Invited Speaker

The Need for New Treatment Options in Refractory Epilepsy
Lieven Lagae
Belgium

Epilepsy remains the most frequent chronic neurological disorder and only 70-80% of patients is adequately controlled with the current anti-epileptic drugs (AEDs). Chronic use of anti-epileptic drugs often is associated with long term side effects (eg bone disease, effect on learning and memory,.). Newer therapies focusing on specific elements in the pathogenesis of epilepsy should be therefore be considered.

In recent years, several pathogenic mutations in the cellular excitatory/inhibitory networks associated with well defined epilepsy syndromes (eg SCN1A mutations in Dravet syndrome) have been described, but these fundamental insights have not yet led to more specific drugs for these syndromes. A notable example is the K+ modulating retigabine, which is currently being studied in neonatal epilepsy syndromes.

It also becomes clear that immune mediated processes are important factors in the generation of epileptic seizures and in the overall epileptogenic process. Mutations in pro-inflammatory components in epilepsy patients have been described. The success of steroid / ACTH and of intravenous immunoglobulins in certain refractory epilepsy syndromes illustrates the potential role of immunological treatments in epilepsy. Another successful approach is the ketogenic diet, targeting the basic energy brain systems. Modified ketogenic diets are also being offered to adults with less severe epilepsy.

Even more important is the insight that optimal treatment of seizures should not be a chronic treatment but a treatment-on-demand. Therefore, several closed loop systems are now being developed that detect the onset of seizures by automatic movement detection or continuous EEG monitoring and start an adequate treatment (such as temporary vagal nerve stimulation) at the onset of the seizure.

Only continuing creativity in bridging the gap between the increasing fundamental knowledge and clinically useful treatments ultimately will benefit the patients with chronic epilepsy.