New presurgical techniques to characterize the focus of epilepsy

Patients with focal epilepsy who do not respond to anti-epileptic medication can be eligible for epilepsy surgery, which might cure this disabling disease. However, the question is which brain tissue is epileptogenic and needs to be removed. Information on the epileptogenic zone can be obtained by seizure semiology, EEG, MRI and other techniques. When we know in which region to search, depth or subdural electrodes can be implanted to record the irritative and seizure onset zone. Recently a zone with high frequency oscillations (HFOs, >80 Hz) has been added which promises better correlation to the epileptogenic zone. The aims of this thesis were to study the added clinical value of new non-invasive techniques and of invasive techniques revealing HFOs, improve our understanding of the patholophysiology and improve our understanding of what matters most to the patients. Epilepsy is a complex disease which makes characterization of a focus difficult: spikes and seizures are probably end-products rather than the cause of epilepsy, the pathophysiology is a complex not-uniform process and the disease is considered focal, but probably a whole epileptogenic network gets involved. The value of non-invasive techniques is related to localization of the suspected focus. In temporal lobe epilepsy, nasopharyngreal electrodes show spikes from mesial origin and two reviewers instead of one will optimally recognize lesions on MRI. Ultimately, EEG-fMRI and MEG might yield extra information. In extra-temporal epilepsy, MEG can help localize the irritative zone, 3 Tesla MRI, more than 1.5 Tesla, can show small abnormalities and EEG-fMRI can clarify other ambiguities. We can improve non-invasive techniques with knowledge on source distribution, reducing artefacts, lowering subjectivity and focussing on changes preceding spikes and seizures. The time has come to study HFOs clinically. Centers have different approaches towards intracranial recordings. In Utrecht the settings are fit to record HFOs intra-operatively, because corticography is performed during most operations. The relation between HFOs, spikes and seizures remains puzzling. On tissue and brain network level, spikes and seizures have most in common, while HFOs and seizures respond similar to external influences. It is striking that seizures occur after an increase in HFOs, spikes increase after seizures and HFOs decrease after spikes. The future of epilepsy surgery lies in a patient-based approach, in combing different methods and to share knowledge between basic research and clinical experience and between centers worldwide.