Chapter 59 - Innovative treatments for epilepsy: radiosurgery and local delivery

Abstract

Despite the advent of numerous new antiepileptic drugs (AEDs) and the more widespread use of epilepsy surgery and vagus nerve stimulation, a significant number of epilepsy patients, estimated to be approximately 30%, continue to have seizures. This provides the impetus for the development of innovative treatments. This chapter will cover radiosurgery and local drug delivery as promising therapeutic avenues for patients with refractory epilepsy. In patients not amenable for resective epilepsy surgery, in addition to multiple subpial transection or electrostimulation, stereotactic radiosurgery or radiotherapy can be considered as a possible treatment option. Using the approach of radiosurgery selective destruction of epileptic tissue is performed, whereas in focal stereotactic therapy functional modulation of epileptic tissue with preservation of important function is considered. Local delivery of epilepsy-modifying compounds are particularly interesting for partial epilepsies in which an epileptic focus can be determined that is responsible for the generation and/or spread of epileptic seizures. Currently, both partial and primary generalized epilepsy are treated with drugs that are administrated systemically one or more times per day. Because AEDs also have an effect on other physiological systems than the epileptic brain region, treatment with AEDs is prone to side-effects. Furthermore, about 25% of patients are medically refractory. One of the underlying causes for this “refractoriness” is insufficient bioavailability of the AEDs at the regions responsible for the seizures. Focal treatment of the epileptic region is a strategy in which bioavailability of the antiepileptic compound is enhanced in the epileptic regions while nonspecific side-effects of the treatment are reduced. Despite the fact that many conceptual and practical hurdles have to be overcome, local delivery may be a promising therapeutic strategy for treating refractory partial epilepsy patients in whom classic routes of AED administration (oral, rectal, parenteral) do not lead to proper seizure control and/or induce severe side-effects.