Andy SEIZURES Jagoda, MD, FACEP Seizures result from any of a variety of pathologic processes that provoke excessive and disorderly neuronal discharge in the cerebral cortex. The manifestations of a seizure reflect the area of the brain in which neurons are discharging. Seizure discharges may be focal or may be generalized throughout the cerebral cortex. Consequently, the clinical spectrum of seizures includes focal or generalized motor activity, altered mental status, sensory or psychic experiences, or autonomic disturbances. An aura or ``warning'' represents the beginning of a partial seizure, which can remain focal or can spread secondarily into a generalized event; a corollary is that patients with a primary generalized seizure disorder do not have an aura. Status epilepticus is the condition in which seizures last more than 30 minutes or in which there are recurrent seizures without a return to baseline mental status between events. Prognosis and Mortality: Seizures account for an estimated 1% to 2% of emergency department visits. The incidence of epilepsy and unprovoked seizures is high in first year of life, decreases throughout childhood, and remains relatively stable and low throughout mid-life. At age 55 the incidence begins to increase with the greatest incidence occurring in persons 75 years and older. The cumulative incidence of all epilepsy is estimated to be 1.2% of the population through age 24, increasing to 4.4% by age 85. The increase in the partial epilepsies coincides with the increase of degenerative, neoplastic, and vascular pathologies seen in the elderly. It is estimated that 60% of partial seizures will have secondary generalization. This is clinically important since morbidity and mortality is associated with generalization and not with events that remain focal yet the high incidence of generalization often favors treatment of focal events despite the potential morbidity associated with anticonvulsant use. There is a projected annual incidence of status epilepticus of 1 in 3000, with an overall mortality of 22%. (1) Over one half of patients presenting to the ED in status epilepticus have no prior seizure history. Cost Effective Strategies: The details of the history and physical examination dictate the urgency and course of any further emergency department evaluation. (2) Of all the laboratory tests, serum glucose determination followed by a serum sodium determination as been found to be the most valuable in diagnosing an unsuspected etiology of a seizure. The decision to measure other electrolytes, creatinine, blood urea nitrogen, calcium, and magnesium is based on the individual patient assessment; generally these tests are of limited value in patients with no underlying medical problems who have returned to their baseline. An arterial blood gas analysis is indicated when hypoxia or an underlying acidosis is suspected. A pregnancy test should be obtained in all women of child-bearing age. Serum anticonvulsant levels should be checked in patients with epilepsy who have had a seizure and in patients for
whom a history cannot be obtained. Alcohol is by far the most common drug of abuse associated with seizures, followed by cocaine. Toxicologic testing is driven by clinical suspicion and findings on examination. Patients who have had a seizure but who are not immunocompromised and who do not have an abnormal mental status, fever, or meningeal signs do not require a lumbar puncture as part of their emergency department evaluation. However, seizures, especially status epilepticus seizures, are associated with hyperthermia, leukocytosis, and altered mental status, thus often forcing consideration of meningitis. Antibiotics, once started, must be continued until cerebrospinal fluid culture results are available. Computed tomographic (CT) scanning of the head should be performed in the emergency department when an acute intracranial event, such as subdural or subarachnoid hemorrhage, is suspected. Patients with a history of acute trauma or malignancy, or with an abnormal neurologic examination, are most likely to have an abnormal imaging study. All patients who have had a first-time seizure need an imaging study, but not necessarily an emergent CT scan obtained in the emergency department. (3) If the patient has a normal mental status and neurologic examination and is judged to be reliable for follow-up, it is reasonable, after consultation with a neurologist, to arrange for outpatient magnetic resonance imaging (MRI). MRI is superior to CT scanning in identifying structural epileptogenic abnormalities. EEG monitoring is not a standard practice in the emergency department, yet there are clear indications for its use on an emergent basis. Any patient with altered mental status in whom nonconvulsive status epilepticus is suspected requires an emergent EEG. An emergent EEG is also indicated in patients with refractory status epilepticus who have been managed with paralysis or barbituate coma. Management Guidelines: Most seizures are self-limited and do not require immediate intervention. If the patient is seen during the seizure, the focus is on protecting the patient from injury. Airway patency should be ensured, but objects should not be inserted into the patient's mouth. Patients who have experienced a seizure once are at risk for recurrent seizure episodes, so proper precautions should be taken to keep the guard rails on stretchers up and to prevent the patient from ambulating unaccompanied. First-Time Seizures: Patients who have a single, unprovoked seizure have about a 35% risk of recurrence within the next 5 years; the risk of recurrences increases to approximately 75% after two or three seizures. When a cause of the seizure is identified, management is based on the underlying pathology. When no cause can be identified, a risk/benefit analysis regarding initiation of antiepileptic therapy must be performed. This is best done in consultation with the physician who will be coordinating the patients diagnostic work-up. Intravenous phenytoin or fosphenytoin loading, 20 mg/kg, can be accomplished quickly and leads to therapeutic blood levels within one hour of the infusions completion. Intravenous phenytion loading can be associated with local infusion site irritation, hypotension, confusion, and ataxia; consequently, infusions should not be run faster
than 50 mg/minute in adults. Fosphenytion is a water-soluble disodium phosphate ester of phenytoin which does not need a propylene glycol vehicle and has a more physiologic pH than phenytoin. It has fewer side effects than phenytoin, though rapid infusion can still cause hypotension, ataxia, and confusion. Fosphenytoin can be given safely by the intramuscular route with 100% bioavailability and therapeutic serum levels within one hour of a loading dose. Oral pheytoin loading is another option; however, it results in unpredictable absorption, with only 60% of patients being therapeutic at 12 hours after a one gram dose. A daily maintenance dose of 300 mg can be given at bedtime, although in some patients divided dosing can provide better seizure control by minimizing variations in the blood level. The evaluation of pregnant patients with new-onset seizures should follow the same principle as in other patients. However, if no etiology is identified, anticonvulsants should be withheld and the patient referred for close follow-up. Eclampsia is an additional consideration in patients at more than 20 weeks' gestation. Recurrence of Seizures in Patients With Known Seizure Disorder: Noncompliance with anticonvulsant medication is by far the most common cause of seizure recurrence in a patient with a known seizure disorder. A patient who has been on phenytoin but has subtherapeutic level should be given supplemental intravenous phenytoin or fosphenytoin to re-establish serum levels in the therapeutic range. IM fosphenytoin is another option and eliminates the need for infusion pumps and cardiac The monitoring. patient can then be discharged with instructions to resume oral dosing within 12 hours. Likewise, patients with subtherapeutic valproic acid levels can be supplemented with intravenous valproic acid administered over one hour rate no faster than 20 mg/min, and discharged on their oral regimen. Patients who have seizures despite therapeutic anticonvulsant levels must be evaluated carefully for precipitating factors such as infection, new anatomic lesions, or new medications. Decisions to increase the drug dose should be made only after communication with the patient's primary care physician. A second anticonvulsant should be added to the patient's regimen only when seizures are refractory to monotherapy and there are clinical signs of toxicity. Alcohol-Related Seizures: Alcohol-related seizures deserve special mention since alcohol use is frequently involved in patients presenting to emergency departments with seizures. Alcohol-withdrawal seizures classically occur 6 to 48 hours after a significant reduction in the serum alcohol level, but they have also been associated with rising blood ethanol levels in some patients. Alcohol-related seizures are temporally associated with alcohol use but are not necessarily solely the result of the alcohol. Alcoholics are susceptible to cerebrovascular insults, trauma, metabolic disorders, and infections, and thus are at increased risk for seizures. Management of the alcoholic who has had a seizure focuses on determining whether the event was a withdrawal seizure or due to another etiology. Patients with a first-time alcohol-related seizure should be evaluated fully in the same manner as any other
patient. Benzodiazepines alone are sufficient to prevent successive withdrawal seizures in the acute setting, but there is no good evidence to support the use of phenytoin either acutely or chronically in the management of alcohol-withdrawal seizures. Patients who have had one alcohol-withdrawal seizure and have been observed to remain seizure-free and at baseline mental status for 6 hours with no evidence of withdrawal can be discharged if a suitable environment is available. Status Epilepticus: The management of convulsive status epilepticus involves simultaneous maintenance of the patient's airway, breathing, and circulation, diagnostic testing, and pharmacologic intervention. (4, 5) Status epilepticus tends to occur more frequently in patients with an underlying neurologic insult, either old or new, and refractory status epilepticus almost always indicates the presence of an underlying central nervous system disorder. Morbidity and mortality in status epilepticus is related to the etiology, duration, and systemic consequences of the event. Table 7 provides the treatment essentials of managing patients in status epilepticus. The pharmacologic management of status epilepticus begins while the patient is being stabilized and diagnostic testing performed. Hypoglycemia is treated immediately with thiamine and dextrose. Antibiotics should be given very early in the management of any patient in whom meningitis or sepsis is suspected. The benzodiazepines diazepam and lorazepam are considered the first-line drugs in the management of status epilepticus. Lorazepam (2 mg/minute up to 10 mg) or diazepam (5 mg/minute up to 20 mg) will stop seizures in the majority of cases. Both drugs are efficacious, but lorazepam is preferred because its anticonvulsant action lasts up to 12 hours, compared with 20 minutes for diazepam. Consequently, if lorazepam terminates the seizure activity, no additional anticonvulsant needs to be immediately given; a long-acting anticonvulsant such as phenytoin must be added when diazepam is used, since otherwise the patient is at high risk of seizure recurrence. (4) When seizures persist despite a full loading dose of a benzodiazepine, phenytoin or forsphenytoin, 20 mg / kg, is added at a rate of 50 mg/min or 150 mg/min respectively. Status epilepticus that does not terminate at this point is usually the result of some significant underlying CNS lesion. If seizures persist, the current recommendation is to give additional phenytoin up to a total dose of 30 mg/kg. If seizures persist after the phenytoin infusion, phenobarbital (20 mg/kg) should be given intravenously at a rate of 100 mg/minute. Since respiratory depression is all but inevitable at that point, intubation is likely to be necessary if it has not already been performed. Patients who continue to seize despite the above interventions should be put into pentobarbital coma by giving 5 mg/kg at 25 mg/minute, followed by 2.5 mg/kg/hour as an infusion. Besides requiring ventilatory support, these patients are at significant risk for hypotension and therefore require hemodynamic monitoring. Many other...