Status epilepticus

Status epilepticus (SE) is a life-threatening condition in which the brain is in a state of persistent seizure. Definitions vary, but currently it is defined as one continuous, unremitting seizure lasting longer than 5 minutes, or recurrent seizures without regaining consciousness between seizures for greater than 5 minutes. Previous definitions used a 30 minute time limit. Treatment is, however, generally started after the seizure has lasted five minutes. It is always considered a medical emergency. There is some evidence that five minutes is sufficient to damage neurons and that seizures are unlikely to self-terminate by that time.

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 patient's first seizure episode and no precipitating factors are known, or if SE happens to a person with epilepsy whose seizures were previously absent or well controlled for a considerable time period). The mortality rate of status epilepticus is estimated at 20%. However, with optimal neurological care, adherence to the medication regimen, and a good prognosis (no other underlying uncontrolled brain or other organic disease), the patient- even people who have been diagnosed with epilepsy- in otherwise good health can survive with minimal or no brain damage, and can decrease their risk of death and even avoid future seizures.

Signs and symptoms
Status epilepticus can be divided into two categories—convulsive and nonconvulsive, the latter of which is underdiagnosed.

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.

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.

Causes
Only 25% of people who experience seizures or status epilepticus have epilepsy. Causes include:
 * Stroke
 * Nerve Gas exposure.
 * Hemorrhage
 * Intoxicants or adverse reactions to drugs
 * 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
 * Taking medicine at wrong times as a result of a time zone change while traveling
 * Dislike of the medication or its side effects
 * Sudden withdrawal from a seizure medication, such causes include:
 * Sudden lack of access to medication due to unexpected circumstances
 * Benzodiazepine withdrawal syndrome resulting from inability to acquire non-prescribed benzodiazepines that were used being abused.
 * 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
 * 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, leading to decreased blood concentrations
 * Developing a resistance to an anticonvulsant already being used
 * Gastroenteritis while on an anticonvulsant, 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
 * Insomnia or sleep deprivation of more than a short duration is often the cause of a (usually, but not always, temporary) loss of seizure control; those whose seizures are inherently severe but otherwise controlled by medication can regress and suffer severe seizures or status epilepticus even if they are still taking their medication unless they regain their rest.

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 its pharmacological effects were longer lasting than those of an equal dose of diazepam. This meant it did not have to be repeatedly injected like diazepam, the effects of which would wear off five to 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, or lorazepam.

Today, the benzodiazepine of choice is lorazepam for initial treatment due to its relatively long (2–8 hr) duration of action when injected, and its rapid onset of action, which is 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. Particularly in children, another increasingly popular treatment choice is buccal and intranasal midazolam, which can be given into the side of the mouth or the nose, respectively. 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 coadministered. Because of diazepam's short duration of action, they were often administered together anyway.

Carbamazepine and valproate
Valproate is available to be given intravenously, and may be used for status epilepticus. Carbamazepine is not available in an intravenous formulation, and does not play a role in status epilepticus.

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, circa 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.

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

Lidocaine
The use of lidocaine in status epilepticus was first reported in 1955 by Bernhard, Boem and Hojeberg. 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. Lidocaine is a sodium channel blocker and has been used where sodium channel dysfunction was suspected. However, in some studies, it was either ineffective or even harmful for most patients. 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 or 2–3 mg/kg.

Ketamine
Ketamine, an NMDA antagonist drug, can be used as a last resort for drug-resistant status epilepticus.

Prognosis
About one in five people who have the disease, a total of 42,000 annually in the United States, will die within 30 days of having an initial SE 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 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.

Epidemiology
In the United States, about 40 cases of SE occur annually per 100,000 people. This includes about 10-20% of all first seizures.