Secondary epileptogenesis is a theory that hypothesizes that uncontrolled seizures in people with epilepsy lead to the development of new sites of seizure onset. This process has often been cited when people experience a new seizure type after a period of poor seizure control. The theory proposes that repeated seizures induce changes in regions of the brain that are regularly recruited into the seizure. These hypothetical changes can then lead to a new, independent seizure onset zone. The concept is based on a number of clinical observations which secondary epileptogenesis could explain. However there are alternative explanations from the clinic as well as from the laboratory that call the process into question. In this review some of the observations that have been used to support the theory will be reviewed, and the many counterarguments will be presented. At this time there is little evidence to support secondary epileptogenesis and much to refute it.

The hypotheses that hippocampal GABAB receptor dysfunction is a long-lasting consequence of early-life seizures, and its dependence on genetic background, were tested. Two strains of rats bred to be prone (FAST) or resistant (SLOW) to amygdala kindling were used. On postnatal day (PND) 10, control rats were injected with saline, and seizure rats with kainic acid to induce status epilepticus (SE) for 2 h. A significantly lower dose of kainic acid was found to induce SE in FAST as compared to SLOW rats. Population excitatory postsynaptic potentials (pEPSPs) and population spikes (PSs) were recorded in CA1 of hippocampal slices of adult rats in vitro, following stimulation of stratum radiatum. Input-output relation of the single-pulse pEPSP and PS did not show a significant difference between seizure and control rats, sex, or strain (FAST and SLOW). Paired-pulse PSs were significantly enhanced at 10-50 ms interpulse intervals, in FAST seizure male rats compared to FAST male controls, but not in other groups. In adult FAST but not SLOW rats, significantly lower suppression of pEPSPs at 250-300 ms following heterosynaptic burst stimulation was found in seizure rats compared to control rats; the heterosynaptic suppression of the pEPSP was blocked by selective GABAB receptor antagonist CGP55845A. The results provide evidence that an early-life SE has a long-lasting effect in decreasing GABAB receptor-mediated presynaptic inhibition in the hippocampus, in FAST but not in SLOW rats.