Cellular Mechanisms of Interictal-Ictal Transitions

Much more is known about processes underlying development of interictal epileptiform discharge than about the mechanisms which convert such localized discharge into ictal episodes and facilitate the spread of epileptogenic activity through adjacent and distant brain regions. It seems reasonable to speculate that those mechanisms known to produce signal amplification and spread of activity in models of epileptogenesis are likely to be involved in interictal-ictal transitions. There are several prerequisites for such processes. First, some type of positive feedback sequence would be required so that increasing activity generated increases in excitability which in turn increased neuronal discharge. This might take place through augmentation of excitatory synaptic drives following use of the circuit (1); recurrent excitatory circuitry (2,3,4); a progressive depression in inhibitory electrogenesis during repetitive activation (5,6,7,8); or activation (inactivation) of membrane currents that are voltage-dependent, and may in some instances be modulated by agonists (9,10,11,12). Other potential positive feedback mechanisms include changes in extracellular microenvironment (13,14,15,16) and ephaptic interactions (17,18).