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Epileptogenesis refers to the processes by which epilepsy is established in a brain and ictogenesis, to the processes generating individual seizures in an epileptic brain. For a long while, our understanding of the latter has been very vague, especially considering those bilateral symmetrical seizures without apparent local onset, which have been termed 'generalized' [1]. Over the last decade, this situation has fundamentally changed in consequence of a series of findings with new and advanced investigations. These converge to shape a new understanding of generalized ictogenesis of which at least the contours have become apparent. It seems, therefore, timely to review these developments.
Early views of generalized ictogenesis
Historically, until long into the 19th and even 20th centuries, epilepsy was mostly considered as synonymous with 'Grand mal' seizures, that is, convulsive seizures with loss of consciousness and affecting the entire musculature, which are today called generalized tonic-clonic seizures (GTCS). Many possible causes were proposed, but the views on ictogenesis, that is, the generation of individual seizures in the brain, remained rather vague. When Hughlings Jackson became aware of the local cortical onset of some seizures, he did not consider these as a different category but defined epilepsy 'as a condition in which there is a sudden excessive transitory discharge of some part of the cortex' ([2], p. 9). However, his cooperation with the neurosurgeon, Victor Horsley, also gave rise to the concept of focal seizures and a surgically removable 'epileptogenous focus' ([2], p. 380).
A landmark event for the nosological understanding of the epilepsies was the advent of EEG, which revealed that, fundamentally, two types of epileptiform discharge existed. One type was consistently localized spikes or sharp waves at the anatomical site of origin of focal seizures (Figure 1). The other type was widespread bilateral symmetric and quasi-synchronous trains of spikes followed by a slow wave (the Spike-and-slow wave pattern) in rhythmic repetition at a frequency of mostly 3-3.5 Hz (Figure 2). The impression on the scalp EEG that this spike-wave (SW) pattern involved the entire convexity gave rise to calling it a generalized discharge. In consequence, the seizures and epilepsies for which this pattern were characteristic (including minor seizure types like absences and brief bilateral myoclonic jerks without impairment of consciousness) came now also...