Chapter 19. Seizures

Status Epilepticus

Essentials of Diagnosis

• A prolonged seizure lasting 5–15 minutes
• Continuous or multiple seizures without intervening periods of consciousness

Clinical Findings

A prolonged seizure lasting more than 5 minutes, or multiple seizure episodes without intervening periods of consciousness defines status epilepticus. Search carefully for seizure activity in the comatose patient. Manifestations may be subtle (eg, deviation of head or eyes; repetitive jerking of fingers, hands, or one side of the face).

Protect the Airway

Insert a nasopharyngeal airway. Administer 100% oxygen by nasal cannula or non-rebreathing face mask and monitor with pulse oximetry. Prepare for possible endotracheal intubation in the event that anticonvulsants fail to terminate the seizure.

Insert an Intravenous Catheter

Obtain blood specimens for glucose, electrolytes, magnesium, and calcium determinations; hepatic and renal function tests; and complete blood count; as well as 3–4 tubes of blood for possible toxicology screen or determination of drug levels (including anticonvulsants if patient is known or suspected to be taking them).

Rule-Out Hypoglycemia

Obtain a bedside glucose and give glucose, 50 mL of 50% solution IV if the patient is hypoglycemic. Note: If malnutrition is suspected, give thiamine, 100 mg IV, slowly prior to, or at the same time as, glucose.

Pharmacological Treatment Protocol

First-Line Agent

Benzodiazepines

Give lorazepam, 2–4 mg (0.05–0.1 mg/kg) IV every 3–4 minutes to 8 mg total in adults and an additional dose of 0.05 mg/kg can be given in children. Diazepam, 5–10 mg (0.25 mg/kg) IV every 3–4 minutes up to 30 mg total dose in adults and 5 mg in children. These drugs have been shown to be equally effective as first-line choices. Lorazepam has a longer duration of action compared to diazepam. Because of this property, lorazepam is currently considered the drug of choice. If venous access cannot be obtained, diazepam can be given rectally, endotracheally, or intraosseously, or midazolam, 0.2 mg/kg, can be given intramuscularly.

Second-Line Agent

Phenytoin or Fosphenytoin

If the seizure persists after adequate doses of benzodiazopines, give phenytoin 20 mg/kg by IV infusion at a rate of 50 mg/min or slower. If the seizure persists, an additional 10 mg /kg is given. Infusion of phenytoin at more rapid rates (especially if given into centrally placed IV lines) can precipitate cardiac arrhythmias or hypotension. These unwanted hemodynamic and cardiac side effects can be avoided by the use of fosphenytoin, a prodrug of phenytoin. Fosphenytoin dosages are expressed as phenytoin equivalents (PE). Advantages of fosphenytoin are that it can be administered faster than phenytoin (150 PE/min) and be given intramuscularly if needed. The standard dose is 20 mg PE/kg IV.

Refractory Status Eepilepticus

There is no accepted standard definition of refractory status epilepticus (RSE). A seizure that continues after the administration of first and second-line treatment within 60 minutes of onset of status is considered RSE. An alternate definition is a seizure that is refractory to loading or protracted maintenance doses of at least three anti-epileptics. Consider one of the following pharmacologic agents for patients with RSE. Intubation will most likely be required for all except valproate and levetiracetam. Continuous EEG monitoring should be considered while using these agents.

Phenobarbital

Administer phenobarbital at a dose of 10–20 mg/kg. Beware of both hypotension and respiratory depression. Endotracheal intubation is often necessary.

Midazolam

Administer midazolam in a loading dose of 0.2 mg/kg followed by an infusion of 0.1–0.4 mg/kg/h. Hypotension is rare compared to propofol.

Propofol

Propofol, a short-acting nonbarbiturate sedative hypnotic is given at a dose of 1–2 mg/kg load followed by an infusion of 6–12 mg/kg/h. Some evidence exists to show that propofol is superior to midazolam and the shorter acting barbiturates to terminate RSE.

Valproic Acid

Successful termination of RSE has been reported with valproic acid administration. Give a loading dose of 20–25 mg/kg IV followed by an infusion of 2 mg/kg/h. The chief advantage of this agent is the excellent safety profile and the ease of administration. Intubation may be avoided when using this agent.

Levetiracetam

RSE has shown to be effective in RSE. Give a dose of 500–2000 mg over 30–60 minutes. The drug has attractive features for RSE with almost no drug interactions, rare allergic reactions and minimal respiratory and cardiovascular effects with IV dosing.

Pentobarbital

Pentobarbital given at a loading dose of 12 mg/kg followed by and infusion of 5 mg/kg/h titrated up to burst suppression on EEG. Hypotension and myocardial depression are prominent side effects.

Measure Arterial Blood Gases and pH

Arterial blood Pco2 is a sensitive indicator of the adequacy of ventilation (hypercapnia is present in proportion to the degree of hypoventilation). Metabolic acidosis due to lactic acidosis resulting from status epilepticus is commonly present for as long as 1 hour after a seizure. This acidosis requires no treatment. Acidosis lasting longer than 1 hour should prompt a search for other causes (Chapter 44).

Maintain Ventilation

Patients in status epilepticus or those given anticonvulsant medications that are strong respiratory depressants may require endotracheal intubation to protect the airway and maintain adequate ventilation. Monitor arterial blood gas measurements to assess adequacy of oxygenation and ventilation.

Rule Out Meningitis

Perform lumbar puncture immediately to rule out meningitis if fever (body temperature > 38.5°C [>101.2°F]) or nuchal rigidity is present. However, the muscle activity of status epilepticus alone produces transient fever higher than 38.5°C (>101.2°F) in up to 79% of patients. Hyperthermia should be treated with passive cooling measures. Status epilepticus may also produce a mild transient cerebrospinal fluid pleocytosis.

Search for the Underlying Cause of Seizure

Common causes of seizures of acute onset are listed in Table 19–1.

Prevention of Injury

Prevent injury to the patient during the seizure by padding the environment. Do not use rigid restraint (fractures may result) or insert objects into the patient's mouth during the seizure.

General Considerations

Seizures can result from a primary central nervous system disorder or may be a manifestation of a serious underlying metabolic or systemic disorder. The distinction is critical, because therapy must be directed at the underlying disorder as well as at control of the seizure.

Clinically, seizures are diagnosed by episodes of loss of consciousness or depressed consciousness and a period of confusion or disorientation (postictal state) following it. The most common type of seizure is generalized tonic–clonic seizure. Firm diagnosis of subtler types of seizures like absence or complex partial may require an electroencephalogram. New onset seizures require a comprehensive ED evaluation (Table 19–2) to find the underlying cause. Patients with a known seizure disorder who present with a seizure require a much less exhaustive investigation depending on the clinical presentation.

New Onset Seizure

Laboratory Evaluation

A comprehensive laboratory evaluation in an otherwise healthy adult with a new onset seizure (who has returned to baseline) is not indicated. Determination of serum sodium and glucose is indicated. A serum pregnancy test is indicated in women of child-bearing age. If the patient has a persistent change in mental status or a focal neurologic deficit, a comprehensive lab evaluation should be considered. Lumbar puncture should be considered if CNS infection is suspected based on clinical presentation (Chapter 42).

CT Scan

When feasible, a CT scan of the head should be performed on all patients with new onset seizures. Deferred outpatient neuroimaging (CT scan or MRI) can be considered if reliable follow-up can be arranged from the ED.

Antiepileptic Therapy

In general, patients with a first seizure, who have returned to baseline, do not need to be started on antiepileptic therapy. Evidence exists that they do not decrease the incidence of recurrent seizure and may actually increase the incidence of a second seizure.

Disposition

Patients with a new onset seizure, who have returned to baseline, have a normal CT scan and lab evaluation can be safely discharged with outpatient follow-up and instructions not to drive or operate machinery. Patients with abnormal head CT scans or persistent focal abnormalities should be hospitalized so that diagnostic studies can be performed and the patient observed.

Known Seizure Disorder

Laboratory Evaluation

Laboratory studies other than measurement of anticonvulsant levels are rarely required in the patient with a history of seizure if they have returned to baseline. If the patient has a persistent change in mental status or a focal neurologic deficit, a comprehensive lab evaluation should be considered.

CT Scan

A CT scan of the head in the patient with a known history of seizures is rarely indicated. If the patient has returned to baseline and has a nonfocal neurologic examination, there is no indication for brain imaging. All others should undergo CT scan if feasible.

Antiepileptic Therapy

The measurement of anticonvulsant levels will assist in guiding therapy. Consider giving loading doses and restarting maintenance doses in patients that have sub-therapeutic levels. Avoid adjusting anticonvulsant doses in patients who are subtherapeutic since noncompliance is common. In patients with therapeutic levels refer the patient for early outpatient follow-up for consideration of adding an additional agent to their regimen.

Disposition

Patients with established seizure disorders may be sent home if they have returned to baseline, if the seizures have not recurred, and if no acute abnormalities are found. They should be referred to their regular source of medical care within a few days. All others should be hospitalized.

Generalized Seizures

Myoclonic and Tonic—Clonic (Generalized Convulsive Seizures)

Generalized seizures with obvious motor components are usually not difficult to diagnose and should be treated as described above. If status epilepticus ensues, the motor component may become subtle in some cases, and may be mistaken as a postictal period. If consciousness is not regained within 20 minutes of the termination of convulsions, the diagnosis of subtle status epilepticus should be considered. It is important to recognize subtle status epilepticus as it bears a dismal prognosis, even when compared to other forms of nonconvulsive status epilepticus.

Absence

Absence seizures usually present with limited or no motor activity despite impairment of consciousness. Patients can be comatose, but frequently present as lethargic or confused. These seizures may be mistaken for complex partial seizures when automatisms are present. It is more common in females than males and is divided into childhood (onset around 6 years old) and juvenile (onset around 12 years old). Therapy consists of valproate given in an IV loading dose of 25 mg/kg in 50 mL NS over 10 minutes. If the patient is on valproate, a level should be drawn and the dose adjusted accordingly. Both absence and complex partial seizures may lead to nonconvulsive status epilepticus if untreated.

Complex Partial Seizures

A detailed history may be required to make this diagnosis. Symptoms vary depending on the anatomic location of the seizure focus. Some patients will experience behavioral or sensory symptoms, as apposed to motor and postural symptoms, prior to generalization of their seizure. Patients may present with automatisms; however, they are usually more pronounced than those of absence seizures. These patients may progress to nonconvulsive status epilepticus. Treatment is identical as for convulsive seizures.

Intracranial Hemorrhage

(See also Chapter 37.) Intracerebral hemorrhage is the most common form of hemorrhagic stroke and results in major disability or death. Bleeding occurs primarily in the brain parenchyma and seizure is common. Prolonged seizure activity leads to increased intracranial pressure, cerebral metabolic demands, release of excitatory neurotransmitters and cerebral acidosis. Morbidity in this population is directly related to the duration of seizure activity. Recommended therapy for these patients includes lorazepam for cessation of seizure activity followed by a loading dose of phenytoin or fosphenytoin. If seizure activity continues, additional benzodiazepines may be needed. If barbiturates are required for seizure control, invasive airway management should be considered.

Mass Lesions

In addition to simple mass effect, many neurophysiologic changes occur in response to the presence of a neoplastic process in the brain. This results in seizures that are potentially less responsive to standard therapy. Seizure may present as the first symptom of a brain tumor. The risk is the most in tumors that are central in location and have slow growth. Clinical trials have shown poor control with standard antiepileptic drugs (AEDs) and current recommendations include therapy for symptomatic patients only. Benzodiazepines and phenytoin or fosphenytoin are appropriate for patients who are seizing. No clear benefit has been shown with AEDs for seizure prophylaxis in this patient population.

Fever

(See also Chapter 50.) Febrile seizures are the most common type of seizures in the pediatric population affecting between 2 and 14% of children worldwide. Most occur in children between the ages of 6 months and 5 years with a peak incidence around 18 months. These generalized seizures usually last less than 15 minutes and are considered fairly benign and are known as simple febrile seizures. Greater attention should be paid to children with complex febrile seizures which is defined as focal seizure, seizure activity greater than 15 minutes or with multiple seizures in close succession. Other causes of seizure with fever must also be investigated, such as herpes encephalitis and bacterial meningitis. Antipyretics do not prevent seizures, but should still be employed for febrile children. The use of AEDs for chronic control of febrile seizures is currently a topic of debate and most studies show no benefit. Benzodiazepines should be used for patients with an active seizure.

Alcohol Withdrawal

Alcohol withdrawal seizures, in and of themselves, are not epilepsy and should be treated symptomatically with benzodiazepines alone. The alcoholic patient may have other reasons for seizure, however, including head injury, poor nutrition, metabolic disturbances and toxic exposures. Attention to these and other possible causes must be made in order to miss other life-threatening conditions in this high-risk population.

Patients with alcohol withdrawal typically have seizures 6–48 hours following cessation of alcohol intake. No AEDs have been shown to be effective preventing this syndrome. Phenytoin is clearly ineffective; phenobarbital and lorazepam, while useful in theory, have not demonstrated efficacy in controlled studies. Benzodiazopines should be used to abort active seizures. Chronic anticonvulsant administration is not necessary for alcohol withdrawal seizures alone. Hospitalization for alcohol withdrawal seizures is usually not needed if the patient can be reliably observed (eg, at a detoxification center or by family or friends) and the seizures treated with benzodiazepines.

Eclampsia

(See also Chapter 38.) Eclampsia is a new onset type seizure in the clinical setting of a women with preeclampsia and no known seizure history. Eclampsia presents with generalized tonic–clonic seizures most commonly; however, simple and complex partial seizure may also be found. Status epilepticus is rare. Significant risk to the mother and fetus mandates delivery as soon as possible. Treatment of eclamptic seizures includes magnesium sulfate 4–6 gm IV loading dose over 15 to 20 minutes followed by a continuous infusion of 2 g/h. Magnesium sulfate has been shown to be superior to benzodiazepines and phenytoin and should be the first-line drug for eclamptic seizures.

Eclampsia may also present in the intrapartum and postpartum periods (usually occurring in the first 48 hours). Late postpartum eclampsia may occur between 48 hours and 4 weeks postpartum. CT scanning is considered appropriate as intracranial hemorrhage is a rare complication of eclampsia.

Drug Overdose

(See also Chapter 47.) Many different drugs can cause seizures. Overdose of isoniazid theophylline, organophosphates and cocaine commonly cause seizures. Treat symptomatic patients with supportive measures and benzodiazepines initially. A detailed history to discover the exact toxin may lead to more specific therapy, including administration of an antidote.