Fever, febrile seizures and epilepsy

Abstract

Seizures induced by fever (febrile seizures) are the most common type of pathological brain activity in infants and children. These febrile seizures and their potential contribution to the mechanisms of limbic (temporal lobe) epilepsy have been a topic of major clinical and scientific interest. Key questions include the mechanisms by which fever generates seizures, the effects of long febrile seizures on neuronal function and the potential contribution of these seizures to epilepsy. This review builds on recent advances derived from animal models and summarizes our current knowledge of the mechanisms underlying febrile seizures and of changes in neuronal gene expression and function that facilitate the enduring effects of prolonged febrile seizures on neuronal and network excitability. The review also discusses the relevance of these findings to the general mechanisms of epileptogenesis during development and points out gaps in our knowledge, including the relationship of animal models to human febrile seizures and epilepsy.

Figure 1

Comparison of latency to seizure onset and of hyperventilation in two established rodent models of experimental febrile seizures [11,13,46]. In the first model (shown in fuchsia), which uses a hair-dryer to emit a warmed stream of air, seizures commence within 2.9 ± 0.1 min after the initiation of the heating procedure. Increase of temperature is rapid, rising from 33.4 ± 0.16 °C to 40.74 ± 0.13 °C (the seizure-threshold temperature) in 2.9 min, with little change in respiratory rates: 161.8 ± 2.6 (n = 12) at baseline and 166.9 ± 4.9 during the minute preceding seizure onset [p = 0.37 versus baseline (values in the graph are shown as mean ± SEM; derived from [31,46]). In the second model, in which rats are placed in a heated chamber, seizures commence approximately 31 min after initiation of the heating procedure, when body temperature rises from 33.4 ± 0.9 to 41.8 ± 0.7 °C. Respiratory rate begins to increase significantly approximately 15 min into the procedure and the increased respiratory rate over approximately 15 min before the onset of the seizures promotes brain alkalosis (derived from [11]).