Origins of Temporal Lobe Epilepsy: Febrile Seizures and Febrile Status Epilepticus

Abstract

Temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS) commonly arise following early-life long seizures, and especially febrile status epilepticus (FSE). However, there are major gaps in our knowledge regarding the causal relationships of FSE, TLE, HS and cognitive disturbances that hamper diagnosis, biomarker development and prevention. The critical questions include: What is the true probability of developing TLE after FSE? Are there predictive markers for those at risk? A fundamental question is whether FSE is simply a marker of individuals who are destined to develop TLE, or if FSE contributes to the risk of developing TLE. If FSE does contribute to epileptogenesis, then does this happen only in the setting of a predisposed brain? These questions are addressed within this review, using information gleaned over the past two decades from clinical studies as well as animal models.

Zinc supplementation prolongs the latency of hyperthermia-induced febrile seizures in rats

“…Although simple FSs have a benign clinical course, focal and prolonged FSs may occasionally be associated with the later development of epilepsy and mesial temporal sclerosis (18). Much effort has been devoted to understanding FS pathogenesis, but little is known.…”

Status Epilepticus

“…These findings indicate that, in at least a proportion of cases, febrile SE can lead to hippocampal injury. It also suggests that the MRI can be a biomarker for those at high risk to develop subsequent hippocampal sclerosis and TLE (Gomes and Shinnar 2011;Patterson et al 2014). Interestingly, in the children whose baseline MRIs after febrile SE were read as normal, the hippocampi did not shrink.…”

“…Models of nonconvulsive SE (NCSE) are limited (Krsek et al 2001;Wong et al 2003;Arcieri et al 2014), and none of the currently available models replicate the key components of the form of NCSE that occurs in the ICU setting. SE can be induced using hyperthermia in young rats and mice; however, to date, this "febrile SE" model has been primarily used to study the epileptogenic process and not SE per se (Dube et al 2010;Patterson et al 2014).…”

“…Whether or not this is a causal association has been the subject of a long dispute (Shinnar 2003). In animal models of hyperthermic seizures in the immature brain, prolonged seizures of 60 min or more will cause development of TLE (Patterson et al 2014). In humans, retrospective series of patients with TLE undergoing evaluation for epilepsy surgery have found that 30% of these patients have a history of prolonged febrile seizures in childhood.…”

Novel Concepts in Epileptogenesis and its Prevention

“…Next, a series of papers dissect the mechanisms of epileptogenesis in each of the major epilepsy etiologies. This section on "mechanisms" is designed to take the "epileptogenesis" discussion to a deeper and more specific level, focusing it on the most frequent and/or challenging epilepsy syndromes, including hippocampal sclerosis, tackled by Patterson et al [6]; the development of epilepsy after head trauma, addressed by Pitkänen and Immonem [7]; and the defiant issue of epileptogenesis in "non-lesional" epilepsies, undertaken by Guerrini and Marini [8]. A separate article by Aronica and Crino [9] brings to the forefront the state-of-the-art understanding of epileptogenesis in developmental brain tumors and malformations of cortical development.…”