Status epilepticus

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Status epilepticus
Spike-waves.png
Generalized 3 Hz spike-and-wave discharges on an electroencephalogram
Specialty Emergency medicine, neurology
Symptoms Regular pattern of contraction and extension of the arms and legs, movement of one part of the body, unresponsive [1]
Duration>5 minutes [1]
Risk factors Epilepsy, underlying problem with the brain [2]
Diagnostic method Blood sugar, imaging of the head, blood tests, electroencephalogram [1]
Differential diagnosis Psychogenic nonepileptic seizures, movement disorders, meningitis, delirium [1]
Treatment Benzodiazepines, fosphenytoin, phenytoin, [1] paraldehyde (rarely used)
Prognosis ~20% thirty-day risk of death [1]
Frequency40 per 100,000 people per year [2]

Status epilepticus (SE), or status seizure, is a medical condition consisting of a single seizure lasting more than 5 minutes, or 2 or more seizures within a 5-minute period without the person returning to normal between them. [3] [1] Previous definitions used a 30-minute time limit. [2] 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 seizures or complex partial seizures. [1] Status epilepticus is a life-threatening medical emergency, particularly if treatment is delayed. [1]

Contents

Status epilepticus may occur in those with a history of epilepsy as well as those with an underlying problem of the brain. [2] These underlying brain problems may include trauma, infections, or strokes, among others. [2] [4] Diagnosis often involves checking the blood sugar, imaging of the head, a number of blood tests, and an electroencephalogram. [1] Psychogenic nonepileptic seizures may present similarly to status epilepticus. [1] Other conditions that may also appear to be status epilepticus include low blood sugar, movement disorders, meningitis, and delirium, among others. [1] Status epilepticus can also appear when tuberculous meningitis becomes very severe.

Benzodiazepines are the preferred initial treatment, after which typically phenytoin is given. [1] Possible benzodiazepines include intravenous lorazepam as well as intramuscular injections of midazolam. [5] A number of other medications may be used if these are not effective, such as phenobarbital, propofol, or ketamine. [1] After initial treatment with benzodiazepines, typical antiseizure drugs should be given, including valproic acid (valproate), fosphenytoin, levetiracetam, or a similar substance(s). [6] While empirically based treatments exist, few head-to-head clinical trials exist, so the best approach remains undetermined. [6] This said, "consensus-based" best practices are offered by the Neurocritical Care Society. [6] Intubation may be required to help maintain the person's airway. [1] Between 10% and 30% of people who have status epilepticus die within 30 days. [1] The underlying cause, the person's age, and the length of the seizure are important factors in the outcome. [2] Status epilepticus occurs in up to 40 per 100,000 people per year. [2] Those with status epilepticus make up about 1% of people who visit the emergency department. [1]

Signs and symptoms

Status epilepticus can be divided into two categories: convulsive and nonconvulsive (NCSE). [1]

Convulsive

Convulsive status epilepticus presents an urgent neurological condition, which is characterized by an elongated and uncontrollable onsets of seizures in which a regular pattern of contraction and extension of the arms and legs will be observed from the patient. [1] [7] The symptoms can be managed by initially introducing a seizure suppressing medication as the first stage of the treatment, which optimally works only for that stage because any delay will reduce the efficacy of those medications. Convulsive status epilepticus commonly affects the elderly and young children, with a mortality rate of up to 20–30% of elderly patients and 0–3% of young children. Patients who survive initial onset are often left with cognitive and neurological defects. [7]

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

Generalized myoclonus is commonly seen in comatose people following cardiopulmonary resuscitation (CPR) and is seen by some as an indication of catastrophic damage to the neocortex; myoclonus status in this situation can usually (but not always) be considered an agonal phenomenon. [8]

Refractory status epilepticus is defined as status epilepticus that continues despite treatment with benzodiazepines and one antiepileptic drug. [9]

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. [10]

Nonconvulsive

Nonconvulsive status epilepticus is a relatively long duration change in a person's level of consciousness without large-scale bending and extension of the limbs due to seizure activity. [11] It is of two main types with either prolonged complex partial seizures or absence seizures. [11] Up to a quarter of cases of SE are nonconvulsive. [11]

In the case of complex partial status epilepticus, the seizure is confined to a small area of the brain, normally the temporal lobe. Absence status epilepticus is marked by a generalized seizure affecting the whole brain. An electroencephalogram (EEG) is needed to differentiate between the two conditions.

The cases of nonconvulsive status epilepticus are characterized by a long-lasting stupor, staring, and unresponsiveness. Recent studies indicated 50% of cases involve patients that are semi-conscious in a way that they can respond but are confused spontaneously. Only 6% have shown a decelerated thought process. About 44% of cases of nonconvulsive status epilepticus are marked by a prolonged or fragmentary coma. [12]

Causes

Only 25% of people who experience seizures or status epilepticus have epilepsy. [13] The following is a list of possible causes:

Diagnosis

Diagnostic criteria vary, though most practitioners diagnose as status epilepticus for: one continuous, unremitting seizure lasting longer than five minutes, [14] or recurrent seizures without regaining consciousness between seizures for greater than five minutes. [1] Previous definitions used a 30-minute time limit. [2]

Nonconvulsive status epilepticus is believed to be under-diagnosed. [15]

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. [16] [17]

Treatments

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

Benzodiazepines are the preferred initial treatment after which typically phenytoin or fosphenytoin is given. [1] [6] 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). [18]

Benzodiazepines

When given intravenously, lorazepam appears to be superior to diazepam for stopping seizure activity. [5] [19] Intramuscular midazolam appears to be a reasonable alternative especially in those who are not in hospital. [5]

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 receptors and low lipid solubility. This causes the drug to remain in the vascular compartment. If lorazepam is not available, or intravenous access is not possible, then diazepam should be given. [20] Alternatively, medication, such as glucagon, should be given through the bone (intraosseously). [6]

In several countries outside North America, such as the Netherlands, [21] intravenous clonazepam is regarded as the drug of first choice. [21] Cited advantages of clonazepam include a longer duration of action than diazepam and a lower propensity for the development of acute tolerance than lorazepam. [22] The use of clonazepam for this indication is not recognized in North America, perhaps because it is not available as an intravenous formulation there. [22]

Particularly in children, another popular treatment choice is midazolam, given into the side of the mouth or the nose. [23] 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 was once another first-line therapy, [24] 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 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. [25] At present, these remain recommended second-line, follow-up treatments in the acute setting per guidelines by groups like Neurocritical Care Society (United States). [6]

Barbiturates

Before the benzodiazepines were invented, barbiturates were used for purposes similar to benzodiazepines in general. Some are still used today in SE[ clarification needed ], 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 phenobarbital. Thiopental or pentobarbital 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; [6] however, in those situations, thiopental is the agent of choice. [26] 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. [6]

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. [24] It was found that all of valproate, phenobarbital, fosphenytoin (phenytoin), midazolam or levetiracetam are considered to the second line drugs after benzodiazepine is used as the first line treatment. It was found that especially valproate in contrast to antiepileptic drugs is more effective to the treatment of nonconvulsive status epilepticus and more commonly used for it. [27]

Others

If this proves ineffective or if barbiturates cannot be used for some reason, then a general anesthetic such as propofol [28] may be tried; sometimes it is used second after the failure of lorazepam. [29] This would entail putting the person on artificial ventilation. Propofol has been shown to be effective in suppressing the jerks seen in myoclonus status epilepticus. [30]

Ketamine, an NMDA antagonist drug, can be used as a last resort for drug-resistant status epilepticus. [31]

Lidocaine has been used in cases that do not improve with other more typical medications. [32] One concern is that seizures often begin again 30 minutes after it is stopped. [32] Additionally, it is not recommended in those with heart or liver problems. [32]

Prognosis

While sources vary, about 16 to 20% of first-time SE patients die; [6] with other sources indicating between 10 and 30% of such patients die within 30 days. [1] Further, 10-50% of first-time SE patients experience lifelong disabilities. [6] In the 30% mortality figure, 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. 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 (no other underlying uncontrolled brain or other organic disease), the person—even people who have been diagnosed with epilepsy—in otherwise good health can survive with minimal or no brain damage, and can decrease risk of death and even avoid future seizures. [13]

Prognosis of refractory status epilepticus

A different prognosis method was developed for refractory status epilepticus (RSE). Prognosis studies have shown that there is no clear structure of the symptoms; since they range from gastrointestinal to flu-like symptoms, which are considered to be mild and only represent 10%, while the remaining majority of 90% of the clinical cases were unknown.[ clarification needed ] It was found that it takes a period of 1 to 14 days for the patient to reach the prodromal stage in which the episode is yet to come for the first time. It was found that the frequency of those initial seizures starts from a short and inconsistent seizures that lasts for a few hours and may extend to few days. It can simply strike to hundreds of seizures per day, which is the stage that needed an urgent medical intervene in which the patient expected to be in the intensive care unit (ICU) as soon as possible. Typically focal seizures are the most common among those cases. [33]

Epidemiology

In the United States, about 40 cases of SE occur annually per 100,000 people. [2] This includes about 10–20% of all first seizures. [34]

Prevalence

It was found that status epilepticus is more prevalent among African Americans than Caucasian Americans by threefold in North London, and that Asian children have recorded a relatively higher susceptibility of developing the more severe form of febrile seizures. These ethnic distribution rates indicate the genetic contribution to the susceptibility of status epilepticus. Also, studies have shown that status epilepticus is more common in males. [34]

Aetiology

Many studies have found out that age is the most related factor to the etiology of status epilepticus, since 52% of febrile seizures was found in children, while for adults acute cerebralvascular cases was more common, side by side with hypoxia and other metabolic causes. [34]

Research

Allopregnanolone is being studied in a clinical trial by the Mayo Clinic to treat super-resistant status epilepticus. [35]

See also

Related Research Articles

<span class="mw-page-title-main">Epilepsy</span> Group of neurological disorders causing seizures

Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. An epileptic seizure is the clinical manifestation of an abnormal, excessive, and synchronized electrical discharge in the neurons. The occurrence of two or more unprovoked seizures defines epilepsy. The occurrence of just one seizure may warrant the definition in a more clinical usage where recurrence may be able to be prejudged. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical activity in the brain. These episodes can result in physical injuries, either directly such as broken bones or through causing accidents. In epilepsy, seizures tend to recur and may have no detectable underlying cause. Isolated seizures that are provoked by a specific cause such as poisoning are not deemed to represent epilepsy. People with epilepsy may be treated differently in various areas of the world and experience varying degrees of social stigma due to the alarming nature of their symptoms.

<span class="mw-page-title-main">Seizure</span> Period of symptoms due to excessive or synchronous neuronal brain activity

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 loss of consciousness, to shaking movements involving only part of the body with variable levels of consciousness, to a subtle momentary loss of awareness. These episodes usually last less than two minutes and it takes some time to return to normal. Loss of bladder control may occur.

<span class="mw-page-title-main">Febrile seizure</span> Seizure associated with high body temperature

A febrile seizure, also known as a fever fit or febrile convulsion, is a seizure associated with a high body temperature but without any serious underlying health issue. They most commonly occur in children between the ages of 6 months and 5 years. Most seizures are less than five minutes in duration, and the child is completely back to normal within an hour of the event. There are two types: simple febrile seizures and complex febrile seizures. Simple febrile seizures involve an otherwise healthy child who has at most one tonic-clonic seizure lasting less than 15 minutes in a 24-hour period. Complex febrile seizures have focal symptoms, last longer than 15 minutes, or occur more than once within 24 hours. About 80% are classified as simple febrile seizures.

Anticonvulsants are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder and borderline personality disorder, since many seem to act as mood stabilizers, and for the treatment of neuropathic pain. Anticonvulsants suppress the excessive rapid firing of neurons during seizures. Anticonvulsants also prevent the spread of the seizure within the brain.

<span class="mw-page-title-main">Diazepam</span> Benzodiazepine sedative

Diazepam, sold under the brand name Valium among others, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is used to treat a range of conditions, including anxiety, seizures, alcohol withdrawal syndrome, muscle spasms, insomnia, and restless legs syndrome. It may also be used to cause memory loss during certain medical procedures. It can be taken orally, as a suppository inserted into the rectum, intramuscularly, intravenously or used as a nasal spray. When injected intravenously, effects begin in one to five minutes and last up to an hour. When taken by mouth, effects begin after 15 to 60 minutes.

<span class="mw-page-title-main">Lorazepam</span> Benzodiazepine medication

Lorazepam, sold under the brand name Ativan among others, is a benzodiazepine medication. It is used to treat anxiety, trouble sleeping, severe agitation, active seizures including status epilepticus, alcohol withdrawal, and chemotherapy-induced nausea and vomiting. It is also used during surgery to interfere with memory formation and to sedate those who are being mechanically ventilated. It is also used, along with other treatments, for acute coronary syndrome due to cocaine use. It can be given orally, transdermal, intravenously (IV), or intramuscularly When given by injection, onset of effects is between one and thirty minutes and effects last for up to a day.

<span class="mw-page-title-main">Midazolam</span> Benzodiazepine used for anesthesia and procedural sedation

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 induces sleepiness, decreases anxiety, and causes anterograde amnesia.

<span class="mw-page-title-main">Myoclonus</span> Involuntary, irregular muscle twitch

Myoclonus is a brief, involuntary, irregular twitching of a muscle, a joint, or a group of muscles, different from clonus, which is rhythmic or regular. Myoclonus describes a medical sign and, generally, is not a diagnosis of a disease. It belongs to the hyperkinetic movement disorders, among tremor and chorea for example. These myoclonic twitches, jerks, or seizures are usually caused by sudden muscle contractions or brief lapses of contraction. The most common circumstance under which they occur is while falling asleep. Myoclonic jerks occur in healthy people and are experienced occasionally by everyone. However, when they appear with more persistence and become more widespread they can be a sign of various neurological disorders. Hiccups are a kind of myoclonic jerk specifically affecting the diaphragm. When a spasm is caused by another person it is known as a provoked spasm. Shuddering attacks in babies fall in this category.

<span class="mw-page-title-main">Levetiracetam</span> Medication

Levetiracetam, sold under the brand name Keppra among others, is a medication used to treat epilepsy. It is used for partial-onset, myoclonic, or tonic–clonic seizures and is taken either by mouth as an immediate or extended release formulation or by injection into a vein.

<span class="mw-page-title-main">Clonazepam</span> Benzodiazepine medication

Clonazepam, sold under the brand names Klonopin and Rivotril, is a medication used to prevent and treat anxiety disorders, seizures, bipolar mania, agitation associated with psychosis, OCD and akathisia. It is a long-acting tranquilizer of the benzodiazepine class. It possesses anxiolytic, anticonvulsant, sedative, hypnotic, and skeletal muscle relaxant properties. It is typically taken orally but is also used intravenously. Effects begin within one hour and last between eight and twelve hours in adults.

Epilepsia partialis continua is a rare type of brain disorder in which a patient experiences recurrent motor epileptic seizures that are focal, and recur every few seconds or minutes for extended periods. It is sometimes called Kozhevnikov's epilepsia named after Russian psychiatrist Aleksei Yakovlevich Kozhevnikov who first described this type of epilepsy.

<span class="mw-page-title-main">Phenobarbital</span> Medication of the barbiturate type

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 epilepsy in developing countries. In the developed world, it is commonly used to treat seizures in young children, while other medications are generally used in older children and adults. In developed countries it is used for veterinary purposes. It may be used intravenously, injected into a muscle, or taken by mouth. The injectable form may be used to treat status epilepticus. Phenobarbital is occasionally used to treat trouble sleeping, anxiety, and drug withdrawal and to help with surgery. It usually begins working within five minutes when used intravenously and half an hour when administered by mouth. Its effects last for between four hours and two days.

<span class="mw-page-title-main">Primidone</span> Barbiturate medication used to treat seizures and tremors

Primidone, sold under various brand names, is a barbiturate medication that is used to treat partial and generalized seizures and essential tremors. It is taken by mouth.

<span class="mw-page-title-main">Clobazam</span> Benzodiazepine class medication

Clobazam, sold under the brand names Frisium, Onfi and others, is a benzodiazepine class medication that was patented in 1968. Clobazam was first synthesized in 1966 and first published in 1969. Clobazam was originally marketed as an anxioselective anxiolytic since 1970, and an anticonvulsant since 1984. The primary drug-development goal was to provide greater anxiolytic, anti-obsessive efficacy with fewer benzodiazepine-related side effects.

<span class="mw-page-title-main">Fosphenytoin</span> Anti-epileptic drug

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. It is used in the acute treatment of convulsive status epilepticus.

Complex partial status epilepticus (CPSE) is one of the non-convulsive forms of status epilepticus, a rare form of epilepsy defined by its recurrent nature. CPSE is characterized by seizures involving long-lasting stupor, staring and unresponsiveness. Sometimes this is accompanied by motor automatisms, such as eye twitching.

Progressive Myoclonic Epilepsies (PME) are a rare group of inherited neurodegenerative diseases characterized by myoclonus, resistance to treatment, and neurological deterioration. The cause of PME depends largely on the type of PME. Most PMEs are caused by autosomal dominant or recessive and mitochondrial mutations. The location of the mutation also affects the inheritance and treatment of PME. Diagnosing PME is difficult due to their genetic heterogeneity and the lack of a genetic mutation identified in some patients. The prognosis depends largely on the worsening symptoms and failure to respond to treatment. There is no current cure for PME and treatment focuses on managing myoclonus and seizures through antiepileptic medication (AED).

Post-traumatic seizures (PTS) are seizures that result from traumatic brain injury (TBI), brain damage caused by physical trauma. PTS may be a risk factor for post-traumatic epilepsy (PTE), but a person having a seizure or seizures due to traumatic brain injury does not necessarily have PTE, which is a form of epilepsy, a chronic condition in which seizures occur repeatedly. However, "PTS" and "PTE" may be used interchangeably in medical literature.

Generally, seizures are observed in patients who do not have epilepsy. There are many causes of seizures. Organ failure, medication and medication withdrawal, cancer, imbalance of electrolytes, hypertensive encephalopathy, may be some of its potential causes. The factors that lead to a seizure are often complex and it may not be possible to determine what causes a particular seizure, what causes it to happen at a particular time, or how often seizures occur.

Febrile infection-related epilepsy syndrome (FIRES), is onset of severe seizures following a febrile illness in someone who was previously healthy. The seizures may initially be focal; however, often become tonic-clonic. Complications often include intellectual disability, behavioral problems, and ongoing seizures.

References

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  26. ↑ Lee S. K. (2020). Diagnosis and Treatment of Status Epilepticus. Journal of epilepsy research, 10(2), 45–54. doi : 10.14581/jer.20008
  27. ↑ Lee S. K. (2020). Diagnosis and Treatment of Status Epilepticus. Journal of epilepsy research, 10(2), 45–54. doi : 10.14581/jer.20008
  28. ↑ Pourrat, X; J .M. Serekian, D. Antier, J. Grassin (June 9, 2001). "Generalized tonic-clonic status epilepticus: therapeutic strategy". Presse Médicale. 30 (20): 1031–6. PMID   11433696.{{cite journal}}: CS1 maint: multiple names: authors list (link) (French).
  29. ↑ 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. S2CID   29378123.
  30. ↑ 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. PMC   1757284 . PMID   12082068.
  31. ↑ Gomes, D; Pimentel, J; Bentes, C; Aguiar de Sousa, D; Antunes, AP; Alvarez, A; Silva, ZC (31 October 2018). "Consensus Protocol for the Treatment of Super-Refractory Status Epilepticus". Acta Médica Portuguesa. 31 (10): 598–605. doi: 10.20344/amp.9679 . PMID   30387431.
  32. 1 2 3 Schmutzhard, E; Pfausler, B (Oct 2011). "Complications of the management of status epilepticus in the intensive care unit". Epilepsia. 52 (Suppl 8): 39–41. doi: 10.1111/j.1528-1167.2011.03233.x . PMID   21967359. S2CID   205692349.
  33. ↑ Sculier, C., & Gaspard, N. (2019). New onset ref,ractory status epilepticus (NORSE). Seizure, 68, 72–78. doi : 10.1016/j.seizure.2018.09.018
  34. 1 2 3 Shorvon, S., & Sen, A. (2020). What is status epilepticus and what do we know about its epidemiology?. Seizure, 75, 131–136. doi : 10.1016/j.seizure.2019.10.003
  35. ↑ "A Study Using SAGE-547 for Super Resistant Status Epilepticus". Mayo Clinic. Archived from the original on 2017-03-08. Retrieved 2017-03-07.
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