Abstract Epilepsy is a common neurological problem.  It has a cumulative incidence of 3-4%.  Basic research aims to reveal the underlying causes of epilepsy so that more effective treatments and preeventative strategies can be developed.  This lecture is a brief progress report on the current state of epilepsy research.  There are over 40 different epileptic syndromes, but most fall into 2 broad groups:  symptomatic focal epilepsies and idiopathic generalized epilepsies.  An example from each group will be presented.

• Introduction
• video - complex partial seizures
• Epilepsy defined
• chronic, recurrent, spontaneous seizures
• epileptic syndromes
• idiopathic vs. symptomatic
• generalized vs. focal
• A focal symptomatic epileptic syndrome:  temporal lobe epilepsy
• clinical characteristics
• hippocampal sclerosis
• hypotheses of temporal lobe epileptogenesis
• A generalized idiopathic epileptic syndrome:  benign familial neonatal convulsions
• clinical characteristics
• genetic factors

 

Zinc-induced collapse of augmented inhibition by GABA in a temporal lobe epilepsy model ,  Buhl EH, Otis TS, Mody I, Science 1996 271:369-73.
Abstract In the kindling model of temporal lobe epilepsy, several physiological indicators of inhibition by gamma-aminobutyric acid (GABA) in the hippocampal dentate gyrus are consistent with an augmented, rather than a diminished, inhibition. In brain slices obtained from epileptic (kindled) rats,  the excitatory drive onto inhibitory interneurons was increased and was paralleled by a reduction in the presynaptic autoinhibition of GABA release. This augmented inhibition was sensitive to zinc most likely after a molecular reorganization of GABAA receptor subunits. Consequently, during seizures, inhibition by GABA may be diminished by the zinc released from aberrantly sprouted mossy fiber terminals of granule cells, which are found in many experimental models of epilepsy and in human temporal lobe epilepsy.
 

A potassium channel mutation in neonatal human epilepsy , Biervert C, Schroeder BC, Kubisch C, Berkovic SF, Propping P, Jentsch TJ, Steinlein OK, Science 1998  279:403-6.
Abstract Benign familial neonatal convulsions (BFNC) is an autosomal dominant epilepsy of infancy, with loci mapped to human chromosomes 20q13.3 and 8q24. By positional cloning, a potassium channel gene (KCNQ2) located on 20q13.3 was isolated and found to be expressed in brain. Expression of KCNQ2 in frog (Xenopus laevis) oocytes led to potassium-selective currents that activated slowly with depolarization. In a large pedigree with BFNC, a five-base pair insertion would delete more than 300 amino acids from the KCNQ2 carboxyl terminus. Expression of the mutant channel did not yield measurable currents. Thus, impairment of potassium-dependent repolarization is likely to cause this age-specific epileptic syndrome.
Supporting material for the Biervert paper.