Primary Seizures in Adults

Primary ictal events in adults may have a genetic origin or may be idiopathic. Onset is typically during childhood or adolescence, but occasionally idiopathic seizures may begin de novo in adulthood. Because idiopathic seizures are rare, a first-time seizure in an adult requires a thorough evaluation.

Focal seizures in adults may be classified as simple partial or complex partial. Simple partial seizures are limited in electrical focus to one cerebral hemisphere and do not cause loss of cognition. Although the specific function of the initiating neurons determines the clinical manifestation of the ictal event (i.e., motor, somatosensory, special sensory, autonomic, or psychic), such clinical manifestations are not sufficiently specific for anatomic localization without an EEG. Typical features of simple partial seizures include focal clonic movements; paresthesias; visual, auditory, olfactory, or gustatory experiences; sweating and flushing; dysphasia; a sense of déjà vu; or a sense of unwarranted fear.10,13 Motor signs, which by definition remain ipsilateral in simple partial seizures, may spread contiguously in a stepwise fashion (Jacksonian march) as neuron recruitment occurs in the motor cortex. There is generally no postictal state after a simple partial seizure.

Complex partial seizures are ictal events that involve impairment of cognition, either at onset or evolving from focal activity. Amnesia for the ictal event is a consistent feature of complex partial seizures, although during the episode the patient may remain responsive to the surroundings. Complex partial seizures typically involve automatisms that are specific to the affected person, such as lip smacking, repeated swallowing or uttering verbal phrases, or picking at clothing. Complex partial seizures generally are associated with an aura, such as a specific smell, taste, visual hallucination, or intense emotional feeling. In contrast with those experiencing generalized seizures, these patients may continue with ongoing motor activity, such as driving an automobile, riding a bicycle, or playing a musical instrument (reactive automatisms), and they may react to their surroundings in a semi-appropriate manner.¹⁰ Partial seizures may progress rapidly to generalized seizures. A postictal state is common after complex partial seizures and may persist for hours.¹³

Generalized seizures in adults may be convulsive or nonconvulsive. By definition, patients lose consciousness in a generalized seizure, and no aura is present. Some patients may experience a brief, vague prodrome or dysphoric state just before the ictal event. Convulsive generalized seizures are typified by the tonic-clonic, or grand mal, seizure, in which the patient loses consciousness, stiffens with generalized muscular hypertonus, and then rhythmically and violently contracts multiple, bilateral, and usually symmetrical muscle groups. The muscular force may be sufficiently vigorous to result in posterior shoulder dislocation or fractures of thoracic spine vertebral bodies; significant tongue and buccal injuries also may be incurred from biting with repeated jaw muscle contractions. Dysautonomia, including transient apnea, is a potential manifestation of convulsive generalized seizures; urinary incontinence is more common than fecal incontinence. A generalized convulsive seizure generally lasts 1 to 2 minutes and is followed by a postictal state, headache, and drowsiness that may persist for hours. This state must be differentiated from altered consciousness attributable to other causes.

Nonconvulsive generalized seizures include absence, or petit mal, seizures; myoclonic seizures; tonic seizures; and atonic seizures. Absence seizures in adults are subclassified further as typical or atypical. Typical absence ictus is characterized by the sudden cessation of normal, conscious activity, followed by a nonconvulsive, dissociative state that persists for a few seconds to several minutes before suddenly terminating. Eye movements, blinking, or automatisms may be present. There is no aura and no postictal state. If the seizure occurs midsentence, then the patient typically will resume speaking at precisely the point of interruption without awareness of the intervening event. Absence seizures typically begin in childhood but occasionally develop in adults. Atypical absence seizures are marked by more complicated motor signs, coexistence with other forms of generalized seizures, inconsistent postictal confusion, and irregular EEG abnormalities.¹³

Atonic seizures are characterized by focal diminution of muscle tone (limb or head) or generalized loss of postural tone in which the head falls forward and then the body slumps to the ground (“drop attack”), usually landing buttocks first (although this can vary depending on the axis of gravity at the time of the fall). Recovery occurs immediately, and there is either no loss or an extremely brief loss of consciousness. In myoclonic-atonic seizures, a brief (less than 100 msec) myoclonic jerk of muscle groups of variable anatomy occurs before the episode of atonia.¹⁰ Because typically no postictal state is associated with these episodes, an altered level of consciousness in a patient after an atonic or myoclonic-atonic seizure should prompt an investigation for head trauma or a toxic or metabolic abnormality.

Status epilepticus is defined as serial seizure activity without interictal recovery or prolonged, continuous seizure activity. Traditionally, status epilepticus was defined as seizure activity lasting longer than 30 minutes, which is the estimated duration necessary for neuronal injury.16,17 However, because an isolated tonic-clonic seizure rarely lasts more than a few minutes, an operational definition of status epilepticus as either a continuous seizure lasting more than 5 minutes or more than two discrete seizures without intervening recovery of consciousness has been advocated.¹⁸ Although it is recognized that the underlying cause of status epilepticus is the predominant factor determining morbidity and mortality, prolonged seizure activity does cause neuronal injury and therefore warrants prompt abortive therapy. Furthermore, status epilepticus may become refractory to treatment over time.^17,19,20

In some cases a patient’s first seizure episode will manifest as status epilepticus. The most common cause of status epilepticus is discontinuation of anticonvulsant medication. This situation may be compounded by barbiturate withdrawal when phenobarbital therapy is abruptly discontinued. Many other causes of status epilepticus have been documented (Box 102-1).^14,16,21,22 After prolonged status epilepticus or after incomplete treatment, the patient may exhibit very subtle manifestations of continued seizure activity, such as small-amplitude twitching of the extremities or jerking of the eyes, or any visible motor activity may cease while seizure activity detectable on the EEG continues.^23–25 Recognition of the latter scenario, termed nonconvulsive status epilepticus, requires a high index of clinical suspicion. Prompt treatment is essential to prevent neuronal damage; mortality approaches 30% if the seizure lasts more than an hour.²⁶ Nonconvulsive status epilepticus may be present in more than 9% of hospitalized patients with prolonged decreased mental status.²⁷

All classes of primary seizures may recur sporadically, randomly, or predictably. Cyclic recurrence has been reported with awakening, sleep deprivation, emotional or physical stress, alcohol, and menses, among other factors. Seizures also may be triggered by specific sensory stimuli, the most common of which is visual stimulation in the form of flashing lights, such as strobe lights, television, and video games.10,28 Seizures also can be caused by auditory, gustatory, tactile, or startle triggers that are specific to the affected person. The most common cause of recurrent primary seizures is medication noncompliance.^13,29

Reactive Seizures in Adults

Reactive or secondary seizures do not result from genetic or idiopathic causes. The conditions that cause reactive seizures may be static (e.g., anatomic scarring), progressive (e.g., degenerative cortical disorders), or transient (e.g., acute electrolyte derangements).

Psychogenic Nonepileptic Seizures

Psychogenic seizures, or pseudoseizures, are functional events that may be associated with alterations in cognition, abnormal movements and behaviors, and autonomic changes. They are not the result of abnormal CNS electrical activity. Psychogenic seizures may be primarily motor and mimic convulsive generalized seizures, including refractory status epilepticus, or they may be nonconvulsive and mimic either absence or complex partial seizures. Although certain features of convulsive psychogenic seizures may suggest the diagnosis, no clinical criteria are 100% specific; simultaneous video and EEG recordings may be required to confirm the diagnosis.77,78

The ED evaluation of these patients is difficult, because epilepsy and pseudoseizures can coexist in a minority of patients.⁷⁹ All but obviously functional abnormalities should be treated as true ictus pending formal neurologic evaluation. Many patients with pseudoseizures are not deliberately attempting to mislead the examining physician. The long-term treatment of patients with confirmed pseudoseizures may include direct confrontation, intensive psychotherapy, and use of a placebo.

Postictal States

The postictal state that follows most generalized seizures typically is characterized by decreased levels of arousal and responsiveness, disorientation, amnesia, and headache. These conditions may persist for only a few minutes or for many hours and may not be consistent from seizure to seizure. The most important consideration in ED management of the postictal state is to monitor and investigate the altered mental status after a seizure; otherwise, dangerous underlying metabolic or toxic abnormalities may be overlooked. At a minimum, airway positioning maneuvers, pulse oximetry, rapid glucose determination, and cardiac rhythm monitoring are necessary.

Two unusual postictal manifestations may provoke particular consternation in the ED: postictal paralysis and neurogenic pulmonary edema. Postictal paralysis, or Todd’s paralysis, may follow generalized or complex partial seizures and is a focal motor deficit that may persist up to 24 hours and may be caused by transient focal cerebral hypoprofusion.⁸⁰ Weakness of one extremity or a complete hemiparesis may occur; in the latter case the patient should be safely restrained to avoid falls caused by a combination of weakness and diminished responsiveness resulting from the 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, although often subclinical, complication of any structural CNS insult, including seizure, trauma, and hemorrhage.⁸¹ Neurogenic pulmonary edema is likely caused by centrally mediated sympathetic discharge and generalized vasoconstriction, coupled with increased pulmonary capillary membrane permeability. After a seizure, neurogenic pulmonary edema can be confused clinically and radiographically with aspiration pneumonia. Otherwise unexplained hypoxia or other clinical evidence of pulmonary congestion after a seizure prompts consideration of neurogenic pulmonary edema. Significant neurogenic pulmonary edema is managed with ventilatory support, including positive end-expiratory pressure.^82,83

A prolonged postictal state raises clinical suspicion for nonconvulsive status epilepticus. After prolonged tonic-clonic seizures, ongoing cerebral epileptic activity may manifest with subtle motor movements such as twitching of the digits or face. EEG is the most definitive way to confirm the diagnosis.²⁶

First-Time Seizures

The essential components of the seizure evaluation in the ED are discussed in Chapter 18. An accurate and thorough history of the ictal event and information about any known or potential precipitants or exposures and the patient’s medical problems are obtained. A thorough physical examination, including a complete neurologic examination, is essential. Any identified focal neurologic deficits must be monitored for progression or resolution. Appropriate ancillary studies may be comprehensive, but if precipitants (e.g., hypoglycemia, intoxication, medication noncompliance) are known, studies may be comparatively limited. Frequently, the cause of the first seizure in an adult cannot be found in the ED.⁸⁴

Although the Academy of Neurology recommends neuroimaging, by either CT or magnetic resonance imaging (MRI), for all adults with an apparently unprovoked first seizure, the usefulness of emergent imaging depends on the clinical situation.⁸⁵ An emergent cranial CT scan is indicated when a serious structural lesion is suspected on clinical grounds, including presence of a new focal deficit, persistent altered mental status, fever, recent trauma, persistent headache, history of cancer, anticoagulant use, suspicion or known history of acquired immunodeficiency syndrome (AIDS), age older than 40 years, and partial-complex seizure.⁸⁶ A reasonable approach is to obtain a brain CT scan on an outpatient, follow-up basis in patients who have recovered completely from the ictal event and in whom no apparent cause has been elucidated. However, if reliable follow-up care is unlikely or even questionable, the CT scan should be obtained in the ED to ensure its completion. In patients with known epilepsy and recurrent seizures, the same considerations apply, but in addition, epileptic patients with a change in seizure pattern, prolonged postictal state, or persistent abnormal mental status should undergo brain CT scan in the ED.

Children with seizures can be evaluated in a similar manner. Those with febrile seizures are not more likely than those with fever alone to have a serious bacterial infection. Children with afebrile seizures who are well appearing can generally be managed as outpatients. Blood tests and other diagnostics are indicated in children younger than 6 months, those who have had a prolonged seizure or postictal state, and those who have a preexisting metabolic disorder or suspected dehydration. Emergent neuroimaging is indicated for children with significant past medical histories or in cases of focal seizures in children younger than 3 years.87,88 Children younger than 6 months may have positive, relevant brain CT findings in 50% of cases.⁸⁹

The decision to initiate anticonvulsant therapy after a single seizure depends on the cause of the seizure. Seizures caused by structural lesions, such as stroke, tumor, or head injury, are likely to recur and may warrant antiepileptic medication. However, such patients also are likely to be admitted to the hospital if the lesion is newly discovered. For patients with a single unprovoked seizure, evidence-based recommendations are that antiepileptic therapy should not be initiated; rather, the patient should be discharged with referral for neurologic consultation.84,86,90,93,94 The rationale for this approach is threefold. First, the diagnosis may be incorrect, especially if the seizure-like activity was not witnessed by experienced medical personnel. It is estimated that 20 to 25% of patients diagnosed as having seizures are eventually determined not to have seizures, with the most frequent alternative diagnoses being cardiovascular and psychopathologic.^95–98 Second, the patient may not have a recurrent seizure. It is estimated that less than 50% of patients who have had a single unprovoked seizure will experience a recurrent seizure within 2 years.^90,99,100 Furthermore, whereas 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 seizure. Third, antiepileptic medications have side effects that may outweigh the benefit of treatment, especially in women of childbearing age, owing to the teratogenic risk of AEDs; in patients with liver, kidney, or hematologic disorders; and in patients already taking multiple medications.

Recurrent Seizures

The initial approach to stabilization of a patient with a known seizure disorder does not differ from that for a patient with new-onset seizure; this includes a rapid blood glucose determination and evaluation for precipitant causes. The most common cause of seizures in a patient with a diagnosed seizure disorder is noncompliance with medications.²⁹ However, supratherapeutic and toxic levels of some anticonvulsants, such as carbamazepine, phenytoin, lamotrigine, and topiramate, can also cause seizures.^105–110 Accordingly, it is prudent to check the serum drug level, if this test is available, before giving a full loading dose of anticonvulsants to patients on long-term therapy. Meanwhile, a thorough history and physical examination focus on intercurrent illness or trauma, drug or alcohol use, potential adverse drug-drug interactions with anticonvulsants, a recent change in anticonvulsant dosage regimens, and any change in ictal pattern or characteristics. Clinical indications dictate the selection of other laboratory or radiographic tests.

Immediate Management

The management of a patient experiencing a seizure begins with active, anticipatory airway management. In generalized ictus, the gag reflex is suppressed, and vomiting often is complicated by aspiration of gastric contents. The patient is placed in a left lateral decubitus position to lessen chances of aspiration. Dentures are removed but kept close by, as they may be needed for a good mask seal to be attained if bag-mask ventilation is required. A bite-block can be placed to protect the tongue and allow access for suctioning, but care should be taken to avoid iatrogenic trauma from forceful placement of intraoral devices.

If the patient is persistently apneic or if an unavoidable airway threat is present, endotracheal intubation is warranted for definitive protection. A benzodiazepine can be used as an induction agent in the hope that its action may terminate the seizure or obviate the need for tracheal intubation. Postintubation sedation with benzodiazepine infusion or propofol infusion is also recommended. Trismus may necessitate use of a short-acting neuromuscular blocking agent to facilitate intubation; long-acting paralytics will mask motor manifestations of ongoing seizures.

In general, the first-line pharmacologic agent for treatment of any active seizure is a parenteral benzodiazepine. Because benzodiazepines directly enhance GABA-mediated neuronal inhibition, they affect clinical and electrical manifestations of seizures. Benzodiazepines are effective in terminating ictal activity in a majority of patients and have been shown to be more effective than phenytoin in terminating status epilepticus.116,117 Although phenobarbital appears to be as effective as the benzodiazepine lorazepam in terminating status epilepticus, the associated high risk of hypoventilation 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 in patients of any age, and all share the following characteristics: rapid onset (seconds to minutes), relatively short duration of anticonvulsant action, a sedative effect, and the potential for hypotension and respiratory depression. Lorazepam has emerged as the drug of choice for the initial management of convulsions, because it terminates seizures rapidly (within 2 minutes) and has a longer duration of action (4-6 hours, compared with 20 minutes for diazepam), thus necessitating fewer repeat doses.^118–121 For this reason, it also is the preferred agent for control of alcohol withdrawal seizures.¹²² Lorazepam is most effective when given intravenously but can also be administered intramuscularly, intranasally, intraosseously, and as a sublingual preparation for out-of-hospital control of seizures in children.¹²³

An advantage of diazepam is that it is in liquid form at room temperature and is therefore available premixed in resuscitation kits, and it can be administered quickly and without a need for reconstitution by the intravenous, endotracheal, or intraosseous route. Its onset of action with intravenous administration is within 10 to 20 seconds, but there is a 50% chance of recurrent seizure within 2 hours if diazepam is used.¹¹⁷ Diazepam can also be administered rectally via suppositories or a rectal gel. Rectal diazepam achieves variable success in seizure cessation, perhaps owing to the dual venous drainage of the rectum. The inferior and middle rectal veins drain into the central circulation via the common iliacs, whereas the superior rectal vein flows into the hepatic portal system. Diazepam placed too deeply into the rectum would undergo first-pass metabolism in the liver, thus limiting bioavailability and clinical effect.

Midazolam’s onset of action is within 1 minute; it is available in both intranasal and buccal formulations,¹²⁴ and among the benzodiazepines it has the least cardiovascular effect.¹²¹ Midazolam is rapidly and reliably absorbed after intramuscular administration and has been shown to be as effective when given intramuscularly as intravenous lorazepam, making it a preferred medication when intravenous access has not yet been established.¹²⁵ Nonintravenous midazolam is as effective as intravenous diazepam, and buccal midazolam is superior to rectal diazepam in achieving symptom control.¹²⁶

Second-line abortive anticonvulsant therapy consists of phenytoin and phenobarbital. Phenytoin reduces the repetitive firing of action potentials through sodium channel blockade, thereby stabilizing neuronal membranes.¹⁰ Phenytoin neither sedates patients nor causes respiratory depression, but rapid intravenous administration of phenytoin in its propylene glycol diluent may cause hypotension and cardiac bradydysrhythmias, as well as local vascular injury, including venous thrombosis and localized tissue necrosis (purple glove syndrome).^127–129 Phenytoin’s onset of action is within 10 to 30 minutes, and intravenous administration typically requires at least 20 minutes.¹³⁰ The duration of action is approximately 24 hours. Continued benzodiazepine administration is appropriate until phenytoin achieves adequate brain levels. Phenytoin is not recommended in toxin-induced seizures, as it is likely to be ineffective and may be harmful in cases of theophylline or tricyclic antidepressant ingestions.³

Fosphenytoin is a water-soluble prodrug form of phenytoin, with a more physiologic pH. Its main advantages are that it is not likely to precipitate during intravenous infusion and that it also can be administered intramuscularly, although the volume required for full loading by the intramuscular route may be in the range of 20 mL or more.¹³¹ Although fosphenytoin can be infused more rapidly, the time to therapeutic concentration of the active drug is the same as for intravenous phenytoin.¹³² The hemodynamic advantages of fosphenytoin over intravenous phenytoin have not proven to be significant.^133,134 Fosphenytoin use is most appropriate when intravenous access is not obtainable or when the intravenous line is of small gauge, as is often the case in children and elders.¹²⁰

If the serum drug level of phenytoin is subtherapeutic in a patient already being treated for seizures, a loading dose can be given intravenously or orally in divided doses over 6 hours. Oral loading of phenytoin is associated with fewer adverse events than loading with either intravenous phenytoin or fosphenytoin,¹³⁴ but it is inadequate when therapeutic activity is required urgently.

Phenobarbital is similar to benzodiazepines in that it binds to and enhances the inhibitory neurotransmitter GABA, thereby acting as a CNS depressant that decreases ictal and physiologic cortical electrical activity. Sedation and depression of respiratory drive and blood pressure must be anticipated, and for this reason nonsedating phenytoin is preferred.¹²¹ The onset of action of phenobarbital is within 15 to 30 minutes, and the duration of action is 48 hours.

Valproic acid administered intravenously has recently been recognized as a safe and effective treatment for seizures, especially in patients with allergies to phenytoin, the elderly, and patients with cardiorespiratory instability who might be at increased risk of adverse events from phenytoin.135–137 Valproic acid administered intravenously has been shown to be as effective as phenytoin in patients with benzodiazepine-refractory status epilepticus, with fewer cardiopulmonary side effects.¹³⁸ Hyperammonemic encephalopathy after valproic acid loading has been reported and should be evaluated by obtaining the serum ammonia level in a patient who does not regain consciousness after seizure resolution.^21,139 Appropriate ED dosage regimens for the benzodiazepines, phenytoin, fosphenytoin, phenobarbital, and valproic acid are listed in Table 102-1.

While these agents are being given to abort ongoing seizure activity, ED management must include a search for underlying reversible causes. This search may prompt administration of dextrose for hypoglycemia, pyridoxine (vitamin B₆) for isoniazid overdose, sodium for hyponatremia, or magnesium for eclampsia.

Eclampsia complicates 1 in 1000 deliveries in the United States and can occur antepartum (91% of cases occur after 28 weeks of gestation), during the peripartal period, and up to 8 weeks postpartum.140–142 Abortive treatment for eclamptic seizures is with magnesium sulfate, which is superior to both diazepam and phenytoin in limiting maternal mortality and preventing further seizures in eclampsia.^143,144 The loading dose of magnesium sulfate is 4 to 6 g, followed by an infusion of 2 g/hr for 24 hours.^75,143,144 Because hypermagnesemia may cause respiratory arrest, it is essential to monitor patients for hyporeflexia, which precedes respiratory compromise. In the uncommon event of respiratory compromise resulting from excessive neuromuscular blockade caused by magnesium sulfate, 1 g of 10% calcium gluconate is an effective reversal agent.⁷⁵ Simultaneous reduction in blood pressure in the eclamptic patient, with use of hydralazine, labetalol, or nicardipine, is recommended.⁷⁵

Nonpregnant patients who continue having seizures in the ED despite management with benzodiazepines, phenytoin, or phenobarbital are likely to meet the clinical criteria for refractory status epilepticus. Additional therapeutic measures include use of valproate, midazolam infusion, propofol infusion, barbiturate coma, and general inhalational anesthesia. Valproate, which increases GABA concentration, may be given intravenously in status epilepticus (see Table 102-1).²³ Another alternative is the use of propofol, a nonbarbiturate anesthetic agent with hypnotic and anticonvulsant activity. Studies suggest that propofol acts at a location other than the benzodiazepine-binding site and modifies the chloride channel by a mechanism that is different from, and possibly synergistic with, those for benzodiazepines and barbiturates. Propofol usually is administered as an intravenous loading dose, followed by an infusion with continuous EEG monitoring to ensure persistent burst suppression.^145,146

Barbiturate coma is effective in terminating seizures by acting as a GABA agonist, although it also suppresses all brainstem function. Neurologic consultation is advisable before induction of barbiturate coma in a patient with refractory status epilepticus. Expected consequences of barbiturate coma include respiratory arrest, myocardial depression, and hypotension. At the same time, intracranial pressure may be decreased, thus increasing cerebral perfusion. The preferred agent for barbiturate coma is pentobarbital (see Table 102-1). Patients who are treated with barbiturate coma require intubation and ventilatory support, continuous cardiac monitoring, and invasive hemodynamic monitoring. Pressors may be required to support the blood pressure.¹⁴⁷

Inhalation anesthetics are one final alternative in the management of refractory ictus. Isoflurane and halothane are the common gases that are available. Halothane is associated with more hemodynamic and hepatotoxic complications. Isoflurane suppresses electrical seizure foci and is easily titratable. Patients managed with inhalational anesthesia require intubation and mechanical ventilation.

The role of newer AEDs, such as lacosamide and levetiracetam, in the management of status epilepticus has not yet been well established.148,149

The visible manifestations of convulsive ictus are extinguished by neuromuscular blockade. When a seizing patient is paralyzed and intubated, it cannot be assumed that pharmacologic therapy has terminated the seizure. Anticonvulsant administration is continued, and EEG monitoring of the patient is arranged. Without EEG, detection of seizure activity in a heavily sedated or paralyzed patient may be impossible.

Long-Term Management

Identifying a new-onset seizure disorder in the ED prompts consideration of the need for further management in the following three areas: pharmacologic, psychosocial, and legal. The primary dilemma is whether or not to initiate prophylactic anticonvulsant therapy after one seizure. The decision to treat should be based on (1) ensuring that the diagnosis of seizure is correct, (2) ascertaining the likelihood of seizure recurrence, (3) assessing the benefit versus risk of anticonvulsant therapy, and (4) discussing with the patient his or her approach to risk.

Even when witnessed in the ED, apparent ictal activity may not be a seizure. Diagnosing a seizure is more difficult when the event resolved before the patient’s arrival at the ED and is based on witness reports. In patients diagnosed with a seizure, 20 to 25% are subsequently found to have been misdiagnosed.150,151

The risk of seizure recurrence is difficult to estimate in the ED setting. In patients with an initial unprovoked seizure, the 2-year risk of recurrence without treatment generally is considered to be less than 50%.90,99,100 The presence of EEG abnormalities suggests greater risk, but this information usually is unavailable in the ED setting. Other factors associated with an increased risk of recurrence are partial (versus generalized) ictus, status epilepticus, a history of intracranial surgery or trauma, and the presence of a persistent neurologic abnormality, such as Todd’s paralysis.

The presence of specific underlying conditions may affect the decision to institute long-term therapy. For example, it would be reasonable to initiate antiepileptic therapy for an initial seizure in an HIV-positive patient when the seizure is not a result of correctable factors such as drug toxicity or metabolic derangement.50,90 Alcohol-related seizures are notoriously unresponsive to anticonvulsants. Prophylaxis against post-traumatic seizures beyond the first week after injury probably is unnecessary,¹⁵² but the occurrence of early post-traumatic seizures should prompt at least short-term initiation of therapy.¹⁵³ Furthermore, if a patient not receiving antiepileptic therapy arrives in the ED with a second seizure, initiation of treatment is warranted because of the estimated 70% risk of recurrent events.¹⁵⁴

The side effects of anticonvulsants can be debilitating for the patient (Table 102-2). These effects should be considered before such therapy is initiated, particularly in women of reproductive age, because many anticonvulsants are teratogenic, and some precipitate failure of oral contraceptives.

In the absence of specific underlying conditions that increase risk of recurrence, evidence does not support the initiation of anticonvulsant therapy from the ED after a single unprovoked seizure in adults.13,101,104,155 If the seizure was provoked, the decision should be based on whether the provoking factor can be corrected; if it cannot, anticonvulsant therapy should be instituted. The anticonvulsant dosage regimen for a patient with known epilepsy should be modified only in consultation with the patient’s physician (Table 102-3).

Drug monotherapy is preferable in anticonvulsant regimens. Choosing the right drug depends on numerous factors, including the type of seizure, comorbid conditions, other medications the patient is taking, and the potential for pregnancy, and it is best determined in consultation with a neurologist, ideally after MRI neuroimaging and an EEG.⁸⁵ However, if an anticonvulsant is to be initiated in the ED, then the choice is among the three medications with the strongest evidence of efficacy in the treatment of a tonic-clonic seizure of either generalized onset or partial onset with secondary generalization: carbamazepine, phenytoin, and valproate.¹⁵⁶ It is essential to inform women of childbearing age that carbamazepine and phenytoin decrease the efficacy of oral contraceptive pills, so a second form of contraception should be used pending consultation with a neurologist. Valproate, although not altering the efficacy of oral contraceptives, carries a high risk of teratogenic effects and is therefore not an ideal first-line agent for women of childbearing years.^157,158

The psychological and social implications of the new diagnosis of a seizure disorder for the patient can be profound. Fear of seizures and stigmatization are common; employability and insurability may be adversely affected. Although the emergency physician is not usually in a suitable position to arrange for counseling, referral to local epilepsy support groups may be helpful.

The diagnosis of a new-onset seizure disorder has legal implications as well. Each state has regulations regarding driving privileges in patients with seizures, and some states require reporting by the physician. Accordingly, ED management must ensure compliance with such regulations, including informing patients about any restrictions. Patients also should be advised to refrain from hazardous or isolated activities until cleared by their primary care physician or neurologist to participate in them. The need for a “medical alert” bracelet or other medical condition identifier should be stressed.

Finally, patients and their families should be counseled about seizure first aid, safety precautions such as avoiding swimming alone and operating dangerous machinery, and triggers for recurrence such as photic stimuli, sleep deprivation, and alcohol.

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