Status epilepticus (SE), or status seizure, is a single

seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...

lasting more than 5 minutes or 2 or more seizures within a 5-minute period without the person returning to normal between them. Previous definitions used a 30-minute time limit. The seizures can be of the tonic–clonic type, with a regular pattern of contraction and extension of the arms and legs, or of types that do not involve contractions, such as

absence seizure Absence seizures are one of several kinds of generalized seizures. These seizures are sometimes referred to as petit mal seizures (from the French for "little illness", a term dated in the late 18th century). Absence seizures are characterized by ...

s or

complex partial seizure Focal seizures (also called partial seizures and localized seizures) are seizures which affect initially only one hemisphere of the brain. The brain is divided into two hemispheres, each consisting of four lobes – the frontal, temporal, parie ...

s. Status epilepticus is a life-threatening medical emergency, particularly if treatment is delayed. Status epilepticus may occur in those with a history of

epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical ...

as well as those with an underlying problem of the

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...

. These underlying brain problems may include trauma, infections, or

stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

s, among others. Diagnosis often involves checking the

blood sugar Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in the blood of humans or other animals. Approximately 4 grams of glucose, a simple sugar, is present in the blo ...

, imaging of the head, a number of blood tests, and an

electroencephalogram Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The biosignals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in the neocortex ...

Psychogenic nonepileptic seizures Psychogenic non-epileptic seizures (PNES) are events resembling an epileptic seizure, but without the characteristic electrical discharges associated with epilepsy. PNES fall under the category of disorders known as functional neurological disor ...

may present similarly to status epilepticus. Other conditions that may also appear to be status epilepticus include

low blood sugar Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose belo ...

, movement disorders,

meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...

, and

delirium Delirium (also known as acute confusional state) is an organically caused decline from a previous baseline of mental function that develops over a short period of time, typically hours to days. Delirium is a syndrome encompassing disturbances in ...

, among others. Status epilepticus can also appear when

tuberculous meningitis Tuberculous meningitis, also known as TB meningitis or tubercular meningitis, is a specific type of bacterial meningitis caused by the ''Mycobacterium tuberculosis'' infection of the meninges—the system of membranes which envelop the central nerv ...

becomes very severe.

Benzodiazepines Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, i ...

are the preferred initial treatment, after which typically

phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence seizures. The intr ...

is given. Possible benzodiazepines include intravenous

lorazepam Lorazepam, sold under the brand name Ativan among others, is a benzodiazepine medication. It is used to treat anxiety disorders, trouble sleeping, severe agitation, active seizures including status epilepticus, alcohol withdrawal, and c ...

as well as intramuscular injections of

midazolam Midazolam, sold under the brand name Versed among others, is a benzodiazepine medication used for anesthesia and procedural sedation, and to treat severe agitation. It works by inducing sleepiness, decreasing anxiety, and causing a loss of a ...

. A number of other medications may be used if these are not effective, such as

phenobarbital Phenobarbital, also known as phenobarbitone or phenobarb, sold under the brand name Luminal among others, is a medication of the barbiturate type. It is recommended by the World Health Organization (WHO) for the treatment of certain types of ep ...

propofol Propofol, marketed as Diprivan, among other names, is a short-acting medication that results in a decreased level of consciousness and a lack of memory for events. Its uses include the starting and maintenance of general anesthesia, sedation f ...

, or

ketamine Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a recreational drug. It is one of the safest anesthetics, as, in contrast with opiates, ether, and propofol, it suppresses ne ...

. After initial treatment with benzodiazepines, typical antiseizure drugs should be given, including valproic acid (valproate), fosphenytoin, levetiracetam, or a similar substance(s). While empirically-based treatments exist, few head-to-head clinical trials exist, so the best approach remains undetermined. This said, "consensus-based" best practices are offered by the Neurocritical Care Society.

Intubation Intubation (sometimes entubation) is a medical procedure involving the insertion of a tube into the body. Patients are generally anesthetized beforehand. Examples include tracheal intubation, and the balloon tamponade with a Sengstaken-Blakemo ...

may be required to help maintain the person's

airway The respiratory tract is the subdivision of the respiratory system involved with the process of respiration in mammals. The respiratory tract is lined with respiratory epithelium as respiratory mucosa. Air is breathed in through the nose to th ...

. Between 10% and 30% of people who have status epilepticus die within 30 days. The underlying cause, the person's age, and the length of the seizure are important factors in the outcome. Status epilepticus occurs in up to 40 per 100,000 people per year. Those with status epilepticus make up about 1% of people who visit the emergency department.

Signs and symptoms

Status epilepticus can be divided into two categories: convulsive and nonconvulsive (NCSE).

Convulsive

Convulsive status epilepticus presents with a regular pattern of contraction and extension of the arms and legs.

Epilepsia partialis continua Epilepsia partialis continua is a rare type of brain disorder in which a patient experiences recurrent motor epileptic seizures that are focal (hands and face), and recur every few seconds or minutes for extended periods (days to years). It is som ...

is a variant involving hour-, day-, or even week-long jerking. It is a consequence of

vascular disease Vascular disease is a class of diseases of the blood vessels – the arteries and veins of the circulatory system of the body. Vascular disease is a subgroup of cardiovascular disease. Disorders in this vast network of blood vessels can cause a ra ...

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

s, or

encephalitis Encephalitis is inflammation of the brain. The severity can be variable with symptoms including reduction or alteration in consciousness, headache, fever, confusion, a stiff neck, and vomiting. Complications may include seizures, hallucinations, ...

, and is drug-resistant. Generalized

myoclonus Myoclonus is a brief, involuntary, irregular (lacking rhythm) twitching of a muscle or a group of muscles, different from clonus, which is rhythmic or regular. Myoclonus (myo "muscle", clonic "jerk") describes a medical sign and, generally, is ...

is commonly seen in

coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...

tose people following

CPR Cardiopulmonary resuscitation (CPR) is an emergency procedure consisting of chest compressions often combined with artificial ventilation in an effort to manually preserve intact brain function until further measures are taken to restore sponta ...

and is seen by some as an indication of catastrophic damage to the

neocortex The neocortex, also called the neopallium, isocortex, or the six-layered cortex, is a set of layers of the mammalian cerebral cortex involved in higher-order brain functions such as sensory perception, cognition, generation of motor commands, sp ...

. Refractory status epilepticus is defined as status epilepticus that continues despite treatment with benzodiazepines and one antiepileptic drug. Super-refractory status epilepticus is defined as status epilepticus that continues or recurs 24 hours or more after the onset of anaesthetic therapy, including those cases where status epilepticus recurs on the reduction or withdrawal of anesthesia.

Nonconvulsive

Nonconvulsive status epilepticus is a relatively long duration change in a person's

level of consciousness An altered level of consciousness is any measure of arousal other than normal. Level of consciousness (LOC) is a measurement of a person's arousability and responsiveness to stimuli from the environment. A mildly depressed level of consciousne ...

without large scale bending and extension of the limbs due to seizure activity. It is of two main types with either prolonged

complex partial seizures Focal seizures (also called partial seizures and localized seizures) are seizures which affect initially only one hemisphere of the brain. The brain is divided into two hemispheres, each consisting of four lobes – the frontal, temporal, parie ...

s. Up to a quarter of cases of SE are nonconvulsive. In the case of complex partial status epilepticus, the seizure is confined to a small area of the brain, normally the

temporal lobe The temporal lobe is one of the four Lobes of the brain, major lobes of the cerebral cortex in the brain of mammals. The temporal lobe is located beneath the lateral fissure on both cerebral hemispheres of the mammalian brain. The temporal lobe ...

. Absence status epilepticus is marked by a generalized seizure affecting the whole brain. An

EEG Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The biosignals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in the neocortex ...

is needed to differentiate between the two conditions. This results in episodes characterized by a long-lasting

stupor Stupor is the lack of critical mental function and a level of consciousness, in which an affected person is almost entirely unresponsive and responds only to intense stimuli such as pain. The word derives from the Latin '' stupor'' ("numbness, inse ...

, staring, and unresponsiveness.

Causes

Only 25% of people who experience seizures or status epilepticus have

. The following is a list of possible causes: *

Stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

Hemorrhage Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vag ...

Intoxicants A psychoactive drug, psychopharmaceutical, psychoactive agent or psychotropic drug is a chemical substance, that changes functions of the nervous system, and results in alterations in perception, mood, consciousness, cognition or behavior. Th ...

or adverse reactions to drugs * Insufficient dosage or sudden withdrawal of a medication (especially

anticonvulsants Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of b ...

) *Insufficient dosage or sudden withdrawal of benzodiazepine(s) medication (akin to alcohol withdrawal); itself a class of antiseizure/anticonvulsant medications * Consumption of alcoholic beverages while on an anticonvulsant, or

alcohol withdrawal Alcohol withdrawal syndrome (AWS) is a set of symptoms that can occur following a reduction in alcohol use after a period of excessive use. Symptoms typically include anxiety, shakiness, sweating, vomiting, fast heart rate, and a mild fever. M ...

* Dieting or fasting while on an anticonvulsant * Starting on a new medication that reduces the effectiveness of the anticonvulsant or changes drug metabolism, decreasing its

half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ato ...

, leading to decreased blood concentrations * Developing a resistance to an anticonvulsant already being used *

Gastroenteritis Gastroenteritis, also known as infectious diarrhea and gastro, is an inflammation of the gastrointestinal tract including the stomach and intestine. Symptoms may include diarrhea, vomiting, and abdominal pain. Fever, lack of energy, and dehydra ...

while on an anticonvulsant, where lower levels of anticonvulsant may exist in the bloodstream due to vomiting of gastric contents or reduced absorption due to mucosal edema * 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 *

Sleep deprivation Sleep deprivation, also known as sleep insufficiency or sleeplessness, is the condition of not having adequate duration and/or quality of sleep to support decent alertness, performance, and health. It can be either chronic or acute and may vary ...

of more than a short duration is often the cause of a (usually, but not always, temporary) loss of seizure control *

Dehydration In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...

– moderate- to severe, especially when combined with any single factor above

Diagnosis

Diagnostic criteria vary, though most practitioners diagnose as status epilepticus for: one continuous, unremitting seizure lasting longer than five minutes, or recurrent seizures without regaining consciousness between seizures for greater than five minutes. Previous definitions used a 30-minute time limit. Nonconvulsive status epilepticus is believed to be under-diagnosed. New-onset refractory status epilepticus (NORSE) is defined as status epilepticus that does not respond to an anticonvulsant and lacks an obvious cause after two days of investigation.

Treatments

are the preferred initial treatment after which typically

fosphenytoin Fosphenytoin, also known as fosphenytoin sodium, and sold under the brand name Cerebyx among others, is a water-soluble phenytoin prodrug that is administered intravenously to deliver phenytoin, potentially more safely than intravenous phenytoin. ...

is given. First aid guidelines for seizures state that, as a rule, an ambulance should be called for seizures lasting longer than five minutes (or sooner if this is the person's first seizure episode and no precipitating factors are known, or if said SE happens to a person with epilepsy whose seizures were previously absent or well-controlled for a considerable time).

Benzodiazepines

When given intravenously,

appears to be superior to

diazepam Diazepam, first marketed as Valium, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is commonly used to treat a range of conditions, including anxiety, seizures, alcohol withdrawal syndrome, muscle spasms, insomnia, a ...

for stopping seizure activity. Intramuscular

appears to be a reasonable alternative especially in those who are not in hospital. The benzodiazepine of choice in North America for initial treatment is lorazepam, due to its relatively long duration of action (2–8 hours) when injected, and particularly due to its rapid onset of action, which is thought to be due to its high affinity for

GABA receptor The GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid (GABA), the chief inhibitory compound in the mature vertebrate central nervous system. There are two classes of GABA receptors: GABAA and ...

s and low

lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...

solubility In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution. The extent of the solubil ...

. This causes the drug to remain in the vascular compartment. If lorazepam is not available, or intravenous access is not possible, then

should be given. Alternatively, medication, such as glucagon, should be given through the bone (intraosseously). In several countries outside North America, such as the

Netherlands ) , anthem = ( en, "William of Nassau") , image_map = , map_caption = , subdivision_type = Sovereign state , subdivision_name = Kingdom of the Netherlands , established_title = Before independence , established_date = Spanish Netherl ...

, intravenous

clonazepam Clonazepam, sold under the brand names Klonopin and Rivotril, is a medication used to prevent and treat seizures, panic disorder, anxiety disorders, and the movement disorder known as akathisia. It is a tranquilizer of the benzodiazepine clas ...

is regarded as the drug of first choice. Cited advantages of clonazepam include a longer duration of action than diazepam and a lower propensity for the development of acute tolerance than lorazepam. The use of clonazepam for this indication is not recognized in North America, perhaps because it is not available as an intravenous formulation there. Particularly in children, another popular treatment choice is midazolam, given into the side of the mouth or the

nose A nose is a protuberance in vertebrates that houses the nostrils, or nares, which receive and expel air for respiration alongside the mouth. Behind the nose are the olfactory mucosa and the sinuses. Behind the nasal cavity, air next passes th ...

. Sometimes, the failure of lorazepam alone is considered to be enough to classify a case of SE as refractory–that is, resistant to treatment.

Phenytoin and fosphenytoin

Phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence seizures. The intr ...

was once another first-line therapy, although the

prodrug A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug ...

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 necessary if they are administered intravenously. Because the hydantoins take 15–30 minutes to work, a benzodiazepine or barbiturate is often coadministered. Because of diazepam's short duration of action, they were often administered together anyway. At present, these remain recommended second-line, follow-up treatments in the acute setting per guidelines by groups like Neurocritical Care Society (United States).

Barbiturates

Before the benzodiazepines were invented, barbiturates were used for purposes similar to benzodiazepines in general. Some are still used today in SE, for instance, 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

Thiopental Sodium thiopental, also known as Sodium Pentothal (a trademark of Abbott Laboratories), thiopental, thiopentone, or Trapanal (also a trademark), is a rapid-onset short-acting barbiturate general anesthetic. It is the thiobarbiturate analog of pe ...

pentobarbital Pentobarbital (previously known as pentobarbitone in Britain and Australia) is a short-acting barbiturate typically used as a sedative, a preanesthetic, and to control convulsions in emergencies. It can also be used for short-term treatment of ...

may also be used for that purpose if the seizures have to be stopped immediately or if the person has already been compromised by the underlying illness or toxic/metabolic-induced seizures; however, in those situations, thiopental is the agent of choice. That said, even when benzodiazepines are available, certain algorithms–including in the United States–indicate the use of phenobarbital as a second- or third-line treatment in SE. Such use is adjunctive. At least one U.S. study showed phenobarbital, when used alone, controlled about 60% of seizures, hence its preference as an add-on therapy.

Carbamazepine and valproate

Valproate Valproate (VPA) and its valproic acid, sodium valproate, and valproate semisodium forms are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in those ...

is available to be given intravenously, and may be used for status epilepticus.

Carbamazepine Carbamazepine (CBZ), sold under the trade name Tegretol among others, is an anticonvulsant medication used primarily in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other medi ...

is not available in an intravenous formulation, and does not play a role in status epilepticus.

Others

If this proves ineffective or if barbiturates cannot be used for some reason, then a

general anesthetic General anaesthetics (or anesthetics, see spelling differences) are often defined as compounds that induce a loss of consciousness in humans or loss of righting reflex in animals. Clinical definitions are also extended to include an induced coma ...

such as

(French). may be tried; sometimes it is used second after the failure of lorazepam. This would entail putting the person on

artificial ventilation Artificial ventilation (also called artificial respiration) is a means of assisting or stimulating respiration, a metabolic process referring to the overall exchange of gases in the body by pulmonary ventilation, external respiration, and interna ...

. Propofol has been shown to be effective in suppressing the jerks seen in

status epilepticus.

Ketamine Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a recreational drug. It is one of the safest anesthetics, as, in contrast with opiates, ether, and propofol, it suppresses ne ...

, an

NMDA antagonist NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the ''N''-Methyl-D-aspartate receptor (NMDAR). They are commonly used as anesthetics for animals and humans; the state of anesthesia they induce ...

drug, can be used as a last resort for drug-resistant status epilepticus.

Lidocaine Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia. When used for local anaesthesia or in nerve blocks, lidoca ...

has been used in cases that do not improve with other more typical medications. One concern is that seizures often begin again 30 minutes after it is stopped. Additionally, it is not recommended in those with heart or liver problems.

Prognosis

While sources vary, about 16 to 20% of first-time SE patients die; with other sources indicating between 10 and 30% of such patients die within 30 days. Further, 10-50% of first-time SE patients experience lifelong disabilities. In the 30% mortality figure, the great majority of these people have an underlying brain condition causing their status seizure such as

brain tumor A brain tumor occurs when abnormal cells form within the brain. There are two main types of tumors: malignant tumors and benign (non-cancerous) tumors. These can be further classified as primary tumors, which start within the brain, and seconda ...

, brain infection, brain trauma, or stroke. However, people with diagnosed epilepsy who have a status seizure also have an increased risk of death if their condition is not stabilized quickly, their medication and sleep regimen adapted and adhered to, and stress and other stimulant (seizure trigger) levels controlled. However, with optimal neurological care, adherence to the medication regimen, and a good

prognosis Prognosis (Greek: πρόγνωσις "fore-knowing, foreseeing") is a medical term for predicting the likely or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) or remain stabl ...

(no other underlying uncontrolled brain or other organic disease), the person—even people who have been diagnosed with

—in otherwise good health can survive with minimal or no brain damage, and can decrease risk of death and even avoid future seizures.

Epidemiology

In the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...

, about 40 cases of SE occur annually per 100,000 people. This includes about 10–20% of all first seizures.

Research

Allopregnanolone Allopregnanolone is a naturally occurring neurosteroid which is made in the body from the hormone progesterone. As a medication, allopregnanolone is referred to as brexanolone, sold under the brand name Zulresso, and used to treat postpartum d ...

is being studied in a clinical trial by the

Mayo Clinic The Mayo Clinic () is a nonprofit American academic medical center focused on integrated health care, education, and research. It employs over 4,500 physicians and scientists, along with another 58,400 administrative and allied health staff, ...

to treat super-resistant status epilepticus.

References

External links

Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society
* {{CNS diseases of the nervous system Medical emergencies Epilepsy Seizure types Wikipedia medicine articles ready to translate Wikipedia emergency medicine articles ready to translate