Lennox-Gastaut syndrome: potential mechanisms of cognitive regression

Lennox-Gastaut (L-G) syndrome is an intractable generalized epilepsy of childhood onset, associated with spike waves at a slow rate and paroxysmal fast activity. These epileptiform discharge patterns are thought to reflect excessive neocortical excitability and arise from neuronal and synaptic features peculiar to the immature central nervous system. The epileptic processes associated with L-G syndrome may lead to enduring patterns of abnormal activity and connectivity. These abnormal patterns compete with normal developmental mechanisms and may result in subsequent impairment and/or regression of cognition. Recurring or prolonged seizures themselves may also damage the brain. We hypothesize that the presence of slow spike waves diverts the brain from normal developmental processes toward seizure-preventing mechanisms. Adding to this burden, antiepileptic medications, sleep disruption, and social isolation all retard cognitive development and the learning process at a crucial time of brain maturation.