CASE REPORT Proc. West. Pharmacol. Soc. 49: 29-32 (2006) Neuropathological Changes in a Patient with Epilepsy Francisca Tristán-Agundis 1 , Sandra Orozco-Suárez 2 , Luisa Rocha-Arrieta 3 , Laura Osorio-Rico 4 , Daniel Rembao- Bojorgues 5 , Antonio Santiago-Holguín 6 , Ricardo Galván-Contreras 7 , Juana Villeda-Hernández 8* 1 Anatomía Patológica Hospital Psiquiátrico Fray Bernardino; 2 Unidad de Investigación Médica en Enfermedades Neurológicas del Centro Médico Nacional; 3 Farmacología CINVESTAV Unidad Sur; 4 Depto. Neuroquimica Instituto Nacional de Neurología y Neurocirugía, z”; 5 Patología, Instituto Nacional de Neurología y Neurocirugía; 6 Ciencias Bilógicas, Instituto Politécnico Nacional; 7 Universidad La Salle; 8 Lab. Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía “M. Velasco Suárez” Insurgentes Sur 3877, Col Fama, Tlalpan México C.P. 14269 *E-mail: villeda_2606@yahoo.com.mx ABSTRACT Epilepsy is a common severe neurological illness that affects more than 50 million people worldwide. Our objective is to report post-mortem findings in a patient with epilepsy of 60 years of duration. Brain weight was 1050 g (Fig. 1) showing frontal and occipital lobe atrophy from the right hemisphere with marked arteriosclerosis and congestion, with dilatation of the ventricles. The microscopic examination showed acute neuronal necrosis, with shrunken and hyperchromatic cells, sponginess between the fibers and displacement of nuclei in cortex, hippocampus and cerebellum. The cortex showed moderate expression of glutamate, phosphorylated neuron- filaments, abundant deposits of Rosenthal fibers, hypomyelinization in the white matter, obstructed vessels with little reaction to smooth muscle actin, and perivascular CD8 + lymphocyte infiltration. In the cerebellum we found neuronal loss that is consistent with the effect of cytotoxic CD8 + lymphocyte infiltration. Phosphorylated neurofilaments in the residue of the Purkinje and granular cells were seen. Reactive microglial cells with vimentin, HLA-DR expression, synaptophysin and glutamate transporter expression were seen in some neurons. There was cellular death by apoptosis in all regions studied and cortical radial gliosis and of the molecular layer. These neuropathological findings show the neuronal loss, the cortical and hippocampal gliosis, the expression of the vimentin and synaptophysin are activated after of the seizures, these proteins may contribute to the repair of brain injury through the migration of neurons and glial cells activated in the brain. INTRODUCTION Epilepsy is a common, severe neurological illness that affects more than 50 million people world-wide. Important causes of chronic epilepsy in the developed world are structural cerebral abnormalities or traumatic and ischaemic lesions [10]. Evidence from imaging studies shows that acute changes may be seen following a single seizure, and longitudinal MRI studies suggest progressive subtle brain atrophy in both hippocampal and extra-hippocampal regions, in association with recurrent seizures [4]. Cortical malformations occur as a result of altered develop- mental programs and are frequently epileptogenic [7]. Pathogenic processes targeting dividing cells and accruing during neuroblast birth and migration tend to result in a reduction in cell numbers as well as error in cell location [5]. In less severe malformation- associated epilepsies there may be a delay of months to years, sometimes with a secondary precipitating event, before seizure onset [6]. These differences suggest that the underlying epileptogenic processes vary, and seizure elimination may require treatment specific to these processes [3]. Malformations due to abnormalities of cortical development or cortical dysplasia are a well-recognized cause of chronic epilepsy. The manifestations of dysplasia are quite diverse and run the spectrum of grossly apparent lesions including agyria and parchigyria, polymicrogyria, and hetertopias to microscopically evident lesions. The etiology of many forms of dysplasia is still not known. The majority of dysplasias probably represent malformative lesions that may be associated with a variety a potential etiologies [12]. Previous studies have reported bilateral hippocampal malformations in a single patient with uncontrolled temporal lobe epilepsy who died unexpectedly, probably as the result of a seizure [4]. In adults with long histories of poorly controlled seizures and repetitive head injury, cognitive decline may be documented and neuronal neurofibrillary tangles can be seen at post-mortem examination. Neuronal loss is also evident in the hilar region of the hippocampus, between the blades of the dentate gyrus. The neurons in this region are comprised of the CA 4 and of the CA 3 sector pyramidal cell layer and the interneurons of the polymorphic cell layer of the dentate gyrus, which runs inferiorly to the granule cell layer [8]. Gliosis of the hilus is also appreciated for GFAP immunostaining. Striking accumulation of neurofilaments can be found immunohistochemically in both the cell body and dendritic processes [10]. 29