FUNCTIONAL MAPPING OF THE LATE STAGES OF STATUS EPILEPTICUS IN THE LITHIUM PILOCARPINE MODEL IN RAT - A (14)C-2-DEOXYGLUCOSE STUDY

Pilocarpine administration to lithium chloride-pretreated rats results initially in discrete convulsive seizures, each behaviorally and elec troencephalographically terminated, which then progress to convulsive activity with waxing-and-waning behavioral and electrographic severity ; finally, a continuous convulsive state ensues, associated electrogra phically with continuous fast spiking. This stage does not last indefi nitely but is followed by a dramatic electrographic change to periodic epileptiform discharges. The purpose of the present study was to dete rmine with the C-14-2-deoxyglucose functional mapping technique what c hanges occur in the seizure anatomic substrate during and after this t ransition, in order to enable inferences about underlying mechanisms. Behavior associated with early and late continuous fast spiking consis ted of head twitching; corresponding deoxyglucose autoradiographs disp layed seizure-induced intense glucose utilization in most forebrain ar eas; extranigral brainstem was normal. At 2-3 h of status, fast spikin g became interrupted by flat periods; periodic complexes soon dominate d the electroencephalogram. Behaviorally, convulsive severity increase d. Despite this dramatic electrographic evolution, little change in ge neralized forebrain metabolic hyperactivation occurred, except that th e zona incerta/pretectal/superior colliculus complex displayed markedl y increased activity. Deoxyglucose studies in late stages of periodic epileptiform discharges established a sequence of further changes. In late periodic discharges with clonic jerks, at 4 h after status entry, generalized forebrain hyperactivation still prevailed, but to a lesse r degree than in early periodic discharges with clonic jerks. At a sti ll later stage, late periodic discharges, subtle convulsive, autoradio graphs revealed constriction of the seizure-activated anatomic substra te: hyperactivation was lost in most of neocortex and thalamus, and in caudal olfactory structures, cortical amygdala, and entorhinal areas, but retained in deep occipital cortex and many limbic areas. In the l ast stage, late periodic discharges, electrical, not associated with c onvulsive behavior, autoradiographs revealed residual activation in on ly Ammon's horn; in contrast, much of the forebrain displayed below-no rmal glucose utilization. These results demonstrate that in the later stages of status epilepticus, the transition from fast spiking to peri odic complexes is not associated with a reduction in the seizure anato mic substrate. The electrographic entity of periodic epileptiform disc harges is not anatomically or behaviorally homogeneous, but proceeds t hrough successive stages characterized initially by a reduction of glu cose utilization within generalized seizure-activated forebrain, then a contraction of the seizure anatomic substrate. Possible mechanisms u nderlying the transition to periodic complexes are discussed.