Epilepsies with Typical Absence Seizures

Absences are generalized nonconvulsive epileptic seizures; in other words, they are seizures without local onset, expressed predominantly by disturbances of consciousness, with no or relatively little motor activity. The 1981 revision of the International Classification of Epileptic Seizures recognizes the following two types of absence seizures depending on their ictal electroencephalographic (EEG) pattern and clinical characteristics: (a) typical absence seizures characterized by an abrupt onset and offset and an EEG discharge of symmetric, synchronous spike-wave complexes recurring regularly at a rhythm of about 3 Hz and (b) atypical absences with a more progressive onset and offset that are often associated with different EEG patterns, including bursts of spike-wave patterns that are often irregular at a rhythm of less than 2.5 Hz and, at times, fast rhythms of small-amplitude or high-voltage 10-Hz activity (Erba and Browne, 1983; Commission on Classification and Terminology of the International League Against Epilepsy, 1981). In actuality, these distinctions are somewhat artificial, and some investigators consider typical absences to be those that occur in idiopathic epilepsy and atypical absences to be those associated with cryptogenic or symptomatic epilepsies, especially the Lennox-Gastaut syndrome (LGS) (Roger and Genton, 1995). However, typical absences may occasionally occur in symptomatic epilepsies (Ferrie et al., 1995).

Typical absence attacks can be classified as “simple” when only impairment of consciousness is present, possibly with simple and limited motor activity, such as eyelid fluttering or jerking or slight elevation of the eyeballs, and as “complex” when automatisms or prominent motor components (myoclonic, tonic, or atonic) are present (Gastaut et al., 1974b). This chapter deals with childhood epilepsies manifested exclusively or predominantly by typical absences, whether simple or complex. Atypical absences are considered elsewhere (see Chapter 4). The term petit mal epilepsy is often used synonymously with typical absence epilepsy (Lennox and Lennox, 1960; Livingston, 1960). However, the former term has been used loosely to designate a number of different epilepsy syndromes with relatively minor symptoms, regardless of the precise description of the seizures and the associated EEG abnormalities. The term has also been variously used in a number of countries (Doose et al., 1970; Kruse, 1968). Thus, the use of the term typical absence epilepsy is preferable, as it avoids the ambiguities associated with the term petit mal.

Typical absence epilepsy does not designate a single type of epilepsy but rather a broad group of epilepsy syndromes with onset at different ages and varying associated seizures, courses, and outcomes. This chapter describes the clinical and EEG manifestations of typical absences and then reviews the several syndromes featuring typical absence attacks. These include the following:

A relatively pure form of typical absence epilepsy of childhood in which very frequent seizures occur in isolation, generally between the ages of 4 and 10 years (also called pyknolepsy) (Janz, 1969).
Typical absence epilepsy of adolescence in which absences occur less frequently than in the childhood type and they are more often associated with tonic-clonic seizures and other forms of attack. Panayiotopoulos et al. (1989a, 1989b) separated the absences observed with juvenile myoclonic epilepsy (JME) from the typical absences of adolescence on the basis of a mild decrease in consciousness and different EEG findings. However, the term absence may not be adequate if no alteration of awareness is observed.
Myoclonic absences, which are also known as clonic absences.

In addition to these syndromes, which are recognized by the International League Against Epilepsy (ILAE) classification, other syndromes with absences have been described (Panayiotopoulos, 1998a; Duncan and Panayiotopoulos, 1995b). These include the following: absences occurring in association with adversion (adversive absences) (Janz, 1969); absences occurring in association with focal features (Dalby, 1969; Bancaud et al., 1965); absences with evidence of a brain lesion, whether fixed or evolving (Sato et al., 1976; Loiseau and Cohadon, 1970; Dalby, 1969;
Lennox and Lennox, 1960); absences induced by intermittent light stimulation, television, and/or eye closure (Jeavons, 1982); absences preceded by generalized tonic-clonic seizures (GTCSs) other than febrile convulsions (Dieterich et al., 1985b). Such cases are not included in the ILAE classification (Commission on Classification and Terminology of the International League Against Epilepsy, 1985, 1989).

EPIDEMIOLOGY AND ETIOLOGY

The epidemiology of typical absences is not well known because of problems with case ascertainment, case definition, and patient-selection bias (Sander, 1995). Typical absences affect predominantly children and adolescents, and females are usually affected more than males. The incidence of typical absences ranges from 0.7 to 4.6 per 100,000 in children and adolescents up to 15 years of age. Granieri et al. (1983) estimated an average incidence of 1.9 per 100,000 in Italy, and Hauser et al. (1991) noted an annual rate of 1.3 per 100,000 population in Rochester, Minnesota. Higher figures (6 per 100,000) were found in children younger than 16 years, compared with 1.4 per 100,000 in the general population in France (Loiseau et al., 1990). The prevalence rate is quite low, but it may be underestimated in epidemiologic studies.

The proportion of patients with typical absences among those with epilepsy is often given as 3% in community-based or hospital-based studies (Sander, 1995).

The etiologic factors of typical absence epilepsy probably vary with the syndrome observed. Girls are more commonly affected than boys, with a ratio of 60% to 40% (Roger, 1974; Dalby, 1969; Gibberd, 1966). Typical absence seizures are mainly a disorder of children and adolescents, although adults are not immune (Loiseau and Cohadon, 1970). Holowach et al. (1962) indicated that 80% of their patients were between 2.5 and 9 years of age at the onset of typical absence. Livingston et al. (1965) found 2.6% of their patients to be younger than 2 years, 55% were between 4 and 8 years, and 93.1% were younger than 13 years. In the series by Dalby (1969), 17% were younger than 4 years, 64% were between 5 and 9 years, 17% were between 10 and 14 years, and only 2% were older than 15 years. The mean age at onset for the patients with typical absence seizures in the study by Oller-Daurella and Sanchez (1981) was 7 years. However, in the series by Lugaresi et al. (1974), 30% of patients had an age at onset of younger than 4 years, and 22.6% had an onset after 10 years of age. This series contained a very high proportion of patients with cerebral lesions, and, thus, it may be biased in favor of the more severe cases. Rare cases in the first year of life have also been reported (Aicardi, 1995; Cavazzuti et al., 1989).

Genetic factors are thought to be of major importance in the causation of typical absence seizures. Family studies indicate that the incidence of seizures or EEG paroxysmal abnormalities in first-degree relatives ranges from 15% to 44% (Degen et al., 1990; Rocca et al., 1987a; Sato et al., 1976; Lugaresi et al., 1973; Currier et al., 1963; Holowach et al., 1962). The occurrence of two cases of typical absence epilepsy in siblings, parents, and offspring is not uncommon (Loiseau and Cohadon, 1970; Lennox and Lennox, 1960). However, the occurrence of other forms of epilepsy in relatives of patients with typical absence seizures is more common than is that of the same typical absence type. Twin studies (Lennox and Lennox, 1960) found a concordance of 75% for typical absence seizures and of 84% for EEG abnormalities in monozygotic twins, whereas no dizygotic pair was concordant. Several investigators (Metrakos and Metrakos, 1970) favored a dominant mode of inheritance, but polygenic transmission appears more likely (Doose and Baier, 1987, 1988; Doose et al., 1973, 1984; Aicardi, 1973). Although a genetic relationship between typical absence epilepsy and other epilepsy syndromes, such as awakening grand mal, has long been known, this relation is, to a large extent, dependent on the syndrome, as the study of pedigrees with several affected members shows (Bianchi and the Italian League Against Epilepsy Collaborative Group, 1995). Juvenile absence epilepsy (JAE) is not usually found in relatives of patients with childhood absences, whereas absences associated with myoclonic phenomena are not encountered in families with pure absence attacks but they may be related to those with JME. Absences are preceded by febrile seizures in approximately 15% to 30% of patients (Wallace, 1991; Olsson, 1990; Hashimoto et al., 1989; Doose et al., 1973). Rare cases of such may be an expression of the spectrum of generalized epilepsy with febrile seizures plus (GEFS+), which can manifest with typical absences (see Chapters 5 and 9).

Linkage of typical absences to several loci has been found in some cases, including 8q24, 15q14, and 6p. In one family, the dominant transmission of absences and other seizure types following febrile seizures in early life was observed within the frame-work of GEFS+ (Wallace et al., 2001) and was associated with a mutation of the γ-aminobutyric acid (GABA) receptor (see Chapter 20). However, the responsible
genes have not been cloned, and no linkage was found in a large number of cases.

Acquired factors may also play a role. Typical absence epilepsy may appear in children with brain lesions, and, at least in some, it is a result of the brain lesions (Ferrie et al., 1995). Perinatal difficulties, infections, or focal damage of undetermined origin are quoted as causes of typical absence epilepsy, but these are rarely proved. Cases of typical absence seizures apparently resulting from progressive brain lesions (Olsson and Hedström, 1991; Broughton et al., 1973), such as brain tumors (Farwell and Stuntz, 1984; Madsen and Bray, 1966) or neuronal lipidosis (Olsson and Hedström, 1991) are on record. Lesions in the mesial or orbital frontal cortex seem especially likely to produce absence seizures (Loiseau and Cohadon, 1970). Bancaud et al. (1974) showed that 3-Hz electrical stimulation of the mesial aspects of the frontal lobes can produce typical absence seizures in epileptic patients. The frequency of acquired brain damage in patients with typical absence attacks is poorly known, and it depends largely on the criteria that are used to define a lesion. Figures of up to 39% have been reported in some series (Bamberger and Matthes, 1959). Dalby (1969) found evidence of brain damage (as judged from the presence of neurologic antecedents, a low intelligence quotient [IQ], or interictal neurologic or pneumoencephalographic abnormalities) in 21% of patients with “pure petit mal,” in 37% of those with absences associated with automatisms, and in 58% of those with “focal petit mal.” Determining the exact significance of such abnormalities relative to strictly defined typical absence seizures is difficult, but they are rare in practice. However, localized brain damage undoubtedly may be a factor at the origin of typical absence. Olsson and Hedström (1991) found that 12 (10%) of 119 unselected children with typical absences had mental retardation and/or neurologic signs.

Typical absence epilepsy (petit mal in the restricted sense of the term) is regarded as the prototype of the primary or idiopathic generalized epilepsies in children (O’Donohoe, 1985; Gastaut et al., 1974b). The use of the term primary implies the absence of underlying brain damage as a cause of seizures (Gastaut, 1973). As was stated already, this absence is not constant.

The origin of the bilaterally synchronous 3-Hz discharge of typical absence epilepsy has received considerable attention (Coulter, 1995; Avoli and Gloor, 1994; Coulter et al., 1990; Gloor et al., 1990; Browne and Mirsky, 1983). A thalamocortical oscillatory system that includes neocortical neurons, the thalamic relay neurons, and neurons of the nucleus reticularis thalami seems to play a major role. GABAergic mechanisms are essential for the maintenance of the oscillations underlying the spike-wave discharges. The thalamic oscillation is dependent on the deactivation of a low calcium (Ca)²⁺ current that occurs when the membrane of the thalamic relay neurons is hyperpolarized (Gloor, 1995; Steriade et al., 1993). In addition to the mild hyperexcitability of the cortex, the excessively strong inhibition of the thalamic relay nuclei by the GABAergic reticular neurons results in the switching of the spindle-generating mechanism to the spike-wave mode (Gloor, 1995). The therapeutic role of ethosuximide is probably due to its decreasing effect on the low Ca T-current (Drinkenburg et al., 1991; Coulter et al., 1990).

Whatever the mechanisms of typical absence attacks, the study of which is beyond the scope of this book, one may consider the paroxysmal instability (in the corticoreticular system or any equivalent circuit) to be genetically determined or to be the result of diffuse pathologic processes involving the cortex or the deep structures implicated in the generation of typical absences.

CLINICAL AND ELECTROENCEPHALOGRAPHIC CHARACTERISTICS OF ABSENCE SEIZURES

Clinical Aspects

The most common and most typical symptomatology of absence epilepsy is that observed in childhood absence epilepsy (CAE), which can, therefore, be used as a paradigm for other syndromes. However, significant differences from this classic type may occur with other syndromes and ages at onset, and a variable course may be seen.

Simple Typical Absence

Simple absences in their most characteristic form in CAE are marked by a profound disturbance but not necessarily complete abolition of awareness, perception, responsiveness, memory, and recollection. Marked variability in the expression of absences may be observed even in the same child, and some patients may remember what they were told during the latter part of an absence. In most children, the impairment of consciousness is profound. When the absence is induced by hyperventilation with the eyes shut, eye opening occurs within the first 3 seconds of the absence
(Panayiotopoulos, 1998a; Duncan and Panayiotopoulos, 1995a). According to Lennox and Lennox (1960), 90% of simple typical absences last between 5 and 15 seconds, and absences lasting more than 30 seconds are rare, occurring in only 3% of patients with typical absence epilepsy. In 14% of patients, both brief and long absences may occur (Loiseau and Cohadon, 1970). Absences lasting less than 5 seconds may be difficult to detect. The onset of an attack is sudden, and the child’s ongoing activity is abruptly interrupted, with the child remaining motionless with a vacant stare. The eyes may drift upward, and slight beating of the eyelids at a rhythm of 3 Hz is common. The end of the attack is as sudden as its onset, and the patient returns to whatever activity he or she was engaged in at the onset of the seizure. Occasionally, a smile with a slightly dazed state is observed for 2 to 3 seconds, possibly indicating a very brief postictal phase (Gastaut and Broughton, 1972). This, however, is uncommon or hardly noticeable, and the lack of definite postictal confusion or fatigue is an essential clue for differentiating typical absences from complex partial seizures of limited expression (Holmes et al., 1987; Penry et al., 1975). The abruptness of both onset and termination is also important for distinguishing typical absences from atypical absences (Erba and Browne, 1983; Gastaut et al., 1974b).

In some typical absence attacks, the impairment of awareness is less profound, and the patient may be directly conscious of the time elapsed after the seizure, without external clues. Some responsiveness may be maintained, and, rarely, only confusion or mental clouding occurs with some memory of events (Browne and Mirsky, 1983; Mirsky and Van Buren, 1965). Only rarely in CAE is the degree of confusion so slight that it goes unnoticed by observers or even by the patient in the absence of specific tests. This occurs only in specific syndromes mostly seen in adults.

Typical absence seizures are of variable frequency. They are repeated several or dozens of times daily in a vast majority of children, but they may occur less frequently in other syndromes. Browne et al. (1983c), using telemetric EEG recording, recorded an average of about 100 seizures per day in 20 patients. In fact, attacks that do not recur daily rarely prove to be typical absences, and these should be accepted as such only with caution. The frequent occurrence of extremely brief “microabsences,” during which the state of consciousness may be almost impossible to assess, makes any precise evaluation of the number of attacks difficult.

Typical absences in children are almost always easily precipitated by hyperpnea, which is one of the most powerful means of confirming the diagnosis without danger.

Photic stimulation is said to induce typical absences in some patients (Roger and Genton, 1995; Loiseau and Cohadon, 1970; Dalby, 1969). The frequency and significance of photic sensitivity is quite variable among the various syndromes with absences (see “Electroencephalographic Aspects”). Photic stimulation, especially watching television at very close range, may be used for self-induction of absences in some patients (mostly adolescents or adults) (Harding and Jeavons, 1994).

A number of factors can facilitate or reduce the occurrence of typical absences. Spike-wave discharges and absences decrease in number when the child focuses his or her attention on a particular task, especially if it is pleasant (Guey et al., 1965, 1969; Lennox and Lennox, 1960). Playful activities have a similar effect, whereas more demanding tasks may increase the frequency of typical absences. Occasionally, typical absences appear selectively in specific activities, whether physical or intellectual (Senanayake, 1989), thus showing that not only the degree of attention but also more complex psychologic factors play a role in the provocation or inhibition of attacks (see Chapter 17).

Simple typical absences seem relatively uncommon. Penry et al. (1975) observed that only 34 (10%) of the 347 typical absence seizures they monitored belonged to that type. This was a referral series, however, so atypical cases were likely overrepresented.

Complex Typical Absence

In complex typical absence seizures, the impairment of consciousness is associated with other phenomena, motor or otherwise. These phenomena are often relatively minor and inconspicuous, so the disturbance of consciousness remains the essential feature. Motor components (Janz, 1969) are part of many absence attacks. An increase in muscle tone, especially in the posterior neck muscles, may occur. This may lead to retropulsion of the head and trunk. Some asymmetry is possible, with resultant gaze deviation and head rotation to one side (versive absences) (Janz, 1969). In typical absences, phasic muscle contractions are limited to clonic jerks of the eyelids that are occasionally accompanied by mild clonias of the deltoid muscles. Diminution of the muscle tone in muscles subserving posture is a common phenomenon during typical absence (Loiseau, 1992; Gastaut et al., 1974b), but its degree is usually mild, producing only a slight slump or causing patients to lose
objects they had in their hands. Hypotonia may result in intermittent or saccadic lowering of the head or arms that sometimes alternates with myoclonic jerks. Tonic loss rarely involves the lower limbs, with resultant falls or a mere sagging of the knees. However, 17% of the patients in the study by Dalby (1969) had atonic phenomena that, in 9%, were severe enough to cause the patient to fall.

Automatisms occur in a high proportion of typical absence seizures. De novo automatisms were present in 60% of the patients in the study by Penry et al. (1975) and in 55% of those in the study by Dalby (1969). Persistence of an action that has already been initiated is common, but the act is usually carried out imperfectly. Oral automatisms (e.g., licking, smacking, and swallowing) are extremely common, and simple gestural automatisms, such as crumbling or scratching movements, crossing the legs, carrying hands to the face, trying to take off the EEG electrodes, or fumbling with clothes, are also common. The patient may also mumble, sing, or utter incoherent words. The probability of automatisms occurring during an absence increases with the duration of the absence (Penry et al., 1975). Automatisms occur only when the loss of consciousness is severe, and they are not observed in patients with only mild impairment of awareness. Though automatisms are highly common in typical absence attacks, they are usually relatively minor in expression and different in character from those in complex partial seizures. Moreover, they stop abruptly at the same time as the EEG discharge, and they do not progressively merge with postictal automatisms and confusion, a frequent occurrence in partial attacks. Autonomic phenomena include changes in respiratory rhythms or apnea, pallor, heart rate modification, and mydriasis (Lennox and Lennox, 1960). Micturition occurs in 5% to 17% of patients (Loiseau and Cohadon, 1970; Janz, 1969; Holowach et al., 1962).

Complex absences are more common than the simple variety (Porter, 1992). However, very complex ictal phenomena are rarely observed; when they are, they are seen only in long-lasting absences and in absence status (see Chapter 16).

Only gold members can continue reading. Log In or Register to continue