REGIONAL CEREBRAL GLUCOSE-METABOLISM IN CHILDREN WITH DETERIORATION OF ONE OR MORE COGNITIVE FUNCTIONS AND CONTINUOUS SPIKE-AND-WAVE DISCHARGES DURING SLEEP

The Landau-Kleffner syndrome (LKS) and the syndrome of continuous spik e-and-wave discharges during slow sleep (CSWS) were originally describ ed, and are still considered separately. The former combines an acquir ed aphasia with spike-and-wave discharges that are activated by slow w ave sleep, behavioural disturbances, and sometimes epileptic seizures. The latter is characterized by continuous spike-and-wave discharges d uring slow wave sleep, usually combined with global intellectual deter ioration and epileptic seizures. These two syndromes shave 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 s eizures before the end of adolescence; (vii) absence of obvious struct ural lesion detected by CT or MRI scan. Therefore, we postulated that these patients might, in fact, be presenting several facets of a singl e process associating the deterioration of cognitive functions and con tinuous spike-and-wave discharges during slow wave sleep. The pathogen esis of this syndrome remains unknown. Seven patients, presenting CSWS associated with neuropsychological deterioration (isolated aphasia, t hree cases; language disturbances with move widespread cognitive deter ioration, three cases; isolated apraxia, one case) were studied using PET with [F-18]fluorodeoxyglucose (FDG). We hoped to find metabolic ar guments in favour of a unifying hypothesis, and to reveal clues as to pathogenesis. We present the retrospective analysis of 21 studies perf ormed between 1986 and 1993, 12 of which were done during sleep. For t hree of these patients, follow-up studies were obtained until recovery . The metabolic patterns were very variable from one patient to anothe r and in the same patient over time. Among the six patients studied du ring the active phase of the affection, our results showed unilateral, focal or regional increase in glucose metabolism of the cortex in fiv e patients. This hypermetabolism was observed during sleep with contin uous spike-and-wave discharges, but also persisted during wakefulness. In the East patient, the metabolic pattern was different: decreased r egional glucose metabolism was observed during wakefulness, whereas du ring 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 sho wed focal or regional, uni- or bilateral decrease in cortical glucose metabolism. Despite this apparent disparity, four basic metabolic char acteristics formed a common pattern in all patients, in line with our unifying postulate: (i) the metabolism of the cortical mantle was high er than in the subcortical structures, especially in the thalamic nucl ei. 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 neurophysiologic al data suggesting a focal origin of the spike-and-wave discharges. (i ii) The metabolic disturbances predominantly involved associative cort ices. The pattern of neuropsychological deterioration is in good agree ment with the topography of the disturbances of cortical glucose metab olism. (iv) The thalamic nuclei remained symmetrical despite significa nt cortical asymmetries, suggesting either that cortico-thalamic neuro ns do not participate in the generation of spike-and-wave discharges o r that they are inhibited bq the pathologic mechanisms. We hypothesize that the acquired deterioration of cognitive function with CSWS is ca used by an alteration of the maturation of one or several associative cortices, primarily involving local interneurons and cortico-cortical associative neurons.