Patologia cirúrgica e post mortem: contribuição para a investigação de epilepsias
Arquivos
Data
2010
Autores
Caboclo, Luís Otávio Sales Ferreira 
Orientadores
Sakamoto, Américo Ceiki
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Objetivos: Estudos realizados a partir da observação clínica a longo prazo de pacientes com epilepsia podem trazer informações valiosas sobre a história natural dessa condição. O exame neuropatológico – em espécimes cirúrgicos ou em autópsias – pode ser útil na investigação das epilepsias. Nesse trabalho, foram estudados pacientes seguidos por períodos longos e submetidos a exame neuropatológico post mortem (PM). Os dados clínicos e neuropatológicos são discutidos. Na segunda parte do trabalho, são apresentados dados de estudos neuropatológicos realizados em pacientes submetidos ao tratamento cirúrgico de epilepsia do lobo temporal (ELT) com esclerose mesial temporal (EMT).
Métodos: Na primeira parte, foram estudados 122 pacientes seguidos durante internação em centro de cuidados a pacientes com epilepsia. Esses pacientes foram submetidos a exame neuropatológico PM do cérebro inteiro. Os dados clínicos foram correlacionados ao achados neuropatológicos. Um subgrupo constituído por 25 pacientes foi estudado com métodos patológicos específicos para a avaliação da reorganização do giro dentado (GD) e de seu papel na epileptogênese. Na segunda parte do trabalho, foi realizado exame neuropatológico no hipocampo e no lobo temporal de pacientes com ELT e EMT submetidos a tratamento cirúrgico. Foram estudados os diferentes padrões de perda neuronal no hipocampo e sua correlação com o prognóstico pós-operatório com relação ao controle de crises; e a ocorrência de perda neuronal e gliose no neocórtex temporal, associadas à EMT nesses pacientes.
Resultados: Em uma série constituída em sua maioria por pacientes com epilepsias graves e crises refratárias ao tratamento com drogas antiepilépticas (DAE), uma parcela significativa (33 pacientes) evoluiu tardiamente com melhora clínica com relação ao controle de crises, não associada ao uso de novas DAE. Observou-se uma incidência elevada de morte súbita e não esperada (SUDEP – sudden unexpected death in epilepsy), que, entretanto, foi menos frequente nos pacientes com melhor evolução clínica. Foi possível ainda identificar um subgrupo de pacientes com epilepsia grave, com crises frequentes e episódios de status epilepticus, que não sofreram SUDEP. Anormalidades hipocampais foram encontradas em 77 pacientes, sendo bilaterais em 36 casos. Malformações do desenvolvimento cortical (MDC) também foram frequentes nesse grupo (19 pacientes), em sua maioria não diagnosticadas em vida. Muitos pacientes apresentaram evidências neuropatológicas de traumatismos crânio-encefálicos (TCE), em sua maioria decorrentes das crises, o que trouxe morbidade adicional a esses pacientes. A reorganização do GD foi um fenômeno frequente nos 25 pacientes estudados, podendo ser bilateral em pacientes com EMT uni ou bilateral (simétrica ou assimétrica) e em pacientes sem EMT. Nos pacientes com ELT operados, aqueles com padrões atípicos de EMT tiveram pior prognóstico pós-operatório. Perda neuronal e gliose no neocórtex temporal foram encontradas em 11% dos pacientes.
Conclusões: Pacientes com crises refratárias de longa data podem, tardiamente, apresentar curso mais benigno com relação ao controle de crises. A despeito da incidência elevada de SUDEP nesses pacientes, um subgrupo de pacientes com epilepsia grave parece ser resistente à morte súbita; esse grupo pode ser objeto de futuros estudos. Anormalidades hipocampais são frequentemente bilaterais em pacientes com epilepsia refratária. MDC podem não ser diagnosticadas em vida, portanto o exame neuropatológico PM pode elucidar a etiologia de casos classificados como epilepsia criptogênica. TCE, frequente em pacientes com epilepsias graves, pode trazer morbidade adicional a esses pacientes. A reorganização do GD foi observada com frequência nesses pacientes, provavelmente ocorrendo em conseqüências às crises repetidas. O estudo patológico de espécimes ressecados em cirurgias para o tratamento da ELT pode trazer informações relevantes com relação à extensão das lesões patológicas além do hipocampo, além de dados sobre o prognóstico pós-operatório.
Objectives: Studies based on long term clinical observation of patients with epilepsy may provide valuable information on the natural history of this condition. Neuropathological examination – in surgical specimens or autopsies – may be useful in the investigation of the epilepsies. In the current work, we studied patients who were followed during long periods of time and for whom post-mortem (PM) neuropathological examination was available. Clinical and neuropathological data are discussed. In the second part of the work, we present data on neuropathological studies conducted in patients who were submitted to surgical treatment of temporal lobe epilepsy (TLE) with mesial temporal sclerosis (MTS). Methods: In the first part of the work, 122 patients were followed during admission in a center for care of patients with epilepsy. These patients underwent PM neuropathological examination of the whole brain. Clinical and neuropathological data were correlated. A subgroup of 25 patients was studied with special pathological methods aimed at the assessment of dentate gyrus (DG) reorganization and its role in epileptogenesis. In the second part, neuropathological examination was conducted in the hippocampus and temporal lobe of patients with TLE and MTS who were submitted to surgical treatment. We studied the different patterns of neuronal loss in the hippocampus and their association with post surgical prognosis with respect to seizures; ant the presence of neuronal loss and gliosis in the temporal neocortex, in association with MTS in these patients. Results: In this series, composed mainly by patients with severe forms of epilepsy and seizures refractory to treatment with antiepileptic drugs (AED), a significant part (33 patients) had late clinical improvement with respect to seizure control, not associated with the use of new AED. A high incidence of SUDEP (sudden unexpected death in epilepsy) was observed, which nevertheless was less frequent in patients with better clinical evolution. We could identify a subgroup of patients with severe epilepsies, with frequent seizures and episodes of status epilepticus, who did not suffer SUDEP. Hippocampal abnormalities were encountered in 77 patients, and were bilateral in 36. Malformations of cortical development (MCD) were also a frequent finding (19 patients), and the majority of cases was not diagnosed during life. Many patients had neuropathological evidence of traumatic brain injury (TBI), usually related to seizures, which brought additional morbidity do these patients. DG reorganization was a common finding in the 25 patients studied to this respect, and may be bilateral in patients with unilateral or bilateral (symmetric or asymmetric) MTS, as well as in patients without MTS. In the operated TLE patients, those with atypical patterns of MTS had worse post surgical prognosis. Neuronal loss and gliosis in the temporal neocortex were observed in 11% of the patients. Conclusions: Patients with longstanding refractory seizures may eventually present a benign course with respect to seizure control. Despite the high incidence of SUDEP in these patients, a subgroup with severe epilepsy appears to be SUDEP-resistant; this group may be the object of future studies. Hippocampal abnormalities are frequently bilateral in patients with refractory epilepsy. MCD might go undiagnosed during life; hence neuropathological examination may help elucidate the etiology of cryptogenic cases. TBI, which are frequent in patients with severe epilepsy, may add morbidity to these patients. DG reorganization was frequently observed in these patients, probably occurring as a consequence of repeated seizures. Pathological studies of surgical specimens resected during surgeries for treatment of TLE may provide relevant information regarding the extension of pathological abnormalities beyond the hippocampus, and also bring data on the post surgical prognosis.
Objectives: Studies based on long term clinical observation of patients with epilepsy may provide valuable information on the natural history of this condition. Neuropathological examination – in surgical specimens or autopsies – may be useful in the investigation of the epilepsies. In the current work, we studied patients who were followed during long periods of time and for whom post-mortem (PM) neuropathological examination was available. Clinical and neuropathological data are discussed. In the second part of the work, we present data on neuropathological studies conducted in patients who were submitted to surgical treatment of temporal lobe epilepsy (TLE) with mesial temporal sclerosis (MTS). Methods: In the first part of the work, 122 patients were followed during admission in a center for care of patients with epilepsy. These patients underwent PM neuropathological examination of the whole brain. Clinical and neuropathological data were correlated. A subgroup of 25 patients was studied with special pathological methods aimed at the assessment of dentate gyrus (DG) reorganization and its role in epileptogenesis. In the second part, neuropathological examination was conducted in the hippocampus and temporal lobe of patients with TLE and MTS who were submitted to surgical treatment. We studied the different patterns of neuronal loss in the hippocampus and their association with post surgical prognosis with respect to seizures; ant the presence of neuronal loss and gliosis in the temporal neocortex, in association with MTS in these patients. Results: In this series, composed mainly by patients with severe forms of epilepsy and seizures refractory to treatment with antiepileptic drugs (AED), a significant part (33 patients) had late clinical improvement with respect to seizure control, not associated with the use of new AED. A high incidence of SUDEP (sudden unexpected death in epilepsy) was observed, which nevertheless was less frequent in patients with better clinical evolution. We could identify a subgroup of patients with severe epilepsies, with frequent seizures and episodes of status epilepticus, who did not suffer SUDEP. Hippocampal abnormalities were encountered in 77 patients, and were bilateral in 36. Malformations of cortical development (MCD) were also a frequent finding (19 patients), and the majority of cases was not diagnosed during life. Many patients had neuropathological evidence of traumatic brain injury (TBI), usually related to seizures, which brought additional morbidity do these patients. DG reorganization was a common finding in the 25 patients studied to this respect, and may be bilateral in patients with unilateral or bilateral (symmetric or asymmetric) MTS, as well as in patients without MTS. In the operated TLE patients, those with atypical patterns of MTS had worse post surgical prognosis. Neuronal loss and gliosis in the temporal neocortex were observed in 11% of the patients. Conclusions: Patients with longstanding refractory seizures may eventually present a benign course with respect to seizure control. Despite the high incidence of SUDEP in these patients, a subgroup with severe epilepsy appears to be SUDEP-resistant; this group may be the object of future studies. Hippocampal abnormalities are frequently bilateral in patients with refractory epilepsy. MCD might go undiagnosed during life; hence neuropathological examination may help elucidate the etiology of cryptogenic cases. TBI, which are frequent in patients with severe epilepsy, may add morbidity to these patients. DG reorganization was frequently observed in these patients, probably occurring as a consequence of repeated seizures. Pathological studies of surgical specimens resected during surgeries for treatment of TLE may provide relevant information regarding the extension of pathological abnormalities beyond the hippocampus, and also bring data on the post surgical prognosis.
Descrição
Citação
CABOCLO, Luís Otávio Sales Ferreira. Patologia cirúrgica e post mortem: contribuição para a investigação das epilepsias. 2010. 197 f. Tese (Doutorado) – Escola Paulista de Medicina, Universidade Federal de São Paulo. São Paulo, 2010.