Abstracts

Rationale: The epileptic encephalopathies are conditions in which neurological deterioration is attributable entirely or partly to epileptic activity and is due to very frequent or severe seizures or severely abnormal EEGs, or both. Evidence for the concept that abnormal EEG is responsible for the cognitive deterioration is the observation that patients can have dramatic improvements in cognition when therapy eliminates or reduces interictal discharges. Interictal spikes (IS), which correspond to a large intracellular depolarization with evoked action potentials, in many ways mimic a “mini-seizure.” IS can result in transitory cognitive impairment with the type of deficit dependent upon where in the cortex the spike arises. However, whether IS result in long standing cognitive impairment is unclear. To date there have been no models of IS without seizures in the immature brains. We report here a model of IS without seizures. Methods: Sixteen rat pups of age P10 had intracranial electrodes placed in the right hippocampal area. Following recovery from surgery, they were then placed in a plastic container located in an exhaust hood that allowed unidirectional flow of air from an inlet connected to an isoflurane and oxygen pump. A cotton swab was placed within the tubing just before the inlet of the container. As isoflurane and oxygen were infused into the chamber the rat was sedated. Breathing was closely monitored and flow rates of isoflurane were adjusted. The implanted intracranial electrode was used for continuous EEG monitoring. Liquid flurothyl was then administered into the cotton swab, at the rate of 0.1 ml per 30-60 seconds or till the EEG started to show single recurrent spikes. The animals were closely monitored for behavioral and EEG indications of ictal behavior. Flurothyl exposure was administered to eight rats for two hours daily for 10 consecutive days. An identical number of sham rats who underwent surgery with intracranial electrodes were also monitored for the same number of hours while receiving only isoflurane and oxygen. Control animals that did not undergo any surgery or exposure to isoflurane, oxygen or flurothyl were also monitored and maintained for comparison. Results: Successful IS were observed in the rodent pups in all eight animals exposed to flurothyl. The rate of spikes production varied from 4-20/min with the frequency directly correlating with amount of flurothyl used. Rates of flurothyl were increased for maximum frequency of spikes without observed or electrographic seizures. Recovery after the procedure was identical and no long term effects were noted. Conclusions: This model is a successful imitation of clinically observed IS and abnormal EEG. It is anticipated that this model will open the doors for further investigation and experiments in this area and help in understanding the effects of IS on brain development.