The paradox of the paroxysm: can seizure precipitants help explain human ictogenesis?

An epileptic brain is permanently in a diseased state, but seizures occur rarely and without warning. Here we examine this paradox, common to paroxysmal diseases. We review the problem in the context of the prototypic acquired epilepsies of the medial temporal lobe. We ask how an epileptic temporal lobe differs from a healthy one and examine biological mechanisms that may explain the transition to seizure. Attempts to predict seizure timing from analyses of brain electrical activity suggest that the neurological processes involved may be initiated significantly before a seizure. Furthermore, whereas seizures are said to occur without warning, some patients say they know when a seizure is imminent. Several factors, including sleep deprivation, oscillations in hormonal levels, or withdrawal from drugs, increase the probability of a seizure. We ask whether these seizure precipitants might act through common neuronal mechanisms. Several precipitating factors seem to involve relief from a neurosteroid modulation of gamma-amino butyric acid receptor type A (GABAA) receptors. We propose tests of this hypothesis.