Introduction and Symposium Overview

Status epilepticus (SE) is a medical emergency that requires immediate identification and treatment. Despite extensive research, it continues to be a major clinical problem throughout the world, with high rates of incidence (approximately 40 per 100,000) and mortality (approximately 26% in adults and 3% in children) (1). However, a number of new insights into the pathogenesis and treatment of SE have improved our understanding and overall clinical management of this condition. This supplement reviews the most up-to-date experimental and clinical research on the diagnosis and treatment of SE in children and adults. Several important and complex issues relative to the definition of status epilepticus must be addressed if we are to understand its underlying pathogenesis and develop effective treatments. In an overview, Dr. Daniel Lowenstein describes the history of SE and the evolution of its definition. For many years, investigators have struggled to identify a specific seizure duration parameter that defines the onset of SE. The "textbook" definition of SE cites seizure duration of 230 min, indicating the point at which seizure-induced neuronal injury begins. However, there are currently no data that clearly support this time interval. The exact duration of seizures that establishes SE remains uncertain and difficult to ascertain. Therefore, Dr. Lowenstein discusses the rationale for using an operational definition of SE that is distinct from a mechanistic definition. The role of underlying etiology, duration of seizures, and age as significant determinants of outcome of SE are reviewed as well. Under normal circumstances, individuals will have a seizure that is self-terminating, but when the mechanisms of termination fail the seizure becomes prolonged. My article examines the pathophysiologic mechanisms occurring in the hippocampus during an acute episode of SE. Although the mechanisms at work during the transition between a self-terminating seizure and the prolonged duration of SE remain unknown, several theories on the pathophysiology of SE have evolved: (a) the hippocampus is consistently activated during SE; (b) loss of y-aminobutyric acid (GABA)-mediated inhibitory synaptic transmission in the hippocampus is a crucial component in the emergence of SE; and (c) glutamatergic excitatory synaptic transmission is an important factor during SE. The focal point of this discussion will be on the alteration of GABAergic inhibition in the hippocampus and other areas of the brain that occurs during the prolonged seizures of SE. Because SE is not a singular entity, it is often followed by severe forms of morbidity, the most common of which is the development of seizures. The long-term consequences of SE are the topic of two presentations. First, Dr. Douglas Coulter discusses the chronic changes that occur in experimental animals after prolonged seizures. An association between seizures originating from or involving the limbic system and an ensuing partial epilepsy has been demonstrated through the development of animal models of temporal lobe epilepsy. These models involve triggering an episode of SE in an experimental animal, leading to the eventual development of recurrent spontaneous seizures of limbic origin. Dr. Coulter reviews the distinct patterns of cell loss, circuit rearrangements, alterations in GABAergic function, and other changes that are evident in the epileptic hippocampus of experimental animals. In addition, Dr. Coulter explores the implications of duplicating experiments involving animal models of temporal lobe epilepsy by conducting studies of the limbic tissue of humans with epilepsy.