A pathogenetic hypothesis of temporal lobe epilepsy

Temporal lobe epilepsy is the most common type of epilepsy in adults. It frequently develops in previously normal nervous tissue, secondary to trauma, tumour or stroke. The disease has a tendency to progress toward generalization and neurologic deficits. The pathogenesis of temporal lobe epilepsy is still unclear. In this article, a hypothesis is proposed suggesting that a cascade of biological events may underlie its development and progression. These include increased excitatory amino acid release, NMDA receptor activation, influx of calcium into neurones, activation of calcium-dependent enzymes (including phospholipase A2), immediate early gene expression, and synthesis of new proteins. Positive and negative feedback loops as well as other events, taking place in parallel, are also hypothesized. The clinical and pharmacological ramifications of this working hypothesis are discussed.