Introduction

Status epilepticus (SE) is defined as an epileptic seizure lasting more than 30 minutes or intermittent seizures lasting more than 30 minutes during which the patient does not regain consciousness between repeated episodes (47, 48). SE represents a major medical and neurological emergency and can be the basis for fixed and lasting neurologic conditions (34). Approximately 10% of patients with previous epilepsy can be expected to experience SE in their lifetime (48); however, SE can be the first epileptic manifestation in a subgroup of patients.

SE occurs mainly in the early years of life (47), a period in which SE and other epileptic events can be more detrimental to further brain development (100). The main neurologic sequelae of SE reported in the literature include cognitive impairment, brain damage–related deficits, and the long-term development of recurrent seizures.

The occurrence of SE without a previous history of epilepsy is not rare and seems to be a function of age at the time of SE (66). The occurrence of SE as the first ictal episode varies from 50% to 80% in several studies of patients with SE (1, 3, 66, 73), and approximately 20% of these patients develop epilepsy later in life (1, 66). SE has also been a strong predictor of seizure intractability in patients with histories of epileptic seizures refractory to antiepileptic drug treatment (87).

In humans, the causal relation linking SE and the further development of epilepsy seems to be related to the cause of SE and has serious implications for the subsequent treatment of these patients (44). Using a simplistic classification, and taking together studies in both adults and children, idiopathic SE does not seem to increase the risk for epilepsy (83, 85), while symptomatic SE is able to facilitate the development of seizure disorders at some time in the future (4, 5, 13, 47, 50, 70). Retrospective studies in patients with partial epilepsy who underwent surgery for temporal lobe epilepsy showed that approximately 50% of the patients reported a history of “severe” or “prolonged” infantile convulsions (38, 39, 61). In a recent study in which only patients with medial temporal lobe epilepsy were evaluated (those with mass lesions were excluded), 81% of patients gave a history of convulsions during early childhood or infancy. Complicated febrile seizures were described by 94% of the patients from whom detailed descriptions of the febrile seizures were obtained (42). On the other hand, prospective studies have shown that the risk for the development of epilepsy is similar for those presenting with SE and for those presenting with an isolated seizure as the first unprovoked ictal event (47, 49, 82–84). Once again, the etiology of SE seems to be determinant, and substantial evidence indicates that febrile or symptomatic SE (26, 65) are most likely to induce later epilepsy.

A common problem for all clinical studies in addressing the issue of whether neurologic sequelae and chronic epilepsy can be accounted for by a previous episode of SE is that of prior unrecognized brain dysfunction or damage that preceded both the SE and the presumed SE-induced neurologic deficit (58). In temporal lobe epilepsy, for example, it has been suggested that mesial temporal sclerosis may represent a sequela of disturbed embryogenesis (80). Another limitation of human clinical-pathologic studies of patients with refractory epilepsy is that surgically resected specimens give only a frozen picture of an “endpoint” process of epileptogenesis. For these reasons, experimental preparations are particularly useful because they allow the study of SE-induced epileptogenesis starting from a “nonpathologic” brain, and the course of neuropathologic changes can be assessed more dynamically.

Over the past decade, the development of new animal models close to human temporal lobe epilepsy has helped investigators assess the problem of whether SE causes later epilepsy. This chapter considers the experimental evidence hypothesizing that epilepsy with spontaneous recurrent seizures following SE implies that the massive epileptic activation during SE and the subsequent neuronal damage may induce plastic changes that underlie the ensuing epileptogenesis (20).