Evaluation of a first seizure

Is it epilepsy?

Marisa Prego-Lopez, MD; Orrin Devinsky, MD

VOL 111 / NO 1 / JANUARY 2002 / POSTGRADUATE MEDICINE

CME learning objectives

• To become familiar with the distinguishing features of epileptic seizure and the conditions that can mimic seizure
• To learn how to recognize various types of seizure
• To understand when and when not to initiate treatment after a first seizure

The authors disclose no financial interest in this article.

This is the first of four articles on seizure management.

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Preview: As a primary care physician, you may encounter patients seeking medical attention for a presumed seizure sometime after the event. How do you approach differential diagnosis and testing to ensure accurate recognition? For patients who have had a first seizure, how do you determine whether treatment is necessary or even desirable? In this article, Drs Prego-Lopez and Devinsky outline a diagnostic approach for differentiating seizure from other conditions that can mimic it and offer strategies for deciding whether and when to prescribe antiepileptic drug therapy.
Prego-Lopez M, Devinsky O. Evaluations of a first seizure: Is it epilepsy? Postgrad Med 2002;111(1):34-48

The first step in evaluating a suspected seizure is to determine whether the event was, in fact, a seizure. Epileptic seizures are behavioral changes resulting from paroxysmal, excessive electrical discharges from the brain. Not all jerks, shakes, and episodic behaviors are seizures (1). For example, tics, tremors, dystonia, and attention-deficit disorder can imitate features of epileptic seizures. Similarly, increased muscle tone after a stroke can result in sustained clonus of the extremity, which may be mistaken for a partial motor seizure. In addition, paroxysmal behaviors are seen in many neurologic, psychiatric, and medical disorders and can imitate epileptic seizures (table 1). The incidence of epilepsy and disorders that mimic it varies by age of the patient, site of presentation (eg, emergency department, primary care office) and, most important, historical features.

Table 1. Nonepileptic paroxysmal disorders that can mimic epileptic seizure

Syncope Reflex (vasovagal, carotid sinus, glossopharyngeal, cough) Decreased cardiac output Decreased left ventricular filling (hypovolemia, orthostatic hypotension, pulmonary embolism) Cardiac arrhythmia Migraine (classic [with auras], basilar, confusional) Cerebrovascular event (transient ischemic attack) Periodic paralysis Sleep disorders (parasomnias, daytime amnestic episodes) Gastrointestinal disorders (reflux, motility disorders) Movement disorders (tics, Tourette's syndrome, nonepileptic myoclonus, paroxysmal choreoathetosis, shuddering attacks) Psychiatric disorders (panic, somatization, dissociation, conversion [nonepileptic psychogenic seizures]) Drug toxicity and substance abuse Breath-holding spells

Disorders that can mimic seizure

Syncope is often mistaken for an epileptic seizure (2). During many syncopal episodes, clonic or myoclonic jerks occur in the distal portions of the extremities. Convulsive syncope occurs when there is severe or prolonged reduction of blood flow to the brain, resulting in an event resembling tonic-clonic seizure. Diagnosis is based on possible provocative factors in the medical history (eg, pain, dehydration), physical examination (eg, orthostatic blood pressure check), and studies such as electrocardiography and tilt table testing (3).

Another common imitator of epileptic seizure is the nonepileptic psychogenic seizure. No single feature reliably differentiates the two disorders. However, many ictal features of nonepileptic psychogenic seizure are uncommon in epileptic seizures (4). For example, such features as gradual onset, stopping and restarting of motor activity, out-of-phase clonic movements of the extremities, vocalization in the middle of the seizure rather than at the start, pelvic thrusting, and lack of body rigidity are more common in psychogenic seizures than in tonic-clonic seizures (4). In addition, the typical duration of a tonic-clonic seizure is 50 to 92 seconds, whereas the range for psychogenic seizures is 20 to 805 seconds (4).

Furthermore, some epileptic seizures have symptoms that are frequently misdiagnosed as psychogenic. Frontal lobe complex partial seizures often last less than 1 minute and sometimes include rocking, kicking, "bicycling," pelvic thrusting, genital manipulation, and cursing. Their lack of postictal symptoms also makes frontal lobe seizures difficult to differentiate from psychogenic seizures. Supplementary motor area seizures can cause tonic or clonic movements involving multiple extremities while preserving consciousness. In contrast, a simple partial seizure that produces psychic symptoms (eg, feelings of fear, sadness, depersonalization, and derealization) may be misdiagnosed as a psychiatric disorder. In any case, establishing the diagnosis of a nonepileptic psychogenic seizure does not exclude the coexistence of epilepsy.

Once a paroxysmal behavioral event is identified as a seizure, the next step is to determine whether it is epilepsy or a secondary effect of another underlying medical condition. Such conditions include hypoxia, hypoglycemia, infection, fever, and toxic substance abuse (eg, alcohol withdrawal, cocaine use). Epilepsy is characterized by recurrent seizures (ie, at least two seizures are needed for diagnosis). Typically, patients who have recurrent seizures caused by clear precipitants, such as alcohol withdrawal or hypoglycemia, are not considered to have epilepsy. Epilepsy can result from either inherited or acquired factors. Head injury, stroke, brain tumor, cortical dysplasia, and infection are common causes of both seizures and epilepsy. In many cases, the cause of epilepsy remains unknown.

Features of epileptic seizures

Epilepsy affects approximately 0.6% of the US population (5). The lifetime risk of seizure is 9% compared with a 3% risk of epilepsy (6). Epileptic seizures are divided into two broad categories--generalized and partial (table 2). Generalized seizures arise from both sides of the brain simultaneously. The causes are categorized as genetic, unknown (idiopathic), or poorly defined (cryptogenic). Partial (ie, focal) seizures occur within one or more restricted regions of the brain and are a secondary effect of a localized physiologic or structural abnormality of the brain (eg, tumor, dysplasia, stroke, trauma).

Table 2. Classification of epileptic seizures

Generalized Absence Myoclonic Tonic Atonic Clonic Tonic-clonic (grand mal seizure) Partial Simple partial (consciousness not impaired) Complex partial (consciousness impaired) Partial with secondary generalization (can be tonic-clonic, tonic, or clonic)

Partial seizures are further classified as simple, complex, or secondarily generalized. Simple partial seizures alter behavior but do not impair consciousness. Complex partial seizures alter consciousness by impairing awareness, responsiveness, and memory. The distinction between simple and complex partial seizures is crucial for determining what recommendations to make to patients regarding restrictions on driving, operating machinery, and swimming alone. Partial seizures can also become secondarily generalized by spreading to the contralateral hemisphere, causing tonic and clonic movements. Differentiation between tonic-clonic seizures of partial onset and those of generalized onset (eg, onset during sleep) can be difficult.

History taking, physical examination, neurologic examination, and diagnostic testing are critical for accurate diagnosis of a paroxysmal event. A thorough workup should help answer the following questions: Was the event a seizure? If so, which type? What is the cause? What is the likelihood of recurrence? Should treatment be initiated?

History of the event

A description of the circumstances surrounding a paroxysmal event can provide important diagnostic clues (table 3). A witnessed, 90-second episode that involved loss of consciousness, stiffening, and jerking of the extremities followed by muscle soreness, headache, and the need to sleep for several hours afterwards strongly suggests a tonic-clonic seizure. In contrast, loss of consciousness after undergoing venipuncture or standing up suggests orthostatic hypotension. A similar event during urination may suggest micturition syncope.

Table 3. Key elements in the history of a suspected seizure

Before the event Unusual stress (eg, severe emotional trauma) Sleep deprivation Recent illness Unusual stimuli (eg, flickering lights) Use of medications and drugs Activity immediately before event (eg, change in posture, exercise) During the event Symptoms at onset (eg, aura) Temporal mode of onset: gradual versus sudden Duration: brief (ictal phase <5 min) versus prolonged Stereotypy: duration and features of episodes nearly identical versus frequently changing Time of day: related to sleep or occuring on awakening Ability to talk and respond appropriately Ability to comprehend Ability to recall events during the seizure Abnormal movements of the eyes, mouth, face, head, arms, and legs Bowel or bladder incontinence Bodily injury After the event Confusion Lethargy Abnormal speech Focal weakness or sensory loss (ie, Todd's paralysis) Headache, muscle soreness, or physical injury

A review of the events leading up to the seizure may reveal factors that suggest it was provoked. Causes of provoked seizures include alcohol withdrawal, substance abuse, hypoxia, fever, electrolyte imbalance, hypoglycemia, and sleep deprivation. Provoked seizures are less likely than other types of seizure to develop into epilepsy.

A reliable witnessed account is an invaluable source for answers to the following questions:

1. What was the patient doing at the onset? Did the event begin with arrested speech, odd behavior, or repetitive actions? Evidence of any focal rhythmic behavior of the face or extremities at the onset suggests partial epilepsy. Unfortunately, although partial epilepsy is the most common type in adults, the focal onset of a seizure is often missed and witnesses' attention is drawn to the person only after an event becomes generalized.

2. What was the patient doing during the event? Witnesses may report one or more of the following signs: tonic movements or posturing seen as stiffening, most often of the extremities or axial body; clonic movements; a rhythmic flexion-extension movement of the extremities; loss of consciousness; incontinence; and tongue biting.

3. What was the duration of the ictal event? This information can be helpful, particularly for differentiating true seizure from psychogenic events, which often last longer.

4. What was the patient doing after the ictal event? Postictal observations may aid in localization. Focal deficits and Todd's paralysis are common findings in patients with structural lesions in the contralateral hemisphere. The presence of various features (eg, postictal confusion) may help differentiation between seizure and syncope. An episode is more likely to be syncope if it:

• Is precipitated by anxiety or pain (eg, venipuncture)
• Occurs after the patient assumes an upright position
• Occurs only when the patient is standing or sitting
• Is associated with facial pallor and diaphoresis
• Is not associated with sustained tonic or clonic movements, bladder incontinence, or biting of the tongue or cheek
• Is not followed by postictal confusion, lethargy, muscle soreness, and headache
• Is followed by a relatively rapid return to baseline

Past medical history

Knowledge of a patient's medical history aids in understanding the cause of the seizure. A history of meningitis, encephalitis, head trauma, cancer, or cerebrovascular disease suggests the cause of epilepsy focus. In diabetic patients, hypoglycemia (usually due to a serum glucose concentration of less than 40 mg/dL [2.22 mmol/L]) or hyperglycemia (serum glucose concentration higher than 300 mg/dL [16.65 mmol/L]) may precipitate seizures. Other metabolic disturbances (eg, hyponatremia, hypocalcemia, hypomagnesemia, hypoparathyroidism, hypothyroidism) also may cause seizures, although the occurrences are rare.

History taking should include a review of the patient's medications. Theophylline, meperidine hydrochloride (Demerol), isoniazid (Nydrazid), antipsychotic drugs (especially clozapine [Clozaril] and phenothiazines), radiocontrast dyes, alkylating agents, and ß-lactam antibiotics are among the most commonly implicated medications in seizure. However, many other drugs can cause seizure, including lidocaine hydrochloride, general anesthetics, tricyclic antidepressants, newer antidepressants (eg, selective serotonin reuptake inhibitors, bupropion hydrochloride [Wellbutrin]), acyclovir (Zovirax), ß-blockers, and decongestants (eg, phenylpropanolamine hydrochloride). Also, seizures can be provoked by alcohol withdrawal as well as use of cocaine, phencyclidine hydrochloride (PCP), and 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy").

The patient's medical history may also suggest a diagnosis other than seizure. For example, a patient with cardiac arrhythmias who collapsed may have had a syncopal episode. In contrast, a patient with a history of atrial fibrillation or a dilated left ventricle is at risk for embolic strokes and may present with a seizure. A history of complex febrile seizures (ie, febrile seizures that are focal or prolonged) or other neurologic disorders in the patient or immediate family members aids differential diagnosis and offers prognostic clues.

Physical examination

A thorough physical examination can help uncover possible causes of a seizure. Findings may include evidence of trauma, infection, malignancy, congenital anomalies, and prior neurologic events (eg, focal weakness, spasticity suggesting previous stroke).

During an emergency department evaluation of a patient immediately after a paroxysmal event, vital signs should be measured and a general medical examination performed. Guidelines for physical examination are as follows:

• Examine the patient for injuries from the seizure or fall.
• Check oxygen saturation and auscultate the chest for possible aspiration.
• Measure heart rhythm and rate, blood pressure, and orthostatic changes for assessment of syncope.
• Auscultate for carotid murmurs or carotid bruits and sources of embolic stroke.
• Check for rapid pulses, which are often present after seizure and may help in evaluation of psychogenic seizures.

An electrocardiogram should be obtained to identify cardiac rhythm, detect possible ischemia, and measure the QT interval. Prolonged QT syndrome often presents with simple or convulsive syncope. Electrocardiography and 24-hour ambulatory continuous electrocardiographic (Holter) monitoring can help identify cardiac arrhythmias. The possibility of a recent myocardial infarction should be considered, particularly in elderly patients, in whom myocardial infarction may occur from the stress of a seizure.

Neurologic examination

The purpose of the neurologic examination is to identify focal or diffuse cerebral dysfunction. This information is particularly helpful in localization-related epilepsy. The presence of various features offers cues to the focus of a seizure. For example, aphasia suggests a left frontal, temporal, or parietal onset. Right or left hemiparesis suggests foci from the contralateral motor cortex.

In initial evaluation of a seizure, patients should be observed for fluency of language, facial asymmetry, gaze preferences, and pupillary asymmetry. The last presents in patients who have herniation from brain swelling caused by parenchymal or epidural bleeding and in those who have a rapidly growing brain tumor. The presence of pronator drift may indicate subtle weakness not detected by strength testing. Sensory deficits suggest parietal lobe dysfunction. An extensor plantar response may be noted for some time after a seizure and is not necessarily a pathologic finding.

Diagnostic testing

Laboratory workup is an essential part of evaluation of seizure. Measurement of glucose, calcium, magnesium, thyroid hormone, and liver enzyme levels, as well as toxicology screening (including blood alcohol levels), may reveal common medical causes of seizures. A complete blood cell count may suggest infection, anemia, or sickle cell disease.

In patients suspected to have had an infection or a fever or to have exhibited abnormal behavior just before the event, lumbar puncture should be performed after assessment of the possible risks of the procedure (eg, coagulopathy, mass lesion). Patients who are immunocompromised because of corticosteroid use, recent transplantation, or HIV infection should undergo cerebrospinal fluid evaluation to detect possible fungal, bacterial, or viral infection. In patients with a systemic malignant condition, cytologic evaluation of cerebrospinal fluid can identify meningeal carcinoma.

The role of imaging studies depends on the stage of evaluation. Immediately after a seizure, computed tomography can detect the presence of bleeding or gross structural lesions. However, magnetic resonance imaging is the study of choice because it is more sensitive and specific for evaluating structural lesions and brain parenchyma. Particular attention should be directed to the hippocampus for evaluation of lesions (eg, mesial temporal sclerosis) and to the cortical architecture for detection of abnormalities (eg, dysplasia).

An electroencephalogram (EEG) can help establish the presence and type of epilepsy, although its value is limited. An estimated 0.4% of adults and 2.8% of children who have never had a seizure may have interictal epileptiform discharges (7). Furthermore, a normal EEG does not refute the diagnosis of epilepsy. The initial EEG reveals epileptiform activity in only 40% of the patients with probable epilepsy (7). Often abnormalities are seen after several EEGs have been obtained. The yield of the test is enhanced by using sleep deprivation activating procedures (eg, hyperventilation, photic stimulation), increasing the recording time, and capturing sleep during testing.

Ambulatory 24-hour EEG recordings can be useful in selected cases. This test should be reserved for patients in whom epileptic seizure is a relatively strong possibility. When abnormal electrical discharges (eg, sharp waves, spikes, spikes and slow waves) or focal slowing suggesting structural abnormalities, or both, are present, conclusions can be made about the type of seizure or location of an irritable focus.

When to initiate treatment

Once the diagnosis of seizure or epilepsy is made, the question of whether or not to treat arises. After a single tonic-clonic seizure, recurrence rates vary from 15% to 60%, depending on several risk factors. After two tonic-clonic seizures, the risk of a third seizure is about 85% (8).

Many variables determine the probability of recurrence in individual patients. A family history of seizure, a spike-and-wave pattern on the EEG, and a history of prior neurologic insult increase the risk of recurrence after a first unprovoked seizure (9). Todd's paralysis, status epilepticus, and acute symptomatic seizures (ie, those occurring immediately after brain insult, such as head trauma) all carry an increased risk of recurrent seizure. Patients seen within the first 24 hours have a higher recurrence rate than those who undergo evaluation 2 to 3 weeks after a seizure (10). Epileptic patients are likely to experience a second seizure within 6 months after the first attack (10).

The question of whether or not to treat a first seizure remains a challenge. What is the risk to the patient by treating versus not treating? Do seizures beget seizures? The answers probably differ for individual patients. Not everyone who has had a seizure needs to be treated at initial presentation. A patient's occupation may influence the decision to treat. For example, truck drivers and heavy machinery operators run a high risk of injury if they have a complex partial or tonic-clonic seizure while at work. In contrast, most physicians would not recommend treatment for a child who had an initial tonic-clonic seizure during sleep.

Many prospective and retrospective studies have evaluated the risk of recurrence after a first seizure. Hauser and associates (11) reported a 5-year recurrence risk of 34%, whereas Hopkins and colleagues (12) found a 3-year risk of 52%. The most important predictors of recurrence are the cause of the seizure (eg, symptomatic cause such as head injury), the detection of focal abnormalities on neurologic examination or imaging studies, and the presence of epileptiform abnormalities on the EEG.

Distinguishing between partial and generalized seizures can help identify patients who need treatment and guide selection of antiepileptic drugs. Drug therapy should be initiated gradually if the situation permits. Agents that can be loaded intravenously include phenytoin sodium (Dilantin) and its prodrug fosphenytoin sodium (Cerebyx), phenobarbital sodium, and valproic acid (Depacon).

The initial choice of antiepileptic agent is based on numerous factors, including seizure type, findings on the EEG, concomitant medications, and past medical history as well as hematologic, hepatic, and renal function. Antiepileptic drugs may produce sedation, psychomotor slowing, and gastrointestinal upset. Rarely, they can cause life-threatening side effects, such as Stevens-Johnson syndrome, liver or bone marrow failure, and pancreatitis. Because of possible teratogenic effects, women of childbearing age who are receiving antiepileptic drug therapy should be given vitamin supplementation, especially with folic acid, to lower the risk of neural tube and other congenital defects.

Summary

The first step in evaluation of a presumed seizure is to determine whether the event was indeed a seizure and which diagnostic studies are needed. The second step is to correctly diagnose the seizure on the basis of the medical history and findings from the physical, neurologic, and laboratory evaluation. The third step is to decide whether drug treatment is necessary. Every paroxsymal event is unique, and not every seizure needs to be treated. When treatment is deemed appropriate, an antiepileptic drug should be chosen after discussion with the patient and consideration of the risk-benefit profile of the available agents.

References

1. Fisher RS, ed. Imitators of epilepsy. New York: Demos Medical Publishing, 1994
2. Devinsky O. Psychogenic seizures and syncope. In: Feldmann E, ed. Current diagnosis in neurology. St Louis: CV Mosby, 1994:1-6
3. Kochiadakis GE, Rombola AT, Kanoupakis EM, et al. Assessment of autonomic function at rest and during tilt testing in patients with vasovagal syncope. Am Heart J 1997;134(3):459-66
4. Gates JR, Ramani V, Whalen S, et al. Ictal characteristics of pseudoseizures. Arch Neurol 1985;42(12):1183-7
5. Hauser WA, Hesdorffer DC. Epilepsy: frequency, causes and consequences. New York: Demos Medical Publishing, 1990:1-51
6. Hauser WA, Kurland LT. The epidemiology of epilepsy in Rochester, Minnesota, 1935 through 1967. Epilepsia 1975;16(1):1-66
7. Walczak TS, Jayakar P. Interictal EEG. In: Engel J Jr, Pedley TA. Epilepsy: a comprehensive textbook. Philadelphia: Lippincott-Raven, 1997:831-48
8. Hauser WA. Should people be treated after a first seizure? Arch Neurol 1986;43(12):1287-8
9. Hauser WA, Anderson VE, Loewenson RB, et al. Seizure recurrence after a first unprovoked seizure. N Engl J Med 1982;307(9):522-8
10. Hart RG, Easton JD. Seizure recurrence after a first, unprovoked seizure. Arch Neurol 1986;43(12):1289-90
11. Hauser WA, Rich SS, Annegers JF, et al. Seizure recurrence after a 1st unprovoked seizure: an extended follow-up. Neurology 1990;40(8):1163-70
12. Hopkins A, Garman A, Clark C. The first seizure in adult life: value of clinical features, electroencephalography, and computerised tomographic scanning in prediction of seizure recurrence. Lancet 1988;1(8588):721-6

Dr Prego-Lopez is a clinical neurophysiology fellow, department of neurology, New York University School of Medicine, New York. Dr Devinsky is professor of neurology, neurosurgery, and psychiatry, New York University School of Medicine, and director, NYU Comprehensive Epilepsy Center, New York. Correspondence: Orrin Devinsky, MD, NYU Comprehensive Epilepsy Center, 403 E 34th St, 4th Floor, New York, NY 10016. E-mail: od4@is4.nyu.edu.

Symposium Index

• INTRODUCTION TO THE SYMPOSIUM by Steven C. Schachter, MD
• EVALUATION OF A FIRST SEIZURE: Is it epilepsy? by Marisa Prego-Lopez, MD, Orrin Devinsky, MD
• NEUROLOGIC CONSULTATION FOR SEIZURES: When, why, and how to pursue by David M. Labiner, MD, Geoffrey L. Ahern, PhD, MD
• APPROPRIATE USE OF MEDICATIONS FOR SEIZURES: Guiding principles on the path of efficacy by Ahmad Beydoun, MD, Erasmo A. Passaro, MD
• IMPROVING THE QUALITY OF LIFE IN EPILEPSY: Nonmedical issues too often overlooked Online by Patricia Osborne Shafer, RN, MN

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