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Multi-recurrent high-grade meningiomas remain an unmet medical need in neuro-oncology when iterative surgeries and radiation therapy sessions fail to control tumor growth. Nevertheless, the last 10years have been marked by multiple advances in the comprehension of meningioma tumorigenesis via the discovery of new driver mutations, the identification of activated intracellular signaling pathways, and DNA methylation analyses, providing multiple potential therapeutic targets. Today, Anti-VEGF and mTOR inhibitors are the most used and probably the most active drugs in aggressive meningiomas. Peptide radioactive radiation therapy aims to target SSTR2A receptors, which are strongly expressed in meningiomas, but have an insufficient effect in most aggressive meningiomas, requiring the development of new techniques to increase the dose applied to the tumor. Based on the multiple potential intracellular targets, multiple targeted therapy clinical trials targeting Pi3K-Akt-mTOR and MAP kinase pathways as well as cell cycle and particularly, cyclin D4-6 are ongoing. Recently discovered driver mutations, SMO, Akt, and PI3KCA, offer new targets but are mostly observed in benign meningiomas, limiting their clinical relevance mainly to rare aggressive skull base meningiomas. Therefore, NF2 mutation remains the most frequent mutation and main challenging target in high-grade meningioma. Recently, inhibitors of focal adhesion kinase (FAK), which is involved in tumor cell adhesion, were tested in a phase 2 clinical trial with interesting but insufficient activity. The Hippo pathway was demonstrated to interact with NF2/Merlin and could be a promising target in NF2-mutated meningiomas with ongoing multiple preclinical studies and a phase 1 clinical trial. Recent advances in immune landscape comprehension led to the proposal of the use of immunotherapy in meningiomas. Except in rare cases of MSH2/6 mutation or high tumor mass burden, the activity of PD-1 inhibitors remains limited; however, its combination with various radiation therapy modalities is particularly promising. On the whole, therapeutic management of high-grade meningiomas is still challenging even with multiple promising therapeutic targets and innovations., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Most of tuberculum sellae meningiomas (TSM) show asymmetric growth. They are usually resected through ipsilateral approaches. The access of the inferior-medial side of the ipsilateral optic nerve might be challenging, which result in increased manipulation of the compromised optic nerve. The contralateral approach has been described to avoid these technical difficulties. Assessing the long-term visual and olfactory outcome, as well as recurrence rate in patients operated for TSM through ipsilateral or contralateral approaches. Single center retrospective cohort study about 94 patients operated on between March 2000 and April 2018. Seventy percent of the preoperative visual acuity loss totally resolved (44%) or showed varying degrees of improvement (26%) after surgery. Seventy-two percent of the preoperative visual field defects evolved favorably (44% recovery, 28% improvement). Eight patients showed aggravated visual disturbances (9%). A contralateral approach seemed to be predictive of visual field defects improvement after surgery (OR = 0.4), with borderline significant results (p = .08). There was a higher rate of postoperative olfactory nerve impairment after a contralateral approach (37% vs 17%, p = .03). Total removal of the tumor fragment entering the optic canal was accomplished in 96% in the contralateral vs 75% in the ipsilateral group (p = .04). The 2-, 5-, and 7-year tumor progression-free survival were 100% in the Simpson grade 2 group, and 85% (n = 17), 74% (n = 11), and 67% (n = 5) in the Simpson grade 4 group, respectively (p = .00). Resection of tuberculum sellae meningiomas through a contralateral approach seems to provide better visual outcome and tumor control at the cost of increased olfactory nerve disorders., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: We aimed to improve the assessment of the drug activity in meningioma clinical trials based on the study of the 3D volume growth rate (3DVGR) in a series of aggressive meningiomas. We secondarily aimed to correlate 3DVGR study with patient outcome., Methods: We performed a post hoc analysis based on volume data and 3DVGR extracted from CEVOREM study including 18 patients with 32 recurrent high-grade meningiomas and treated with everolimus and octreotide. The joint latent class model was used to classify tumor 3DVGR undertreatment., Results: Class 1 includes lesions responding to treatment with decrease in volume in the first 3 months, and then a stabilization thereafter (9.5% of tumors) (mean pretreatment 3DVGR = 6.13%/month; mean undertreatment 3DVGR = -18.7%/month within 3 first months and -0.14%/month after the 3 first months). Class 2 includes lesions considered as stable or with a slight increase in volume undertreatment (65.5%) (mean pretreatment 3DVGR = 6.09%/month; undertreatment 3DVGR = -0.09% within the first 3 months). Class 3 includes lesions without 3DVGR decrease (25%) (mean pretreatment 3DVGR = 46.9%/month; mean undertreatment 3DVGR = 19.2%/month within the first 3 months). Patients with class 3 lesions had a significantly worse progression-free survival (PFS) rate than class 1 and 2 ones., Conclusions: Tumor 3DVGR could be helpful to detect early signal of drugs antitumoral activity or nonactivity. This volume response classification could help in the assessment of drug activity in tumors with mostly volume stabilization and rare response as aggressive meningiomas even with a low number of patients in complement to 6 months PFS., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Aggressive meningiomas that progress after surgery/radiotherapy represent an unmet medical need. Strong and constant expression of SSTR2A receptors and activation of the Pi3K/Akt/mTOR pathway have been demonstrated in meningiomas. The combination of everolimus, an mTOR inhibitor, and octreotide, a somatostatin agonist, has shown additive antitumor effect in vitro . The phase II CEVOREM trial investigated the efficacy of this combination on recurrent meningiomas., Patients and Methods: Patients with documented recurrent tumor progression ineligible for further surgery/radiotherapy were eligible to receive octreotide (30 mg/d, day 1) and everolimus (10 mg/d, days 1-28). The primary endpoint was the 6-month progression-free survival rate (PFS6). The secondary endpoints were overall survival, response rate, tumor growth rate according to central review, and safety., Results: A total of 20 patients were enrolled, including 2 with World Health Organization (WHO) grade I tumors, 10 with WHO grade II tumors, and 8 with WHO grade III tumors; furthermore, 4 patients harbored NF2 germline mutation. The overall PFS6 was 55% [95% confidence interval (CI), 31.3%-73.5%], and overall 6- and 12-month survival rates were 90% (95% CI, 65.6%-97.4%) and 75% (95% CI, 50.0%-88.7%), respectively. A major decrease (>50%) was observed in the growth rate at 3 months in 78% of tumors. The median tumor growth rate decreased from 16.6%/3 months before inclusion to 0.02%/3 months at 3 months ( P < 0.0002) and 0.48%/3 months at 6 months after treatment ( P < 0.0003)., Conclusions: The combination of everolimus and octreotide was associated with clinical and radiological activity in aggressive meningiomas and warrants further studies. Decrease in the tumor volume growth rate should be considered a complementary and sensitive endpoint to select potentially effective drugs for recurrent meningiomas., (©2020 American Association for Cancer Research.)

Parasellar spaces remain particularly singular, comprising the most important neurovascular structures such as the internal carotid artery and optic, oculomotor, and trigeminal nerves. Meningiomas are one of the most frequent tumors arising from parasellar spaces. In this location, meningiomas remain mostly benign tumors with WHO grade I and a meningothelial subtype. Progestin intake should be investigated and leads mostly to conservative strategies. In the case of benign nonsymptomatic tumors, observation should be proposed. Tumor growth will lead to the proposition of surgery or radiosurgery. In the case of an uncertain diagnosis and an aggressive pattern, a precise diagnosis is required. For cavernous sinus and Meckel's cave lesions, complete removal is rarely considered, leading to the proposition of an endoscopic endonasal or transcranial biopsy. Optic nerve decompression could also be proposed via these approaches. A case-by-case discussion about the best approach is recommended. A transcranial approach remains necessary for tumor removal in most cases. Vascular injury could lead to severe complications. Cerebrospinal fluid leakage, meningitis, venous sacrifice, visual impairment, and cranial nerve palsies are more frequent complications. Pituitary dysfunctions are rare in preoperative assessment and in postoperative follow-up but should be assessed in the case of meningiomas located close to the pituitary axis. Long-term follow-up is required given the frequent incomplete tumor removal and the risk of delayed recurrence. Radiosurgery is relevant for small and well-limited meningiomas or intra-cavernous sinus postoperative residue, whereas radiation therapy and proton beam therapy are indicated for large, extended, nonoperable meningiomas. The place of the peptide receptor radionuclide therapyneeds to be defined. Targeted therapy should be considered in rare, recurrent, and aggressive parasellar meningiomas., (© 2020 S. Karger AG, Basel.)

OBJECTIVE Meningiomas express somatostatin receptor subtype 2 (SST2), which is targeted by the somatostatin analog octreotide. However, to date, using somatostatin analog therapy for the treatment of these tumors in clinical practice has been debated. This study aims to clarify the in vitro effects of octreotide on meningiomas for precise clinical applications. METHODS The effects of octreotide were analyzed in a large series of 80 meningiomas, including 31 World Health Organization (WHO) Grade II and 4 WHO Grade III tumors, using fresh primary cell cultures to study the impact on cell viability, apoptosis, and signal transduction pathways. RESULTS SST2 mRNA was detected in 100% of the tested meningiomas at levels similar to those observed in other SST2-expressing tumors, neuroendocrine tumors, or pituitary adenomas. Octreotide significantly decreased cell proliferation in 88% of meningiomas but did not induce cell death. On average, cell proliferation was more inhibited in the meningioma group expressing a high level of SST2 than in the low-SST2 group. Moreover, octreotide response was positively correlated to the level of merlin protein and inversely correlated to the level of phosphorylated p70-S6 kinase, a downstream effector of the PI3K/Akt/mammalian target of rapamycin (mTOR) pathway. Octreotide inhibited Akt phosphorylation and activated tyrosine phosphatase without impacting the extracellular regulated kinase (ERK) pathway. CONCLUSIONS Octreotide acts exclusively as an antiproliferative agent and does not promote apoptosis in meningioma in vitro. Therefore, in vivo, octreotide is likely to limit tumor growth rather than induce tumor shrinkage. A meta-analysis of the literature reveals an interest in octreotide for the treatment of WHO Grade I tumors, particularly those in the skull base for which the 6-month progression-free survival level reached 92%. Moreover, somatostatin analogs, which are well-tolerated drugs, could be of interest for use as co-targeting therapies for aggressive meningiomas.

Treatment for recurrent and aggressive meningiomas remains an unmet medical need in neuro-oncology, and chemotherapy exhibits limited clinical activity, if any. Merlin expression, encoded by the NF2 gene, is lost in a majority of meningiomas, and merlin is a negative regulator of mTORC1. The sst2 somatostatin receptor, targeted by octreotide, is highly expressed in meningiomas. To investigate new therapeutic strategies, we evaluated the activity of everolimus (mTOR inhibitor), BKM-120 and BEZ-235 (new Pi3K/Akt/mTOR inhibitors), octreotide and a combined treatment (octreotide plus everolimus), on cell proliferation, signaling pathways, and cell cycle proteins, respectively. The in vitro study was conducted on human meningioma primary cells extracted from fresh tumors, allowing the assessment of somatostatin analogs at the concentration levels used in patients. The results were correlated to WHO grades. Further, everolimus decreased cell viability of human meningiomas, but concomitantly, induced Akt activation, reducing the antiproliferative effect of the drug. The new Pi3K inhibitors were not more active than everolimus alone, limiting their clinical relevance. In contrast, a clear cooperative inhibitory effect of octreotide and everolimus was observed on cell proliferation in all tested meningiomas, including WHO grades II-III. Octreotide not only reversed everolimus-induced Akt phosphorylation but also displayed additive and complementary effects with everolimus on downstream proteins involved in translation (4EB-P1), and controlling cell cycle (p27Kip1 and cyclin D1). We have demonstrated a co-operative action between everolimus and octreotide on cell proliferation in human meningiomas, including aggressive ones, establishing the basis for a clinical trial.

Advances in transsphenoidal surgery and endoscopic techniques have opened new perspectives for cavernous sinus (CS) approaches. The aim of this study was to assess the advantages and disadvantages of limited endoscopic transsphenoidal approach, as performed in pituitary adenoma surgery, for CS tumor biopsy illustrated with three clinical cases. The first case was a 46-year-old woman with a prior medical history of parotid adenocarcinoma successfully treated 10 years previously. The cavernous sinus tumor was revealed by right third and sixth nerve palsy and increased over the past three years. A tumor biopsy using a limited endoscopic transsphenoidal approach revealed an adenocarcinoma metastasis. Complementary radiosurgery was performed. The second case was a 36-year-old woman who consulted for diplopia with right sixth nerve palsy and amenorrhea with hyperprolactinemia. Dopamine agonist treatment was used to restore the patient's menstrual cycle. Cerebral magnetic resonance imaging (MRI) revealed a right sided CS tumor. CS biopsy, via a limited endoscopic transsphenoidal approach, confirmed a meningothelial grade 1 meningioma. Complementary radiosurgery was performed. The third case was a 63-year-old woman with progressive installation of left third nerve palsy and visual acuity loss, revealing a left cavernous sinus tumor invading the optic canal. Surgical biopsy was performed using an enlarged endoscopic transsphenoidal approach to the decompress optic nerve. Biopsy results revealed a meningothelial grade 1 meningioma. Complementary radiotherapy was performed. In these three cases, no complications were observed. Mean hospitalization duration was 4 days. Reported anatomical studies and clinical series have shown the feasibility of reaching the cavernous sinus using an endoscopic endonasal approach. Trans-foramen ovale CS percutaneous biopsy is an interesting procedure but only provides cell analysis results, and not tissue analysis. However, radiotherapy and radiosurgery have proven effective for SC meningiomas. When histological diagnosis is required, limited endoscopic transsphenoidal approach appears as a safe, fast, and useful alternative to the classical endocranial approach. Also, a tailored enlargement of the approach could be performed if optic nerve decompression is required. The feasibility of CS endoscopic transsphenoidal biopsy has prompted us to consider CS biopsy when the diagnosis of CS meningioma is uncertain., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Objective: Resection of a parasagittal meningioma invading the superior sagittal sinus (SSS) needs the reconstruction of the sinus by a patch or a venous graft depending of sinus invasion degree., Method: We present here a case of a 21-year-old man who underwent radical removal of a radio-induced parasagittal meningioma totally invading the posterior third of the sinus. For its reconstruction, we used the patient's left superficial femoral vein without valves as an autograft, by realizing two end-to-end anastomoses between the sinus and the graft after an en-bloc removal of the meningioma and the invaded sinus., Results: Two years after surgery, clinical examination of the patient was strictly normal and the femoral venous graft was still patent on CT angiograms., Conclusion: The superficial femoral vein without valves seems to be convenient for SSS reconstruction., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Meningeal solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) are distinct entities in the World Health Organization (WHO) classification of central nervous system (CNS) tumors while they belong to the same spectrum of tumors in other locations. Well-defined histological prognostic factors are also lacking for these tumors. In order to clarify the relationship between SFT and HPC and to find histological and immunohistochemical prognostic factors, we carried out a retrospective study in 89 patients. The following histological parameters were recorded: hypercellularity, collagenic areas, cytonuclear atypias, necrosis, mitotic count per 10 high-power fields, vasculo-nervous adherences defined by engulfment of vessel or nerve by the tumor, brain infiltration. We found overlapping histological and immunohistochemical features between SFT and HPC. The most relevant histological prognostic factors in the whole cohort for both progression-free survival (PFS) and overall survival (OS) in univariate analysis were hypercellularity, high mitotic count (>5 per 10 high-power fields) and necrosis. On the basis of these results, we propose a new grading scheme for these tumors which was of pronostic value for both PFS and OS in uni- and multivariate analysis. As extent of surgery was also a prognostic factor for both PFS and OS in univariate analysis, we propose that management of SFT/HPC might be based both on quality of removal and histological grade., (© 2011 The Authors; Brain Pathology © 2011 International Society of Neuropathology.)

Unlabelled: The recurrence and progression of treated intracranial meningiomas highlights the problem of the type of follow-up that should be used and whether early complementary treatment is indicated. The aim of this study was to evaluate different biochemical markers involved in cell proliferation and transformation to identify new prognostic factors in intracranial meningiomas. Between 1989 and 2003, 120 intracranial meningiomas were studied biochemically. The levels of estrogen receptors (RE), progesterone receptors (RP), cathepsin B (CB), cathepsin L (CL), stefin A (ATA), stefin B (STB), cystatin C (CYSC), urokinase (u-PA), type 1 plasminogen activator inhibitors (PAI-1), cathepsin D (CD) and thymidine kinase activity (TK) were measured in tumor extracts using biochemical assays., Results: Out of 120 meningiomas, 73 were grade I, 39 grade II and eight grade III according to the WHO classification. Of these patients, 17 showed recurrence. The mean follow-up was 47 months. Monofactorial analysis showed that expression of progesterone receptors (RP) had an inverse correlation with recurrence (p=0.0025 %) and that thymidine kinase activity (TK), cathepsin L (CL), the WHO grade and the degree of tumor resection correlated with recurrence (p<0.05). Principal component analysis and linear discriminant analysis confirmed these results. The results of this study confirm the importance of biological parameters (PR, CL, TK) as prognostic factors for the risk of recurrence in intracranial meningiomas.

Objective: To investigate the respective role of fractionated radiotherapy (FR) and gamma knife stereotactic (GKS) radiosurgery in cavernous sinus meningioma (CSM) treatment., Methods: The authors report the long-term follow-up of two populations of patients harboring CSMs treated either by FR (Group I, 38 patients) or GKS radiosurgery (Group II, 36 patients). There were 31 females with a mean age of 53 years in Group I and 29 females with a mean age of 51.2 years in Group II. In 20 patients (Group I) and 13 patients (Group II), FR and GKS radiosurgery were performed as an adjuvant treatment. In 18 patients (Group I) and in 23 patients (Group II), FR and GKS radiosurgery were performed as first line treatment. In our early experience with GKS radiosurgery (1992, date of gamma knife availability in the department), patients with tumors greater than 3 cm, showing close relationship with the optic apparatus (<3 mm) or skull base dural spreading, were treated by FR. Secondarily, with the advent of new devices and our growing experience, these criteria have evolved., Results: The median follow-up period was 88.6 months (range, 42-168 mo) for Group I and 63.6 months (range, 48-92 mo) for Group II. According to Sekhar's classification, 26 (68.4%) patients were Grade III to IV in Group I and 10 (27.8%) patients in Group II (P < 0.05); 23 (60.5%) patients had extensive lesions in Group I and 7 (19.4%) patients in Group II (P < 0.05). Mean tumor volume was 13.5 cm in Group I and 5.2 cm in Group II (P < 0.05). Actuarial progression-free survival was 94.7% and 94.4% in Group I and II, respectively. Clinically, improvement was seen for 24 (63.2%) patients in Group I and for 21 (53.8%) patients in Group II (P > 0.05). Radiologically, 11 (29%, Group I) patients and 19 (Group II, 52.7%) patients showed tumor shrinkage (P = 0.04). Transient morbidity was 10.5% in Group I and 2.8% in Group II. Permanent morbidity was 2.6% in Group I and 0% in Group II., Conclusion: FR and GKS radiosurgery are safe and efficient techniques in treatment of CSMs, affording comparable satisfactory long-term tumor control. However, GKS radiosurgery provides better radiological response, is far more convenient, and fits into most patients lives much better than FR. Therefore, in the authors' opinion, GKS radiosurgery should be advocated in first intention for patients with CSMs, whereas conventional radiotherapy should be reserved for cases that are not amenable to this technique, thus making these two therapeutic modalities not alternative but complementary tools in CS meningioma treatment strategy.

Background: Management of unresectable progressive meningioma remains controversial and constitutes a major challenge since therapeutic options including chemotherapy and hormone modulation are limited. Recent data have suggested that hydroxyurea treatment may have an antitumoral effect. The purpose of this prospective phase II study was to evaluate the efficacy of hydroxyurea treatment for unresectable progressive meningioma., Methods: From 1997 to 1999, consecutive patients presenting unresectable meningioma with clinically and/or neuroradiologically documented progression were considered for entry into this protocol. Previous radiotherapy was not a mandatory inclusion criteria. Treatment consisted of continuous oral administration of hydroxyurea at a dose of 20 mg/kg per day. Follow-up assessment included physical examination, computed tomography (CT), and magnetic resonance imaging (MRI) performed every three months, as well as regular blood testing. The primary endpoint was documentation of objective response by MRI or CT., Results: The intent-to-treat population was 43 patients with at least 18 months follow-up. Median age was 60.4 years. Twenty-eight patients had undergone surgery following initial diagnosis. The meningioma was located in the skull base in 67% of patients. Histology was benign in 18 and atypical in 10. The eligible population included 36 patients with documented progressive disease at the time of inclusion; with progression documented clinically in 29 (67.5%) and/or radiologically in 20 (46%). In 7 patients, clinical or radiological progression could not be confirmed. The intent-to-treat analysis at median 26 months follow-up revealed objective response to hydroxyurea in only 3 patients (7%) including one on the basis of improvement in visual symptoms and two on MRI analysis. Progressive disease was observed clinically or radiologically in 26 patients (60.5%). Of the eligible population (n=36), 2 achieved an objective response and 13 (36%) exhibited stabilization under hydroxyurea therapy, while 21 (58%) progressed under treatment. Overall tolerance was good but anemia (grade I-II) and asthenia (grade I-II) were observed in 28% and 23.5% respectively. Treatment was discontinued in 3 patients because of chronic skin toxicity in one and anemia and asthenia in two., Conclusion: Hydroxyurea treatment is of marginal efficacy for meningioma and must not be considered as an alternative if radiotherapy or surgery is feasible. New efficient medical treatments are still required for progressive meningiomas.

This report describes a case of metastatic meningioma involving the first thoracic vertebral body in a 63-year-old woman. The patient was treated surgically 10 years earlier for a benign meningioma of the right parietal vault. Local recurrence was diagnosed in 1992. Despite the gamma-knife radiosurgery, recurrence required surgical treatment in 1999. Histological findings were compatible with atypical meningioma (grade II WHO). One year later, the patient presented left C8 cervicobrachial neuralgia. Investigation led to discovery of a D1 tumor that was a metastasis of the atypical intracranial meningioma. A resection of the vertebral T1 body with C7-T2 osteosynthesis was performed with an excellent recovery and no postoperative complication.

It is known that, following radiotherapy, secondary cancer may occur after a long latent period. Few cytogenetic studies have been reported on tumors of the central nervous system occurring after radiotherapy. We report the cytogenetic study of six cases of radiation-induced meningiomas. In all cases, we observed the same chromosome abnormality, der(1)(1qter-->1p11::22q12-->22pter). SKY and CGH techniques allowed us to identify the chromosomal abnormalities. We suggest that a gene localized on 1p13 is involved in radiation-induced meningiomas.

Objective: We report the long-term follow-up of 31 patients with cavernous sinus meningiomas who were treated either with surgery and radiotherapy (RT) or with RT alone. This retrospective review was undertaken to compare long-term efficacy and morbidity of RT with or without previous surgery versus complete, aggressive surgical removal., Methods: Between 1980 and 1997, we performed a retrospective study of 31 patients harboring cavernous sinus meningiomas. The patient group comprised 25 women and 6 men. Patients were divided into two therapeutic categories: patients treated with surgery and RT (Group I, 17 patients) and patients treated with RT alone (Group II, 14 patients). Twenty-five patients (14 in Group I and 11 in Group II) were treated for primary tumors, and 6 patients (3 in Group I and 3 in Group II) were treated for recurrent disease. All three patients who were treated by RT alone at the time of recurrent disease had had previous surgery as initial treatment. Tumor control, treatment morbidity, and functional outcomes were evaluated for all patients. Twenty-eight patients were alive at the time of analysis, with a median follow-up period of 6.1 years., Results: The progression-free survival rate was 92.8% at 10-year follow-up. Only two patients exhibited tumor progression after initial treatment. One of the patients who experienced tumor regrowth 4 years after surgery and RT benefited from additional conventional external beam radiation, and this patient exhibited no evidence of tumor progression at the last follow-up examination 6 years later. Two patients experienced cranial nerve impairment after surgery, and no patients developed late radiation toxicity. Follow-up status as measured by the Karnofsky Performance Scale deteriorated in 7% of patients and was the same or improved in 93% of patients., Conclusion: The results of combined surgery and RT or RT alone indicated a high rate of tumor control and a low risk of complications. Complete aggressive surgical removal of cavernous sinus meningiomas is associated with an increased incidence of morbidity and mortality and does not demonstrate a better rate of tumor control. Conventional external beam radiation seems to be an efficient and safe initial or adjuvant treatment of these lesions, and these findings should serve as a basis for evaluating new alternatives such as radiosurgery or stereotactic RT.

Object: The authors sought to assess the functional tolerance and tumor control rate of cavernous sinus meningiomas treated by gamma knife radiosurgery (GKS)., Methods: Between July 1992 and October 1998, 92 patients harboring benign cavernous sinus meningiomas underwent GKS. The present study is concerned with the first 80 consecutive patients (63 women and 17 men). Gamma knife radiosurgery was performed as an alternative to surgical removal in 50 cases and as an adjuvant to microsurgery in 30 cases. The mean patient age was 49 years (range 6-71 years). The mean tumor volume was 5.8 cm3 (range 0.9-18.6 cm3). On magnetic resonance (MR) imaging the tumor was confined in 66 cases and extensive in 14 cases. The mean prescription dose was 28 Gy (range 12-50 Gy), delivered with an average of eight isocenters (range two-18). The median peripheral isodose was 50% (range 30-70%). Patients were evaluated at 6 months, and at 1, 2, 3, 5, and 7 years after GKS. The median follow-up period was 30.5 months (range 12-79 months). Tumor stabilization after GKS was noted in 51 patients, tumor shrinkage in 25 patients, and enlargement in four patients requiring surgical removal in two cases. The 5-year actuarial progression-free survival was 92.8%. No new oculomotor deficit was observed. Among the 54 patients with oculomotor nerve deficits, 15 improved, eight recovered, and one worsened. Among the 13 patients with trigeminal neuralgia, one worsened (contemporary of tumor growing), five remained unchanged, four improved, and three recovered. In a patient with a remnant surrounding the optic nerve and preoperative low vision (3/10) the decision was to treat the lesion and deliberately sacrifice the residual visual acuity. Only one transient unexpected optic neuropathy has been observed. One case of delayed intracavernous carotid artery occlusion occurred 3 months after GKS, without permanent deficit. Another patient presented with partial complex seizures 18 months after GKS. All cases of tumor growth and neurological deficits observed after GKS occurred before the use of GammaPlan. Since the initiation of systematic use of stereotactic MR imaging and computer-assisted modern dose planning, no more side effects or cases of tumor growth have occurred., Conclusions: Gamma knife radiosurgery was found to be an effective low morbidity-related tool for the treatment of cavernous sinus meningioma. In a significant number of patients, oculomotor functional restoration was observed. The treatment appears to be an alternative to surgical removal of confined enclosed cavernous sinus meningioma and should be proposed as an adjuvant to surgery in case of extensive meningiomas.

We report an unusual case of a cauda equina meningioma occurring in a young girl. This tumor was neurinoma-like. No meningeal attachment was identified in the neuroradiological study and during its microsurgical removal.

The correlation between cytogenetic and histopathological findings were analysed in 189 meningiomas. The tumors were classified according to increasing degrees of anaplasia. We observed normal karyotype or only monosomy 22 in grade 1 (benign) tumors, while in grade 3 (anaplastic) only 1.5% of karyotypes were normal. Grade 2 (atypical) and 3 (anaplastic) tumors showed complex structural abnormalities. Loss of chromosome 14 were only found in grade 3. In cases with complex structural rearrangements, fluorescence in situ hybridization technique (FISH) has been realized and permitted a best identification of abnormalities. In our series, five patients recurred. They presented chromosomal abnormalities. These complex karyotypes in recurrent meningiomas might indicate aggressive tumor characteristics. Our results indicate histolopathological and cytogenetics correlations might represent a prognostic factor in meningiomas.

Integrins form a family of cell adhesion molecules. CD44 glycoproteins are found in a wide variety of isoforms; the most common, CD44s (standard) is widely distributed, and functions as an adhesion molecule. In this study, we have investigated immunohistochemically the distribution of some VLA integrins (alpha2, alpha5 and alpha6 chains of beta1 integrins) and CD44s in 44 meningioma specimens and normal arachnoid villi. Meningiomas were of meningothelial (16), transitional (13) and fibroblastic (15) subtypes. There were 13 grade I, 19 grade II and 12 grade III (27%). Immunoprecipitates were quantified by image analysis and correlated with clinical (age, sex, location) and morphological data (histological subtypes and grades). VLA alpha5 chain was expressed by normal arachnoid villi (mainly cap cells) and by 42 out of 44 meningioma specimens. Expression was lower in fibroblastic meningiomas (P=0.02). VLA alpha2 and alpha6 chains were not observed in normal arachnoid villi. VLA alpha2 was expressed by 15 meningiomas, VLA alpha6 by 10. Interestingly, meningiomas expressing either VLA alpha2 or alpha6 were usually of grade III (P< or =(0.05). CD44s was found on various parts of arachnoid villi and in all meningiomas although expression was higher in meningothelial and transitional than in fibroblastic (P< or =0.001). These results show that VLA alpha5 and CD44s are widely expressed by arachnoid villi and meningiomas, in contrast to VLA alpha2 and VLA alpha6. It was noted that high grade meningiomas (III) express VLA alpha2 and alpha6 suggesting that changes in integrin pattern expression are a feature of these meningiomas. Moreover, strong CD44s expression characterizes meningothelial and transitional meningiomas. Previous studies have shown that high NCAM expression is a feature of fibroblastic meningiomas whereas meningothelial and transitional meningiomas expressed mainly E-Cadherin, and that polysialylated NCAM expression was restricted to high grade meningiomas. Taken together these features suggest that each cell adhesion molecule has a characteristic pattern of expression according to meningioma subtype and grade. No correlation was seen between integrins and CD44s expression and clinical data.

A 46 year-old woman presented with a weakness of the left side. MRI of the brain showed a left temporal meningioma, a left temporal lobe herniation and two high-signals in the right cerebral peduncle. The involvement of the pyramidal tract in the foot of the cerebral peduncle, in this case, results from temporal lobe hemiation. These findings are different from the mechanisms reported in other cases of ipsilateral hemiplegia. The ipsilateral hemiplegia syndrome was classically described by Ectors in relation to a meningioma of the foot of the third frontal circonvolution. Pathophysiological theories of ipsilateral hemiplegia are reviewed.

The authors present eleven cases of middle fossa floor meningiomas. They describe the anatomical and clinical features of these tumors in this rare localisation. They emphasize the strait anatomical relations with the cranial base, eight cases were inserted above the superior surface of the petrous bone, two above the endocranial face of the horizontal part of the greater sphenoid wing, one above the horizontal part of the temporal squama. Headache (6 cases) and memory loss (4 cases) are the most frequent clinical feature, seizures (2 cases) and neuropsychologic troubles were probably undervalued. Auditory signs were present in three cases. There was no visual defect and cranial nerve impairment. They insist on the necessity to obtain a complete preoperative temporal bone CT scan exploration. They think that a well advised surgical act is sufficient for these meningiomas inserted above weak structures and with good prognosis: there's no recurrence in this study with a follow up from 12 to 132 months.