Marta Brell

Prognostic Significance of O6-Methylguanine-DNA Methyltransferase Determined by Promoter Hypermethylation and Immunohistochemical Expression in Anaplastic Gliomas

Purpose: Anaplastic gliomas constitute a heterogeneous group of tumors with different therapeutic responses to adjuvant chemotherapy with alkylating agents. O6-Methylguanine-DNA methyltransferase (MGMT), a DNA repair protein, is one of the implicated factors in glioma chemoresistance.The prognostic value of MGMT remains controversial due in part to the fact that previous published studies included heterogeneous groups of patients with different tumor grades. The aim of this study was to evaluate the prognostic significance of MGMT in patients with anaplastic glioma. Experimental Design: Ninety-three patients with anaplastic glioma were analyzed for MGMT protein expression by immunohistochemistry. In addition, for those patients from whom a good yield of DNA was obtained (n = 40), MGMT promoter methylation profile was analyzed by methylation-specific PCR. MGMT prognostic significance was evaluated together with other well-known prognostic factors. Results: Fifty-one tumors (54.8%) showed nuclear staining of MGMT. There was a trend towards longer overall survival for those patients with negative MGMT immunostaining (hazard ratio, 1.66; P = 0.066). In a secondary analysis including those patients who actually received chemotherapy (n = 72), the absence of MGMT expression was independently associated with better survival (hazard ratio, 2.12; P = 0.027). MGMT promoter methylation was observed in 50% of the analyzed tumors. No statistical correlation between MGMT expression and MGMT promoter hypermethylation was observed. Conclusions: Unlike previous studies, we did not find a correlation between MGMT promoter methylation and survival. However, we observed a correlation between MGMT protein expression and survival in those patients who received chemotherapy thus suggesting that the absence of MGMT expression is a positive predictive marker in patients with anaplastic glioma.

Ki-67 proliferative index predicts clinical outcome in patients with atypical or anaplastic meningioma

Meningiomas represent the second most common central nervous system neoplasms in adults and account for 26% of all primary brain tumors. Although most are benign, between 5% and 15% of meningiomas are atypical (grade II) whereas 1–2% are anaplastic meningiomas (grade III). Although histological grade is the most relevant prognostic factor, there are some unusual cases in which establishing a diagnosis of high‐grade meningioma following 2000 World Health Organization (WHO) histological criteria is extremely difficult. Therefore, the aim of the present study was to evaluate the predictive value of Ki‐67 labeling index and its contribution to current WHO classification in predicting tumor recurrence and overall survival in patients with high‐grade meningiomas. A total of 28 patients (with 16 atypical meningiomas and 12 anaplastic meningiomas) were evaluated for demographic, clinical, radiological and therapeutic variables, and for Ki‐67 immunohistochemistry. Median Ki‐67 labeling index in the whole series was 7.0 (0.5–31.5) with no differences with respect to the histological grade (P = 0.87). In the univariate analysis, Ki‐67 labeling index and postoperative Karnofsky performance status were identified as significant prognostic factors of tumor recurrence and overall survival. The multivariate analysis demonstrated that Ki‐67 labeling index is the only independent predictor of both tumor recurrence and overall survival. More importantly, this predictive value was maintained in both patients with atypical and patients with anaplastic meningioma.

Factors influencing surgical complications of intra-axial brain tumours.

Summary Object. Extensive surgical resection remains nowadays the best treatment available for most intra-axial brain tumours. However, postoperative sequelae can outweigh the potential benefits of surgery. The goal of this study has been to review the results of this treatment in our Department in order to quantify morbidity and mortality and determine predictive risk factors for each patient. Method. We report a retrospective study of 200 patients submitted to a craniotomy for intra-axial brain tumours including gliomas and metastases. Postoperative major complications are analysed and related to different variables. An exhaustive review of the literature concerning the main controversial points about primary and metastatic brain tumours surgery is done. Findings. The overall major complication rate was 27.5%, with neurological complications being the most frequently encountered. We did not find a statistically significant relation between them and the grade of eloquence of the tumoural area. Infratentorial tumour location, previous radiotherapy and reoperations were factors strongly related to the incidence of regional complications. Age over 60 and severe concomitant disease were risk factors for systemic complications. Interpretation. The results from published series concerning surgical complications after craniotomies for brain tumours are not comparable because of the lack of homogeneity between them. The knowledge of the complications rate in each particular neurosurgical department turns out essentially to provide the patient with tailored information about risks before surgery.

Intracranial retrograde dissemination in filum terminale myxopapillary ependymomas

SummaryMyxopapillary ependymomas (ME) are considered benign tumours (WHO grade I) of the central nervous system with long term survival rates and a tendency to local recurrence. However an aggressive course has occasionally been described, leading to CSF dissemination and even systemic metastases.We describe the case of a 23-year-old man diagnosed with intracranial subarachnoid dissemination of a filum terminale ME three years after the initial diagnosis.We have performed a careful review of the literature on CSF dissemination in ME and finally propose treatment of these cases.

Isolated cerebral vasculitis associated with rheumatoid arthritis

Central nervous system involvement in rheumatoid arthritis is infrequent. Inflammatory lesions described in the literature are limited to rheumatoid nodules and vasculitis. We report on a 71-year-old woman who presented with a 1-month history of headache and dysarthria, and who had suffered seropositive rheumatoid arthritis without extra-articular complications, for 15 years. Magnetic resonance imaging showed a high-intensity image in FLAIR-weighted sequences in the right cerebral hemisphere, with meningeal gadolinium enhancement. A brain biopsy revealed necrotizing and lymphocytic vasculitis in the meninges as well as cerebral parenchyma. The patient received treatment with high-dose intravenous methylprednisolone with radiological improvement at 6-month follow-up. She remained neurologically asymptomatic in subsequent years. Three years after the onset of neurological symptoms, she was admitted to the hospital with choluria and jaundice. On the fiftieth day of hospitalization, she died from bronchopneumonia. The autopsy showed no signs of vasculitis. Cerebral vasculitis is an infrequent complication in RA. High-doses of intravenous corticosteroids may be an effective treatment.

O6-Methylguanine-DNA methyltransferase protein expression by immunohistochemistry in brain and non-brain systemic tumours: systematic review and meta-analysis of correlation with methylation-specific polymerase chain reaction

BackgroundThe DNA repair protein O6-Methylguanine-DNA methyltransferase (MGMT) confers resistance to alkylating agents. Several methods have been applied to its analysis, with methylation-specific polymerase chain reaction (MSP) the most commonly used for promoter methylation study, while immunohistochemistry (IHC) has become the most frequently used for the detection of MGMT protein expression. Agreement on the best and most reliable technique for evaluating MGMT status remains unsettled. The aim of this study was to perform a systematic review and meta-analysis of the correlation between IHC and MSP.MethodsA computer-aided search of MEDLINE (1950-October 2009), EBSCO (1966-October 2009) and EMBASE (1974-October 2009) was performed for relevant publications. Studies meeting inclusion criteria were those comparing MGMT protein expression by IHC with MGMT promoter methylation by MSP in the same cohort of patients. Methodological quality was assessed by using the QUADAS and STARD instruments. Previously published guidelines were followed for meta-analysis performance.ResultsOf 254 studies identified as eligible for full-text review, 52 (20.5%) met the inclusion criteria. The review showed that results of MGMT protein expression by IHC are not in close agreement with those obtained with MSP. Moreover, type of tumour (primary brain tumour vs others) was an independent covariate of accuracy estimates in the meta-regression analysis beyond the cut-off value.ConclusionsProtein expression assessed by IHC alone fails to reflect the promoter methylation status of MGMT. Thus, in attempts at clinical diagnosis the two methods seem to select different groups of patients and should not be used interchangeably.

Fractura evolutiva de cráneo en la infancia. Presentación de 12 casos

Resumen La fractura evolutiva de craneo (FEC) es una complicacion poco frecuente del traumatismo craneoencefalico (TCE) en la infancia. Consiste en una fractura con un desgarro dural subyacente, que se ensancha progresivamente hasta constituir un defecto craneal. Su fisiopatologia, asi como algunos aspectos del manejo terapeutico, son todavia controvertidos. Se presenta una revision retrospectiva de 12 casos diagnosticados y tratados entre los anos 1980 y 2002 en nuestra institucion. Once pacientes eran menores de 3 anos y uno tenia 5 anos en el momento del traumatismo. La causa mas frecuente de TCE fue la caida. En la radiografia inicial, 11 pacientes tenian fracturas con diastasis y solamente un paciente tenia fractura lineal. El hallazgo tomografico comun a todos los casos fue contusion cortical subyacente a la fractura. El intervalo promedio entre traumatismo y presentacion de las FEC fue de 11,6 semanas. La localizacion preferente de las FEC fue en la region parietal. El diagnostico se hizo por palpacion de un defecto craneal y se confirmo con radiografia. Se encontraron lesiones asociadas en la TAC y RMN preoperatoria, como hidrocefalia, encefalomalacia, quistes leptomeningeos, herniacion de tejido encefalico y dilatacion ventricular ipsilateral. Todos los pacientes fueron sometidos a reparacion plastica de la duramadre y el defecto craneal se cubrio con fragmentos oseos. Solo un paciente preciso craneoplastia con malla de titanio. Todas las fracturas de craneo en edad pediatrica deben controlarse hasta constatar su reparacion. Los pacientes menores de 3 anos con fracturas inicialmente diastasadas y con evidencia en la TAC o RMN de laceracion dural, tienen mayor probabilidad de desarrollar una FEC. En estos casos se recomienda el tratamiento precoz para evitar un dano cerebral progresivo.

Neuroendoscopic Treatment of Intracranial Tuberculoma: Case Report

Neuroendoscopic Treatment of Intracranial Tuberculoma: Case Report Intracranial tuberculoma rarely are seen in industrialized countries and represent only a small part of all intracranial space-occupying lesions. In most cases, conservative therapy provides good results. When treatment is not effective or lesion enlarged, surgery is recommended. Role of surgery in patients with intracranial tuberculomas is not yet established. This report describes a case of symptomatic intracranial tuberculoma and minimally invasive surgical option of treatment with ventricular neuroendoscopic aspiration.