Abnormal radial and/or tangential cortical lamination in the temporal lobe cortex associated to Hippocampal Sclerosis (HS) is now classified as focal cortical dysplasia (FCD) type IIIa in the current ILAE FCD classification. In these cases, the temporal cortex may show architectural abnormalities or hypertrophic neurons outside layer V. Five variants of FCD type IIIa have been recognized: HS with architectural abnormalities in the temporal lobe; HS with Temporal Lobe Sclerosis (TLS), HS with TLS and heterotopic neurons in subcortical white matter, HS with TLS and small “lentiform” heterotopias in subcortical white matter; and HS without TLS but with small “lentiform” subcortical heterotopias. One of these types of histological features is frequently found in specimens of patients with temporal lobe epilepsy. Temporal lobe epilepsy due to dysplasia type IIIa is a common epileptic disorder and a common cause for refractory seizures. Also, the patients with temporal lobe epilepsy can suوٴered from depressive, psychotic disorders, visual or verbal memory disturbances leading to poor quality of life. A great majority of patients with TLE due to HS reports an initial precipitating injury before six years of age (called first hit). $Ñ–er that, disabling seizures that evolve to intractability appears months or years letter. For these patients, standard temporal lobectomy has become the most eوٴective treatment. Cerebral specimens obtained throughout this procedure reveal a wide and variable immunohistochemistry features such as: neuronal loss in CA1, CA3, CA4 hippocampal regions, astrogliosis, granular cell dispersion in dentate gyrus and cortical disorganization without cytomegalic or balloon cells. In spite of well-known natural history, clinical presentation and histological features of this epileptic syndrome, little is known about the molecular mechanism that causes this clinic and histopathological disorder. Either, it is understood the relation among the first hit, the second hit, TLE and histopathological features.