Alobar holoprosencephaly and Trisomy 13 (Patau syndrome)

Holoprosencephaly (HPE) is a congenital defect of the brain, median structures, and face resulting from an incomplete cleavage of the primitive brain during early embryogenesis. The authors report a case of trisomy 13 syndrome diagnosed at prenatal follow up. The preterm newborn lived only 5 hours, and died because of severe respiratory failure. The autopsy findings disclosed facial, skull, limbs, cardiac, and cerebral malformations. Among the latter, the presence of alobar HPE, the central theme of this report, was evident. The most common nonrandom chromosomal abnormality in patients with HPE is trisomy 13. The most severe variant, namely alobar HPE, is shown in this case report. Discussion on this severe anomaly, along with the case report with details of Patau’s syndrome, is the goal of this report

GEOCHEMISTRY AND PETROGENESIS OF THE SERRA DA MACAMBIRA PLUTON, NEOPROTEROZOIC OF THE SERIDO BELT, BORBOREMA PROVINCE (NE BRAZIL)

O plúton Serra da Macambira intrude ortognaisses do Complexo Caicó e metassupracrustais do Grupo Seridó, no Domínio Rio Grande do Norte da Província Borborema, compreendendo enclaves intermediários (quartzo monzonitos e biotita tonalitos), monzogranitos porfiríticos, sienogranitos e monzogranitos equigranulares, diques tardios de granitos e pegmatitos. Os quartzo monzonitos contêm microclina, plagioclásio, biotita, hornblenda e pouco quartzo, enquanto os biotita tonalitos não apresentam hornblenda. Os granitos porfiríticos e equigranulares portam biotita e raramente hornblenda, mostram texturas mirmequítica e pertítica, além de plagioclásio zonado, que caracteriza a relevância da cristalização fracionada na sua evolução. Os diques graníticos são hololeucocráticos, com textura granofírica indicando condições de colocação hipabissais. Os granitos equigranular e porfirítico mostram características geoquímicas similares, sendo interpretados como produtos de diferenciação do mesmo magma. Esses granitos apresentam padrão de Elementos Terras Raras (ETR) com anomalia negativa de Eu, enriquecimento em ETR leves, razão (La/Yb)N entre 8,9 e 24,6 e YbN entre 8,2 e 45,4, variando de ligeiramente metaluminosos a ligeiramente peraluminosos e seguindo a trajetória cálcio-alcalina de alto-K. Modelos geoquímicos utilizando elementos maiores e traços sugerem que o magma foi formado a partir de 20-35% de fusão parcial da crosta continental inferior, deixando um resíduo composto por K-feldspato, plagioclásio, quartzo, hornblenda, ortopiroxênio, apatita, magnetita, ilmenita e zircão. A evolução magmática envolveu 20-25% de cristalização fracionada, gerando um cumulato de plagioclásio, K-feldspato, biotita, hornblenda, titanita, magnetita, apatita, zircão e alanita, formando as rochas que constituem o plúton. Diagramas discriminantes aliados a feições texturais e estruturais permitem posicioná-lo em contexto de geração e colocação tardi- a pós-tectônico, durante o colapso da orogênese Brasiliana.. The Serra da Macambira pluton intrudes Caicó Complex orthogneisses and metasediments of the Seridó Group of the Rio Grande do Norte Domain in the Borborema Province. The Serra da Macambira pluton comprises intermediate enclaves (quartzbearing monzonite and biotite-bearing tonalite), porphyritic monzogranite, equigranular syenogranite to monzogranite, and late granitic and pegmatitic dykes. The quartz-bearing monzonite has mainly Kfeldspar, plagioclase, biotite, hornblende, whereas in biotite-bearing tonalite hornblende is absent. Porphyritic and equigranular granites display mainly biotite and rare hornblende, myrmequite and pertitic textures, and zoned plagioclase indicating the relevance of fractional crystallization during magma evolution. Granitic dykes are hololeucocratic and granophyric demonstrating conditions of hypabissal crystallization. Equigranular and porphyritic granites have similar geochemical characteristics, which suggest they were formed from similar parental magmas. Such granitic rocks have Rare Earth Element (REE) patterns with negative Eu anomalies and light REE enrichment (normalized La/Yb from 8.9 to 24.6, and normalized Yb from 6.2 to 45.5). They are metaluminous to slightly peraluminous, following a classical high-K calc-alkaline path. Major and trace element contents suggest that the parental magma was generated by 20-35% partial melting of hydrated lower continental crust, leaving a restite of orthopyroxene, plagioclase, quartz, K-feldspar, hornblende, apatite, magnetite, ilmenite, and zircon. Such magma evolved through 20-25% of fractional crystallization, with a cumulate composed by plagioclase, K-feldspar, biotite, hornblende, titanite, magnetite, apatite, zircon and allanite. Discriminant diagrams and textural and structural characteristics may imply that the Serra da Macambira pluton is a late- to post-collisional intrusion formed during the collapse stage of the Neoproterozoic Brasiliano / Pan-African orogeny

Thanatophoric dysplasia: case report of an autopsy complemented by postmortem computed tomographic study

Thanatophoric dysplasia (TD) is one of the most common lethal skeletal dysplasias, which was first designated as thanatophoric dwarfism and described in 1967. The authors report a case of a Caucasian girl with TD, born to a 31-year-old woman without comorbidities. The newborn presented respiratory distress immediately after delivery, progressing to death in less than 2 hours. An autopsy was carried out after postmortem tomographic examination. The autopsy findings depicted extensive malformations of the skeletal system and the brain. The aim of this report is to discuss the pathogenesis and correlate the morphologic features of TD that were disclosed at the tomography and the autopsy

Morphometric brain changes during aging: Results from a Brazilian necropsy sample.

The present study aimed to establish the morphometric brain changes during aging in a necropsy series from Brazil and determine whether sexual dimorphisms interfere in these changes. Methods:A cross-sectional study was conducted at the São Paulo Autopsy Service in Brazil where, after informed consent, data was gathered from next of kin interview with reference to clinical status prior to death. Brain weight, volume and density measurements were taken and then adjusted for head circumference. Descriptive statistics and tests of hypothesis and correlations were applied, considering a p-value of 0.05. Results:414 subjects, mostly men (60.4%), with a mean age of 67.1 years, were included. The mean brain weight of the sample was 1219.2g±140.9and mean volume was 1217mL±152.3. The mean brain density of the sample was 1.0g/mL±0.09. Values differed between males and females in terms of weight and volume. Brain weight decreased during aging by about 45g per decade (r= -0.300; p<0.01) and volume by about 43mL (r= -0.278; p<0.00). Mean density of the sample was 1.0 g/mL in both genders. Conclusions:Brain weight and volume (with or without corrections) decreased during aging, and these reductions were more pronounced in women. Density remained unchanged for both genders. Further studies are needed to investigate factors associated to these reductions

Ataxia de Friedreich: estudo clínico e molecular de 25 pacientes

INTRODUCTION: Friedreich's ataxia is a neurodegenerative disorder whose clinical diagnostic criteria for typical cases basically include: a) early age of onset (< 20 or 25 years), b) autosomal recessive inheritance, c) progressive ataxia of limbs and gait, and d) absence of lower limb tendon reflexes. METHODS: We studied the frequency and the size of expanded GAA and their influence on neurologic findings, age at onset, and disease progression in 25 Brazilian patients with clinical diagnosis of Friedreich's ataxia - 19 typical and 6 atypical - using a long-range PCR test. RESULTS: Abnormalities in cerebellar signs, in electrocardiography, and pes cavus occurred more frequently in typical cases; however, plantar response and speech were more frequently normal in this group when the both typical and atypical cases were compared. Homozygous GAA expansion repeats were detected in 17 cases (68%) - all typical cases. In 8 patients (32%) (6 atypical and 2 typical), no expansion was observed, ruling out the diagnosis of Friedreich's ataxia. In cases with GAA expansions, foot deformity, cardiac abnormalities, and some neurologic findings occurred more frequently; however, abnormalities in cranial nerves and in tomographic findings were detected less frequently than in patients without GAA expansions. DISCUSSION: Molecular analysis was imperative for the diagnosis of Friedreich's ataxia, not only for typical cases but also for atypical ones. There was no genotype-phenotype correlation. Diagnosis based only on clinical findings is limited; however, it aids in better screening for suspected cases that should be tested. Evaluation for vitamin E deficiency is recommended, especially in cases without GAA expansion.INTRODUÇÃO: A ataxia de Friedreich é uma doença neurodegenerativa e os critérios clínicos diagnósticos para os casos típicos incluem: a) idade de início precoce (< 20 ou 25 anos); b) herança autossômica recessiva; c) ataxia progressiva; e d) abolição dos reflexos tendinosos profundos. MÉTODOS: Estudou-se a freqüência e o tamanho das expansões GAA e a sua influência nos achados neurológicos, idade de início e progressão da doença, em 25 pacientes brasileiros com diagnóstico clínico de ataxia de Friedreich - 19 típicos e 6 atípicos, por PCR. RESULTADOS: Anormalidades sugestivas de comprometimento cerebelar, no ECG e a presença de pés cavos ocorreram com maior freqüência nos casos típicos; contudo, a resposta plantar e a fala mostraram-se mais freqüentemente normal neste grupo, quando comparados casos típicos e atípicos. A expansão GAA em homozigose foi detectada em 17 casos (68%) - todos típicos e, em 8 (32%) (6 atípicos e 2 típicos), não foi observada nenhuma expansão, excluindo-se o diagnóstico de ataxia de Friedreich. Deformidade de pés, anormalidades cardíacas e alguns achados neurológicos ocorreram mais freqüentemente, nos casos com expansão GAA, contudo, sinais de comprometimento dos pares cranianos e alterações dos achados tomográficos foram detectados menos frequentemente do que em pacientes sem expansão. DISCUSSÃO: A análise molecular é imprescindível para o diagnóstico de ataxia de Friedreich, não só para os casos típicos como também para os atípicos. Não há qualquer correlação entre o genótipo e o fenótipo. O diagnóstico baseado apenas nos achados clínicos é limitado, embora facilite a triagem para melhor selecionar os casos suspeitos que merecem ser testados. A dosagem sérica da vitamin E é recomendada , especialmente nos casos sem expansão GAA

Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma

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

Post-Mortem diagnosis of dementia by informant interview.

The diagnosis of normal cognition or dementia in the Brazilian Brain Bank of the Aging Brain Study Group (BBBABSG) has relied on postmortem interview with an informant. Objectives:To ascertain the sensitivity and specificity of postmortem diagnosis based on informant interview compared against the diagnosis established at a memory clinic. Methods:A prospective study was conducted at the BBBABSG and at the Reference Center for Cognitive Disorders (RCCD), a specialized memory clinic of the Hospital das Clínicas, University of São Paulo Medical School. Control subjects and cognitively impaired subjects were referred from the Hospital das Clínicas to the RCCD where subjects and their informants were assessed. The same informant was then interviewed at the BBBABSG. Specialists' panel consensus, in each group, determined the final diagnosis of the case, blind to other center's diagnosis. Data was compared for frequency of diagnostic equivalence. For this study, the diagnosis established at the RCCD was accepted as the gold standard. Sensitivity and specificity were computed. Results:Ninety individuals were included, 45 with dementia and 45 without dementia (26 cognitively normal and 19 cognitively impaired but non-demented). The informant interview at the BBBABSG had a sensitivity of 86.6% and specificity of 84.4% for the diagnosis of dementia, and a sensitivity of 65.3% and specificity of 93.7% for the diagnosis of normal cognition. Conclusions:The informant interview used at the BBBABSG has a high specificity and sensitivity for the diagnosis of dementia as well as a high specificity for the diagnosis of normal cognition

IDH1 mutations in a Brazilian series of Glioblastoma

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Albert Einstein Jewish HospitalUniversidade de São Paulo Faculdade de Medicina Department of NeurologyUniversidade de São Paulo Faculdade de Medicina Department of PathologyCancer Institute of São PauloFundação Pio XII Barretos Cancer HospitalFederal University of São Paulo School of Medicine Department of NeurologyFederal University of São Paulo School of Medicine Department of PathologyNove de Julho HospitalAlbert Einstein Jewish HospitalUNIFESP, EPM, Department of NeurologyUNIFESP, EPM, Department of PathologyFAPESP: 04/12133-6SciEL