Navegando por Palavras-chave "Neuropathology"
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- ItemAcesso aberto (Open Access)Caracterização dos subtipos histopatológicos de esclerose hipocampal e sua relação com os dados clínicos, neuropsicológicos e imaginológicos(Universidade Federal de São Paulo (UNIFESP), 2016-10-25) Jardim, Anaclara Prada [UNIFESP]; Yacubian, Elza Marcia Targas [UNIFESP]; http://lattes.cnpq.br/2533199994145143; http://lattes.cnpq.br/7193349685632426; Universidade Federal de São Paulo (UNIFESP)Hippocampal sclerosis (HS) is the commonest histopathological finding in mesial temporal lobe epilepsy and neuropathological subtypes of HS are defined by the qualitative patterns of neuronal loss as assessed on NeuN immunohistochemistry. HS, however, may appear intermediate (Ind-HS) or difficult to classify. HS subtypes have been reported to predict memory deficits and seizure outcome following surgery. The purpose of this study was to verify if quantitative analysis using dendritic marker MAP2 would provide a more stringent classification of HS. Furthermore, analyse if HS subtypes, as well as alteration of hippocampal axonal networks, regenerative capacity and neurodegeneration correlated with MRI hippocampal volumes, accompanying memory deficits, and post-operative seizure outcome. This study was performed in two different centres in Brazil and England. The total number of patients selected was 154 (101 type 1 HS, 23 type 2, 2 type 3, 11 no-HS and 18 Ind-HS). Quantitative analysis was carried out on NeuN and MAP2 and a labelling index (LI) calculated for hippocampal subfields. Markers for hippocampal regenerative activity (MCM2, nestin, olig2, calbindin), degeneration (AT8/phosphorylated TAU), mossy-fibre pathway re-organization (ZnT3), and presence of basal dendrites on granule cells were also evaluated. Pathology measures were correlated with clinical, imaging, memory test scores, and post-operative outcomes, at one year following surgery. The mean MAP2 LI in CA4 in Ind-HS was statistically aligned with type 2 HS but not with NeuN labelling. Moderate and severe memory deficits were noted in all HS types. Memory deficits were correlated with multiple pathology factors including lower NeuN or MAP2 LI in CA4, CA1, dentate gyrus and subiculum, poor preservation of the mossy fibre pathway and fewer basal dendrites on granule cells. Smaller hippocampal volumes were associated with type 1 and 2 HS and with CA1, CA3, and CA4 neuronal density. Type 1 HS patients had better seizure control following surgery. Decline in memory at one year associated with AT8 labelling in the subiculum and dentate gyrus and the density of nestin-labelled cells in CA4, but not with HS subtype. We conclude that MAP2 is a useful adjunct in the classification of HS. The smaller hippocampal volumes on MRI indicate significant neuronal loss and HS pattern. HS subtype classification alone is not predictive of memory function, which was associated with multiple pathology factors including hippocampal axonal pathways, regenerative capacity and degenerative changes.
- ItemAcesso aberto (Open Access)O impacto da duração da epilepsia em uma série de pacientes com epilepsia do lobo temporal mesial e esclerose hipocampal unilateral(Universidade Federal de São Paulo (UNIFESP), 2019-05-30) Duarte, Jeana Torres Corso [UNIFESP]; Yacubian, Elza Marcia Targas [UNIFESP]; http://lattes.cnpq.br/2533199994145143; http://lattes.cnpq.br/5091144674653531; Universidade Federal de São Paulo (UNIFESP)Hippocampal sclerosis (HS) is the commonest pathology found in patients with epilepsy of temporal lobe onset undergoing corticoamygdalohippocampectomy (CAH) and is present in as many as 80% of these cases (Blümcke et al., 2002; Williamson et al., 1993). However, there is still controversy whether HS is a progressive pathology or not. The purpose of this study was to evaluate if the duration of epilepsy influences MRI volumes of the hippocampus, amygdala, parahippocampal gyrus, entorhinal cortex and temporal pole of both hemispheres, ictal and interictal electroencephalographic patterns and epileptogenic hippocampus neuronal cell density and dentate gyrus granular cells distribution in patients with refractory mesial temporal lobe epilepsy due to hippocampal sclerosis (MTLE/HS). Seventy-seven patients with refractory MTLE/HS submitted to surgery were included. Histopathological analysis included: (1) quantitative: hippocampal subfields and total estimated hippocampal cell density (HCD), thickness of the dentate gyrus – normal, thinning or dispersion; (2) qualitative: type of HS and granule cells pathology in the dentate gyrus (normal, neuronal cell loss, dispersion and bilamination). Ictal and interictal EEG were analysed as follows: 1) Ictal EEG: number of localized, lateralized, non-lateralized, focal to bilateral tonic-clonic seizures and switch of lateralization as well as seizures beginning contralateral to HS were determined; 2) Interictal EEG: interictal epileptiform discharges (IEDs) were considered bilateral when ≥20% of independent IEDs were contralateral to HS. Automated MRI-derived measurements from bilateral temporal structures (hippocampus, amygdala, parahippocampal gyrus, temporal pole, entorhinal cortex) were obtained for 58 subjects. Histopathological and imaging findings were compared with data from specimens obtained in autopsies of age-matched individuals and living controls, respectively, and the data were adjusted for the age at epilepsy onset and the frequency of focal impaired awareness seizures/month. Forty-two (54.5%) patients presented right HS. The greater the duration of epilepsy, the smaller the total estimated HCD (p = 0.025; r = - 0.259). Patients with a normal distribution of the granular cells had a shorter epilepsy duration than those with dispersion (p=0.018) or thinning (p=0.031). There was no relation between electroencephalographic ictal or interictal patterns and epilepsy duration. A reduced ipsilateral hippocampal volume (r = -0.551, p = 0.017) and a smaller hippocampal asymmetry index (r = -0.414, p = 0.002) were correlated to a longer epilepsy duration. The estimated HCD was correlated to the volume of the ipsilateral hippocampus (r=0.420, p=0.001). Our study showed an increasing atrophy of the ipsilateral hippocampus in patients with a longer epilepsy duration. Our data suggest that this reduction in hippocampal volume is related to neuronal loss. Besides that, we also showed an increased probability of exhibiting an abnormal distribution of the granular cells in the dentate gyrus in patients with longer epilepsy duration.
- ItemSomente MetadadadosImproved detection of incipient vascular changes by a biotechnological platform combining post mortem MRI in situ with neuropathology(Elsevier B.V., 2009-08-15) Grinberg, Lea Tenenholz; Amaro Junior, Edson; Silva, Alexandre Valotta da [UNIFESP]; Silva, Rafael Emidio da; Sato, Joao Ricardo; Santos, Denis Dionizio dos; Pacheco, Silmara de Paula; Lucena Ferretti, Renata Eloah de; Paraizo Leite, Renata Elaine; Pasqualucci, Carlos Augusto; Teipel, Stefan J.; Flatz, Wilhelm H.; Heinsen, Helmut; Brazilian Aging Brain Study Grp; Univ Wurzburg; Universidade de São Paulo (USP); Inst Israelita Ensino & Pesquisa Albert Einstein; Universidade Federal de São Paulo (UNIFESP); Universidade Federal do ABC (UFABC); Univ Rostock; Univ MunichThe histopathological counterpart of white matter hyperintensities is a matter of debate. Methodological and ethical limitations have prevented this question to be elucidated.We want to introduce a protocol applying state-of-the-art methods in order to solve fundamental questions regarding the neuroimaging-neuropathological uncertainties comprising the most common white matter hyperintensities [WMHs] seen in aging. By this protocol, the correlation between signal features in in situ, post mortem MRI-derived methods, including DTI and MTR and quantitative and qualitative histopathology can be investigated. We are mainly interested in determining the precise neuroanatomical substrate of incipient WMHs. A major issue in this protocol is the exact co-registration of small lesion in a tridimensional coordinate system that compensates tissue deformations after histological processing.The protocol is based on four principles: post mortem MRI in situ performed in a short post mortem interval, minimal brain deformation during processing, thick serial histological sections and computer-assisted 3D reconstruction of the histological sections.This protocol will greatly facilitate a systematic study of the location, pathogenesis, clinical impact, prognosis and prevention of WMHs. (C) 2009 Elsevier B.V. All rights reserved.