eMedicine Specialties > Neurology > Neurological Emergencies

Status Epilepticus

Author: Mark Spitz, MD, Professor, Department of Neurology, University of Colorado Health Sciences Center
Coauthor(s): Frank Lum, MD, Instructor, Department of Neurology, University of Colorado Health Sciences Center; Jose E Cavazos, MD, PhD, Assistant Professor, Departments of Medicine (Neurology), Pharmacology, and Physiology, University of Texas Health Science Center at San Antonio; Edward Maa, MD, Epilepsy Fellow, Department of Neurology, University of Colorado Health Science Center
Contributor Information and Disclosures

Updated: Mar 8, 2007

Introduction

Background

Status epilepticus (SE) is a common, life-threatening neurologic disorder. It is essentially an acute, prolonged epileptic crisis. The first description of SE 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, SE 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 SE persisted for 30 minutes. Therefore, the time for the definition was shortened. The working group on SE 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." (Dodson, 1993). More recently, authors suggest that SE 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 (Lowenstein).

Treiman classification

The predominant type of seizure further refines the definition of SE, 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:

• Generalized convulsive SE
• Subtle SE
• Nonconvulsive SE
  • Absence SE
  • Complex partial SE
• Simple partial SE

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

Subtle SE

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

Nonconvulsive SE

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

Absence SE

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 SE 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 SE 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 SE 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 SE: (1) Complex partial SE usually manifests with recurring cycles of 2 separate phases: ictal and interictal. In contrast, absence SE usually occurs as 1 continuous episode of variable intensity. (2) Stereotyped automatisms can be seen in both complex partial and absence SE, though they tend to be richer in complex partial SE than in absence SE. Anxiety, aggression, fear, and irritability may be most common in complex partial SE, but they can be seen in both types. (3) EEG is the best way to differentiate absence SE 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.

• Hyperthermia, which frequently occurs in SE, is caused by motor activity as well as central sympathetic drive. In 90 patients with SE, 75 had hyperthermia with temperatures reaching 42°C (Aminoff, 1980). Hyperthermia has been correlated with poor neurologic outcomes and should be treated aggressively.
• A mild leukocytosis (primarily due to demargination) is common in both blood and cerebrospinal fluid (CSF). In a study of 80 patients, 50 without evidence of infection had WBC count elevations from 12.7-28.8 X 10⁹/L (12,700-28,800 cells/µL). Bands should not be seen. CSF pleocytosis is common but the cell-count elevations are usually modest. In 1 study, only 4 of 65 patients had greater than 30 cells in the CSF (Aminoff, 1980).
• On a receptor level, GABAergic mechanisms fail and seizures become pharmacoresistent (Naylor 2005).

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.

• For generalized convulsive SE, the mortality rate in is high. In the 1998 Veterans Administration (VA) study, the SE Cooperative Study Group reported mortality rates of 27% for overt generalized convulsive SE and 65% for subtle generalized convulsive SE. DeLorenzo et al (1995) reported a mortality rate of 21% in patients with generalized SE, defining mortality as death occurring within 30 days. Aicardi and Chevrie (1970) examined 239 children with generalized convulsive SE that lasted longer than an hour. Twenty-six died, and 88 had permanent neurologic damage (47 of whom had been neurologically intact before the episode).
• According to Hauser (1990), no more than 2% of patients die directly from SE, and severe systemic disease and an acute CNS insult in association with the SE are predictive of a poor outcome.
• In a prospective study of 24 patients who died, 10 had a gradual decrease in mean arterial pressure and/or heart rate. The remaining 14 had no cardiac changes until the time of death. About 90% of patients with cardiac decompensation had a history of many risk factors for atherosclerotic cardiovascular disease, whereas only 30% of those without acute cardiac decompensation had clinically significant risk factors (Boggs, 1998).

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.

Clinical

History

• Generalized convulsive SE is usually easy to diagnose, but an understanding of its evolution from overt convulsions through subtle SE is important. Patients may present with an undramatic clinical picture if they have subtle SE at the time of presentation.
• Treiman and coworkers (1990, 1992, 1995) described the clinical and EEG changes accompanying generalized convulsive SE.
  • The event usually begins with a series of generalized tonic, clonic, or tonic-clonic seizures that often are dramatic.
    • Each seizure is discrete; the motor activity stops abruptly, coincident with the end of the electrographic seizure.
    • Each convulsion is followed by gradual recovery, and then the next seizure occurs.
  • If the condition is not treated or is treated inadequately, SE persists, and the motor manifestations become less dramatic than before.
    • Eventually, only subtle movements (eg, nystagmoid jerks of the eyes or twitching of the shoulder) may be seen, that is, subtle status.
    • If SE continues, all motor activity may stop, though EEG seizures persist (ie, electrical generalized convulsive SE).
• The paradoxical evolution of apparent clinical improvement is important to understand. The clinician unfamiliar with this phenomenon may stop treatment because of the apparent improvement.
  • Treatment should be continued until the EEG seizure activity has resolved completely.
  • In some patients, the underlying encephalopathic insult is so severe that only a few (or no) generalized convulsions occur before subtle convulsive activity develops.
  • Finally, as the patient evolves from generalized tonic-clonic status into subtle and then electrical generalized tonic-clonic SE, the manifestations become less intermittent and more continuous than before.

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

• Many patients who present in convulsive SE do not have a history of seizures.
  • In people with known epilepsy, the most common cause is a change in medication; the change may be directed by physician or due to intentional or unintentional and abrupt cessation (eg, being placed on nothing-by-mouth [NPO] status before surgery). Pharmacologic nonadherence is the most common cause of SE in patients with known epilepsy.
  • Other causes include head trauma, stroke, cardiac arrest, CNS infection, and neoplasm.
• Age significantly affects etiology of SE.
  • In patients younger than 16 years, the most common cause was fever and/or infection (36%); in contrast, this accounted for only 5% in adults (DeLorenzo, 1995).
  • The same study revealed that the most common precipitant in adults was cerebrovascular disease (25%), whereas this factor caused only 3% of pediatric cases.
  • In a more refined study that focused on children, Shinnar et al (1997) found that more than 80% of children younger than 2 years had SE of febrile or acute symptomatic origin, whereas cryptogenic and remote symptomatic causes were more common in older children than in younger children.
• In more recent series of SE, HIV infection and use of illicit drugs were reported with increased frequency.
• Other diagnostic considerations include nonepileptic seizures (NES) and abnormal behaviors.
  • Formerly called psychogenic seizures, NES, have been known to cause continuous, convulsive activity of concern in SE. Although rare, NES must be considered. SE is associated with several behavioral characteristics that help distinguish it from a nonepileptic event. Epileptic seizures usually have the following characteristics:
    • The seizures are stereotyped. If seizures with bizarre behaviors are stereotyped, they are often true epileptic seizures.
    • The convulsive activity is sustained without pauses. Motor activity during a NES often is punctuated by brief periods of rest. Epileptic convulsions are usually sustained without pause until the end of each individual seizure.
    • During an epileptic seizure, behaviors stereotypically and predictably evolve.
    • When seizure activity spreads, it usually follows the organization of the homunculus.
  • Behaviors, such as pelvic thrusting, head turning from side to side, and bizarre vocalizations are usually not seen in epileptic seizures.
    • The exception to this rule is seizure of frontal-lobe onset.
    • Although clinical features are usually helpful, the ultimate test to differentiate between epileptic seizures and NES is EEG.

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