Navegando por Palavras-chave "Temporal lobe epilepsy"

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    Absence of gender effect on amygdala volume in temporal lobe epilepsy
    (Elsevier B.V., 2010-11-01) Silva, Ivaldo [UNIFESP]; Lin, Katia; Jackowski, Andrea P. [UNIFESP]; Centeno, Ricardo da Silva [UNIFESP]; Pinto, Magali L. [UNIFESP]; Carrete, Henrique [UNIFESP]; Yacubian, Elza Márcia Targas [UNIFESP]; Amado, Debora [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); HGCR
    Sexual dimorphism has already been described in temporal lobe epilepsy with mesial temporal sclerosis (TLE-MTS). This study evaluated the effect of gender on amygdala volume in patients with TLE-MTS. One hundred twenty-four patients with refractory unilateral or bilateral TLE-MTS who were being considered for epilepsy surgery underwent a comprehensive presurgical evaluation and MRI. Amygdalas of 67 women (27 with right; 32 with left, and 8 with bilateral TLE) and 57 men (22 with right, 30 with left, and 5 with bilateral TLE) were manually segmented. Significant ipsilateral amygdala volume reduction was observed for patients with right and left TLE. No gender effect on amygdala volume was observed. Contralateral amygdalar asymmetry was observed for patients with right and left TLE. Although no gender effect was observed on amygdala volume, ipsilateral amygdala volume reductions in patients with TLE might be related to differential rates of cerebral maturation between hemispheres. (C) 2010 Elsevier Inc. All rights reserved.
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    Aplicação do carisbamato como agente neuroprotetor e modificador da epileptogênese no modelo do lítio-pilocarpina: avaliação da expressão protéica e das alterações neuroquímicas cerebrais
    (Universidade Federal de São Paulo (UNIFESP), 2015-05-31) Silva, Jose Eduardo Marques Carneiro da [UNIFESP]; Fernandes, Maria Jose da Silva [UNIFESP]; Cassel, Jean-Christophe; http://lattes.cnpq.br/7203360175231963; http://lattes.cnpq.br/1946105440212102; Universidade Federal de São Paulo (UNIFESP)
    Introdução: O modelo de epilepsia induzido por pilocarpina apresenta as principais características fisiopatológicas da epilepsia do lobo temporal (ELT) humana. O carisbamato (CRS) é um agente anticonvulsivante com ação neuroprotetora e modificadora da epileptogênese em modelos experimentais de ELT (50% de ratos submetidos ao modelo lítio-pilocarpina tratados com carisbamato desenvolvem crises de ausência, ao invés de crises límbicas). O estudo teve como objetivos determinar parâmetros neuroquímicos e histológicos na elucidação de mecanismos envolvidos com os efeitos do carisbamato. Métodos: A cartografia da atividade cerebral foi feita por imuno-histoquímica para c-Fos, 4h após o status epilepticus (SE). A concentração de monoaminas e aminoácidos no hipocampo, tálamo e córtex piriforme foi mensurada por HPLC no mesmo período. Os grupos estudados foram: DZP (tratamento com lítio e pilocarpina - Li-Pilo, e diazepam 1h após SE); CRS (tratamento com Li-Pilo e carisbamato 1 h após SE); CT (tratamento com salina). O perfil da expressão proteica no hipocampo, foi obtido por proteômica com eletroforese bidimensional, 2 meses após o SE. Os grupos utilizados nesse estudo foram: CT, DZP, CRS-EA, CRS-ELT (ratos submetidos ao Li-Pilo, tratados com 2 doses diárias de CRS com início 1 h após SE, durante 7 dias, e que desenvolveram crises de ausência ou límbicas, respectivamente). Resultados: O grupo DZP apresentou aumento da marcação de c-Fos em todas as áreas estudadas com exceção do núcleo talâmico mediodorsal (MD). A marcação no grupo CRS foi mais intensa nos núcleos talâmicos MD e laterodorsal (LD) quando comparado ao grupo DZP. O estudo neuroquímico mostrou redução de noradrenalina (NA), e aumento em sua taxa de utilização no hipocampo, tálamo e córtex piriforme (Pir) no grupo DZP versus controle. Houve redução na concentração de NA no tálamo e Pir com aumento na taxa de utilização no grupo CRS. A dopamina (DA) aumentou no hipocampo do grupo DZP e a taxa de utilização reduziu no hipocampo do grupo CRS. O grupo DZP mostrou aumento da taxa de utilização de serotonina (5-HT) no tálamo, e o grupo CRS apresentou aumento na concentração no hipocampo e Pir com redução da taxa de utilização no Pir. Houve aumento de GABA e glutamina (GLN) no hipocampo, e de GLN no tálamo do grupo DZP. O grupo CRS apresentou aumento de aspartato (ASP) e de GLN no hipocampo e no tálamo. Os dados obtidos com a proteômica nos grupos foram: DZP versus CT-5 proteínas diferencialmente expressas (2 aumentadas e 3 reduzidas); CRSEA versus CT-13 proteínas diferencialmente expressas (2 aumentadas e 11 reduzidas); CRS-ELT versus CT-7 proteínas diferencialmente expressas (2 aumentadas e 5 reduzidas); CRS-ELT versus DZP-2 proteínas expressas (1 aumentada e 1 reduzida); CRS-EA versus CRS-ELT-11 proteínas diferencialmente expressas (5 aumentadas e 6 reduzidas). Conclusão: O MD pode ser uma região chave na compreensão dos mecanismos envolvidos com o efeito modificador da epileptogênese pelo carisbamato. A DA, NA, GABA et 5-HT podem estar envolvidas com a modulação das crises pelo carisbamato. Os achados da proteômica apontam para uma redução no metabolismo celular nos animais tratados com carisbamato que apresentam crises de ausência.
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    Auras and clinical features in temporal lobe epilepsy: A new approach on the basis of voxel-based morphometry
    (Elsevier B.V., 2010-05-01) Castilho Garcia Santana, Maria Teresa [UNIFESP]; Jackowski, Andrea Parolin [UNIFESP]; Silva, Henrique Hattori da [UNIFESP]; Sales Ferreira Caboclo, Luis Otavio [UNIFESP]; Centeno, Ricardo Silva [UNIFESP]; Bressan, Rodrigo A. [UNIFESP]; Carrete, Henrique [UNIFESP]; Targas Yacubian, Elza Marcia [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    MRI investigations in patients with temporal lobe epilepsy (TLE) with mesial temporal sclerosis (MTS) have demonstrated structural abnormalities extending beyond ipsilateral hippocampus which may be studied through voxel-based morphometry (VBM). We investigated brain morphology related to clinical features in patients with refractory TLE with MIS using VBM. One hundred patients with unilateral TLE with MTS (59 left) and 30 controls were enrolled. VBM5 was employed to analyze (1) hemispheric damage, (2) influence of initial precipitating injury (IPI): 23 patients with febrile seizures and 19 with status epilepticus, and (3) types of auras classified as: mesial, including psychic auras (19 patients); anterior mesio-lateral, as autonomic symptoms, specially epigastric auras (27 patients) and neocortical, which included auditory, vertiginous, somatosensory and visual auras (16 patients). (1) Left TLE patients presented more widespread gray matter volume (GMV) reductions affecting ipsilateral hippocampus, temporal neocortex, insula and also left uncus, precentral gyrus, thalamus, parietal lobule, cuneus and bilateral cingulum. (2) Febrile seizures group presented ipsilateral GMV reductions in hippocampus, neocortical temporal, frontal and occipital cortices, insula and cingulum. Status epilepticus group presented more widespread GMV reductions involving temporal and amygdala, particularly right TLE group, who presented greater extension of GMV reduction in the entorhinal cortex. Significant reductions in hippocampus, amygdala and insula were seen in patients with anterior mesio-lateral auras. This study evaluated a large number of TLE-MTS patients showing structural damage extending beyond hippocampus, and different types of IPI associated with the extension of brain damage. Subtypes of auras are related to different clusters of areas of GMV reductions in VBM. for the first time, we have demonstrated GMV reductions anatomically correspondent to psychic (mesial areas) and autonomic auras (mesial and insular areas) reproducing previous cortical stimulation studies. (C) 2010 Elsevier B.V. All rights reserved.
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    Auras in temporal lobe epilepsy with hippocampal sclerosis: Relation to seizure focus laterality and post surgical outcome
    (Elsevier B.V., 2012-05-01) Ferrari-Marinho, Taissa [UNIFESP]; Caboclo, Luís Otávio Sales Ferreira [UNIFESP]; Marinho, Murilo Martinez [UNIFESP]; Centeno, Ricardo Silva [UNIFESP]; Neves, Rafael Scarpa da Costa [UNIFESP]; Santana, Maria Teresa Castilho Garcia de [UNIFESP]; Britto, Fernanda dos Santos [UNIFESP]; Carrete Junior, Henrique [UNIFESP]; Yacubian, Elza Márcia Targas [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    We examined the relationship between presence and frequency of different types of auras and side of lesion and post surgical outcomes in 205 patients with medically intractable mesial temporal lobe epilepsy (MTLE) with unilateral hippocampal sclerosis (HS). With respect to the number of auras, multiple auras were not associated with side of lesion (p=0.551). the side of HS was not associated with the type of auras reported. One hundred fifty-seven patients were operated. the occurrence of multiple auras was not associated with post-surgical outcome (p=0.740). the presence of extratemporal auras was significantly higher in patients with poor outcome. in conclusion, this study suggests that the presence of extratemporal auras in patients with MTLE-HS possibly reflects extratemporal epileptogenicity in these patients, who otherwise showed features suggestive of TLE. Therefore, TLE-HS patients undergoing pre-surgical evaluation and presenting clinical symptoms suggestive of extratemporal involvement should bemore extensively evaluated to avoid incomplete resection of the epileptogenic zone. (C) 2012 Elsevier Inc. All rights reserved.
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    Avaliação dos padrões de resiliência em pacientes com epilepsia refratária do lobo temporal submetidos à córtico-amigdalo-hipocampectomia
    (Universidade Federal de São Paulo (UNIFESP), 2015-07-31) Brandalise, Maria Helena [UNIFESP]; Araujo Filho, Gerardo Maria de [UNIFESP]; Barbosa, George Souza; http://lattes.cnpq.br/3919088456441783; http://lattes.cnpq.br/5244164212495829; http://lattes.cnpq.br/8017644702075896; Universidade Federal de São Paulo (UNIFESP)
    O objetivo do presente estudo foi o de avaliar os padrões de resiliência em pacientes com epilepsia refratária do lobo temporal por esclerose mesial temporal (ELT-EMT) submetidos à córtico-amigdalohipocampectomia (CAH) e com recorrência das crises através de um instrumento estruturado (Quest_Resiliência), bem como para medir os possíveis impactos negativos da ansiedade e dos sintomas depressivos no desenvolvimento da resiliência nesses pacientes. Métodos: Sessenta pacientes com idade entre 18 e 65 anos, acompanhados no Ambulatório de Epilepsias da Universidade Federal de São Paulo, com o diagnóstico clínico e eletroencefalográfico de ELT-EMT, que haviam sido submetidos à CAH e que apresentavam recorrência das crises epilépticas no momento do estudo foram incluídos, após a assinatura do Termo de Consentimento Livre e Esclarecido. A coleta dos dados foi realizada no período de Abril a Julho de 2013. Os instrumentos utilizados foram: Questionário sócio-demográfico, Quest_Resiliência, Inventário da Depressão de Beck (BDI) e Inventário da ansiedade Traço-Estado (IDATE). Resultados: O estudo mostrou níveis satisfatórios de resiliência ao estresse em pacientes com ELT-EMT submetidos à CAH e que apresentaram recidiva de crises. Tais resultados indicam que os pacientes podem beneficia-se de intervenções que possibilitem o enfrentamento do estresse. No entanto, observou-se um importante impacto negativo dos sintomas de ansiedade e sintomas depressivos no desenvolvimento da resiliência nesses pacientes Conclusão: Em função da escassez de pesquisas sobre os padrões de resiliência em pacientes com ELT-EMT e da alta prevalência de co-morbiades psiquiátricas, os estudos que podem apoiar o desenvolvimento de resiliência são necessários nessa população.
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    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.
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    Correlação entre memória, espectroscopia por ressonância magnética e descargas interictais em pacientes com epilepsia mesial do lobo temporal
    (Universidade Federal de São Paulo (UNIFESP), 2009-06-24) Mantoan, Marcele Araujo Silva [UNIFESP]; Yacubian, Elza Márcia Targas [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Purpose: To examine the relationship between memory function, proton magnetic resonance spectroscopy (1H-MRS) abnormalities and interictal epileptiform discharges (IEDs) lateralization in patients with temporal lobe epilepsy (TLE) related to unilateral mesial temporal sclerosis (MTS). Methods: We assessed performance on selected tests of memory function and intelligence quotient (IQ) in 29 right-handed outpatients and 24 healthy control subjects. The frequency and lateralization of IEDs were visually assessed on 30 min awake and 30 min sleep EEG samples. All patients had a single-voxel 1H-MRS at 1.5 T over both hippocampi. Results: There was a significant difference in IQ results; mean IQ was 83.2 in the patient and 92.4 in the control groups (p < 0.001). Patients with left and right MTS did not differ across measures of IQ, Logical Memory immediate and delayed recall and Rey-Osterrieth Complex Figure immediate and delayed recall; both groups showed impairment when compared to controls. Right MTS group showed no impairment in Rey Auditory Verbal Learning Test (RAVLT) delayed recall when compared to controls. However, in RAVLT post interference, both left and right MTS groups, performed worse than controls (left, p<0.001; right, p<0.045). There was a negative correlation between IQ and duration of epilepsy in left MTS group (p=0.031) as well as between RAVLT total and duration of epilepsy in the same group (p=0.022). There was a correlation between NAA/(Cho+Cr) ratios and verbal functions and also of IEDs and verbal functions. In the left MTS group, there was a negative correlation between NAA/(Cho+Cr) ratio and duration of epilepsy (p=0.027) and between total NAA and IEDs (p=0.006) in contralateral mesial temporal structures.Conclusion: These findings suggest that the IEDs and NAA/(Cho+Cr) ratios, which reflect neural metabolism, are closely related to verbal memory function in mesial temporal lobes. Higher interictal activity in EEG was associated with a decline of total NAA in contralateral mesial temporal structures.
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    Correlation between memory, proton magnetic resonance spectroscopy, and interictal epileptiform discharges in temporal lobe epilepsy related to mesial temporal sclerosis
    (Elsevier B.V., 2009-11-01) Silva Mantoan, Marcele Araujo [UNIFESP]; Sales Ferreira Caboclo, Luis Otavio [UNIFESP]; Figueiredo Ferreira Guilhoto, Laura Maria de [UNIFESP]; Lin, Katia [UNIFESP]; Silva Noffs, Maria Helena da [UNIFESP]; Silva Tudesco, Ivanda de Souza [UNIFESP]; Belzunces, Erich [UNIFESP]; Carrete, Henrique [UNIFESP]; Bussoletti, Renato Tavares [UNIFESP]; Centeno, Ricardo Silva [UNIFESP]; Sakamoto, Americo Ceiki [UNIFESP]; Targas Yacubian, Elza Marcia [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Objective: the aim of the study described here was to examine the relationship between memory function, proton magnetic resonance spectroscopy ((1)H-MRS) abnormalities, and interictal epileptiform discharge (IED) lateralization in patients with temporal lobe epilepsy (TLE) related to unilateral mesial temporal sclerosis.Methods: We assessed performance on tests of memory function and intelligence quotient (IQ) in 29 right-handed outpatients and 24 controls. IEDs were assessed on 30-minute-awake and 30-minute-sleep EEG samples. Patients had (1)H-MRS at 1.5 T.Results: There was a negative correlation between IQ (P = 0.031) and Rey Auditory Verbal Learning Test results (P = 0.022) and epilepsy duration: between (1)H-MRS findings and epilepsy duration (P = 0.027); and between N-acetylaspartate (NAA) levels and IEDs (P = 0.006) in contralateral mesial temporal structures in the left MTS group. (1)H-MRS findings, IEDs, and verbal function were correlated.Conclusions: These findings suggest that IEDs and NAA/(Cho + Cr) ratios reflecting neural metabolism are closely related to verbal memory function in mesial temporal sclerosis. Higher interictal activity on the EEG was associated with a decline in total NAA in contralateral mesial temporal structures. (C) 2009 Elsevier Inc. All rights reserved.
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    A critical and descriptive approach to interictal behavior with the Neurobehavior Inventory (NBI)
    (Elsevier B.V., 2012-11-01) Oliveira, Guilherme Nogueira M. de; Kummer, Arthur; Marchetti, Renato Luiz; Araujo Filho, Gerardo Maria de [UNIFESP]; Salgado, Joao Vincius; David, Anthony S.; Teixeira, Antonio Lúcio [UNIFESP]; Hosp Felicio Rocho; Universidade Federal de Minas Gerais (UFMG); Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP); Kings Coll London
    Purpose: the purpose of this study was to test the psychometric properties of the Neurobehavior Inventory (NBI) in a group of temporal lobe epilepsy (TLE) patients from a tertiary care center, correlating its scores with the presence of psychiatric symptoms.Methods: Clinical and sociodemographic data from ninety-six TLE outpatients were collected, and a neuropsychiatric evaluation was performed with the following instruments: Mini-Mental State Examination (MMSE), structured psychiatric interview (MINI-PLUS), Neurobehavior Inventory (NBI), and Hamilton Depression Rating Scale (HAM-D).Results: Some traits evaluated by the NBI showed adequate internal consistency (mean inter-item correlation between 0.2 and 0.4) and were frequent, such as religiosity (74%) and repetitiveness (60.4%). Principal component analysis showed three factors, named here as emotions (Factor 1), hyposexuality (Factor 2), and unusual ideas (Factor 3). Depressive symptoms on HAM-D showed a strong association with emotions and hyposexuality factors. When patients with left TLE and right TLE were compared, the former exhibited more sadness (p=0.017), and the latter, a greater tendency toward sense of personal destiny (p=0.028).Conclusion: Depression influences NBI scoring, mainly emotionality and hyposexuality traits. Neurobehavior Inventory subscales can be better interpreted with an appropriate evaluation of comorbid mood and anxiety disorders. Compromise in left temporal mesial structures is associated with increased tendency toward sad affect, whereas right temporal pathology is associated with increased beliefs in personal destiny. (C) 2012 Elsevier Inc. All rights reserved.
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    Decreased expression of proteins involved in energy metabolism in the hippocampal granular layer of rats submitted to the pilocarpine epilepsy model
    (Elsevier B.V., 2014-02-21) Araujo, Bruno Henrique Silva [UNIFESP]; Torres, Laila Brito [UNIFESP]; De Lima-Stein, Mariana Leão [UNIFESP]; Cabral, Francisco Romero; Herai, Roberto Hirochi; Okamoto, Oswaldo Keith; Cavalheiro, Esper Abrão [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Hosp Israelita Albert Einstein; Fac Ciencias Med Santa Casa São Paulo; Univ Calif San Diego; Universidade de São Paulo (USP)
    Long-term structural and functional changes in the hippocampus have been identified as the primary physiopathological basis for temporal lobe epilepsy. These changes include reactive gliosis and granule cell axonal sprouting within the dentate gyrus. the intimate mechanisms of these changes are beginning to be revealed. Here, we show the possibility of using laser capture microdissection (LCM) to isolate the dentate granular cell layer of Wistar rats submitted to the pilocarpine model of epilepsy. Using two-dimensional gel electrophoresis (2-D PAGE) and mass spectrometry for laser-captured cells, we identified molecular events that could be altered as part of the epileptic pathogenic process. According to our results, eight proteins related to energy metabolism were differentially expressed between both the control and pilocarpine-treated animals. These results provide, for the first time, new molecular insights into the altered protein profile of the epileptogenic dentate gyrus and can contribute to a better understanding of the phenomena involved in the genesis and maintenance of the epileptic state. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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    Does the patient's hand hold the key to preventing secondary generalization in mesial temporal lobe epilepsy?
    (Elsevier B.V., 2013-07-01) Pedroso Uchida, Carina Goncalves [UNIFESP]; Barsottini, Orlando Graziani Povoas [UNIFESP]; Sales Ferreira Caboclo, Luis Otavio [UNIFESP]; Araujo Filho, Gerardo Maria de [UNIFESP]; Centeno, Ricardo Silva [UNIFESP]; Carrete Junior, Henrique [UNIFESP]; Targas Yacubian, Elza Marcia [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    This study aimed to analyze the impact of ictal dystonic posturing (DP) in postoperative seizure outcome and to assess the influence of DP in generalized tonic clonic seizure (GTCS) occurrence during video-EEG monitoring of patients with temporal lobe epilepsy with mesial temporal sclerosis. the impact of DP on surgical outcome remains controversial. Moreover, DP has been recently associated with brain networks avoiding GTCS occurrence.Five hundred twenty-seven seizures of 171 patients who were submitted to standard anterior temporal lobectomy (ATL) between 2002 and 2010, with at least one year of post-surgical follow-up, were retrospectively analyzed and classified as with or without DP and as evolving or not to GTCS. the ictal semiologic correlates of DP, timing elapsed since precedent seizure and antiepileptic drug (AED) intake before each seizure were evaluated. Seizure outcome after ATL was assessed according to Engel's scale.Fifty-eight out of 171 patients (34%) exhibited ictal DP, of which 91.5% were always unilateral and contralateral to the operated side. DP was related to shorter seizures (p = 0.007) and a much lower likelihood of the seizure evolving to GTCS (p = 0.001), even during AED withdrawal (p = 0.002). There was no association between DP and prognosis regarding seizure control as the result of the surgical resection, either in patients with shorter or in those with longer period of follow-up. Our data support the hypothesis that DP reflects a brain network activation that helps avoid GTCS, even during AED withdrawal. (C) 2013 Elsevier B.V. All rights reserved.
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    Efeito do exercício físico forçado sobre a arquitetura do sono em ratos com epilepsia do lobo temporal
    (Universidade Federal de São Paulo (UNIFESP), 2016-06-30) Lima, Cristiano de [UNIFESP]; Tufik, Sergio [UNIFESP]; http://lattes.cnpq.br/1375290481822767; http://lattes.cnpq.br/1073873643557490; Universidade Federal de São Paulo (UNIFESP)
    Patients with epilepsy present sleep disturbances, which may adversely impact quality of life, which can in turn, facilitate the seizure occurrence. Evidences from human and animals studies have demonstrated that exercise can exert beneficial effects such as reduction of seizure susceptibility and improvement of quality of life of individuals with epilepsy. Exercise has been found beneficial for enhancing the quality of sleep in patients with neurological disorders. In this regard, analysis of sleep patterns induced by exercise could provide information about the mechanisms by which exercise can exert positive influence on epilepsy. To investigate the influence of an acute exercise session on sleep pattern in rats with temporal lobe epilepsy (TLE), in addition to serum levels total testosterone and corticosterone. Twenty male Wistar rats were randomly distributed into 4 groups: control (C); acute exercise (EX); epilepsy (E) and epilepsy acute exercise (EEX). Two sleep electrocorticography recordings were performed during the light phase [(baseline and Day 2 (after acute physical exercise session)]. The following sleep parameters were evaluated: wakefulness, slow wave sleep (SWS), rapid eye movement (REM) sleep and total sleep time (TST). After baseline recording, the exercise groups (EX and EEX) were submitted to exercise session on a motor-driven treadmill at 12 m/min for 30 min. Twelve hours later, the rats were submitted to the second sleep recording. At baseline it was observed a higher wakefulness and a lower TST, SWS and REM sleep of animals with epilepsy compared to rats treated with saline. After acute exercise it was observed an increase in TST, SWS and a decrease of wakefulness in EEX (+11.10%, +20.29% and -11.25%, respectively) and EX (+5.20%, +11.60% and - 8.12%, respectively) groups. These results suggest that acute exercise positively impacted on the sleep patterns of rats with TLE and the influence of exercise on sleep demonstratred to be an excellent non-drug alternative for this population, contributing to a regenerative sleep and consolidated. Key-words: epilepsy, temporal lobe epilepsy, physical exercise, sleep and electrocorticogram.
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    Efeito do tratamento com brilhant blue G, um bloqueador do receptor P2X7, potencializado com células-tronco mesenquimais no hipocampo de animais epilépticos crônicos
    (Universidade Federal de São Paulo (UNIFESP), 2017-06-30) Moreira, Diego Marques [UNIFESP]; Monteiro, Beatriz de Oliveira [UNIFESP]; Romariz, Simone Amaro Alves [UNIFESP]; http://lattes.cnpq.br/9325741054357205; http://lattes.cnpq.br/0245964878412260; http://lattes.cnpq.br/9937060994528698; Universidade Federal de São Paulo (UNIFESP)
    Epilepsy has as its main characteristic the manifestation of spontaneous and recurrent seizures that develop from neuronal changes in certain areas of the central nervous system. It has recently been shown that the P2X7 receptor (P2X7r) is overexpressed in the brain of chronic epileptic animals and in experimental models for various neurodegenerative diseases, supporting the hypothesis that P2X7 participates in pathways involved in neurodegeneration. In addition, blocking P2X7r with Brilliant Blue G (BBG), a P2X7r antagonist capable of crossing the blood-brain barrier, prevents the death of neural cells induced by status epilepticus (SE) in the epileptogenic phase Mesenchymal stem cells have paracrine properties, that is, they are able to release trophic factors that lead to a decrease in the inflammatory, apoptotic process and increase in cell proliferation at the injured site. Currently, the stem cell study has been suggested as possible treatments for neurodegenerative diseases, due to its ability to decrease neuroinflammatory processes and also due to its ability to differentiate in neurons. Thus, our work investigated the therapeutic potential of P2X7 receptor blockers, BBG, combined with mesenchymal stem cell transplantation in the chronic period of pilocarpine-induced epilepsy. This study contributed to the understanding of the mechanisms involved in hippocampal repair promoted by BBG and by mesenchymal stem cells in epilepsy. Adult male Wistar rats were treated with pilocarpine for an S.E. induction, and 14 days after recovery of substances subjected to stereotactic surgery for intrahippocampal MSC administration.After surgery, the rats were kept on observation for chronic seizures recording for 90 days, and treated with BBG from the 30th to the 60th day after SE (16 injections on interquartered days). As MSC donors were used by C57 / BL6EGFP mice All procedures were duly authorized by the institution's ethics committee under opinion # 8977 (Annex II). The results obtained in this study are the transplantation of MSC in epileptic rats, concomitantly with the treatment with BBG, to act in the preservation of cells and the reduction of seizures, thus indicating therapeutic potential.We conclude that the protective activity in the CTM-BBG group indicates that the decrease in inflammation in epilepsy is a critical piece for a reduction of seizures.The inflammatory mechanisms involved in epilepsy need to be better explo red.
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    Effects of acute physical exercise in the light phase of sleep in rats with temporal lobe epilepsy
    (Elsevier Science Bv, 2017) de Lima, Cristiano[UNIFESP]; Arida, Ricardo Mario [UNIFESP]; Andersen, Monica Levy [UNIFESP]; Polesel, Daniel Ninello [UNIFESP]; Fernandes de Alvarenga, Tathiana Aparecida [UNIFESP]; Vancini, Rodrigo Luiz; Matos, Gabriela [UNIFESP]; Tufika, Sergio [UNIFESP]
    Objective: Our aim was to investigate the influence of an acute exercise session on sleep pattern in rats with temporal lobe epilepsy (TLE). Methods: Twenty male Wistar rats were randomly assigned to 4 groups: control (C)
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    Estudo da ação da lovastatina no desenvolvimento do modelo experimental de epilepsia induzido pela pilocarpina em ratos
    (Universidade Federal de São Paulo (UNIFESP), 2011-06-29) Gouveia, Telma Luciana Furtado [UNIFESP]; Naffah-Mazzacoratti, Maria da Graca [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Introduction: Inflammation has been associated with several neurodegenerative diseases and experimental and clinical data suggest a crucial role in inflammatory processes in the development of epilepsy, particularly in seizure-generating mechanisms (ictogenesis) and transformation of a normal neuronal network into a network generating seizures. Lovastatin, a drug used in the reduction of cholesterol synthesis, is also related to the inflammatory response and can modulate cytokine production reducing the oxidative stress. Objectives: This study aimed to analyze the action of lovastatin in different stages of development model of epilepsy induced by pilocarpine in rats. Methods: Male Wistar rats were analyzed in three periods of the pilocarpine-induced epilepsy (350mg/kg) into phases: acute (24h), silent (15 days) and chronic (30 days after the 1st spontaneous seizure) and for each period of this model we used 4 groups of animals: saline-treated, lovastatin (Lova), pilocarpine (Pilo) and pilocarpine + lovastatin (Pilo+ Lova). Treatment with lovastatin (20 mg / kg) begun 2 h after the onset of status epilepticus (SE) and was administered for 15 days, twice a day the animals in the silent and chronic phases. The brain was processed for performing real-time PCR and immunohistochemistry of IL-1ƒÀ, IL-6, TNF-ƒ¿, IL-10 and kinin B1 and B2 receptors and quantification of amino acids in the hippocampus. Besides, the hippocampal tissue was processed for Nissl techniques and Neo-Timm. In addition, body temperature was measured in the acute phase and the duration of the silent period and seizure frequency in chronic phase was analyzed. Results: Treatment with lovastatin in Pilo + Lova group showed decreased expression of mRNA and proteins IL-1ƒÀ and TNF-ƒ¿ in the three phases of this model, We also noted reduction of kinin B1 and B2 receptor in the acute and IL-6 into acute and silent periods. There was an increased expression of IL-10 in the chronic phase of this model. There was no change in amino acids levels in the hippocampus of rats from Pilo+Lova group when compared to Pilo group. We observed a normalization of body temperature of rats subjected to SE and treated with lovastatin. There was no significant difference between the group Pilo and Pilo + Lova on the duration of the silent phase and in seizure frequency. We observed a preservation of neurons in CA1 and also a reduction of mossy fiber sprouting in Pilo+ Lova group as compared to the Pilo group in the chronic phase of the model. Conclusion: This study demonstrated that treatment with lovastatin decreased number of important parameters related to the neuronal damage induced by SE in the hippocampus of rats at different stages of the experimental model of epilepsy induced by pilocarpine.
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    Expression and activity of thimet oligopeptidase (TOP) are modified in the hippocampus of subjects with temporal lobe epilepsy (TLE)
    (Wiley-Blackwell, 2014-05-01) Rodrigues Simoes, Priscila Santos [UNIFESP]; Visniauskas, Bruna [UNIFESP]; Perosa, Sandra Regina [UNIFESP]; Yacubian, Elza Márcia Targas [UNIFESP]; Centeno, Ricardo [UNIFESP]; Canzian, Mauro; Lopes-Cendes, Iscia; Maurer Morelli, Claudia Vianna; Carrete, Henrique [UNIFESP]; Cavalheiro, Esper Abrão [UNIFESP]; Tufik, Sergio [UNIFESP]; Chagas, Jair Ribeiro [UNIFESP]; Naffah-Mazzacoratti, Maria da Graca [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP); Universidade Estadual de Campinas (UNICAMP)
    ObjectiveThimet oligopeptidase (TOP) is a metalloprotease that has been associated with peptide processing in several nervous system structures, and its substrates include several peptides such as bradykinin, amyloid beta (A), and major histocompatibility complex (MHC) class I molecules. As shown previously by our research group, patients with temporal lobe epilepsy (TLE) have a high level of kinin receptors as well as kallikrein, a kinin-releasing enzyme, in the hippocampus.MethodsIn this study, we evaluated the expression, distribution, and activity of TOP in the hippocampus of patients with TLE and autopsy-control tissues, through reverse-transcription polymerase chain reaction (RT-PCR), enzymatic activity, Western blot, and immunohistochemistry. in addition, hippocampi of rats were analyzed using the pilocarpine-induced epilepsy model. Animals were grouped according to the epilepsy phases defined in the model as acute, silent, and chronic.ResultsIncreased TOP mRNA expression, decreased protein levels and enzymatic activity were observed in tissues of patients, compared to control samples. in addition, decreased TOP distribution was also visualized by immunohistochemistry. Similar results were observed in tissues of rats during the acute phase of epilepsy model. However, increased TOP mRNA expression and no changes in immunoreactivity were found in the silent phase, whereas increased TOP mRNA expression and increased enzymatic activity were observed in the chronic phase.SignificanceThe results show that these alterations could be related to a failure in the mechanisms involved in clearance of inflammatory peptides in the hippocampus, suggesting an accumulation of potentially harmful substances in nervous tissue such as A, bradykinin, and antigenic peptides. These accumulations could be related to hippocampal inflammation observed in TLE subjects.
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    Gender and hemispheric differences in temporal lobe epilepsy: A VBM study
    (W B Saunders Co Ltd, 2014-04-01) Santana, Maria Teresa Castilho Garcia de [UNIFESP]; Jackowski, Andrea Parolin [UNIFESP]; Britto, Fernanda dos Santos [UNIFESP]; Sandim, Gabriel Barbosa [UNIFESP]; Caboclo, Luís Otávio Sales Ferreira [UNIFESP]; Centeno, Ricardo Silva [UNIFESP]; Carrete Junior, Henrique [UNIFESP]; Yacubian, Elza Márcia Targas [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Purpose: Gender differences are recognized in the functional and anatomical organization of the human brain. Differences between genders are probably expressed early in life, when differential rates of cerebral maturation occur. Sexual dimorphism has been described in temporal lobe epilepsy with mesial temporal sclerosis (TLE-MTS). Several voxel-based morphometry (VBM) studies have shown that TLE-MTS extends beyond mesial temporal structures, and that there are differences in the extent of anatomical damage between hemispheres, although none have approached gender differences. Our aim was to investigate gender differences and anatomical abnormalities in TLE-MTS.Methods: VBM5 was employed to analyze gender and hemispheric differences in 120 patients with TLE-MTS and 50 controls.Results: VBM abnormalities were more widespread in left-TLE; while in women changes were mostly seen in temporal areas, frontal regions were more affected in men.Conclusions: Our study confirmed that gender and laterality are important factors determining the nature and severity of brain damage in TLE-MTS. Differential rates of maturation between gender and hemispheres may explain the distinct areas of anatomical damage in men and women. (C) 2013 British Epilepsy Association. Published by Elsevier B.V. All rights reserved.
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    Hippocampal proteomic profile in temporal lobe epilepsy
    (Liga Brasileira de Epilepsia (LBE), 2012-01-01) Persike, Daniele Suzete [UNIFESP]; De Lima-Stein, Mariana Leão [UNIFESP]; Amorim, Rebeca Padrão [UNIFESP]; Cavalheiro, Esper Abrão [UNIFESP]; Yacubian, Elza Márcia Targas [UNIFESP]; Centeno, Ricardo Silva [UNIFESP]; Carrete Junior, Henrique [UNIFESP]; Schenkman, Sergio [UNIFESP]; Canzian, Mauro; Fernandes, Maria Jose da Silva [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
    In this study we used proteomics approaches to obtain the protein profile of human epileptic hippocampi (N=6) and control hippocampi obtained from autopsy (N=6). We used two-dimensional gel electrophoresis (2-D) coupled to HPLC and Mass spectroscopy (MALDI-TOF) to identify proteins differentially expressed. Nine proteins were differentially expressed comparing the hippocampus of patients with the hippocampus of control. Proteins that were increased in the hippocampus of patients with TLE were: isoform 1 of serum albumin, HSP 70, dihydropyrimidinase-related protein 2, isoform 1 of myelin basic protein, proton ATPase catalytic subunit A, and dihydrolipoyllysine-residue acethyltransferase component of pyruvate dehydrogenase complex. The expression of isoform 3 of spectrin alpha chain (fodrin) was down-regulated while the proteins glutathione S-transferase P and the DJ-1 (PARK7) were detected only in the hippocampus of patients with TLE. Taken together, our results provide evidence supporting a direct link between metabolic disturb and oxidative damage related to pathophysiology of TLE. Besides, indicates biomarkers for further investigations as therapies targeted to epilepsy.
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    Impact of hippocampal subfield histopathology in episodic memory impairment in mesial temporal lobe epilepsy and hippocampal sclerosis
    (Academic Press Inc Elsevier Science, 2017) Comper, Sandra Mara [UNIFESP]; Jardim, Anaclara Prada [UNIFESP]; Corso, Jeana Torres [UNIFESP]; Gaca, Larissa Botelho [UNIFESP]; Silva Noffs, Maria Helena [UNIFESP]; Penteado Lancellotti, Carmen Lucia; Cavalheiro, Esper Abrao [UNIFESP]; Centeno, Ricardo Silva [UNIFESP]; Targas Yacubian, Elza Marcia [UNIFESP]
    Objective: The objective of the study was to analyze preoperative visual and verbal episodic memories in a homogeneous series of patients with mesial temporal lobe epilepsy (MTLE) and unilateral hippocampal sclerosis (HS) submitted to corticoamygdalohippocampectomy and its association with neuronal cell density of each hippocampal subfield. Methods: The hippocampi of 72 right-handed patients were collected and prepared for histopathological examination. Hippocampal sclerosis patterns were determined, and neuronal cell density was calculated. Preoperatively, two verbal and two visual memory tests (immediate and delayed recalls) were applied, and patients were divided into two groups, left and right MTLE (36/36). Results: There were no statistical differences between groups regarding demographic and clinical data. Cornu Ammonis 4 (CA4) neuronal density was significantly lower in the right hippocampus compared with the left (p = 0.048). The groups with HS presented different memory performance the right HS were worse in visual memory test [Complex Rey Figure, immediate (p = 0.001) and delayed (p = 0.009)], but better in one verbal task [RAVLT delayed (p = 0.005)]. Multiple regression analysis suggested that the verbal memory performance of the group with left HS was explained by CA1 neuronal density since both tasks were significantly influenced by CA1 [Logical Memory immediate recall (p = 0.050) and Logical Memory and RAVLT delayed recalls (p = 0.004 and p = 0.001, respectively)]. For patients with right HS, both CA1 subfield integrity (p = 0.006) and epilepsy duration (p = 0.012) explained Complex Rey Figure immediate recall performance. Ultimately, epilepsy duration also explained the performance in the Complex Rey Figure delayed recall (p < 0.001). Significance: Cornu Ammonis 1 (CA1) hippocampal subfield was related to immediate and delayed recalls of verbal memory tests in left HS, while CAl and epilepsy duration were associated with visual memory performance in patients with right HS. (C) 2017 Elsevier Inc. All rights reserved.
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    Investigação do papel de compostos de telúrio (iv) e nitroalcenos na epilepsia induzida por lítio-pilocarpina
    (Universidade Federal de São Paulo (UNIFESP), 2016-12-21) Predebon, Gabriela de Melo [UNIFESP]; Fernandes, Maria Jose da Silva [UNIFESP]; http://lattes.cnpq.br/7203360175231963; http://lattes.cnpq.br/3145440792736832; Universidade Federal de São Paulo (UNIFESP)
    Introduction: Epilepsy is a disorder characterized by the propensity of the brain to generate seizures and the temporal lobe epilepsy (TLE) is the most common type. The hippocampal sclerosis (HS) is the main pathophysiological feature of TLE. The experimental model of epilepsy induced by lithium pilocarpine (LiPilo) reproduces the main pathophysiolocal characteristics of human TLE. It is increasing the number of researchers interested in identifyng new therapeutic targets for treat drug-resistent seizures. In this study, the effect of compounds of Tellurium (Te) and Nitroalkenes (Nitro) were tested for neuroprotective and anticonvulsant effects in the LiPilo model of epilepsy. These compounds had beneficial effects in models of inflammatory, cardiovascular and neurodegenerative diseases being promising molecules for the treatment of TLE.Aims:Evaluate the effects of the TeCG (Dichloro(E)-1-(1-chloro-2-(4-methoxyphenyltellanyl)vinyl)cyclohexanol), Nitro-1 ((E)-1-nitro-4-(2-nitrovinyl)benzene) and Nitro-13 ((E)-1nitro-4-(2nitroprop-1-en-1-yl)benzeno) after SE induced by LiPiloon their ability to modify the epileptogenesis.Methods: The cytotoxicity of TeCG, TeC, Nitro-1 and Nitro-13 was evaluated in C-12 cells by concentration-response curves (0.1?M to 50?M). The cell protection property of the compounds was analyzed by means of flow cytometry with labeling of propidium iodide, after incubation of the cells with the aggressive agent hydrogen peroxide (H2O2, 30?M).Permeability of TeCwere analyzed in vitro(0.1?M)at different times 2, 5, 24 and 48 hours, and in vivo (0.04mg/ kg, i.p.) was applied 30 minutes after beginning of SE. Electroencephalographic (EEG) was used to evaluate the ability of TeCG (0,04mg/kg, i.p), Nitro-1 and Nitro-13 (2mg/kg, i.p) to block behavioral seizures. Neuronal cell death in hippocampal sub-regions (CA1, CA3 and Hilo) was analyzed by Fluoro-JadeB (FJ-B) in the following groups: Control, Pilo+Vehicle, Saline+TeCG, Saline+Nitro-1, Saline+Nitro-13, Pilo+TeCG, Pilo+Nitro-1 and Pilo+Nitro-13. Results:Our results showed that TeCG and TeC at doses below 10?M and 50?M, respectively, had no toxic effects. TeCG had cytoprotective effect against H2O2 at concentrations of 0.1?M and 1?M. TeC crossed the plasmatic membrane of PC-12 cells after 2 hours of incubationand the blood brain barrier of Wistar rats after 24 hours from the beginning of SE. Nitro-1 and Nitro-13 had non-toxic effect below at 40?M and both compounds had cytoprotective effect against H2O2in concentration of 0.1?M. TeCG treatment did not change the electroencephalographic seizures, but had neuroprotective effect in the hippocampal subfields CA1, CA3 and Hilo. Nitro-1 had neuroprotective effect in CA3 and Hilo, and Nitro-13 caused neuroprotection in CA1, CA3 and Hilo. Conclusion:The compounds TeCG, Nitro-1 andNitro-13 presented cytoprotective effects of PC-12 cells incubated with the deleterious agent H2O2.They also presented neuroprotective effect in hippocampal brain areas of rats subjected to LiPilo model. These compounds should be better evaluated for the potential seizure-modifying effects.