Status epilepticus

(medicine) Occurrence of prolonged, generalized epileptic seizures in rapid succession with brief intervals of coma.

Definition

Status epilepticus is a term describing a state of continuous seizure activity. In the past, 30 minutes of continuing seizure or frequent attacks that prevent recovery was required for the definition of status to be met. However, since most seizures last less than four to five minutes, it is now understood that any seizure that continues five minutes or longer should be potentially considered as status epilepticus, and managed accordingly.

Description

Nearly all types of seizures have the potential of occurring in a continuous or repeated fashion. There are two general categories: generalized status and focal status, depending on the clinical features of the situation. Generalized status can preferentially manifest with tonic, clonic, absence, and/or myoclonic seizures. Hence, status can be merely a prolongation of commonly observed individual seizure types. Non-convulsive status epilepticus can manifest with sustained or repeating complex partial seizures with a change in mental status, or simply as a focal seizure with limited physical signs but without alteration of consciousness. Status can occur in individuals who have epilepsy already. However, in some cases, the first seizure that a person experiences can be status epilepticus.

Demographics

The epidemiology of status epilepticus varies depending on the study. However, in the United States the incidence is approximately up to 40 per 100,000 individuals. Therefore more than 100,000 cases of status occur annually. Up to 10% of all first-time seizures are situations of status epilepticus. The mortality of status epilepticus is roughly 20%. Those most at risk are the very young or the elderly. The causes of death vary depending on the age of the patient, presence of medical complications, duration of the uncontrollable seizures, and the underlying cause of the status epilepticus.

Causes and symptoms

The exact pathophysiology of why a seizure evolves into status is complex and not fully understood. However, status epilepticus has many causes, some of which are the same as causes of seizures in general. In infants, status can occur in the setting of perinatal hypoxia or anoxia (low oxygen or lack of oxygen) that injures the brain. Also, illness such as meningitis that can cause seizures can also be severe enough to cause status epilepticus. Metabolic disorders of infancy and childhood that can be causes of epilepsy can also produce status epilepticus. In adults, infections of the brain, strokes, brain tumors, and severe head trauma can cause seizures and hence status epilepticus.

Clinically, status epilepticus is basically a prolonged seizure situation. Individual seizures occurring frequently enough to impair full recovery to baseline function can be a manifestation of status epilepticus as well. A limited seizure such as an arm jerking without alteration of consciousness is called a simple or focal seizure. If it occurs continuously, the term epilepsy partialis continua is used. This is the least serious of the different types of status epilepticus. The more dangerous type is, of course, generalized tonic/clonic status. This is because cardiac arrhythmias or blood pressure changes can be life threatening. Also, breathing and oxygenation can be compromised, and patients may require ventilator assistance. Complex partial seizures and absence seizures are manifested with an alteration of consciousness. When these particular seizures become status, patients may simply appear confused or agitated. Since they are not having convulsions, they may be misdiagnosed as having a psychiatric symptom. Nevertheless, prompt and accurate diagnosis is important for proper management.

Diagnosis

When convulsions are occurring, status is typically easily recognized. However, subtle status, as in complex partial or absence status, may necessitate an electroencephalogram (EEG) for diagnosis. The EEG is not only used for initial diagnosis, but is often left running for longer periods to monitor response to treatment. The recognition of seizure activity is only one of the urgent tasks in the care of the patient. The other major issue is to rapidly identify the cause of seizures and the status epilepticus. This involves testing blood for at least glucose, electrolytes, liver function, and illicit substances. Very low blood glucose or extreme changes in sodium, for example, can cause seizures. Infections such as meningitis can cause status. Rapidly assessed levels of older, commonly used seizure medications such as phenytoin, Phenobarbital, carbamazepine, and valproic acid are sometimes sought in cases where there is no available history from the patient. Indeed, one of the most frequent causes of status is low anticonvulsant levels in a patient with a history of epilepsy.

Treatment team

Patients in status epilepticus will often necessitate a neurologist to guide the management from the emergency department through the rest of the hospital stay. Social workers are important for discharge plans because many patients who survive status epilepticus may need skilled nursing or rehabilitation to fully recover prior to being discharged home.

Treatment

The treatment of status depends on identifying quickly the underlying cause, if any. In cases of hypoglycemia, thiamine must be administered just prior to glucose supplementation. This is because some individuals, alcoholics for example, may be deficient in thiamine and a correction of glucose levels without thiamine supplementation can cause a condition known as Wernicke's encephalopathy. Sodium must be corrected slowly or a condition called central pontine myelinolysis can occur. A computed tomography (CT) scan of the brain is often ordered to evaluate for any brain trauma. A lumbar puncture may be performed to determine if there is meningitis so appropriate antibiotics can be used. Overall, in cases that an identifiable cause of status can be found, the key to successful treatment is the management of the underlying cause itself. There are published guidelines for the treatment of seizures themselves. Initially, a sedative such as lorazepam or diazepam is given, which can stop many seizures at least temporarily while a longer-acting anticonvulsant such as phenytoin takes effect. If seizures persist, then the addition of Phenobarbital is typically added. Since this particular medication, when fully loaded, causes respiratory depression, an anesthesiologist is consulted to manage ventilator assistance. Status epilepticus is managed and treated in an intensive care unit with EEG monitoring to continually assess the response to seizure medications. When Phenobarbital fails to stop the ongoing seizures, a number of other medications are considered, such as a midazolam drip or propofol. Anesthetic dosages of these particular medications are usually effective in suppressing seizure activity. Approximately every 24 hours, the dosage is reduced to determine if seizures recur or not. The severity of status can vary widely. Sometimes, it is effectively treated within one to two hours and other times the status is severe and extremely resistant to treatment and lasts for weeks. In such cases, the mortality rate is significant because of risk of medical complications such as pneumonia and blood clots.

Recovery and rehabilitation

The recovery from status epilepticus will depend on its duration. If status can be effectively stopped in a relatively short period of time, complete neurological recovery is possible. The longer the seizures persist, the greater the chance of cerebral injury. Also, the longer the status epilepticus, the more difficult it is to stop. A complication of status epilepticus can actually be the development of epilepsy in a percentage of cases.

Prognosis

The prognosis with status epilepticus will depend on the duration of status and co-existing medical problems. The prognosis is good for recovery if status can be stopped in a relatively short period of time (hours) and there are no complications such as infection, active cardiac problems, or other active medical issues. However, prognosis for complete recovery is less favorable as status persists for long periods of time. Co-existing medical problems will complicate management and chance for a negative outcome.

Special concerns

It is important to be on the lookout for subtle status situations that may go unrecognized. An EEG is a relatively easy way to rule in or rule out presence of active seizures. It is crucial to respond urgently to status epilepticus because the longer the seizures continue the more difficult they are to stop.

Resources

BOOKS

Browne, T. R., and G. L. Holmes. Handbook of Epilepsy, 2nd edition. Philadelphia: Lippinocott Williams & Wilkins, 2000.

Engel, Jr., J., and T. A. Pedley. Epilepsy: A Comprehensive Textbook. Philadelphia: Lippincott-Raven, 1998.

Hauser, W. A., and D. Hesdorffer. Epilepsy: Frequency, Causes, and Consequences. New York: Demos Publications, 1990.

Wyllie, E. The Treatment of Epilepsy: Principles and Practice, 3rd edition. Philadelphia: Lippincott Williams & Wilkins. 2001.

PERIODICALS

Epilepsy Foundation of America's Working Group on Status Epilepticus. "Treatment of Convulsive Status Epilepticus: Recommendations of the JAMA." Journal of the American Medical Association 270 (1993): 854–859.

Hesdorffer, D. C., G. Logroscino, G. Cascino, J. F. Annegers, and W. A. Hauser. "Risk of Unprovoked Seizure after Acute Symptomatic Seizure: Effect of Status Epilepticus." Annals of Neurology 44 (1998): 908–912.

ORGANIZATIONS

American Epilepsy Society. 342 North Main Street, West Hartford, CT 06117-2507. (860) 586-7505. http://www.aesnet.org.

Epilepsy Foundation of America. 4351 Garden City Drive, Landover, MD 20785-7223. (800) 332-1000. http://www.epilepsyfoundation.org.

Internation League Against Epilepsy. Avenue Marcel Thiry 204, B-1200, Brussels, Belgium. + 32 (0) 2 774 9547; Fax: + 32 (0) 2 774 9690. http://www.epilepsy.org.

Roy Sucholeiki, MD

A seizure lasting more than 30 minutes, or a series of seizures without pause between them. Patient often does not respond to medication.

Status epilepticus
Classification and external resources
ICD-10	G41.
ICD-9	345.3
eMedicine	emerg/554
MeSH	D013226

Status epilepticus (SE) refers to a life-threatening condition in which the brain is in a state of persistent seizure. Definitions vary, but traditionally it is defined as one continuous unremitting seizure lasting longer than 30 minutes ^[1], or recurrent seizures without regaining consciousness between seizures for greater than 30 minutes (or shorter with medical intervention). There is some evidence that 5 minutes is sufficient to damage neurons and that seizures are unlikely to self-terminate by that time. First aid guidelines for seizures state that an ambulance should be called for seizures lasting longer than 5 minutes^[2].

Contents 1 Causes 2 Occurrence 3 Variants 3.1 Convulsive 3.2 Nonconvulsive 4 Treatments 4.1 Benzodiazepines 4.2 Phenytoin and fosphenytoin 4.3 Barbiturates 4.4 General anesthetics 4.5 Lidocaine 5 Expected outcome 6 References 7 External links

Causes

This condition is most common in known epileptics. Within known epileptics, it can be caused by:

• Insufficient dosage of a medication already prescribed to the patient. Such causes of this include:
  • Forgetfulness on the part of the patient in taking scheduled doses, or failure to take doses at the scheduled times
  • Dislike of the medication or its side effects
  • Patient's rationing of the medication. This is usually due to patient's difficulty in affording medication, or temporary or permanent lack of access.
  • Failure to maintain a therapeutic level following a change in a patient's physiological needs. This may be the result of a patient growing (into adolescence or adulthood), gaining weight, pregnancy, or childbirth.
• Sudden withdrawal from a seizure medication. Such causes include:
  • Sudden lack of access to medication due to unexpected circumstances
  • Lack of ability of patient to communicate medication needs to others, leading to absence of doses
  • Physician's decision to discontinue medication
• Consumption of alcoholic beverages while on an anticonvulsant, or alcohol withdrawal. For this among other reasons, most patients who have active seizure disorders or who are on anticonvulsants are advised to altogether avoid consuming alcohol.
• Dieting or fasting while on an anticonvulsant. Those with epilepsy or who are on anticonvulsants are advised to consult with their physicians prior to dieting or fasting.
• Consuming certain food products that interact badly with an anticonvulsant (rare)
• Starting on a new medication that reduces the effectiveness of the anticonvulsant
• Developing a resistance to an anticonvulsant already being used
• Injury to the patient. This may be the result of a sports injury, motor vehicle accident, fall, physical abuse, or other injury that affects the brain. Though such injuries may trigger a seizure in anyone, those with a known seizure disorder are more susceptible.
• Gastroenteritis while on an anticonvulsant. This is because the digestive system may force out the anticonvulsant, thereby rendering the body with a lack of protection.
• Developing a new, unrelated condition in which seizures are coincidentally also a symptom, but are not controlled by an anticonvulsant already used
• Metabolic disturbances—such as affected kidney and liver

This condition may also occur as the first known seizure in new epileptics, accounting for about 10% of cases. In non-epileptics, causes may include:

• Brain disorders, such as:
  • Meningitis
  • Encephalitis
  • Brain tumors
  • Abscess
  • Traumatic brain injury
• Sepsis
• Some autoimmune disorders
• Extremely high fever, especially in children
• Low glucose levels
• Eating disorders
• Nerve agents such as soman

^[3]

Occurrence

In the United States, approximately 40 cases of status epilepticus occur annually out of every 100,000 members of the population. This includes about 10-20% of all first seizures^[4].

Variants

Status epilepticus can be divided into two categories—convulsive and nonconvulsive, the latter of which is underdiagnosed^{[citation needed]}.

Convulsive

Epilepsia partialis continua is a variant involving hour, day, or even week-long jerking. It is a consequence of vascular disease, tumours, or encephalitis, and is drug-resistant.

Generalized myoclonus is commonly seen in comatose patients following CPR and is seen by some as an indication of catastrophic damage to the neocortex.^[5]

Nonconvulsive

Complex partial status epilepticus, or CPSE, and absence status epilepticus are rare forms of the condition which are marked by nonconvulsive seizures. In the case of CPSE, the seizure is confined to a small area of the brain, normally the temporal lobe. But the latter, absence status epilepticus, is marked by a generalised seizure affecting the whole brain, and an EEG is needed to differentiate between the two conditions. This results in episodes characterized by a long-lasting stupor, staring and unresponsiveness.

Treatments

Diazepam that can be inserted rectally is often prescribed to caregivers of epileptics. This enables treatment of multiple seizures prior to being able to seek medical care.

Benzodiazepines

Shortly after it was introduced in 1963, diazepam became the first choice for SE. Even though other benzodiazepines such as clonazepam were useful, diazepam was relied upon almost exclusively. This began to change in 1975 with a preliminary study on lorazepam conducted by Waltregny and Dargent, who found that its pharmacological effects were longer lasting than those of an equal dose of diazepam.^[6] This meant it did not have to be repeatedly injected like diazepam,^[7] the effects of which would wear off 5–15 minutes later in spite of its 30-hour half-life (due to extensive redistribution of diazepam outside the vascular compartment as diazepam is highly lipid soluble). It has also been found that patients who were first tried on diazepam were much more likely to require endotracheal tubing than patients who were first tried on phenobarbital, phenytoin,^[8] or lorazepam.^[9]

Today, the benzodiazepine of choice is lorazepam for initial treatment due to its long (2–8 hour) duration of action and rapid onset of action, thought to be due to its high affinity for GABA receptors and to its low lipid solubility which causes it to remain in the vascular compartment. If lorazepam is not available, or intravenous access is not possible, then diazepam should be given.^[10] Particularly in children another, increasingly popular treatment choice is buccal midazolam, which can be given into the side of the mouth^[11] . Sometimes, the failure of lorazepam alone is considered to be enough to classify a case of SE as refractory.

Phenytoin and fosphenytoin

Phenytoin was once another first-line therapy, although the prodrug fosphenytoin can be administered three times as fast and with far fewer injection site reactions. If these or any other hydantoin derivatives are used, then cardiac monitoring is a must if they are administered intravenously. Because the hydantoins take 15–30 minutes to work, a benzodiazepine or barbiturate is often co-administered. Because of diazepam's short duration of action, they were often administered together anyway.

Barbiturates

Before the benzodiazepines were invented, there were the barbiturates, which are still used today if benzodiazepines or the hydantoins are not an option. These are used to induce a barbituric coma. The barbiturate most commonly used for this is phenobarbital. Thiopental or pentobarbital may also be used for that purpose if the seizures have to be stopped immediately or if the patient has already been compromised by the underlying illness or toxic/metabolic-induced seizures; however, in those situations, thiopental is the agent of choice.

The failure of phenobarbital therapy does not preclude the success of a lengthy comatose state induced by a stronger barbiturate such as secobarbital. Such was the case for Ohori, Fujioka, and Ohta ca. 1998, when they induced a 10-month long coma (or "anesthesia" as they called it) in a 26-year-old woman suffering from refractory status epilepticus secondary to viral encephalitis and then tapered her off the secobarbital very slowly while using zonisamide at the same time.^[12]

General anesthetics

If this proves ineffective or if barbiturates cannot be used for some reason, then a general anesthetic such as propofol^[13] is tried; sometimes it is used second after the failure of lorazepam.^[14] This also means putting the patient on artificial respiration. Propofol has been shown to be effective in suppressing the jerks seen in myoclonus status epilepticus, but as of 2002^[update], there have been no cases of anyone going into myoclonus status epilepticus, undergoing propofol treatment, and then not dying anyway.^[15]

Lidocaine

The use of lidocaine in status epilepticus was first reported in 1955 by Bernhard, Boem and Hojeberg.^[16] Since then, it has been used in cases refractory to phenobarbital, diazepam, and phenytoin, and has been studied as an alternative to barbiturates and general anesthetics.^[17][18] Lidocaine is a sodium channel blocker and has been used where sodium channel dysfunction was suspected.^[19] However, in some studies, it was either ineffective or even harmful for most patients.^[20] The last is not so surprising in light of the fact that lidocaine has been known to cause seizures in humans and laboratory animals at doses greater than 15 µg/mL^[21] or 2–3 mg/kg.^[22]

Expected outcome

About one in five, a total of 42,000 annually in the United States, will die within 30 days of having an initial status epilepticus seizure. The great majority of these people have an underlying brain condition causing their status seizure such as brain tumor, brain infection, brain trauma or stroke. However, people with diagnosed epilepsy who have a status seizure also have an increased risk of death.^[23]

References

1. ^ Annals of Emerg Med 2004; 43(5): 605-625
2. ^ http://www.epilepsyfoundation.org/about/types/types/statusepilepticus.cfm
3. ^ name="soman">McDonough, John H.; A. Benjamin, Joseph D. McMonagle, Thomas Rowland, Shih Tsung-Ming (February 2004). "Effects of fosphenytoin on nerve agent-induced status epilepticus". Drug and Chemical Toxicology 27 (1): 27–39. doi:10.1081/DCT-120027895. PMID 15038246. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=15038246&dopt=ExternalLink. 
4. ^ http://www.answers.com/topic/status-epilepticus
5. ^ Wijdicks, Eelco F. M.; Parisi JE, Sharbrough FW (February 1994). "Prognostic value of myoclonus status in comatose survivors of cardiac arrest". Annals of Neurology 35 (2): 239–43. doi:10.1002/ana.410350219. PMID 8109907. 
6. ^ Waltregny, Alain; Jérôme Dargent (September/October 1975). "Preliminary study of parenteral lorazepam in status epilepticus". Acta Neurologica Belgica 75 (5): 219–29. PMID 3939. 
7. ^ Walker, JE; RW Homan, MR Vasko, IL Crawford, RD Bell, WG Tasker (September 1979). "Lorazepam in status epilepticus". Annals of Neurology 6 (3): 207–13. doi:10.1002/ana.410060305. PMID 43112. 
8. ^ Orr, Richard A.; Robert J. Dimand, Shekhar T. Venkataraman, Valerie A. Karr, Kathleen J. Kennedy (September 1991). "Diazepam and intubation in emergency treatment of seizures in children". Annals of Emergency Medicine 20 (9): 1009–13. doi:10.1016/S0196-0644(05)82981-6. PMID 1877765. http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WB0-4G82KTB-G&_coverDate=09%2F30%2F1991&_alid=434858892&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=6696&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=fab697f11c8e05b7fe0405b1d34a6f7d. 
9. ^ Appleton, Richard; A. Sweeney, Imti Choonara, Joan Robson, Elizabeth Molyneux. (August 1995). "Lorazepam versus diazepam in the acute treatment of epileptic seizures and status epilepticus". Developmental Medicine and Child Neurology 37 (8): 682–8. PMID 7672465. 
10. ^ Pang, Trudy; Lawrence J. Hirsch (July 2005). "Treatment of Convulsive and Nonconvulsive Status Epilepticus". Current Treatment Options in Neurology 7 (4): 247–259. doi:10.1007/s11940-005-0035-x. PMID 15967088. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=15967088&dopt=ExternalLink. 
11. ^ name="buccal-midazolam"DM, Walker; Teach SJ (06/2006). "Update on the acute management of status epilepticus in children". Current Opinions in Paediatrics 18 (3): 239-244. 
12. ^ Ohori, Nobuhira; Fujioka Y, Ohta M. (May 1998). "[Experience in managing refractory status epilepticus caused by viral encephalitis under long-term anesthesia with barbiturate: a case report]". Rinsho Shinkeigaku 38 (5): 474–7. PMID 9806000.  (Japanese)
13. ^ Pourrat, X; JM Serekian, D Antier, J. Grassin (June 9, 2001). "[Generalized tonic-clonic status epilepticus: therapeutic strategy]". Presse Médicale 30: 1031–6. PMID 11433696.  (French).
14. ^ Marik, Paul E.; Joseph Varon (2004). "The management of status epilepticus". Chest 126 (2): 582–91. doi:10.1378/chest.126.2.582. PMID 15302747. http://www.chestjournal.org/cgi/content/full/126/2/582. 
15. ^ Wijdicks, Eelco F.M. (July 2002). "Propofol in myoclonus status epilepticus in comatose patients following cardiac resuscitation". Journal of Neurology Neurosurgery and Psychiatry 73 (1): 94–5. doi:10.1136/jnnp.73.1.94. PMID 12082068. http://jnnp.bmjjournals.com/cgi/content/full/73/1/94. 
16. ^ Bernhard, CG; Bohm E, Hojeberg S (August 1955). "A new treatment of status epilepticus; intravenous injections of a local anesthetic (lidocaine)". AMA Archives of Neurology and Psychiatry 74 (2): 208–14. PMID 14397899. 
17. ^ Aggarwal, Praveen; Jyoti Prakash Wali (May 1993). "Lidocaine in refractory status epilepticus: a forgotten drug in the emergency department". American Journal of Emergency Medicine 11 (3): 243–4. doi:10.1016/0735-6757(93)90135-X. PMID 93257009. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=8489668&dopt=ExternalLink. 
18. ^ Sugiyama, N; Hamano S, Mochizuki M, Tanaka M, Eto Y (November 2004). "[Efficacy of lidocaine on seizures by intravenous and intravenous-drip infusion]". No to Hattatsu 36 (6): 451–4. PMID 15560386.  (Japanese)
19. ^ Sawaishi Yukio; Yano Tamami, Enoki Masamichi, and Takada Goro (February 2002). "Lidocaine-dependent early infantile status epilepticus with highly suppressed EEG". Epilepsia 43 (2): 201–4. doi:10.1046/j.1528-1157.2002.25301.x. PMID 11903470. 
20. ^ Tanabe Takuya; Suzuki Shuuhei, Shimakawa Shuichi, Yamashiro Kuniteru, Tamai Hiroshi (January 1999). "Problems of intravenous lidocaine treatment in status epilepticus or clustering seizures in childhood". No to Hattatsu 31 (1): 14–20. PMID 10025129.  (Japanese)
21. ^ DeToledo, John C. (June 2000). "Lidocaine and Seizures". Therapeutic Drug Monitoring 22 (3): 320–322. doi:10.1097/00007691-200006000-00014. PMID 10850400. 
22. ^ Steven C. Schachter. "Lidocaine". epilepsy.com/professionals. http://professionals.epilepsy.com/page/local_lidocaine.html.  Adapted from: Najjar S, Devinsky O, Rosenberg AD, et al. (2002). "Procedures in epilepsy patients". in ed. Ettinger AB and Devinsky O. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann. pp. 499–513. ISBN 0-7506-7241-2. 
23. ^ http://www.epilepsyfoundation.org/about/types/types/statusepilepticus.cfm

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External links

• Status Epilepticus Information from the Epilepsy Foundation
• Information about Seizures and Syndromes: Epilepsy Foundation
• Seizure Categorization: Epilepsy Foundation

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