AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

The term status epilepticus may be used to describe any continuing type of seizure. This discussion focuses on generalized convulsive status epilepticus (GCSE). Generalized refers to abnormal excessive cortical electrical activity, while convulsive refers to the motor activity of a seizure. Recently, the concept of subtle status epilepticus has emerged. Subtle status epilepticus consists of electrical seizure activity that endures when the associated movements are fragmentary or even absent. This is confusing and is sometimes called a type of nonconvulsive status epilepticus. Subtle status epilepticus, epileptic encephalopathy, and even ICU status are all terms used to refer to this clinical condition of dissociated cortical epileptiform activity from convulsive motor movements.

Traditionally, status epilepticus was defined as 30 minutes of continuous seizure activity or a series of seizures without return to full consciousness between the seizures. Many believe that a shorter period of seizure activity causes neuronal injury and that seizure self-termination is unlikely after 5 minutes; some suggest times as brief as 5 minutes to define status epilepticus.¹ For purposes of this review, a duration of 5 minutes of continuous generalized convulsive activity is used arbitrarily as part of the definition of GCSE as well as recurrent seizures without a return to consciousness between seizures.

Pathophysiology

Significant physiologic changes accompany GCSE. Many of these systemic responses are thought to result from the catecholamine surge that accompanies the seizures. Hypertension, tachycardia, cardiac arrhythmias, and hyperglycemia are examples of these systemic effects. Body temperature may increase in patients following the vigorous muscle activity that accompanies GCSE (but, of course, infectious etiologies also must be considered in febrile patients). Lactic acidosis is common after a single generalized motor seizure and resolves with termination of the seizure.

Cerebral metabolic demand increases greatly with GCSE; however, cerebral blood flow and oxygenation are thought to be preserved or even elevated early in the course of GCSE. Research with paralyzed and artificially ventilated animals concluded that neuronal loss after focal or generalized status epilepticus is linked to the abnormal neuronal discharges and not simply to the systemic effects of GCSE. The hippocampus seems especially vulnerable to damage by this mechanism.

On a neurochemical level, seizures are sustained by an imbalance of 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.

Frequency

United States

Approximately 50,000-200,000 cases of status epilepticus occur per year (using traditional epidemiologic definitions).²

Mortality/Morbidity

• The overall mortality rate is about 20%; death most often is related to an underlying cause of brain injury.³
• The mortality rate is highest in elderly patients with hypoxic or ischemic central nervous system (CNS) insults.

Sex

Males and females are affected equally.

Age

• Status epilepticus occurs in all age groups but more frequently at the extremes of age.
• In the neonatal group, status epilepticus may be related to perinatal hypoxic insults or metabolic disorders.
• At the other extreme of age, elderly persons have an increased incidence of status epilepticus secondary to ischemic CNS insults.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• A history of epilepsy frequently is elicited.
• 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.
• In roughly one third of cases, status epilepticus is the initial presentation of a seizure disorder.
• Noncompliance with medications is the rule rather than the exception.
• The history may suggest associated injuries, such as a fall or involvement in a motor vehicle accident.

Physical

• Generalized convulsive status epilepticus (GCSE) 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.
• Psychogenic seizures may be, at times, indistinguishable from GCSE based on appearance alone.
• • One study noted that when confronted by pseudoseizures, physicians immediately assumed that a neurologic emergency was present and embarked on an aggressive course of pharmacotherapy, neglecting physical examination and historical information. In this study, unresponsiveness without movement was the most common presentation.⁴
  • Other reviews of psychogenic status epilepticus note other frequently seen presentations, including asynchronous extremity movement, forward pelvic thrusting, and geotropic eye movements (a physical finding that indicates the eyes deviating toward the ground in a nonphysiologic manner whether the head is turned left or right).⁵
• 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 in any patient who does not regain 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.

Causes

The causes of status epilepticus represent an imperfect division into 3 groups.

• In roughly one third of cases, an exacerbation of an idiopathic seizure disorder is thought to be the cause (this is a diagnosis of exclusion).
• In another one third of cases, the episode of status epilepticus represents the first onset of a seizure disorder (a diagnosis of exclusion).
• A myriad of other conditions may precipitate status epilepticus, including toxic or metabolic causes and anything that might cause cortical structural damage.
• • Stroke (remote or acute)
  • Hypoxic injury
  • Tumor
  • Subarachnoid hemorrhage
  • Trauma
  • Toxicologic etiology (eg, cocaine, theophylline, isoniazid, alcohol withdrawal)
  • Electrolyte abnormalities (eg, hyponatremia, hypernatremia, hypercalcemia, hepatic encephalopathy)
  • Infectious etiology (eg, meningitis, brain abscess, encephalitis)
  • A variety of toxins, notably sympathomimetics, may precipitate status epilepticus
  • Isoniazid (INH) may cause seizures and is unique in having a specific antidote, pyridoxine (B-6).

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Catatonia
Coma
Psychogenic nonepileptic seizures (PNES) (pseudoseizures)
Repetitive extensor or flexor posturing
Stimulant intoxication

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Clinical information should guide the ordering of laboratory tests.
• • Several studies have shown the low yield of multiple laboratory tests in the evaluation of patients presenting with a single seizure.⁶
  • However, status epilepticus should prompt a search for the etiology of status epilepticus or potentially reversible conditions.
• Perform rapid glucose determination shortly after the patient's arrival.
• Obtain additional electrolyte levels, particularly sodium.
• Calcium level abnormalities are an infrequent cause of status epilepticus, but serum calcium level should be obtained in certain patients, notably those with a history of malignancy.
• Toxicologic testing initially should be directed toward determining anticonvulsant levels in a patient with a history of seizures. Theophylline toxicity is a notable exception, since detection of toxic levels would alter therapy.
• Arterial blood gas (ABG) determination following an episode of generalized seizures reveals a metabolic acidosis.
• • ABG level determination may be useful to monitor oxygenation and effective ventilation and to discover any unexpected acid-base abnormalities. Metabolic acidosis 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 Toxicity, Isoniazid).

Imaging Studies

• For patients with new-onset seizures or status epilepticus, noncontrast CT in the ED is the procedure of choice because of the availability and the utility of the test in detecting acute hemorrhage. Consider neuroimaging if a question exists about the etiology of the status epilepticus or if the episode is difficult to control. Imaging is often deferred if the patient is known to have epilepsy and the seizure pattern is not unusual for the individual.
• MRI offers better anatomic detail than CT scan, but the longer test time, difficulties with patient management, and uneven availability all weigh against use of MRI by the emergency physician at this time.
• 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.

Other Tests

• Electroencephalogram
• • EEG is not routinely available in the ED.
  • Because of the possibility of subtle GCSE, an EEG should be strongly considered if the patient is not starting to awaken within 20-30 minutes after seizure cessation.
  • EEG availability varies greatly at different institutions.
  • Normally, EEG is obtained through neurologic consultation.

Procedures

• Consider a lumbar puncture (LP) if CNS infection is in the differential diagnosis. Initiate antibiotic therapy if CNS or systemic infection is strongly suspected.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Prehospital Care

• Supportive care, including ABCs, must be addressed in the prehospital setting.
• Historic clues may be evident to EMS providers.
• If the seizure fails to stop within 4-5 minutes or if the patient is continuing to seize at the time of EMS 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 (PR).

Emergency Department Care

• Recognition of status epilepticus may be easy or difficult. The patient with sequential, generalized major motor convulsions is obvious; the patient with nonconvulsive or subtle status is a diagnostic dilemma.
• Psychogenic nonepileptic seizures may be, at times, indistinguishable from GCSE. A brief period of observation for atypical features, as described above (see Physical), may lead to the conclusion that the patient has nonepileptic seizures and does not need anticonvulsant therapy.
• Regardless of the clinical manifestations of generalized status epilepticus, aggressive supportive care and prompt termination of electrical seizure activity are the goals.
• Care is individualized to the patient; for example, 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.
• Initiate rapid glucose determination and correction.
• Establish intravenous access, ideally in a large vein. Intravenous administration is the preferred route for anticonvulsant administration because it allows therapeutic tissue levels to be attained more rapidly. Begin cardiac and other hemodynamic monitoring.
• Begin administration of anticonvulsant medication if seizure activity does not terminate within 4-5 minutes. If EMS history has already defined status epilepticus, treatment should begin immediately.

Consultations

• Neurologists, ideally those with special expertise in epilepsy, are the consultants of choice for status epilepticus.
• Other medical conditions or referral patterns may involve pediatricians, internists, or neurosurgeons.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

"Seizures beget seizures" is a generally accepted clinical axiom. The argument follows that earlier treatment is more effective than later treatment in halting status epilepticus. Current consensus is that a benzodiazepine, notably lorazepam (Ativan), is the initial class of drug for the treatment of status epilepticus. A phenytoin, phenytoin sodium or fosphenytoin (Cerebyx), generally is agreed upon as the next drug to be administered.

Failure to respond to optimal benzodiazepine and phenytoin loading operationally defines refractory status epilepticus. No data clearly support a best third-line drug, controlled trials are lacking, and recommendations vary greatly. The list of third-line drugs includes phenobarbital, midazolam, propofol, pentobarbital, valproate, levetiracetam, and lidocaine. A general principle is to maximize benzodiazepine and phenytoin dosages before adding an additional agent. Many of these drugs are classified as category D in pregnancy. However, these drugs may be used in life-threatening situations, such as GCSE.

Drug Category: Benzodiazepines

These agents are used commonly as the first drug for treatment of GCSE. Lorazepam, when available, is thought to be the most effective and has a longer seizure half-life than diazepam.

Drug Category: Anticonvulsants

These agents are used to terminate clinical and electrical seizure activity as rapidly as possible and to prevent seizure recurrence.

Drug Category: Anesthetics

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 status epilepticus, lidocaine is indicated during refractory status only and is supported only by anecdotal reports. The consensus seems to be moving toward propofol or midazolam infusions for refractory status epilepticus.

Drug Category: Barbiturates

This class of anticonvulsant may be useful when the condition fails to respond to phenytoin and benzodiazepines. This is the 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.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Emergency physicians must stop the seizures, stabilize the patient's medical condition, look for the etiology of the seizures, coordinate care with appropriate physicians, and make disposition to the appropriate service and medical unit.
• Care of the patient may involve interaction with a number of specialty or primary care physicians, including neurologists, neurosurgeons, internists, pediatricians, family practitioners, or intensivists.
• Continuous EEG monitoring may be desirable if a question exists about termination of status epilepticus or the presence of subtle status epilepticus.
• Coordinate treatment of associated injuries or complications with the inpatient service.

Further Outpatient Care

• Most patients with status epilepticus are admitted to the hospital not only for seizure control but also for treatment of other medical conditions that may be causing the seizures.
• • Patients with a flurry of seizures that are easily controlled might conceivably be discharged after several hours of observation.
  • The presence and capability of caretakers, proximity to the hospital, and comorbid medical conditions all factor into this decision.

Transfer

• Failure to terminate the seizures or need for critical care may be reasons for transfer. Transfer to a facility with expertise in this area may be desirable after the patient's condition has been stabilized.

Deterrence/Prevention

• Encourage anticonvulsant therapy compliance and alcohol abstinence.
• Emphasize the importance of regular medical attention for medication adjustment.
• Arrange for follow-up visits to adjust medications and for further medical workup and care.

Complications

• Complications of status epilepticus are many. As discussed in Pathophysiology section, current thought is that the abnormal electrical discharges themselves may cause neuronal damage.
• Systemic complications
• • Hyperthermia
  • Acidosis
  • Hypotension
  • Respiratory failure
  • Rhabdomyolysis
  • Aspiration

Prognosis

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

Patient Education

• Reinforcement of compliance with prescribed medications at routine clinical encounters may be helpful.
• For excellent patient education resources, visit eMedicine's Brain and Nervous System Center. Also, see eMedicine's patient education article Seizures Emergencies.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to diagnose and treat the underlying cause of the seizures is a major pitfall because status epilepticus is often secondary to another pathologic process.
• Failure to recognize associated injuries or complications, such as aspiration pneumonia, is a potential problem.
• Failure to identify subtle or nonconvulsive status epilepticus in the patient with a coma or altered mental status but without convulsive motor seizures is an increasingly recognized pitfall.
• Seizures in association with hypertension in late pregnancy (or postpartum) may represent eclampsia.

Special Concerns

• A paradox currently exists in that the criterion standard for diagnosing status epilepticus, the EEG, rarely is available in the acute-care setting.
• • The work of Treiman et al suggests that electrical status epilepticus often persists when clinical seizure activity has ceased.⁷
  • High clinical suspicion for continued unresponsiveness from this subtle status epilepticus is necessary along with timely consultations and occasional insistence on obtaining EEG.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Lowenstein DH, Bleck T, Macdonald RL. It's time to revise the definition of status epilepticus. Epilepsia. Jan 1999;40(1):120-2. [Medline].
2. DeLorenzo RJ, Hauser WA, Towne AR, Boggs JG, Pellock JM, Penberthy L, et al. A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia. Neurology. Apr 1996;46(4):1029-35. [Medline].
3. Lowenstein DH, Alldredge BK. Status epilepticus. N Engl J Med. Apr 2 1998;338(14):970-6. [Medline].
4. Leis AA, Ross MA, Summers AK. Psychogenic seizures: ictal characteristics and diagnostic pitfalls. Neurology. Jan 1992;42(1):95-9. [Medline].
5. Jagoda A, Richey-Klein V, Riggio S. Psychogenic status epilepticus. J Emerg Med. Jan-Feb 1995;13(1):31-5. [Medline].
6. ACEP Clinical Policies Committee; Clinical Policies Subcommittee on Seizures. Clinical policy: Critical issues in the evaluation and management of adult patients presenting to the emergency department with seizures. Ann Emerg Med. May 2004;43(5):605-25. [Medline].
7. Treiman DM, Meyers PD, Walton NY, Collins JF, Colling C, Rowan AJ, et al. A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group. N Engl J Med. Sep 17 1998;339(12):792-8. [Medline].
8. Aggarwal P, Wali JP. Lidocaine in refractory status epilepticus: a forgotten drug in the emergency department. Am J Emerg Med. May 1993;11(3):243-4. [Medline].
9. Epilepsy Foundation of America's Working Group. Treatment of convulsive status epilepticus. Recommendations of the Epilepsy Foundation of America's Working Group on Status Epilepticus. JAMA. Aug 18 1993;270(7):854-9. [Medline].
10. Fountain NB, Lothman EW. Pathophysiology of status epilepticus. J Clin Neurophysiol. Jul 1995;12(4):326-42. [Medline].
11. Huff JS. Status epilepticus: a systematic approach to assessment, differential diagnosis, and outcome-effective management. Emerg Med Rep. 1997;18(14):137-48.
12. Kumar A, Bleck TP. Intravenous midazolam for the treatment of refractory status epilepticus. Crit Care Med. Apr 1992;20(4):483-8. [Medline].
13. Limdi NA, Shimpi AV, Faught E, Gomez CR, Burneo JG. Efficacy of rapid IV administration of valproic acid for status epilepticus. Neurology. Jan 25 2005;64(2):353-5. [Medline].
14. Lowenstein DH, Alldredge BK. Status epilepticus at an urban public hospital in the 1980s. Neurology. Mar 1993;43(3 Pt 1):483-8. [Medline].
15. Prasad A, Worrall BB, Bertram EH, Bleck TP. Propofol and midazolam in the treatment of refractory status epilepticus. Epilepsia. Mar 2001;42(3):380-6. [Medline].
16. Privitera MD, Strawsburg RH. Electroencephalographic monitoring in the emergency department. Emerg Med Clin North Am. Nov 1994;12(4):1089-100. [Medline].
17. Wheless JW, Vazquez BR, Kanner AM, Ramsay RE, Morton L, Pellock JM. Rapid infusion with valproate sodium is well tolerated in patients with epilepsy. Neurology. Oct 26 2004;63(8):1507-8. [Medline].

Article Last Updated: Sep 13, 2007