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

Continuous convulsive activity in status epilepticus generally does not occur suddenly in response to the inciting epileptogenic agent, but is rather the culmination of a stereotyped sequence of stages. Initially seizures are discrete, then undergo waxing-and-waning of convulsive/ electroencephalographic severity. Following a transitional EEG-recorded fast-and-slow spiking phase, continuous fast spiking with invariant convulsive behavior ensues. We sought to map the seizure anatomic substrates corresponding to these stages, utilizing the C-14-2-deoxyglucose technique, in order to make inferences about underlying mechanisms. The lithium-pilocarpine status epilepticus model in rat was employed. Cerebral autoradiographs associated with discrete seizures revealed non-uniform cerebral metabolic activation, with rostral cortical and olfactory areas especially involved. Portions of basal ganglia were also activated, consistent with projections from seizure-activated areas. Successive stages of status entry displayed additional limbic and cortical activation, along with subcortical projection sites, so that by fast-and-slow spiking most forebrain areas were recruited. Based on these results, a model is proposed whereby cyclical seizure-attenuating mechanisms cause, in the initial stages of status entry, fluxing of seizure anatomic extents between small and large cerebral domains, with corresponding cycling of convulsive severity. In the later stages of status entry, these mechanisms become ineffective, resulting in steady-state maximal forebrain recruitment, associated with continuous and invariant convulsive behavior and electrographic fast spiking.