Landau-Kleffner Syndrome and Syndrome of Continuous Spike-Waves of Slow Sleep

SYNDROME OF EPILEPTIC APHASIA WITH SEIZURE DISORDER

Since Landau and Kleffner (1957) described six children who developed aphasia after apparently normal acquisition of language, the association of unusual types of aphasia with electroencephalographic (EEG) abnormalities and, often, a seizure disorder has been recognized as a specific syndrome.

The Landau-Kleffner syndrome (LKS) is currently defined as an acquired childhood aphasia with mainly bitemporal paroxysmal EEG abnormalities, a seizure disorder without demonstrable focal brain lesions, and a regression or stabilization of the disease after a variable time (Tassinari et al., 2002). Even though cases with paroxysmal EEG recordings but no seizures are not epilepsy in the strictest sense, they are covered in this chapter because they do not differ in any other way from the most common cases with clinical attacks. The EEG abnormalities are often very marked, and they tend to increase during slow sleep, often producing continuous spike-waves of slow sleep (CSWS), also termed electrical status epilepticus of sleep (ESES), thus suggesting a close relationship between LKS and the “syndrome of CSWS.” (In this chapter, for the sake of clarity, the terms CSWS and ESES are used to designate the EEG abnormalities, and CSWS syndrome refers to the electroclinical picture.)

Before onset, the affected children have normal motor and intellectual development, and their language is at a normal level for their age. The language disturbances develop over a relatively brief period. The loss of acquired language is usually total or profound, but nonverbal skills are generally completely or at least relatively preserved. Behavioral disturbances of various types can be observed in up to two-thirds of patients (Tassinari et al., 2002; Deonna, 1991; Sawhney et al., 1988; Dugas et al., 1982), and persistance of the aphasia is not rare (Beaumanoir, 1992; Paquier et al., 1992; Deonna, 1991; Dulac et al., 1983a). The epilepsy tends to remit before adulthood. All patients consistently display paroxysmal EEG abnormalities that commonly are bilateral and that often have a predominantly temporal or posterior location. Clinical seizures are experienced by 75% to 85% of patients at some time, although they do not necessarily appear at the very beginning of the disorder. The course is initially progressive, but fluctuations, stabilization, or improvement of speech may occur over the years, although long follow-up is available for only a few cases.

Cases of temporary aphasia following unilateral status epilepticus, as well as postictal aphasia occurring in association with certain types of transient attacks, particularly brief complex partial seizures, probably belong to different epilepsy syndromes, so these are not considered here (see Chapters 10 and 16).

At least 248 publications on this topic have appeared in the last 32 years (Panayiotopoulos, 1999), and the syndrome is diagnosed increasingly often (Beaumanoir, 1992; Paquier et al., 1992). Not all patients with acquired aphasia associated with seizure disorder display the same clinical, EEG, and evolutive features, which suggests the possibility of subgroups within the syndrome and raises the question of the criteria used to define the syndrome.

Etiologic Data

Reported cases of the syndrome of acquired epileptic aphasia indicate that its onset occurs between 18 months (Uldall et al., 2000) and 13 years of age. In most, the onset is between 4 and 7 years of age, with three-fourths of the cases appearing before the age of 7 years. Late-onset cases have been reported, however (Dugas et al., 1995).

Among affected patients, males are more preponderant than females. Beaumanoir (1992) found 98 boys and only 59 girls. Most patients appeared normal before the onset of the syndrome. Extensive studies have failed to detect an identifiable cause. By definition, no evidence of structural brain pathology is found. However, a few cases with similar presentations,
including the same intense EEG anomalies, and a focal lesion have been recorded; these may, in fact, be due to the same epileptic mechanism, which, in these cases, is initiated by a lesion instead of being purely “functional” (Galanopoulou et al., 2000; Cole et al., 1988; Lou et al., 1977). Worster-Drought (1971) suspected an inflammatory cause, but no positive data are available to support this hypothesis. Lou et al. (1977) reported inflammatory infiltrates in a biopsy specimen of temporal lobe in a patient with Landau syndrome. Their findings, however, were not entirely convincing. No organic cause was demonstrated in another patient submitted to brain biopsy (McKinney and McGreal, 1974), and the computed tomographic (CT) and magnetic resonance scan results are almost always normal. Positron emission tomography (PET) studies have variably shown areas of hypometabolism or hypermetabolism (Maquet et al., 1990). Pascual-Castroviejo et al. (1992) found abnormal arteriograms in four patients, and they considered these individuals to have arteritis that was limited to the central nervous system. They claimed that they had obtained excellent results with the combined use of steroids and calcium-entry blockers. However, the significance of these findings has been disputed (Deonna, 1991). One case of neurocysticercosis associated with LKS has also been recorded (Otero et al., 1989).

Epilepsy Characteristics and Electroencephalographic Abnormalities

Seizures

Seizures are the first manifestation of the syndrome in about 60% of patients. In the remaining patients, aphasia is the first manifestation, and 17% to 25% of the patients with this syndrome do not have clinical attacks (Gordon, 1997c; Beaumanoir, 1992; Dulac et al., 1983a; Deonna et al., 1977). The frequency of seizures is quite variable; many patients have one or few fits, and others may have several attacks daily. The seizures do not represent a major problem, and episodes of status epilepticus seem unusual (Deonna et al., 1977). The attacks, which may be either diurnal or nocturnal, are often well controlled by drug treatment (Mantovani and Landau, 1980). A precise description of the seizures in 44 patients (Beaumanoir, 1992; Dulac et al., 1983a) indicated that 19 had partial motor seizures with or without generalization that, at times, was followed by Todd paralysis; 7 had complex partial seizures; 7 had atypical absences, often with atonia of head; and 17 had generalized motor attacks, which often were the first epileptic manifestation (Bureau et al., 1995a). Facial and ocular myoclonias have also been mentioned (Morrell et al., 1995; Dulac et al., 1983a), but tonic seizures have not been reported. In most patients, the seizures seem to remit before adulthood (Beaumanoir, 1992; Dulac et al., 1983a; Mantovani and Landau, 1980). In exceptional cases (Cole et al., 1988), the epilepsy persists into adult life and represents a major problem, at times necessitating surgery.

Neurophysiologic Abnormalities

EEG abnormalities, by definition, are present in all patients. The background rhythms are usually normal, but slow waves in the theta range are occasionally present in the same regions as the spikes. The repetitive spikes or sharp waves or spike-wave complexes of high amplitude are generally bilateral, but, frequently, they are prevalent over the temporal and parietal regions (Beaumanoir, 1992; Hirsch et al., 1990; Dulac et al., 1983a; Shoumaker et al., 1974; Gascon et al., 1973). They rarely, if ever, involve the anterior temporal areas (Deonna et al., 1977). Contrary to expectations, the paroxysms predominate over the right hemisphere as often as they do over the left, and, when they are unilateral, they may shift from side to side.

The paroxysmal activity is usually predominant over the temporal areas (Beaumanoir, 1992). A striking feature in most cases is the variability of the EEG abnormalities with regard to time and intensity. Nakano et al. (1989) used brain-mapping techniques to study the topographic features of the discharges. Using the methohexital-suppression test, Morrell et al. (1995) demonstrated that spikes on one side always anticipated those on the contralateral side by 20 to 40 ms, thus suggesting that one hemisphere has a leading role. Magnetoencephalography has confirmed that the spikes originate on the dorsal surface of the superior temporal gyrus (Paetau et al., 1999). Other investigators also showed that the spikes could interfere with the auditory evoked responses (Seri et al., 1998; Isnard et al., 1995), which strongly implicates the auditory cortex in the genesis of the epileptic activity.

Multifocal discharges are common, and the spike or sharp-wave foci may resemble those observed in benign partial epilepsy of childhood (Dulac et al., 1983a; Billard et al., 1981). In keeping with this, the frequency and intensity of discharges often are considerably augmented in slow sleep. Massa et al. (2000) compared
the EEG features in seven children with LKS with those of seven other children with benign rolandic epilepsy and suggested that some patterns, including the presence of unilateral slow-wave foci, bilateral independent spike-waves discharges, and an increase of spike-wave discharges by more of 40% in the first sleep cycle, were predictors of the continuous paroxysms. In slow sleep, a prominent increase is often seen in the activity of spike foci that is accompanied by the disappearance of the landmarks of sleep (Billard et al., 1990; Kellerman, 1978), an aspect reminiscent of that of the so-called ESES or CSWS (Billard et al., 1981, 1990; Hirsch et al., 1990). However, some investigators (Giovanardi Rossi et al., 1999; Genton et al., 1990b; Tiberge et al., 1988) have noted that the paroxysmal activity may continue during rapid eye movement (REM) sleep in patients with the LKS, in contrast with its disappearance at this stage in cases of “electrical status epilepticus of slow sleep,” and they have suggested that this might differentiate the two syndromes. The EEG abnormalities tend to subside with increasing age. Dulac et al. (1983a) noted that they had disappeared by the age of 15 years in 17 of 18 adolescents.

Characteristics of Language Disturbances

The typical language disturbance in epileptic aphasia is a marked deficit of auditory comprehension, which differs from the usual features of the more common aphasias of childhood. This may be so profound that many of the children are initially considered deaf. Indeed, a disturbed understanding of language is often the first manifestation, and the progressive disappearance of spoken language follows, apparently as a consequence of the receptive disturbance (Kaga, 1999; Paetau et al., 1991; Billard et al., 1990; Hrachovy et al., 1979). Kaga (1999) suggested that the language disorder evolves in a systematized manner, beginning with sensory aphasia, followed by auditory agnosia and finally by word deafness. The full deficit evolves over weeks or even months, although an abrupt onset or a sudden aggravation following the occurrence of a seizure has been reported in some cases (Dugas et al., 1982; Deonna et al., 1977; Shoumaker et al., 1974). In at least some patients, the disturbance in auditory gnosia appears to extend beyond the verbal field. These children are not able to recognize other sounds, such as the cries of animals or other familiar sounds. The tonal audiograms are, however, normal, indicating that the defect is an inability to decode sounds, which is a necessary step in language understanding (Rapin et al., 1988). The affected children understand little or no spoken language, and, consequently, their verbal expression deteriorates. Their visual-verbal abilities, on the other hand, may be remarkably well preserved and they can be taught to lip read and write quite well. However, errors in reading and spelling are not uncommon. Auditory inattentiveness is present in some patients, who may have difficulties localizing the origin of a sound (Beaumanoir, 1983).

Some cases of fluent aphasia (Lerman et al., 1991; Rapin et al., 1977), as well as the use of jargon (Mantovani and Landau, 1980; Rapin et al., 1977; Landau and Kleffner, 1957), have been reported. Paraphasias, asyntaxia, and verbal stereotypies are common in those children who are not completely mute, and such abnormalities may lead to a misdiagnosis of autism or psychosis (Dugas et al., 1982). The difficulties may extend to written language, although this is affected less than verbal expression is. All patients, however, do not have the same type of language disturbance. Dugas et al. (1982) found that, in 6 of 77 patients, the aphasia was predominantly expressive, and Deonna et al. (1977, 1982) has emphasized the complexity of the problem and the likelihood of diverse mechanisms being at play in different cases.

The authors’ personal experience also indicates great variability in the language disturbance. In some children, the expressive component of language is more affected than is auditory gnosia, which was also the case in two of the original patients of Landau and Kleffner. One of our patients (Chevrie-Muller et al., 1991) had very marked expressive and repetition difficulties, and her EEG abnormalities were also atypical, with continuous spike-waves in wakefulness and in sleep on some tracings that did not have a clear relationship to the phasic disturbances.

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