Thesis defense Valerio d'Amore (Donders series 222)

8 June 2016

Promotors: prof. dr. E. van Luijtelaar, prof. dr. F. Nicoletti

copromotors: dr. C. van Rijn, dr. R. Ngomba

The role of group I metabotropic glutamate receptors in absence epilepsy

Epilepsy is a chronic disease of the brain characterized by an enduring predisposition to generate epileptic seizures (Fisher et al., 2014). This disease largely influences the patient’s life. It is one of the most common neurological disorders requiring long-term health care contact (Forsgren, 1992; Sander et al., 1996). Worldwide approximately 50 million people have epilepsy (Banerjee, 2009). One in 26 people will develop epilepsy during their lifetime (Hesdorffer et al., 2011).
Epilepsy is an expression of various brain disorders – not only a single disease. Consequently, any investigations or treatment needs to be individualized. The epilepsies represent a heterogeneous group of disorders with different electrographic, etiologies, behavioural and seizure patterns. In 1985, the first concept of epileptic syndromes was brought into consideration. Etiology was only ever mentioned briefly in the 1969, 1981, and 1989 International League Against Epilepsy (ILAE) classifications of seizures and syndromes, as well as later publications (Gastaut, 1969; Luders et al., 2004). In the 1989 classification of epilepsies, these classes were given: localization-related epilepsies and syndromes, generalized epilepsies and syndromes, epilepsies and syndromes, undetermined whether focal or generalized, and special syndromes. In its 2010 report the last ILAE Commission confined its revisions to “new terminology and concepts” instead of “proposing a new classification (in the sense of organization) of epilepsies.”
This outmost current ILAE definition states that: “Epilepsy is a disorder of the brain characterized by an enduring predisposition to arise epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition. In this current classification from 2010 the terms “symptomatic”, “idiopathic” and “cryptogenic” have been changed by “structural-metabolic”, “genetic” and “unknown” but they do not list etiologic categories any further (see Table 1 middle panel) (Berg et al., 2010).
Epilepsy should primary be classed according to etiology, succeed by a narration of the semiology of the seizure. However, this current classification has also been criticized and authors have deliberated the necessity for a more up-to-date way to the grouping of epileptic seizures and epilepsies (Luders et al., 2012).
In clinical practice the diagnosis of epilepsy is founded on the clinical history and physical inspection. However, it is important to get a detail picture of the seizure’s semiology as possible. Ictal symptoms, i.e. symptoms during the seizures, particularly at onset, are determined by the localization of seizure foci. Moreover, it is also significant to evaluate differential diagnoses like syncope, arrhythmia and non-epileptic seizures, since a wrong diagnosis of epilepsy is often common (Chadwick et al., 2002). Interictal electroencephalogram (EEG) can provide information about the diagnosis of epilepsy, although a normal EEG cannot exclude the diagnosis of epilepsy.