Ictal electrographic pattern of focal subcortical seizures induced by sound in rats

It is now recognized that both generalized and focal seizures may originate in subcortical structures. The well-known types of focal subcortically-driven seizures are gelastic seizures in patients with the hypothalamic hamartoma and sound-induced seizures in rodents with audiogenic epilepsy. The seizures are generated by subcortical intrinsically epileptogenic focus, the hamartoma in humans and the inferior colliculus (IC) in rodents. In patients with gelastic epilepsy additional seizure types may develop with time that are supposed to result from secondary epileptogenesis and spreading of epileptic discharges to the cortex. Repeated audiogenic seizures can also lead to development of additional seizure behavior and secondary epileptic activation of the cortex. This process, named audiogenic kindling, may be useful for studying secondary subcortico-cortical epileptogenesis. Using intracollicular and intracortical recordings, we studied an ictal electrographic pattern of focal subcortical seizures induced by repeated sound stimulation in Wistar audiogenic-susceptible rats. The audiogenic seizures, representing brief attacks of paroxysmal unidirectional running, were accompanied by epileptiform abnormalities in the IC, mostly on the side ipsilateral to run direction, and enhanced rhythmic 8-9 Hz activity in the cortex. With repetition of the subcortical seizures and kindling development, a secondary cortical discharge began to follow the IC seizure. The secondary discharge initially involved the cortex homolateral to the side of dominant subcortical epileptiform abnormalities and behaviorally expressed as limbic (partial) clonus. Kindling progression was associated with bilateralization of the secondary cortical discharge, an increase in its amplitude and duration, intensification of associated behavioral seizures (from partial clonus to generalized tonic-clonic convulsions). Thus, ictal recordings during brief audio genic running seizures showed their focal subcortical origin. Repetition of the subcortical seizures may result in secondary subcortico-cortical epileptogenesis manifested by emergence and progressive intensification of epileptiform discharges in the cortex. (C) 2016 Elsevier B.V. All rights reserved.