Seizure Disorders

Emergency management

Bibliography
Rosen's Emergency Medicine -Concepts and Clinical Practice 8th Ed

28/09/2020

Vaidyaratnam Ayurveda College | Ollur | Thrissur

For Internal Circulation only

 Seizure Disorders

PERSPECTIVE which is difficult to define and difficult to document.9,10 Finally,

partial seizures may become generalized (partial with secondary
A seizure is the clinical manifestation of excessive, abnormal corti- generalization).
cal neuron activity. The physical manifestation depends on the Inexperienced witnesses may provide histories that are insuffi-
area of brain cortex involved and, to a lesser extent, on the specific cient for accurate categorization of seizures. However, when an
underlying abnormality. Ictal event is the more general term used accurate history is available, secondary (reactive) seizures typically
to describe the seizure or seizure-like episode. Patients who have are generalized, not partial, in nature. The definitive differentia-
recurring seizures without consistent provocation have epilepsy, a tion among these classifications may require electroencephalo-
term that encompasses many disparate clinical syndromes. Sei- gram (EEG) recording during the seizure, sometimes in association
zures may also occur as a predictable response to certain toxic, with simultaneous video recording.11,12
pathophysiologic, or environmental stresses; these are reactive or Seizures in children, as in adults, are classified as primary (idio-
secondary seizures, and patients who experience these do not have pathic) and secondary (symptomatic or reactive). The term crypto-
epilepsy. In the United States, 10% of people experience at least genic is used sometimes when seizures are thought to be secondary
one seizure in their lifetime; the cumulative incidence of epilepsy but no cause has been identified. The history is a vital diagnostic
is 3%.1 tool in evaluating seizures in children, as the actual seizure activity
More than 1 million patients visit U.S. emergency departments is usually not observed.
(EDs) every year for seizure care.2 The evaluation of patients with Other important terms to describe ictal events include status
seizures in the ED can be complex and difficult. A careful history epilepticus, in which seizures are prolonged or occur serially
must be elicited to determine the presence of ictal events that without an intervening return to a normal neurologic condition;
represent epilepsy, exposure to ictogenic stimuli (e.g., alcohol, spasm, which is a specific, debilitating seizure syndrome that
cocaine), significant underlying illness (e.g., meningitis, hypox- occurs in infants; and myoclonus, which refers to rhythmic, shock-
emia, hypoglycemia, intracranial mass), or provocative stimuli like muscle contractions also typical for specific seizure syn-
(e.g., sleep deprivation in an epileptic). The physical examination dromes. The postictal period is an interval after a seizure, of
focuses on the identification of focal neurologic abnormalities, variable duration, usually characterized by impaired cognition but
systemic illness, and signs of toxic exposure. If the patient contin- sometimes also marked by such diverse physiologic manifestations
ues to experience seizure activity, airway protection and abortive as self-limited focal motor paralysis (Todd’s paralysis) or neuro-
therapy must be provided.3 Laboratory and radiographic evalua- genic pulmonary edema.
tion are guided by historical and physical findings and may be
limited or unnecessary in some cases. Finally, the appropriate dis- PRINCIPLES OF DISEASE
position of a patient in the ED with a seizure or with a history of
a recent seizure requires an understanding of the underlying The pathophysiology of seizures at the neuronal level is in-
illness, likelihood of recurrence, indications for maintenance completely understood, with most of what is known coming
pharmacologic therapy, and state reporting regulations. from animal studies in which either electrical or pharmacologic
In addition to the distinction between primary (epileptic) and stimulation is applied directly to brain cortex. To produce general-
secondary (reactive) seizures, many other classifications of ictal ized ictus, stimuli must be simultaneously applied to both hemi-
events have been proposed.4-8 Seizures are termed generalized or spheres. Some studies show the concept of recruitment, which
focal (partial) depending on the clinical manifestations. General- occurs when the initiating neurons’ abnormal, increased electrical
ized seizures result from an abnormal electrical event that simul- activity activates adjacent neurons and propagates until the thala-
taneously involves both cerebral hemispheres and is accompanied mus and other subcortical structures are recruited. The clinical
by loss of consciousness; in partial seizures, abnormal activity is seizure activity typically, but not always, reflects the focus of
limited to part of one cerebral hemisphere only. Generalized sei- initiation.10,13
zures usually are characterized by rhythmic, tonic-clonic muscle What prompts such initiation is unclear. Proposed mecha-
contractions, or convulsions, although nonconvulsive generalized nisms include disruption of normal structure, whether congenital,
seizures also occur. Partial seizures can be differentiated further maturational, or acquired (as with scar tissue), and disruption of
into seizures during which cognition is maintained (simple partial) local metabolic or biochemical function. The latter mechanism is
and seizures during which cognition is impaired (complex partial). better understood because the roles of two neurotransmitters—
The term cognition refers to involvement of at least two of five acetylcholine, which is excitatory to cortical neurons, and
features—perception, attention, emotion, memory, and executive γ-aminobutyric acid (GABA), which is inhibitory—have been
function—and replaces the previously used term consciousness, more fully characterized. In sensitive neurons, such as those at an

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ictogenic focus, subtle changes in the local concentrations of these seizure, and no aura is present. Some patients may experience a
neurotransmitters can produce sustained membrane depolariza- brief, vague prodrome or dysphoric state just before the ictal event.
tion, ultimately followed by local hyperpolarization and recruit- Convulsive generalized seizures are typified by the tonic-clonic, or
ment. Recruitment may follow contiguous paths or extend along grand mal, seizure, in which the patient loses consciousness, stiff-
diverse integrated circuits that are deep and cross the midline.10,13 ens with generalized muscular hypertonus, and then rhythmically
When the ictal discharge extends below the cortex to deeper and violently contracts multiple, bilateral, and usually symmetri-
structures, the reticular activating system in the brainstem may be cal muscle groups. The muscular force may be sufficiently vigor-
affected, altering consciousness. In generalized seizures, the focus ous to result in posterior shoulder dislocation or fractures of
often is subcortical and midline, which explains the prompt loss thoracic spine vertebral bodies; significant tongue and buccal
of consciousness and bilateral involvement. Seizures typically are injuries also may be incurred from biting with repeated jaw
self-limited; at some point, the hyperpolarization subsides and the muscle contractions. Dysautonomia, including transient apnea, is
electrical discharges from the focus terminate. This termination a potential manifestation of convulsive generalized seizures;
may be related to reflex inhibition, loss of synchrony, neuronal urinary incontinence is more common than fecal incontinence. A
exhaustion, or alteration of the local balance of acetylcholine and generalized convulsive seizure generally lasts 1 to 2 minutes and
GABA in favor of inhibition.10 is followed by a postictal state, headache, and drowsiness that may
The systemic manifestations of convulsive ictal activity include persist for hours. This state must be differentiated from altered
hypertension, tachycardia, tachypnea, and hyperglycemia from consciousness attributable to other causes.
sympathetic stimulation. With more prolonged convulsions, skel- Nonconvulsive generalized seizures include absence, or petit mal,
etal muscle damage, lactic acidosis, and, rarely, frank rhabdomy- seizures; myoclonic seizures; tonic seizures; and atonic seizures.
olysis may ensue.10,14,15 Autonomic discharge and bulbar Absence seizures in adults are subclassified further as typical or
muscle involvement may result in urinary or fecal incontinence, atypical. Typical absence ictus is characterized by the sudden ces-
vomiting (with significant aspiration risk), tongue biting, and sation of normal, conscious activity, followed by a nonconvulsive,
airway impairment. dissociative state that persists for a few seconds to several minutes
before suddenly terminating. Eye movements, blinking, or autom-
atisms may be present. There is no aura and no postictal state. If
CLINICAL FEATURES the seizure occurs midsentence, then the patient typically will
Primary Seizures in Adults resume speaking at precisely the point of interruption without
awareness of the intervening event. Absence seizures typically
Primary ictal events in adults may have a genetic origin or may be begin in childhood but occasionally develop in adults. Atypical
idiopathic. Onset is typically during childhood or adolescence, but absence seizures are marked by more complicated motor signs,
occasionally idiopathic seizures may begin de novo in adulthood. coexistence with other forms of generalized seizures, inconsistent
Because idiopathic seizures are rare, a first-time seizure in an adult postictal confusion, and irregular EEG abnormalities.13
requires a thorough evaluation. Atonic seizures are characterized by focal diminution of muscle
Focal seizures in adults may be classified as simple partial or tone (limb or head) or generalized loss of postural tone in which
complex partial. Simple partial seizures are limited in electrical the head falls forward and then the body slumps to the ground
focus to one cerebral hemisphere and do not cause loss of cogni- (“drop attack”), usually landing buttocks first (although this can
tion. Although the specific function of the initiating neurons vary depending on the axis of gravity at the time of the fall).
determines the clinical manifestation of the ictal event (i.e., motor, Recovery occurs immediately, and there is either no loss or an
somatosensory, special sensory, autonomic, or psychic), such clini- extremely brief loss of consciousness. In myoclonic-atonic seizures,
cal manifestations are not sufficiently specific for anatomic local- a brief (less than 100 msec) myoclonic jerk of muscle groups of
ization without an EEG. Typical features of simple partial seizures variable anatomy occurs before the episode of atonia.10 Because
include focal clonic movements; paresthesias; visual, auditory, typically no postictal state is associated with these episodes, an
olfactory, or gustatory experiences; sweating and flushing; dyspha- altered level of consciousness in a patient after an atonic or
sia; a sense of déjà vu; or a sense of unwarranted fear.10,13 Motor myoclonic-atonic seizure should prompt an investigation for head
signs, which by definition remain ipsilateral in simple partial sei- trauma or a toxic or metabolic abnormality.
zures, may spread contiguously in a stepwise fashion (Jacksonian Status epilepticus is defined as serial seizure activity without
march) as neuron recruitment occurs in the motor cortex. There interictal recovery or prolonged, continuous seizure activity.
is generally no postictal state after a simple partial seizure. Traditionally, status epilepticus was defined as seizure activity
Complex partial seizures are ictal events that involve impairment lasting longer than 30 minutes, which is the estimated duration
of cognition, either at onset or evolving from focal activity. necessary for neuronal injury.16,17 However, because an isolated
Amnesia for the ictal event is a consistent feature of complex tonic-clonic seizure rarely lasts more than a few minutes, an oper-
partial seizures, although during the episode the patient may ational definition of status epilepticus as either a continuous
remain responsive to the surroundings. Complex partial seizures seizure lasting more than 5 minutes or more than two discrete
typically involve automatisms that are specific to the affected seizures without intervening recovery of consciousness has been
person, such as lip smacking, repeated swallowing or uttering advocated.18 Although it is recognized that the underlying cause
verbal phrases, or picking at clothing. Complex partial seizures of status epilepticus is the predominant factor determining mor-
generally are associated with an aura, such as a specific smell, taste, bidity and mortality, prolonged seizure activity does cause neuro-
visual hallucination, or intense emotional feeling. In contrast with nal injury and therefore warrants prompt abortive therapy.
those experiencing generalized seizures, these patients may con- Furthermore, status epilepticus may become refractory to treat-
tinue with ongoing motor activity, such as driving an automobile, ment over time.17,19,20
riding a bicycle, or playing a musical instrument (reactive automa- In some cases a patient’s first seizure episode will manifest as
tisms), and they may react to their surroundings in a semi- status epilepticus. The most common cause of status epilepticus
appropriate manner.10 Partial seizures may progress rapidly to is discontinuation of anticonvulsant medication. This situation
generalized seizures. A postictal state is common after complex may be compounded by barbiturate withdrawal when phenobar-
partial seizures and may persist for hours.13 bital therapy is abruptly discontinued. Many other causes of status
Generalized seizures in adults may be convulsive or nonconvul- epilepticus have been documented (Box 102-1).14,16,21,22 After pro-
sive. By definition, patients lose consciousness in a generalized longed status epilepticus or after incomplete treatment, the patient
 4
Etiology of Status Epilepticus: auditory, gustatory, tactile, or startle triggers that are specific to
BOX 102-1 Common Causative Disorders the affected person. The most common cause of recurrent primary
seizures is medication noncompliance.13,29
Metabolic Disturbances
Hepatic encephalopathy
Hypocalcemia Reactive Seizures in Adults
Hypoglycemia or hyperglycemia
Hyponatremia Reactive or secondary seizures do not result from genetic or
Uremia idiopathic causes. The conditions that cause reactive seizures
may be static (e.g., anatomic scarring), progressive (e.g., degen-
Infectious Processes erative cortical disorders), or transient (e.g., acute electrolyte
CNS abscess derangements).
Encephalitis
Meningitis
Withdrawal Syndromes
Seizures Caused by Metabolic Derangements
Alcohol Hypoglycemia is a common metabolic cause of reactive seizures.
Antiepileptic drugs Ictal activity can occur when the plasma glucose level is less than
Baclofen
45 mg/dL, although some patients may manifest neurologic dis-
Barbiturates
Benzodiazepines turbances even at higher levels.30 A rapid bedside glucose test is an
integral part of the evaluation of the patient exhibiting seizure
CNS Lesions activity. Convulsive and nonconvulsive seizures and generalized
Acute hydrocephalus and partial seizures all may occur during hypoglycemia.31-34
Anoxic or hypoxic insult Patients at the extremes of age are particularly susceptible to
Arteriovenous malformations
Brain metastases
glucose stress during acute illness. Hypoglycemia also may result
Cerebrovascular accident from insulin reaction, a deliberate insulin or hypoglycemic agent
Chronic epilepsy overdose, alcoholism, poor nutrition, and sepsis. Hypoglycemic
Eclampsia seizures respond to glucose therapy; anticonvulsants and benzo-
Head trauma diazepines are unnecessary. At times, however, prolonged seizures
Intracerebral hemorrhage may cause hypoglycemia. Seizures that do not cease after cor-
Neoplasm rection of low blood glucose deserve further evaluation and
Neurosurgery treatment.
Posterior reversible leukoencephalopathy Cation derangements, notably hypernatremia and hyponatre-
Remote structural injury
mia, hypomagnesemia, and hypocalcemia, are other common
Intoxication metabolic causes of ictal activity.35,36 Hypo-osmolar and hyperos-
Bupropion molar states can precipitate seizures. Disorders of sodium, the
Camphor primary cation in the extracellular fluid compartment and the
Clozapine primary determinant of serum osmolarity, are most common.
Cyclosporine Hyponatremia is the most frequently identified electrolyte disor-
Flumazenil
Fluoroquinolones
der in hospitalized patients, and sodium levels less than 120 mEq/L
Imipenem often are associated with seizures.37,38 The rate at which the sodium
Isoniazid level decreases, and not the absolute magnitude of the decrease,
Lead determines the risk for neurologic manifestation.37 Correcting
Lidocaine hyponatremia should be undertaken slowly to avoid osmotic
Lithium demyelination. If seizures are persistent, administration of hyper-
Metronidazole tonic (3%) saline may be indicated.37 Hypernatremia will result in
Theophylline cerebral edema and seizures in the setting of rapid elevation of
Tricyclic antidepressants serum sodium to greater than 160 mEq/L or during aggressive
CNS, central nervous system. correction of subacute hyponatremia.36,39
Hypercalcemia reduces neuronal excitability and rarely causes
seizures; significant hypocalcemia (below 7.5 mEq/L), however, is
associated with ictal activity. Hypocalcemia may result from hypo-
may exhibit very subtle manifestations of continued seizure activ- parathyroidism, renal failure, or acute pancreatitis and typically is
ity, such as small-amplitude twitching of the extremities or jerking associated with hypomagnesemia, which also can precipitate sei-
of the eyes, or any visible motor activity may cease while seizure zures, particularly at serum levels less than 1 mEq/L. Hypomag-
activity detectable on the EEG continues.23-25 Recognition of the nesemia is seen most often as a result of poor nutrition, especially
latter scenario, termed nonconvulsive status epilepticus, requires a in alcoholic patients. Patients with significant hypomagnesemia or
high index of clinical suspicion. Prompt treatment is essential to hypocalcemia are treated empirically for both disorders.35,36
prevent neuronal damage; mortality approaches 30% if the seizure Nonketotic hyperosmolar hyperglycemia can be associated with
lasts more than an hour.26 Nonconvulsive status epilepticus may seizure activity. Partial seizures, including partial status, predomi-
be present in more than 9% of hospitalized patients with pro- nate. These seizures do not respond to anticonvulsants; rather,
longed decreased mental status.27 they are best managed with gradual correction of fluid deficits and
All classes of primary seizures may recur sporadically, ran- glucose excess.40-42
domly, or predictably. Cyclic recurrence has been reported with Seizures may complicate the course and treatment of renal
awakening, sleep deprivation, emotional or physical stress, alcohol, failure.43 Ictal activity occasionally complicates uremic encepha-
and menses, among other factors. Seizures also may be triggered lopathy, more commonly occurs as a result of acute fluid and
by specific sensory stimuli, the most common of which is visual electrolyte shifts during dialysis (dialysis disequilibrium syndrome),
stimulation in the form of flashing lights, such as strobe lights, and can be a complication of immunosuppressive therapy after
television, and video games.10,28 Seizures also can be caused by renal transplantation.
 5

Thyroid hormones lower seizure threshold, and consequently the treatment of choice for serious salicylate and lithium toxicity.
Graves’ disease and thyrotoxicosis may occasionally manifest as Dilantin administration is contraindicated in cases of ingestion
seizures, including status epilepticus.44 Seizures also occur with because its sodium channel blocking actions can worsen the
hypoparathyroidism as a result of secondary hypocalcemia.14 hemodynamic impact of the ingestion.3
Because of its prevalence in urban ED patient populations,
Seizures Caused by Infectious Diseases cocaine toxicity warrants special mention. Seizures may occur
after isolated recreational use or chronic abuse, after overdose,
Infectious diseases can cause seizures independent of a purely and in “body packers” and “body stuffers.”56 Cocaine-related sei-
febrile mechanism. These seizures generally result from primary zures may be a manifestation of direct CNS toxicity or an indirect
central nervous system (CNS) infections but occasionally arise result of hypoxemia from cardiac toxicity.57 Seizures in cocaine-
from other septic sources. The most important ictogenic infec- intoxicated patients are managed as part of the overall toxic reac-
tions are meningitis, encephalitis, cerebral abscess, cerebral para- tion, which often includes high fever, rhabdomyolysis, and cardiac
sitosis, and human immunodeficiency virus (HIV) disease and arrhythmias. A benzodiazepine is the appropriate initial therapeu-
associated opportunistic infections, with their protean CNS mani- tic agent.
festations. Cerebral malaria is a common cause in developing Ethyl alcohol use and abuse are additional common toxic causes
countries.45 of seizures; up to 40% of seizure patients in the ED have alcohol-
Seizures may result from the acute inflammatory response that related seizures.58 Ictal events may occur with acute inebriation
occurs with bacterial or viral meningitis. During the acute course but are more common during withdrawal from alcohol.59 With-
of illness, 15% of patients with bacterial meningitis will have at drawal seizures are typically generalized and recurrent and begin
least one seizure,46 and surviving patients have an increased risk within 6 hours of cessation of or decrease in alcohol consumption.
of epilepsy.47 Viral meningoencephalitides, the most common of Through a phenomenon termed kindling, the risk and severity of
which are caused by the herpes simplex virus, also are associated seizures increase with each episode of withdrawal. Kindling means
with seizures. These seizures may be generalized or partial, often that with each episode of alcohol withdrawal, the seizure threshold
recur during the acute phase of the illness, and may persist after is lower. Alcoholic patients with seizures should also be evaluated
the illness has resolved.48 for related, concomitant ictogenic problems (e.g., hypoglycemia,
The parasitic CNS infection neurocysticercosis is relatively electrolyte derangements, head trauma, coingestion of other
common in areas of the United States where there is a population toxins, pregnancy). The preferred treatment for alcohol-associated
of immigrants from Latin America. Seizures complicate 50 to 90% seizures is with benzodiazepines, as these drugs substitute for the
of neurocysticercosis cases.49 Latent syphilis can cause adult-onset GABA-enhancing effect of ethanol in the CNS.
seizures. Primary HIV disease of the CNS with its attendant infec-
tious and mass lesion complications constitutes a significant cause Seizures Caused by Trauma
of generalized and partial seizures. Common HIV-associated
infections and conditions include toxoplasmosis, lymphoma, and Post-traumatic seizures can occur acutely as a result of blunt or
the demyelinating infection progressive multifocal leukoencepha- penetrating head trauma or as a post-traumatic sequela. Immedi-
lopathy.50 Choosing an antiepileptic drug (AED) for an HIV- ate post-traumatic seizures occur within 24 hours of injury. Epi-
infected patient with seizures is done in consultation with dural, subdural, and intracerebral hematomas and traumatic
infectious disease and neurology specialists because of the well- subarachnoid hemorrhages all can be acutely ictogenic, particu-
recognized increase in adverse effects of AEDs and the interactions larly as intracranial pressure rises. More often, however, the onset
between AEDs and antiviral medications. of seizure activity is delayed for at least several hours. Early post-
traumatic seizures occur within 1 week of injury, whereas late
Seizures Caused by Drugs and Toxins post-traumatic seizures occur after 1 week. Immediate and early
post-traumatic seizures are more common in children than in
The list of substances reported to cause seizures either as an adults, and children also are more likely than adults to be pre-
idiosyncratic side effect of therapeutic use or as a manifestation sented in status epilepticus in the immediate or early post-
of toxic overdose is extensive.22,51 The recognition of this etiologic traumatic phase.60
category is crucial in the ED setting. Seizure activity is a dire The severity of head injury correlates with the likelihood of
sign of toxicity and may herald the onset of life-threatening post-traumatic seizures. Although seizures rarely occur after mild
instability. traumatic brain injury, the incidence approaches 30% in patients
Seizures may occur after therapeutic doses of antimicrobials, with depressed skull fracture.60,61 Antiepileptic drugs are recom-
cardiovascular agents, neuroleptics, and sympathomimetics.52 Sei- mended for prophylaxis against post-traumatic seizures occurring
zures also may result from exposure to plant toxins, insecticides, within the first 7 days after severe brain injury in adults; however,
rodenticides, and hydrocarbons. Certain over-the-counter supple- they have not been shown to be effective in preventing late post-
ments also have been associated with seizures, either alone or traumatic seizures.62,63
through adverse interactions with prescription medications.53,54
The most common drug-associated and toxin-associated seizures Seizures Associated with Malignancy or Vasculitis
occur, however, in conjunction with illicit drugs, such as cocaine,
amphetamines, and phencyclidine; with overdoses of anticholin- Seizures are a common manifestation of primary and metastatic
ergic agents, such as cyclic antidepressants and antihistamines; as CNS neoplasms. They also may complicate cancer treatment as a
a manifestation of withdrawal from ethyl alcohol and sedative- result of postsurgical scarring or chemotherapy-related electrolyte
hypnotics; and with toxic levels and deliberate overdoses of diverse derangements, hematologic abnormalities, or immunosuppres-
medications, including aspirin, theophylline, meperidine, isonia- sion. Although any CNS tumor can be ictogenic, low-grade and
zid, lithium, and anticonvulsants, including phenytoin, carbam- slow-growing primary neoplasms (e.g., well-differentiated gliomas
azepine, lamotrigine, and topiramate.51,55 Standard ED therapeutic and oligodendrogliomas) are implicated most commonly.64 In
measures are usually effective for management of toxic seizures. such cases, seizures, which most often are partial with secondary
In some cases, specific antidotal therapy is available, such as alka- generalization, may be the initial clinical manifestation. A new-
linization for cyclic antidepressant and salicylate overdoses, and onset seizure in a patient with a non-CNS primary malignancy,
pyridoxine (vitamin B6) for isoniazid overdose. Hemodialysis is such as melanoma and tumors of the lung, breast, colon, germ
 6
75
cells, or renal cells, prompts consideration of CNS metastasis and labetalol, or nifedipine is recommended. Postpartum eclampsia
warrants neuroimaging. represents 25% of eclamptic seizures, can occur up to 8 weeks
Seizures also may be the presenting manifestation of CNS vas- after delivery, and can be seen in women without preceding
culitis in patients with systemic lupus erythematosus and poly- preeclampsia.76
arteritis nodosa and are usually complex partial seizures that give
a general indication of the acute inflammatory focus. Secondary Psychogenic Nonepileptic Seizures
generalization may also occur.65
Psychogenic seizures, or pseudoseizures, are functional events that
Seizures Caused by Strokes, Arteriovenous may be associated with alterations in cognition, abnormal
Malformations, Aneurysms, and Migraines movements and behaviors, and autonomic changes. They are
not the result of abnormal CNS electrical activity. Psychogenic
Ischemic or hemorrhagic stroke is the cause of new-onset seizures seizures may be primarily motor and mimic convulsive
in 40 to 54% of elderly patients.66 The overall incidence of seizures generalized seizures, including refractory status epilepticus, or they
with stroke ranges from 4 to 15%; more than one half occur within may be non-convulsive and mimic either absence or complex
the first week after stroke. The incidence of epilepsy after stroke is partial seizures. Although certain features of convulsive psychogenic
4 to 9%.67,68 Seizures that occur acutely with stroke are thought to seizures may suggest the diagnosis, no clinical criteria are 100%
result from local metabolic alterations in the CNS; these events are specific; simultaneous video and EEG recordings may be required
transient, and the seizures often are focal and self-limited. Seizures to confirm the diagnosis.77,78
that develop later are more likely to be generalized. The ED evaluation of these patients is difficult, because epilepsy
Convulsive seizures occur in 6 to 26% of patients with and pseudoseizures can coexist in a minority of patients.79 All but
subarachnoid hemorrhage after aneurysmal rupture; 8 to 15% obviously functional abnormalities should be treated as true ictus
of patients will experience nonconvulsive seizures.69 Seizures pending formal neurologic evaluation. Many patients with pseu-
also occur in conjunction with unruptured cerebrovascular aneu- doseizures are not deliberately attempting to mislead the examining
rysms and arteriovenous malformations.70 Arteriography may be physician. The long-term treatment of patients with confirmed
required to confirm the diagnosis; unruptured arteriovenous mal- pseudoseizures may include direct confrontation, intensive
formations are easier to detect on an enhanced cranial computed psychotherapy, and use of a placebo.
tomography (CT) scan than are smaller, unruptured aneurysms.
Seizures also may arise in concert with vascular headaches, Postictal States
either coincidentally, by migrainous activation of an epileptic
focus, or after vascular headache has induced cerebral infarction The postictal state that follows most generalized seizures typically
that becomes an epileptic focus.71 is characterized by decreased levels of arousal and responsiveness,
disorientation, amnesia, and headache. These conditions may
Seizures Caused by Degenerative Disease persist for only a few minutes or for many hours and may not be
of the Central Nervous System consistent from seizure to seizure. The most important consider-
ation in ED management of the postictal state is to monitor and
In approximately 3% of patients with multiple sclerosis, focal or investigate the altered mental status after a seizure; otherwise,
generalized seizures develop during the course of their illness. dangerous underlying metabolic or toxic abnormalities may be
These seizures must be differentiated from the tonic spasms that overlooked. At a minimum, airway positioning maneuvers, pulse
may occur in multiple sclerosis.72 oximetry, rapid glucose determination, and cardiac rhythm
CNS degeneration associated with aging, including dementia monitoring are necessary.
and Alzheimer’s disease, increases the risk of reactive seizures and Two unusual postictal manifestations may provoke particular
epilepsy.66,73 The elderly also are more likely to have other ictogenic consternation in the ED: postictal paralysis and neurogenic pul-
problems (e.g., stroke, brain neoplasm, toxic and metabolic dis- monary edema. Postictal paralysis, or Todd’s paralysis, may follow
turbances, blunt head trauma from falls). Maintenance treatment generalized or complex partial seizures and is a focal motor deficit
of elder patients with epilepsy often is complicated by drug-drug that may persist up to 24 hours and may be caused by transient
interactions, and breakthrough seizures may result even when focal cerebral hypoprofusion.80 Weakness of one extremity or a
patients are compliant. Although the incidence of unprovoked complete hemiparesis may occur; in the latter case the patient
seizures increases after age 60 years, the management of these should be safely restrained to avoid falls caused by a combination
patients must include a thorough evaluation for causes of second- of weakness and diminished responsiveness resulting from the
ary seizures.66 postictal state. Todd’s paralysis is associated with a high likelihood
of an underlying structural cause for the seizure.
Neurogenic pulmonary edema is a relatively common,
Gestational Seizures
although often subclinical, complication of any structural CNS
Seizures associated with pregnancy are divided into two catego- insult, including seizure, trauma, and hemorrhage.81 Neurogenic
ries: gestational epilepsy, in which hormonal and metabolic changes pulmonary edema is likely caused by centrally mediated sympa-
exacerbate underlying epilepsy or adversely influence serum levels thetic discharge and generalized vasoconstriction, coupled with
of anticonvulsants, and eclampsia or toxemia, which is a gesta- increased pulmonary capillary membrane permeability. After a
tional hypertensive encephalopathy manifesting with seizures, seizure, neurogenic pulmonary edema can be confused clinically
hypertension, coma, proteinuria, and edema. For the former, anti- and radiographically with aspiration pneumonia. Otherwise
epileptic therapy should be tailored by the patient’s neurologist unexplained hypoxia or other clinical evidence of pulmonary
and obstetrician to maximize seizure control and minimize the congestion after a seizure prompts consideration of neurogenic
risk of teratogenic effects.74 pulmonary edema. Significant neurogenic pulmonary edema is
Convulsive generalized status epilepticus in pregnancy managed with ventilatory support, including positive end-
jeopardizes both mother and fetus. The definitive treatment for expiratory pressure.82,83
eclamptic seizures is magnesium sulfate and immediate delivery A prolonged postictal state raises clinical suspicion for noncon-
of the fetus; benzodiazepines are useful adjuncts to magnesium. vulsive status epilepticus. After prolonged tonic-clonic seizures,
Simultaneous reduction in blood pressure with use of hydralazine, ongoing cerebral epileptic activity may manifest with subtle motor
 7

movements such as twitching of the digits or face. EEG is the most a recurrent seizure within 2 years.90,99,100 Furthermore, whereas
definitive way to confirm the diagnosis.26 treatment decreases the risk of early recurrent seizure, it does not
affect long-term prognosis of epilepsy,90,101-103 nor does it have an
impact on patient quality of life,104 with the exception of driving
limitations, which are prolonged in a patient with recurrent
DIAGNOSTIC STRATEGIES seizure. Third, antiepileptic medications have side effects that may
First-Time Seizures outweigh the benefit of treatment, especially in women of child-
bearing age, owing to the teratogenic risk of AEDs; in patients with
The essential components of the seizure evaluation in the ED are liver, kidney, or hematologic disorders; and in patients already
discussed in Chapter 18. An accurate and thorough history of the taking multiple medications.
ictal event and information about any known or potential precipi-
tants or exposures and the patient’s medical problems are obtained. Recurrent Seizures
A thorough physical examination, including a complete neuro-
logic examination, is essential. Any identified focal neurologic The initial approach to stabilization of a patient with a known
deficits must be monitored for progression or resolution. Appro- seizure disorder does not differ from that for a patient with new-
priate ancillary studies may be comprehensive, but if precipitants onset seizure; this includes a rapid blood glucose determination
(e.g., hypoglycemia, intoxication, medication noncompliance) are and evaluation for precipitant causes. The most common cause
known, studies may be comparatively limited. Frequently, the of seizures in a patient with a diagnosed seizure disorder is non-
cause of the first seizure in an adult cannot be found in the ED.84 compliance with medications.29 However, supratherapeutic and
Although the Academy of Neurology recommends neuroimag- toxic levels of some anticonvulsants, such as carbamazepine, phe-
ing, by either CT or magnetic resonance imaging (MRI), for all nytoin, lamotrigine, and topiramate, can also cause seizures.105-110
adults with an apparently unprovoked first seizure, the usefulness Accordingly, it is prudent to check the serum drug level, if this
of emergent imaging depends on the clinical situation.85 An emer- test is available, before giving a full loading dose of anticonvulsants
gent cranial CT scan is indicated when a serious structural lesion to patients on long-term therapy. Meanwhile, a thorough history
is suspected on clinical grounds, including presence of a new focal and physical examination focus on intercurrent illness or trauma,
deficit, persistent altered mental status, fever, recent trauma, per- drug or alcohol use, potential adverse drug-drug interactions with
sistent headache, history of cancer, anticoagulant use, suspicion or anticonvulsants, a recent change in anticonvulsant dosage regi-
known history of acquired immunodeficiency syndrome (AIDS), mens, and any change in ictal pattern or characteristics. Clinical
age older than 40 years, and partial-complex seizure.86 A reason- indications dictate the selection of other laboratory or radio-
able approach is to obtain a brain CT scan on an outpatient, graphic tests.
follow-up basis in patients who have recovered completely from
the ictal event and in whom no apparent cause has been eluci-
dated. However, if reliable follow-up care is unlikely or even ques- DIFFERENTIAL CONSIDERATIONS
tionable, the CT scan should be obtained in the ED to ensure its
completion. In patients with known epilepsy and recurrent sei- Even when a “seizure” is witnessed in the ED, other abnormal
zures, the same considerations apply, but in addition, epileptic movements and states of consciousness can be confused with ictal
patients with a change in seizure pattern, prolonged postictal state, activity. The most common misdiagnoses are cardiovascular
or persistent abnormal mental status should undergo brain CT (syncope) and psychogenic, but other considerations in the dif-
scan in the ED. ferential diagnosis include hyperventilation and breath-holding,
Children with seizures can be evaluated in a similar manner. certain toxic and metabolic states, transient ischemic attacks, nar-
Those with febrile seizures are not more likely than those with colepsy, and some movement disorders.13,96,111-114
fever alone to have a serious bacterial infection. Children with At times the diagnosis can be difficult in a patient who is seen
afebrile seizures who are well appearing can generally be managed after an unwitnessed fall and unprovoked loss of consciousness.
as outpatients. Blood tests and other diagnostics are indicated in Syncope, whether vasodepressive (e.g., “vagal” or micturition
children younger than 6 months, those who have had a prolonged syncope), orthostatic, or arrhythmogenic (e.g., paroxysmal ven-
seizure or postictal state, and those who have a preexisting meta- tricular tachycardia or fibrillation, long QT syndrome), may be
bolic disorder or suspected dehydration. Emergent neuroimaging confused with ictal events. Differentiating among these may be
is indicated for children with significant past medical histories or particularly difficult when episodes are recurrent; hence the con-
in cases of focal seizures in children younger than 3 years.87,88 sideration “fit versus faint.” A tonic phase preceding tonic-clonic
Children younger than 6 months may have positive, relevant brain activity is not seen with syncope, and the tonic-clonic movements
CT findings in 50% of cases.89 in patients with seizures are much more forceful and are more
The decision to initiate anticonvulsant therapy after a single prolonged than the “twitches” sometimes associated with fainting.
seizure depends on the cause of the seizure. Seizures caused by Tongue biting and urinary incontinence rarely occur with syncope
structural lesions, such as stroke, tumor, or head injury, are likely but are common with seizures. Most seizures are characterized by
to recur and may warrant antiepileptic medication. However, such a postictal state in which patients are confused and may complain
patients also are likely to be admitted to the hospital if the lesion of headache, which is not a feature of syncope. Retrograde amnesia
is newly discovered. For patients with a single unprovoked seizure, also suggests an ictal diagnosis.
evidence-based recommendations are that antiepileptic therapy Hyperventilation syndrome can be associated with mood dis-
should not be initiated; rather, the patient should be discharged turbances, paresthesias, and posturing movements of the distal
with referral for neurologic consultation.84,86,90,93,94 The rationale extremities. Manifestations of toxic and metabolic disorders that
for this approach is threefold. First, the diagnosis may be incorrect, mimic ictus include delirium tremens and alcoholic blackouts, the
especially if the seizure-like activity was not witnessed by experi- alteration in consciousness associated with hypoglycemia and
enced medical personnel. It is estimated that 20 to 25% of patients acute intermittent porphyria, the buccolingual spasms of phency-
diagnosed as having seizures are eventually determined not to clidine intoxication, and the tonic spasms caused by tetanus,
have seizures, with the most frequent alternative diagnoses being strychnine, and camphor.13 Nonictal CNS events, such as transient
cardiovascular and psychopathologic.95-98 Second, the patient may ischemic attacks, transient global amnesia, and atypical migraines,
not have a recurrent seizure. It is estimated that less than 50% of may manifest in a manner similar to absence seizures and postictal
patients who have had a single unprovoked seizure will experience states such as Todd’s paralysis. Carotid sinus hypersensitivity,
 8
which can result even from a tight necktie, may cause sudden falls In general, the first-line pharmacologic agent for treatment of
that mimic drop attacks.115 Narcolepsy (recurrent irresistible any active seizure is a parenteral benzodiazepine. Because benzo-
daytime sleepiness), especially when it occurs with cataplexy diazepines directly enhance GABA-mediated neuronal inhibition,
(sudden falls), may be associated with hallucinations and abnor- they affect clinical and electrical manifestations of seizures. Ben-
mal movements. It can be differentiated from seizure activity by zodiazepines are effective in terminating ictal activity in a majority
the history and response to stimulation. Movement disorders, of patients and have been shown to be more effective than phe-
such as hemiballismus and tics, usually are associated with other nytoin in terminating status epilepticus.116,117 Although phenobar-
neurologic problems. Finally, dissociative states such as fugue and bital appears to be as effective as the benzodiazepine lorazepam in
panic attacks can be confused with seizures. An EEG is an appro- terminating status epilepticus, the associated high risk of hypoven-
priate diagnostic option in unclear cases. tilation and hypotension limits its use as a first-line agent.117
The most commonly used benzodiazepines include diazepam,
lorazepam, and midazolam (Table 102-1). All three may be used
MANAGEMENT in patients of any age, and all share the following characteristics:
Immediate Management rapid onset (seconds to minutes), relatively short duration of anti-
convulsant action, a sedative effect, and the potential for hypoten-
The management of a patient experiencing a seizure begins with sion and respiratory depression. Lorazepam has emerged as the
active, anticipatory airway management. In generalized ictus, the drug of choice for the initial management of convulsions, because
gag reflex is suppressed, and vomiting often is complicated by it terminates seizures rapidly (within 2 minutes) and has a longer
aspiration of gastric contents. The patient is placed in a left lateral duration of action (4-6 hours, compared with 20 minutes for
decubitus position to lessen chances of aspiration. Dentures are diazepam), thus necessitating fewer repeat doses.118-121 For this
removed but kept close by, as they may be needed for a good mask reason, it also is the preferred agent for control of alcohol with-
seal to be attained if bag-mask ventilation is required. A bite-block drawal seizures.122 Lorazepam is most effective when given intra-
can be placed to protect the tongue and allow access for suction- venously but can also be administered intramuscularly, intranasally,
ing, but care should be taken to avoid iatrogenic trauma from intraosseously, and as a sublingual preparation for out-of-hospital
forceful placement of intraoral devices. control of seizures in children.123
If the patient is persistently apneic or if an unavoidable airway An advantage of diazepam is that it is in liquid form at room
threat is present, endotracheal intubation is warranted for defini- temperature and is therefore available premixed in resuscitation
tive protection. A benzodiazepine can be used as an induction kits, and it can be administered quickly and without a need for
agent in the hope that its action may terminate the seizure or reconstitution by the intravenous, endotracheal, or intraosseous
obviate the need for tracheal intubation. Postintubation sedation route. Its onset of action with intravenous administration is within
with benzodiazepine infusion or propofol infusion is also recom- 10 to 20 seconds, but there is a 50% chance of recurrent seizure
mended. Trismus may necessitate use of a short-acting neuromus- within 2 hours if diazepam is used.117 Diazepam can also be
cular blocking agent to facilitate intubation; long-acting paralytics administered rectally via suppositories or a rectal gel. Rectal diaz-
will mask motor manifestations of ongoing seizures. epam achieves variable success in seizure cessation, perhaps owing

Table 102-1 Medications Used in the Abortive Treatment of Status Epilepticus in the Emergency Department
MEDICATION ADULT DOSE PEDIATRIC DOSE COMMENTS
Initial Therapy
Diazepam 10 mg IV or 10-20 mg PR 0.15 mg/kg IV; 0.2-0.5 mg/kg May repeat in 5-10 min; monitor
PR (max 20 mg) respiratory status
Lorazepam 4 mg IV <13 kg: 0.1 mg/kg IV (max Preferred intravenous benzodiazepine; may
2 mg); 13-39 kg: 2 mg IV; repeat in 10 min; monitor respiratory status
>39 kg: 4 mg IV
Midazolam 10 mg IV, IM, IN, buccally 0.2 mg/kg IV, IN (max 5 mg); Preferred intramuscular benzodiazepine;
0.5 mg/kg buccal (max 5 mg); may repeat in 10 min; monitor respiratory
<13 kg: 0.2 mg/kg IM (max status
5 mg); 13-39 kg: 5 mg IM;
>39 kg: 10 mg IM
Second-Tier Treatments
Phenytoin 20-mg/kg intravenous infusion 20-mg/kg intravenous infusion May cause hypotension and dysrhythmia
Fosphenytoin 20-mg PE/kg intravenous infusion or 20-mg PE/kg intravenous
20 mg PE/kg IM infusion
Valproic sodium 20-40 mg/kg IV infusion Max dose 60 mg/kg/day
Pentobarbital 10- to 20-mg/kg intravenous bolus then 0.5- Titrate according to EEG; intubation and
3.0 mg/kg/hr hemodynamic support required
Phenobarbital 5-15 mg/kg IV bolus then 0.5-5.0 mg/kg/hr Intubation likely required
Midazolam infusion 0.05-2 mg/kg/hr 0.5-2 mg/kg/hr Monitor respiratory status
Propofol infusion 1-2 mg/kg intravenous bolus then 20-200 μg/ Intubation required
kg/hr infusion
Isoflurane inhalation Titrate according to EEG; intubation and
hemodynamic support required

Brophy GM, et al: Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 17:3-23, 2012.
EEG, electroencephalogram; ET, endotracheally; IM, intramuscularly; IN, intranasally; IV, intravenously; PR, rectally.
 9

to the dual venous drainage of the rectum. The inferior and encephalopathy after valproic acid loading has been reported and
middle rectal veins drain into the central circulation via the should be evaluated by obtaining the serum ammonia level in a
common iliacs, whereas the superior rectal vein flows into the patient who does not regain consciousness after seizure resolu-
hepatic portal system. Diazepam placed too deeply into the rectum tion.21,139 Appropriate ED dosage regimens for the benzodiaze-
would undergo first-pass metabolism in the liver, thus limiting pines, phenytoin, fosphenytoin, phenobarbital, and valproic acid
bioavailability and clinical effect. are listed in Table 102-1.
Midazolam’s onset of action is within 1 minute; it is available While these agents are being given to abort ongoing seizure
in both intranasal and buccal formulations,124 and among the activity, ED management must include a search for underlying
benzodiazepines it has the least cardiovascular effect.121 Mid- reversible causes. This search may prompt administration of dex-
azolam is rapidly and reliably absorbed after intramuscular trose for hypoglycemia, pyridoxine (vitamin B6) for isoniazid over-
administration and has been shown to be as effective when given dose, sodium for hyponatremia, or magnesium for eclampsia.
intramuscularly as intravenous lorazepam, making it a preferred Eclampsia complicates 1 in 1000 deliveries in the United States
medication when intravenous access has not yet been estab- and can occur antepartum (91% of cases occur after 28 weeks of
lished.125 Nonintravenous midazolam is as effective as intravenous gestation), during the peripartal period, and up to 8 weeks
diazepam, and buccal midazolam is superior to rectal diazepam in postpartum.140-142 Abortive treatment for eclamptic seizures is with
achieving symptom control.126 magnesium sulfate, which is superior to both diazepam and phe-
Second-line abortive anticonvulsant therapy consists of phe- nytoin in limiting maternal mortality and preventing further sei-
nytoin and phenobarbital. Phenytoin reduces the repetitive firing zures in eclampsia.143,144 The loading dose of magnesium sulfate is
of action potentials through sodium channel blockade, thereby 4 to 6 g, followed by an infusion of 2 g/hr for 24 hours.75,143,144
stabilizing neuronal membranes.10 Phenytoin neither sedates Because hypermagnesemia may cause respiratory arrest, it is
patients nor causes respiratory depression, but rapid intravenous essential to monitor patients for hyporeflexia, which precedes
administration of phenytoin in its propylene glycol diluent respiratory compromise. In the uncommon event of respiratory
may cause hypotension and cardiac bradydysrhythmias, as well as compromise resulting from excessive neuromuscular blockade
local vascular injury, including venous thrombosis and localized caused by magnesium sulfate, 1 g of 10% calcium gluconate is an
tissue necrosis (purple glove syndrome).127-129 Phenytoin’s onset of effective reversal agent.75 Simultaneous reduction in blood pres-
action is within 10 to 30 minutes, and intravenous administration sure in the eclamptic patient, with use of hydralazine, labetalol, or
typically requires at least 20 minutes.130 The duration of action is nicardipine, is recommended.75
approximately 24 hours. Continued benzodiazepine administra- Nonpregnant patients who continue having seizures in the ED
tion is appropriate until phenytoin achieves adequate brain levels. despite management with benzodiazepines, phenytoin, or pheno-
Phenytoin is not recommended in toxin-induced seizures, as it is barbital are likely to meet the clinical criteria for refractory status
likely to be ineffective and may be harmful in cases of theophylline epilepticus. Additional therapeutic measures include use of val-
or tricyclic antidepressant ingestions.3 proate, midazolam infusion, propofol infusion, barbiturate coma,
Fosphenytoin is a water-soluble prodrug form of phenytoin, and general inhalational anesthesia. Valproate, which increases
with a more physiologic pH. Its main advantages are that it is GABA concentration, may be given intravenously in status epilep-
not likely to precipitate during intravenous infusion and that it ticus (see Table 102-1).23 Another alternative is the use of propofol,
also can be administered intramuscularly, although the volume a nonbarbiturate anesthetic agent with hypnotic and anticonvul-
required for full loading by the intramuscular route may be in the sant activity. Studies suggest that propofol acts at a location other
range of 20 mL or more.131 Although fosphenytoin can be infused than the benzodiazepine-binding site and modifies the chloride
more rapidly, the time to therapeutic concentration of the active channel by a mechanism that is different from, and possibly syn-
drug is the same as for intravenous phenytoin.132 The hemody- ergistic with, those for benzodiazepines and barbiturates. Propofol
namic advantages of fosphenytoin over intravenous phenytoin usually is administered as an intravenous loading dose, followed
have not proven to be significant.133,134 Fosphenytoin use is most by an infusion with continuous EEG monitoring to ensure persis-
appropriate when intravenous access is not obtainable or when tent burst suppression.145,146
the intravenous line is of small gauge, as is often the case in chil- Barbiturate coma is effective in terminating seizures by acting
dren and elders.120 as a GABA agonist, although it also suppresses all brainstem func-
If the serum drug level of phenytoin is subtherapeutic in a tion. Neurologic consultation is advisable before induction of
patient already being treated for seizures, a loading dose can be barbiturate coma in a patient with refractory status epilepticus.
given intravenously or orally in divided doses over 6 hours. Oral Expected consequences of barbiturate coma include respiratory
loading of phenytoin is associated with fewer adverse events than arrest, myocardial depression, and hypotension. At the same time,
loading with either intravenous phenytoin or fosphenytoin,134 but intracranial pressure may be decreased, thus increasing cerebral
it is inadequate when therapeutic activity is required urgently. perfusion. The preferred agent for barbiturate coma is pentobar-
Phenobarbital is similar to benzodiazepines in that it binds to bital (see Table 102-1). Patients who are treated with barbiturate
and enhances the inhibitory neurotransmitter GABA, thereby coma require intubation and ventilatory support, continuous
acting as a CNS depressant that decreases ictal and physiologic cardiac monitoring, and invasive hemodynamic monitoring. Pres-
cortical electrical activity. Sedation and depression of respiratory sors may be required to support the blood pressure.147
drive and blood pressure must be anticipated, and for this reason Inhalation anesthetics are one final alternative in the manage-
nonsedating phenytoin is preferred.121 The onset of action of phe- ment of refractory ictus. Isoflurane and halothane are the common
nobarbital is within 15 to 30 minutes, and the duration of action gases that are available. Halothane is associated with more hemo-
is 48 hours. dynamic and hepatotoxic complications. Isoflurane suppresses
Valproic acid administered intravenously has recently been electrical seizure foci and is easily titratable. Patients managed
recognized as a safe and effective treatment for seizures, especially with inhalational anesthesia require intubation and mechanical
in patients with allergies to phenytoin, the elderly, and patients ventilation.
with cardiorespiratory instability who might be at increased risk The role of newer AEDs, such as lacosamide and levetiracetam,
of adverse events from phenytoin.135-137 Valproic acid administered in the management of status epilepticus has not yet been well
intravenously has been shown to be as effective as phenytoin established.148,149
in patients with benzodiazepine-refractory status epilepticus, The visible manifestations of convulsive ictus are extinguished
with fewer cardiopulmonary side effects.138 Hyperammonemic by neuromuscular blockade. When a seizing patient is paralyzed
 10

and intubated, it cannot be assumed that pharmacologic therapy 2-year risk of recurrence without treatment generally is con-
has terminated the seizure. Anticonvulsant administration is con- sidered to be less than 50%.90,99,100 The presence of EEG abnor-
tinued, and EEG monitoring of the patient is arranged. Without malities suggests greater risk, but this information usually is
EEG, detection of seizure activity in a heavily sedated or paralyzed unavailable in the ED setting. Other factors associated with an
patient may be impossible. increased risk of recurrence are partial (versus generalized) ictus,
status epilepticus, a history of intracranial surgery or trauma,
Long-Term Management and the presence of a persistent neurologic abnormality, such as
Todd’s paralysis.
Identifying a new-onset seizure disorder in the ED prompts con- The presence of specific underlying conditions may affect the
sideration of the need for further management in the following decision to institute long-term therapy. For example, it would be
three areas: pharmacologic, psychosocial, and legal. The primary reasonable to initiate antiepileptic therapy for an initial seizure in
dilemma is whether or not to initiate prophylactic anticonvulsant an HIV-positive patient when the seizure is not a result of correct-
therapy after one seizure. The decision to treat should be based on able factors such as drug toxicity or metabolic derangement.50,90
(1) ensuring that the diagnosis of seizure is correct, (2) ascertain- Alcohol-related seizures are notoriously unresponsive to anticon-
ing the likelihood of seizure recurrence, (3) assessing the benefit vulsants. Prophylaxis against post-traumatic seizures beyond the
versus risk of anticonvulsant therapy, and (4) discussing with the first week after injury probably is unnecessary,152 but the occur-
patient his or her approach to risk. rence of early post-traumatic seizures should prompt at least
Even when witnessed in the ED, apparent ictal activity may not short-term initiation of therapy.153 Furthermore, if a patient not
be a seizure. Diagnosing a seizure is more difficult when the event receiving antiepileptic therapy arrives in the ED with a second
resolved before the patient’s arrival at the ED and is based on seizure, initiation of treatment is warranted because of the esti-
witness reports. In patients diagnosed with a seizure, 20 to 25% mated 70% risk of recurrent events.154
are subsequently found to have been misdiagnosed.150,151 The side effects of anticonvulsants can be debilitating for the
The risk of seizure recurrence is difficult to estimate in the patient (Table 102-2). These effects should be considered before
ED setting. In patients with an initial unprovoked seizure, the such therapy is initiated, particularly in women of reproductive

Table 102-2 Important Adverse Effects and Drug-Drug Interactions of Antiepileptic Drugs
GENERIC NAME TRADE NAME IMPORTANT ADVERSE EFFECTS P450 LIVER ENZYME METABOLIZERS*
Carbamazepine Tegretol Rash, leukopenia, hyponatremia, cardiac dysrhythmias (elderly), weight Inducer
gain
Clonazepam Klonopin Sedation, ataxia, irritability No
Ethosuximide Zarontin Sedation, ataxia, nausea, anorexia
Felbamate Felbatol Rare fatal aplastic anemia, hepatotoxicity, headache, anorexia, vomiting, Inducer
insomnia
Fosphenytoin Cerebyx Nystagmus, ataxia, sedation, headache Inducer
Gabapentin Neurontin Sedation, ataxia, tremor No
Lamotrigine Lamictal Hypersensitivity reaction (risk of renal failure, liver failure, DIC), rash (SJS, Inducer and inhibitor†
TEN), ataxia, headache, nausea
Levetiracetam Keppra Emotional lability, sedation, dizziness, infections (colds) No
Oxcarbazepine Trileptal Hyponatremia, rash, dizziness, headache, fatigue Inducer and inhibitor
Phenobarbital Luminal Sedation, depression, cognitive slowing, decline in libido, osteomalacia Inducer
Phenytoin Dilantin Gingival hyperplasia, hirsutism, nystagmus, ataxia, sedation, nausea, Inducer
osteoporosis, leukopenia, phenytoin hypersensitivity syndrome‡
Pregabalin Lyrica Weight gain No
§
Primidone Mysoline Sedation, depression, cognitive slowing, decline in libido, acute toxicity Inducer
after first dose
Tiagabine Gabitril Dizziness, depression, tremor, poor concentration No
Topiramate Topamax Cognitive slowing, anorexia, nephrolithiasis, paresthesias, metabolic Inducer
acidosis, rare glaucoma
Valproate Depakote Thrombocytopenia, tremor, weight gain, male-pattern hair loss, rare No
hepatotoxicity, osteoporosis
Zonisamide Zonegran Sedation, cognitive slowing, ataxia, anorexia, rash No

Data from Engel J Jr, Pedley TA (eds): Epilepsy: A Comprehensive Textbook, 2nd ed. Philadelphia, Lippincott Williams & Wilkins, 2008; Harden CL, Leppik I: Optimizing therapy
of seizures in women who use oral contraceptives. Neurology 67:S56, 2006; French JA, et al: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new onset
epilepsy: Report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American
Epilepsy Society [see comment]. Neurology 62:1252, 2004; and Mattson RH: Efficacy and adverse effects of established and new antiepileptic drugs. Epilepsia 36:S13, 1995.
DIC, disseminated intravascular coagulation; SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis.
*All inducers of liver enzymes reduce the efficacy of oral contraceptives.
†
Oral contraceptive pills also reduce Lamictal serum levels.
‡
Phenytoin hypersensitivity syndrome includes rash, fever, hepatitis, lymphoid hyperplasia, and blood dyscrasias. Side effects of intravenous phenytoin include hypotension,
arterioventricular block, and purple glove syndrome (edema, pain, and discoloration of the limb distal to the site of infusion).
§
Primidone is a congener of phenobarbital.
 11

Table 102-3 Medications Used for Long-Term Anticonvulsant Therapy in Adults

MAINTENANCE THERAPEUTIC NUMBER OF
MEDICATION INDICATIONS DOSE (mg/day)* ROUTE RANGE (µg/mL) DAILY DOSES
Carbamazepine Partial and generalized seizures 800-1600 Oral 4-12 2 or 3
Clonazepam Absence seizures 1.5-8 Oral 20-80 2 or 3
Ethosuximide Absence seizures 750-1250 Oral 40-100 2
Felbamate Refractory epilepsy only 2400-3600 Oral N/A 3 or 4
Gabapentin Partial seizures 900-3600 Oral N/A 3
Lamotrigine Partial, generalized, and absence seizures 100-500 Oral N/A 2
Levetiracetam Partial, generalized, and absence seizures 1000-3000 Oral, IV N/A 2
Oxcarbazepine Partial and generalized seizures 1200-2400 Oral N/A 2
Phenobarbital Partial and generalized seizures 90-150 Oral, intravenous 20-40 2-3
Phenytoin Partial and generalized seizures 300-400 Oral, intravenous, 10-20 1-3
intramuscular
Pregabalin Partial seizures 150-600 Oral N/A 2-3
Primidone Partial and generalized seizures 750-1250 Oral 5-12 3-4
Tiagabine Partial seizures (adjunct) 32-56‡ Oral N/A 2-4
Topiramate Partial and generalized seizures 200-400 Oral N/A 2
Valproate Partial, generalized, and absence seizures 1000-3000 Oral, intravenous 50-100 1-3
Zonisamide Partial, generalized, and absence seizures 100-400 Oral 20-30§ 1-2

Data from Engel J Jr, Pedley TA (eds): Epilepsy: A Comprehensive Textbook, 2nd ed. Philadelphia, Lippincott Williams & Wilkins, 2008; Mattson RH: Efficacy and adverse effects of
established and new antiepileptic drugs. Epilepsia 36:S13, 1995; Perucca E: Clinical pharmacology and therapeutic use of the new antiepileptic drugs. Fundam Clin Pharmacol
15:405, 2001; and Drugs for Epilepsy. Treatment Guidelines from the Medical Letter 6:37, 2008.
N/A, not applicable.
*Adjust dose for hepatic or renal disease and with use of other medications.
‡
If patient is not taking enzyme-reducing antiepileptic drugs, then daily dose should be halved (16-28).
§
Some studies indicate a range of 10-50 mg/L.

age, because many anticonvulsants are teratogenic, and some pre- used pending consultation with a neurologist. Valproate, although
cipitate failure of oral contraceptives. not altering the efficacy of oral contraceptives, carries a high risk
In the absence of specific underlying conditions that increase of teratogenic effects and is therefore not an ideal first-line agent
risk of recurrence, evidence does not support the initiation of for women of childbearing years.157,158
anticonvulsant therapy from the ED after a single unprovoked The psychological and social implications of the new diagnosis
seizure in adults.13,101,104,155 If the seizure was provoked, the decision of a seizure disorder for the patient can be profound. Fear of
should be based on whether the provoking factor can be corrected; seizures and stigmatization are common; employability and insur-
if it cannot, anticonvulsant therapy should be instituted. The anti- ability may be adversely affected. Although the emergency physi-
convulsant dosage regimen for a patient with known epilepsy cian is not usually in a suitable position to arrange for counseling,
should be modified only in consultation with the patient’s physi- referral to local epilepsy support groups may be helpful.
cian (Table 102-3). The diagnosis of a new-onset seizure disorder has legal implica-
Drug monotherapy is preferable in anticonvulsant regimens. tions as well. Each state has regulations regarding driving privi-
Choosing the right drug depends on numerous factors, including leges in patients with seizures, and some states require reporting
the type of seizure, comorbid conditions, other medications the by the physician. Accordingly, ED management must ensure com-
patient is taking, and the potential for pregnancy, and it is best pliance with such regulations, including informing patients about
determined in consultation with a neurologist, ideally after MRI any restrictions. Patients also should be advised to refrain from
neuroimaging and an EEG.85 However, if an anticonvulsant is to hazardous or isolated activities until cleared by their primary care
be initiated in the ED, then the choice is among the three medica- physician or neurologist to participate in them. The need for a
tions with the strongest evidence of efficacy in the treatment of a “medical alert” bracelet or other medical condition identifier
tonic-clonic seizure of either generalized onset or partial onset should be stressed.
with secondary generalization: carbamazepine, phenytoin, and Finally, patients and their families should be counseled about
valproate.156 It is essential to inform women of childbearing age seizure first aid, safety precautions such as avoiding swimming
that carbamazepine and phenytoin decrease the efficacy of oral alone and operating dangerous machinery, and triggers for recur-
contraceptive pills, so a second form of contraception should be rence such as photic stimuli, sleep deprivation, and alcohol.
 12

KEY CONCEPTS
■ The possibility of reactive seizures should be considered in all patients in the ED with seizures or recent
history of seizures, including patients with a history of epilepsy. The most common cause of reactive
seizures is hypoglycemia. The most common cause of recurrent primary seizures is medication
noncompliance.
■ Seizures may be confused with nonictal states, including syncope, movement disorders, and
psychiatric disorders.
■ Neuroimaging is recommended for patients with seizures who have head trauma, persistently abnormal
mental status, focal neurologic abnormality, or HIV disease.
■ Primary abortive therapy for seizures in the ED setting is with a benzodiazepine; second-line agents
include phenytoin and phenobarbital.