Pathogenesis of Lennox-Gastaut syndrome: considerations and hypotheses.

No other epilepsy more substantially combines cryptogenicity and intractability than does Lennox-Gastaut Syndrome. Although antecedent neurological conditions have preceded LGS in some patients, others with similar ills fail to develop this syndrome, and precise charting of the pathway between any presumed aetiology and the epilepsy has eluded researchers. Despite these frustrations, LGS has elicited a host of publications over the years, possibly because it combines features of many other epileptic disorders and thereby occupies a crossroads position among them. Lacking a comprehensive experimental model of LGS, this article combines relevant data from several clinical and basic sources in order to formulate a concept of pathogenesis. Data are presented to suggest that the occurrence of factors enhancing excitability during a vulnerable period of cortical and thalamic development may permanently imprint a bilateral, diffuse epileptogenic system upon the mammalian brain.