Neuroimaging and neuropathology of Dravet syndrome

Abstract

Brain magnetic resonance imaging (MRI) studies in patients with Dravet syndrome and SCN1A mutations have shown abnormal findings in a small minority of patients. The origin of the structural abnormalities--such focal brain atrophy, cortical dysplasia, and hippocampal sclerosis--observed in some children remains unclear. There seems to be no correlation between the presence of MRI abnormalities and duration of epilepsy, age at seizure onset, or the frequency of episodes of status epilepticus having occurred early in life. Recent descriptions of Rasmussen syndrome and of the hemiconvulsion-hemiplegia syndrome in isolated patients with SCN1A mutations are of uncertain meaning but might indicate that co-occurring immunomediated or seizure-induced structural changes can, in turn, become a substrate for the severe epileptic encephalopathy. The few available neuropathologic studies of Dravet syndrome have provided inconsistent findings, including evidence of subtle brain malformation. However, the underlying dysfunction of the SCN1A gene might confer to the brain a unique profile of vulnerability whose consequences are not easily disclosed by neuropathology and require specific experimental settings to be fully appreciated. There would seem to be value in studies in animal models of these aspects, as well as prospective studies in humans, with a particular view to establishing if earlier diagnosis and efforts at seizure control may influence the development of any clinical, imaging, or pathologic deterioration.