Brain maturational aspects relevant to pathophysiology of infantile spasms.

Infantile spasms (IS) are so typically associated with West syndrome that the term IS, properly referred to as a seizure type, is currently used synonymously with this severe infantile epilepsy. This chapter reviews some clinical and experimental observations relevant to IS pathophysiology with particular regard to maturational aspects that may account for IS age-related expression. Neither the cortical nor the brain stem generator hypotheses account for all the clinical features of IS. It is suggested that IS are generated whenever a cortical discharge is able to influence some archaic circuit located putatively in the brain stem through either an excitatory or a disinhibitory mechanism. This may occur with the highest probability during a developmental window in which IS typically occur, when N-methyl-D-aspartate (NMDA) transmission is particularly facilitated due a reduced sensitivity of NMDA receptors to the Mg2+ block. Interestingly, in this age range (0-18 postnatal day in rat), flexion spasms can be elicited experimentally by NMDA administration. These data provide an important key to further investigating IS pathophysiology, thus allowing us to design more effective strategies aimed at counteracting this harmful infantile epilepsy.