The Comprehensive Evaluation and Treatment of Epilepsy: A Practical Guide

02215

Preface

Steven C. Schachter, M.D.; Donald L. Schomer, M.D.

The primary objective of caring for patients with epilepsy is to restore their functional capacity to its maximal potential. In diagnosing epilepsy in patients, planning treatment, and providing follow-up care, it is important that the physician be familiar with current diagnostic and therapeutic protocols. Often this information is not included in textbooks of general neurology beyond an overview. Further, the care of patients with epilepsy often requires a team approach, utilizing medical and social service professionals in addition to the patient’s family, friends, and coworkers. In these cases, the physician must take into account psychosocial, cognitive, educational, and vocational issues in addition to pharmacologic considerations. Guidelines for this process are generally unavailable in neurology textbooks.

The purpose of this book, therefore, is to provide current information about epilepsy in a comprehensive, easy-to-use, and practical form. It is particularly intended for general neurologists and neurologically oriented primary care physicians.

Each chapter is organized under headings presented as commonly asked clinical questions pertaining to the subject of the chapter. Each of these questions is listed in the contents of the book, a feature that should help the busy practitioner find the answer to a particular question in the midst of a hectic clinic session.

The first three chapters cover the initial management of patients with seizures. Chapter 1 discusses the classification of seizures and epilepsy syndromes and the spectrum of EEG abnormalities associated with seizure disorders. Chapter 2 addresses the optimal radiographic evaluation of epilepsy patients. Chapter 3 presents the medical therapy of seizures.

Subsequent chapters detail the factors that contribute to intractable seizures (Chapter 4), including psychosocial aspects of epilepsy (Chapter 5), neuropsychologic problems associated with temporal lobe epilepsy (Chapter 6), and related psychiatric disorders (Chapter 7). The diagnosis and treatment of status epilepticus (Chapter 8) and nonepileptic seizures (Chapter 9) are then presented, followed by discussions of ambulatory EEG monitoring (Chapter 10), epilepsy surgery (Chapter 11), endocrine aspects of partial seizures (Chapter 12), and epilepsy in the elderly (Chapter 13). Chapter 14 provides guidelines for referring patients to comprehensive epilepsy centers.

In summary, this book represents our current body of knowledge about epilepsy, formulated for general neurologic or medical practice. The field of epilepsy is rapidly changing as new therapies are introduced, genetic breakthroughs are announced, and new imaging modalities are invented. The editors hope that the clinical approach to epilepsy reflected in this book will provide a foundation on which the reader can integrate these new advances with compassionate care of patients with seizures.

The editors express their appreciation to Cathy Somer and Loraine Karol for editorial assistance.

Chapter 1

Classification of Seizures and the Epilepsies

Gregory L. Holmes, M.D.

HOW ARE SEIZURES CLASSIFIED?

One of the first priorities facing the physician when evaluating a patient with epileptic seizures is to determine seizure type and, when possible, the epileptic syndrome. This determination is critical because seizure type and epileptic syndrome to a great extent determine the type of evaluation the patient will receive, as well as the type of therapy.

Seizures are classified into two basic groups: partial and generalized (Table 1.1).¹ Partial seizures involve only a portion of the brain at the onset. Seizures can be further divided into those in which consciousness is not impaired (simple partial) and those in which it is (complex partial). Both types of partial seizures can spread, resulting in 2° generalized tonic-clonic seizures. Primary generalized seizures are those in which the first clinical changes indicate the initial involvement of both hemispheres. There is usually impairment of consciousness during generalized seizures, although some seizures, such as the myoclonic type, may be so brief that impairment of consciousness cannot be assessed. Space limitations do not permit detailed descriptions of all the seizure types.

Table 1.1

International Classification of Epileptic Seizuresa

I. Partial Seizures

 A. Simple partial seizures

   1. With motor signs

     a. Focal motor without march

     b. Focal motor with march (Jacksonian)

     c. Versive

     d. Postural

     e. Phonatory

   2. With somatosensory or special-sensory symptoms

     a. Somatosensory

     b. Visual

     c. Auditory

     d. Olfactory

     e. Gustatory

     f. Vertiginous

   3. With autonomic symptoms or signs

   4. With psychic symptoms

     a. Dysphasia

     b. Dysmnesic

     c. Cognitive

     d. Affective

     e. Illusions

     f. Structured hallucinations

 B. Complex partial seizures

   1. Simple partial seizures

     a. With simple partial features

     b. With automatisms

   2. With impairment of consciousness at onset

     a. With impairment of consciousness only

     b. With automatisms

 C. Partial seizures evolving to secondarily generalized seizures

   1. Simple partial seizures evolving to generalized seizures

   2. Complex partial seizures evolving to generalized seizures

   3. Simple partial seizures evolving to complex partial seizures evolving to generalized seizures

II. Generalized Seizures

 A. Absence seizures

   1. Typical absence seizures

     a. Impairment of consciousness only

     b. With mild clonic components

     c. With atonic components

     d. With tonic components

     e. With automatisms

     f. With autonomic components

   2. Atypical absence seizures

 B. Myoclonic seizures

 C. Clonic seizures

 D. Tonic seizures

 E. Tonic-clonic seizures

 F. Atonic seizures

a Modified from Ref 1.

HOW CAN THE PHYSICIAN DISTINGUISH BETWEEN SIMPLE PARTIAL AND COMPLEX PARTIAL SEIZURES?

Simple partial seizures (SPS) can occur at any age. The signs or symptoms of this type of seizure depend on the location of the focus of the seizure.² Seizures involving the motor cortex most commonly consist of rhythmic to semirhythmic clonic activity of the face, arm, or leg. Diagnosing this type of seizure is usually not difficult. Seizures with somatosensory, autonomic, and psychic symptoms (hallucinations, illusions, deja vu) may be more difficult to diagnose.³ Psychic symptoms usually occur as a component of a complex partial seizure.

Complex partial seizures (CPS), formerly termed temporal lobe or psychomotor seizures, are one of the most common seizure types encountered in both children and adults.³ This type of seizure may be preceded by a simple partial seizure that may serve as a warning to the patient (i.e., aura) of a more severe seizure to come. It is important to realize that the aura may enable the clinician to determine the cortical area in which the seizure is beginning.

By definition, all patients with CPS have impaired consciousness; thus the patient either does not respond to commands or responds in an abnormally slow manner. Although CPS may be characterized by simple staring and impaired responsiveness, behavior is usually more complex during the seizure. Automatisms (involuntary motor activity) are common during the period of impaired consciousness in CPS. Automatic behavior is variable and may consist of activities such as facial grimacing, gesturing, chewing, lip smacking, finger snapping, and repeating phrases; the patient does not recall this activity after the seizure.⁴,⁵ Although variable, CPS usually last from 30 s to several minutes. In contrast, absence seizures (described later) usually last less than 15 s.⁶ Most patients have some degree of postictal impairment, such as tiredness or confusion.

WHAT ARE THE TYPES OF GENERALIZED SEIZURES?

GENERALIZED TONIC-CLONIC SEIZURES

There is rarely any difficulty in correctly diagnosing generalized tonic-clonic (GTC) seizures (formerly termed grand mal seizures). The only caution is that toddlers with breath-holding attacks and adults and children with syncope may have brief generalized tonic-clonic seizures at the end of the attack.⁷ Those brief seizures should not be treated with antiepileptic drugs.

Some patients may have a simple partial seizure (aura) preceding the loss of consciousness. As previously described, this indicates that the seizure was simple partial in onset. As the seizure spreads in the cortex, the seizure develops into a GTC seizure. The seizure would then be classified as a simple partial seizure with secondary generalization.⁸ The loss of consciousness usually occurs simultaneously with the onset of a generalized stiffening of the flexor or the extensor muscles (termed tonic phase). After the tonic phase, generalized jerking of the muscles (clonic activity) occurs. A GTC seizure is almost always associated with deep postictal sleep.

ABSENCE SEIZURES

The revised classification of epileptic seizures by the International League against Epilepsy categorizes absence seizures as generalized seizures, indicating bihemispheric initial involvement clinically and electroencephalographically. Many children with absence seizures can be further categorized as having a characteristic epileptic syndrome.

The terms typical and atypical absence seizures were used in the International Classification of Epileptic Seizures to describe and categorize the various absence types. The simple typical absence consists of the sudden onset of impaired consciousness, usually associated with a blank facial appearance without other motor or behavioral phenomena. This subtype is actually relatively rare and comprised only 9% of 374 absence seizures video-recorded from 48 patients by Penry et al.⁹ The complex typical absence, alternatively, is accompanied by other motor, behavioral, or autonomic phenomena.

Clonic components may be subtle and most frequently consist of eye blinking. Clonic activity may range from nystagmus to rapid jerking of the arms. Changes in tone often include a tonic postural contraction leading to flexion or hypertonic extension. Although a decrease in tone rarely causes a fall, the decrease may lead to nodding of the head or the dropping of objects.

Automatisms are the most common clinical accompaniment, occurring in 44% of 476 typical absence seizures studied by simultaneous video-electroencephalography radiotelemetry in 27 patients.⁶ Automatisms are semipurposeful behaviors of which the patient is unaware and subsequently cannot recall. They may be either perseverative, reflecting the continuation of preictal activities, or de novo. Simple behaviors, such as rubbing the face or hands, licking the lips, chewing, grimacing, scratching, or fumbling with clothes, tend to be de novo automatisms. Complex activities, such as dealing cards, playing patty-cake, or handling a toy, are generally perseverative. Speech, if it occurs, is usually perseverative and is often slowed and dysarthric, but speech may be totally normal and may include both expressive and receptive aspects.

Autonomic phenomena associated with absence seizures include pupil dilatation, pallor, flushing, sweating, salivation, piloerection, and even urinary incontinence. Neither the autonomic changes nor the automatisms distinguish absence from other seizure types.

Atypical absence seizures have traditionally been characterized as having less abrupt onset or cessation, more pronounced changes in tone, and longer duration than typical absence seizures.⁶,¹⁰,¹¹ They usually begin before 5 years of age and are associated with other generalized seizure types and mental retardation.

Holmes et al.⁶ compared 426 typical and 500 atypical absence seizures in 54 children. The atypical absence seizure lasted significantly longer, on average, than the typical absence seizure. A change in facial expression or the appearance of a blank stare was the most common initial clinical manifestation in either type. A pause or slowing of motor activity was also frequently noted as the initial finding in either seizure type. Either diminished postural tone or tonic or myoclonic activity was significantly more likely to be the initial clinical feature in atypical than in typical absences.

A blank stare or change in facial expression was the sole clinical finding in only 16% of typical and 28% of atypical absences. Automatisms, eye blinking, and lip smacking occurred more commonly in typical absences. A change in postural tone—either an increase or a decrease—was more commonly seen in atypical absences. Automatisms were more common in typical than in atypical absences and were usually perseverative, often consisting of playing with a toy or game. De novo automatisms were associated with longer spells and most commonly consisted of rubbing the face or hands or smiling.

Both typical and atypical absences started abruptly without an aura, lasted from a few to 30 s, and ended abruptly. Both were frequently associated with eye blinking, lip smacking, a decrease in tone, and automatisms. Although statistically significant differences can be identified, there is considerable overlap between the two seizure types and they most likely represent a clinical continuum. This overlap pertains to the electroencephalogram (EEG) and proposed pathophysiology as well.

Electroencephalography

The EEG signature of a typical absence seizure is the sudden onset of 3-Hz generalized symmetrical spike- or multiple spike-and-slow wave complexes (Fig. 1.1, A–C). The voltage of the discharges is often maximal in the frontocentral regions. The frequency tends to be faster (about 4 Hz) at the onset and slower (down to 2 Hz) toward the end of discharges if they persist longer than 10 s. The spike-and-wave discharge may be precipitated by hyperventilation or photic stimulation. The ictal discharges during an atypical absence seizure are more variable. They occur at frequencies between 1.5 and 2.5 Hz or may be faster than 2.5 Hz, but they are irregular or asymmetric in voltage.

Figure 1.1 (A) Typical absence seizure. Note generalized onset of seizure. The child stops tapping her finger shortly after the onset of the seizure.

Figure 1.1 (B) Absence seizure continues. Note generalized spike-and-wave discharges.

Figure 1.1 (C) End of absence seizure. Note that the child begins tapping finger again.

The interictal EEG background is generally normal in typical and abnormal in atypical absences. Utilizing the preceding ictal EEG criteria to classify absence seizures, Holmes et al.⁶ found that only 44% of 27 patients with typical absences had normal EEG backgrounds. Diffuse slowing was seen in 22% and paroxysmal spikes or sharp waves were seen in 37%. Conversely, only 11% of 27 patients with atypical absences had a normal interictal EEG. Diffuse slowing and focal or multifocal spikes or sharp waves were seen in 85% of patients.

The discharges are more numerous during all sleep states except rapid eye movement (REM) sleep. The bursts have a modified appearance in sleep: they are briefer and are irregular and they slow to 1.5–2.5 Hz. Hyperventilation, photic stimulation, and hypoglycemia will activate typical absence seizures, but hyperventilation is the most effective procedure.

Clinical effects are generally perceived to accompany discharges lasting longer than 3 seconds. Detailed neuropsychologic investigations have demonstrated functional impairment from a spike-and-wave burst of any duration. Auditory reaction times were delayed 56% of the time when a stimulus was presented at the onset of the EEG paroxysm¹² and were abnormal 80% of the time when the stimulus was delayed 0.5 s. Responsiveness may improve as the paroxysm continues.

In atypical absences, the ictal EEG is more heterogeneous, showing 1.5- to 2.5-Hz slow spike-and-wave or multiple spike-and-wave discharges that may be irregular or asymmetric (Fig. 1.2). The interictal EEG is usually abnormal, reflecting slowing and multifocal epileptiform features.

Figure 1.2 Atypical absence seizure with slow spike-and-wave

CLONIC SEIZURES

Clonic seizures are similar to GTC seizures but consist only of rhythmic or semirhythmic contractions of a group of muscles. These jerks can involve any muscle group, although the arms, neck, and facial muscles are most commonly involved. Clonic seizures are more common in children than adults.

MYOCLONIC SEIZURES

Myoclonic seizures are characterized by sudden, brief (< 350 milliseconds), shocklike contractions that may be generalized or confined to the face and trunk or to one or more extremities, or even to individual muscles or groups of muscles.³ Myoclonic seizures result in short bursts of synchronized electromyographic activity, which often involves simultaneous activation of agonist and antagonist muscles. The contractions of muscles are quicker than the contractions with clonic seizures. Any group of muscles can be involved in the jerk. Myoclonic seizures may be dramatic, causing the patient to fall to the ground, or they may be subtle, resembling tremors. Because of the brevity of the seizures, it is not possible to determine if consciousness is impaired. Myoclonus may occur as a component of an absence seizure or at the beginning of a GTC seizure. Myoclonic seizures are usually associated with generalized spike-and-wave