Status Epilepticus

Status epilepticus (SE) is a common, life-threatening neurologic disorder. It is essentially an acute, prolonged epileptic crisis. The first description of Status epilepticus in the medical literature was in a Babylonian text from the first millennium BC. The author recognized the severity of the condition, "If an epilepsy demon falls many times upon him on a given day, he seven times punishes him and possesses him, his life will be spared. If he falls upon him eight times, his life may not be spared" (Wilson, 1990).

In early studies, Status epilepticus was defined by its duration, that is, as continuous seizures occurring for longer than 1 hour. Clinical and animal experiences later showed that pathologic changes and prognostic implications occurred when Status epilepticus persisted for 30 minutes. Therefore, the time for the definition was shortened. The working group on Status epilepticus of the Epilepsy Foundation (formerly the Epilepsy Foundation of America) formulated the current definition: "More than 30 minutes of continuous seizure activity or two or more sequential seizures without full recovery of consciousness between seizures.". More recently, authors suggest that Status epilepticus be defined as any seizure lasting longer than 5 minutes based on natural history data that show typical generalized convulsive seizures that resolve spontaneously after 3-5 minutes.

Treiman classification
The predominant type of seizure further refines the definition of Status epilepticus, and several classification schemes have been proposed. Rona and Luders (2005) have suggested a detailed semiologic classification along 3 axes: (1) the type of brain function predominantly compromised, (2) the body part involved, and (3) The evolution over time. However, Celesia (1976) and Treiman (1994) proposed simpler schemes, which are still more useful than other systems for emergency treatment decisions.
The Treiman classification is used in this article, as follows:

The most frequent and potentially dangerous type of Status epilepticus is generalized convulsive Status epilepticus, which is the subject of most of this article. Nonconvulsive Status epilepticus and partial Status epilepticus are discussed briefly.

Subtle SE
Although subtle Status epilepticus is, by definition, nonconvulsive, it should be distinguished from other nonconvulsive types of Status epilepticus. The prognosis of patients with subtle Status epilepticus, contrary to those with nonconvulsive Status epilepticus, is dismal. It is considered the most severe clinical stage of generalized convulsive Status epilepticus, and is characterized by a dissociation between the electrical brain activity and the predicted motoric response of generalized convulsive Status epilepticus.

Nonconvulsive SE
Nonconvulsive Status epilepticus is divided into 2 categories, absence Status epilepticus and complex partial Status epilepticus. Differentiating these subtypes is important, since they indicate major differences in treatment, etiology, and prognosis.

Absence Status epilepticus
On clinical presentation, a clear change in the level of consciousness is observed. Most patients are not comatose but lethargic and confused, with decreased spontaneity and slow speech.

The ictal electroencephalograph (EEG) during typical absence Status epilepticus demonstrates generalized spike and wave discharges. The frequency may be slower than 3 Hz, and the waveforms (though bilaterally synchronous) are often irregular, poorly formed, and discontinuous, especially in the late stages. In adults and in some children, the apparently bisynchronous EEG discharges may represent complex partial Status epilepticus as opposed to true absence SE.

About 3% of patients with previous absence seizures have absence status (Lennox, 1960). Approximately 10% of adults with childhood-onset absence seizures experience absence SE (Cascino, 1993). About 75% of all cases of absence SE occur before the age of 20 years. When it occurs in adults, the patients are often elderly. The mean age of onset of absence SE in adults is 51 years (Porter, 1983).

Typical absence Status epilepticus that occurs in children or adolescents who have primary or idiopathic generalized epilepsy (which includes absence seizures) readily responds to treatment. In contrast, absence SE in the symptomatic, primary generalized epilepsies (eg, Lennox-Gastaut syndrome) is often more difficult to control.

The following issues should be considered in the differential diagnoses of absence Status epilepticus: (1) Complex partial Status epilepticus usually manifests with recurring cycles of 2 separate phases: ictal and interictal. In contrast, absence Status epilepticus usually occurs as 1 continuous episode of variable intensity. (2) Stereotyped automatisms can be seen in both complex partial and absence Status epilepticus, though they tend to be richer in complex partial Status epilepticus than in absence Status epilepticus. Anxiety, aggression, fear, and irritability may be most common in complex partial Status epilepticus, but they can be seen in both types. (3) EEG is the best way to differentiate absence Status epilepticus from complex partial SE. (4) Other possibilities include a postictal state and encephalopathies from toxic-metabolic causes, drugs, trauma, or infection. Psychiatric causes should be considered.
No deaths or long-term morbidity due to typical absence SE have been reported. Whether absence SE in children with developmental dementia and myoclonic/astatic epilepsy is injurious to the brain is controversial. Differentiating absence SE from other causes is important because many mimics of absence SE can lead to irreversible neuronal damage if they are not aggressively treated.

Benzodiazepines and valproate are the treatments of choice. Valproic acid is available in intravenous (IV) form. The theoretical advantage is that it can be continued long term after the acute episode. Valproate is loaded at a dose of 25 mg/kg IV in a 50-mL solution and infused over 10 minutes. The next dose is given 3 hours later, after which every-6-hour dosing can be started. The drug should never be given intramuscularly (IM). Ethosuximide also can be useful, but is not available in parenteral form.

Complex partial SE
Complex partial SE is rare. Although many cases of prolonged complex partial SE have been described without long-term neurologic sequelae, negative outcomes can occur. No method to differentiate the cases associated with a poor outcome is known.
In patients with isolated complex partial seizures, the origin is usually in the temporal lobe. In contrast, patients with complex partial SE usually have an extratemporal focus. Shorvon (1995) believes that at least 15% of patients with complex partial epilepsy have a history of nonconvulsive SE.
Treatment is the same as that for convulsive SE.

Simple partial SE
By definition, simple partial SE consists of seizures localized to a discrete area of cerebral cortex, and it does not alter consciousness. Because this form is rare, no good studies have been done to determine its incidence.
Diagnosis is primarily based on clinical findings. Because of the relatively small area of cerebral cortical involvement, results of conventional scalp EEG are frequently uncharacteristic of the clinical ictal activity, or they may be normal.
Simple partial SE, in contrast to convulsive SE, is not associated high rates of morbidity or mortality. Outcomes seem to be related to the underlying etiology, the duration of the SE, the age of the patient, and the medical complications, as in convulsive SE. Treatment involves the same drugs and general pharmacologic principles as those used for convulsive SE. However, the relatively low morbidity and mortality rates suggest that aggressive treatment might not be needed. For example, if first-line drugs are ineffective, the clinician may elect not to use a general anesthetic agent to stop simple partial SE.

Pathophysiology
Numerous systemic and primary brain changes occur during convulsive SE. Most evidence suggests that permanent brain damage is caused more by ongoing seizure activity than by systemic factors. Neuropathologic animal studies by Meldrum and Horton (1973) demonstrated that prolonged seizure activity results in pathologic changes after 30 minutes; after 60 minutes, neurons begin to die. These observations parallel findings in human clinical studies, which have shown that the duration of SE is directly correlated with morbidity and mortality rates. The longer the SE persists, the more likely that neurons are damaged by excitatory neurotransmitters. Sustained seizure activity also progressively reduces gamma- aminobutyric acid (GABA) inhibition.

Several important systemic changes are associated with generalized convulsive SE.
In the early stages of SE, prominent elevation in systemic arterial pressure is seen. In a study of 21 patients, White et al (1961) found a mean elevation of systolic pressure of 85 mm Hg and an elevation of diastolic pressure of 42 mm Hg. As SE continues, blood pressures may decrease to levels below their former baseline.
Marked acidosis usually occurs. In a study of 70 spontaneously ventilating patients with SE, 23 had a pH of less than 7.0 (Aminoff, 1980). The acidosis has both a respiratory and a metabolic component, but it usually should not be treated. The induced acidosis is not correlated with the degree of neuronal injury, and acidosis is known to be an anticonvulsant.

Convulsive SE affects not only the mechanical aspects of breathing but also causes pulmonary edema. Many of the medications used to treat SE (specifically benzodiazepines and barbiturates) inhibit respiratory drive both individually and synergistically when given in combination. A patient who has already received a full loading dose of benzodiazepines and who is being given barbiturates for convulsive status epilepticus should be electively intubated before this combination is administered.

FREQUENCY
United States
Extrapolating from a population-based study in Richmond, VA, DeLorenzo et al (1996) estimated that 50,000-200,000 cases occur annually in the United States.

Mortality/Morbidity
Mortality rates related to SE have decreased over the last 60 years, probably in relation to faster diagnosis and more aggressive treatment than before.
The probability of death is closely correlated with age. In prospective population-based studies, DeLorenzo et al (2001) found that the overall mortality rate was 22% for the entire population, 13% for young adults, 38% for the elderly, and >50% for those older than 80 years.

Age
Most cases of SE, up to 70%, occur in children. However, the incidence of SE is highest in the population older than 60 years, at 83 cases per 100,000 population (Waterhouse, 2001).
See also Mortality/Morbidity above and Causes below.

History

Physical
A number of features on physical examination may provide information about the underlying cause of SE. Evidence of track marks might suggest SE secondary to the use of illicit, or street, drugs. Features on neurologic examination can also be helpful. Papilledema, a sign of increased intracranial pressure, suggests a possible mass lesion or brain infection. Lateralized neurologic features, such as increased tone, asymmetric reflexes, or lateralized features of the movement during SE itself, are suggestive of the seizures beginning in a localized region of the brain, and they may suggest a structural brain abnormality.

Causes