Insights into the pathophysiology of psychomotor regression in CSWS syndromes from FDG‐PET and EEG‐fMRI

Abstract

SUMMARYEpilepsy syndromes with continuous spikes-andwaves during slow sleep (CSWS) are age-related epileptic encephalopathies characterized by the development of various types of psychomotor regression in close temporal concordance with the appearance of the electroencephalography (EEG) pattern of CSWS. Functional cerebral imaging studies performed in children with CSWS have shown evidence for the existence of increase in metabolism or perfusion at the site of the epileptic focus, associated with decrease in metabolism or perfusion in distant and connected brain areas. Longitudinal [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) studies and effective connectivity analyses have suggested the existence of a pathophysiologic link between increases and decreases in metabolism/perfusion that could be explained by the theory of remote inhibition. These findings highlight that the psychomotor regression observed in CSWS syndromes is not only related to the neurophysiologic impairment at the site of the epileptic foci but also to epilepsy-induced neurophysiologic changes in distant connected brain areas. KEY WORDS: Continuous spikes-and-waves during slow sleep, [18F]-Fluorodeoxyglucose, Positron emission tomography, EEG combined fMRI, Remote inhibition, Surrounding inhibition.Epilepsy syndromes with continuous spikes-and-waves during slow sleep (CSWS) are age-related epileptic encephalopathies characterized by the development of various types of psychomotor regression in close temporal concordance with the appearance of the electroencephalography (EEG) pattern of CSWS (Tassinari et al., 2000). This EEG pattern consists of sleep-related activation and diffusion of spike-wave (SW) discharges, usually during more than 85% of non-REM (rapid eye movement) sleep (Tassinari et al., 2000). A minority of CSWS cases have been associated with cortical or thalamic lesions (symptomatic cases), whereas in the other cases, the etiology is unknown (De Tige et al., 2006). In some of the latter cases, the existence of a continuum ranging from asymptomatic carriers of centrotemporal spikes to epilepsies with CSWS is suspected (De Tige et al., 2006).Epilepsy syndromes with CSWS are characterized by an acute phase defined by the emergence of psychomotor deficits, various types of seizures, and CSWS activity at around 3-8 years of age (Holmes & Lenck-Santini, 2006). This acute phase is followed by a recovery phase in which the patient's clinical condition improves together with the remission of the CSWS pattern. Recovery spontaneously occurs at around 15 years of age but it may be prompted by using antiepileptic drugs (AEDs) including corticosteroids (Holmes & Lenck-Santini, 2006). This biphasic evolution suggests that CSWS activity largely contributes to the psychomotor deficits observed in these patients (Holmes & Lenck-Santini, 2006). However, some authors still consider CSWS activity as an epiphenomenon reflecting the underlying brain pathology, rather than the direct cause of the psychomotor regression (Aldenkamp & Arend...

Neuropsychological impairment in early-onset hydrocephalus and epilepsy with continuous spike-waves during slow-wave sleep: A case report and literature review

“…suggested, basing on functional cerebral imaging studies, cognitive impairment in children with CSWS may also be related to neurophysiological changes in far brain areas connected with the site of EEG foci. [14] We suggest that serial neuropsychological assessments should be performed, during the follow-up, in patients with early-onset hydrocephalus and CSWS to test and verify the cognitive and behavioral pattern that we found in our case.…”

Optimizing statistical parametric mapping analysis of 18F-FDG PET in children

“…Based on young adults as controls, the results are not univocal. De Tiege et al did succeed detecting areas of remote inhibition in children aged 5 to 11 years with a particular epileptic encephalopathy and to see them vanish when epilepsy and cognitive deficits recover [24,39,40]. Some authors showed a high SPM performance (86%) for correct localization of the seizure onset zone in adolescents (12 to 15 years) [26], but others achieved a rate of only 13% in children from the age of 3 [14].…”

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

“…They usually extend beyond the epileptic focus and may involve distant areas connected to it (25,30). An EEG-functional MRI approach proved that such widespread hypometabolism resulted from both surrounding and remote inhibition, which might sustain the neuropsychologic impairment (34,35).…”