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A novel histomolecular tumor of the central nervous system, the “intracranial mesenchymal tumor (IMT), FET-CREB fusion-positive” has recently been identified in the literature and will be added to the 2021 World Health Organization Classification of Tumors of the Central Nervous System. However, our latest study using DNA-methylation analyses has revealed that intracranial FET-CREB fused tumors do not represent a single molecular tumor entity. Among them, the main subgroup presented classical features of angiomatoid fibrous histiocytoma, having ultrastructural features of arachnoidal cells, for. Another tumor type with clear cell component and histopathological signs of aggressivity clustered in close vicinity with clear cell sarcoma of soft tissue. Herein, we report one case of IMT with a novel SMARCA2-CREM fusion which has until now never been described in soft tissue or the central nervous system. We compare its clinical, histopathological, immunophenotypic, genetic and epigenetic features with those previously described in IMT, FET-CREB fusion-positive. Interestingly, the current case did not cluster with IMT, FET-CREB fusion-positive but rather presented histopathological (clear cell morphology with signs of malignancy), clinical (with a dismal course with several recurrences, metastases and finally the patient’s death), genetic (fusion implicating the CREM gene), and epigenetic (DNA-methylation profiling) similarities with our previously reported clear cell sarcoma-like tumor of the central nervous system. Our results added data suggesting that different clinical and histomolecular tumor subtypes or grades seem to be included within the terminology “IMT, FET-CREB fusion-positive”, and that further series of cases are needed to better characterize them.

OBJECTIVE The role of surgery in the treatment of malignant gliomas in the elderly is not settled. The authors conducted a randomized trial that compared tumor resection with biopsy only—both followed by standard therapy—in such patients. METHODS Patients ≥ 70 years of age with a Karnofsky Performance Scale (KPS) score ≥ 50 and presenting with a radiological suspicion of operable glioblastoma (GBM) were randomly assigned between tumor resection and biopsy groups. Subsequently, they underwent standard radiotherapy during the first years of the trial (2008–2017), with the addition of adjunct therapy with temozolomide when this regimen became standard (2017–2019). The primary endpoint was survival, and secondary endpoints were progression-free survival (PFS), cognitive status (Mini-Mental State Examination), autonomy (KPS), quality of life (European Organisation for Research and Treatment of Cancer [EORTC] QLQ-C30 and QLQ-BN20), and perioperative morbidity and mortality. RESULTS Between 2008 and 2019, 107 patients from 9 centers were enrolled in the study; 101 were evaluable for analysis because a GBM was histologically confirmed (50 in the surgery arm and 51 in the biopsy arm). There was no statistically significant difference in median survival between the surgery (9.37 months) and the biopsy (8.96 months, p = 0.36) arms (adjusted HR 0.79, 95% CI 0.52–1.21, p = 0.28). However, the surgery group had an increased PFS (5.06 vs 4.02 months; p = 0.034) (adjusted HR 0.50, 95% CI 0.32–0.78, p = 0.002). Less deterioration of quality of life and KPS score evolution than in the biopsy group was observed. Surgery was not associated with increased mortality or morbidity. CONCLUSIONS This study suggests that debulking surgery is safe, and—compared to biopsy—is associated with a less severe deterioration of quality of life and autonomy, as well as a significant although modest improvement of PFS in elderly patients suffering from newly diagnosed malignant glioma. Although resection does not provide a significant survival benefit in the elderly, the authors believe that the risk/benefit analysis favors an attempt at optimal tumor resection in this population, provided there is careful preoperative geriatric evaluation. Clinical trial registration no.: NCT02892708 (ClinicalTrials.gov)

Background Considering that pediatric high-grade gliomas (HGGs) are biologically distinct from their adult counterparts, the objective of this study was to define the landscape of HGGs in adolescents and young adults (AYAs). Methods We performed a multicentric retrospective study of 112 AYAs from adult and pediatric Ile-de-France neurosurgical units, treated between 1998 and 2013 to analyze their clinicoradiological and histomolecular profiles. The inclusion criteria were age between 15 and 25 years, histopathological HGG diagnosis, available clinical data, and preoperative and follow-up MRI. MRI and tumoral samples were centrally reviewed. Immunohistochemistry and complementary molecular techniques such as targeted/next-generation sequencing, whole exome sequencing, and DNA-methylation analyses were performed to achieve an integrated diagnosis according to the 2016 World Health Organization (WHO) classification. Results Based on 80 documented AYA patients, HGGs constitute heterogeneous clinicopathological and molecular groups, with a predominant representation of pediatric subtypes (histone H3-mutants, 40%) but also adult subtypes (isocitrate dehydrogenase [IDH] mutants, 28%) characterized by the rarity of oligodendrogliomas, IDH mutants, and 1p/19q codeletion and the relative high frequency of “rare adult IDH mutations” (20%). H3G34-mutants (14%) represent the most specific subgroup in AYAs. In the H3K27-mutant subgroup, non-brainstem diffuse midline gliomas are more frequent (66.7%) than diffuse intrinsic pontine gliomas (23.8%), contrary to what is observed in children. We found that WHO grade has no prognostic value, but molecular subgrouping has major prognostic importance. Conclusions HGGs in AYAs could benefit from a specific classification, driven by molecular subtyping rather than age group. Collaborative efforts are needed from pediatric and adult neuro-oncology teams to improve the management of HGGs in AYAs.

Background 1p/19q-codeleted anaplastic gliomas have variable clinical behavior. We have recently shown that the common 9p21.3 allelic loss is an independent prognostic factor in this tumor type. The aim of this study is to identify less frequent genomic copy number variations (CNVs) with clinical importance that may shed light on molecular oncogenesis of this tumor type. Materials and Methods A cohort of 197 patients with anaplastic oligodendroglioma was collected as part of the French POLA network. Clinical, pathological, and molecular information was recorded. CNV analysis was performed using single-nucleotide polymorphism arrays. Computational biology and feature selection based on the random forests method were used to identify CNV events associated with overall survival and other clinical-pathological variables. Results Recurrent chromosomal events were identified in chromosomes 4, 9, and 11. Forty-six focal amplification events and 22 focal deletion events were identified. Twenty-four focal CNV areas were associated with survival, and five of them were significantly associated with survival after multivariable analysis. Nine out of 24 CNV events were validated using an external cohort of The Cancer Genome Atlas. Five of the validated events contain a cancer-related gene or microRNA: CDKN2A deletion, SS18L1 amplification, RHOA/MIR191 copy-neutral loss of heterozygosity, FGFR3 amplification, and ARNT amplification. The CNV profile contributes to better survival prediction compared with clinical-based risk assessment. Conclusion Several recurrent CNV events, detected in anaplastic oligodendroglioma, enable better survival prediction. More importantly, they help in identifying potential genes for understanding oncogenesis and for personalized therapy. Implications for Practice Genomic analysis of 197 anaplastic oligodendroglioma tumors reveals recurrent somatic copy number variation areas that may help in understanding oncogenesis and target identification for precision medicine. A machine learning multivariable model built using this genomic information enables better survival prediction.

While neurosurgery plays a marginal role in the treatment of ischemic strokes, and while the development of endovascular techniques has reduced its contribution to the treatment of subarachnoid haemorrhages resulting from an aneurysm, it still has a role to play in the event of a compressive haematoma. The overall improvement of the health status of elderly patients and the progress made in different medical fields have resulted in a more aggressive surgical approach in patients in the third, or even fourth age.

BACKGROUND The role of surgery for the treatment of malignant gliomas in patients 70 years of age or older is unsettled. We conducted a randomized trial that compared surgical resection of the tumor and biopsy only, both followed by standard therapy, in such patients. MATERIAL AND METHODS Patients aged 70 years and older, with a KPS of at least 50, presenting with a radiological suspicion of an operable glioblastoma (GBM) were randomly assigned between tumor resection and biopsy. Subsequently, they underwent standard radiotherapy during the first years of the trial (2008–2017), with the adjunction of concomitant and adjuvant temozolomide when this regimen became standard (2017–2019). The primary end point was survival; secondary endpoints were progression free survival (PFS), cognitive status (MMS), autonomy (KPS), quality of life (EORTC QLQ C30 and BN20), and perioperative morbidity/ mortality. RESULTS From 2008 to 2019, 107 patients from 9 centers were enrolled in the study, of whom 101 were evaluable for analysis because the diagnosis of GBM was histologically confirmed (50 patients in the “surgery” arm and 51 patients in the “biopsy” arm). There was no statistically significant difference of median survival between the “surgery” arm (9.37 mo) and the “biopsy” arms (8.96 mo, p=0.36). However, the surgery group had increased PFS (5.06 mo vs 4.02 mo; p=0.034; p=0.002 on multivariate analysis) and better QOL (e.g. physical and cognitive functioning, motor dysfunction, fatigue) and KPS score evolution as compared to the “biopsy” group. Surgery was not associated with increased mortality or morbidity. CONCLUSION This study suggests that optimal debulking surgery does not provide a significant survival benefit in elderly patients suffering from newly diagnosed malignant glioma, but resection improves QOL and autonomy with a significant though modest improvement of PFS.

BACKGROUND Considering that paediatric high-grade gliomas (HGGs) are biologically distinct from their adult counterparts, the objective of this study was to define the landscape of HGGs in adolescents and young adults (AYAs). METHODS We performed a multicentric retrospective study of 112 AYAs from adult and paediatric Ile-de-France neurosurgical units, treated between 1998 and 2013 to analyse their clinicoradiological and histomolecular profiles. The inclusion criteria were age between 15 and 25-years, histopathological HGG diagnosis, available clinical data, pre-operative and follow-up MRI. MRI and tumoral samples were centrally reviewed. Immunohistochemistry and complementary molecular techniques such as targeted/next generation sequencing, whole exome sequencing and DNA-methylation analyses were performed to achieve an integrated diagnosis according to the 2016 WHO classification. RESULTS Based on 80 documented AYA patients, HGGs constitute heterogeneous clinicopathological and molecular groups, with a predominant representation of paediatric-subtypes (Histone H3-mutants, 40%) but also adult-subtypes (IDH-mutants, 28%) characterized by the rarity of oligodendrogliomas, IDH-mutant and 1p/19q co-deleted and the relative high frequency of “rare adult IDH mutations” (20%). H3G34-mutants (14%) represent the most specific subgroup in AYAs. In the H3K27-mutant subgroup, the non-brainstem diffuse midline gliomas are more frequent (66.7%) than diffuse intrinsic pontine gliomas (23.8%), contrary to children. We found that WHO grade has no prognostic value, but molecular subgrouping has major prognostic importance. CONCLUSIONS HGGs in AYAs could benefit from a more personalized neuro-oncological management, driven by molecular subtyping rather than age group. Collaborative efforts are needed from paediatric and adult neuro-oncology teams to improve the management of HGGs in AYAs.

A growing literature supports maximal safe resection followed by standard combined chemoradiotherapy (i.e. maximal first-line therapy) for selected elderly glioblastoma patients. To assess the prognostic factors from recurrence in elderly glioblastoma patients treated by maximal safe resection followed by standard combined chemoradiotherapy as first-line therapy. Multicentric retrospective analysis comparing the prognosis and optimal oncological management of recurrent glioblastomas between 660 adult patients aged of

While neurosurgery plays a marginal role in the treatment of ischemic strokes, and while the development of endovascular techniques has reduced its contribution to the treatment of subarachnoid haemorrhages resulting from an aneurysm, it still has a role to play in the event of a compressive haematoma. The overall improvement of the health status of elderly patients and the progress made in different medical fields have resulted in a more aggressive surgical approach in patients in the third, or even fourth age.

Glioblastoma patients often require chronic administration of steroids due to peri-tumoral edema. Preliminary studies showed that treatment with Angiotensin-II Receptor Blockers (ARBs) for high blood pressure might be associated with reduced peri-tumoral edema. In this study, we aim to radiologically assess the effect of ARBs on peri-tumoral edema. We conducted a cross-sectional survey on patients with newly diagnosed GBM. Patients treated with ARBs for high blood pressure were paired to non ARB-treated patients based on similar age, tumor location and tumor size. Patients taking steroids at the time of pre-operative Magnetic Resonance Imaging were excluded from the study. In each pair of patients, we compared the volumes of peri-tumoral hyper T2-Fluid Attenuated Inversion Recovery (FLAIR) signal and the Apparent Diffusion Coefficient (ADC) in the same area. Eleven (11) ARB-treated patients were selected and paired to 11 non ARB-treated controls. Volumes of peri-tumoral hyper T2-FLAIR signal were significantly lower in the ARB-treated group than in the non ARB-treated group (p = 0.02). Additionally, peri-tumoral ADCs were also significantly lower in the treated group (p = 0.02), suggesting that the peri-tumoral area in this group had less edematous features. These results suggest that ARBs may reduce the volume of peri-tumoral hyper T2-FLAIR signal by decreasing edema.

We assessed prognostic factors in relation to OS from progression in recurrent glioblastomas. Retrospective multicentric study enrolling 407 (training set) and 370 (external validation set) adult patients with a recurrent supratentorial glioblastoma treated by surgical resection and standard combined chemoradiotherapy as first-line treatment. Four complementary multivariate prognostic models were evaluated: Cox proportional hazards regression modeling, single-tree recursive partitioning, random survival forest, conditional random forest. Median overall survival from progression was 7.6 months (mean, 10.1; range, 0-86) and 8.0 months (mean, 8.5; range, 0-56) in the training and validation sets, respectively (p = 0.900). Using the Cox model in the training set, independent predictors of poorer overall survival from progression included increasing age at histopathological diagnosis (aHR, 1.47; 95% CI [1.03-2.08]; p = 0.032), RTOG-RPA V-VI classes (aHR, 1.38; 95% CI [1.11-1.73]; p = 0.004), decreasing KPS at progression (aHR, 3.46; 95% CI [2.10-5.72]; p

Objectives: We aimed to study the potential clinical relevance of 9p allelic loss, with or without copy number variation, in 1p/19q codeleted anaplastic oligodendroglial tumors (AOTs). Methods: This study enrolled 216 patients with 1p/19q codeleted AOT. The prognostic value of 9p allelic loss was investigated using a French nation-wide prospective registry, POLA (prise en charge des tumeurs oligodendrogliales anaplasiques) and high-density single nucleotide polymorphism arrays. We validated our results using the Repository of Molecular Brain Neoplasia Data (REMBRANDT) dataset. Results: The minimal common region of allelic loss in chromosome arm 9p was 9p21.3. Allelic loss of 9p21.3, detected in 41.7% of tumors, was associated with shorter progression-free and overall survival rates in univariate ( p = 0.008 and p p = 0.009 and p = 0.009, respectively). This finding was validated in the REMBRANDT dataset in univariate and multivariate analysis ( p = 0.01 and p = 0.01, respectively). Conclusion: Our study highlights a novel potential prognostic biomarker in 1p/19q codeleted AOT. Further prospective studies are warranted to investigate our finding.

Surgical excision of brain metastases has been well evaluated in unique metastases. Two randomized phase III trial have shown that combined with adjuvant whole brain radiotherapy, it significantly improves overall survival. However, even in the presence of multiple brain metastases, surgery may be useful. Also, even in lesions amenable to radiosurgery, surgical resection is preferred when tumors displayed cystic or necrotic aspect with important edema or when located in highly eloquent areas or cortico-subcortically. Furthermore, surgery may have a diagnostic role, in the absence of histological documentation of the primary disease, to rule out a differential diagnosis (brain abscess, lymphoma, primary tumor of the central nervous system or radionecrosis). Finally, the biological documentation of brain metastatic disease might be useful in situations where a specific targeted therapy can be proposed. Selection of patients who will really benefit from surgery should take into account three factors, clinical and functional status of the patient, systemic disease status and characteristics of intracranial metastases. Given the improved overall survival of cancer patients partially due to the advent of effective targeted therapies on systemic disease, a renewed interest has been given to the local treatment of brain metastases. Surgical resection currently represents a valuable tool in the armamentarium of brain metastases but has also become a diagnostic and decision tool that can affect therapeutic strategies in these patients.

The incidence of glioblastoma (GBM) has increased in patients aged 70 years or older, and will continue to grow. Elderly GBM patients have been excluded from most clinical trials; furthermore, optimal care management as well as benefit/risk ratio of GBM treatments are still being debated. This study describes oncological patterns of care, prognostic factors, and survival for patients ≥70 years in France. We identified patients over 70 with newly diagnosed and histologically confirmed GBM on data previously published by the French Brain Tumor DataBase. We included 265 patients. Neurological deficits and mental status disorders were the most frequent symptoms. The surgery consisted of resection (RS n = 95) or biopsy (B n = 170); 98 patients did not have subsequent oncological treatment. After surgery, first-line treatment consisted of radiotherapy (RT n = 76), chemotherapy (CT n = 52), and concomitant radiochemotherapy (CRC n = 39). The median age at diagnosis was 76, 74, and 73 years, respectively, for the untreated, B + RT and/or CT, RS ± RT and/or CT groups. Median survival (in days, 95 % CI) with these main strategies, when analyzed according to surgical groups, was: B-CT n = 41, 199[155–280]; B-CRC n = 21, 318[166–480]; B-RT n = 37, 149[130–214]; RS-CT n = 11, 245[211–na]; RS-CRC n = 18, 372[349–593]; RS-RT n = 39, 269[218–343]. This population study for elderly GBM patients is one of the most important in Europe, and could be considered as a historical cohort to compare future treatments. Moreover, we can hypothesize that elderly patients (versus patients

BACKGROUND: The aim of this study was to correlate MRI features and molecular characteristics in anaplastic oligodendrogliomas (AOs). METHODS: The MRI characteristics of 50 AO patients enrolled in the French national network for high-grade oligodendroglial tumors were analyzed. The genomic profiles and IDH mutational statuses were assessed using high-resolution single-nucleotide polymorphism arrays and direct sequencing, respectively. The gene expression profiles of 25 1p/19q-codeleted AOs were studied on Affymetrix expression arrays. RESULTS: Most of the cases were frontal lobe contrast-enhanced tumors (52%), but the radiological presentations of these cases were heterogeneous, ranging from low-grade glioma-like aspects (26%) to glioblastoma-like aspects (22%). The 1p/19q codeletion (n = 39) was associated with locations in the frontal lobe (P = .001), with heterogeneous intratumoral signal intensities (P = .003) and with no or nonmeasurable contrast enhancements (P = .01). The IDH wild-type AOs (n = 7) more frequently displayed ringlike contrast enhancements (P = .03) and were more frequently located outside of the frontal lobe (P = .01). However, no specific imaging pattern could be identified for the 1p/19q-codeleted AO or the IDH-mutated AO. Within the 1p/19q-codeleted AO, the contrast enhancement was associated with larger tumor volumes (P = .001), chromosome 9p loss and CDKN2A loss (P = .006), genomic instability (P = .03), and angiogenesis-related gene expression (P < .001), particularly for vascular endothelial growth factor A and angiopoietin 2. CONCLUSION: In AOs, the 1p/19q codeletion and the IDH mutation are associated with preferential (but not with specific) imaging characteristics. Within 1p/19q-codeleted AO, imaging heterogeneity is related to additional molecular alterations, especially chromosome 9p loss, which is associated with contrast enhancement and larger tumor volume.

Surgical excision in brain metastases has been well evaluated in unique metastases. Two randomized phase III trials have shown that combined with adjuvant whole brain radiotherapy, it significantly improves overall survival. However, even in the presence of multiple brain metastases, surgery may be useful in large, symptomatic or life-threatening lesions (posterior fossa tumor with mass effect). Also, even in lesions amenable to radiosurgery, surgical resection is preferred when tumors displayed cystic or necrotic aspect with important edema or when located in highly eloquent areas or cortico-subcortically. Furthermore, surgery may have a diagnostic role, in the absence of histological documentation of the primary disease, if the radiological aspect is atypical to rule out differential diagnosis (brain abscess, lymphoma, primary tumor of the central nervous system) or in case of suspicion of progression after irradiation to differentiate radionecrosis from a genuine progression of brain disease. Finally, the issue of biological documentation of brain disease may arise in situations where a specific targeted therapy can be proposed. If the surgical indications are relatively well defined, the selection of patients who will really benefit from surgery should take into account three factors, clinical and functional status of the patient, systemic disease status and characteristics of intracranial metastases. Given the improved survival of cancer patients due to the advent of effective targeted therapies on systemic disease, a renewed interest has been given to local therapy (surgery or radiosurgery) in brain metastases. Surgical resection currently represents a valuable tool in the armamentarium of brain metastases but has also become a diagnostic and decision tool that can affect therapeutic strategies in these patients.

International audience; BACKGROUND:To assess the influence of the time interval between surgical resection and standard combined chemoradiotherapy on survival in newly diagnosed and homogeneously treated (surgical resection plus standard combined chemoradiotherapy) glioblastoma patients; while controlling confounding factors (extent of resection, carmustine wafer implantation, functional status, neurological deficit, and postoperative complications).METHODS:From 2005 to 2011, 692 adult patients (434 men; mean of 57.5 ± 10.8 years) with a newly diagnosed glioblastoma were enrolled in this retrospective multicentric study. All patients were treated by surgical resection (65.5% total/subtotal resection, 34.5% partial resection; 36.7% carmustine wafer implantation) followed by standard combined chemoradiotherapy (radiotherapy at a median dose of 60 Gy, with daily concomitant and adjuvant temozolomide). Time interval to standard combined chemoradiotherapy was analyzed as a continuous variable and as a dichotomized variable using median and quartiles thresholds. Multivariate analyses using Cox modeling were conducted.RESULTS:The median progression-free survival was 10.3 months (95% CI, 10.0-11.0). The median overall survival was 19.7 months (95% CI, 18.5-21.0). The median time to initiation of combined chemoradiotherapy was 1.5 months (25% quartile, 1.0; 75% quartile, 2.2; range, 0.1-9.0). On univariate and multivariate analyses, OS and PFS were not significantly influenced by time intervals to adjuvant treatments. On multivariate analysis, female gender, total/subtotal resection and RTOG-RPA classes 3 and 4 were significant independent predictors of improved OS.CONCLUSIONS:Delaying standard combined chemoradiotherapy following surgical resection of newly diagnosed glioblastoma in adult patients does not impact survival.

CERVOXY COLL; International audience; BACKGROUND: The standard of care for newly diagnosed glioblastoma is maximal safe surgical resection, followed by chemoradiation therapy. We assessed carmustine wafer implantation efficacy and safety when used in combination with standard care. METHODS: Included were adult patients with (n = 354, implantation group) and without (n = 433, standard group) carmustine wafer implantation during first surgical resection followed by chemoradiation standard protocol. Multivariate and case-matched analyses (controlled propensity-matched cohort, 262 pairs of patients) were conducted. RESULTS: The median progression-free survival was 12.0 months (95% CI: 10.7-12.6) in the implantation group and 10.0 months (9.0-10.0) in the standard group and the median overall survival was 20.4 months (19.0-22.7) and 18.0 months (17.0-19.0), respectively. Carmustine wafer implantation was independently associated with longer progression-free survival in patients with subtotal/total surgical resection in the whole series (adjusted hazard ratio [HR], 0.76 [95% CI: 0.63-0.92], P = .005) and after propensity matching (HR, 0.74 [95% CI: 0.60-0.92], P = .008), whereas no significant difference was found for overall survival (HR, 0.95 [0.80-1.13], P = .574; HR, 1.06 [0.87-1.29], P = .561, respectively). Surgical resection at progression whether alone or combined with carmustine wafer implantation was independently associated with longer overall survival in the whole series (HR, 0.58 [0.44-0.76], P \textless .0001; HR, 0.54 [0.41-0.70], P \textless .0001, respectively) and after propensity matching (HR, 0.56 [95% CI: 0.40-0.78], P \textless .0001; HR, 0.46 [95% CI: 0.33-0.64], P \textless .0001, respectively). The higher postoperative infection rate in the implantation group did not affect survival. CONCLUSIONS: Carmustine wafer implantation during surgical resection followed by the standard chemoradiation protocol for newly diagnosed glioblastoma in adults resulted in a significant progression-free survival benefit

This report, an audit requested by the French government, describes oncological patterns of care, prognostic factors, and survival for patients with newly diagnosed and histologically confirmed glioblastoma multiforme (GBM) in France. The French Brain Tumor DataBase, which is a national multidisciplinary (neurosurgeons, neuropathologists, radiotherapists, neurooncologists, epidemiologists, and biostatisticians) network, prospectively collected initial data for the cases of GBM in 2004, and a specific data card was used to retrospectively collect data on the management and follow-up care of these patients between January 1, 2004, and December 1, 2006. We recorded 952 cases of GBM (male/female ratio 1.6, median age 63.9 years, mean preoperative Karnofsky performance status [KPS] 79). Surgery consisted of resection (RS; n = 541) and biopsy (n = 411); 180 patients did not have subsequent oncological treatment. After surgery, first-line treatment (n = 772) consisted of radiotherapy (RT) and temozolomide (TMZ) concomitant +/- adjuvant in 314 patients, RT alone in 236 patients, chemotherapy (CT) alone in 157 patients, and other treatment modalities in 65 patients. Median overall survival was 286 days (95% CI, 266-314) and was significantly affected by age, KPS, and tumor location. Median survival (days, 95% CI) associated with these main strategies, when analyzed by a surgical group, were as follows: RS + RT-TMZ((n=224)): 476 (441-506), biopsy + RT-TMZ((n=90)): 329 (301-413), RS + RT((n=147)): 363 (331-431), biopsy + RT((n=89)): 178 (153-237), RS + CT((n=61)): 245 (190-361), biopsy + CT((n=96)): 244 (198-280), and biopsy only((n=118)): 55 (46-71). This study illustrates the usefulness of a national brain tumor database. To our knowledge, this work is the largest report of recent GBM management in Europe.

Introduction Analyse de l’efficacite et de la tolerance des implants de carmustine (Gliadel ® ) deposes lors d’une exerese en association avec le protocole Stupp pour le traitement de premiere intention des glioblastomes supratentoriels de l’adulte nouvellement diagnostiques.’ Materiel/methode Etude cas-temoin et etude appariee en score de propension chez 787 glioblastomes avec (groupe Implantation) et sans (groupe Standard) implantation de Gliadel ® en association avec le protocole Stupp. Resultats La survie sans progression mediane etait de 12,0 mois (95 % CI 10,7–12,6) dans le groupe implantation et de 10,0 mois (95 % CI : 9,0–10,0) dans le groupe standard. Le hazard ratio de progression tumorale dans le groupe implantation en comparaison du groupe standard etait de 0,81 (95 % CI 0,69–0,94 ; p = 0,004) dans l’etude cas-temoin et de 0,78 (95 % CI 0,63–0,95 ; p = 0,016) dans l’etude appariee. La survie globable mediane etait de 21,0 mois (95 % CI 19,7–23,4) chez les patients ayant eu du Gliadel ® au cours de l’evolution de la maladie (en premiere intention et/ou en recidive) et de 17,6 mois (95 % CI 16,0–19,0) chez les patients n’en ayant jamais eu. Le hazard ratio de deces dans le groupe ayant eu du Gliadel ® au cours de l’evolution de leur maladie en comparaison du groupe n’en ayant jamais etait de 0,76 (95 % CI 0,65–0,90 ; p = 0,001) dans l’etude cas-temoin et de 0,73 (95 % CI 0,62–0,86 ; p p Conclusion L’implantation peroperatoire de Gliadel ® au cours d’une chirurgie de resection large associee au protocole Stupp pour le traitement de premiere intention des glioblastomes offre un gain de survie significatif avec une tolerance acceptable.

Prevention of secondary insults, such as hyperthermia, is a major goal after traumatic brain injury. The aim of our study was to identify risk factors for early hyperthermia in severe head-injured patients.Retrospective cohort study.A 17-bed multidisciplinary ICU of a 700-bed teaching hospital.A total of 101 adult patients admitted from January 1999 to December 2001 requiring continuous monitoring of intracranial pressure according to international guidelines.Forty-four patients experienced early hyperthermia (at least one episode of body temperature38.5 degrees C within the first 2 days). On univariate analysis five variables were associated with early hyperthermia: sex; body temperature; white blood cell count on admission; prophylactic use of acetaminophen; and diabetes insipidus within 2 days. On multivariate analysis, white blood cell count14.5 x 10(9)/l on admission (odds ratio, 7.1; 95% confidence interval, 2.4-20.5; p=0.001) and a body temperature on admission36 degrees C (odds ratio, 6.7; 95% confidence interval, 2.3-20.1) were strong risk factors of early hyperthermia. Prophylactic use of acetaminophen was negatively associated with early hyperthermia (odds ratio, 0.1; 95% confidence interval, 0.02-0.4). Patients who experienced early hyperthermia were less prone to have good recovery (GOS=5; p=0.03). More patients with severe or moderate disability (GOS=3 or 4) experienced early hyperthermia ( p=0.01).We identified a subgroup of patients at high risk of early hyperthermia, which is common in severe head-injured patients. These results could have clinical implications for prevention of hyperthermia after traumatic brain injury in adults.

Forestier's disease, also known as diffuse idiopathic skeletal hyperostosis (DISH), is a pathology of vertebral bodies characterised by exuberant osteophytis formation. Forestier's disease is usually managed conservatively. Surgical resection of the osteophytes is reported to be an effective treatment for severe cases and/ or cases with airway obstruction. We report a 55-year-old man presenting with 6 months' progressive dysphagia and dysphonia. He was managed successfully with an anterior cervical osteophytectomy without fusion. A literature review is included.

Object. The goal of this study was to determine the somatotopical structure—function relationships of the primary motor cortex in individual patients by using functional magnetic resonance (fMR) imaging. This was done to assess whether there is a displacement of functional areas compared with anatomical landmarks in patients harboring brain tumors close to the central region, and to validate these findings with intraoperative cortical stimulation.Methods. One hundred twenty hemispheres in 60 patients were studied by obtaining blood oxygen level—dependent fMR images in patients while they performed movements of the foot, hand, and face on both sides. There was a good correspondence between anatomical landmarks in the deep portion of the central sulcus on axial slices and the somatotopical organization of primary motor areas. Pixels activated during hand movements were centered on a small characteristic digitation; those activated during movements in the face and foot areas were located in the lower portion of the central sulcus (lateral to the hand area) and around the termination of the central sulcus, respectively. In diseased hemispheres, signal-intensity changes were still observed in the projection of the expected anatomical area. The fMR imaging data mapped intraoperative electrical stimulation in 92% of positive sites.Conclusions. There was a high correspondence between the somatotopical anatomy and function in the central sulcus, which was similar in normal and diseased hemispheres. The fMR imaging and electrical stimulation data were highly concordant. These findings may enable the neurosurgeon to locate primary motor areas more easily during surgery.

¶ Indications of surgical treatment for lesions in the central nervous system depend on the risk of a definitive neurological deficit, related to the benefit of resection. Detection of eloquent areas is then necessary because of major individual variability. Neuro-imaging functional techniques are in development and are beginning to be efficient for cortical sensorymotor mapping, but still lack sensitivity and specificity for language mapping, and remain unable to give real-time data during surgery and to perform sub-cortical mapping. The more precise and reliable method of functional mapping is represented by the intra-operative direct electrical stimulations (DES), which allow identification and preservation of essential pathways for motricity, sensibility and language, at each level of the central nervous system (cortico-subcortical). We report our experience of DES in the surgery of tumours and vascular malformations located in supra-tentorial brain eloquent areas, with a consecutive series of 60 patients operated on under general or local anaesthesia, from November 1996 until May 1999 in our department at La Salpetriere Hospital. Presenting symptoms in the 60 subjects (39 males, 21 females, mean age: 45 years) were seizures in 37 cases with normal clinical examination, and mild neurological deficit in 29 cases. MRI showed 60 supra-tentorial brain lesions: 30 precentral, 12 postcentral, 14 perisylvian in the dominant hemisphere, 4 deep-seated. All subjects underwent surgical resection using DES, with supratentorial cortico-subcortical mapping under general anaesthesia for motor areas detection in 43 cases and under local anaesthesia for sensori-motor and/or language tasks in 17 cases. The final histological diagnosis was 44 gliomas (31 low-grade and 13 high-grade), 9 metastasis, 3 cavernomas, 4 arteriovenous malformations (AVM). Resection was total or subtotal in 52 cases (87%) and partial in 8 cases (13%). 29 patients had no post-operative deficit, while the other 31 patients were impaired post-operatively, with in all cases, except 3, a complete recovery delayed for 15 days to 3 months (overall morbidity: 5%). The median follow up was 14 months. Intra-operative direct electrical stimulations of the central nervous system constitute a reliable, precise and safe method, allowing the realization of a functional mapping useful for all operations of lesions located in eloquent areas. This technique allows a minimization of definitive post-operative neurological deficit, and concurrently an improvement in the quality of resection.

There are few studies of poor methodological quality on the risk of thromboembolism in head and neck surgery. The incidence of symptomatic deep vein thrombosis is estimated between, 0.1% and 0.6%. The patient's risk factors (cancer, alcoholism, smoking, malnutrition) determine for the assessment of the potential benefit of thromboembolism prophylaxis. No method can be recommended based on the literature. In patients receiving anticoagulant therapy undergoing superficial head and neck surgery or dental extraction, the literature suggest to continue anticoagulation throughout the perioperative period.

Surgical excision in brain metastases has been well evaluated in unique metastases. Two randomized phase III trials have shown that combined with adjuvant whole brain radiotherapy, it significantly improves overall survival. However, even in the presence of multiple brain metastases, surgery may be useful in large, symptomatic or life-threatening lesions (posterior fossa tumor with mass effect). Also, even in lesions amenable to radiosurgery, surgical resection is preferred when tumors displayed cystic or necrotic aspect with important edema or when located in highly eloquent areas or cortico-subcortically. Furthermore, surgery may have a diagnostic role, in the absence of histological documentation of the primary disease, if the radiological aspect is atypical to rule out differential diagnosis (brain abscess, lymphoma, primary tumor of the central nervous system) or in case of suspicion of progression after irradiation to differentiate radionecrosis from a genuine progression of brain disease. Finally, the issue of biological documentation of brain disease may arise in situations where a specific targeted therapy can be proposed. If the surgical indications are relatively well defined, the selection of patients who will really benefit from surgery should take into account three factors, clinical and functional status of the patient, systemic disease status and characteristics of intracranial metastases. Given the improved survival of cancer patients due to the advent of effective targeted therapies on systemic disease, a renewed interest has been given to local therapy (surgery or radiosurgery) in brain metastases. Surgical resection currently represents a valuable tool in the armamentarium of brain metastases but has also become a diagnostic and decision tool that can affect therapeutic strategies in these patients.

Objective Epidermal growth factor receptor (EGFR) is an operationally specific antigen in malignant gliomas; it is overexpressed in > 60% of these tumors, whereas its expression is very low in normal brain. This study aimed to evaluate whether an adequate amount of an anti-EGFR monoclonal antibody (MAb) could reach a tumor after a single intravenous administration. Methods This study was open, nonrandomized, and uncontrolled. Single doses (20, 40, 100, 200, or 400 mg) of the murine MAb EMD55900 (MAb 425) were administered intravenously before surgery to 30 patients with malignant brain tumors. Serum samples were taken at defined time intervals during infusion, to determine EMD55900 concentrations, and 10, 21, and/or 42 days after infusion, to evaluate the development of human anti-mouse antibodies. Tumor samples were investigated for EGFR and EMD55900 contents. Results Tolerance to EMD55900 was good. Increased liver transaminase levels were noted for three patients with Grade 1 toxicity. Twenty patients developed significant human anti-mouse antibody titers, without correlation with the administered dose. The median half-life of EMD55900 in serum ranged from 6 hours for 20 mg to 24 hours for 400 mg. In the membrane fractions of the tumors, EGFR saturation by EMD55900 varied with the injected dose of MAb. No binding was detected after a 20-mg dose. After doses of 40, 100, 200, and 400 mg, the mean saturation levels were 33, 73, 89, and 71%, respectively. Conclusion This study indicates that a single intravenous administration of EMD55900 is well tolerated and produces substantial in vivo tumor binding with doses > 100 mg.

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

Study design A case report. Objective To illustrate a rare case of oncogenous osteomalacia caused by a spinal thoracic myopericytoma. Summary of background data Osteomalacia related to a tumor is well known. The cause of the disorder is usually a highly vascularized, benign tumor of mesenchymal origin. Location of the tumor in the spine is very rare. Removal of the tumor is followed by resolution of osteomalacia. Methods Diagnosis of oseomalacia was established on the presence of cardinal clinical, biologic, and radiologic features of osteomalacia. Localization of the tumor at T5 and T6 levels was obtained by magnetic resonance imaging. Surgical treatment consisted in a circumferential correction-fusion with hemivertebrectomy of T5 and T6 and tumor removal. Results Tumor removal was rapidly followed by disappearance of the clinical symptoms of osteomalacia, and by correction of hypophosphatemia. At 2-years follow-up, no recurrence of the tumor was detectable on imaging studies-the correction fusion remained stable. Histologically, the tumor was classified as a myopericytoma. There was no relapse of the clinical features of osteomalacia. However, secondary recurrence of the biologic markers due to an incomplete tumor removal was disclosed. Conclusion Removal of the tumor was followed by healing of the clinical features of osteomalacia, demonstrating the causal connection between the myopericytoma and the osteopathy.

BACKGROUND: A significant morbidity in glioblastoma (GBM) patients is related to peri-tumoral edema, which requires chronic administration of steroids. Preliminary studies have shown that treatment with Angiotensin-II receptor blockers (ARBs) for high blood pressure might be associated with reduced peri-tumoral edema. Our goal in this study was to radiologically assess the effect of ARBs on peri-tumoral vasogenic edema. METHODS: We conducted a cross-sectional survey on patients with newly diagnosed GBM. Patients treated with ARBs for high blood pressure were paired to non ARB-treated patients, based on similar age, tumor location and longest diameter. Patients taking steroids at the time of their pre-operative Magnetic Resonance Imaging were not eligible for this study. In each pair of patients, we compared the volumes of peri-tumoral hyper T2 FLAIR signal and the apparent diffusion coefficient (ADC) selected in the same area. RESULTS: Eleven (11) patients treated with ARBs were selected and paired to 11 non ARB-treated controls. Volumes of peri-tumoral hyper T2 FLAIR signal were significantly lower in the ARB-treated group than in the non ARB-treated group (p = 0.02). Peri-tumoral ADCs were also significantly lower in the treated group (p = 0.02), suggesting that brain surrounding the tumor had less edematous characteristics when patients were treated with ARBs. CONCLUSION: All together, these results suggest that ARBs could reduce the volume of peri-tumoral hyper T2 FLAIR signal by decreasing vasogenic edema.

BACKGROUND Although the existence of a motor defect in discogenic sciatica is a sign of severity, the literature does not provide evidence for an immediate requirement for surgery. OBJECTIVE To assess the course of sciatica with discogenic paresis and to determine possible prognostic factors for recovery or improvement. STUDY DESIGN This open prospective multicenter study included patients with discogenic sciatica with paresis that had been developing for less than 1 month and was rated < or =3 on a 5-grade scale. Pain, the strength of 11 muscles, return to work, and analgesic intake were assessed at 1, 3, and 6 months. Recovery and improvement were defined by pain not exceeding 20 mm or < or =50% of the initial pain score and a score of either 5 (recovery) or 4 (improvement) for the weakest muscle at inclusion. RESULTS Sixty-seven patients were enrolled; 39 (58%) patients were treated surgically and 28 (42%) medically. Surgically treated patients differed from medically treated patients by a higher rate of extruded herniation, a higher number of paretic muscles (6.3 vs. 5; P = 0.051), and a longer course of sciatica (31.4 vs. 17.3 days; P = 0.034). At 6 months, 7 (10.4%) patients were lost to follow-up; 32 (53.3%) had improved, including 18 (30%) recovered, 33 (85%) back to work and having a professional activity, and 22 (39%) still taking analgesics. The only significant difference between recovered and not recovered patients was mean age at inclusion (43 vs. 51 years, P = 0.034). There were no significant differences between improved and not improved patients. Moreover, the outcome was not different in the two treatment groups: there were 17 (53%) improvements in surgically treated patients, including 8 (25%) recoveries, and 14 (56%) improvements in medically treated patients, including 8 (40%) recoveries. CONCLUSION This pilot study showed no difference between surgical or medical management for recovery or improvement in patients with discogenic paresis. These results need confirmation by a randomized study.

International audience; PURPOSE: To determine whether the blood flow abnormalities frequently associated with arteriovenous malformations (AVMs) can alter functional magnetic resonance (MR) imaging evaluation of language lateralization and whether reorganization of language function occurs in patients with brain AVMs. MATERIALS AND METHODS: Eleven patients with left-hemisphere brain AVMs and 10 age-matched control subjects were examined with 1.5-T blood oxygen level-dependent (BOLD) functional MR imaging. Verbal fluency, sentence repetition, and story listening tasks were performed. The functional MR imaging laterality index in the frontal and temporal lobes was defined as the (L - R)/(L + R) ratio, where L and R are the numbers of activated pixels in the left and right hemispheres, respectively. Statistical analyses were performed with Wilcoxon signed rank, Fisher exact, and Kruskal-Wallis tests. RESULTS: Control subjects had left-sided language dominance, although symmetric pixel counts were observed in the frontal lobes in two subjects and in the temporal lobes in one subject. Six patients had left-sided language dominance similar to that observed in control subjects. Five of these patients had AVMs outside frontal or temporal language areas, without flow abnormalities. Five patients had abnormally right-sided asymmetric indexes (below mean control subject value - 2 SDs), which suggested language reorganization (P

BackgroundzzCysticercosis is the most frequent parasitic infection of the nervous system. Most lesions are intracranial, and spinal involvement is rare. We describe here in two cases of neurocysticercosis (NCC) in the brain and one in the spinal cord that illustrate three distinct mechanisms leading to symptomatic acute hydrocephalus. Case ReportzzHydrocephalus was related to intracranial NCC in two of them. In the first case the hydrocephalus was due to an extensive arachnoiditis to the craniocervical junction, while in the second it was caused by obstruction of Magendie’s foramen in the fourth ventricle by the scolex of Taenia solium. For the third patient, hydrocephalus revealed cysticercosis of the cauda equina due to the scolex. ConclusionszzNCC should be considered as a possible diagnosis for patients suffering from hydrocephalus when they originate from or have traveled in endemic areas, MRI of the spine is mandatory to search for intraspinal lesions.

OBJECTIVE Surgery of the insula represents a technical challenge, because of the proximity of the internal capsule to the lenticulostriate arteries and the lack of certainty concerning its functionality. Using intraoperative direct cerebral stimulation, combined with neuronavigation, the authors operated on 12 insular gliomas. On the basis of this experience, the physiopathological and surgical implications are discussed. METHODS A low-grade insular glioma, revealed by seizures, was diagnosed in 12 right-handed patients with a normal neurological status. Preoperative magnetic resonance imaging showed that, according to Yaşargil's classification system, three patients harbored Type 3 lesions and nine patients had Type 5 lesions (10 tumors on the right side and 2 on the left dominant side). All patients underwent surgery using direct cerebral stimulation, under general anesthesia in nine patients (motor mapping) and under local anesthesia in three patients (sensorimotor and language mapping). Ultrasonography and/or neuronavigation was used in all cases. Preoperative angio-computed tomographic scanning showed the lenticulostriate arteries in two patients. RESULTS The internal capsule was systematically detected, and the language areas were identified within the left insula in the awake patients. The lenticulostriate arteries were seen in two patients. Seven patients presented an immediate postoperative deficit; six of them recovered completely within 3 months. Four resections were total, six were subtotal, and two were partial (left insula). CONCLUSION The use of intraoperative direct cerebral stimulation and neuronavigation allows surgery of the insula with minimization of the risk of sequelae, but its use is still limited with regard to the dominant hemisphere, owing to the essential role of this structure in language.

Object. In this study the authors sought to estimate the frequency, seriousness, and delay of rebleeding in a homogeneous series of 20 patients whom they treated between May 1987 and May 1997 for arteriovenous fistulas (AVFs) that were revealed by intracranial hemorrhage (ICH). The natural history of intracranial dural AVFs remains obscure. In many studies attempts have been made to evaluate the risk of spontaneous hemorrhage, especially as a function of the pattern of venous drainage: a higher occurrence of bleeding was reported in AVFs with retrograde cortical venous drainage, with an overall estimated rate of 1.8% per year in the largest series in the literature. However, very few studies have been designed to establish the risk of rebleeding, an omission that the authors seek to remedy.Methods. Presenting symptoms in the 20 patients (17 men and three women, mean age 54 years) were acute headache in 12 patients (60%), acute neurological deficit in eight (40%), loss of consciousness in five (25%), and generalized seizures in one (5%). Results of the clinical examination were normal in five patients and demonstrated a neurological deficit in 12 and coma in three. Computerized tomography scanning revealed intracranial bleeding in all cases (15 intraparenchymal hematomas, three subarachnoid hemorrhages, and two subdural hematomas). A diagnosis of AVF was made with the aid of angiographic studies in 19 patients, whereas it was a perioperative discovery in the remaining patient. There were 12 Type III and eight Type IV AVFs according to the revised classification of Djindjian and Merland, which meant that all AVFs in this study had retrograde cortical venous drainage. The mean duration between the first hemorrhage and treatment was 20 days. Seven patients (35%) presented with acute worsening during this delay due to radiologically proven early rebleeding. Treatment consisted of surgery alone in 10 patients, combined embolization and surgery in eight, embolization only in one, and stereotactic radiosurgery in one. Three patients died, one worsened, and in 16 (80%) neurological status improved, with 15 of 16 AVFs totally occluded on repeated angiographic studies (median follow up 10 months).Conclusions. The authors found that AVFs with retrograde cortical venous drainage present a high risk of early rebleeding (35% within 2 weeks after the first hemorrhage), with graver consequences than the first hemorrhage. They therefore advocate complete and early treatment in all cases of AVF with cortical venous drainage revealed by an ICH.

BACKGROUND Ganglioglioma is a lesion rarely encountered in the pineal region. Only six cases have been published to our knowledge. METHODS AND RESULTS We present the case of a 38-year-old male suffering from a pineal ganglioglioma that was totally removed by surgery. Histological diagnosis was made by light microscopy using immunostaining for synaptophysin. We review the few radiological and pathological data available in the literature concerning this very rare lesion for which surgery alone provides excellent results. CONCLUSION The possibility of long term remission obtained by surgery alone and the lack of specificity of clinical and radiological features of ganglioglioma are additional reasons for an aggressive surgical management of pineal tumors when tumor markers and cytopathological examination of the cerebrospinal fluid are not contributive.

OBJECTIVE: Three-dimensional computed tomographic angiography (CTA) is a recently developed imaging modality. We demonstrate the value of this noninvasive method in replacing digital subtraction angiography (DSA) in the detection of aneurysms of the circle of Willis in patients with subarachnoid hemorrhage admitted to our institution. METHODS: A helical acquisition was performed for computed tomographic scans obtained for 120 patients with a 1 mm per second table speed and a 1-mm collimation, 1:1 pitch. Axial source images were transferred on a console Advantage Windows workstation (General Electric, Milwaukee, WI) and CTA was obtained using maximum intensity projection reconstruction. All patients had undergone DSA of the circle of Willis (80 patients preoperatively and 40 postoperatively). RESULTS: A total of 129 aneurysms were detected in 107 patients. Three-dimensional CTA disclosed nothing abnormal in 13 patients. Ninety-two patients sustained one aneurysm, 10 patients sustained two, 3 patients sustained three, and 2 patients sustained four. All results were confirmed by DSA. In two cases, aneurysms of the middle cerebral artery were detected by CTA but not by DSA. When using angiographic views, the aneurysm was always masked by a branch of the middle cerebral artery. CONCLUSION: The sensitivity of three-dimensional CTA is comparable with that of DSA, and its specificity is 100%. Because CTA is simple, quick, noninvasive, and reliable, we think that it can eventually replace DSA.

Although intracranial cavernomas are known to cause haemorrhage, data concerning the frequency, severity and delay of recurrent bleedings are controversial. We report a series of 6 patients with histologically proven cavernoma, presenting with early clinical signs and radiological proof of rebleeding, that is occurring in the first month after initial overt haemorrhage. These 6 cases have been selected from a series of 142 patients seen between 1980 and 1995 in our department with cavernous angiomas or so-called AOVMs, of whom 93 presented with clinical symptoms of haemorrhage (34 patients presented symptoms of one or more rebleeding, but only 6 had radiological proof). All patients suffered neurological worsening due to the rebleeding, with an increase of the size of the haematoma on the CT scan. Five MRIs were performed at the acute stage: 3 showed evidence of cavernoma (60%). All patients underwent surgery at the acute stage of the rebleeding, with 5 improvements and 1 stabilization. A cavernous angioma was found in 5 cases at first surgery, but a further operation was necessary in the last patient to find and remove the cavernoma, after a second rebleeding following the first intervention. Our series reveals a high frequency of rebleeding after a first intracranial haemorrhage from a cavernous angioma, and highlights the precocity of such rebleedings. Therefore, we advocate early aggressive surgical management: in cases of cavernoma revealed by a first clinical overt haemorrhage, when there is strong radiological suspicion at the acute stage; and in all cases of rebleeding, even without radiological evidence of malformation, in the absence of vascular risk factors. Surgical indication must be discussed in particular cases of cavernomas of the brain stem when neither the haematoma nor the cavernoma reach the surface, and in deep supratentorial cavernomas, when the neurological status is good, because of the therapeutic risk.

For the non-operable malignant glioma patients, prognosis remains poor, with a survival of 8 months for the glioblastomas (G), and 15 months for anaplastic astrocytomas (AA). 27 histologic proven malignant gliomas (17 AA and 10 G) were treated between April 1991 and June 1992. Median age was 48 years. The therapeutic protocol consisted of three courses of intra arterial chemotherapy (IAC) with ACNU, at intervals of six weeks, and a localised 60 Gy radiotherapy between the first and the second IAC course. 72 courses of IAC were delivered (2,4 per patient). Response rate was 51,8%. Median survival (MS) was 13 months, with a survival rate of 28% at 24 months. For the AA, MS was 21 months, with a survival rate of 37% at 24 months. For the G, median survival was 10 months. Responders were 65 % for AA, 30% for G. Non responders all died before 24 months had relapsed with a MS of 9 months. 54% of responding patients had a 2 years survival. Toxicity were acceptable with 7% of haematological toxicity and a partial loss of visual acuity in 11% of the cases. No chronic neurological sequellae were noted. We compare theses results with two previous trials, concerning inoperable patients, treated by an association of radiotherapy and systemic chemotherapy. Survival seems to be equivalent with HeCNU and with this treatment, but toxicity decreases with ACNU. Early radiotherapy does not increase complications. This treatment can be used for patients with inoperable malignant gliomas.