Overview: Idiopathic Generalized Epilepsies

Transcription

1 Epilepsia, 44(Suppl. 2):2 6, 2003 Blackwell Publishing, Inc International League Against Epilepsy Overview: Idiopathic Generalized Epilepsies Richard H. Mattson Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, U.S.A. Summary: The idiopathic generalized epilepsies (IGEs) are an underemphasized topic. Two reasons for this relative lack of attention are that these epilepsies tend to be more easily controlled than the symptomatic partial and generalized epilepsies, and they are not as common. Because IGE usually arises in childhood or adolescence, these epilepsies may be thought of as a pediatric problem. However, a large number of patients continue to have seizures in adult life. Many exciting developments in understanding the pathophysiology, genetic etiology, and expanded treatment options warrant a reexamination of this important group of the epilepsies. This article reviews the more common IGE syndromes and associated seizure types as the first step in identifying the recent advances in our knowledge of these syndromes. Key Words: Idiopathic generalized epilepsy (IGE) Epilepsies and seizure types Various IGE syndromes Epilepsy syndromes. As used in the International Classification of the Epilepsies and Epilepsy Syndromes, the term idiopathic refers to a disease that is self-originating or spontaneously arising (1 4). For other medical conditions, the term idiopathic may be used to mean unknown, but that is not the case in epilepsy. As detailed by Dr. Noebels in this supplement, many of the IGEs have a known genetic cause (5). Epilepsies with an unknown or hidden cause are termed cryptogenic (1 3). The diagnosis of an IGE has important treatment and prognostic implications (2). DIFFERENT SEIZURE TYPES ASSOCIATED WITH EPILEPSY The term epilepsy refers not to a specific disease but to a heterogeneous group of chronic disorders characterized by a tendency to have recurrent seizures (6). According to J. Hughlings Jackson, who made the first step toward defining contemporary epileptology with his research, a seizure is an occasional sudden, excessive, rapid, and local discharge of gray matter (6) an abnormal discharge of cortical neurons (7). The different kinds of seizures were classified in 1981 by the International League Against Epilepsy (ILAE) into two categories, partial and generalized, with a third designation for unclassified seizures outside these parameters (8). Some of the generalized seizures are the types seen in IGE. Address correspondence and reprint requests to Dr. R. H. Mattson at Department of Neurology, Yale University School of Medicine, P.O. Box , New Haven, CT , U.S.A. richard.mattson@yale.edu Generalized seizures There are six classes of generalized seizures absence, myoclonic, tonic-clonic (or clonic-tonic-clonic), atonic, tonic, and clonic characterized on the basis of clinical symptoms and electroencephalogram (EEG) abnormalities. The first three listed (absence, myoclonic, and tonic-clonic) are associated with IGE. Absence seizures Absence seizures usually present during childhood or adolescence. Patients experience a momentary loss of consciousness lasting 3 15 s, which often goes undetected, except for brief staring spells, eyelid flutter, or minor automatisms that are dependent on the duration of the seizure. The child is unresponsive and has no memory of what went on when the seizure occurred (1,2). The only diagnostic test for absence seizures is an EEG tracing with a normal background and a typical 3-Hz spike-and-wave complex during the seizures. Consistent with the sudden onset of absence seizures, the ending is abrupt, both clinically and electrically, and shows no postictal EEG slowing. Hyperventilation often provokes these seizures and can be used as a diagnostic tool with an EEG (6). Children are more likely to experience absence seizures into adulthood when there is a family history of epilepsy, when the child has other types of seizures in addition to absence seizures, or when the first onset of the seizures is late in childhood (1 4). Absence status occurs in some patients and may be seen in adult life (4,9). Myoclonic seizures The second seizure type associated with idiopathic epilepsy is myoclonic seizures, which typically have an 2

2 IDIOPATHIC GENERALIZED EPILEPSIES 3 onset around adolescence and persist throughout adulthood. They are characterized by sudden, brief, arrhythmic jerks, predominantly in the arms, but also involve other extremities. The movements are usually bilateral but are sometimes more obvious on one side than the other, which can be misleading and result in the wrong diagnosis. The jerking lasts 1 s and may occur as a single event or often as a series of multiple movements. These seizures may be associated with a fall. There usually is no obvious loss of consciousness. Myoclonic seizures tend to occur in the early morning shortly after awakening. They may be triggered by photic or sensory stimulation or sleep deprivation. The typical EEG pattern seen with myoclonic seizures is the generalized polyspike-wave burst (1 4,6,8,10). Tonic-clonic seizures The third type of generalized seizure, and the one that most frequently brings people to medical attention, is the tonic-clonic or clonic-tonic-clonic seizure, often called a grand mal seizure. It can occur alone or with absence and/or myoclonic seizures (1,2). When a patient presents with a tonic-clonic seizure, it is especially important to determine whether it is associated with idiopathic epilepsy or with a symptomatic partial epilepsy. Frequently, there is no other information about the attack except that it was convulsive in nature. The prognosis, evaluation, and response to treatment are significantly different, depending on the type of tonic-clonic seizure. There are two types of generalized tonic-clonic seizures: primary or secondary. The primary generalized tonic-clonic seizures are associated with IGE, while secondary tonic-clonic seizures are associated with partial or symptomatic epilepsies. Primary generalized tonic-clonic seizures have a usual onset during childhood or adolescence, but they may appear even later. They occur without prior warning or aura and involve the whole brain. The patient has a normal brain with no evidence of brain dysfunction or disease other than seizures, except coincidentally. The EEG pattern for primary tonic-clonic seizures is generalized spike-and-wave or polyspike wave. The response of this type of tonic-clonic seizure to treatment is excellent, with 75 85% of patients achieving complete control (11). Secondary generalized tonic-clonic seizures initially can occur at any age. Patients may experience an aura because the seizures start as a partial seizure that spreads to the whole brain as a generalized tonic-clonic seizure. Neurological examination and imaging studies in these patients result in abnormal findings. The EEG pattern may reveal sharp waves and/or spikes of focal origin. The prognosis for patients with secondary generalized tonic-clonic seizures varies because the seizures may begin at any time of life and have multiple etiologies. Primary generalized tonic-clonic seizures consist of several motor responses, including tonic extension of the limbs, which lasts s, followed by a clonic phase of rhythmic jerking of the extremities for s. During the seizure, the patient loses consciousness and may remain unconscious for a period of time after the jerking movements stop. Commonly, during the tonic phase, there is momentary cessation of breathing and the patient may be incontinent. The patient may also bite the tongue or inside of the cheek. Postictal confusion and fatigue or sleep usually follows. The EEG pattern is variable and often obscured. EPILEPSIES AND EPILEPTIC SYNDROMES The ILAE revised its original classification of epileptic seizures and adopted a new classification of epilepsies and epileptic syndromes (1). Epileptic syndromes were characterized by the type of seizures associated with each syndrome and other aspects, including the age of onset, diurnal pattern, family history, response to treatment, prognosis, etiology, and severity. The epilepsy syndrome was of critical importance in determining the expectation of treatment and the long-term prognosis. The revised classification system organized epilepsies into two 2-part divisions, generalized and localizationrelated (focal, partial), which were further subdivided into idiopathic (primary) and symptomatic or cryptogenic (secondary). The idiopathic epilepsies have no specific cause but are assumed to have a genetic etiology. The epilepsies that are idiopathic almost always have onset in childhood or adolescence, although there are exceptions; some patients develop these kinds of epilepsies after the second decade of life or, rarely, even later. The symptomatic epilepsies differ from the idiopathic epilepsies by having a known cause, such as head trauma, or there is some evidence of brain or neurological dysfunction. In cryptogenic epilepsies, the etiology or site of abnormality may not be detectable or is hidden. Idiopathic epilepsies tend to be more responsive to treatment, in contrast to the symptomatic epilepsies, overall. Table 1 presents a comparison of the characteristics of idiopathic and symptomatic epilepsies. TABLE 1. Epilepsy types Idiopathic (primary) Onset in childhood Probably genetic Good antiepileptic drug response Favorable prognosis Normal brain Symptomatic (secondary) Onset at any age Multiple etiologies Variable response Variable prognosis Brain pathology

3 4 R. H. MATTSON TABLE 2. Idiopathic generalized epilepsies Childhood absence epilepsy (pyknolepsy) Juvenile absence epilepsy Juvenile myoclonic epilepsy Epilepsy with grand mal (generalized tonic-clonic) seizures on awakening Idiopathic generalized epilepsies There are a number of different epilepsy syndromes within the group of IGEs. They include benign neonatal familial convulsions, benign neonatal convulsions, benign myoclonic epilepsy in infancy, childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and epilepsy with grand mal seizures on awakening. The latter group overlaps juvenile absence and myoclonic epilepsy in most characteristics but has few or no absence or myoclonic seizures. At times, all of these IGE syndromes exhibit some overlap (4). This discussion will focus on three of the epilepsy syndromes: childhood absence, juvenile absence, and juvenile myoclonic epilepsies (Table 2). An ILAE Task Force has undertaken a revision of the classification (7), but controversy suggests no change will occur soon (12). In any case, the working revision does not significantly modify the classification of the IGEs. Childhood absence epilepsy According to the ILAE classification, childhood absence epilepsy (CAE) is associated with a characteristic triad of elements: very frequent brief absence seizures; normal intelligence and development; and bilateral synchronous, symmetrical 3-Hz spike-wave discharge EEG pattern with a normal background, as shown in Fig. 1 (1, 2). CAE accounts for 2 15% of the cases of childhood epilepsy. Typically, CAE onset is between 4 8 years of age, with peak onset at age 6 7 years. The EEG pattern is characteristically spike-and-wave. Because these absence attacks frequently occur and are very brief, lasting only a few seconds, the term pyknolepsy is sometimes used. Often, these seizures are the only type the patients have; however, 40% also develop generalized tonicclonic seizures as they reach adolescence (1 4). Juvenile absence epilepsy Juvenile absence epilepsy (JAE) is another category delineated by the ILAE as a distinct idiopathic epileptic syndrome (1,2). JAE onset is at age years, slightly older than for CAE. Peak onset is between years. The frequency of absence seizures in JAE is considerably lower than with CAE, and impairment of consciousness is less severe. In addition to the absence seizures, patients may have occasional tonic-clonic seizures and sporadic, infrequent myoclonic jerks. There is no visual FIG. 1. Childhood absence. Electroencephalogram tracing courtesy of Patricia K. Crumrine, M.D., Department of Pediatrics, University of Pittsburgh School of Medicine. (Printed with permission.)

4 IDIOPATHIC GENERALIZED EPILEPSIES 5 FIG. 2. Juvenile myoclonic epilepsy. Electroencephalogram tracing courtesy of Patricia K. Crumrine, M.D., Department of Pediatrics, University of Pittsburgh School of Medicine. (Printed with permission.) or other sensory precipitation. The seizures often persist for many years, but they usually respond well to treatment. Juvenile myoclonic epilepsy Juvenile myoclonic epilepsy (JME), another of the idiopathic epileptic syndromes, occurs far more commonly than is diagnosed (1 5,10). This syndrome is characterized by myoclonic seizures that appear with tonic-clonic seizures in most patients and absence seizures in about one third (10). The age of onset varies from 8 to 26 years and peaks at years (10). Because the absence and myoclonic seizures are brief or not frequent, they may be unrecognized, and the syndrome often goes undiagnosed until the child reaches adolescence and has a tonic-clonic seizure. The typical EEG pattern seen with JME is that of myoclonic seizures, with polyspike-wave bursts (Fig. 2). Characteristically, JME persists throughout the remainder of the patient s lifetime, but otherwise, examination of these patients shows them to be normal (10). CONCLUSION The IGEs are those syndromes or diseases that are a primary epilepsy condition and are thought or known to have a genetic cause. Various characteristics make up the main epilepsy groups. These include seizure types, age of onset, diurnal pattern of occurrence, family history, prognosis, and response to treatment, among other descriptors. The main types include CAE, JAE, and epilepsy with grand mal on awakening. Some overlap of these syndromes can be observed. These epilepsies are accompanied by generalized spike-wave discharges on the EEG. The IGEs have received less attention than the symptomatic partial epilepsies, perhaps due to easier management and less prevalence (although estimated to constitute one quarter of the incidence of epilepsy). A convergence of human and animal experimental studies is providing a clearer understanding of the pathophysiology of absence attacks and the associated spike-wave electrical discharge. New understanding of the genetic basis of these disorders may allow us to reclassify some of these disorders as diseases rather than as epilepsy syndromes. With the introduction of many new antiepileptic drugs in the past decade, we have been provided a broader choice of options for management. REFERENCES 1. Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia 1989;30: Dreifuss FE, Nordil DR. Classification of epilepsies in childhood. In: Pellock JM, Dodson WE, Bourgeois BFD, eds. Pediatric epilepsy, 2nd ed. New York: Demos Medical Publishing, 2001:69 80.

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