3 - Genetic models of the epilepsies

Summary

Introduction

The normal human brain can produce seizures upon stimulation with a convulsant drug or an electrical current. This capacity of intact brain is not, however, tantamount to epilepsy. Rather, the disease occurs in response to a multifaceted etiology in which genetically determined ‘seizure susceptibility factors’ play a crucial role. Therefore, seizuretriggering mechanisms may be activated in epileptic patients by potentially unrecognized variations in intrinsic neuronal activity or by input from environmental stimuli that do not cause seizures in normal people. The complex pathophysiological interplay between combinations of these various factors determines the seizure disorder that will be exhibited by a given patient.

The genetic animal models of the epilepsies fill a special niche in epileptology because they provide the means for examining questions relating to the fundamental mechanisms of seizure predisposition. They can also be used to investigate the mechanisms by which seizures occur, as can neurologically normal animals. Seizures can be initiated in almost all mammals, including neurologically normal humans. Humans with epilepsy, however, are neurologically distinctive: they exhibit seizures in response to stimuli that do not cause such episodes in normal human subjects.