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Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e

Chapter 171: Seizures Joshua G. Kornegay

FIGURE 171–1.

INTRODUCTION AND PATHOPHYSIOLOGY

A seizure is an episode of abnormal neurologic function caused by inappropriate electrical discharge of brain neurons. Neuronalelectrical discharge, in its most simple form, can be thought of as the homeostasis of glutaminergic (excitatory) and γ-aminobutyric acid (inhibitory) activity. The seizure is the clinical attack experienced by the patient in the setting of inappropriateexcitatory activity. Some patients with "epileptic" electroencephalographic (EEG) discharges may not experience any overtclinical symptoms. Some seizure-like episodes may be due to causes other than abnormal brain electrical activity, but suchattacks are not true seizures.

Epilepsy is a clinical condition in which an individual is subject to recurrent seizures. It implies a fixed, more excitatory conditionof the brain with a lower seizure threshold. The term epileptic does not refer to an individual with recurrent seizures caused byreversible conditions such as alcohol withdrawal, toxins, hypoglycemia, or other metabolic derangements.

Primary, or idiopathic, seizures are those in which no evident cause can be identified. Secondary, or symptomatic, seizures are aconsequence of an identifiable neurologic condition, such as a mass lesion, previous head injury, or stroke. Electrical stimulationof the brain, convulsant potentiating drugs, profound metabolic disturbances, or a sharp blow to the head all may cause reactiveseizures in otherwise normal individuals. Reactive seizures are generally self-limited, and a reactive seizure is not considered tobe a seizure disorder or epilepsy.

There are further definitions of seizures based on clinical factors: a provoked seizure has an acute precipitating event within 7days of the insult; an unprovoked seizure has no acute precipitating factor or may result from a very remote incident; status

epilepticus is seizure activity for ≥5 minutes or two or more seizures without regaining consciousness between seizures1; andrefractory status epilepticus is persistent seizure activity despite the IV administration of adequate amounts of two antiepilepticagents.

SEIZURE CLASSIFICATION

The International League Against Epilepsy recommends dividing seizures into two major groups: generalized seizures and partialseizures (Table 171–1). When there are inadequate data to categorize the seizure, the seizure is considered unclassified.

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Table 171–1

Classification of Seizures

Generalized seizures (consciousness always lost)

Tonic-clonic seizures (grand mal)

Absence seizures (petit mal)

Others (myoclonic, tonic, clonic, or atonic seizures)

Partial (focal) seizures

Simple partial (no alteration of consciousness)

Complex partial (consciousness impaired)

Partial seizures with secondary generalization (Jacksonian march)

Unclassified (inadequate information)

GENERALIZED SEIZURES

Generalized seizures are thought to be caused by a nearly simultaneous activation of the entire cerebral cortex, perhaps causedby an electrical discharge originating deep in the brain and spreading outward. The attacks begin with abrupt loss ofconsciousness. Loss of consciousness may be the only clinical manifestation of the seizure (as in absence attacks), or there maybe a variety of motor manifestations (e.g., tonic posturing, clonic jerking of the body and extremities).

Generalized tonic-clonic seizures (grand mal) are the most familiar and dramatic of the generalized seizures. In a typical attack,the patient suddenly becomes rigid (tonic phase), trunk and extremities are extended, and the patient falls to the ground. As thetonic phase subsides, there is increasing coarse trembling that evolves into a symmetric, rhythmic (clonic) jerking of the trunkand extremities. Patients are o�en apneic during this period and may be cyanotic. They o�en urinate and may vomit. As theattack ends, the patient is le� flaccid and unconscious, o�en with deep, rapid breathing. Typical attacks last from 60 to 90seconds; bystanders generally overestimate the duration of the seizure. Consciousness returns gradually, and postictalconfusion, myalgias, and fatigue may persist for several hours or more.

Absence seizures (petit mal) are very brief, generally lasting only a few seconds. Patients suddenly develop alteredconsciousness but no change in postural tone. They appear confused, detached, or withdrawn, and current activity ceases. Theymay stare or have twitching of the eyelids. They may not respond to voice or to other stimulation and may exhibit involuntarymovements or lose continence. The attack ceases abruptly, and the patients typically resume previous activity without postictalsymptoms. Patients and witnesses may be unaware that anything has happened. Classic absence seizures occur in school-agechildren and are o�en attributed by parents or teachers to daydreaming or inattention. The attacks can occur as frequently as100 or more times daily and may result in poor school performance. They usually resolve as the child matures. Similar attacks inadults are more likely to be minor complex partial seizures and should not be termed absence. The distinction is importantbecause the causes and treatment of the two seizures are di�erent.

PARTIAL (FOCAL) SEIZURES

Partial seizures are due to electrical discharges beginning in a localized region of the cerebral cortex. The discharge may remainlocalized or may spread to involve nearby cortical regions or the entire cortex. Focal seizures are more likely to be secondary to alocalized structural lesion of the brain.

In simple partial focal seizures, the seizure remains localized, and consciousness and mentation are not a�ected. It is possible todeduce the likely location of the initial cortical discharge from the clinical features at the onset of the attack. For example,

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unilateral tonic or clonic movements limited to one extremity suggest a focus in the motor cortex, whereas visual symptomssuggest an occipital focus. Bizarre olfactory or gustatory hallucinations suggest a focus in the medial temporal lobe. Suchsensory phenomena, known as auras, are o�en the initial symptoms of attacks that then become more widespread, termedsecondary generalization.

Complex partial seizures are focal seizures in which consciousness or mentation is a�ected. They are o�en caused by a focaldischarge originating in the temporal lobe and are sometimes referred to as temporal lobe seizures. Complex partial seizures arecommonly misdiagnosed as psychiatric problems because symptoms can be so bizarre. Symptoms may include automatisms,visceral symptoms, hallucinations, memory disturbances, distorted perception, and a�ective disorders. Common automatismsinclude lip smacking, fiddling with clothing or buttons, or repeating short phrases. Visceral symptoms o�en consist of asensation of "butterflies" rising up from the epigastrium. Hallucinations may be olfactory, gustatory, visual, or auditory. Theremay be complex distortions of visual perception, time, and memory. A�ective symptoms may include intense sensations of fear,paranoia, depression, elation, or ecstasy. Because such seizures result in alterations of thinking and behavior, they werepreviously referred to as psychomotor seizures, but to avoid any confusion with psychiatric illness, the term complex partialseizure is preferred.

As noted, a focal seizure may spread to involve both hemispheres, mimicking a typical generalized seizure. For the purpose ofclassification, diagnosis, and treatment, such attacks are still regarded as focal seizures. In some patients, the discharge mayspread so rapidly that no focal symptoms are evident, and the correct diagnosis may depend entirely on demonstration of thefocal discharge on an EEG recording.

CLINICAL FEATURES

HISTORY

When a patient presents a�er the event, the first step is to determine whether the episode was truly a seizure. Obtain a carefulhistory of the details of the attack from the patient and any bystanders who witnessed the attack. Inquire about the physicaldescription of the attack, because witnesses may mislabel the activity and mistake nonseizure activity as a seizure.

Important avenues of inquiry include the presence of a preceding aura, abrupt or gradual onset, progression of motor activity,loss of bowel or bladder control, presence of oral injury, and whether the activity was localized or generalized and symmetric orunilateral. Ask about the duration of the episode and determine the presence of postictal confusion or lethargy.

Next, determine the clinical context of the episode. If the patient is a known epileptic, clarify the baseline seizure pattern. If theattack is consistent with the previous seizure pattern, identify precipitating factors of the current seizure. Common precipitatingfactors include missed doses of antiepileptic medications; recent alterations in medication, including dosage change orconversion from brand name; sleep deprivation; increased strenuous activity; infection; electrolyte disturbances; and alcohol orsubstance use or withdrawal.

If there is no previous history of seizures, a more detailed inquiry is needed. Symptoms such as unexplained injuries, nocturnaltongue biting, or enuresis suggest previous unwitnessed or unrecognized seizures. Ask about a history of recent or remote headinjury. Ask about any previous similar episodes that may be suspect as seizures. Persistent, severe, or sudden headache suggestsintracranial pathology. Pregnancy or recent delivery raises the possibility of eclampsia. A history of metabolic or electrolyteabnormalities, hypoxia, systemic illness (especially cancer), coagulopathy or anticoagulation, exposure to industrial orenvironmental toxins, drug ingestion or withdrawal, and alcohol use may point to predisposing factors (Table 171–2).

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Table 171–2

Common Causes of Provoked (Secondary) Seizures

Trauma (recent or remote)

Intracranial hemorrhage (subdural, epidural, subarachnoid, intraparenchymal)

Structural CNS abnormalities

Vascular lesion (aneurysm, arteriovenous malformation)

Mass lesions (primary or metastatic neoplasms)

Degenerative neurologic diseases

Congenital brain abnormalities

Infection (meningitis, encephalitis, abscess)

Metabolic disturbances

Hypo- or hyperglycemia

Hypo- or hypernatremia

Hyperosmolar states

Uremia

Hepatic failure

Hypocalcemia, hypomagnesemia (rare)

Toxins and drugs (many)

Cocaine, lidocaine, antidepressants, theophylline, isoniazid

Mushroom toxicity (Gyromitra spp.)

Hydrazine (rocket fuels)

Alcohol or drug withdrawal

Eclampsia of pregnancy (may occur up to 8 weeks postpartum)

Hypertensive encephalopathy

Anoxic-ischemic injury (cardiac arrest, severe hypoxemia)

PHYSICAL EXAMINATION

Immediately obtain a complete set of vital signs and a point-of-care glucose determination. In the post-seizure setting, focus theinitial exam on checking for injuries, especially to the head or spine, as a result of the seizure itself. A posterior shoulderdislocation is an injury that is easy to overlook. Lacerations of the tongue and mouth, dental fracture, and pulmonary aspirationare also frequent sequelae.

Perform a directed, complete neurologic examination and subsequent serial examinations. Follow the patient's level ofconsciousness and mentation closely to avoid missing nonconvulsant status epilepticus (see below). A transient focal deficit(usually unilateral) following a simple or complex focal seizure is referred to as Todd's paralysis and should resolve within 48hours.

DIAGNOSIS

Clinical features that help to distinguish seizures from other, nonseizure attacks include:

Abrupt onset and termination. Some focal seizures are preceded by auras that can last 20 to 30 seconds, but most attacks beginabruptly. Attacks reported to develop over several minutes or longer should be regarded with suspicion. Most seizures last only 1or 2 minutes, unless the patient is in status epilepticus.

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Lack of recall. Except for simple partial seizures, patients usually cannot recall the details of an attack.

Purposeless movements or behavior during the attack.

Most seizures, except for simple absence attacks or simple partial seizures, are followed by a period of postictal confusion andlethargy.

DIFFERENTIAL DIAGNOSIS

Many episodic disturbances of neurologic function may be mistaken for seizures (seizure mimics). A complete review of theseconditions is too lengthy for inclusion here, but several important entities are mentioned (Table 171–3).

Table 171–3

Paroxysmal Disorders: Di�erential Diagnosis

Seizures

Syncope

Pseudoseizures or psychogenic seizures

Hyperventilation syndrome

Migraine headache

Movement disorders

Syncope usually presents with prodromal symptoms, such as lightheadedness, diaphoresis, nausea, and "tunnel vision."However, cardiac syncope may occur suddenly without any prodromal warning. Syncope may be associated with injury,incontinence, or even brief tonic-clonic activity. Recovery is usually rapid, with no postictal-like symptoms. For furtherdiscussion see chapter 52, "Syncope."

Pseudoseizures can be extremely di�icult to distinguish from true seizures and may occur in a patient who also has adocumented seizure disorder. Pseudoseizures are psychogenic in origin and are o�en associated with a conversion disorder,panic disorder, psychosis, impulse control disorder, Munchausen syndrome, or malingering. Suspect the diagnosis ofpseudoseizures when seizures occur in response to emotional upset or only occur with witnesses present. These attacks areo�en bizarre and highly variable. Patients o�en are able to protect themselves from noxious stimuli during the attack.Characteristic movements include side-to-side head thrashing, rhythmic pelvic thrusting, and clonic extremity motions that arealternating rather than symmetric. Incontinence and injury are uncommon, and there is usually no postictal confusion. Patientswill o�en stop the seizure-like activity on command. Accurate diagnosis of pseudoseizures may require prolonged EEG or videomonitoring to demonstrate normal EEG activity during an attack. The lack of a lactic acidosis or elevated prolactin level drawnwithin 10 to 15 minutes of the cessation of seizure-like activity makes true seizures much less likely.

Hyperventilation syndrome can be misdiagnosed as a seizure disorder. A careful history will reveal the gradual onset of theattacks with shortness of breath, anxiety, and perioral numbness. Such attacks may progress to involuntary spasm (especiallycarpopedal) of the extremities and even loss of consciousness, although postictal symptoms are rare. Asking the patient tohyperventilate o�en reproduces the episodes.

Movement disorders, such as dystonia, chorea, myoclonic jerks, tremors, or tics, may occur in a variety of neurologic conditions.Consciousness is always preserved during these movements, and the patient can o�en temporarily suppress the movements.

Migraine headaches may be preceded by an aura similar to that seen in some partial seizures. The most common migraine aurais the scintillating scotoma. Migraine headaches may also be accompanied by focal neurologic symptoms, such as homonymoushemianopsia or hemiparesis. However, active movement disorders are inconsistent with migraine.

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LABORATORY TESTING

Individualize the use of laboratory studies. In a patient with a well-documented seizure disorder who has had a singleunprovoked seizure, the only tests that may be needed are a glucose level and pertinent anticonvulsant medication levels.

In the case of an adult with a first seizure or unclear seizure history, more extensive studies are usually needed and depend onthe clinical context. Obtain serum glucose, basic metabolic panel, lactate, calcium, magnesium, a pregnancy test, and toxicologystudies. Consider assays for anticonvulsant drug levels. A seizure may result in a lactate-driven, wide anion gap metabolic

acidosis.2 Most lactate abnormalities will clear within 30 minutes. The prolactin level may also be elevated for a brief period (15

to 60 minutes) immediately a�er a seizure.3 These tests can prove helpful in distinguishing true seizures from a pseudoseizure.

Interpret the results of anticonvulsant levels with caution. If the patient history is limited, a positive serum assay foranticonvulsant drugs suggests (but does not prove) the presence of a chronic seizure disorder. The usual therapeutic and toxiclevels indicated in laboratory reports are helpful only as rough guides. The therapeutic level of a drug is the level that providesadequate seizure control without unaccepTable side e�ects. A marked change in previously stable drug levels may indicatenoncompliance, a change in medication, malabsorption of a drug, or ingestion of a potentiating or competing drug. A very lowserum anticonvulsant drug level suggests noncompliance with medication and is the most common cause of a breakthroughseizure.

IMAGING

Obtain a CT scan of the head in the ED for patients with a first-ever seizure or a change in established seizure patterns to evaluate

for a structural lesion. A noncontrast CT is an appropriate screening tool.4,5 Obtain a CT scan if there is any concern for an acuteintracranial process based on history, comorbidities, or findings on physical examination. Concern for an acute intracranialprocess is an important indication for obtaining CT imaging, even if there is a coexistent metabolic process.

Because many important processes, such as tumors or vascular anomalies, may not be evident on noncontrast studies, a follow-up contrast-enhanced CT or MRI is o�en needed. Almost one-quarter of adults with new-onset seizure will have visualized

pathology on follow-up MRI, with rates increasing to as high as 53% in those with onset of a focal seizure.6 The timing of furtherimaging studies can be discussed with the consulting neurologist.

Obtain other radiographic studies as indicated by the clinical presentation to avoid missing injuries acquired as a result of theseizure. Obtain radiographs of the cervical spine if there is suspicion of head or neck trauma. Chest radiographs may revealprimary or metastatic tumors or aspiration. Shoulder radiographs may help rule out posterior dislocations. Specialexaminations, such as cerebral angiography, are rarely part of the ED evaluation.

LUMBAR PUNCTURE

Lumbar puncture in the setting of an acute seizure is indicated if the patient is febrile or immunocompromised or ifsubarachnoid hemorrhage is suspected and the noncontrast head CT is normal. For further discussion, see chapters 166,"Spontaneous Subarachnoid and Intracerebral Hemorrhage" and 174, "Central Nervous System and Spinal Infections."

ELECTROENCEPHALOGRAPHY

Although EEG is very helpful, it is o�en not readily available in most EDs. Emergent EEG can be considered in the evaluation of apatient with persistent, unexplained altered mental status to evaluate for nonconvulsive status epilepticus, subtle statusepilepticus, paroxysmal attack when a seizure is suspected, or ongoing status epilepticus a�er chemical paralysis for intubation.Patients in whom an emergent EEG is warranted typically require neurologic consultation and admission to a critical caresetting.

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TREATMENT OF UNCOMPLICATED SEIZURES

PATIENTS WITH ACTIVE SEIZURES

Typically, little is required during the course of an active seizure other than supportive and patient protective measures. Ifpossible, turn the patient to the side to reduce the risk of aspiration. It is usually not necessary or even possible to ventilate apatient e�ectively during a seizure, but once the attack subsides, clear the airway. Suction and airway adjuncts should be readilyavailable. It is not necessary or recommended to give IV anticonvulsant medications during the course of an uncomplicatedseizure. Most seizures will self-resolve within 5 minutes. Any unnecessary sedation at this point will complicate the evaluation

and result in a prolonged decrease in level of consciousness.7 Seizures that fail to abate a�er 5 minutes are considered statusepilepticus and require more aggressive medical interventions (see "Status Epilepticus" section, below).

PATIENTS WITH A HISTORY OF SEIZURES

Proper management of a patient with a well-documented seizure disorder who presents a�er one or more seizures depends onthe particular circumstances of the case. Identify and correct potential precipitants that may lower the seizure threshold. Manyseizures occur because of failure to take anticonvulsant medication as prescribed. Some anticonvulsants have very short serumhalf-lives, and missing even a single dose may result in a sharp drop in serum levels. If anticonvulsant levels are very low,supplemental doses are appropriate, and the regular regimen can be restarted or adjusted. A loading dose is also frequentlyprovided. Without a loading dose, the patient may not achieve anticonvulsant e�ects for days to weeks and is at risk forsubsequent seizures. Because there are no data comparing parenteral versus oral replacement, this issue is le� to the discretion

of the medical provider8 and should be based on knowledge of pharmacology. For example, the oral loading dose of phenytoinis 20 milligrams/kg given in three divided doses every 2 to 4 hours, a time frame not accepTable for a typical ED stay, so the IVroute is needed to achieve the proper loading dose.

In the known or suspected noncompliant patient, obtain a serum anticonvulsant level before administering a supplemental orloading dose to avoid drug toxicity. If anticonvulsant levels are adequate and the patient has had a single attack, specifictreatment may not be needed if the seizure pattern and frequency fall within the expected range for the patient. Ifanticonvulsant levels are not locally available (e.g., levetiracetam or lacosamide), and there is a missed dose or noncompliance,give the usual dose in the ED before discharge.

Even well-controlled patients may have occasional breakthrough seizures. Attempt to identify any precipitants or conditions thathave lowered the seizure threshold. If none is found, a change or adjustment of medication may be needed and should be madein consultation with the patient's primary care physician or neurologist. If the maintenance dose is increased, ensure follow-upwithin 1 to 3 days. There are no specific guidelines for the duration of ED observation in the situation of an individual with a priorhistory of seizures. Some clinicians discharge patients with seizures resulting from nontherapeutic anticonvulsant levels a�eradministration of a loading dose of an anticonvulsant if vital signs are normal and the mental status has returned to baseline.Ideally, discharge patients with a reliable family member or friend and with medical follow-up arranged, as above.

PATIENTS WITH A FIRST UNPROVOKED SEIZURE

Guidelines do not recommend hospital admission or initiation of anticonvulsant therapy in the patient with a first unprovoked

seizure, as long as the patient has returned to neurologic baseline.1,8 The most important predictors of seizure recurrence arethe underlying cause of the seizure and the results of the EEG. The decision to begin outpatient treatment with antiepilepticsdepends on the risk of recurrent seizures weighed against the risk–benefit ratio of anticonvulsant therapy. In general, patientswith a first unprovoked seizure who have a normal neurologic examination, no acute or chronic medical comorbidities, normaldiagnostic testing including noncontrast head CT, and normal mental status can safely be discharged from the ED. Initiation ofantiepileptic medication may be deferred to the outpatient setting where further studies, including an EEG and MRI, can be

performed.1,4,8 Consider consultation and/or admission for patients who do not meet the above criteria.

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Patients with provoked (secondary) seizures due to an identifiable underlying condition (Table 171–2) o�en require admissionand should generally be treated to minimize seizure recurrence.

The ideal initial antiepileptic regimen is a single-drug therapy that controls seizures with minimum toxicity. If treatment isinitiated, drug selection is based on the type of seizure and should be done in consultation with a neurologist. Antiepilepticagents, such as valproate, lamotrigine, topiramate, levetiracetam, and oxcarbazepine, are options for adults with new-onset

seizures.5,9 Consider developing common protocols between emergency medicine and neurology when treatment of new-onsetseizures is initiated from the ED.

Instruct discharged patients to take precautions to minimize the risks for injury from further seizures. Swimming, working withhazardous tools or machines, and working at heights should be prohibited. Driving is prohibited until cleared by the neurologistor primary care physician. Driving privileges should conform to state law, and it may be up to the emergency physician todocument seizure activity with the Department of Motor Vehicles.

SPECIAL POPULATIONS

HUMAN IMMUNODEFICIENCY VIRUS

Mass lesions, encephalopathy, herpes zoster, toxoplasmosis, Cryptococcus, neurosyphilis, and meningitis are all seen more

frequently in this population and can all provoke seizure activity.10,11

Perform an extensive investigation for the cause of the seizure. If no space-occupying lesion is identified on noncontrast head CTscan and there is no evidence of increased intracranial pressure, perform a lumbar puncture to exclude CNS infection. If noexplanation for seizures is found, then obtain a contrast-enhanced head CT or MRI.

NEUROCYSTICERCOSIS

Neurocysticercosis is caused by a CNS infection with the larval stage of the tapeworm Taenia solium and is the most common

cause of provoked (secondary) seizures in the developing world.12 The most common form of disease is parasitic invasion ofbrain parenchyma and cyst formation. Over 1 to 2 years, the cyst degenerates and becomes fibrotic, leaving a focal area of scarand calcification. Seizures are the most common clinical manifestation of neurocysticercosis and most frequently occur as theparasite is degenerating. In 80% to 90% of cases, the lesions resolve within 3 to 6 months, leaving the patient free of seizures. Up

to 20% of patients will continue to have seizures and require ongoing therapy with antiepileptic medications.12

In most cases, neuroimaging in neurocysticercosis is nondiagnostic. CT or MRI may demonstrate a 1- to 2-cm cystic lesion withthin walls and a 1- to 3-mm mural nodule (the parasite), a localized area of ring-like enhancement with surrounding edema, acalcified lesion, or hydrocephalus. Definitive diagnosis relies on a combination of the patient's clinical picture, exposure history,serologic testing, and neuroimaging.

Seizures in neurocysticercosis are typically controlled by antiepileptic monotherapy. Definitive treatment of neurocysticercosis is

controversial and highly variable, depending on the number, location, and viability of the parasites within the CNS.13,14

Antiparasitics (praziquantel and albendazole) and steroids are best initiated in consultation with an infectious disease specialistor neurologist.

PREGNANCY

The management of seizures (or control of epilepsy) during pregnancy requires a multidisciplinary approach. Most seizures inpregnancy are not first-time seizures, and initial evaluation is generally as discussed earlier, with the addition of an obstetricevaluation to determine gestational age and fetal well-being.

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When a woman beyond 20 weeks of gestation develops seizures in the setting of hypertension, edema, and proteinuria, thecondition is defined as eclampsia. Magnesium sulfate has long been used to treat eclampsia with good results. In eclampticwomen, magnesium sulfate infusion compared to diazepam and phenytoin resulted in a >50% reduction in recurrence of

seizures and a lower incidence of pneumonia, intensive care unit admission, and assisted ventilation.15,16,17 Detailed discussionof seizures in pregnancy is discussed in chapter 100, "Maternal Emergencies a�er 20 Weeks of Pregnancy and in the PostpartumPeriod."

ALCOHOL ABUSE

Seizures and alcohol use are associated through missed doses of medication, sleep deprivation as an epileptogenic trigger,increased propensity for head injury, toxic co-ingestions, electrolyte abnormalities, and withdrawal seizures. Benzodiazepines indoses su�icient to manage withdrawal symptoms will usually a�ord adequate protection from acute seizures. These doses are

o�en very large and need to be given in an escalating fashion.18 Evaluate and treat the alcohol-abusing patient with a firstseizure as any other patient with a first-time seizure. Detailed discussion of alcohol withdrawal seizures is provided in chapter292, "Substance Use Disorders."

STATUS EPILEPTICUS

Status epilepticus can occur in patients with a history of seizures or can be a first epileptic event. The most common causes ofstatus epilepticus include subtherapeutic antiepileptic levels; preexisting neurologic conditions, such as prior CNS infection,trauma, hemorrhage, or stroke; acute stroke; anoxia or hypoxia; metabolic abnormalities; and alcohol or drug intoxication or

withdrawal.19

Status epilepticus is a single seizure ≥5 minutes in length or two or more seizures without recovery of consciousness between

seizures.1,20,21 A�er 5 minutes, seizures are less likely to spontaneously terminate, less likely to be controlled with antiepilepticdrugs, and more likely to cause neuronal damage. Status epilepticus is a neurologic emergency, and treatment should beinitiated in all patients with continuous seizure activity lasting more than 5 minutes.

As seizures surpass the 5-minute mark, dramatic changes occur at the cellular level. Decreased expression and internalization ofγ-aminobutyric acid receptors, coupled with increased expression of both glutamine and N-methyl-d-aspartate receptors, lead to

a greatly diminished seizure threshold.22,23 The blood–brain barrier is also compromised, leading to CNS penetration of

potassium and albumin, both of which are hyperexcitatory CNS chemicals.24 A�er 20 minutes, hypotension, hypoxia, metabolicacidosis, hyperthermia, and hypoglycemia are present. Additionally, cardiac dysrhythmias, rhabdomyolysis, and pulmonary

edema can develop.25 A�er 2 hours of seizure activity, neurotoxic amino acids and calcium are released into cells, leading to

permanent neuronal necrosis and apoptosis.22 The hyperexcitatory milieu makes standard antiseizure therapies much lesse�ective in seizure termination.

In nonconvulsive status epilepticus, the patient is comatose or has fluctuating abnormal mental status or confusion, but no overtseizure activity is present. The diagnosis is challenging and is typically made by EEG. Findings suggestive of nonconvulsive statusepilepticus include a prolonged postictal period a�er a generalized seizure; subtle motor signs such as twitching, blinking, and

eye deviation; fluctuating alterations in mental status; or unexplained stupor and confusion in the elderly.25

Epilepsia partialis continua is focal tonic-clonic seizure activity with normal alertness that most commonly a�ects the distal legor arm.

TREATMENT OF STATUS EPILEPTICUS

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The goal of treatment is seizure control as soon as possible and within 30 minutes of presentation (Figure 171–1). Examination;identification of potential causes; checking the airway, breathing, and circulation; and treatment all begin simultaneously. Directa focused history and physical examination toward possible causes and subsequent injuries.

FIGURE 171–1.

Guidelines for management of active seizures and status epilepticus. ICU = intensive care unit; PE = phenytoin equivalents.

Establish large-bore IV access and determine a bedside glucose. Administer normal saline, avoiding IV fluids containing glucosebecause phenytoin is not compatible with glucose-containing solutions. Place the patient on oxygen, a cardiac monitor, a pulseoximeter, and end-tidal capnography.

In established status epilepticus, consider endotracheal intubation for airway protection, oxygenation, and ventilation. If aparalytic agent is used for intubation, use a short-acting agent so as not to mask ongoing seizure activity. Arrange for continuousEEG monitoring as soon as possible a�er paralytic agents have been used.

Initial laboratory evaluation includes blood glucose, a metabolic panel including calcium and magnesium, lactate, and ifappropriate, a pregnancy test, a toxicology screen, and anticonvulsant levels.

Administer glucose IV if hypoglycemia is suspected or confirmed. Monitor temperature continuously, and treat hyperthermiawith passive cooling. Place a urinary catheter to monitor urine output, and insert a nasogastric tube to help prevent aspiration.

If toxic ingestion is suspected as the cause of seizures, proceed with GI decontamination (as appropriate). Do not attempt lumbarpuncture during status epilepticus. If bacterial meningitis or encephalitis is suspected, start empiric antibiotic or antiviraltherapy. Status epilepticus can induce a brief peripheral leukocytosis as well as a mild cerebrospinal fluid pleocytosis.Radiographic studies, such as a CT scan, will usually need to be delayed until seizures are controlled.

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ANTICONVULSANT DRUGS IN STATUS EPILEPTICUS

The drugs most o�en used in the therapy of status epilepticus are the benzodiazepines (lorazepam or, if not available, diazepam)and phenytoin or fosphenytoin (Figure 171–1). Benzodiazepines are used in patients with continuous or very frequent seizures totemporarily control the seizures until more specific agents can be given. IV lorazepam (2 to 4 milligrams) and IV diazepam (5 to 10

milligrams) have equal e�icacy in controlling status epilepticus.8 Compared to diazepam, lorazepam has a slightly slower onset(3 vs 2 minutes) but a significantly longer duration of action (12 to 24 hours vs 15 to 60 minutes) and is associated with fewerseizure recurrences. In one prehospital study, IM midazolam demonstrated decreased seizure time and fewer intensive care unit

admissions when compared to lorazepam if no IV access was available26; however, IV lorazepam is still considered the initial

agent of choice. Lorazepam is also more e�ective than phenytoin or phenobarbital as the initial drug.27 Respiratory depressionand hypotension may occur, especially in young children and in patients taking alcohol, barbiturates, narcotics, or othersedatives. In patients with di�icult IV access and emergent need for seizure control, there may be a role for rectal diazepam gel orbuccal midazolam. Although there have been no trials in adults, rectal diazepam has been used by EMS providers in childrenwith good success for years, and recent trials of buccal midazolam (0.5 milligram/kg, up to 10 milligrams) show more e�icacy

than rectal diazepam in the pediatric population.28,29

In established status epilepticus, follow benzodiazepines with a longer-acting antiepileptic agent: fosphenytoin or phenytoin,

levetiracetam, valproate, or lacosamide. One of these antiepileptic agents should be started within 20 minutes of diagnosis.1

Fosphenytoin is a water-soluble prodrug of phenytoin that is converted to phenytoin in the plasma. Fosphenytoin has similartime of onset, e�ectiveness, and cardiac e�ects as phenytoin. It has much fewer infusion-site reactions due to the lack ofpropylene glycol and ethanol as the diluents. Fosphenytoin may be infused quickly, and for that reason, it is preferred overphenytoin. Fosphenytoin dosing is expressed as phenytoin equivalents (PE) to prevent confusion. The loading dose is 20 PE/kg,

which can be infused at 150 PE/minute over 10 to 15 minutes.9 Fosphenytoin can also be given IM, which may be useful if thepatient does not have IV access.

The loading dose for phenytoin is 20 milligrams/kg IV. Doses in excess of the usual 1000 milligrams are o�en required. Due tomyocardial depression from its propylene glycol diluent, phenytoin is typically infused no faster than a rate of 25 milligrams perminute (taking about 1 hour to administer). The rate may be increased to 50 milligrams per minute during status epilepticus aslong as hypotension does not develop. Place patients on a cardiac monitor, with blood pressure assessments every 5 to 15

minutes during the infusion and every 15 minutes for 1 hour a�er infusion.30 Phenytoin should not be mixed with any glucose-containing IV fluid and should not be given IM due to erratic absorption. The drug is contraindicated in patients with second- orthird-degree atrioventricular block. Other adverse e�ects include infusion site reactions, hypotension, and cardiacdysrhythmias. If side e�ects develop, stop the infusion and restart at a lower rate a�er side e�ects have resolved.

Valproic acid is e�ective but has serious side e�ects compared to the agents listed above. The U.S. Food and Drug Administrationhas issued a black box warning for hepatic failure and pancreatitis, and valproic acid should not be administered along with

phenytoin. The dose is 20 milligrams/kg IV.1,9,22,31,32

Levetiracetam is very e�ective, is quick to administer, and has few interactions and side e�ects. The precise mechanism of actionis unknown, but it may inhibit voltage-dependent calcium channels and facilitate γ-aminobutyric acid inhibitory transmission.The dose is 20 milligrams/kg IV. Although it is not yet approved by the Food and Drug Administration for status epilepticus, it is

rapidly gaining favor as a first-line drug for established status epilepticus.1,9,33,34,35

Lacosamide is a potential alternative for status epilepticus with limited availability and limited data on its use. The dose is 200

milligrams IV given over 15 minutes.1,36

REFRACTORY STATUS EPILEPTICUS

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2. 

Refractory status epilepticus is defined as persistent seizure activity despite the IV administration of adequate amounts of two

antiepileptic agents and usually exceeds 60 minutes.1 One study found that up to 31% of patients with status epilepticus went on

to develop refractory status epilepticus.37

Various approaches to refractory status epilepticus have been suggested (Figure 171–1).1,7,9,22,32–43 Overall, there are fewcontrolled trials that strongly support a single agent or combination of agents. Current recommendations include propofol,

midazolam, and barbiturates such as phenobarbital or pentobarbital given as infusions.1 All of these agents can lead tohypotension, sometimes requiring concomitant vasopressor use, and require intubation. Ideally, treatment is in consultationwith a neurologist and in an intensive care setting, because advanced respiratory support, cardiovascular support, and EEGmonitoring are all needed.

Propofol is a widely used, lipophilic, general anesthetic that has come into favor for refractory status epilepticus. It can bestarted as an infusion at typical rates of 2 to 10 milligrams/kg/h and titrated up to e�ect seizure cessation. Propofol has theadded benefit of a short half-life, allowing for quicker neurologic recovery a�er seizure control is achieved. At higher doses (>40milligrams/kg/h), patients are at increased risk for hemodynamic instability, including hypotension, as well as propofol infusion

syndrome.1,7,9,22,39

Midazolam is an easily titrated, infusible benzodiazepine that can also be used in the ongoing treatment of refractory status

epilepticus. Midazolam can be started at 0.05 to 0.4 milligram/kg/h and is titrated up to seizure cessation.1,9,40 Midazolam canaccumulate in peripheral so� tissues, particularly with renal insu�iciency, leading to a prolonged recovery period.

Barbiturates, such as phenobarbital (up to 20 milligrams/kg IV) or pentobarbital, may be considered as third-line drugs inpatients whose seizures are not controlled despite full loading doses of benzodiazepines and other agents. However, patients in

refractory status may not respond to barbiturates. One study found no added seizure control with phenobarbital.32 Asubsequent meta-analysis showed improved seizure control with pentobarbital compared to propofol or midazolam but no

di�erences in mortality.38 Respiratory depression and hypotension are more common when using barbiturates, especially at

higher doses or when diazepam or lorazepam is also given.1,9,22 Additionally, midazolam and propofol have the advantage over

barbiturates of having a shorter half-life and rapid clearance, allowing for earlier extubation and clinical assessment.1 For thesereasons, current recommendations are to use propofol and midazolam infusions as first- and second-line agents, respectively, in

refractory status epilepticus with barbiturates as third-line agents.1,9,22,39,40

Finally, ketamine may also be considered as a third-line agent in refractory status epilepticus. Ketamine is an N-methyl-d-

aspartate receptor antagonist and helps block the hyperexcitatory pathway, which is thought to be a greater culprit in refractorystatus epilepticus. Ketamine can be administered as a bolus dose of 0.5 to 4.5 milligrams/kg or as an infusion up to 5milligrams/kg/h. Multiple case reports and one retrospective study have demonstrated its safe use and likely benefit in

terminating refractory status epilepticus.22,41,42,43

REFERENCES

Cadena  R: Understanding ACEP's clinical policy on seizures. Emergency Physicians Monthly , 20–21 September 2014.http://www.epmonthly.com/features/current-features/understanding-acep-s-clinical-policy-on-seizures/. Accessed November24, 2014.

Lipka  K, Bulow  H: Lactic acidosis following convulsions. Acta Anaesthesiol Scand . 2003; 47: 616. [PubMed: 12699523]  

4/5/2019

13/16

3. 

4. 

5. 

6. 

7. 

8. 

9. 

10. 

11. 

12. 

13. 

14. 

15. 

Chen  DK, So  YT, Fisher  RS: Use of serum prolactin in diagnosing epileptic seizures. Neurology . 2005; 65: 668. [PubMed: 16157897]  

American College of Emergency Physicians: Critical issues in the evaluation and management of adult patients presenting tothe emergency department with seizures. Ann Emerg Med . 2004; 43: 605.

[PubMed: 15111920]  

Hope  OA, Zeber  JE, Kessin  N, et al. : New-onset geriatric epilepsy care: race, setting of diagnosis, and choice of antiepilepticdrug. Epilepsia . 2009; 50: 285.

[PubMed: 19054416]

Hakami  T, et al. : MRI-identified pathology in adults with new-onset seizures. Neurology . 2013; 81: 920. [PubMed: 23925763]  

Dionisio  S, Brown  H, Boyle  R, Blum  S: Managing the generalized tonic-clonic seizure and preventing progress to statusepilepticus: a stepwise approach. Int Med J . 2013; 43: 739.

[PubMed: 23614871]

Hu�  JS, Melnick  ER, Tomaszewski  CA, et al. : Clinical policy: critical issues in the evaluation and management of adultpatients presenting to the emergency department with seizures. Ann Emerg Med . 2014; 63: 437.

[PubMed: 24655445]  

Schmidt  D, Schachter  SC: Drug treatment of epilepsy in adults. Br Med J . 2014; 348: g254. [PubMed: 24583319]

Pesola  GR, Westfal  RE: New-onset generalized seizures in patients with AIDS presenting to an emergency department. AcadEmerg Med . 1998; 5: 905.

[PubMed: 9754504]  

Modi  G, Modi  M, Martinus  I, et al. : New-onset seizures associated with HIV infection. Neurology . 2000; 55: 1558. [PubMed: 11094114]  

Rajshekhar  V, Jeyaseelan  L: Seizure outcome in patients with a solitary cerebral cysticercus granuloma. Neurology . 2004; 62:2236

[PubMed: 15210888]  

White  AC: Neurocysticercosis: updates on epidemiology, pathogenesis, diagnosis, and management. Annu Rev Med . 2000;51: 187.

[PubMed: 10774460]  

Garcia  HH, Evans  CA, Nash  TE, et al. : Current consensus guidelines for treatment of neurocysticercosis. Clin Microb Rev .2002; 15: 747.

[PubMed: 126865]

Duley  L, Henderson-Smart  D: Magnesium sulphate versus diazepam for eclampsia. Cochrane Database Sys Rev . 2000; 2:CD000127.

[PubMed: 14583910]

4/5/2019

14/16

16. 

17. 

18. 

19. 

20. 

21. 

22. 

23. 

24. 

25. 

26. 

27. 

28. 

Witlin  AG, Sibai  BM: Magnesium sulfate therapy in preeclampsia and eclampsia. Obstet Gynecol . 1998; 92: 883. [PubMed: 9794688]  

Magpie Trial Collaboration Group: Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? TheMagpie Trial: a randomized placebo-controlled trial. Lancet . 2002; 359: 1877.

[PubMed: 12057549]

Gold  JA, Rimal  B, Nolan  A, et al. : A strategy of escalating doses of benzodiazepines and phenobarbital administrationreduces the need of mechanical ventilation in delirium tremens. Crit Care Med . 2007; 35: 724.

[PubMed: 17255852]  

Chen  JW, Wasterlain  CG: Status epilepticus: pathophysiology and management in adults. Lancet Neurol . 2006; 5: 246. [PubMed: 16488380]  

Lowenstein  DH, Bleck  T, Macdonald  RL: It's time to revise the definition of status epilepticus. Epilepsia . 1999; 40: 120. [PubMed: 9924914]  

Shorvon  SD, Baulac  TM, Cross  H, et al. : The drug treatment of status epilepticus in Europe: consensus document from aworkshop at the first London colloquium of status epilepticus. Epilepsia . 2008; 49: 2177.

[PubMed: 18638280]

Shorvon  S, Ferlisi  M: The treatment of super-refractory status epilepticus: a critical review of available therapies and aclinical treatment protocol. Brain . 2011; 134: 2802.

[PubMed: 21914716]  

Smith  KR, Kittler  JT: The cell biology of synaptic inhibition in health and disease. Curr Opin Neurobiol . 2010; 20: 550. [PubMed: 20650630]  

Friedman  A: Blood-brain barrier dysfunction, status epilepticus, seizures, and epilepsy: a puzzle of a chicken and egg.Epilepsia . 2011; 52: 19.

[PubMed: 21967353]  

Shah  AM, Vashi  A, Jagoda  A: Review article: convulsive and non-convulsive status epilepticus: an emergency medicineperspective. Emerg Med Australas . 2009; 21: 352.

[PubMed: 19840084]  

Silbergleit  R, Durkalski  V, Lowerstein  D, et al. : RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial): double-blinded randomized clinical trial of the e�icacy of intramuscular midazolam versus intravenous lorazepam in the prehospitaltreatment of status epilepticus by paramedics. Epilepsia . 2011; 52(Suppl 8): 45.

[PubMed: 21967361]  

Treiman  DM, Meyers  PD, Walton  NY, et al. : A comparison of four treatments for generalized convulsive status epilepticus. NEngl J Med . 1998; 339: 792.

[PubMed: 9738086]  

McIntyre  J, Robertson  S, Norris  E, et al. : Safety and e�icacy of buccal midazolam versus rectal diazepam for emergencytreatment of seizures in children: a randomized controlled trial. Lancet . 2005; 366: 205.

[PubMed: 16023510]  

4/5/2019

15/16

29. 

30. 

31. 

32. 

33. 

34. 

35. 

36. 

37. 

38. 

39. 

40. 

Mpimbaza  A, Ndeezi  G, Staedke  S, et al. : Comparison of buccal midazolam with rectal diazepam in the treatment ofprolonged seizures in Ugandan children: a randomized clinical trial. Pediatr . 2008; 121: e58.

[PubMed: 18166545]

Meek  PD, Davis  SN, Collin  DM, et al. : Guidelines for nonemergency use of parenteral phenytoin products: proceedings of anexpert panel consensus process. Panel on Nonemergency Use of Parenteral Phenytoin Products. Arch Intern Med . 1999; 159:2639.

[PubMed: 10597754]  

Agarwal  P, Kumar  N, Chandra  R, et al. : Randomized study of intravenous valproate and phenytoin in status epilepticus.Seizure . 2007; 16: 527.

[PubMed: 17616473]  

Sinha  S, Naritoku  DK: Intravenous valproate is well tolerated in unstable patients with status epilepticus. Neurology . 2000;55: 722.

[PubMed: 10980746]  

Wheless  JW, Treiman  DM: The role of the newer antiepileptic drugs in the treatment of generalized convulsive statusepilepticus. Epilepsia . 2008; 49(Suppl 9): 74.

[PubMed: 19087120]  

Gamez-Leyva  G, Aristín  JL, Fernández  E, et al. : Experience with intravenous levetiracetam in status epilepticus. CNS Drugs .2009; 23: 983.

[PubMed: 19845418]  

Aiguabella  M, Falip  M, Villaneuva  V, et al. : E�icacy of intravenous levetiracetam as an add-on treatment in status epilepticus:a multicenter observational study. Seizure . 2011; 20: 60.

[PubMed: 21145758]  

Santamarina  E, Toledo  M, Suerias  M, et al. : Usefulness of intravenous lacosamide in status epilepticus. J Neurol . 2013; 260:3122.

[PubMed: 24122063]  

Mayer  SA, Claassen  J, Lokin  J, et al. : Refractory status epilepticus, frequency, risk factors, and impact on outcome. ArchNeurol . 2002; 59: 205.

[PubMed: 11843690]  

Classen  J, Hirsch  LJ, Emerson  RG, Mayer  SA: Treatment of status epilepticus if first drug fails. Epilepsia . 2002; 40(Suppl 7):243.

Stecker  MM, Kramer  TH, Raps  EC, et al. : Treatment of refractory status epilepticus with propofol: clinical andpharmacokinetic findings. Epilepsia . 1998; 39: 18.

[PubMed: 9578008]  

Prasad  A, Worrall  BB, Bertram  EH, et al. : Propofol and midazolam in the treatment of refractory status epilepticus.Epilepsia . 2001; 42: 380.

[PubMed: 11442156]  

4/5/2019

16/16

41. 

42. 

43. 

44. 

45. 

46. 

Kramer  AH: Early ketamine to treat refractory status epilepticus. Neurocrit Care . 2012; 16: 299. [PubMed: 22237581]  

Synowiec  AS, Singh  DS, Yenugadhati  V, et al. : Ketamine use in the treatment of refractory status epilepticus. Epilepsy Res .2012; 105: 183.

[PubMed: 23369676]

Gaspard  N, Foreman  B, Judd  LM, et al. : Intravenous ketamine for the treatment of refractory status epilepticus: aretrospective multicenter study. Epilepsia . 2013; 54: 1498.

[PubMed: 23758557]  

USEFUL WEB RESOURCES

American Academy of Neurology — http://www.aan.com

American Epilepsy Society — http://www.aesnet.org/

Epilepsy Foundation — http://www.epilepsyfoundation.org

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