PubMed1995
The Landau-Kleffner syndrome (LKS) and the syndrome of continuous spike-and-wave discharges during slow sleep (CSWS) were originally described, and are still considered, separately. The former combines an acquired aphasia with spike-and-wave discharges that are activated by slow wave sleep, behavioural disturbances, and sometimes epileptic seizures. The latter is characterized by continuous spike-and-wave discharges during slow wave sleep, usually combined with global intellectual deterioration and epileptic seizures. These two syndromes share many common features: (i) onset during childhood; (ii) deterioration of cognitive functions that were previously normally acquired; (iii) seizure type; (iv) EEG pattern; (v) pharmacological reactivity; (vi) regression of the neuropsychological symptoms, of the EEG abnormalities and of the seizures before the end of adolescence; (vii) absence of obvious structural lesion detected by CT or MRI scan. Therefore, we postulated that these patients might, in fact, be presenting several facets of a single process associating the deterioration of cognitive functions and continuous spike-and-wave discharges during slow wave sleep. The pathogenesis of this syndrome remains unknown. Seven patients, presenting CSWS associated with neuropsychological deterioration (isolated aphasia, three cases; language disturbances with more widespread cognitive deterioration, three cases; isolated apraxia, one case) were studied using PET with [18F]fluorodeoxyglucose (FDG). We hoped to find metabolic arguments in favour of a unifying hypothesis, and to reveal clues as to pathogenesis. We present the retrospective analysis of 21 studies performed between 1986 and 1993, 12 of which were done during sleep. For three of these patients, follow-up studies were obtained until recovery. The metabolic patterns were very variable from one patient to another and in the same patient over time. Among the six patients studied during the active phase of the affection, our results showed unilateral, focal or regional increase in glucose metabolism of the cortex in five patients. This hypermetabolism was observed during sleep with continuous spike-and-wave discharges, but also persisted during wakefulness. In the last patient, the metabolic pattern was different: decreased regional glucose metabolism was observed during wakefulness, whereas during sleep, the metabolic pattern in the temporal areas varied during the course of the affection. After recovery, the metabolic pattern in four children (including the seventh patient) was either normal or showed focal or regional, uni- or bilateral decrease in cortical glucose metabolism. Despite this apparent disparity, four basic metabolic characteristics formed a common pattern in all patients, in line with our unifying postulate: (i) the metabolism of the cortical mantle was higher than in the subcortical structures, especially in the thalamic nuclei. This metabolic pattern is characteristic of an immature brain. (ii) The metabolic abnormalities involved focal or regional areas of the cortex. This finding is in good agreement with recent neurophysiological data suggesting a focal origin of the spike-and-wave discharges. (iii) The metabolic disturbances predominantly involved associative cortices. The pattern of neuropsychological deterioration is in good agreement with the topography of the disturbances of cortical glucose metabolism. (iv) The thalamic nuclei remained symmetrical despite significant cortical asymmetries, suggesting either that cortico-thalamic neurons do not participate in the generation of spike-and-wave discharges or that they are inhibited by the pathologic mechanisms. We hypothesize that the acquired deterioration of cognitive function with CSWS is caused by an alteration of the maturation of one or several associative cortices, primarily involving local interneurons and cortico-cortical associative neurons.