Assuntos
Córtex Cerebral/patologia , Diabetes Mellitus Tipo 2/diagnóstico , Diagnóstico por Computador , Imagem de Difusão por Ressonância Magnética/métodos , Transtornos de Enxaqueca/diagnóstico , Angiografia Cerebral , Angiografia Coronária , Diabetes Mellitus Tipo 2/complicações , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Transtornos de Enxaqueca/complicaçõesRESUMO
BACKGROUND AND PURPOSE: With appropriate selection, temporal lobe epilepsy is potentially curable with surgical intervention achieving seizure freedom in ~80% of individuals. MR imaging-based identification of MTS remains central to the selection process but currently relies on qualitative visual analysis. We sought to determine if new ultrastructural hippocampal details seen on 3T MR imaging had histopathologic correlates and whether these could serve as a useful tool in MTS identification. MATERIALS AND METHODS: Patients undergoing selective anterior temporal lobectomy (n = 5) were scanned using 3T MR imaging preoperatively. En bloc resections were rescanned and subsequently prepared for histopathologic analysis of all hippocampal layers in the CA1-3 regions. Using a newly identified landmark from 3T FSTIR coronal images in 20 patients with histologically confirmed MTS, blinded studies compared ipsilateral and contralateral sides to generate threshold measurements for application in a fast quantitative analysis tool. RESULTS: Histopathologic analysis and correlation with 3T imaging of en bloc resections identified the low-intensity signal as the stratum lacunosum. MTS was associated with extensive gliosis throughout the CA1-3 regions, with loss of tissue thickness in the stratum pyramidale most pronounced in CA1. Fast quantitative analysis by using the stratum lacunosum as a landmark provided a test that identifies MTS with a SN of 70% and SP of 85%. CONCLUSIONS: Here we delineated ultrastructural hippocampal details seen on 3T MR imaging in both the in vivo and ex vivo setting, correlating these with histopathologic features consistent with MTS, and provided preliminary data suggesting their utility in the development of a quantitative analysis assessment tool for application in surgical-candidate selection.
Assuntos
Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/patologia , Hipocampo/patologia , Imageamento por Ressonância Magnética/métodos , Esclerose Múltipla/complicações , Esclerose Múltipla/patologia , Adulto , Epilepsia do Lobo Temporal/cirurgia , Estudos de Viabilidade , Feminino , Hipocampo/cirurgia , Humanos , Masculino , Esclerose Múltipla/cirurgia , Seleção de Pacientes , Cuidados Pré-Operatórios , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
The brain is an exceedingly rare site of metastasis in medullary thyroid carcinoma (MTC). A 50-year-old female who had a history of micro-MTC 11 years prior developed a cerebellar metastasis which was incidentally discovered. Imaging revealed a right cerebellar hemispheric mass with contrast enhancement on CT scans. Histopathologic exam demonstrated a metastatic tumour composed of nodules and sheets of large tumour cells with abundant cytoplasm. Immunohistochemistry confirmed the origin from a MTC. This case report highlights the unique features of an unusual metastatic brain tumour, which followed an indolent course for a long time despite multiple distant metastases.
Assuntos
Neoplasias Encefálicas/secundário , Carcinoma Medular/secundário , Neoplasias da Glândula Tireoide/patologia , Carcinoma Neuroendócrino , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
The 22q11.2 deletion syndrome (22qDS) is the most common microdeletion syndrome in humans. Its multisystem manifestations include congenital anomalies and neuropsychiatric disorders such as schizophrenia. Structural neuroimaging shows various abnormalities, but no postmortem brain studies exist. We report neuropathologic findings in 3 individuals from a cohort of 100 adults with a confirmed 22q11.2 deletion. All 3 had schizophrenia. Postmortem examination of Case 1, a 44-year-old male, revealed bilateral periventricular nodular heterotopia in the frontal lobes and ectopic neurons scattered throughout the frontal white matter. Cases 2 (male, aged 22 years) and 3 (female, 52 years) showed no evidence of migration abnormalities, but both had extensive astrocytic gliosis and focal collections of macrophages in the cerebral white matter, suggestive of cerebrovascular pathology. Review of magnetic resonance imaging findings available for 66 other subjects in the cohort revealed polymicrogyria in one and right cerebellar disorganization in another of the 26 subjects with schizophrenia. The results support previous neuroimaging reports suggesting that neuronal migration abnormalities may be a feature of 22qDS. Both early developmental brain abnormalities and fetal and later microvascular pathology may play a role in the pathogenesis of the neuropsychiatric phenotype of 22qDS, including white matter abnormalities and schizophrenia.
Assuntos
Encéfalo/patologia , Síndrome de DiGeorge/patologia , Fibras Nervosas Mielinizadas/patologia , Neurônios/patologia , Esquizofrenia/patologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Synovial sarcoma is a distinctive soft tissue neoplasm with monophasic and biphasic forms. It is typically a deep-seated soft tissue tumour of the extremities of young adults and occasional cases have been described in large peripheral nerves. A rare example has a predominance of the glandular component and may mimic metastatic carcinoma. Here, a unique synovial sarcoma with <1% spindle cell component involving the posterior tibial nerve is decribed. In addition to having only small bands or islands of stroma, there was also mucin dissection of the surrounding soft tissue. Isolated glands were seen "floating" in pools of mucin. There was abundant intracellular mucin present as well. These latter two findings have not been described in synovial sarcoma thus far, to our knowledge. The diagnosis was confirmed by molecular detection of the t(X;18) by reverse transcription-PCR and confirmed by dual colour break apart fluorescence in situ hybridisation, in a second laboratory. Mucinous, gland predominant synovial sarcoma must be recognised to avoid misdiagnosis of metastatic carcinoma or a glandular malignant peripheral nerve sheath tumour when occurring in a peripheral nerve.
Assuntos
Adenocarcinoma Mucinoso/diagnóstico , Neoplasias do Sistema Nervoso Periférico/diagnóstico , Sarcoma Sinovial/diagnóstico , Adenocarcinoma Mucinoso/secundário , Biomarcadores Tumorais/metabolismo , Cromossomos Humanos Par 18 , Cromossomos Humanos X , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias do Sistema Nervoso Periférico/genética , Neoplasias do Sistema Nervoso Periférico/patologia , Sarcoma Sinovial/genética , Sarcoma Sinovial/patologia , Nervo Tibial , Translocação GenéticaRESUMO
Mutations of the parkin gene are a cause of autosomal recessive juvenile parkinsonism. Although the parkin gene has been isolated from mouse, rat, and human, little is known about its expression in neural and nonneural tissues during development. In this study, we used a polyclonal antibody to a peptide downstream of the parkin ubiquitin domain to investigate (1) the differential expression of parkin isoforms in protein extracts from fetal and adult mouse tissues, and (2) the distribution of parkin in mouse fetal tissues at different developmental stages and in adult CNS tissues. By Western blot analyses, at least three isoforms of parkin of 22, 50, and 55 kDa were differentially expressed in mouse tissues. The p22 and p50 isoforms were found in fetal and adult mouse CNS tissues, while the p55 isoform was found only in adult tissues. The p50 isoform is the predominant form in both fetal and adult tissues. Immunolocalization in mouse fetuses showed that parkin was expressed only after neuronal differentiation. Although parkin was localized throughout the cytoplasm, the highest level of parkin was found in the neurites of both fetal and adult neurons.
Assuntos
Encéfalo/embriologia , Encéfalo/metabolismo , Ligases/biossíntese , Transtornos Parkinsonianos/metabolismo , Ubiquitina-Proteína Ligases , Fatores Etários , Animais , Anticorpos , Química Encefálica , Dopamina/fisiologia , Epitopos/imunologia , Imuno-Histoquímica , Isomerismo , Ligases/química , Ligases/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , CoelhosRESUMO
Human ataxin-2 contains a polyglutamine repeat that is expanded in patients with spinocerebellar ataxia type 2 (SCA2). Ataxin-2 is highly conserved in evolution with orthologs in mouse, Caenorhabditis elegans, and Drosophila melanogaster. It interacts at its C-terminus with ataxin-2 binding protein 1, A2BP1. This study presents a highly conserved mouse ortholog of A2BP1, designated A2bp1. The amino acid sequence of the human and mouse protein is 97.6% identical. This remarkable degree of conservation supports the fact that these proteins have an important basic function in development and differentiation. Sequence analysis reveals the existence of RNA binding motifs. The A2bp1 transcript was found in various regions of the CNS including cerebellum, cerebral cortex, brain stem, and thalamus/hypothalamus. The A2bp1 protein was detected by immunocytochemistry in the CNS and connective tissue of the mouse embryo starting at stage E11, as well as in the heart at all stages. Mouse embryos showed varying expression of A2bp1 at all stages. Previous studies in other model systems had implicated the orthologs of ataxin-2 and A2BP1 in development. This study suggests a role for A2bp1 in embryogenesis as well as in the adult nervous system, possibly mediated by a function in RNA distribution or processing.
Assuntos
Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Animais , Ataxinas , Proteínas de Transporte/química , Cromossomos/genética , Clonagem Molecular , Sequência Conservada , Embrião de Mamíferos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Biblioteca Genômica , Humanos , Camundongos , Modelos Animais , Dados de Sequência Molecular , Proteínas do Tecido Nervoso , Especificidade de Órgãos , Filogenia , Proteínas/genética , Células de Purkinje/metabolismo , Fatores de Processamento de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA , Mapeamento de Híbridos Radioativos , Homologia de Sequência de AminoácidosRESUMO
Ataxin-2, the gene product of the human spinocerebellar ataxia type 2 (SCA2) gene, is a protein of unknown function. Ataxin-2 interacts with ataxin-2-binding-protein 1 (A2BP1), a member of a novel family of putative RNA-binding proteins. Because the sequences of ataxin-2 and A2BP1 are evolutionarily conserved, we investigated functional aspects and expression pattern in the nematode Caenorhabditis elegans. Human ataxin-2 has 20.1% amino acid identity and 43.9% similarity to its C. elegans ortholog, designated ATX-2, that encodes a predicted 1026 aa protein. One of the worm orthologs of human A2BP1 is the numerator element FOX-1, with an overall 29.8% aa identity. We studied the expression pattern of atx-2 using the endogenous promotor coupled with a GFP expression vector. Atx-2 was widely expressed in the adult worm with strong expression in muscle and nervous tissue. It was also heavily expressed in the embryo. In order to elucidate the function of atx-2 and fox-1, we conducted RNA interference (RNAi) studies. The interfering dsRNA was introduced into larval L4 stage worms of the N2 strain by microinjection or soaking. DsRNA representing the full-length atx-2 gene resulted in arrested embryonic development in the offspring of all 58 microinjected worms. Nomarski imaging showed embryos in different stages of developmental arrest, indicating an essential role of atx-2 for early embryonic development. When fox-1 was targeted by RNAi, there was a marked reduction in the number of eggs per worm. The results presented here underline previous findings about the interaction of human ataxin-2 and A2BP1.