Is epilepsy a progressive disorder? Prospects for new therapeutic approaches in temporal-lobe epilepsy

During the past decade, it has become apparent that neural circuits undergo activity-dependent reorganisation. In pathological disorders with recurring episodes of excessive neural activity, such as temporal-lobe epilepsy, brain circuits can undergo continual remodelling. For clinical practice, seizure-induced remodelling implies that after a diagnosis of epilepsy, recurring seizures can cause continuing neural reorganisation and potentially contribute to progressive severity of the epilepsy and to cognitive and behavioural consequences. The alterations induced by seizures include neuronal death and birth, axonal and dendritic sprouting, gliosis, molecular reorganisation of membrane and extracellular-matrix proteins, and intermediates involved in cellular homoeostasis. These changes are influenced by genetic background and seizure type, thus identification of genetic risk factors should be a priority. Therapeutic modification of seizure-induced molecular and cellular responses offers new opportunities for intervention beyond seizure suppression.