OBJECTIVES: High-throughput sequencing of genomes, exomes, and disease-focused gene panels is becoming increasingly common for molecular diagnostics. However, identifying a single clinically relevant pathogenic variant among thousands of genetic polymorphisms is a challenging task. Publicly available genomic databases are useful resources to filter out common genetic variants present in the population and enable the identification of each disease-causing variant. Based on our experience applying these technologies at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, Brazil, we recognized that the Brazilian population is not adequately represented in widely available genomic databases. METHODS: Here, we took advantage of our 5-year experience as a high-throughput sequencing core facility focused on individuals with putative genetic disorders to build a genomic database that may serve as a more accurate reference for our patient population: SELAdb. RESULTS/CONCLUSIONS: Currently, our database comprises a final cohort of 523 unrelated individuals, including patients or family members managed by different clinics of HCFMUSP. We compared SELAdb with other publicly available genomic databases and demonstrated that this population is very heterogeneous, largely resembling Latin American individuals of mixed origin, rather than individuals of pure European ancestry. Interestingly, exclusively through SELAdb, we identified a spectrum of known and potentially novel pathogenic variants in genes associated with highly penetrant Mendelian disorders, illustrating that pathogenic variants circulating in the Brazilian population that is treated in our clinics are underrepresented in other population databases. SELAdb is freely available for public consultation at: http://intranet.fm.usp.br/sela

Abstract Background: Different inflammatory cells (i.e., CD4, CD8, CD20 and CD68) are involved in pathogenesis of DM muscle. In this context, the aim of this study was to assess and compare these inflammatory cell phenotyping in muscle samples of treatment naive juvenile and adult patients with dermatomyositis. Methods: This is a cross-sectional study, in which 28 untreated juvenile and 28 adult untreated dermatomyositis patients were included. Immunohistochemical analysis was performed on serial frozen muscle sections. Inflammatory cell phenotyping was analyzed quantitatively in endomysium, perimysium, and perivascular (endomysium and perimysium) area. Results: Mean age at disease onset was 7.3 and 42.0 years in juvenile and adult dermatomyositis, respectively. Both groups had comparable time duration from symptom's onset to biopsy performance. CD4 and CD8 positive cells distributions were similar in both groups in all analyzed area, except for more predominance of CD4 in perimysium at juvenile muscle biopsies. The CD20 and CD68 positive cells were predominantly observed in adult muscle biopsy sections, when compared to juvenile samples, except for similar distribution of CD20 in perivascular endomysium, and CD68 in perimysium. Conclusions: These data show that the differences between juvenile and adult dermatomyositis may be restricted not only to patients' age, but also to different inflammatory cell distribution, particularly, in new-onset disease. Further studies are necessary to confirm the present study data and to analyze meaning of the different inflammatory cell phenotyping distribution finding in these both diseases.

OBJETIVO: Analisar as expressões associadas de STMN1, MELK e FOXM1 na procura de alvos alternativos de tratamento em glioblastoma (GBM) e revisar os papeis funcionais relevantes de STMN1 na biologia do câncer. MÉTODO: As expressões de STMN1, MELK e FOXM1 foram estudadas por PCR quantitativo e suas coexpressões foram analisadas em dois coortes independentes de GBM. A revisão dos artigos publicados em revistas indexadas na procura dos aspectos funcionais múltiplos de STMN1 foi conduzida focando-se nos estudos mais recentes discutindo o seu papel em câncer, quimiorresistência e vias de sinalização envolvendo MELK e FOXM1. RESULTADOS: Observou-se expressões associadas significantes de MELK e FOXM1 com STMN1. Adicionalmente, a revisão da literatura salientou a relevância do STMN1 na progressão do câncer. CONCLUSÃO: STMN1 é muito importante nos eventos relacionados ao desenvolvimento e progressão do câncer, como proliferação celular, migração e resistência ao tratamento. Desta forma, STMN1 pode ser um forte alvo terapêutico em um grande número de cânceres humanos. Em GBM, o tumor cerebral mais agressivo, MELK/FOXM1/STMN1 apresentaram significativa associação em suas expressões gênicas, indicando, portanto, MELK e FOXM1 como alvos alternativos para terapia em substituição ao STMN1, que apresenta alta expressão no tecido cerebral normal. Perseverar nos estudos funcionais para o entendimento da via de sinalização do STMN1 é relevante para melhorar os esquemas terapêuticos para câncer.

OBJECTIVE: To analyze the associated expression of STMN1, MELK and FOXM1 in search of alternative drugable target in glioblastoma (GBM) and to review relevant functional roles of STMN1 in cancer biology. METHOD: STMN1, MELK and FOXM1 expressions were studied by quantitative PCR and their coexpressions were analyzed in two independent glioblastoma cohorts. A review of articles in indexed journals that addressed the multiple functional aspects of STMN1 was conducted, focusing on the most recent reports discussing its role in cancer, in chemoresistance and in upstream pathways involving MELK and FOXM1. RESULTS: Significant associated expressions of MELK and FOXM1 were observed with STMN1 in GBM. Additionally, the literature review highlighted the relevance of STMN1 in cancer progression. CONCLUSION: STMN1 is very important to induce events in cancer development and progression, as cellular proliferation, migration, and drug resistance. Therefore, STMN1 can be an important therapeutic target for a large number of human cancers. In glioblastoma, the most aggressive brain tumor, the MELK/FOXM1/STMN1 presented significant associated expressions, thus pointing MELK and FOXM1 as alternative targets for therapy instead of STMN1, which is highly expressed in normal brain tissue. Continuous functional research to understand the STMN1 signaling pathway is worthwhile to improve the therapeutic approaches in cancer.

OBJETIVOS: ANKRD1 codifica "ankyrin repeat domain containing protein 1" e tem um papel importante na miogênese e possivelmente também na angiogênese. Microvasculopatia é considerada como um ponto central e uma alteração patológica precoce na dermatomiosite (DM), levando à hipóxia e à atrofia perifascicular muscular. Estas alterações poderiam estimular genes envolvidos na miogênese e angiogênese como ANKRD1. Portanto, analisamos a expressão de ANKRD1 em biópsias musculares de DM e correlacionamos com outros parâmetros de hipóxia e alterações histológicas. MÉTODOS: O RNA total foi extraído de biópsias de músculos congelados de 29 pacientes com DM. Como grupo controle, foram usadas 20 biópsias de músculo de pacientes adultos com miopatia não-inflamatória. O gene que codifica a subunidade alfa do fator 1 induzido por hipóxia (HIF1A) foi analisado para estimar o grau de hipóxia. Os níveis de expressão dos transcritos ANKRD1 e HIF1A foram determinados por PCR quantitativa em tempo real. RESULTADOS: Níveis aumentados de expressões de ANKRD1 e HIF1A foram observados em DM quando comparados ao grupo controle (P<0,001, ambos os genes). Além disso, ANKRD1 e HIF1A apresentaram coexpressão (r=0,703, P=0,001) e seus níveis de expressão correlacionaram-se também positivamente com atrofia perifascicular (r=0,420, P=0,023 e r=0,404, P=0,030, respectivamente). CONCLUSÕES: Nossos resultados demonstraram aumento de expressão de ANKRD1 na DM, que correlacionou com a expressão de HIF1A e atrofia perifascicular. Investigações adicionais do envolvimento de ANKRD1 no mecanismo de miogênese e angiogênese devem ser realizadas.

OBJECTIVES. The ANKRD1 gene codes for the ankyrin repeat domain containing protein 1 and has an important role in myogenesis and possibly also in angiogenesis. Microvasculopathy is a cornerstone and an early pathological marker of change in dermatomyositis, leading to hypoxia and muscle perifascicular atrophy. These alterations could upregulate genes involved in myogenesis and angiogenesis such as ANKRD1. Therefore, we analyzed ANKRD1 expression in muscle biopsies of dermatomyositis and correlated with other hypoxia parameters and with histological changes. METHODS. Total RNA was extracted from frozen muscle biopsies samples of 29 dermatomyositis patients. A control group consisted of 20 muscle biopsies from adult patients with non-inflammatory myopathy diseases. The gene coding for hypoxia-inducible factor 1, alpha subunit (HIF1A), was analyzed to estimate the degree of hypoxia. ANKRD1 and HIF1A transcript expression levels were determined by quantitative real time PCR. RESULTS. Significantly higher ANKRD1 and HIF1A expression levels were observed in dermatomyositis relative to the control group (P<0.001, both genes). In addition, ANKRD1 and HIF1A were coexpressed (r=0.703, P=0.001) and their expression levels correlated positively to perifascicular atrophy (r=0.420, P=0.023 and r=0.404, P=0.030, respectively). CONCLUSIONS. Our results demonstrate ANKRD1 overexpression in dermatomyositis correlated to HIF1A expression and perifascicular atrophy. ANKRD1 involvement in myogenesis and angiogenesis mechanisms indicates that further investigation is worthwhile.

OBJETIVO: ASCT2 e LAT1 são transportadores de aminoácidos envolvidos no transporte de glutamina e desempenham um papel no crescimento tumoral. Estudos prévios mostraram uma associação de ASCT2 com proliferação celular através da maquinaria de tradução do mTOR; tem sido mostrado que o LAT1 é um marcador prognóstico devido à sua relação com invasão tumoral, invasão vascular microscópica e metástase. Este estudo analisou a expressão gênica de ASCT2 e LAT1 em astrocitomas de diferentes graus e sua correlação com desfecho clínico em pacientes com glioblastoma. METODO: Este é um estudo observacional com análise de expressão de RNAm de ASCT2 e LAT1 em 153 amostras de astrocitomas humanos, distribuídas em diferentes graus de malignidade segundo a OMS (23 astrocitomas de grau I ou astrocitoma pilocítico, 26 de astrocitoma de grau II ou astrocitoma de baixo grau, 18 de astrocitoma de grau III ou astrocitoma anaplásico, 86 de astrocitoma de grau IV ou glioblastoma (AGIV ou GBM); estes foram comparados com 22 amostras cerebrais não neoplásicas. RESULTADOS: Foi observada uma hiperexpressão de ambos os genes, particularmente nos astrocitomas malignos (GIII & GBM). Além disso, a hiperexpressão LAT1 impactou negativamente na sobrevida global em um grupo de pacientes com GBM. CONCLUSÃO: LAT1 é mais expresso em astrocitomas de grau maior. Isso leva a um pior prognóstico entre os pacientes com GBM e pode ser um potencial alvo terapêutico.

OBJECTIVE: ASCT2 and LAT1 are aminoacid transporters involved in glutamine transport and play a role in tumor growth. Previous studies have shown an association of ASCT2 to cell proliferation through the mechanistic Target of Rapamycin (mTOR) translational machinery; LAT1 has been shown as a prognostic marker due to its relation to tumor invasion, microscopic vascular invasion and metastasis. This study analyzed the gene expression of ASCT2 and LAT1 in astrocytomas of different grades and how this correlates to clinical outcome in glioblastoma patients. METHOD: This is an observational study with ASCT2 and LAT1 mRNA expression analysis in 153 samples of human astrocytomas, distributed in different World Health Organization (WHO) grades of malignancy (23 at grade I or pilocytic astrocytoma, 26 at grade II or low-grade astrocytoma, 18 at grade III or anaplastic astrocytoma, 86 at grade IV astrocytoma or glioblastoma (AGIV or GBM)); these were compared to 22 non-neoplastic brain samples. RESULTS: Significant hyperexpression of both genes was observed particularly in malignant astrocytomas (GIII & GBM). Moreover, LAT1 hyperexpression impacted negatively in the overall survival in a subset of GBM patients. CONCLUSION: LAT1 is more expressed in higher grade astrocytomas. It leads to a poorer prognosis among GBM patients and may be a potential therapeutical target.

INTRODUÇÃO Astrocitomas são os tumores cerebrais mais frequentes. Nestes tumores foi observada maior expressão do receptor de Interleucina-13 α2 (IL13RA2). A cascata de sinalização da Interleucina-13 pode estar associada com a migração celular, após sua ligação com o receptor de Interleucina-13 α1 (IL13Rα1). OBJETIVO: Investigar os níveis de expressão dos receptores de Interleucina-13 (IL13RA1 e IL13RA2) em astrocitomas difusamente infiltrativos e avaliar o envolvimento da Interleucina-13 na migração celular de duas linhagens de glioblastoma. MÉTODOS: A expressão dos receptores IL13RA foi analisada por PCR em tempo real, em 128 amostras de astrocitomas e 18 amostras de tecido cerebral não neoplásico, provenientes de cirurgia de epilepsia do lobo temporal. E o impacto da quantidade de IL-13 (10ng/ml e 20ng/ml) em ensaio de migração celular. RESULTADOS: As amostras de Glioblastoma apresentaram maior expressão de IL13RA1 and IL13RA2 comparados com astrocitomas de baixo grau e os casos não-neoplásicos. Nas células U87MG e A172 foi observado maior nível de expressão de IL-13RA1 do que IL-13RA2. Uma diferença significativa na taxa de migração foi obtida em células A172 tratadas com 10 ng/mL comparadas com o controle: as células tratadas apresentaram menor migração que as células não tratadas. As células U87MG tratadas com 20ng/mL de IL-13 apresentaram menor migração celular que as células não tratadas. A diferença na migração celular indica que o caminho de sinalização de IL13Rα1 não foi ativado e foi inibido pelo IL-13Rα2, diminuindo a migração celular. Esse impacto ocorreu com uma concentração menor de IL-13 nas células A172 ao contrário da U87MG, porque as células A172 possuem uma razão IL-13RA2/A1 maior. CONCLUSÃO: os resultados sugerem que os receptores de IL-13 podem ser utilizados como possíveis alvos para a diminuição da migração celular tumoral.

INTRODUCTION: Astrocytomas are common brain tumors. Increased expression levels of Interleukin-13 Receptor α2 (IL-13RA2) have been reported in astrocytomas. The Interleukin-13 signaling pathway may be associated with cell migration when binding to Interleukin-13 Receptor α1. OBJECTIVE: To investigate Interleukin-13 Receptor α1 (IL-13RA1) and IL13RA2 expression levels in human diffusely infiltrative astrocytomas and test the involvement of Interleukin-13 levels in cell migration in two glioblastoma cell lines. METHODS: IL13RA expression levels were accessed by quantitative real time PCR in 128 samples of astrocytomas and 18 samples of non-neoplastic brain tissues from temporal lobe epilepsy surgery. The impact of IL-13 levels (10 and 20 ng/mL) on cell migration was analyzed by the wound assay in U87MG and A172 cells. RESULTS: Glioblastoma presented higher IL13RA1 and IL13RA2 expression levels compared to lower grades astrocytomas and to non-neoplastic cases. U87MG and A172 cells presented higher expression levels of IL-13RA1 vs. IL-13RA2. A significant difference in migration rate was observed in A172 cells treated with 10 ng/mL of IL-13 vs. control: treated cells presented slower migration than non-treated cells. U87MG cells treated with IL-13 20ng/mL presented slower migration than non-treated cells. This indicates that the IL13Rα1 signaling pathway was not activated, indeed inhibited by the decoy IL-13Rα2, slowing cell migration. This impact occurred with a lesser concentration of IL-13 on the A172 than on the U87MG cell line, because A172 cells have a higher IL-13RA2/A1 ratio. CONCLUSION: The present results suggest IL-13 receptors as possible targets to decrease tumor cell migration.

RESUMO OBJETIVO: Determinar a prevalência de mutações no DNA mitocondrial (DNAmt) em casos com achados compatíveis com o diagnóstico de síndrome de Leigh em um Servicro de Neurologia brasileiro, e comparar essas descobertas entre os pacientes que apresentam ou não essas mutações. MÉTODO: Seis pontos de mutações do DNAmt (T8993G, T8993C, T8851C, G1644T, T9176C e T3308C) foram analisados por PCR e digestão com endonuclease em 32 pacientes com diagnóstico presuntivo de síndrome de Leigh, de acordo com a distribuição em diferentes faixas etárias. RESULTADOS: Dois pacientes no subgrupo abaixo de 4 anos de idade apresentaram as mutações T8993G e T8993C do DNAmt. Os sintomas clínicos e os achados de neuroimagens destes dois pacientes foram similares aos dos casos sem mutações detectadas. CONCLUSÃO: Como a confirmaçãoo molecular é fundamental tanto para o aconselhamento genético como para a orientação terapêutica, enfatizamos o benefício da pesquisa de mutações no DNAmt em pacientes com fenótipo de Síndrome de Liegh abaixo de 4 anos de idade. O sequenciamento em larga escala do genoma mitocondrial e do exoma completo por tecnologia de sequenciamento de nova geração poderá ser uma alternativa futura no estabelecimento do diagnóstico molecular nesta síndrome genética extensamente heterogênea.

OBJECTIVE: To determine the prevalence of mitochondrial DNA (mtDNA) mutations in cases with findings compatible with the diagnosis of Leigh syndrome in a Brazilian Neurological Service, and to compare those findings between the patients presenting or not these mutations. METHOD: We analyzed six mtDNA point mutations (T8993G, T8993C, T8851C, G1644T, T9176C, and T3308C) by PCR and endonuclease digestion in 32 patients with presumptive diagnosis of Leigh syndrome, according to distribution across different age ranges. RESULTS: We found two patients, in the subgroup under 4 years of age, presenting T8993G and T8993C mutations. Their clinical symptoms and neuroimaging findings were similar when compared to those patients not harboring these mutations. CONCLUSION: As the molecular confirmation is pivotal for both the precise genetic counselling and therapeutic guidance, we emphasise the benefit of screening for mtDNA mutation in Leigh syndrome patients under 4 years old. Mitochondrial whole genome and whole exome analysis by next-generation sequencing technology maybe a future alternative for molecular diagnosis of this extensive genetic heterogeneous syndrome.

OBJECTIVES: 1) To correlate the methylation status of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter to its gene and protein expression levels in glioblastoma and 2) to determine the most reliable method for using MGMT to predict the response to adjuvant therapy in patients with glioblastoma. BACKGROUND: The MGMT gene is epigenetically silenced by promoter hypermethylation in gliomas, and this modification has emerged as a relevant predictor of therapeutic response. METHODS: Fifty-one cases of glioblastoma were analyzed for MGMT promoter methylation by methylation-specific PCR and pyrosequencing, gene expression by real time polymerase chain reaction, and protein expression by immunohistochemistry. RESULTS: MGMT promoter methylation was found in 43.1% of glioblastoma by methylation-specific PCR and 38.8% by pyrosequencing. A low level of MGMT gene expression was correlated with positive MGMT promoter methylation (p = 0.001). However, no correlation was found between promoter methylation and MGMT protein expression (p = 0.297). The mean survival time of glioblastoma patients submitted to adjuvant therapy was significantly higher among patients with MGMT promoter methylation (log rank = 0.025 by methylation-specific PCR and 0.004 by pyrosequencing), and methylation was an independent predictive factor that was associated with improved prognosis by multivariate analysis. DISCUSSION AND CONCLUSION: MGMT promoter methylation status was a more reliable predictor of susceptibility to adjuvant therapy and prognosis of glioblastoma than were MGMT protein or gene expression levels. Methylation-specific polymerase chain reaction and pyrosequencing methods were both sensitive methods for determining MGMT promoter methylation status using DNA extracted from frozen tissue.

Cellular energy metabolism is one of the main processes affected during the transition from normal to cancer cells, and it is a crucial determinant of cell proliferation or cell death. As a support for rapid proliferation, cancer cells choose to use glycolysis even in the presence of oxygen (Warburg effect) to fuel macromolecules for the synthesis of nucleotides, fatty acids, and amino acids for the accelerated mitosis, rather than fuel the tricarboxylic acid cycle and oxidative phosphorylation. Mitochondria biogenesis is also reprogrammed in cancer cells, and the destiny of those cells is determined by the balance between energy and macromolecule supplies, and the efficiency of buffering of the cumulative radical oxygen species. In glioblastoma, the most frequent and malignant adult brain tumor, a metabolic shift toward aerobic glycolysis is observed, with regulation by well known genes as integrants of oncogenic pathways such as phosphoinositide 3-kinase/protein kinase, MYC, and hypoxia regulated gene as hypoxia induced factor 1. The expression profile of a set of genes coding for glycolysis and the tricarboxylic acid cycle in glioblastoma cases confirms this metabolic switch. An understanding of how the main metabolic pathways are modified by cancer cells and the interactions between oncogenes and tumor suppressor genes with these pathways may enlighten new strategies in cancer therapy. In the present review, the main metabolic pathways are compared in normal and cancer cells, and key regulations by the main oncogenes and tumor suppressor genes are discussed. Potential therapeutic targets of the cancer energetic metabolism are enumerated, highlighting the astrocytomas, the most common brain cancer.

A doença de Pompe (DP) é uma miopatia originada do acúmulo lisossomal de glicogênio, devido à deficiência da enzima α-glicosidase ácida (GAA), sendo descritas formas de inicio precoce e tardio. Neste estudo analisamos retrospectivamente o perfil clinico e patológico de 3 irmãos portadores de doença de Pompe de inicio tardio. MÉTODO: O diagnóstico foi realizado mediante apresentação clinica de distrofia de cinturas associado a comprometimento respiratório, sendo confirmado por biópsia muscular e análise da atividade e genotipagem da GAA. RESULTADOS: Os exames clínicos e laboratoriais demonstram envolvimento muscular devido à deficiência da GAA, com uma mutação c.-32-3C>A em homozigose. CONCLUSÃO: Relatamos os aspectos clínicos e laboratoriais de 3 irmãos afetados por doença de Pompe de início tardio. Enfatizamos a importância de incluir esta patologia no diagnóstico diferencial das distrofias de cinturas, uma vez que para esta patologia específica existe a possibilidade terapêutica através de reposição enzimática.

Pompe's disease (PD) is a metabolic myopathy caused by the accumulation of lysosomal glycogen, secondary to acid α-glucosidase (GAA) enzyme deficiency. Childhood and late-onset forms are described, differing by the age of onset and symptoms. In this study were analyzed affected siblings with Pompe's disease (PD) and their distinct clinical and pathological presentations. METHOD: Diagnosis was performed by the clinical presentation of limb-girdle dystrophies and respiratory compromise. Confirmatory diagnoses were conducted by muscle biopsy, GAA activity measurement and by GAA gene genotyping. RESULTS: The findings suggested muscular involvement due to GAA deficiency. GAA genotyping showed they are homozygous for the c.-32-3C>A mutation. CONCLUSION: Herein we reported a family where three out of five siblings were diagnosed with late-onset PD, although it is a rare metabolic disease inherited in an autossomal recessive manner. We emphasize the importance of including this presentation within the differential diagnoses of the limb-girdle dystrophies once enzyme replacement therapy is available.

INTRODUCTION: Astrocytic gliomas are the most common intracranial central nervous system neoplasias, accounting for about 60% of all primary central nervous system tumors. Despite advances in the treatment of gliomas, no effective therapeutic approach is yet available; hence, the search for a more realistic model to generate more effective therapies is essential. OBJECTIVE: To develop an experimental malignant astrocytoma model with the characteristics of the human tumor. METHOD: Primary cells from subcutaneous xenograft tumors produced with malignant astrocytoma U87MG cells were inoculated intracerebrally by stereotaxis into immunosuppressed (athymic) Rowett rats. RESULTS: All four injected animals developed non-infiltrative tumors, although other glioblastoma characteristics, such as necrosis, pseudopalisading cells and intense mitotic activity, were observed. CONCLUSION: A malignant astrocytoma intracerebral xenograft model with poorly invasive behavior was achieved in athymic Rowett rats. Tumor invasiveness in an experimental animal model may depend on a combination of several factors, including the cell line used to induce tumor formation, the rat strains and the status of the animal's immune system.

OBJETIVO: Os ependimomas são tumores neuroepiteliais raros na localização intracraniana, porém um dos mais freqüentes na medula espinhal. Os autores analisaram as características destes tumores para determinar a sobrevida e probabilidade de recidiva nos pacientes. MÉTODO: Elementos da apresentação clínica, localização da lesão, duração de sintomatologia, grau de ressecção e tratamento complementar de 34 doentes com ependimoma intracraniano e 31 de medula espinhal operados nos últimos dez anos foram revisados e correlacionados com o período para a ocorrência da recidiva e a sobrevida. RESULTADOS: Houve correlação estatística apenas entre o grau da ressecção e a localização dos ependimomas intracranianos, embora, este não se tenha mostrado um marcador de recidiva. A avaliação dos dados clínicos dos pacientes com ependimoma medular não permitiu definir correlação com a sobrevida e sobre a probabilidade de recorrência. CONCLUSÃO: A localização do tumor intracraniano está relacionada ao grau de ressecção, entretanto isso não foi um fator preditivo para a sobrevida.

OBJECTIVE: Ependymomas are rare intracranial neuroepithelial tumors and the most common location is intramedullary. The aim was to analyze the characteristics of these tumors to determine the patients' overall survival and the likelihood of recurrence. METHOD: Data of clinical presentation, tumor location, duration of symptoms, degree of resection and complementary treatment of 34 patients with intracranial ependymoma and 31 with intramedullary ependymoma who underwent surgery in the last ten years were collected and correlated with the recurrence time and overall survival. RESULTS: There was statistically significant correlation between the degree of resection and intracranial tumor location, although it is not a hallmark of recurrence. Data analyses of intramedullary ependymoma did not show correlation with overall survival and likelihood of recurrence. CONCLUSION: The location of the intracranial tumor is connected with the degree of resection; however it is not a predictive factor to overall survival.

PROPÓSITO: Foi sugerido que mitocondriopatias possam ser responsáveis por uma proporção substancial de acidentes vasculares cerebrais de etiologia indeterminada. Realizamos um estudo preliminar de pesquisa de mutações relacionadas à síndrome de MELAS (encefalomiopatia mitocondrial, acidose lática e episódios "stroke-like") em pacientes jovens com acidentes vasculares cerebrais criptogênicos. MÉTODO: As mutações mitocondriais A3243G e T3271C em 38 indivíduos com menos de 46 anos. Grupo 1: 15 pacientes com acidentes vasculares cerebrais criptogênicos; Grupo 2: 3 pacientes com diagnóstico de síndrome de MELAS, incluindo episódios "stroke-like"; Grupo 3: 20 voluntários saudáveis. RESULTADOS: A mutação A3243G esteve ausente em todos os indivíduos dos Grupos 1 e 3 mas esteve presente em todos os indivíduos do Grupo 2. CONCLUSÃO: Nossos resultados sugerem que não há utilidade em pesquisar estas mutações para diagnosticar formas oligossintomáticas de MELAS em acidentes vasculares cerebrais criptogênicos na ausência de características da síndrome. Sugerimos que o quadro clínico deva guiar a solicitação de pesquisas de mutações relacionadas a mitocondriopatias nestes pacientes .

PURPOSE: It has been suggested that mitochondrial disease may be responsible for a substantial proportion of strokes of indetermined origin. We have preliminarily screened for MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) mutations in young patients with cryptogenic strokes. METHOD: The mitochondrial mutations A3243G and T3271C were investigated in 38 subjects aged less than 46 years. Group 1: 15 patients with cryptogenic strokes; Group 2: 3 patients with diagnosis of MELAS syndrome, including stroke-like episodes; Group 3: 20 healthy subjects. RESULTS: The A3243G mutation was absent in all subjects in Groups 1 and 3 but was present in all subjects in Group 2. CONCLUSION: Our results do not support screening for these mutations to diagnose oligosymptomatic forms of MELAS in cryptogenic strokes in the absence of other features of the syndrome. We suggest that clinical findings should guide mitochondrial genetic testing.

OBJETIVO: Os dados são conflitantes em relação a risco de acidente cerebrovascular associado a polimorfismo do gene 5,10-metilenetetrahidrofolato redutase C677T, o qual predispõe a hiperhomocisteinemia. Um estudo de meta-análise sugere que o genotipo 5,10-metilenetetrahidrofolato redutase 677TT poderia ter uma pequena influência em determinar susceptibilidade a acidente cerebrovascular. MÉTODOS: Analisamos este polimorfismo em indivíduos brasileiros com acidente cerebrovascular isquêmico, baseando-se em um estudo de caso-controle. RESULTADOS: Comparamos os genótipos 5,10-metilenetetrahidrofolato redutase em grupos de indivíduos com acidente cerebrovascular isquêmico (n=127) e controle normal (n=126), e encontramos Odds Ratio de 1,97 (IC 95% 0,84 - 4,64) em uma análise multivariada, na qual os resultados foram ajustados a características clínicas basais dos indivíduos estudados. DISCUSSÃO: Nossos estudos indicam que o genótipo 5,10-metilenetetrahidrofolato redutase C677T não é um fator de risco para acidente cerebrovascular isquêmico entre indivíduos brasileiros.

PURPOSE: Data are conflicting concerning the risk for ischemic stroke associated with a common polymorphism in the gene encoding 5,10-methylenetetrahydrofolate reductase C677T, which predisposes carriers to hyperhomocysteinemia. A meta-analysis study suggested that the 5,10-methylenetetrahydrofolate reductase 677TT genotype might have a small influence in determining susceptibility to ischemic stroke. METHODS: We analyzed the 5,10-methylenetetrahydrofolate reductase 677TT genotype polymorphism in Brazilian subjects with ischemic stroke, using a case-control design. RESULTS: We compared 5,10-methylenetetrahydrofolate reductase genotypes in groups of subjects presenting ischemic stroke (n = 127) and normal control (n = 126) and found an odds ratio of 1.97 (95% CI, 0.84-4.64) in a multivariate analysis in which results were adjusted to baseline clinical characteristics of study participants. CONCLUSION: We found that the homozygous 5,10-methylenetetrahydrofolate reductase C677T genotype was not a risk factor for ischemic stroke in these Brazilian subjects.