This article deals only with indications for adults.

Meningiomas in patients with long-term exposition to progestins: Characteristics and outcome.

OBJECTIVE: The aim of this study was to describe progestin-associated meningiomas' characteristics, outcome and management. MATERIAL AND METHODS: We included 53 patients operated on and/or followed in the department for meningioma with progestin intake longer than one year and with recent drug discontinuation. RESULTS: Cyproterone acetate (CPA), nomegestrol acetate (NomA), and chlormadinone acetate (ChlA) were involved in most cases. Mean duration of progestin drugs intake was 17.5 years. Tumors were multiple in 66% of cases and were located in the anterior and the medial skull base in 71% of cases. Transitional subtype represented 16/25 tumors; 19 meningiomas were WHO grade I and 6 were grade II. The rate of transitional subtype and skull base location was significantly higher compared to matched operated meningioma general population. No difference was observed given WHO classification. But Ki67 proliferation index tends to be lower and 5/6 of the WHO grade II meningiomas were classified as WHO grade II because of brain invasion. Strong progesterone receptors expression was observed in most cases. After progestin discontinuation, a spontaneous visual recovery was observed in 6/10 patients. Under CPA (n=24) and ChlA/NomA (n=11), tumor volume decreased in 71% and 18% of patients, was stabilized in 25% and 64% of patients, and increased in 4% and 18% of patients, respectively. Volume outcome was related to meningioma location. CONCLUSIONS: Outcome at progestins discontinuation is favorable but different comparing CPA versus ChlA-NomA and comparing tumor location. Long-term follow-up is required. In most cases, simple observation is recommended and surgery should be avoided.

[A pulmonary tumor that racks our brains!] / Une tumeur pulmonaire à se creuser les méninges !

We report the case of a 74-year-old woman who, as part of the follow-up for two breast cancers, presented a 2cm long lung nodule. A microscopic examination of the biopsy under a scanner showed a proliferation of epithelial appearance but whose immunophenotypic profile did not permit a precise diagnosis (negativity of CK7, GATA3, TTF1, negative estrogen receptors but positive progesterone receptors). Wedge resection surgery was performed. Extemporaneous and definitive microscopic examination showed a well-defined lesion made up of lobules of cohesive-looking cells, frequently forming coils. The tumor cells showed some intranuclear inclusions and a few psammomas while the immunohistochemical study showed diffuse expression of EMA, SSTR2A and progesterone receptor markers and a low proliferation index. A diagnosis of a pulmonary localization of a meningioma was proposed. The radiological assessment of the entire neuraxis did not show any other lesion leading to the final diagnosis of primary intra-pulmonary meningioma. This is an exceptional tumor with a difficult histopathological diagnosis of biopsy material, which must familiar to the pathologists. It is associated with an excellent prognosis. Our observation aims to illustrate the macroscopic and microscopic aspects and to present the data from the recent literature review.

[Cystic meningioma of falx cerebri: About one case and literature review]. / Meningiome kystique de la faux du cerveau : A propos d'un cas clinique et revue de litterature.

Cystic meningioma of the falx is a rare extra-axial tumor, representing 4 to 7% of all intracranial meningioma. We report the case of a 23 years old patient with relative personal health history who has presented for nearly two years generalized headache associated with left hemiparesis. The head CT scan and MRI showed a right posterior parietal tumor with a cystic and fleshy component which was interpreted as glioma. The patient was operated and the intraoperative aspect was an extra axial lesion inserted to the middle tier of the falx cerebri with a clear cleavage plan with the cerebrum. A total ablation of the lesion was down and the histological study confirm the diagnosis. The cystic meningioma is a rare variant of intracerebral meningioma of which only histology makes it possible give the diagnosis of certainty.

Le méningiome kystique de la faux est une tumeur extra-axiale rare, représentant 4 à 7% des méningiomes intracrâniens. Nous rapportons le cas d'une patiente de 23 ans aux antécédents personnels de santé relative qui présentait depuis près de deux ans des céphalées généralisées associées à un déficit de l'hémicorps gauche. Le scanner et l'IRM préopératoire ont montré un processus tumoral pariétal postérieur droit avec une double composante kystique et charnue qui a été interprétée en préopératoire comme gliome. La patiente a été opérée et l'aspect peropératoire était celui d'une lésion extra-axiale insérée aux tiers moyen de la faux du cerveau avec un plan de clivage franc avec le cerveau adjacent. Une exérèse totale de la lésion est réalisée et l'étude histologique a confirmé le diagnostic. Le méningiome kystique est une variante rare de méningiome intracrânien dont seule l'histologie permet de donner le diagnostic de certitude.

[Skull base meningioma: Clinical and radiological efficacy based on a quantitative volumetric analysis]. / Méningiomes de la base du crâne : efficacité clinique et radiologique basée sur une analyse volumétrique quantitative.

PURPOSE: To date, no correlation has been found between clinical and radiological efficacy after irradiation of skull base meningiomas. However, the evaluation of the radiological response was most often made by questionable methods that may have underestimated the radiological effectiveness of radiotherapy. The objective of this work is to verify this hypothesis by quantitative volumetric analysis. MATERIAL AND METHODS: Data from 35 patients treated with either helical tomotherapy (45.7%) or fractionated stereotactic radiotherapy (54.3%) were retrospectively analysed. These were mainly women (94%) aged 59 (43-81) with lesions mainly of the cavernous sinus (60%). There was a median of 2 (1-4) symptoms and the main symptoms were visual impairment (39%), cranial nerve deficits (23.4%) and headaches (17.2%). RESULTS: Median tumour volume decreased significantly (P<0.05) from 9.6mL (0.3-36.6) to 6.8mL (0.1-26.5) after median follow-up of 44 months (24-77). Sixty-three percent of patients had an improvement of at least one symptom. In univariate analysis, clinical efficacy (P<0.05), radiotherapy technique (P<0.05), tumor topography (P<0.05) and initial tumor volume (P<0.05) were predictive factors for radiological response. In multivariate analysis, only the inverse correlation between radiological response and initial tumor volume remained significant (ρ: -0.47 95% CI -3.2 to 5.7; P<0.05). CONCLUSION: The quantitative volumetric monitoring demonstrates a major radiological efficiency of radiotherapy. However, no clear correlation between clinical and radiological efficacy was found.

[Management of tumoral epilepsy in meningioma surgery: Review of the literature and survey of French national practices]. / Gestion de l'épilepsie tumorale dans la chirurgie des méningiomes : revue de la littérature et enquête sur les pratiques nationales.

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.

[Use of the PELICAN software for the creation and export of standardized pathology reports in central nervous system tumors: Example of meningiomas]. / Utilisation du logiciel PELICAN pour la saisie et l'export de comptes rendus standardisés dans les tumeurs du système nerveux central : application aux méningiomes.

INTRODUCTION: PELICAN ("Partager Efficacement en Laboratoire les Informations des Comptes rendus ANatomopathologiques") is a software, which generates standardized reports, and allows to automatically create a database. It has been used in central nervous system tumor pathology at the University Hospital of Nancy since 2014. The purpose of this article was to illustrate the use of this application for meningiomas, with a first statistical evaluation. MATERIALS AND METHODS: The export of data included all cases of meningiomas recorded in the PELICAN application until July 2018. The PELICAN application is a Microsoft Excel file containing a software, written in Visual Basic for Applications, and used by the pathologist to create the report. The main clinical data were collected from the Hérault Register census form. Follow-up was systematically reported for atypical meningiomas. RESULTS: Two hundred and ninety-five meningiomas were analyzed, including 250 grade I meningiomas, 42 grade II meningiomas, and 3 grade III meningiomas. Grade II meningiomas were characterized by a significantly higher proportion of men (P=0.002) and dural infiltration (P<0.001), a significant increase in the Ki-67 index (P<0.0001), and a significant decrease in progesterone receptor expression (P<0.001). In atypical meningiomas, a Ki-67 index of more than 20 % was significantly correlated with a shorter progression-free survival (P=0.032). CONCLUSION: The PELICAN software is an easy-to-use tool that allows to generate standardized reports and feed a database, opening very interesting perspectives from an epidemiological and scientific point of view.

[Acute visual loss related to sphenoid meningioma]. / Troubles visuels aigus associés aux méningiomes sphénoïdaux.

Meningiomas represent about 20% of intracranial tumors. Involvement of the medial sphenoid wing includes anterior clinoid, cavernous sinus and superior orbital fissure meningiomas. Due to the proximity of these tumors to the optic nerve, typically progressive unilateral vision loss, over several months to years, is the classic clinical presentation. We report three cases of acute monocular vision loss, two transient and one permanent, ipsilateral to a sphenoid meningioma. Ophthalmological involvement with sphenoid meningiomas is most often chronic, due to interruption of axoplasmic flow and demyelination of the optic nerve by local compression. However, vascular involvement with ischemia of the optic nerve or transient low blood flow secondary to compression of the carotid branches vascularizing these structures is another possible mechanism. In our series, two patients had amaurosis fugax, and one patient had sudden, persistent visual loss in relation to acute anterior ischemic optic neuropathy on the side of the meningioma. The mean age of patients with acute visual manifestations was 62 years. These ischemic and non-compressive visual symptoms, ipsilateral to sphenoid meningiomas, are difficult to interpret. Whether these temporary visual disturbances of vascular origin should be considered an early sign of future severe or permanent visual impairment when no optic nerve compression is observed is not certain. The place of these acute visual disturbances in the therapeutic decision, particularly surgical, remains to be defined. Larger multicentric prospective studies are needed to better understand the role of local circulatory factors attributable to meningioma in the occurrence of these acute visual signs.

[Base of the skull meningioma: Efficacy, clinical tolerance and radiological evaluation after radiotherapy]. / Méningiomes de la base du crâne : efficacité et tolérance clinique, efficacité radiologique et cinétique tumorale après radiothérapie.

Skull base meningioma leads to functional disturbances, which can significantly alter the quality of life. The optimal management of these lesions, whose goals are neurological preservation and tumour local control, is not yet clearly established. It is widely recognized that the goal of a radical excision should be abandoned despite the advances in the field of microsurgery of skull base lesions. Although less morbid, partial tumour excision would be associated with increased risk of local tumour recurrence. Although discussed both exclusive and adjuvant have proven to be highly successful in terms of clinical improvement and local control. Various radiation techniques have demonstrated their efficacy in the management of this pathology. However, high rates of clinical improvement are in contrast with low rates of radiological improvement. The notion of clinical and radiological dissociation appeared. However, in most of these studies, the analysis of the radiological response could be subject of legitimate criticism. This work proposes to review the local control, the efficacy and the clinical tolerance and the radiological response of the various radiation techniques for the meningioma of the base of the skull and to demonstrate the interest of quantitative volumetric analyses in the follow-up of meningioma after radiotherapy.

[Oculoplastic complications of the excision of meningiomas with orbital extension]. / Complications oculoplastiques de l'exérèse des méningiomes à extension orbitaire.

INTRODUCTION: Meningiomas with orbital extension are the most frequent benign orbital tumors. The few studies available on the postoperative complications of their excision focus on the postoperative evolution of proptosis, visual acuity and visual field deficits. The goal of our study was to highlight the oculoplastic complications secondary to their excision. MATERIAL AND METHOD: We identified all cases of meningiomas with orbital extension undergoing excision either neurosurgically or via an orbital approach in the ophthalmology and neurosurgery departments of Pasteur university medical center in Nice between February 2011 and January 2017. The data collection included the postoperative presence of proptosis, oculomotor disturbance, lid disorders, dry eye and trigeminal nerve damage. RESULTS: Twenty-nine patients were included; 89.7 % were women. The mean age was 55 years. Postoperative complications included 25 % residual proptosis; 40.7 % oculomotor disturbance, 75 % of which regressed at least partially; 50 % ptosis, 21 % of which did not regress; 40 % dry eye; and in 21.4 % the trigeminal nerve was involved. CONCLUSION: The management of meningiomas with orbital extension is difficult due to their anatomical location and requires joint neurosurgical and oculoplastic management. Sufficient follow-up is required before recommending surgery for oculomotor disturbances. The frequency of occurrence of ptosis with potential recommendation for surgery requires caution given the occurrence of trigeminal nerve involvement and dry eye syndrome.

Molecular genetics of meningiomas: Building the roadmap towards personalized therapy.

New advances have recently been made in the field of molecular genetics and mouse modeling of meningiomas, opening new perspectives for future treatments. Recent genome-wide genotyping and exome sequencing studies have confirmed the pivotal role of NF2 in meningioma tumorigenesis, concerning roughly half of the tumors, and unraveled new mutations in non-NF2 meningiomas concerning AKT1, SMO, KLF4 and TRAF7. The molecular mechanisms underlying tumorigenesis of high histological grades have been progressively deciphered with the recent discovery of TERT promoter mutations in progressing tumors. A better understanding of the genetics and clinical behavior of high-grade meningiomas is mandatory in order to better design future clinical trials. New genetically engineered mouse models of benign and histologically aggressive meningioma represent a substantial resource for the establishment of relevant pre-clinical trials. By studying the mechanisms underlying these new tumorigenesis pathways and the corresponding mouse models, we should be able to offer personalized chemotherapy to patients with surgery- and radiation-refractory meningiomas in the near future.

Management of multiple tumors in neurofibromatosis type 2 patients.

INTRODUCTION: Neurofibromatosis type 2 is characterized by the presence of bilateral vestibular schwannomas. However, other nervous system tumors may also occur. Therefore, the management of NF2 patients is complex and requires a multidisciplinary discussion in a specialized center. MATERIALS AND METHODS: All recent articles concerning tumors other than vestibular schwannoma in NF2 disease were reviewed, using PubMed databases. RESULTS: Intracranial meningiomas occur in 50% of NF2 patients, and are often multiple. Surgery remains the main treatment and should be performed in cases of growing tumors. The role of antiangiogenic therapy is currently under evaluation and the role of radiosurgery still remains to be defined in NF2 disease. Spinal tumors occur in about half of NF2 patients. Surgery should be discussed when radiological tumor progression is demonstrated, even if spinal tumors are asymptomatic, in order to preserve neurological function and good quality of life. As regards lower cranial nerve schwannomas, radiosurgery appears to be a more appropriate treatment for growing tumor with a small volume in order to avoid post-operative complications, especially swallowing disorders. Facial nerve schwannomas may appear, on MRI, like vestibular schwannomas. The diagnosis should be suspected when the facial palsy is an early symptom during cerebello-pontine tumor progression. Trigeminal schwannomas are frequent in NF2 disease and fortunately they are often asymptomatic. Among major neurofibromatosis types, peripheral nerve sheath schwannomas are only present in patients with NF2 disease and schwannomatosis. Surgical resection is required when the cutaneous schwannomas is painful or when tumor progression is observed and causes symptoms. CONCLUSION: Tumors other than vestibular schwannoma are also associated with a poor prognosis in NF2 patients. Surgery remains the main treatment in most cases. Each treatment decision in NF2 disease requires a complete evaluation of all cranial and spinal locations of the disease in order to establish surgical priorities and strategies.

Descriptive epidemiology of 13,038 newly diagnosed and histologically confirmed meningiomas in France: 2006-2010.

PURPOSE: This work describes the clinical epidemiology and pathology for patients undergoing surgery for newly diagnosed meningiomas in France between 2006 and 2010. METHODS: The methodology is based on a multidisciplinary national network previously established by the French Brain Tumor DataBase (FBTDB) (in French: Recensement national histologique des tumeurs primitives du système nerveux central [RnhTPSNC]), and the active participation of the scientific societies involved in neuro-oncology in France. RESULTS: From 2006 to 2010, 13,038 incident cases of meningioma with histological validation were identified and analyzed (9769 women, 3269 men, resection 98.2%, cryopreservation 20.5%). For each histological subtype of meningioma (meningothelial, fibrous, transitional, psammomatous, angiomatous, rare variety, microcystic, secretory, lymphoplasmacyte-rich, clear-cell, chordoid, rhabdoid, metaplastic, atypical, papillary, anaplastic and not otherwise specified), number of cases, sex, median age, cryopreservation and surgery were reported. Among the various histological subtypes, atypical meningioma (grade II) slightly, but significantly, increased after 2007. Headache, sensory-motor impairments and seizures were the most frequent clinical symptoms. Time between the first clinical symptom and surgery ranged from 0 to 314 months, and was <3 months in 37% of cases. At the time of surgery, 9% of patients were asymptomatic. DISCUSSION/CONCLUSION: Given the number of meningiomas not histologically-validated, we can estimate that the gross incidence rate for meningiomas operated in France is about 4.2 per 100,000 person/year. To our knowledge, this work is the most important study evaluating the different subtypes of meningiomas and it validates the relevance of histological databases for central nervous system tumors.

Fractionated radiotherapy and radiosurgery of intracranial meningiomas.

This review focuses on the role of radiosurgery and fractionated radiotherapy in the management of intracranial meningiomas, which are the most common benign intracranial tumors. Whenever feasible, surgery remains a cornerstone of treatment in effective health care treatment where modern radiotherapy plays an important role. Irradiation can be proposed as first-line treatment, as adjuvant treatment, or as a second-line treatment after recurrence. Stereotactic radiosurgery consists of delivering, a high-dose of radiation with high precision, to the tumor in a single-fraction with a minimal exposure of surrounding healthy tissue. Stereotactic radiosurgery, especially with the gamma knife technique, has reached a high level of success for the treatment of intracranial meningiomas with excellent local control and low morbidity. However, stereotactic radiosurgery is limited by tumor size,<3-4cm, and location, i.e. reasonable distance from the organs at risk. Fractionated radiation therapy is an interesting alternative (5 to 6weeks treatment time) for large inoperable tumors. The results of fractionated radiation therapy seem encouraging as regards both local control and morbidity although long-term prospective studies are still needed.

Visceral and bone metastases of a WHO grade 2 meningioma: A case report and review of the literature.

Meningiomas represent the most common tumours of the central nervous system in adults. Risk factors include ionizing radiation, female hormones exposure, head trauma, cell phone use, breast cancer and family history of meningioma. Despite complete surgical resection, natural history of meningiomas often includes local recurrence but very few metastatic meningiomas have been reported. Here, we report the case of a metastatic meningioma. A 43-year-old woman was firstly treated for a symptomatic parietal meningioma WHO grade II by surgical resection followed by an irradiation of the surgical bed. After surgical resection and irradiation, the patient recovered incompletely. Two months after the end of the radiation treatment, the patient presented at the emergency unit for sciatic pain revealing bone metastases that has been histologically confirmed. Moreover, imaging led to the diagnosis of liver and lungs metastasis. Despite lack of guidelines for metastatic meningioma, few treatments have been used and published for recurrent and multiple meningioma management. In case studies, some partial responses have been seen with mifepristone and improved progression-free survival rates have been obtained with hydroxyurea and sunitinib. Metastasis in meningioma is very uncommon and no specific management has been described. Hydroxyurea, sunitinib and mifepristone could be options if no clinical trial data is available.