Status Epilepticus – Important Symptoms, Causes, Diagnosis, Treatment

What is Status Epilepticus

Status epilepticus refers to a seizure that fails to remit.

While traditionally defined as 30 minutes of continuous seizure activity, a widely accepted current definition is at least 5 minutes of continuous seizures or two or more seizures with incomplete recovery of consciousness in between them.

Status epilepticus is a seizure or a series of seizures that lasts 5 minutes or longer.

What is the current definition of Status Epilepticus? 

Status Epilepticus is defined as 5 minutes or more of the following:

1. Continuous clinical and/or electrographic seizure activity; or

2. Recurrent seizure activity without recovery of consciousness (returning to baseline) between seizures.

How is Status epilepticus classified?

Classified into convulsive or nonconvulsive status epilepticus

• Convulsive. This is a sudden shaking of the body that cannot be controlled. Convulsive status epilepticus is a medical emergency. It can be characterized as either primary or secondary generalized seizures.
• Non convulsive. This kind of seizure is more subtle. It may include slowed or absent speech, rapid breathing, a dazed appearance, tiredness (lethargy), and confusion. Nonconvulsive status epilepticus refers to either absence or complex partial status epilepticus.

In either case, the patient does not have major motor seizures but is abnormal cognitively and may appear to be in a fugue state. Absence status appears to have no morbidity (unless injuries occur during the status), but complex partial status may lead to permanent cognitive deficits.

Status epilepticus is a medical emergency. Seizures that last for a long time (prolonged seizures) can lead to brain damage or even death.

What is convulsive Status Epilepticus? 

Convulsive Status Epilepticus is defined as convulsions that are associated with rhythmic jerking of the extremities.

Characteristic findings of generalized convulsive SE are generalized tonic–clonic movements of the extremities and mental status impairment (coma, lethargy, confusion).

Focal neurologic deficits may be associated with the postictal period.

What are the underlying causes of Status Epilepticus? 

Acute Processes	Chronic Processes
Toxic–metabolic disturbances: electrolyte abnormalities, hypoglycemia, renal failure Drugs: toxicity, withdrawal, AED noncompliance	Chronic ethanol abuse in setting of ethanol intoxication or withdrawal
CNS inflammation: meningitis, encephalitis, abscess, autoimmune encephalitis, paraneoplastic syndromes	CNS tumors
Vascular: ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, cerebral sinus thrombosis, hypertensive encephalopathy, PRES	Remote CNS pathology (e.g., stroke, abscess, TBI, cortical dysplasia)
Head trauma with or without epidural or subdural hematoma, hypoxia, cardiac arrest, sepsis	Preexisting epilepsy: breakthrough seizures or discontinuation of AEDs

CNS , Central nervous system; AED , antiepileptic drugs; TBI , traumatic brain injury; PRES , posterior reversible encephalopathy syndrome.

What are the most common causes of status epilepticus

The most common causes of status epilepticus in a more or less descending order of frequency are given below

Subtherapeutic antiepileptic drugs (AED)

Remote brain injury

Stroke

Head trauma

Hypoglycemia and hyperglycemia

Electrolyte imbalance (Mg, Ca, Na)

Hepatic or renal failure

Sepsis

Anoxic brain injury

Drug intoxications

Alcohol withdrawal

Hypertensive encephalopathy

Central nervous system infections

Neoplasms

Congenital malformations

Cryptogenic

Autoimmune encephalitis

Paraneoplastic syndromes

Other causes:

• low blood concentration of antiepileptic drugs in patients with chronic epilepsy (34%)
• remote symptomatic causes (24%)
• cerebrovascular accidents (22%)
• anoxia or hypoxia (10%)
• metabolic causes (10%)
• alcohol and drug withdrawal (10%)
• Overdose of alcohol, drugs, or medicine
• High fever (febrile seizures)
• Failure to take epilepsy medicines or taking a dose that is too low
• Very low blood sugar (glucose)
• Imbalance of minerals (electrolytes) in the body
• Head injury (trauma)
• Infection, such as meningitis
• Stroke
• Brain or nervous system tumors
• Brain disorders that get worse over time (progressive neurodegenerative diseases)

What increases the risk?

Your child is more likely to develop this condition if he or she has:

• An existing seizure disorder, such as epilepsy.
• A family history of seizure disorders.
• A genetic disorder.
• A disorder that is passed from parent to child (inherited).
• A mother who used or abused alcohol or drugs during pregnancy.
• A history of traumatic brain injuries.
• A recent change in seizure or epilepsy medicine, or failure to take seizure or epilepsy medicine as told.

What are the symptoms of Status epilepticus?

Symptoms of this condition depend on the kind of seizure your child is having.

Symptoms of Convulsive status epilepticus:

• Jerking muscle spasms of the arms and legs.
• Confusion, mental impairment, or loss of consciousness.
• Falling.
• Difficulty breathing.
• Inability to move (paralysis) or weakness that lasts for hours to days after the seizure.

Symptoms of Non convulsive status epilepticus:

• Daydreaming, staring, or a confused state.
• Subtle movements or twitching in the eye or face.
• Seeing, hearing, tasting, smelling, or feeling things that are not real (hallucinations).
• General mistrust of others (paranoia).
• Agitation or aggression.
• False beliefs (delusions).
• Severe loss of contact with reality (psychosis).
• Laughter.
• Nausea or vomiting.
• Uncontrollable shaking (tremors).

Non convulsive seizures may be hard to recognize and may only be identified through a machine that monitors the electrical activity of the brain (electroencephalogram, EEG).

How is status epilepticus diagnosed?

This condition may be diagnosed based on:

• Your child’s medical history and a physical exam.
• Results of an EEG.
• Imaging tests, such as CT scans or MRI. These check for signs of head trauma or tumors.
• Blood tests to check for:
  • Vitamin and electrolyte levels.
  • Signs of infection.
  • Levels of seizure medicine.
• Removing a sample of the fluid that surrounds the spine (lumbar puncture) to check for infection.

What are the initial diagnostic tests for convulsive Status Epilepticus?

All Patients	Based on Clinical Presentation
Finger stick glucose	LP
CBC, BMP, calcium (total and ionized), magnesium	Liver function tests, serial troponins, type and hold, coagulation studies, arterial blood gas
Head CT scan (appropriate for most cases), rule out stroke, ICH, cerebral venous sinus thrombosis	Brain MRI
AED levels	Comprehensive toxicology panel
Continuous EEG monitoring	Autoimmune disease screening

CBC , Complete blood count; BMP, basic metabolic panel; LP , lumbar puncture; CT , computed tomography; ICH , Intracranial hemorrhage; MRI , magnetic resonance imaging; AED , antiepileptic drug; EEG , electroencephalograph.

How is Status Epilepticus treated?

This condition requires emergency treatment to prevent injury or damage to the brain. Treatment may include:

• Providing supportive care, such as oxygen and breathing assistance.
• Giving anti-seizure medicines to reduce or stop the seizure.
• Monitoring blood pressure, heart rate, and breathing.
• Managing the underlying cause of the seizure, such as giving glucose for low blood sugar.
• Making a care plan to treat any conditions that may have caused the status epilepticus.

How is Status Epilepticus treated? 

The principal goal of treatment is to stop both clinical and electrographic seizure activity immediately.

The following timeline usually followed:

• 0 to 2 minutes: Evaluate airway patency, breathing, and circulation, and obtain finger stick glucose.

• 0 to 5 minutes: Obtain peripheral IV access, reverse thiamine deficiency, treat hypoglycemia (thiamine given before dextrose), administer benzodiazepines, resuscitate hemodynamics, and then send basic laboratory studies.

• Administer first-line treatment benzodiazepines

First-Line Benzodiazepines

Medications	LorazEPam (IV)	Midazolam (IM, IntranasalLY, Buccally)	Diazepam (IV, Rectally)
Dose	0.1 mg/kg IV up to 4 mg per dose, may repeat in 5-10 minutes	0.2 mg/kg IM up to maximum of 10 mg	0.15 mg/kg IV up to 10 mg per dose, may repeat in 5 minutes. 20 mg rectally
Adverse events	Hypotension, respiratory depression	Hypotension, respiratory depression	Hypotension, respiratory depression
Half-life	12-14 hours	1-7 hours	18-20 hours IV, about 46 hours rectally

IM , Intramuscularly; IV , intravenously.

6 to 10 minutes: Administer second-line treatment, screen for the underlying cause of SE, and immediately begin treatment of life-threatening causes of SE (e.g., meningitis, intracranial mass lesion).

If the patient stops seizing, the next goal is rapid attainment of therapeutic levels of an antiepileptic drug (AED) and continued dosing for maintenance therapy.

If first-line drugs fail, then second-line agents must be given to stop SE. In patients with known epilepsy who have been on an AED before admission, it is reasonable to provide an IV bolus of this AED, if available, prior to initiating an additional agent.

This may include additional boluses that will result in higher than normal target concentrations of the AED to achieve the desired therapeutic response (i.e., cessation of seizure activity).

What are the preferred second line medications for Status Epilepticus?

Second Line Treatment Agents for Status Epilepticus

Medication	Fosphenytoin	Valproic Acid	Phenobarbital	Levetiracetam	Midazolam CI
Dose	20 mg PE/kg IV, may give an additional 5 mg/kg	20-40 mg/kg IV, may give an additional 20 mg/kg	20 mg/kg IV, may give an additional 5-10 mg/kg	1000-3000 mg IV	Initial dosing 0.2 mg/kg; rate of 2 mg/minCI: 0.05-2 mg/kg/h
Adverse events	Hypotension, arrhythmias	Pancreatitis, thrombocytopenia, hepatotoxicity, hyperammonemia,	Hypotension, respiratory depression	None	Respiratory depression, hypotension
Half-life	12-29 hours	10-12 hours	24-110 hours	6-8 hours	1-7 hours
Total level	15-20 μg/mL	80-140 μg/mL	20-50 mg/mL	12-46 mg/mL	NA

CI , Continuous infusion; PE , phenytoin equivalent; NA , not available.

How is absence status epilepticus treated? 

Absence status is treated with intravenous diazepam or derivatives, not with phenytoin or the barbiturates.

Intravenous valproate also can be an effective therapy.

How is complex partial status epilepticus treated? 

Complex partial status is usually not associated with life-threatening systemic complications but may result in impairment of memory function and should be treated aggressively, similar to generalized tonic–clonic status.

However, one may decide to initiate therapy with nonsedating AEDs before using anesthetic agents.

How is convulsive status epilepticus treated? 

Generalized tonic–clonic or convulsive status epilepticus is a medical emergency, and every effort should be made to stop the seizures as quickly as possible.

Sequelae are more frequent if seizures are not stopped within 60 minutes of onset. The initial approach includes administration of thiamine followed by glucose when glucose levels are low or unknown and correction of electrolyte imbalances.

Hyperthermia, which may accompany status epilepticus, should be aggressively controlled. Initial specific therapy should include a benzodiazepine (e.g., lorazepam, 0.1 mg/kg intravenously infused at 1 to 2 mg/min). If seizures continue, a second dose can be given. Regardless, second-line therapy in the form of a longer acting AED is initiated.

Intravenous fosphenytoin should be given at a rate up to 150 mg/min with cardiac monitoring.

If the patient still continues to have seizures, other options include intravenous valproate or phenobarbital. Intravenous levetiracetam and lacosamide have also been used in this situation. If the patient is resistant to phenytoin, phenobarbital, and lorazepam, anesthesia should be administered.

Choices for this include midazolam, propofol, and pentobarbital. An outline for the treatment of status epilepticus is presented in the below table

Protocol for Treatment of Generalized Tonic Clonic Status Epilepticus

Time	Action
0-5 minutes	Provide for maintenance of vital signs. Maintain airway. Give oxygen. Observe and examine patient.
6-10 minutes	Obtain 50 mL of blood for glucose, calcium, magnesium, electrolytes, blood urea nitrogen, liver functions, anticonvulsant levels, CBC, and toxicology screen. Begin normal saline IV and give 50 mL of 50% glucose and 100 mg of thiamine. Monitor ECG, blood pressure, and, if possible, EEG.
11-30 minutes	Use intravenous lorazepam to stop seizures, 0.1 mg/kg at 1-2 mg/min.
11-30 minutes	If seizures continue, load with phenytoin using fosphenytoin 20 mg phenytoin equivalents (PE)/kg at 150 mg PE/min. If cardiac arrhythmia or hypotension occurs, slow the infusion rate.
31-60 minutes	If seizures persist 10-20 minutes after administration of phenytoin, give an additional 10 PE/kg. If seizures continue, intubate patient. Consider phenobarbital at a rate of 50-100 mg/min until seizures stop or 20 mg/kg is given. Alternatively move to anesthetic agents.
After 60 minutes of status	Review laboratory results and correct abnormalities. Arrange for anesthesia, neuromuscular blockade, and EEG monitoring. Options include midazolam (0.15-0.2 mg/kg load, then 0.06-1.1 mg/kg/h) or propofol (1-2 mg/kg load, then 3-10 mg/kg/h), or barbiturate anesthesia (pentobarbital, 6-15 mg/kg loading dose, then 0.5-5 mg/kg/h). Pentobarbital often causes circulatory collapse, so be prepared to administer a pressor agent such as dopamine.

CBC , Complete blood count; ECG , electrocardiogram; EEG , electroencephalography.

Data from Lowenstein DH, Alldredge BK: Status epilepticus. N Engl J Med 338(14):970-976, 1998, and Treiman DM, Meyers PD, Walton NY, et al.: A comparison of four treatments for generalized convulsive status epilepticus. N Engl J Med 339(12):792-798, 1998.

What is Refractory Status Epilepticus (RSE)? 

Refractory Status Epilepticus is diagnosed when patients continue to experience either clinical or electrographic seizures after receiving adequate doses of an initial benzodiazepine followed by a second acceptable AED.

What is the treatment of Refractory Status Epilepticus? 

Treatment recommendations are to use continuous infusion AEDs to suppress seizures. Patients with RSE require assisted ventilation and cardiovascular monitoring

Infusions Used in Refractory Status Epilepticus (RSE)

Medications	Midazolam	Propofol	Pentobarbital	Thiopental
Dose	Initial: 0.2 mg/kg; administer at an infusion rate of 2 mg/min	Loading dose: 1-2 mg/kg, start at 20 mcg/kg/min	Initial: 5-15 mg/kg, at an infusion rate ≤50 mg/min	2-7 mg/kg, administer at an infusion rate ≤50 mg/min
CI: 0.05-2 mg/kg/h	CI: 30-200 mcg/kg/min	CI: 0.5-5 mg/kg/h	CI: 0.5-5 mg/kg/h
Breakthrough SE: 0.1-0.2-mg/kg bolus, increase CI rate by 0.05-0.1 mg/kg/h every 3-4 hours	Breakthrough SE: increase CI rate by 5-10 mcg/kg/min every 5 minutes or 1-mg/kg bolus plus CI titration	Breakthrough SE: 5-mg/kg bolus, increase CI rate by 0.5-1 mg/kg/h every 12 hours	Breakthrough SE: 1-2-mg/kg bolus, increase CI rate by 0.5-1 mg/kg/h every 12 hours
Adverse events	Respiratory depression, hypotension (less compared to other three agents, hence preferred)	Hypotension (especially with loading dose in critically ill patients), respiratory depression, cardiac failure, rhabdomyolysis metabolic acidosis renal failure (PRIS)	Hypotension, respiratory depression, cardiac depression, paralytic ileus	Hypotension, respiratory depression, cardiac depression
At high doses, complete loss of neurologic function
Half-life	1-7 hours	3-12 hours	15-50 hours

CI , Continuous infusion; PRIS , propofol-related infusion syndrome.

What is the goal target in Refractory Status Epilepticus? 

Dosing of continuous infusion AEDs for RSE should be titrated to cessation of electrographic seizures or burst suppression.

How long should the infusions be maintained? 

A period of 24 to 48 hours of electrographic control is recommended prior to slow withdrawal of continuous infusion AEDs for RSE.

During the transition from continuous infusion AEDs in Refractory Status Epilepticus, it is recommended to use maintenance AEDs and monitor for recurrent seizures by continuous EEG during the titration period.

What are the indications for continuous EEG monitoring? 

Continuous EEG monitoring should be initiated within 1 hour of SE onset if ongoing seizures are suspected.

The duration of continuous EEG monitoring should be at least 48 hours in comatose patients to evaluate for nonconvulsive seizures.

Indication for Continuous Electroencephalogram (cEEG) Monitoring

Recent clinical seizure or SE without return to baseline >10 minutes

Coma, including postcardiac arrest

Epileptiform activity or periodic discharges on initial 30 minutes EEG

Intracranial hemorrhage including TBI, SAH, ICH

Suspected nonconvulsive seizures in patients with altered mental status

SE , Status epilepticus; TBI , traumatic brain injury; SAH , subarachnoid hemorrhage; ICH , intracranial hemorrhage.

When after the cessation of convulsive seizures should nonconvulsive Status epilepticus be suspected? 

If the patient’s level of consciousness does not improve after 20 to 30 minutes following cessation of convulsive movements or mental status remains abnormal 30 to 60 minutes after convulsive activity ceases, ongoing nonconvulsive SE must be considered.

What is the semiological spectrum of nonconvulsive seizures? 

Positive symptoms include agitation/aggression, automatisms, blinking, crying, delirium, delusions, echolalia, facial twitching, laughter, nausea/vomiting, nystagmus/eye deviation, perseveration, psychosis, and tremulousness. 

Negative symptoms include anorexia, aphasia/mutism, amnesia, catatonia, coma, confusion, lethargy, and staring.

What is the benzodiazepine trial for the diagnosis of nonconvulsive Status epilepticus? 

A patient experiencing rhythmic or periodic focal or generalized epileptiform discharges on EEG with neurologic impairment should have EEG, pulse oximetry, blood pressure, ECG, and respiratory rate monitored, and sequential small doses of rapidly acting short-duration benzodiazepine such as midazolam at 1 mg/dose should be administered.

Between doses, repeated clinical and EEG assessment must be performed.

The trial is stopped after any of the following:

• Persistent resolution of the EEG pattern (and exam repeated);

• Definite clinical improvement;

• Respiratory depression, hypotension, or other adverse effect; or

• A maximum dose is reached (such as 0.2 mg/kg midazolam, though higher may be needed if on chronic benzodiazepines).

How should nonconvulsive Status epilepticus be treated? 

Management is less well defined for nonconvulsive Status epilepticus as compared to convulsive SE due to the lack of randomized studies.

Expert opinion recommends using noncoma-inducing agents initially such as IV fosphenytoin, valproate, and levetiracetam in addition to intermittent benzodiazepines to avoid intubation and drug-induced coma.

For refractory nonconvulsive Status epilepticus treatment should be individualized but can include either midazolam or propofol infusions.

Follow these instructions at home:

Medicines

• Give over-the-counter and prescription medicines only as told by your child’s health care provider.
• Keep all medicines, drugs, and alcohol out of your child’s reach.

Safety

• Make sure that everyone who cares for your child knows that he or she is prone to seizures. All of your child’s caregivers should be given instructions about how to help your child in case of a seizure. In general, a witness to a seizure should:
  • Cushion and support your child’s head and body.
  • Move your child away from dangerous places, such as the street.
  • Move sharp objects out of the area.
  • Turn your child on his or her side. If your child vomits this will help keep their airway clear.
  • Avoid unnecessarily restraining your child. This will not stop the seizure.
  • Not place anything in your child’s mouth.
  • Call for emergency medical help.
  • Stay with your child until he or she recovers.
• Follow recommendations from your child’s health care provider about:
  • Activity restrictions.
  • Driving restrictions, if your child drives.

General instructions

• If your child is using alcohol or drugs, talk with his or her health care provider about ways to help him or her stop.
• Help your child avoid infection and high fever by:
  • Having members of your household wash their hands often.
  • Treating high fever as directed by your child’s health care provider.
• Manage your child’s long-term (chronic) conditions, such as diabetes or high blood pressure, if applicable.
• Keep all follow-up visits as told by your child’s health care provider. This is important.

Contact a health care provider if:

• Your child develops new symptoms.
• Your child injures herself or himself during a seizure.
• Your child has a seizure that lasts for less than 5 minutes.

Get help right away if:

• Your child has a seizure or several seizures that last 5 minutes or longer.
• Your child has a seizure while in water.
• Your child has unexplained pain or fever a few days after having a seizure.
• Your child has a serious injury while having a seizure.
• Your child has trouble breathing after a seizure.
• Your child stops breathing after a seizure.
• Your child’s behavior does not return to normal after having a seizure.

These symptoms may represent a serious problem that is an emergency. Do not wait to see if the symptoms will go away. Get medical help right away. Call your local emergency services (911 in the U.S.).

Summary

• Status epilepticus is an emergency. If your child has a seizure or several seizures that last for 5 minutes or longer, call your local emergency services (911 in the U.S.).
• Children who already have a seizure disorder, such as epilepsy, are more at risk for status epilepticus.
• Symptoms of convulsive status epilepticus include jerking muscle movements, confusion, loss of consciousness, or falling.
• Symptoms of non-convulsive status epilepticus are often hard to identify. They may include confusion or subtle eye or hand movements.
• Make sure everyone who cares for your child knows that he or she is prone to seizures, and knows first aid for dealing with seizures.