ABSTRACT
A major concern associated with ZIKV infection is the increased incidence of microcephaly with frequent calcifications in infants born from infected mothers. To date, postmortem analysis of the central nervous system (CNS) in congenital infection is limited to individual reports or small series. We report a comprehensive neuropathological study in ten newborn babies infected with ZIKV during pregnancy, including the spinal cords and dorsal root ganglia (DRG), and also muscle, pituitaries, eye, systemic organs, and placentas. Using in situ hybridization (ISH) and electron microscopy, we investigated the role of direct viral infection in the pathogenesis of the lesions. Nine women had Zika symptoms between the 4th and 18th and one in the 28th gestational week. Two babies were born at 32, one at 34 and 36 weeks each and six at term. The cephalic perimeter was reduced in four, and normal or enlarged in six patients, although the brain weights were lower than expected. All had arthrogryposis, except the patient infected at 28 weeks gestation. We defined three patterns of CNS lesions, with different patterns of destructive, calcification, hypoplasia, and migration disturbances. Ventriculomegaly was severe in the first pattern due to midbrain damage with aqueduct stenosis/distortion. The second pattern had small brains and mild/moderate (ex-vacuo) ventriculomegaly. The third pattern, a well-formed brain with mild calcification, coincided with late infection. The absence of descending fibres resulted in hypoplastic basis pontis, pyramids, and cortico-spinal tracts. Spinal motor cell loss explained the intrauterine akinesia, arthrogryposis, and neurogenic muscle atrophy. DRG, dorsal nerve roots, and columns were normal. Lympho-histiocytic inflammation was mild. ISH showed meningeal, germinal matrix, and neocortical infection, consistent with neural progenitors death leading to proliferation and migration disorders. A secondary ischemic process may explain the destructive lesions. In conclusion, we characterized the destructive and malformative consequences of ZIKV in the nervous system, as reflected in the topography and severity of lesions, anatomic localization of the virus, and timing of infection during gestation. Our findings indicate a developmental vulnerability of the immature CNS, and shed light on possible mechanisms of brain injury of this newly recognized public health threat.
Subject(s)
Brain/pathology , Microcephaly/pathology , Pregnancy Complications, Infectious , Spinal Cord/pathology , Zika Virus Infection/congenital , Zika Virus Infection/pathology , Adolescent , Adult , Brain/diagnostic imaging , Eye/diagnostic imaging , Eye/pathology , Female , Humans , Infant, Newborn , Male , Microcephaly/diagnostic imaging , Microcephaly/etiology , Muscle, Skeletal/pathology , Pituitary Gland/diagnostic imaging , Pituitary Gland/pathology , Pregnancy , Spinal Cord/diagnostic imaging , Young Adult , Zika Virus Infection/complications , Zika Virus Infection/diagnostic imagingABSTRACT
AIMS: To study the expression of Bcl-2, Bcl-x, as well the presence of cleaved caspase-3 in neurofibromas and malignant peripheral nerve sheath tumors. The expression of Bcl-2 and Bcl-x and the presence of cleaved caspase 3 were compared to clinicopathological features of malignant peripheral nerve sheath tumors and their impact on survival rates were also investigated. MATERIALS AND METHODS: The evaluation of Bcl-2, Bcl-x and cleaved caspase-3 was performed by immunohistochemistry using tissue microarrays in 28 malignant peripheral nerve sheath tumors and 38 neurofibromas. Immunoquantification was performed by computerized digital image analysis. CONCLUSIONS: Apoptosis is altered in neurofibromas and mainly in malignant peripheral nerve sheath tumors. High levels of cleaved caspase-3 are more common in tumors with more aggressive histological features and it is associated with lower disease free survival of patients with malignant peripheral nerve sheath tumors.
Subject(s)
Caspase 3/metabolism , Neoplasm Proteins/metabolism , Nerve Sheath Neoplasms/metabolism , bcl-2-Associated X Protein/metabolism , bcl-X Protein/metabolism , Adult , Aged , Aged, 80 and over , Female , Humans , Immunohistochemistry , Male , Middle Aged , Nerve Sheath Neoplasms/pathology , Neurofibroma/metabolism , Neurofibroma/pathology , Tissue Array Analysis , Young AdultABSTRACT
Objetivo - Avaliar, as alterações cardíacas e sua evolução no decurso da síndrome da imunodeficiência adquirida e realizar correlação de dados clínicos e patológicos. Métodos - Foram estudados, prospectivamente, 21 pacientes entre 19 e 42 anos, (4 mulheres) internados com diagnóstico da síndrome da imunodeficiência adquirida e acompanhados até o óbito. Além dos exames de rotina, foram feitos ECG e ecocardiograma a cada 6 meses. Após o óbito, realizou-se estudo macro e microscópico. Resultados - As indicações mais freqüentes de internação foram: diarréia ou pneumonias de repetição, tuberculose, toxoplasmose ou sarcoma de Kaposi. Na avaliação cardíaca, mais freqüentemente, foram encontrados pericardite aguda ou crônica (42 por cento) e miocardiopatia dilatada (19 por cento). Quatro casos tiveram como causa mortis disfunções cardíacas, respectivamente, endocardite bacteriana, pericardite com derrame, miocardite bacteriana e infecção por Toxoplasma gondii. Conclusão - Algumas alterações cardíacas graves levaram ao óbito. Na maioria, houve boa correlação entre dados clínicos e anatomopatológicos. Avaliação cardíaca foi importante mesmo nos casos assintomáticos para se detectar alterações precoces e tratá-las convenientemente.
