Status Epilepticus


Practice Essentials

Status epilepticus (SE) is a common, life-threatening neurologic disorder that is essentially an acute, prolonged epileptic crisis (see the image below). SE can represent an exacerbation of a preexisting seizure disorder or the initial manifestation of a seizure disorder (epilepsy), or it can represent an insult other than a seizure disorder. Among such insults, SE can occur in the context of an acute cerebral injury, or be due to a systemic process or illness, in a patient with or without a remote cerebral injury. In patients with known epilepsy, the most common cause of SE is a change in medication. Most seizures terminate spontaneously; SE represents a failure of seizure termination.

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Focal status epilepticus. Electroencephalograph (EEG) in a patient with epilepsia partialis continua caused by Rasmussen encephalitis before hemispher....

Signs and symptoms

By clinical history, nonmotor simple partial status epilepticus involves subjective sensory disturbances, including the following:

Epilepsy partialis continua, or focal status epilepticus of the motor cortex, may occur in various contexts, with some authors subdividing it into type I (nonprogressive) and type II (progressive).

Type I epilepsy partialis continua features include the following:

Type II epilepsy partialis continua features include the following:

Type I complex partial status epilepticus refers to recurrent, recognizable complex partial seizures without recovery between seizures. Type II represents continuous, ongoing complex partial seizure activity. The sequence of constellation of features in complex partial status epilepticus is as follows:

  1. Serious medical, surgical, or neurologic illness
  2. A brief convulsive seizure
  3. Protracted stupor with fluctuating neurologic findings, subtle nystagmus, or focal twitching

In addition, complex partial status epilepticus may have the following characteristics:

See Clinical Presentation for more detail.


Examination for status epilepticus includes the following:


The Luders and Rona semiologic classification consists of 3 axes, as follows[1] :

The Treiman classification is as follows:

The International League Against Epilepsy (ILAE) classification[2] consists of 4 axes, as follows:


The workup for potential status epilepticus is similar to that for any self-limited seizure but is done more expeditiously to confirm the diagnosis and to abort or limit the seizures.

Stat laboratory studies that should be obtained include the following:

Other tests that may be appropriate depending on the clinical setting include the following:

Imaging studies

Imaging modalities used to evaluate status epilepticus may include the following:


If a central nervous system infection is suspected, consider performing a lumbar puncture (after neuroimaging to rule out potential cerebral herniation).

See Workup for more detail.


Aggressive treatment is necessary for status epileptics. Clinicians should not wait for blood level results before administering a loading dose of phenytoin, regardless of whether the patient is already taking phenytoin.


Most patients with status epilepticus who are treated aggressively with a benzodiazepine, fosphenytoin, and/or phenobarbital experience complete cessation of their seizures. If status epilepticus does not stop, general anesthesia is indicated.

Medications used in the treatment of status epilepticus include the following:

Supportive therapy

Supportive care in patients with status epilepticus includes the following:


Surgical intervention for status epilepticus is a last resort and rarely performed.[5, 6, 7, 8] Operative procedures depend on the etiology of this condition and may consist of ablating a structural abnormality, hemispherectomy, subpial resection, or placement of a vagus nerve stimulator.

See Treatment and Medication for more detail.


Status epilepticus (SE) is a common, life-threatening neurologic disorder. It is essentially an acute, prolonged epileptic crisis.[2]

Etiologically, SE can be imperfectly divided into 3 groups. SE can represent an exacerbation of a pre-existing seizure disorder, the initial manifestation of a seizure disorder, or an insult other than a seizure disorder (see Etiology). In patients with known epilepsy, the most common cause is a change in medication.

Recognition of SE may be easy or difficult. SE in the patient with sequential, generalized major motor convulsions is obvious; the patient with nonconvulsive or subtle SE presents a diagnostic dilemma (see Differentials).

Aggressive treatment is necessary. Maintenance of vital signs, including respiratory function, is of major importance. Early treatment measures are performed in concert with diagnostic studies (see Treatment).[9, 10] Treatment guidelines for status epilepticus have been proposed[11]  and have been confirmed in updated reviews. However, there is more to learn about the anticonvulsant of choice in cases of prolonged or refractory SE.

Go to Epilepsy and Seizures for an overview of this topic. Also see Pediatric Status Epilepticus.

Historical aspects

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."[12]

Wolf et al described a case of probable 3-day absence stupor documented in Austria in 1501.[13] Several descendants of the affected person in this historical case have been shown to have a primary idiopathic epileptic syndrome.

Definition of status epilepticus

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."[14]

Many believe that a shorter period of seizure activity causes neuronal injury and that seizure self-termination is unlikely after 5 minutes.[15] Consequently, Lowenstein and others have suggested a duration of longer than 5 minutes as part of the a criterion for SE, if the seizure type is one in which typical generalized convulsive seizures resolve spontaneously after 3-5 minutes.[16] The Epilepsy Foundation working group recommended that emergency department physicians treat seizures as SE if seizure activity has continued for more than 10 minutes.[14]

Classification of status epilepticus

The term status epilepticus may be used to describe continuing seizure of any type.

The predominant type of seizure further refines the definition of SE, and several classification schemes have been proposed.

Categorization of SE cases is no simple matter because they often exhibit characteristics of both focal and generalized processes. Considerable literature has been devoted to this question over the last 30 years, beginning with Geier et al in 1976,[17] Ellis and Lee in 1978,[18] and Niedermeyer et al in 1979.[19]

Several investigators have suggested that the bulk of these indeterminate examples are instances of focal onset episodes of status that have secondarily generalized, in the same manner as many focal onset seizures. EEGs of patients with these conditions fail to capture the onset of status; therefore, this critical element is lost.

Some of these instances are characterized by diffuse, slow (< 3 Hz) spike-and-wave activity, albeit with focal predominance. In many instances, interictal recordings demonstrate focal discharges that further implicate a focal process. Whether such cases are best grouped with focal status remains controversial.

Luders and Rona[1] 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. Celesia[20] and Treiman[21] proposed simpler schemes, which are more useful than other systems for emergency treatment decisions.

The Treiman classification is as follows:

Generalized convulsive status epilepticus

Generalized convulsive SE is the most frequent and potentially dangerous type of SE. Generalized refers to the abnormal excessive cortical electrical activity, while convulsive refers to the motor activity of a seizure.

Subtle status epilepticus

Subtle SE consists of electrical seizure activity in the brain that endures when the associated motor responses are fragmentary or even absent.

The terminology is confusing, since subtle SE is sometimes designated a type of nonconvulsive SE (NCSE). Although subtle SE is, by definition, nonconvulsive, it should be distinguished from other NCSE. Subtle SE is considered the most severe clinical stage of generalized convulsive SE and patients with subtle SE, in contrast to that of those with NCSE, have a dismal prognosis.

Nonconvulsive status epilepticus

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.

In one review,[10] NCSE has been further subdivided according to the age of occurrence, as follows:

Several epileptic syndromes, such as electrical status epilepticus in slow-wave sleep (ESES), would be classified under the "NCSE only in childhood" category.

Absence status epilepticus

On clinical presentation, a clear change in the level of consciousness is observed in patients with absence SE. Most patients are not comatose but are lethargic and confused, with decreased spontaneity and slow speech. Absence SE is also known as absence stupor because of the apparent state of low alertness.

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 2.6% of patients with absence seizures have had an episode of absence SE earlier in their lives.[22] Approximately 10% of adults with childhood-onset absence seizures experience absence SE.[23] 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.

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.

Four issues should be considered in the differential diagnoses of absence SE. First, 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.

Second, 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.

Third, EEG is the best way to differentiate absence SE from complex partial SE.

Fourth, 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.

Complex partial status epilepticus

Complex partial SE is rare. Although many cases of prolonged complex partial SE without long-term neurologic sequelae have been described, negative outcomes can occur. No criteria for differentiating the cases associated with a poor outcome are known.

Complex partial SE that arises in the limbic cortex (eg, mesial temporal lobe) causes signs and symptoms such as staring, unresponsiveness, automatisms, atypical anxiety, rising abdominal symptoms, déjà vu, or more profound stupor. Complex partial SE of frontal-lobe origin may produce clinical symptoms indistinguishable from cases of temporal-lobe origin.

While isolated complex partial seizures usually originate in the temporal lobe, complex partial SE usually has an extratemporal focus. Shorvon believes that at least 15% of patients with complex partial epilepsy have a history of nonconvulsive SE.[24]

Simple partial status epilepticus

By definition, simple partial SE consists of seizures that are localized to a discrete area of cerebral cortex and produce no alteration in consciousness. Because this form of epilepsy is rare, no good studies have been done to determine its incidence.

Focal SE can arise in any region of the cortex. When motor cortex is affected, the condition is termed epilepsia partialis continua (EPC), which characteristically involves repetitive, often rhythmic, unilateral focal twitching of the limbs and/or face, usually with preservation of consciousness. This sparing of consciousness subcategorizes EPC as a form of simple partial SE.

Other regions of cortex similarly may generate focal SE. These cases are characterized by predictable phenotypes depending on the function of the particular region involved. For example, episodes of focal SE involving primary sensory cortex are expected to be associated with focal sensory symptoms, and occipital focal SE causes focal visual symptoms (eg, flashing spots of light, colorful visual hallucinations). Focal SE of language cortex typically causes aphasia, termed ictal aphasia.

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.

In contrast to convulsive SE, simple partial SE is not associated with 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.


On a neurochemical level, seizures are sustained by excess excitation and reduced inhibition. Glutamate is the most common excitatory neurotransmitter and the NMDA (N-methyl-D-aspartate) receptor subtype is involved. Gamma-aminobutyric acid (GABA) is the most common inhibitory neurotransmitter. Failure of inhibitory processes is increasingly thought to be the major mechanism leading to status epilepticus.

Most seizures terminate spontaneously. Which processes are involved in seizure termination and why or how these processes fail in status epilepticus are active areas of inquiry.

Significant physiologic changes accompany generalized convulsive SE. Many of these systemic responses (eg, tachycardia, cardiac arrhythmias, hyperglycemia) are thought to result from the catecholamine surge that accompanies the seizures.

In the early stages of SE, prominent elevation in systemic arterial pressure is seen. In a study of 21 patients, White et al found a mean elevation of systolic pressure of 85 mm Hg and an elevation of diastolic pressure of 42 mm Hg.[25] As SE continues, blood pressures may decrease to levels below their former baseline.

Body temperature may increase in patients, as a result of the vigorous muscle activity and central sympathetic drive that accompany generalized convulsive SE (but, of course, infectious etiologies also must be considered in febrile patients). In a study by Aminoff and Simon, 75 of 90 patients with SE had hyperthermia, with temperatures reaching 42°C.[26] Hyperthermia has been correlated with poor neurologic outcomes and should be treated aggressively.

Marked acidosis usually occurs. In a study of 70 spontaneously ventilating patients with SE, 23 had a pH of less than 7.0.[26] The acidosis has both a respiratory and a metabolic component. The acidosis usually should not be treated; it does not correlate with the degree of neuronal injury, and acidosis is known to have an anticonvulsant effect. The acidosis resolves with termination of the seizure.

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 one study, only 4 of 65 patients had greater than 30 cells in the CSF.[26]

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 with convulsive SE who has already received a full loading dose of benzodiazepines should be electively intubated before being given.

Cerebral metabolic demand increases greatly with generalize convulsive SE. However, cerebral blood flow and oxygenation are thought to be preserved or even elevated early in the course.

Research with paralyzed and artificially ventilated animals concluded that neuronal loss after focal or generalized SE is linked to the abnormal neuronal discharges and not simply to the systemic effects of the seizures. For example, Meldrum and Horton demonstrated that prolonged seizure activity results in pathologic changes after 30 minutes; after 60 minutes, neurons begin to die.[27] The hippocampus seems especially vulnerable to damage by this mechanism.

These observations parallel findings in human clinical studies, which have shown that the duration of SE correlates directly with morbidity and mortality rates. The longer the SE persists, the more likely that neurons will be damaged by excitatory neurotransmitters. Sustained seizure activity also progressively reduces GABA inhibition. On a receptor level, GABAergic mechanisms fail and seizures become pharmacoresistent.[28]

Neuronal death probably results from the inability to handle large increases in intracellular calcium brought about by prolonged exposure to excitatory neurotransmitters. However, changes in gene expression that are induced by SE result in alterations in the number or subunit composition of ion channels, receptors, cell metabolism, and neuronal connectivity.[10, 29]

The observation that prior history of epilepsy is associated with a better prognosis might be related to the fact that brief seizures might result in upregulation of neuroprotective mechanisms. This may serve as a form of adaptive tolerance.[10]

Alterations in the availability of existing receptors during SE might occur relatively quickly. This might contribute to responsiveness to benzodiazepines.[30]

SE in the developing brain seems to have lesser consequences despite a greater susceptibility to seizures.[31] This might be due to better adaptive mechanisms to cope with excitotoxicity.


Etiologically, SE can be imperfectly divided into 3 groups. SE can represent an exacerbation of a pre-existing seizure disorder, the initial manifestation of a seizure disorder, or an insult other than a seizure disorder.

In patients with known epilepsy, the most common cause is a change in medication; the change may be directed by physician (eg, placing the patient on nothing-by-mouth [NPO] status before surgery) or may be due to abrupt cessation on the patient’s part, whether intentional or unintentional.

A myriad of other conditions may precipitate SE, including toxic or metabolic causes and anything that might produce cortical structural damage, as follows:

In more recent series of SE, HIV infection and use of illicit drugs were reported with increased frequency.

Causes of SE vary significantly with age. DeLorenzo et al reported that in patients younger than 16 years, the most common cause was fever and/or infection (36%); in contrast, this accounted for only 5% of SE in adults.[32] In adults, the most common precipitant 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 found that in children younger than 2 years with SE, more than 80% of cases were of febrile or acute symptomatic origin.[33] In contrast, cryptogenic and remote symptomatic causes were more common in older children than in younger children.


Extrapolating from a population-based study in Richmond, VA, DeLorenzo et al estimated that 50,000-200,000 cases of SE occur annually in the United States.[34] In 1994, Shorvon estimated that cases of nonconvulsive SE occurred at an annual rate of 15-20 per 100,000 population, of which only 3-4 were clearly instances of complex partial SE.[35] This finding is in accordance with Celesia's early estimates in 1976[20]  and holds up in modern epidemiological studies.[36]  Mortality rate from status epilepticus varies by etiology, clinical and electrographic features, and age, but ranges from 12–28%.[37]  

True absence status (ie, generalized, ongoing, 3-Hz spike-and-wave activity) may account for fewer patients with nonconvulsive SE than previously believed. Nonconvulsive SE, and by extension focal SE, is believed to be frequently overlooked.

Epilepsy partialis continua is rare by comparison, even in pediatric epilepsy referral centers, though it is overwhelmingly a syndrome of children. In the author's series of 41 patients with focal SE who were referred from a tertiary referral center that treated adults over 15 years, only 3 had epilepsy partialis continua.

Sex and race in status epilepticus

SE affects males and females equally. SE is not believed to have a predilection for any particular racial or ethnic group.

Age-related differences in incidence

The age frequency of SE probably follows the same curve as that of the incidence of seizures generally. This J -shaped curve reflects the high frequency in the young and the increasing incidence with advancing age. Up to 70% of SE cases occur in children. However, the incidence of SE is highest in the population older than 60 years, at 83 cases per 100,000 population.[38]

Focal status epilepticus probably obeys a similar age relationship, though the data are understandably limited. In the author's study of adults with focal SE, the age range was 15-91 years with a mean age of 62 years. Most available studies are retrospective; prospective data on the age-related incidence of focal SE are still lacking.


Prognosis is related most strongly to the underlying process causing SE. For example, if meningitis is the etiology, the course of that disease dictates outcome. Patients with SE from anticonvulsant irregularity or those with alcohol-related seizures generally have a favorable prognosis if treatment is commenced rapidly and complications are prevented.

A multivariate analysis by Drislane et al identified presentation in coma and SE caused by anoxia/hypoxia as indicators of a poor prognosis.[39] However, in a small case series of cardiac arrest patients who developed postanoxic SE, predictors of a favorable outcome included preserved brainstem reactions, cortical somatosensory evoked potentials, and EEG reactivity.[40] These patients were treated with therapeutic hypothermia.

The more advanced the stage of SE, the less favorable the response to treatment. In the Veterans Affairs Status Epilepticus Cooperative study, 56% of patients who were first seen with overt, generalized convulsive SE responded to initial treatment. Only 15% of the individuals with subtle, generalized convulsive SE responded to initial treatment.[41] Treating nonconvulsive SE is urgent because longer duration of this condition correlates with a worse prognosis.[42]

Mortality from status epilepticus

Mortality rates related to SE have decreased over the last 60 years, probably in relation to faster diagnosis and more aggressive treatment. The probability of death is closely correlated with age. In prospective population-based studies, DeLorenzo et al found mortality rates of 13% for young adults, 38% for the elderly, and >50% for those older than 80 years.[34]

In 1998, the Veterans Affairs Status Epilepticus Cooperative Study Group reported mortality rates of 27% for overt generalized convulsive SE and 65% for subtle generalized convulsive SE.[41] DeLorenzo et al reported a mortality rate of 21% in patients with generalized SE, defining mortality as death occurring within 30 days.[32]

Aicardi and Chevrie examined 239 children with generalized convulsive SE that lasted longer than an hour; 26 died, and 88 had permanent neurologic damage (47 of whom had been neurologically intact before the episode).[43]

Death most often is related to an underlying cause of brain injury.[44] According to Hauser, no more than 2% of patients die directly from SE.[45]

In a prospective study of 24 SE 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.[46]

Prognosis in nonconvulsive status epilepticus

Models of partial epilepsy have demonstrated profound and long-lasting neurologic changes after experimental SE. In human studies, occasional patients have reportedly had profound memory and behavioral changes after episodes of complex partial SE. In some reports, the duration of the status was linked with these lasting memory deficits. However, most cohorts of patients with nonconvulsive did not undergo prestatus and poststatus neuropsychologic testing to permit direct comparison.

Krumholz and colleagues described 7 cases of serious morbidity and 3 deaths in patients with complex partial SE.[47] The study has been criticized because many of the patients had severe neurologic or medical insults in addition to status, which may have been pivotal in the genesis of their residual neurologic deficits. Nonetheless, 3 patients had prolonged memory and/or other cognitive deficits, possibly provoked by their SE.

Data from available studies suggest that nonconvulsive SE alone usually does not cause irreversible neurologic injury, though rare instances may occur. However, nonconvulsive SE appears so often in the company of serious neurologic or medical injury that clinically significant morbidity and mortality are common.

Patients with focal motor SE (ie, epilepsy partialis continua) have a particularly poor prognosis if they are untreated in the setting of Rasmussen encephalitis.

In the author's series of patients with focal SE, patients with new neurologic insults (eg, acute stroke) or those whose SE occurred postoperatively had a mortality rate of 67%. Those with a history of epilepsy did well overall. In this group, SE was usually precipitated by a new toxic and/or metabolic or other medical aggravator and had little to no lasting neurologic aftereffects.

The author compared patients with recurrent seizures with those who had ongoing, continuous seizure activity. No difference in outcome was observed between the subgroups of focal SE.

Patient Education

Reinforcement of compliance with prescribed medications at routine clinical encounters may be helpful in preventing SE. For patient education information, see the Brain and Nervous System Center, as well as Seizures Emergencies and Epilepsy.


Generalized convulsive status epilepticus (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[48, 49, 50] described the clinical and electroencephalographic (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 SE. 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 SE into subtle and then electrical generalized tonic-clonic SE, the manifestations become less intermittent and more continuous than before.

Persons accompanying the patient may be able to provide important information. A history of epilepsy frequently is elicited. Among patients with established epilepsy, noncompliance with medications is the rule rather than the exception. In roughly one third of cases, status epilepticus is the initial presentation of a seizure disorder.

In those without epilepsy, the history may suggest associated injuries, such as a fall or involvement in a motor vehicle accident. A history of systemic or CNS neoplasms, infections, metabolic disorders, toxic ingestions, alcohol cessation, and many other conditions may give clues to the precipitating cause of seizures.

Nonmotor simple partial status epilepticus

By clinical history, nonmotor simple partial SE involves subjective sensory disturbances, including the following:

These focal phenomena with preserved consciousness are not uncommon as self-limited seizures, and they most often occur as auras associated with complex partial and secondarily generalized seizures. However, in rare cases, they persist in an ongoing or recurrent fashion that fulfills the criteria for focal SE.

Because these particular forms of SE involve sensory disturbances with preserved consciousness, no helpful clinical signs are associated with them. The gradual evolution of nonmotor simple partial SE into overt complex partial or generalized SE helps provide clinically apparent confirmation of these rare forms of FSE.

In rare instances, a focal or generalized seizure may precede such an episode of SE. However, long-lasting focal sensory disturbances after convulsive seizures often represent a transient postictal phenomenon rather than focal SE. EEG often helps in making this clinical distinction.

Epilepsy partialis continua

Focal SE of the motor cortex, known as epilepsy partialis continua, may occur in various contexts. Some authors subdivide epilepsy partialis continua into type I (nonprogressive) and type II (progressive).

Type I epilepsy partialis continua features intermittent, semirhythmic, and involuntary twitching involving a discrete subset of muscles. Although any group of muscles may exhibit these features, it is observed most commonly in the face and ipsilateral distal hand musculature. Myoclonus of this variety may evolve into a partial or generalized convulsion.

Many other attendant historical symptoms may be present, depending on the nature of the focal insult. These symptoms heavily influence the ultimate clinical outcome in this setting.

Type I classically occurs after acute insults to the sensorimotor cortex. These insults may be infectious (eg, Russian spring-summer encephalitis), neoplastic, immune mediated, structural, traumatic, metabolic, or vascular.

Nonketotic hyperglycemic diabetes, particularly in association with hyponatremia, occasionally causes epilepsy partialis continua, often in patients with a preexisting focal CNS lesion (eg, stroke). Epilepsy partialis continua may be a feature of mitochondrial disorders such as mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) and myoclonic epilepsy with ragged-red fiber disease (MERRF).[51]

The syndrome of childhood epilepsy with rolandic spikes (ie, benign rolandic epilepsy) may occasionally involve epilepsy partialis continua. Patients have prolonged speech arrest, facial twitching, and sialorrhea, in episodes that are clinically similar to those of the syndrome, though more prolonged than usual.

Type II epilepsy partialis continua, the progressive form, is usually linked with Rasmussen encephalitis, a unique and rare epilepsy syndrome that predominantly affects children. Children with Rasmussen encephalitis historically had a variety of seizures, including simple and complex partial seizures with occasional secondary generalization; epilepsy partialis continua is yet another seizure type these patients have.

In addition to seizures, patients have gradual loss of unilateral function, and in parallel, imaging studies show focal or unilateral hemispheric atrophy. The typical age of onset is 5-10 years, though the range is broad, and rare cases are reported in adults.

Intellectual skills may become impaired to various degrees, and language skills may be affected, depending on the age of onset and the laterality of the process. Pathologic findings include cortical atrophy, reactive gliosis including microglial nodules, and some perivascular lymphocytosis, occasionally with necrotic features.

Although the subject of intense scrutiny, the etiology of Rasmussen encephalitis remains unknown. Numerous attempts to identify a consistent viral pathogen have failed. An autoimmune hypothesis based on a glutamate receptor subtype has been suggested, but this remains unproven in humans.

Complex partial status epilepticus

Complex partial SE often begins with a history of recurrent or prolonged simple partial seizures, or it may follow or precede a generalized convulsive seizure. Patients are often confused and have variable responsiveness. Memory of the event is usually impaired. Behavior may fluctuate or be bizarre.

Many patients have clinical automatisms, as with typical complex partial seizures, including repetitive lip-smacking, fumbling, or swallowing movements. Subtle nystagmus may be observed.

The range of confusion can be great, with some patients having mildly diminished responsiveness and with others in frank stupor or in a catatonic state. Aphasia and other localizing signs and symptoms (eg, focal weakness) may accompany complex partial SE.

Type I complex partial SE refers to recurrent, recognizable complex partial seizures without recovery between seizures. Type II represents continuous, ongoing complex partial seizure activity. Clinical cycling may be most indicative of type I, though this clinical inference may not be highly reliable.

Clinically distinguishing complex partial SE from absence (generalized) nonconvulsive SE may be problematic; an EEG showing focal or lateralized features may be helpful. EEG is a particularly valuable tool in this setting because treatment options may partly depend on this distinction. Knowledge of the patient's interictal EEG and clinical syndrome, when possible, may also help make this important clinical distinction.

As in generalized SE, patients with focal SE often have an established history of epilepsy, and subtherapeutic anticonvulsant levels or other new metabolic or systemic stressors may be implicated in the expression of FSE. Alternatively, acute or chronic focal cerebral injuries of various kinds (especially, vascular insults) may provide the substrate for new-onset focal seizures and SE.

Refractory and super-refractory status epilepticus

Refractory status epilepticus is defined as recurrent seizures in spite of treatment with two anticonvulsants (including a benzodiazepine); super-refractory status epilepticus is defined as recurrent seizures in spite of anticonvulsants and anaesthetic therapy beyond the 24-hour mark.[52] Mechanisms behind these two conditions are thought to involve internalization of GABA receptors and increase in the number of glutamate receptors on the cell surface, among other factors. Also at the cellular level, refractory and super-refractory status epilepticus is characterized by a change in the ion concentration surrounding the cell; mitochondrial dysfunction; changes in the vasculature and opening of the blood-brain barrier.[53] These changes, along with excitotoxicity (glutamatergic excess), contribute to cerebral injury with status epilepticus—and in particular, refractory and super-refractory status epilepticus.

Physical Examination

Generalized convulsive status epilepticus often is recognizable to the clinician at the bedside when typical rhythmic tonic-clonic activity is present. Consciousness is impaired. Rarely, status epilepticus may present as a persistent tonic seizure.

A number of features on physical examination may provide information about the underlying cause of SE. Needle 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.

Rapid repeated extensor or flexor posturing may be confused with convulsive activity by a casual observer. Repetitive myoclonus in a comatose patient following diffuse hypoxic brain injury may simulate generalized seizures. The physiologic origin of the myoclonic jerks may not be cortical. The myoclonus usually is limited in duration to several hours.

Suspect subtle status epilepticus or transformed status epilepticus in any patient who does not have improving level of consciousness within 20-30 minutes of cessation of generalized seizure activity. The motor expression of the abnormal cortical electrical activity may change so that a flicker of an eyelid or twitch of an extremity is the only sign of the ongoing generalized electrical discharges. Motor activity may be absent even in the presence of ongoing electrical status epilepticus.

Associated injuries that may be present in patients with seizures include tongue lacerations (typically lateral), shoulder dislocations, head trauma, and facial trauma.


Complications of status epilepticus are many. Systemic complications include the following:

Approach Considerations

The approach to potential status epilepticus (SE) should be conducted similarly to that for any self-limited seizure, but clearly in an expeditious fashion. Prompt diagnosis facilitates medical intervention to abort or limit SE.

The workup should include stat laboratory work. Fever should prompt a thorough search for sources of infection, with blood culture and urinalysis. Lumbar puncture (after neuroimaging to rule out potential cerebral herniation) is indicated if a CNS infection is suspected. Fever, stiff neck, headache, and photophobia are signs and symptoms that may suggest such infection.

The risk of lasting morbidity or mortality is usually lower with focal SE than with generalized convulsive SE. This affords extra opportunities to pursue tests that can confirm the diagnosis, reveal associated etiologic processes (some of which may be morbid), and provide insight into fruitful treatment strategies.

Simple partial status epilepticus/epilepsy partialis continua

In patients with preserved consciousness and sensory or motor symptoms compatible with focal SE, a history of epilepsy may help focus the workup tremendously. In particular, if seizures in SE are the same as previous focal seizures, the patient is not apt to have a newly acquired CNS lesion.

Instead, the SE episode may reflect subtherapeutic anticonvulsant levels, new toxic or metabolic derangements, intercurrent infection (usually outside of the CNS), recent stress, or sleep deprivation, as in any breakthrough seizure in a patient with known epilepsy. In some situations, no new precipitant can be found, though one should be sought aggressively.

In patients without a previous diagnosis of epilepsy, an aggressive search for a new or preexistent focal CNS lesion is paramount. Because patients with established epilepsy are not immune to new CNS lesions, a search for a new CNS process should be considered if their established epileptic focus does not seem to account for the ongoing SE.

Search for a new focal lesion early because certain acute processes pose high rates of morbidity and may require treatment independent of the SE. For example, quickly finding a new cardioembolic stroke due to atrial fibrillation is pivotal because this condition must be dealt with swiftly, in parallel with focal SE, if both apply.

Complex partial status epilepticus

The approach to a patient with a confusional or stuporous picture that suggests complex partial SE (CPSE) is similar to the approach in simple partial SE and epilepsy partialis continua. The first pivotal step is including CPSE in the differential diagnosis. Numerous authors report that CPSE is often overlooked and that correct diagnosis is often considerably delayed. This problem stems from the close clinical overlap between CPSE and other, more common encephalopathies in hospitalized patients.

When CPSE occurs in the setting of previous epilepsy, search for new medical stressors (eg, toxins, metabolic derangements, alcohol, proconvulsant medications, subtherapeutic anticonvulsants, intercurrent illness, hypoxemia) that may trigger its expression.[59]

Another common clinical scenario leading to CPSE, especially in patients without previous epilepsy, involves overt yet self-limited generalized convulsion, often in the context of a new serious medical illness, after surgery, or after an acute CNS process. In this familiar scenario, the patient does not have the expected timely recovery to neurologic baseline after the brief convulsion.

Anticonvulsants are often started in response to the overt seizure, though frequently with inconsistent attention to blood levels. The patient's persistent stupor is initially misattributed to the concomitant medical illness or a diminished recuperative ability (in older patients) to the newly acquired CNS process. Potentially diagnostic EEGs may be wrongly deferred after that new-onset convulsion in this setting because the overt seizure is long over and the diagnosis of CPSE is overlooked.

Numerous authors have highlighted the frequent association of CPSE with previous or late generalized convulsive seizures. This constellation of features includes the following sequence:

  1. Serious medical, surgical, or neurological illness
  2. A brief convulsive seizure
  3. Protracted stupor with fluctuating neurologic findings, subtle nystagmus, or focal twitching

The presence of these elements should prompt consideration of CPSE and expedient EEG evaluation. After EEG results confirm CPSE, the workup proceeds as outlined for simple partial status epilepticus/epilepsy partialis continua.

Laboratory Studies

The presence of SE should prompt a search for its etiology, and in particular for potentially reversible conditions. Clinical information should guide the ordering of laboratory tests.

Laboratory studies that should be obtained on an emergency basis include the following:

Emergent glucose assessment is particularly important because both hyperglycemia and hypoglycemia can be associated with SE. Rapid turnaround of anticonvulsant drug levels may be particularly helpful in guiding treatment choices in patients with well-established epilepsy who on long-term therapy.

Arterial Blood Gases

Arterial blood gas (ABG) measurement may be useful to monitor oxygenation and ventilation efficacy and to discover any unexpected acid-base abnormalities. An episode of generalized seizures will typically result in a metabolic acidosis, but this should correct rapidly following seizure cessation as the lactate generated by vigorous muscle contractions is metabolized. Profound metabolic acidosis and continuing seizures might raise the possibility of isoniazid poisoning (see Isoniazid Toxicity in Emergency Medicine).


EEG is the criterion standard for diagnosing EEG, and some authors believe that EEG should be a routine part of management of SE.[3, 4] Nevertheless, EEG is rarely available in the acute-care setting; normally, it is obtained through neurologic consultation. When EEG is unavailable for the acute workup, presumptive treatment strategies must occasionally be started before EEG confirmation becomes available.

Because of the possibility of subtle SE, an EEG should be strongly considered if the patient is not starting to awaken within 20-30 minutes after seizure cessation. High clinical suspicion for continued unresponsiveness from this subtle SE is necessary, along with timely consultations and occasional insistence on obtaining EEG.

Several groups have shown that electrical SE often persists when clinical seizure activity has ceased.[41, 60] DeLorenzo et al prospectively examined 64 patients who clinically appeared to have controlled SE. These patients were comatose and had no overt clinical signs of convulsive activity. However, EEG demonstrated persistent seizures in 48%, and 14% of these patients had nonconvulsive SE (predominantly of the complex partial type).[60]

EEG is often helpful in solidifying the diagnosis of focal SE, and it may be crucial in differentiating focal SE from some of the other mimics. Simple partial seizure activity occasionally lacks an EEG correlate. The absence of ongoing epileptiform activity does not completely exclude simple partial SE. However, absence of an EEG correlate should at least call the diagnosis of focal SE into question. Many patients with EPC have a repetitive discharge on EEG that is time-locked to the motor activity.

Because recurring complex partial seizures without interval neurologic recovery constitutes CPSE, a single EEG lacking ongoing partial seizure activity does not entirely preclude the diagnosis; the study may have been performed between seizures. Repeated or prolonged EEG recordings may be crucial in confirming CPSE

Although not always required for the diagnosis of status, EEG can be extremely useful to validate the diagnosis and often helps in categorizing the type of status. See the images below.

View Image

Focal status epilepticus. Electroencephalograph (EEG) in a patient with epilepsia partialis continua caused by Rasmussen encephalitis before hemispher....

View Image

Focal status epilepticus. Electroencephalograph (EEG) in a 35-year-old patient with a history of intractable partial epilepsy, in complex partial stat....

View Image

Focal status epilepticus. This electroencephalographic (EEG) fragment was obtained at approximately 12:39 on May 10, 18 hours after the onset of compl....

Computed Tomography

CT scanning of the brain is often helpful in evaluating for a structural lesion (eg, brain tumor, infarction, abscess, hemorrhage) that may underlie SE. Noncontrast CT is the imaging procedure of choice for emergency department patients with SE. However, a neuroimaging study should never be allowed to impede rapid and aggressive treatment of the disorder. Imaging is often deferred if the patient is known to have epilepsy and the seizure pattern is not unusual for the individual.

Magnetic Resonance Imaging

Brain MRI is rarely indicated in the acute phase of generalized convulsive SE. Although MRI provides more information than CT, it is more time consuming, and the additional information rarely affects immediate treatment and evaluation.

In contrast, in a patient with simple partial SE that does not match previous seizures, the search for an epileptic focus should include brain imaging, preferably with MRI (or CT if MRI is unavailable) to look for a new lesion (eg, new stroke, mass lesion). Currently, many centers offer advanced MRI, such as diffusion-weighted, perfusion, and susceptibility-weighted imaging.[61] These newer methods can be particularly helpful in identifying acute cerebral ischemia.

Nevertheless, MRIs may be problematic in focal SE because the SE itself can cause a wide range of MRI abnormalities, many of which are transient. Repeat imaging over weeks to months may be helpful to clarify their interpretation.

Chest Radiography

Chest radiography may be used to assess for aspiration or endotracheal tube positioning.

If clinically indicated, other plain radiographs may be useful to assess fractures or dislocations.

Lumbar Puncture

If CNS infection is in the differential diagnosis, consider a lumbar puncture (after appropriate head imaging to ensure safety).

Initiate antibiotic therapy if CNS or systemic infection is strongly suspected.

Approach Considerations

Both generalized tonic-clonic status epilepticus (SE) and subtle SE must be treated aggressively. Maintenance of vital signs, including respiratory function, is of major importance. Any indication of respiratory insufficiency should be addressed by intubation.

Early treatment measures are performed in concert with diagnostic studies. The treating physician should not wait for a blood level to return from a laboratory test before giving the patient a loading dose of phenytoin. The same protocol should be followed regardless of whether the patient is already taking phenytoin. Assume that the patient is noncompliant because this is the most common cause of SE in patients with known epilepsy.

Even if the patient has been compliant and even if phenytoin levels were already in the therapeutic range (10-20 µg/mL), data suggest that 20-30 µg/mL is more effective than 10-20 µg/mL in stopping seizures.

High doses can cause ataxia and sedation. Because the patient is likely to be hospitalized after the SE is controlled, these adverse effects are less important than they would be in a patient being treated on an outpatient basis. SE is a life-threatening situation, and the patient will be admitted to the hospital after treatment. Therefore, if treatment errs, it should err on the side of excessive medication. Temporary adverse effects are preferred to irreversible brain damage or death.

Finally, systemic acidosis is not a major concern because it is usually transient, and medical treatment to normalize acidosis can lead to a rebound metabolic alkalosis when the SE stops. In addition, evidence suggests that acidosis has antiseizure effects.

The approach to treatment of motor focal SE—specifically, epilepsy partialis continua—is similar to that with generalized convulsive SE. However, the urgency of treatment and the extremes to which a physician may elect to go to terminate the seizure are tempered.

The basic principles of emergency care (ie, attention to airway, breathing, and circulation [ABCs] apply to focal as well as to generalized SE. Although generalized convulsive SE frequently jeopardizes the ABCs, epilepsy partialis continua only infrequently does so.

See the image below for management algorithms for convulsive status epilepticus.

View Image

Treatment algorithms for convulsive status epilepticus.

Treatment Guidelines

In 2016, the American Epilepsy Society (AES) issued new guidelines for the treatment of SE. The guidelines provide a time-dependent treatment algorithm that includes four phases.[62]

In the stabilization phase, standard first-aid for seizures should be initiated.

In the initial therapy phase, a benzodiazepine (specifically IM midazolam, IV lorazepam, or IV diazepam) is recommended as initial therapy.

In the second phase, options include IV fosphenytoin, valproic acid, or levetiracetam. If none of these is available, IV phenobarbital is a reasonable alternative.

In the third phase, if a patient experiences 40+ minutes of seizure activity, treatment considerations should include repeating second-line therapy or anesthetic doses of thiopental, midazolam, pentobarbital, or propofol.


Prehospital Care

Supportive care, including ABCs, must be addressed in the prehospital setting. If the seizure fails to stop within 4-5 minutes or if the patient is continuing to seize at the time of emergency medical system (EMS) personnel arrival, prompt administration of anticonvulsants may be necessary.

Because of the refrigeration requirements and the infrequent use of most anticonvulsants, diazepam (Valium) is often the only anticonvulsant available in the prehospital setting. Diazepam may be administered intravenously (IV) or per rectum. Midazolam (Versed) is available in some EMS systems and is currently the subject of study because of the option for intramuscular and intranasal administration.

If persons who know the patient, or who witnessed the onset of the seizures, are present at the scene, EMS providers may be able to collect information that offers clues to the cause of the SE.

Emergency Department Care

Regardless of the clinical manifestations of generalized SE, aggressive supportive care and prompt termination of electrical seizure activity are the goals. Care is individualized to the patient.

Establish intravenous access, ideally in a large vein. Intravenous administration is the preferred route for anticonvulsant administration because it allows therapeutic levels to be attained more rapidly. Begin cardiac and other hemodynamic monitoring.

Administer a 50-mL bolus of 50% dextrose IV and 100 mg of thiamine. If seizure activity does not terminate within 4-5 minutes, start anticonvulsant medication. If EMS history has already defined SE, treatment should begin immediately. In some settings where drug intoxication might be likely, consider also adding naloxone at 0.4-2.0 mg IV to the dextrose bag.

Administer diazepam (0.15 mg/kg) or lorazepam (0.1 mg/kg) IV over 5 minutes, followed by fosphenytoin or phenytoin. Fosphenytoin is preferable, as it provides the advantage of a potentially rapid rate of administration with less risk of venous irritation (eg, to avoid the risk of purple-glove syndrome with phenytoin).

Fosphenytoin is given in a dose of 15-20 mg phenytoin equivalents [PE]/kg, at a rate not to exceed 150 mg PE/min). The dose of phenytoin is 18-20 mg/kg, at a rate not to exceed 50 mg/min). Never mix phenytoin with a 5% dextrose solution; put it in a normal saline solution to minimize the risk of crystal precipitation.

Ensure airway control. Nasopharyngeal airway placement is sufficient for some patients, particularly if the seizures are stopped and the patient is awakening. For other patients, endotracheal intubation is necessary. In neuromuscular paralysis, rapid sequence induction is necessary at times. Use short-acting paralytics to ensure that ongoing seizure activity is not masked. Use EEG monitoring if long-acting paralytics are used and if a question exists about seizure cessation.

Correct any metabolic imbalances. Control hyperthermia.

If seizures continue after 20 minutes, give additional fosphenytoin (10 mg PE/kg IV) or phenytoin (10 mg/kg IV). Aim for a total serum phenytoin level of about 22-25 µg/mL.

In patients with epilepsy partialis continua who had been receiving AED treatment, knowledge of the patient's usual regimen and current levels may be pivotal. As an alternative to fosphenytoin or phenytoin, supplementation of their routine medication (guided by stat AED levels) may help suppress their seizures.

Failure to respond to optimal benzodiazepine and phenytoin loading operationally defines refractory status epilepticus. If seizures continue after 20 minutes, give phenobarbital (15 mg/kg IV). Use caution when adding barbiturates to benzodiazepines because their coadministration may potentiate ventilatory failure. This may be especially true for patients (eg, elderly patients) with impaired drug clearance.

For this reason, especially in the setting of partially treated epilepsy partialis continua or simple partial SE, in which the morbidity of the underlying illness is less than in generalized convulsive SE, a tempered approach may be preferred. Incremental doses of phenobarbital may offer satisfactory efficacy in these uncommon settings and may be safer than full intravenous loading doses, which increase the risk of respiratory suppression.

Alternatives to phenobarbital that are shorter acting and allow for periodic neurologic assessments include the following[63, 64] :

If seizures continue, consider administering general anesthesia with medications such as propofol, midazolam, or pentobarbital. Ketamine infusion can alternatively (or additionally) be used in the treatment of refractory status epilepticus, with some evidence of safety and efficacy. These agents are given by IV drip and titrated to a burst-suppression pattern in the EEG trace. In a patient with epilepsy partialis continua or simple partial SE, one might even consider rapid oral loading of one of the newer AEDs (eg, topiramate[68] ), depending on the ongoing clinical urgency. Lacosamide is a novel antiepileptic drug available in IV form; though anecdotally it appears safe, its effectiveness in treatment of refractory SE is unknown.

If the patient promptly becomes alert after receiving a benzodiazepine or other AED, that tends to corroborate the diagnosis of SE. Nevertheless, the failure to become alert by no means excludes the diagnosis of SE. Most patients remain sleepy or stuporous after the resolution of a prolonged episode of SE, whether focal or generalized.

For this reason, bedside EEG assessment can be invaluable in guiding treatment decisions. This is true not only early in the treatment paradigm but also late to help gauge the patient's recovery and to ensure that he or she is not having repeated subclinical seizures. Portable computer-aided EEG monitoring (LTM system) can be particularly helpful in this task.

Antiepileptic Drug Selection

Benzodiazepines are the preferred first-line agents. According to 2016 guidelines from the American Epilepsy Society (AES), any of three benzodiazepines — intramuscular (IM) midazolam, intravenous (IV) lorazepam, or IV diazepam — should be given if first-aid stabilization measures don't stop the seizure within 5 minutes.[62] Although diazepam is familiar to paramedics and emergency physicians, a consensus has evolved among neurologists and epileptologists that lorazepam may be preferred in this setting because of its long distribution half-life. 

A comparison of initial IV treatment for overt generalized convulsive SE by Treiman et al found that lorazepam was more effective than phenytoin alone.[41] Lorazepam was not more effective than phenobarbital or diazepam plus phenytoin, but it was easier to use. Not studied was fosphenytoin, which is theoretically a significant improvement over phenytoin.

A 2014 Cochrane Database review found intravenous lorazepam is better than intravenous diazepam or intravenous phenytoin alone for cessation of seizures.[69]

Intravenous valproic acid has been shown in a pilot study to be equal to or better than phenytoin in aborting generalized SE, and it has been used in some cases of focal status epilepticus.[70, 71]

The use of levetiracetam (Keppra) in treatment of refractory SE has been examined, in part due to its availability in intravenous form, although its use in treating focal SE remains investigational.[72, 73, 74] Anecdotal reports describe the beneficial use of topiramate in some cases of focal SE.

There are several intravenous formulations of antiepileptic drugs (AEDs) at different stages of development.[75] Some of these might be able to help refractory cases with SE as adjunctive therapy.

No data clearly support a best third-line drug. Controlled trials are lacking, and recommendations vary greatly. While phenobarbital has historically been among the most widely used, the list of third-line drugs also includes intravenous agents such as midazolam, propofol, pentobarbital, valproate, levetiracetam, lidocaine,[76] , ketamine[67] } and others. Lacosamide, a novel antiepileptic drug available for intravenous injection, may be used safely as adjunctive therapy for SE, but little data exist on its efficacy.[77]

A clinical practice trend seems to be for use of propofol as a third-line agent, often initiated during induction for endotracheal intubation. However, propofol infusion syndrome and increased mortality is reported when used at high doses and for prolonged periods.[66]

Absence status epilepticus

Benzodiazepines and valproate are the treatments of choice for absence SE. 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. Ethosuximide also can be useful, but is not available in parenteral form.

Medication Summary

Most patients with status epilepticus (SE) who are treated aggressively with a benzodiazepine, fosphenytoin, and/or phenobarbital experience complete cessation of their seizures. If SE does not stop, general anesthesia is indicated. The use of pentobarbital, thiopental, midazolam infusion, propofol, levetiracetam, topiramate, valproate, and inhaled anesthetic agents has been described for this purpose.

Lorazepam (Ativan)

Clinical Context:  Lorazepam is preferred by most neurologists for treatment of SE because of its more prolonged CNS action. It is less fat-soluble than diazepam and therefore takes slightly longer (5-10 min) to stop seizures. It has a smaller volume of distribution than diazepam. Serum concentrations reach 50% of Cmax at 20 min. Lorazepam clears from the brain slower than diazepam but loses protective effect over 30-120 min.

It is important to monitor the patient's blood pressure after administering a dose. Adjust as necessary.

Diazepam (Diastat, Valium)

Clinical Context:  Diazepam is an extremely lipid-soluble agent that quickly enters the brain in first pass and often stops seizures in 1-2 min. It rapidly distributes to other stores of body fat. Its serum concentration decreases to 20% of maximum concentration (Cmax) 20 min after IV infusion. Individualize dosage and increase cautiously to avoid adverse effects.

Midazolam (Versed)

Clinical Context:  Midazolam is used as an alternative agent in termination of refractory SE. Because midazolam is water soluble rather than fat soluble, it takes approximately 3 times longer than diazepam to peak EEG effects. Thus, the clinician must wait 2-3 min to fully evaluate sedative effects before repeating a dose.

Class Summary

These are first-line agents for treating SE. They rapidly achieve therapeutic CNS concentrations after IV administration and act to potentiate action of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS, and rapidly abrogate ongoing seizure activity. Their effect is temporary, which is a limitation; diazepam begins to redistribute out of CNS within minutes. Lorazepam, when available, is thought to be the most effective and has a longer seizure half-life than diazepam. Because the effect is time limited, loading of a traditional AED, such as phenytoin, is recommended soon after administration to help mitigate seizure recurrence.

Phenytoin (Dilantin, Phenytek)

Clinical Context:  Phenytoin blocks sodium channels in the CNS. It may act in the motor cortex, where it may inhibit spread of seizure activity. The activity of brainstem centers responsible for tonic phase of grand mal seizures also may be inhibited. The dose should be individualized.

A mainstay in the treatment of SE, phenytoin must be administered slowly and therefore takes longer than benzodiazepines to enter the brain. Phenytoin has the advantage of being a long-term anticonvulsant and can be administered orally after acute illness.

Phenytoin is not water soluble, and must be solubilized in propylene glycol carrier with pH 12 to prepare IV form; therefore, it cannot be given at a rate faster than 50 mg/min without risk of significant hypotension and cardiac arrhythmias, as well as major risk of potential irritation at IV site and vascular compromise of the infused limb. Therefore, its use in SE should be avoided if possible.

Fosphenytoin (Cerebyx)

Clinical Context:  A phosphorylated phenytoin prodrug, fosphenytoin is highly water-soluble at physiologic pH and therefore is easier to administer than phenytoin. It is hydrolyzed rapidly and completely to phenytoin by endogenous phosphatases after a mean of 8 min and therefore can be administered more rapidly than standard phenytoin. Fosphenytoin also eliminates the risk of phlebitis and purple-glove syndrome seen with phenytoin, while achieving therapeutic CNS levels as quickly as phenytoin.

To avoid the need to perform molecular weight–based adjustments when converting between fosphenytoin and phenytoin sodium doses, the fosphenytoin dose is expressed as phenytoin equivalents (PE).

IM administration of fosphenytoin has been approved. However IV is still the route of choice for SE. Cardiac monitoring is required when this agent is administered IV but is not required for IM administration.

Class Summary

These agents are used to terminate clinical and electrical seizure activity and to prevent seizure recurrence. Since the full antiepileptic effect of phenytoin, whether given as fosphenytoin or parenteral phenytoin, is not immediate, use of these agents usually follows administration of an IV benzodiazepine.


Clinical Context:  Phenobarbital works at CNS GABA receptors to potentiate CNS inhibition. It exhibits anticonvulsant activity in anesthetic doses. Phenobarbital is the best-studied barbiturate in treatment of SE.

In SE, achieving therapeutic levels as quickly as possible is important. IV dose may require approximately 15 min to attain peak levels in the brain. To terminate generalized convulsive SE, administer up to 15-20 mg/kg. If the patient has received a benzodiazepine, the potential for respiratory suppression significantly increases. Ventilation and intubation may be necessary. Hypotension may require treatment.

Phenobarbital is generally used after phenytoin or fosphenytoin fails. However, it can be used in lieu of phenytoin in certain circumstances.

If the IM route is chosen, administer this agent into a large muscle such as the gluteus maximus or vastus lateralis or other areas where risk of encountering nerve trunk or major artery is low. Permanent neurologic deficit may result from injection into or near peripheral nerves.

Restrict IV use to conditions in which other routes are not possible, either because patient is unconscious or because prompt action is required.

A trend is to recommend agents other than phenobarbital (propofol, midazolam, other barbiturates) for refractory SE.

Pentobarbital (Nembutal)

Clinical Context:  A short-acting barbiturate with sedative, hypnotic, and anticonvulsant properties, pentobarbital can produce mood alteration at all levels of CNS. Use only in refractory status when other agents have failed. Patients need intubation and respiratory support.

Class Summary

This class of anticonvulsant may be useful when SE fails to respond to phenytoin and benzodiazepines. It is the most commonly used third-line drug, but midazolam, propofol, and others are increasingly used in preference to phenobarbital, although no rigorous evidence supports the use of one third-line drug over another.

Propofol (Diprivan)

Clinical Context:  A phenolic compound unrelated to other types of anticonvulsants, propofol has general anesthetic properties when administered IV. There are increasing anecdotal reports of its use in refractory status epilepticus. Intubation and ventilation are required. Hypotension may require treatment.

Class Summary

These agents stabilize the neuronal membrane so the neuron is less permeable to ions. This prevents the initiation and transmission of nerve impulses, thereby producing the local anesthetic effects. In SE, lidocaine is indicated for refractory cases only and its use is supported only by anecdotal reports. The consensus seems to be moving toward propofol or midazolam infusions for refractory status epilepticus.


Julie L Roth, MD, Neurologist, Epilepsy and General Neurology, Comprehensive Epilepsy Program, Rhode Island Hospital; Assistant Professor, Department of Neurology, The Warren Alpert Medical School of Brown University

Disclosure: Nothing to disclose.


Andrew S Blum, MD, PhD, Director, Adult Epilepsy and EEG Laboratory, Comprehensive Epilepsy Program, Rhode Island Hospital; Associate Professor of Neurology, The Warren Alpert Medical School of Brown University

Disclosure: Received royalty from Springer Publishing for editor of text, the clinical neurophysiology primer.

Chief Editor

Stephen A Berman, MD, PhD, MBA, Professor of Neurology, University of Central Florida College of Medicine

Disclosure: Nothing to disclose.


Norberto Alvarez, MD Assistant Professor, Department of Neurology, Harvard Medical School; Consulting Staff, Department of Neurology, Boston Children's Hospital; Medical Director, Wrentham Developmental Center

Norberto Alvarez, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, and Child Neurology Society

Disclosure: Nothing to disclose.

Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association

Disclosure: UCB Pharma Honoraria Speaking, consulting; Lundbeck Honoraria Speaking, consulting; Cyberonics Honoraria Speaking, consulting; Glaxo Smith Kline Honoraria Speaking, consulting; Pfizer Honoraria Speaking, consulting; Sleepmed/DigiTrace Honoraria Speaking, consulting

Jose E Cavazos, MD, PhD, FAAN Associate Professor with Tenure, Departments of Neurology, Pharmacology, and Physiology, Program Director of the Clinical Neurophysiology Fellowship, University of Texas School of Medicine at San Antonio; Co-Director, South Texas Comprehensive Epilepsy Center, University Hospital System; Director of the San Antonio Veterans Affairs Epilepsy Center of Excellence and Neurodiagnostic Centers, Audie L Murphy Veterans Affairs Medical Center

Jose E Cavazos, MD, PhD, FAAN is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society, and American Neurological Association

Disclosure: GXC Global, Inc. Intellectual property rights Medical Director - company is to develop a seizure detecting device. No conflict with any of the Medscape Reference articles that I wrote or edited.

Daniel J Dire, MD, FACEP, FAAP, FAAEM Clinical Professor, Department of Emergency Medicine, University of Texas Medical School at Houston; Clinical Professor, Department of Pediatrics, University of Texas Health Sciences Center San Antonio

Daniel J Dire, MD, FACEP, FAAP, FAAEM is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American Academy of Pediatrics, American College of Emergency Physicians, and Association of Military Surgeons of the US

Disclosure: Nothing to disclose.

Rick Kulkarni, MD Attending Physician, Department of Emergency Medicine, Cambridge Health Alliance, Division of Emergency Medicine, Harvard Medical School

Rick Kulkarni, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine

Disclosure: WebMD Salary Employment

Edward H Maa, MD Chief of Comprehensive Epilepsy Program, Department of Neurology, Denver Health and Hospitals; Assistant Professor, Department of Neurology, University of Colorado School of Medicine and Veterans Affairs Medical Center

Edward H Maa, MD is a member of the following medical societies: American Academy of Neurology and American Epilepsy Society

Disclosure: UCB Pharma Honoraria Speaking and teaching

Erasmo A Passaro, MD, FAAN Director, Comprehensive Epilepsy Program/Clinical Neurophysiology Lab, Bayfront Medical Center, Florida Center for Neurology

Erasmo A Passaro, MD, FAAN is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, American Medical Association, and American Society of Neuroimaging

Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; UCB Honoraria Speaking and teaching; Pfizer Honoraria Speaking and teaching; Forest Honoraria Speaking and teaching

Mark Spitz, MD Professor, Department of Neurology, University of Colorado Health Sciences Center

Mark Spitz, MD is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, and American Epilepsy Society

Disclosure: pfizer Honoraria Speaking and teaching; ucb Honoraria Speaking and teaching; lumdbeck Honoraria Consulting

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment


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Focal status epilepticus. Electroencephalograph (EEG) in a patient with epilepsia partialis continua caused by Rasmussen encephalitis before hemispherectomy. The patient had long-standing, intractable partial epilepsy since the first decade of life. Seizures included complex partial with occasional secondary generalization and repetitive myoclonus involving the left side of the body. Note the frequent epileptiform discharges at 1-2 Hz involving the right frontocentral channels. These were evident on many of the patient's routine EEGs. Clinical myoclonus is often correlated with high-voltage bursts of such activity.

Focal status epilepticus. Electroencephalograph (EEG) in a patient with epilepsia partialis continua caused by Rasmussen encephalitis before hemispherectomy. The patient had long-standing, intractable partial epilepsy since the first decade of life. Seizures included complex partial with occasional secondary generalization and repetitive myoclonus involving the left side of the body. Note the frequent epileptiform discharges at 1-2 Hz involving the right frontocentral channels. These were evident on many of the patient's routine EEGs. Clinical myoclonus is often correlated with high-voltage bursts of such activity.

Focal status epilepticus. Electroencephalograph (EEG) in a 35-year-old patient with a history of intractable partial epilepsy, in complex partial status epilepticus. The patient underwent a rapid antiepileptic drug taper as an inpatient for long-term video/EEG monitoring as a presurgical candidate. On clinical observation, the patient abruptly stopped and stared, exhibiting automatisms. This first of 2 EEG fragments covers approximately 30 seconds and illustrates the start and evolution of a seizure in the right temporal lobe. The onset appears to be at Sp2 and T4. Note the time of the event, 18:35 on May 9.

Focal status epilepticus. This electroencephalographic (EEG) fragment was obtained at approximately 12:39 on May 10, 18 hours after the onset of complex partial status epilepticus originating in the right temporal lobe, in a 35-year-old patient with a history of intractable partial epilepsy. Other EEG acquisitions over the interval were identical. On clinical observation, the patient was lethargic, sluggish, and vague, with variable responsivity to examiners. Note the persistent epileptiform discharges at 1.5-2.5 Hz with phase reversal mainly at Sp2 though infrequently shifting to Sp1 and F7. The bulk of the discharges are maximal at Sp2, reflecting their mesial temporal origin, with rare, subtle, and low-amplitude reflection from lateral neocortical channels (F8). Background activities are slow with admixed beta frequencies. This finding corresponds to complex partial status epilepticus.

Treatment algorithms for convulsive status epilepticus.

Treatment algorithms for convulsive status epilepticus.

Focal status epilepticus. Electroencephalograph (EEG) in a patient with epilepsia partialis continua caused by Rasmussen encephalitis before hemispherectomy. The patient had long-standing, intractable partial epilepsy since the first decade of life. Seizures included complex partial with occasional secondary generalization and repetitive myoclonus involving the left side of the body. Note the frequent epileptiform discharges at 1-2 Hz involving the right frontocentral channels. These were evident on many of the patient's routine EEGs. Clinical myoclonus is often correlated with high-voltage bursts of such activity.

Focal status epilepticus. Electroencephalograph (EEG) in a 35-year-old patient with a history of intractable partial epilepsy, in complex partial status epilepticus. The patient underwent a rapid antiepileptic drug taper as an inpatient for long-term video/EEG monitoring as a presurgical candidate. On clinical observation, the patient abruptly stopped and stared, exhibiting automatisms. This first of 2 EEG fragments covers approximately 30 seconds and illustrates the start and evolution of a seizure in the right temporal lobe. The onset appears to be at Sp2 and T4. Note the time of the event, 18:35 on May 9.

Focal status epilepticus. This electroencephalographic (EEG) fragment was obtained at approximately 12:39 on May 10, 18 hours after the onset of complex partial status epilepticus originating in the right temporal lobe, in a 35-year-old patient with a history of intractable partial epilepsy. Other EEG acquisitions over the interval were identical. On clinical observation, the patient was lethargic, sluggish, and vague, with variable responsivity to examiners. Note the persistent epileptiform discharges at 1.5-2.5 Hz with phase reversal mainly at Sp2 though infrequently shifting to Sp1 and F7. The bulk of the discharges are maximal at Sp2, reflecting their mesial temporal origin, with rare, subtle, and low-amplitude reflection from lateral neocortical channels (F8). Background activities are slow with admixed beta frequencies. This finding corresponds to complex partial status epilepticus.