Basic mechanisms of status epilepticus.

This chapter reviews two main aspects of the basic mechanisms of status epilepticus--acute factors, which are important in inducing status epilepticus in an in vitro brain slice model of status epilepticus, and the acute and chronic epileptogenic consequences of status epilepticus. Status epilepticus is difficult to produce in vitro in normal extracellular medium. This suggests that seizure-terminating mechanisms are normally quite robust. To produce long- duration, self-sustained epileptic discharges in vitro, we have found it necessary to include reciprocally connected entorhinal cortex with our hippocampal slices. Doing so closes the normal excitatory limbic loop in the brain. We found incorporation of the full loop in our brain-slice preparations necessary to bring about epileptic discharges of long duration that fit the definition of status epilepticus. Reentrant activation from distant sites may be necessary for maintenance of status epilepticus-like activity of long duration. Similar requirements may exist for generalized tonic-clonic status epilepticus discharges, but as yet no data support or refute this hypothesis. There are both acute and chronic consequences of an episode of status epilepticus. Acute consequences are alterations in membrane potential and membrane properties of hippocampal pyramidal cells accompanied by alterations in neurotransmitter-activated conductances and receptor expression. Some of these acute alterations in receptor and transmembrane iongradient associated with status epilepticus may be critically involved in the development of drug resistance during the late stages of status epilepticus. Long-term consequences of status epilepticus in the limbic system include alterations in patterns of expression of neurotransmitter receptors and in the function of excitatory and inhibitory synapses, cell loss, and circuit rearrangements within the limbic system. An episode of status epilepticus that involves the limbic system clearly elicits brain damage, at least among adult animals. This brain damage can contribute to the development of epilepsy, or a condition of recurrent, spontaneous seizures. Conversely, development of an epileptic condition enhances the susceptibility of the limbic system to trigger status epilepticus discharges.