Regional cerebral glucose metabolism in children with deterioration of one or more cognitive functions and continuous spike-and-wave discharges during sleep

Abstract

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 a...

18F-FDG PET Reveals Frontotemporal Dysfunction in Children with Fever-Induced Refractory Epileptic Encephalopathy

“…Hypometabolic areas in FIRES are also consistent with neuropsychologic findings, as previously reported in other epilepsy conditions: low cognitive functioning with the extent and bilaterality of frontal hypometabolism (36), language disorders with external temporal involvement and, particularly, receptive troubles with posterior parietotemporal hypometabolism (37), behavior disorders with orbitofrontal hypometabolism, and major sociocognitive troubles with bilateral hypometabolism of the superior temporal gyrus (according to PET findings in autistic children (38)). A quite similar network has been identified in children with aggressive behavior (39).…”

An in computo investigation of the Landau-Kleffner syndrome

“…A large majority of authors agree on the fact that the main EEG characteristic in LKS is consituted by highamplitude spike-waves, organized in various foci, with a predominence over temporal and parieto-occipital areas (Beaumanoir, 1992;Maquet et al, 1995).…”

“…The waking EEG shows focal, multifocal or bilateral spike-wave discharges, the topography of which fluctuates with time (Maquet et al, 1995). These spike-wave discharges increase during slow-wave sleep and may become continuous.…”

Frontal Lobe Epilepsies: Neuropsychological and Behavioral Consequences in Children

“…There are also reports of bizarre behavior (Kyllerman et al, 1996;Morikawa et al, 1995), emotional lability, anxiety and phobia (Morikawa et al, 1995), and of autistic-like behavior (Bulteau et al, 1995;Kyllerman et al, 1996), although a case of CSWS with autistic regression is a rare occurrence: McVicar et al (2005) conducted a retrospective review of children with language regression studied at their Institute for more than 12 years, finding that only 10 children had ESES, only one of whom had a history of autism and language regression. Some works report a deterioration of language with a tendency toward expressive aphasia with lexical and syntactic difficulties, and a generally preserved comprehension (Debiais et al, 2007;MacAllister & Schaffer, 2007), learning difficulties at school, poor reasoning and short-term memory deficits (De Negri et al, 1997;Tassinari et al, 1992;, and also motor impairments, such as ataxia, dystonia and dyspraxia (Maquet et al, 1995;Tassinari et al, 2000). Roulet-Perez et al (1993) reported clinical manifestations suggestive of a poor functioning in skills correlated to executive functions.…”