Page 11 - scheppingen

GENERAL INTRODUCTION & OUTLINE OF THE THESIS
Epilepsy
Epilepsy is one of the most common chronic neurological disorders, affecting more than 50 million people worldwide 1. According to the definition proposed by the International League Against Epilepsy (ILAE) in 2005, epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiological, cognitive, psychological, and social consequences of this condition 2. This definition is usually practically applied as having two unprovoked seizures more than 24 hours apart. In 2014, the ILAE accepted recommendations of a taskforce altering the practical defi- nition for special circumstances that do not meet the two unprovoked seizures criteria 3. The taskforce proposed that epilepsy is defined by any of the following conditions: (1) at least two unprovoked (or reflex) seizures occurring more than 24 hours apart; (2) one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years; (3) diagnosis of an epilepsy syndrome 3. Furthermore, it was recommended not to use the term “disorder”, since it implies a functional disturbance, not necessarily lasting; whereas the term disease may (but not always) convey a more lasting derangement of normal function. In addition, the term “disorder” is poorly understood by the public and minimizes the serious nature of epilepsy. The ILAE and the International Bureau for Epilepsy (IBE) have recently agreed that epilepsy is best considered to be a disease 3. An epileptic seizure is defined as a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain 3, 4. The most common medical management of epilepsy consists of pharmacotherapy with a wide range of antiepileptic drugs (AEDs) in order to suppress seizures. Until now, AEDs that can prevent or cure epilepsy do not exist. Besides the fact that the use of AEDs is asso- ciated with adverse effects, including cognitive impairment, which becomes particularly inimical when chronically used by patients 5-7, one of the main problems is that about 30% of all epilepsy patients do not adequately respond to AEDs and continue to expe- rience debilitating refractory seizures. These patients are classified as having drug-re- sistant epilepsy 8-10, a diagnosis with poor prognostic implications that include physical injury, psychosocial dysfunction, reduced quality of life, and stigmatization of affected individuals 11. Furthermore, drug-resistant epilepsy costs in Europe exceed €15-20 billion per year 12, 13. Drug-resistant epilepsy is defined as an epilepsy that fails to achieve seizure freedom following adequate trials of two tolerated and appropriately chosen and used AED schedules 8-10. Patients with drug-resistant epilepsy have a very low, only 3%, prob- ability to respond to additional AEDs. An alternative therapy for a subset of patients with drug-resistant epilepsy is high-frequency stimulation of the vagus nerve, deep brain regions (via depth electrodes) or cortical areas (via subdural electrodes or through tran- scranial magnetic stimulation) 14, 15. Although this leads to symptom relief in part of the patients, there are still patients that suffer from uncontrolled seizures 14, 16. For only a few, carefully selected drug-refractory patients surgical removal of the seizure onset zone is an alternative to get symptom relief. However, resection does not necessarily lead to seizure freedom, depending on the etiology and natural history of the epilepsy, and candidates for surgery should have a distinct seizure focus and a good prospect for resection of the indicated region without significant cognitive or neurological deficits 17-20. Another option is the ketogenic diet, which consists of an excessive amount of fat
9
one