Status epilepticus (SE) may be defined classically as seizure activity that lasts longer than 30 minutes or repeated seizures between which the child does not return to the baseline level of consciousness. Some studies have challenged the duration of a seizure before it can be called SE, and progressively shorter times are being used in the definition. In convulsive SE, the child has a prolonged, generalized tonic-clonic seizure or the repetition of such seizures without a return to full consciousness between episodes. In nonconvulsive SE, such as absence status and complex partial status, the clinical presentation is a change in mental state that often manifests as prolonged twilight or semicoma. In epilepsia partialis continua, consciousness is preserved in the presence of continuous, focal motor activity. Most SE episodes in children appear to be generalized convulsive in character. Of those SE episodes beginning with partial seizures, most secondarily generalize. Careful history taking and observation suggest that most (64% of adults and children) SE episodes begin as partial seizures that generalize so the final character is generalized.

The burden of SE is significant. The overall (in adults and children) incidence of SE appears to be 41 to 61 per 100,000, and SE results in an estimated 42,000 deaths (in children and adults) per year in the United States. The age distribution of SE suggests two age peaks: during the first year of life (the time of the highest frequency of SE) and in individuals 60 years old or older. In children, 21% of all cases of SE occur in the first year of life, and 64% occur in the first 5 years. Approximately 12% of patients with newly diagnosed epilepsy have a seizure lasting 30 minutes or longer. Most cases of SE occur in children, and fewer than 25% occur as idiopathic events. The occurrence of SE should prompt a full diagnostic workup. Previously, overall short-term mortality figures as high as 30% were reported, but investigators have reported more recently a mortality rate of 3% to 6% in children. The long-term mortality rate in children has been found to be 7% over the subsequent 10 years. This decrease in mortality rates is the result of faster diagnosis and support, combined with better medical treatment and improved intensive care. Death usually is attributable to the underlying cause of SE rather than to a prolonged seizure. When this information is considered, mortality related to prolonged seizures per se has been reported to occur in as few as 1% to 2% of cases. SE can be associated with significant mortality rates and morbidity that can include epileptic brain damage, neurologic cognitive defects, and continuing recurrent seizures.

Three factors appear to be related to mortality and morbidity: duration of SE, age, and cause. Greater incidence of mortality is observed if SE lasts longer than 1 hour. Prolonged seizures can lead to a series of metabolic derangements that potentially can cause neuronal damage. Tonic-clonic SE that progresses beyond 60 minutes may be associated with severe, permanent brain damage or death. The significance of prolonged or refractory SE, frequently defined as seizures having a duration of longer than 1 hour, has been observed in humans and experimental animals. In animals with experimentally induced seizures lasting less than 1 hour, reversible neuronal injuries are produced. However, if the duration of seizure is greater than 1 hour, neuronal death involving susceptible regions, including the hippocampus, amygdala, thalamus, and middle cerebral cortical layers, is observed. This neuronal death occurs even if a patient is well ventilated and irrespective of metabolic derangements. Neuron-specific enolase, a marker for brain injury, is significantly elevated after prolonged SE. Initial increases in cerebral blood flow and glucose consumption are followed after 60 to 120 minutes of seizure activity by decreased cerebral blood flow but continuing glucose consumption. Excessive enhancement of local metabolic rates may result in selective cell death. Animal studies in adult rats have demonstrated that the hippocampus is particulaly susceptible and may undergo reorganization that leads to a reduction of seizure threshold. One longitudinal quantitative magnetic resonance imaging study in adults demonstrated progressive loss of hippocampal volume in patients with temporal lobe epilepsy, whereas other studies have demonstrated decreases in the ratio of N-acetylaspartic acid (NAA) to choline on magnetic resonance spectroscopy following SE, findings suggesting neuronal loss after seizures has occurred. The initial systemic effects of SE include an increase in plasma catecholamines, an increase in blood pressure, tachycardia, and hyperpyrexia. These effects are self-correcting with the cessation of SE. Late effects that may be less amenable to correction include hypotension, hypoglycemia, acidosis, pulmonary edema, hyperpyrexia, and rhabdomyolysis. They may contribute to significant mortality rates and morbidity. These findings in humans and animal models emphasize the importance of ensuring prompt cessation of SE and of managing and correcting the systemic effects of SE.

In most series, mortality rates are significantly lower in children. One study found that the overall mortality rate was less than 5% in children versus 26% in adults and more than 50% in adults older than 80 years of age. Differences in origin in children versus adults contribute to this observation. SE may occur in the setting of an acute illness, in patients with established epilepsy, or as a first unprovoked seizure. Causes can be classified as idiopathic, remote symptomatic, febrile, acute symptomatic, or associated with progressive encephalopathy. Although 6% to 12% of SE episodes in children represent a first unprovoked seizure, a cause should be investigated.

Infectious processes, toxic or metabolic disorders, and chronic forms of encephalopathy, as well as the sudden withdrawal of antiepileptic drugs, may underlie or precipitate this condition in children. In patients with known epilepsy, antiepileptic drug noncompliance or low levels should be considered. If a child has a known preexistent neurologic or other medical abnormality, complications such as shunt malfunction, central nervous system (CNS) hemorrhage or infection should be considered. In adults, anoxic/hypoxic-ischemic insults account for a significant incidence of mortality; these causes are uncommon in children. Etiologic factors observed more frequently in children include infections of the CNS (meningoencephalitis), metabolic aberrations, febrile seizures, and “idiopathic” epilepsy. These conditions have a lower incidence of associated mortality and morbidity. In children, most
fatalities are associated with acute insult to the CNS or progressive neurologic disorders.