Mechanisms of genetic epilepsies

Abstract

Abstract Epilepsy is one of the most common neuro­logical disorders. As early as the time of Hip­pocrates (460-370 BC), it was reported on as the “holy disease”. Today it is known that an epileptic seizure is a consequence of synchro­nous discharges of neuronal populations in the brain, which abruptly and usually without an observable cause evoke involuntary be­havioural dysfunction or impaired conscious­ness. Epilepsies can have various causes and lead to extensive implications for the every­day life of affected patients. Up to 50% of all epilepsies are caused by genetic defects, in particular the so-called idiopathic epilep­sies, which occur without easily observable structural alterations in the brain. Genetical­ly caused dysfunctions of neuronal ion chan­nels play a central role in the formation of such epilepsies. The ion channels control the ion flux over the cell membrane of neurons and thus present the basis for the excitabili­ty of these neurons. Therefore, medications used in epilepsy treatment affect predomi­nantly ion channels. However, common an­ticonvulsants have limited success, not only because one third of epilepsy patients exhibit pharmacoresistance, but also because of the secondary effects which can dramatically af­fect their quality of life. Furthermore, current therapeutic approaches are mainly symp­tomatic and do not act on the epileptogenic mechanisms, which are still largely unknown. In this review article we will highlight the cur­rent main topics of our research on genetical­ly caused epilepsies, their pathomechanisms and therapeutic options.