Long-Term Outcome of Temporal Lobe Epilepsy Surgery in 621 Patients With Hippocampal Sclerosis: Clinical and Surgical Prognostic Factors.

Temporal lobe epilepsy (TLE) is the most common type of focal epilepsy and is frequently drug-resistant (DR) to antiseizure medication (ASM), corresponding to approximately one-third of the cases. When left inadequately treated, it can worsen the quality of life, cognitive deficits, and risk of death. The standard treatment for drug-resistant TLE is the surgical removal of the structures involved, with good long-term outcome rates of 60-70 % and a low rate of adverse effects. The goal of successful treatment is sustained seizure freedom. In our study, we evaluated sustained long-term (up to 23 years) surgical outcomes in 621 patients with DR-TLE associated with hippocampal sclerosis, who underwent a temporal lobectomy. We analyzed the main predictive factors that influence the surgical outcome related to seizure control, through a longitudinal and retrospective study, using a multivariable regression model. We found that 73.6% of the patients were free from disabling seizures (Engel Class I), maintained over time in 65% of patients followed up to 23 years after surgery. We found that four independent variables predicted seizure outcomes. The presence of dysmnesic and olfactory aura predicted a less favorable outcome. The history of febrile seizure and the surgical technique predicted a good outcome. Regarding the type of surgical technique, the standard anteromesial temporal lobectomy (ATL) led to significantly better outcomes (78.6% Engel Class I) when compared to the selective amygdalohippocampectomy via subtemporal approach (67.2% Engel Class I; p = 0.002), suggesting that the neuronal networks involved in the epileptogenic zone may be beyond mesial temporal structures. The multivariable regression model with the above-mentioned predictor variables revealed an ExpB = 3.627 (N = 621, p < 0.001), indicating that the model was able to distinguish between patients with a seizure-free. We conclude that epilepsy surgery is a safe procedure, with low rates of postoperative complications and good long-term results.

Apoptosis related microRNAs and MGMT in glioblastoma cell lines submitted to treatments with ionizing radiation and temozolomide.

AIM: To evaluate the effect of radiotherapy and temozolomide on the expression of miRNAs apoptotic (miRNAs-21, -221, -222 (anti-apoptotic) and miRNAs-15a, -16 (pro-apoptotic)) and the gene MGMT in glioblastoma cell lines. BACKGROUND: The limited knowledge of the molecular biology of malignant gliomas may hinder the development of therapeutic modalities. In this scenario, one of the greatest advances of recent years was the identification of microRNAs. These molecules have an important role in biological processes involving cancer, including glioblastoma. MATERIALS AND METHODS: Trypan blue was used to verify the cell viability, and real time PCR to quantify the expression of microRNAs and gene 24, 48 and 120 h after exposure to treatments. RESULTS: There was a statistically significant decrease of expression of miR-15a between 48 and 120 h in line T98 G treated with radiation, increased expression of miR-15a between 24 and 120 h in line U251 treated with radiation and temozolomide, and increased expression of miR-16 between 24 and 120 h in line U251 treated with radiation alone and when combined with temozolomide. There was a decrease in MGMT gene expression, between 24 and 48 h in U343 cells treated with temozolomide. CONCLUSIONS: Ionizing radiation and temozolomide modified the expression of miRNAs studied and MGMT.

Morphological and immunohistochemical analysis of apoptosis in the cerebellum of rats subjected to focal cerebral ischemia with or without alcoholism model

ABSTRACT PURPOSE: To evaluated histopathological changes, morphometric and expression of proteins CASPASE-3, BCL-2 and XIAP related to apoptosis in the cerebellum after induction of temporary focal cerebral ischemia followed by reperfusion, with or without a model of chronic alcoholism. METHODS: Fifty Wistar rats were used and divided into: control group (C), sham group (S), ischemic group (I), alcoholic group (A), and ischemic and alcoholic group (IA). The cerebellum samples collected were stained for histopathological and morphometric analysis and immunohistochemistry study. RESULTS: Histopathological changes were observed a greater degree in animals in groups A and IA. The morphometric study showed no difference in the amount of cells in the granular layer of the cerebellum between the groups. The expression of CASPASE-3 was higher than BCL-2 and XIAP in the groups A and IA. CONCLUSION: We observed correlation between histopathological changes and the occurrence of apoptosis in cerebellar cortex.

Educational program on fatigue for brain tumor patients: possibility strategy?

OBJECTIVE: To evaluate the effectiveness of an educational program on improvement of fatigue and quality of life of patients with high-grade glioma during radiotherapy and chemotherapy treatment. METHOD: This is a longitudinal, experimental study. Twenty-three patients with high-grade glioma were randomly assigned to one of two groups. Both groups completed the Functional Assessment of Cancer Therapy: Fatigue questionnaire and the Beck Depression Inventory, and one of the groups received the educational intervention. RESULTS AND CONCLUSIONS: The groups did not show any change in quality of life and fatigue in this study, for this reason, the educational program did not present any significant difference. However, there was a significant difference in depressive symptoms during the educational program showing positive evidence for its applicability.

Sarcoma radioinduzido pós-tratamento de glioblastoma: relato de caso / Radiation induced sarcoma after treatment of glioblastoma: case report / Sarcoma inducido por la radiación después del tratamiento de glioblastoma: reporte de un caso

Introdução: O glioblastoma multiforme é a neoplasia de sistema nervoso central mais letal, com sobrevida média em torno de 13 meses e a de pior prognóstico dentre todos os gliomas. A abordagem terapêutica do glioblastoma consiste em neurocirurgia com ressecção máxima possível do volume tumoral, seguida de radioterapia e quimioterapia. A radioterapia reduz o risco de recidiva tumoral por meio de lesão direta e indireta ao ácido desoxirribonucleico tumoral. Os efeitos em longo prazo da radioterapia incluem necrose tecidual, vasculopatia e neoplasia induzida pela radiação. Os tumores malignos intracranianos secundários mais reportados incluem meningiomas, gliomas e sarcomas. O período de latência entre a radioterapia de crânio e o surgimento de lesões radioinduzida varia na literatura entre seis meses a 47 anos, com média de 18,7 anos. Relato de caso: O presente relato descreve o surgimento de sarcoma fusocelular de alto grau radioinduzido após dez meses em paciente que recebeu tratamento de glioblastoma no Hospital das Clínicas de Ribeirão Preto da Universidade de São Paulo. Conclusão: A raridade dessa associação se deve provavelmente à baixa sobrevida dos pacientes com glioblastoma, limitando assim o tempo para desenvolvimento de neoplasias secundárias.

Introduction: Glioblastoma multiforme and neoplasia is the deadliest cancer of the central nervous system, with survival rates averaging around 13 months and it shows the worst prognosis among all gliomas. The therapeutic approach of glioblastoma is based on a full neurosurgical resection of the tumor volume followed by radiotherapy and chemotherapy. Radiotherapy reduces the risk of recurrence by direct and indirect deoxyribonucleic acid damage of the tumor. The long-term effects of radiotherapy include tissue necrosis, vascular injury and neoplasia induced by radiation. The majority of secondary intracranial tumors and most commonly reported include meningiomas, gliomas and sarcomas. The latency period between the cranial radiotherapy and the onset of radiation-induced injuries in the literature varies between six months to 47 years, with an average of 18.7 years. Case report: This report describes the onset of spindle cell sarcoma of highly radiation-induced after ten months in a patient who received treatment of Glioblastoma at the General Hospital of the University of Sao Paulo Medical School, Ribeirao Preto. Conclusion: The rarity of this association is probably due to poor survival of patients with Glioblastoma, thus limiting the time for development of secondary malignancies.

Introducción: El glioblastoma multiforme es el cáncer más mortal del sistema nervioso central, con una supervivencia media acerca de 13 meses, y tiene el peor pronóstico entre todos los gliomas. El enfoque terapéutico del glioblastoma es la resección neurocirugica completo del volumen del posible tumor, seguido por radioterapia y quimioterapia. La radioterapia reduce el riesgo de reincidencia debido a daño directo e indirecto para el ácido desoxirribonucleico del tumor. Los efectos a largo plazo de la terapia de radiación incluyen necrosis de los tejidos, lesión vascular y el cáncer inducido por radiación. Los tumores intracraneales malignos secundarios más comunes incluyen meningiomas, gliomas y sarcomas. El período de latencia entre la radioterapia craneal y la aparición de las lesiones inducidas por radio en la literatura varía entre seis meses a 47 años, con una media 18,7 años. Caso clínico: Este caso describe la aparición de sarcoma de células fusiformes de grado alto inducida por radiación después de diez meses en un paciente que recibió tratamiento de glioblastoma en el Hospital das Clínicas de Ribeirão Preto, de la Universidad de Sao Paulo. Conclusión: Esta asociación poco común es probablemente debida a la mala supervivencia de los pacientes con glioblastoma, lo que limita el tiempo para el desarrollo de neoplasias malignas secundarias.

Educational program on fatigue for brain tumor patients: possibility strategy? / Programa educativo para fadiga em pacientes com tumor cerebral: possibilidade de estratégia?

ABSTRACT Objective To evaluate the effectiveness of an educational program on improvement of fatigue and quality of life of patients with high-grade glioma during radiotherapy and chemotherapy treatment. Method This is a longitudinal, experimental study. Twenty-three patients with high-grade glioma were randomly assigned to one of two groups. Both groups completed the Functional Assessment of Cancer Therapy: Fatigue questionnaire and the Beck Depression Inventory, and one of the groups received the educational intervention. The groups did not show any change in quality of life and fatigue in this study, for this reason, the educational program did not present any significant difference. However, there was a significant difference in depressive symptoms during the educational program showing positive evidence for its applicability.

RESUMO Objetivo Verificar a efetividade de um programa educativo na melhora da fadiga e dos sintomas depressivos em pacientes com glioma de alto grau durante o tratamento com radioterapia e quimioterapia. Método Trata-se de estudo longitudinal e experimental. Foram incluídos 23 pacientes com glioma de alto grau e divididos aleatoriamente em 2 grupos. Os dois grupos responderam os questionários Functional Assessment of Cancer Therapy: Fatigue e Inventário de Depressão de Beck, porém somente um foi inserido ao programa educativo. Resultados e Conclusões Os grupos não apresentaram alteração na fadiga ao longo desse estudo, assim o programa educativo não mostrou diferença significativa, porém nos sintomas depressivos, o programa educativo trouxe diferença quando estava sendo realizado mostrando evidências positivas para sua aplicabilidade.

Atypical and anaplastic meningiomas in a public hospital in São Paulo State, Brazil.

UNLABELLED: Atypical/anaplastic (World Health Organization (WHO) grades II and III) are less common and have poorer outcomes than benign meningiomas. This study aimed to analyze the outcome of patients with these tumors. METHOD: Overall/recurrence-free survivals (RFS) and the Karnofsky Performance Scale of 52 patients with grades II (42) and III (9) meningiomas surgically treated were analyzed (uni/multivariate analysis). RESULTS: Total/subtotal resections were 60.8%/35.3%. Patients <60 years-old and grade II tumors had longer survival. Grade II tumors, total resection and de novo meningioma had better RFS (univariate analysis). Patients >60 years-old, de novo meningioma and radiotherapy had longer survival and patients <60 years-old and with grade II tumors had longer RFS (multivariate analysis). Recurrence rate was 51% (39.2% Grade II and 66.7% Grade III). Operative mortality was 1.9%. CONCLUSION: Age <60 years-old, grade II tumors and de novo meningiomas were the main predictors for better prognosis among patients with grades II and III meningiomas.

Atypical and anaplastic meningiomas in a public hospital in São Paulo State, Brazil / Meningiomas atípicos e anaplásicos em um hospital público de São Paulo, Brasil

Atypical/anaplastic (World Health Organization (WHO) grades II and III) are less common and have poorer outcomes than benign meningiomas. This study aimed to analyze the outcome of patients with these tumors.Method Overall/recurrence-free survivals (RFS) and the Karnofsky Performance Scale of 52 patients with grades II (42) and III (9) meningiomas surgically treated were analyzed (uni/multivariate analysis).Results Total/subtotal resections were 60.8%/35.3%. Patients <60 years-old and grade II tumors had longer survival. Grade II tumors, total resection andde novo meningioma had better RFS (univariate analysis). Patients >60 years-old, de novo meningioma and radiotherapy had longer survival and patients <60 years-old and with grade II tumors had longer RFS (multivariate analysis). Recurrence rate was 51% (39.2% Grade II and 66.7% Grade III). Operative mortality was 1.9%.Conclusion Age <60 years-old, grade II tumors and de novomeningiomas were the main predictors for better prognosis among patients with grades II and III meningiomas.

Meningiomas atipicos/anaplásticos (graus II e III da World Health Organization (WHO)) são menos comuns e tem prognóstico pior que os benignos. Este estudo visa analisar o prognóstico de pacientes com estes tumores.Método Sobrevida/sobrevida livre de doença (SLD) e índice de Karnofsky de 52 pacientes com meningiomas graus II (42) e III (9) tratados cirurgicamente foram avaliados (análises uni/multivariada).Resultados Pacientes <60 anos e com tumores grau II tiveram sobrevida mais longa. Tumores grau II , ressecção total e meningioma de novotiveram melhor SLD (análise univariada). Pacientes >60 anos, meningiomade novo e radioterapia tiveram sobrevida mais longa e, pacientes <60 anos e com tumores grau II tiveram SLD mais longa (análise multivariada). Recidiva ocorreu em 51% (39.2% Graus II e 66,7% Graus III). A mortalidade operatória foi 1,9%.Conclusão Idade <60 anos, meningiomas grau II e de novo foram preditores de melhor prognóstico entre pacientes com meningiomas graus II/ III.

Beta-tubulin expression In the hippocampus Of patients with mesial temporal lobe epilepsy / Expressão de beta-tubulina no hipocampo de pacientes com epilepsia do lobo temporal mesial / Expresión de beta-tubulina en el hipocampo de los pacientes con epilepsia del lóbulo temporal mesial

Introduction: The neuronal loss and abnormal mossy fibers sprouting are frequently observed in patients with mesial temporal lobe epilepsy (MTLE). Beta-tubulin, a cytoskeleton protein, is critical for the maintenance of the neuritic structure. Objective: Considering the axonal reorganization in patients with MTLE, our objective was to analyze the beta-tubulin expression in the hippocampus of these patients. Methods: We evaluated the hippocampus of 38 MTLE patients and seven control cases. Histological sections were submitted to neo-Timm histochemistry to evaluate the sprouting of mossy fiber, and to immunohis- tochemistry for neuronal density evaluation (NeuN) and beta-tubulin expression. Results: The MTLE group showed lower neuronal density than the control group in the granular layer (GL), hilus, CA4, CA3, CA1, and presubiculum. The MTLE group showed higher gray value on the neo-Timm staining when compared to the control group in GL, IML, and outer mo- lecular layer (OML), and sprouting of thicker mossy fibers in the IML. When compared to the control group, group MTLE showed higher beta-tubulin expression in GL and lower expression in CA3 region. The aberrant sprouting of mossy fibers correlated inversely with the beta-tubulin expression in several subs of the hippocampal formation. Conclusions: The differential expression of beta-tubulin in the regions CA3 and GL of the MTLE group, as well as its correlation with neuronal loss and the mossy fiber sprouting, suggests a possible role of this protein in the neuropathological changes that occur in the hippocampus in chronic cases of MTLE.

Introdução: A perda neuronal e o brotamento anormal de fibras musgosas são observados com frequência em pacientes com epilepsia do lobo temporal mesial (ELTM). A beta-tubulina, uma proteína do citoesqueleto, é essencial para a manutenção da estrutura neurítica. Objetivo: Considerando a reorganização axonal nos pacientes com ELTM, nosso objetivo foi analisar a expressão de beta-tubulina no hipo- campo desses pacientes. Métodos: Foram avaliados 38 hipocampos de pacientes com ELTM e sete casos controle. Cortes histológicos foram submetidos à histoquímica de neo-Timm para avaliação do neobrotamento de fibras musgosas e à imuno-histoquímica para avaliações da densidade neuronal (NeuN) e da expressão de beta-tubulina. Resultados: O grupo ELTM apresentou menor densidade neuronal do que o grupo controle na camada granular (CG), hilo, CA4, CA3, CA1 e no pró-subículo. O grupo ELTM apresentou maior valor de cinza na coloração neo-Timm com relação ao grupo controle na CG, CMI e camada molecular externa (CME) e neobrotamento mais espesso de fibras musgosas na CMI. O grupo ELTM apresentou maior expressão de beta-tubulina na CG e menor expressão na região de CA3, quando comparado ao grupo controle. O neobrotamento aberrante de fibras musgosas correlacionou-se inversamente com a expressão de beta-tubulina em diversos subcampos da formação hipocampal. Conclusões: A expressão diferencial da beta-tubulina nas regiões da CA3 e CG do grupo ELTM, assim como suas correlações com a perda neuronal e o neobrotamento de fibras musgosas sugerem uma possível participação dessa proteína nas alterações neuropatológicas que ocorrem no hipocampo nos casos crônicos de ELTM.

Introducción: La pérdida neuronal y la brotación anormal de fibras musgosas se observan con frecuencia en los pacientes con epilepsia del lóbulo temporal mesial (ELTM). La beta-tubulina, una proteína del citoesqueleto, es crítica para el mantenimiento de la estructura neurítica. Objetivo: Teniendo en cuenta la reorganización axonal en pacientes con ELTM, nuestro objetivo fue analizar la expresión de beta-tubulina en el hipocampo de estos pacientes. Métodos: Se evaluó el hipocampo de 38 pacientes con ELTM y siete casos de control. Cortes histológicos fueron sometidos a la histoquímica neo-Timm para evaluar la brotación de fibras musgosas, y a inmunohistoquímica para la evaluación de la densidad neuronal (NeuN) y la expresión de beta-tubulina. Resultados: El grupo ELTM mostró una menor densidad neuronal que el grupo control en la capa granular (CG), hilo, CA4, CA3, CA1 y pró-subículo. El grupo ELTM mostró mayor valor de gris en la tinción neo-Timm en comparación con el grupo control en CG, CMI y en la capa externa molecular (CME), y la brotación de fibras musgosas más gruesas en la CMI. El grupo ELTM mostró una mayor expresión de beta- tubulina en CG y expresión más baja en la región CA3, cuando se compara con el grupo control. La brotación aberrante de fibras musgosa está inversamente correlacionada con la expresión de beta-tubulina en varios subcampos de la formación del hipocampo. Conclusiones: La expresión diferencial de beta-tubulina en las regiones CA3 y CG del grupo ELTM, así como su correlación con la pérdida neuronal y el surgimiento de fibras musgosas, sugiere un posible papel de esta proteína en los cambios neuropatológicos que se producen en el hipocampo en los casos crónicos de ELTM.

Foramen magnum meningiomas: surgical treatment in a single public institution in a developing country.

OBJECTIVE: To analyze the clinical outcome of patients with foramen magnum (FM) meningiomas. METHOD: Thirteen patients (11 Feminine / 2 Masculine with FM meningiomas operated on through lateral suboccipital approach were studied. Clinical outcome were analyzed using survival (SC) and recurrence-free survival curves (RFSC). RESULTS: All tumors were World Health Organization grade I. Total, subtotal and partial resections were acchieved in 69.2%, 23.1% and 7.7%, respectively, and SC was better for males and RFSC for females. Tumor location, extent of resection and involvement of vertebral artery/lower cranial nerves did not influence SC and RFSC. Recurrence rate was 7.7%. Operative mortality was 0. Main complications were transient (38.5%) and permanent (7.7%) lower cranial nerve deficits, cerebrospinal fluid fistula (30.8%), and transient and permanent respiratory difficulties in 7.7% each. CONCLUSIONS: FM meningiomas can be adequately treated in public hospitals in developing countries if a multidisciplinary team is available for managing postoperative lower cranial nerve deficits.

Foramen magnum meningiomas: surgical treatment in a single public institution in a developing country / Meningiomas do forame magno: tratamento cirúrgico em uma instituição pública em um país em desenvolvimento

Objective: To analyze the clinical outcome of patients with foramen magnum (FM) meningiomas. Method: Thirteen patients (11 Feminine / 2 Masculine with FM meningiomas operated on through lateral suboccipital approach were studied. Clinical outcome were analyzed using survival (SC) and recurrence-free survival curves (RFSC). Results: All tumors were World Health Organization grade I. Total, subtotal and partial resections were acchieved in 69.2%, 23.1% and 7.7%, respectively, and SC was better for males and RFSC for females. Tumor location, extent of resection and involvement of vertebral artery/lower cranial nerves did not influence SC and RFSC. Recurrence rate was 7.7%. Operative mortality was 0. Main complications were transient (38.5%) and permanent (7.7%) lower cranial nerve deficits, cerebrospinal fluid fistula (30.8%), and transient and permanent respiratory difficulties in 7.7% each. Conclusions: FM meningiomas can be adequately treated in public hospitals in developing countries if a multidisciplinary team is available for managing postoperative lower cranial nerve deficits. .

Objetivo: Analisar as evoluções clínicas de 13 pacientes com meningiomas do forame magno (FM). Método: Foram estudados 13 pacientes com meningiomas do FM (11 Feminino / 2 Masculino) operados por abordagem suboccipital lateral. As evoluções clínicas foram analisadas usando curvas de sobrevida (SC) e de sobrevida livre de doença (RFSC). Resultados: Os 13 tumores eram Grau I da Organização Mundial de Saúde. Ressecções total, subtotal and parcial foram obtidas em 69,2%, 23,1 e 7,7%, respectivamente. A SC foi melhor para homens e a RFSC foi melhor para mulheres. Localização/ extensão da ressecção/envolvimento da artéria vertebral/nervos cranianos baixos não influenciaram a SC/RFSC. A taxa de recorrência foi 7,7%. A mortalidade operatória foi zero. As principais complicações foram déficits de nervos cranianos baixos transitórios (38,5%) e permanentes (7,7%); fístula de líquido cefalorraquidiano (30,8%) e dificuldades respiratórias transitórias e permanentes em 7,7% cada. Conclusões: Meningiomas do FM podem ser adequadamente tratados em hospitais públicos em países em desenvolvimento se houver uma equipe multidisciplinar para cuidar de déficits de nervos cranianos baixos pós-operatórios. .

Extra and intradural spinal Hemangioblastoma / Hemangioblastoma espinhal extra e intradural / Hemangioblastoma espinal extra e intradural

Hemangioblastomas of the central nervous system (CNS) are low-grade highly vascularized tumors that may be sporadic or associated with Von Hippel-Lindau disease. Extradural hemangioblastomas are uncommon and those located extra and intradurally are even rarer. This study uses an illustrative case and literature review to discuss the difficulties to consider the correct diagnosis and to select the best surgical approach. A 57 years-old white male patient presented with myelopathy and right C5 radiculopathy. The images showed a lobulated, hourglass shaped, highly enhanced extra/intradural lesion that occupied the spinal canal and widened the C4-C5 right intervertebral foramen. Total resection of the intradural lesion was achieved through a posterior approach, but the extradural part could only be partially removed. Complete improvement was observed after four months of follow-up and the residual tumor has been followed up clinically and radiologically. Even though the preoperative impression was of a spinal schwannoma, the histopathological examination revealed grade I hemangioblastoma as per WHO. Despite their rarity, current complementary exams allow considering the diagnosis of hemangioblastoma preoperatively. That is essential to a better surgical planning in view of the particular surgical features of this lesion.

Hemangioblastomas do sistema nervoso central são lesões de baixo grau de malignidade, altamente vascularizadas, que podem se apresentar esporadicamente ou associadas com a doença de Von Hippel-Lindau. Hemangioblastomas extradurais são incomuns e os extra e intradurais são ainda mais raros. Este estudo usa um caso ilustrativo e revisão da literatura para discutir as dificuldades de considerar o diagnóstico correto e selecionar a melhor abordagem cirúrgica. Um paciente do sexo masculino, branco, com 57 anos de idade apresentou-se com mielopatia e radiculopatia de C5 à direita. As imagens mostraram lesão extra-intradural lobulada, em forma de ampulheta, com alta impregnação após contraste, que ocupava o canal vertebral e estreitava o forame intervertebral de C4-C5 à direita. A ressecção total da lesão intradural foi alcançada através de abordagem posterior, mas a porção extradural só pôde ser parcialmente removida. Melhora total dos sintomas foi observada após quatro meses e o tumor residual tem sido seguido clínica e radiologicamente. Embora a impressão pré-operatória tenha sido de um schwannoma espinal, o exame histopatológico revelou hemangioblastoma grau I, segundo a OMS. Apesar de sua raridade, exames complementares atuais permitem o correto diagnóstico pré-operatório. Isto é essencial para melhor programação cirúrgica, tendo em vista as características particulares desta lesão.

Hemangioblastomas del sistema nervioso central (SNC) son tumores altamente vascularizados, de grado bajo, que pueden ser esporádicos o vinculados a la enfermedad de Von Hippel-Lindau. Hemangioblastomas extradurales no son comunes, y aquellos localizados extra e intraduralmente son aún más raros. Este estudio usa un caso ilustrativo y la revisión de la literatura para analizar las dificultades cuanto a considerar el diagnóstico correcto y para seleccionar el mejor abordaje quirúrgico. Un paciente, hombre blanco de 57 años de edad, presentaba mielopatía con radiculopatía C5 derecha. Las imágenes mostraban lesión extra/intradural, muy acrecentada, con forma de ampolla y lobulada, la cual ocupaba el conducto espinal y ensanchaba el agujero intervertebral derecho C4-C5. La resección de la lesión intradural fue conseguida mediante un abordaje posterior, pero la parte extradural solamente pudo ser removida parcialmente. La mejoría completa fue observada después de cuatro meses de seguimiento y el tumor residual ha sido acompañado clínica y radiológicamente. Aunque la impresión preoperatoria era de schwannoma espinal, el examen histopatológico reveló hemangioblastoma grado I según la Organización Mundial de la Salud. A pesar de su rareza, los actuales exámenes complementarios permiten considerar, preoperativamente, el diagnóstico de hemangioblastoma. Esto es esencial para hacer un mejor planeamiento quirúrgico, teniendo en cuenta los aspectos quirúrgicos peculiares de esta lesión.

Pre, intra and post-ischemic hypothermic neuroprotection in temporary focal cerebral ischemia in rats: morphometric analysis.

OBJECTIVE: To evaluate the neuroprotection of mild hypothermia, applied in different moments, in temporary focal cerebral ischemia in rats. METHODS: Rats was divided into Control (C), Sham (S), Ischemic-control(IC), Pre-ischemic Hypothermia (IH1), Intra-ischemic Hypothermia (IH2), and Post-ischemic Hypothermia (IH3) groups. Morphometry was performed using the KS400 software (Carl Zeiss®) in coronal sections stained by Luxol Fast Blue. Ischemic areas and volumes were obtained. RESULTS: Statistically, blue areas showed difference for C vs. IC, IC vs. IH1 and IC vs. IH2 (p=0.0001; p=0.01; p=0.03), and no difference between C vs. S, IC vs. IH3 and IH vs. IH2 (p=0.39; p=0.85; p=0.63). Red areas showed difference between C vs. IC, IC vs. IH1 and IC vs. IH2 (p=0.0001; p=0.009; p=0.03), and no difference between C vs. S, IC vs. IH3 and IH1 vs. IH2 (p=0.48; p=0.27; p=0.68). Average ischemic areas and ischemic volumes showed difference between IC vs. IH1 and IC vs. IH2 (p=0.0001 and p=0.0011), and no difference between IC vs. IH3 and IH1 vs. IH2 (p=0.57; p=0.79). CONCLUSION: Pre-ischemic and intra-ischemic hypothermia were shown to be similarly neuroprotective, but this was not true for post-ischemic hypothermia.

Pre, intra and post-ischemic hypothermic neuroprotection in temporary focal cerebral ischemia in rats: morphometric analysis / Neuroproteção hipotérmica pré, intra e pós-isquêmica na isquemia cerebral focal temporária em ratos: análise morfométrica

OBJECTIVE: To evaluate the neuroprotection of mild hypothermia, applied in different moments, in temporary focal cerebral ischemia in rats. METHODS: Rats was divided into Control (C), Sham (S), Ischemic-control(IC), Pre-ischemic Hypothermia (IH1), Intra-ischemic Hypothermia (IH2), and Post-ischemic Hypothermia (IH3) groups. Morphometry was performed using the KS400 software (Carl Zeiss®) in coronal sections stained by Luxol Fast Blue. Ischemic areas and volumes were obtained. RESULTS: Statistically, blue areas showed difference for C vs. IC, IC vs. IH1 and IC vs. IH2 (p=0.0001; p=0.01; p=0.03), and no difference between C vs. S, IC vs. IH3 and IH vs. IH2 (p=0.39; p=0.85; p=0.63). Red areas showed difference between C vs. IC, IC vs. IH1 and IC vs. IH2 (p=0.0001; p=0.009; p=0.03), and no difference between C vs. S, IC vs. IH3 and IH1 vs. IH2 (p=0.48; p=0.27; p=0.68). Average ischemic areas and ischemic volumes showed difference between IC vs. IH1 and IC vs. IH2 (p=0.0001 and p=0.0011), and no difference between IC vs. IH3 and IH1 vs. IH2 (p=0.57; p=0.79). CONCLUSION: Pre-ischemic and intra-ischemic hypothermia were shown to be similarly neuroprotective, but this was not true for post-ischemic hypothermia.

OBJETIVO: Avaliar a neuroproteção da hipotermia leve, aplicada em diferentes momentos, durante isquemia cerebral focal temporária em ratos. MÉTODOS: Ratos foram divididos em grupos: Controle (C), Sham (S), Controle-isquêmico (IC), Hipotermia Pré-isquêmica (IH1), Hipotermia Intra-isquêmica (IH2) e Hipotermia Pós-isquêmica (IH3). A morfometria foi realizada em secções coronais coradas por Luxol Fast Blue através do programa KS400 (Carl Zeiss®). Foram calculados áreas e volumes isquêmicos. RESULTADOS: Estatisticamente, áreas azuis demonstraram diferença entre os grupos C vs. IC, IC vs. IH1 e IC vs. IH2 (p=0,0001; p=0,01; p=0,03), e nenhuma diferença entre C vs. S, IC vs. IH3 e IH vs. IH2 (p=0,39; p=0,85; p=0,63). Áreas vermelhas demonstraram diferença entre C vs. IC, IC vs. IH1 e IC vs. IH2 (p=0,0001; p=0,009; p=0,03), e nenhuma diferença entre C vs. S, IC vs. IH3 e IH1 vs. IH2 (p=0,48; p=0,27; p=0,68). Áreas isquêmicas médias e volumes isquêmicos demonstraram diferença entre os grupos IC vs. IH1 e IC vs. IH2 (p=0,0001 and p=0,0011), e nenhuma diferença entre IC vs. IH3 and IH1 vs. IH2 (p=0,57; p=0,79). CONCLUSÃO: Hipotermias pré-isquêmica e intra-isquêmica demonstraram neuroproteção em grau semelhante, o que não ocorreu com hipotermia pós-isquêmica.

Amygdala gene expression of NMDA and GABA(A) receptors in patients with mesial temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common form of partial epilepsy and affects 40% of the patients. Seizures arising from the mesial temporal lobe structures (i.e., amygdala and hippocampus) are common, whereas neocortical seizures are rare. In recent years, many studies aimed to identify the pattern of gene expression of neurotransmitters involved in molecular mechanisms of epilepsy. We used real-time PCR to quantify the expression of GABA(A) (subunits α1, ß1, ß2) and NMDA (subunits NR1, NR2A, and NR2B) receptor genes in amygdalae of 27 patients with TLE and 14 amygdalae from autopsy controls. The NR1 subunit was increased in patients with epilepsy when compared with controls. No differences were found in expression of NMDA subunits NR2A and NR2B or in α1, ß1, and ß2 subunits of GABA(A) receptors. Our results suggest that the NR1 subunit of NMDA receptors is involved in the amygdala hyperexcitability in some of the patients with TLE.

Neuroproteção hipotérmica e isquemia cerebral: aspectos experimentais e aplicalçao neurocirúrgica: [revisão] / Hypothermia, neuroprotection and cerebral ischemia: experimental aspects and neurosurgical aplications: [review]

A hipotermia é uma estratégia de neuroproteção promissora. Seus efeitos benéficos são extremamente evidentes em estudos de isquemia cerebral experimental. Por outro lado, sua aplicação no cenário neurocirúrgico, principalmente em procedimentos neurovasculares, é controversa. Este artigo é uma revisão de aspectos experimentais e possíveis aplicações neurocirúrgicas da hipotermia na isquemia cerebral.

Expression of HSP70 in cerebral ischemia and neuroprotetive action of hypothermia and ketoprofen / Expressão de HSP70 na isquemia cerebral e a ação neuroprotetora da hipotermia e do cetoprofeno

Heat shock proteins (HSPs) are molecular chaperones that bind to other proteins to shepherd them across membranes and direct them to specific locations within a cell. Several injurious stimuli can induce Hsp70 expression, including ischemia. This study aimed to investigate the pattern of expression of protein (immunohistochemistry) and gene (real-time PCR) Hsp70 in experimental focal cerebral ischemia in rats by occlusion of the middle cerebral artery for 1 hour and the role of neuroprotection with hypothermia (H) and ketoprofen (K). The infarct volume was measured using morphometric analysis defined by triphenyl tetrazolium chloride. It was observed increases in the protein (p=0.0001) and gene (p=0.0001) Hsp70 receptor in the ischemic areas that were reduced by H (protein and gene: p<0.05), K (protein: p<0.001), and H+K (protein: p<0.01 and gene: p<0.05). The Hsp70 increases in the ischemic area suggests that the Hsp70-mediated neuroexcitotoxicity plays an important role in cell death and that the neuroprotective effect of both, H and K are directly involved with the Hsp70.

Proteínas de choque térmico (HSPs) são chaperones moleculares que se ligam a outras proteínas para atravessar as membranas e encaminhá-las para locais específicos dentro de uma célula. Vários estímulos nocivos podem induzir a expressão de Hsp70, incluindo isquemia. Este estudo teve como objetivo investigar o padrão de expressão protéica (imunohistoquímica) e gênica (PCR em tempo real) de Hsp70 na isquemia cerebral focal experimental em ratos pela oclusão da artéria cerebral média durante 1 hora e o papel da neuroproteção com hipotermia (H) e cetoprofeno (C). O volume de infarto foi calculado através da análise morfométrica definido por cloreto de trifenil tetrazólio. Foi observado aumento na expressão proteína (p=0,0001) e gênica (p=0,0001) de Hsp70 nas áreas isquêmicas que foram reduzidas pela H (proteína e gene: p<0,05), C (proteína: p<0,001) e H+K (proteína: p<0,01 e gene: p<0,05). O aumento de Hsp70 na área isquêmica sugere que a neuroexcitotoxicidade mediada pela Hsp70 desempenha um papel importante na morte celular e que o efeito neuroprotetor tanto da H quanto do C está diretamente envolvido com a Hsp70.

Caspase-3 and Bcl-2 expression in glioblastoma: an immunohistochemical study / Expressão de caspase-3 e Bcl-2 em glioblastomas: um estudo imunohistoquímico

The unfavorable prognosis of malignant gliomas can also be explained by the incomplete knowledge of their molecular pathways. Studies regarding the regulatory process of apoptosis in glioblastoma (GBM), the most common malignant glioma, are few, and better knowledge of the expression of pro and anti-apoptotic proteins could collaborate with the development of new treatments founded on molecular basis. The objective of this study was to evaluate by immunohistochemistry the expression of caspase-3 and Bcl-2 in 30 samples of GBMs. The expression of caspase-3 (mean 17.67 percent) was lower than Bcl-2 (mean 30.92 percent), a statistically significant result (p<0.0001), suggesting low apoptotic activity in these tumors. Other studies of proteins related to the intrinsic and extrinsic pathway of apoptosis are required to provide additional information of this mechanism in GBMs.

O prognóstico desfavorável dos gliomas malignos também pode ser explicado pelo pouco conhecimento dos seus mecanismos moleculares. Estudos relacionados à regulação do processo de apoptose em glioblastoma (GBM), o glioma maligno mais comum, são poucos, e o melhor conhecimento da expressão de proteínas pró e anti-apoptóticas poderia colaborar com o desenvolvimento de novos tratamentos fundamentados sobre a base molecular. O objetivo deste estudo foi avaliar por imunohistoquímica, a expressão de caspase-3 e Bcl-2 em 30 amostras de GBM. A expressão de caspase-3 (média de 17,67 por cento) foi menor que a de Bcl-2 (média de 30,92 por cento), com resultado estatisticamente significante (p<0.0001), sugerindo menor atividade apoptótica nestes tumores. Outros estudos envolvendo proteínas relacionadas à via extrínseca e intrínseca da apoptose são necessários para fornecer informações complementares deste mecanismo em GBMs.

ICAM-1 (Lys469Glu) and PECAM-1 (Leu125Val) polymorphisms in diffuse astrocytomas.

Cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1) play an important role in glioma invasion and angiogenesis. The aim of this study was to investigate whether specific genetic polymorphisms of ICAM-1 and PECAM-1 could be associated with glioma development and progression. Single-nucleotide polymorphism in codon 469 of ICAM-1 and codon 125 of PECAM-1 were examined in 158 patients with astrocytomas and 162 controls using polymerase chain reaction and restriction enzyme analysis. The distribution of PECAM-1 polymorphic genotypes in astrocytomas did not show any significant difference. However, a specific ICAM-1 genotype (G/G, corresponding to Lys469Glu) exhibited higher frequency in grade II astrocytomas compared to controls, grade III, and grade IV astrocytomas; suggesting that this polymorphism could be involved in the development of grade II astrocytomas.

Impact of a program for the prevention of traffic accidents in a Southern Brazilian city: a model for implementation in a developing country.

BACKGROUND: Traffic accidents constitute the main cause of death in the first decades of life. Traumatic brain injury is the event most responsible for the severity of these accidents. The SBN started an educational program for the prevention of traffic accidents, adapted from the American model "Think First" to the Brazilian environment, since 1995, with special effort devoted to the prevention of TBI by using seat belts and motorcycle helmets. The objective of the present study was to set up a traffic accident prevention program based on the adapted Think First and to evaluate its impact by comparing epidemiological variables before and after the beginning of the program. METHODS: The program was executed in Maringá city, from September 2004 to August 2005, with educational actions targeting the entire population, especially teenagers and young adults. The program was implemented by building a network of information facilitators and multipliers inside the organized civil society, with widespread population dissemination. To measure the impact of the program, a specific software was developed for the storage and processing of the epidemiological variables. RESULTS: The results showed a reduction of trauma severity due to traffic accidents after the execution of the program, mainly TBI. CONCLUSIONS: The adapted Think First was systematically implemented and its impact measured for the first time in Brazil, revealing the usefulness of the program for reducing trauma and TBI severity in traffic accidents through public education and representing a standardized model of implementation in a developing country.