Epileptogenesis

Abstract

Epileptogenesis is a chronic process that can be triggered by genetic or acquired factors, and that can continue long after epilepsy diagnosis. In 2015, epileptogenesis is not a treatment indication, and there are no therapies available in clinic to treat individuals at risk of epileptogenesis. However, thanks to active research, a large number of animal models have become available for search of molecular mechanisms of epileptogenesis. The first glimpses of treatment targets and biomarkers that could be developed to become useful in clinic are in sight. However, the heterogeneity of the epilepsy condition, and the dynamics of molecular changes over the course of epileptogenesis remain as challenges to overcome.

Figure 1.

Definitions of epileptogenesis. (A) Previously, epileptogenesis was considered to be represented by the latent period, which has been defined as the time between the precipitating insult and the occurrence of the first unprovoked clinical seizure. Thus, the temporal development of acquired epilepsy was previously considered to be a step function of time. (B) More recently, based on several experimental and clinical observations, epileptogenesis is now considered to extend beyond the latent period, which is still defined as the time from the precipitating injury and the first clinical seizure. However, the observations that subconvulsive seizures may well have occurred before the first clinical seizure and that seizure frequency and severity progressively increase over time both indicate the epileptogenesis can continue indefinitely (based on data from Williams et al. 2009 and Kadam et al. 2010).

Figure 2.

Development of epilepsy after status epilepticus (SE) (Hesdorffer et al. 1998), stroke (Graham et al. 2013), and traumatic brain injury (TBI) (Annegers et al. 1998) in humans. Note the similarity in the rate of epileptogenesis after severe TBI, stroke (average of different types of stroke) (Graham et al. 2013), and acute symptomatic seizure (AsS) without SE.