From a First Seizure to Chronic Epilepsy – A Structural and Functional Study
Doctoral thesis
Date of Examination:2025-01-16
Date of issue:2025-01-23
Advisor:Prof. Dr. Niels K. Focke
Referee:Prof. Dr. Niels K. Focke
Referee:Dr. Igor Kagan
Sponsor:CONAHCYT
Sponsor:DAAD
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Description:PhD thesis
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Abstract
English
Diagnosing epilepsy after a first unprovoked seizure is challenging, especially in patients without detectable lesions on standard magnetic resonance imaging (MRI) and without interictal epileptiform discharges (IEDs) in the electroencephalogram (EEG). In such cases, more expensive and time-consuming evaluations like sleep-deprived EEG or prolonged EEG/video-EEG monitoring may be necessary. However, misdiagnosis rates in adults still range from 5% to 26%, often leading to delayed or inappropriate pharmacological treatment. This highlights the need for new tools and methods to improve the accuracy and promptness of epilepsy diagnosis. While functional connectivity (FC) and diffusion tensor imaging (DTI) have shown promise in identifying patterns across various epilepsy syndromes, research has predominantly focused on chronic cases. There is a significant lack of studies examining brain changes associated to a first unprovoked seizure, which is crucial for understanding epileptogenesis and improving diagnosis and treatment. This dissertation presents three studies addressing the structural and functional brain changes that occur in association to a first unprovoked seizure, prior to an epilepsy diagnosis. Study I retrospectively evaluated source-space low-density EEG-derived metrics—power and the imaginary part of coherency (ImCoh)—from non-lesional, IED-free, unmedicated patients after a first unprovoked seizure, comparing them with healthy controls. We further investigated whether specific differences in these metrics existed between patients who developed epilepsy and those who remained seizure-free for at least six months. Study II was a prospective analysis where we employed DTI to determine if patients who developed epilepsy within a one-year follow-up exhibited distinct patterns of white matter alterations compared to those who did not. We also evaluated patients with chronic epilepsy. In Study III, utilizing the same cohort as in Study II, we used source-reconstructed high-density EEG power and ImCoh to evaluate untreated, non-lesional patients after a first unprovoked seizure without visible IEDs. We compared those who developed epilepsy to those who did not and assessed network differences among first-seizure patients, chronic idiopathic generalized epilepsy (IGE) patients, chronic non-lesional focal epilepsy patients, and healthy controls. Overall, this dissertation fills a critical knowledge gap regarding brain changes associated with a first unprovoked seizure. It provides insights into the early stages of epileptogenesis and highlights how structural and functional connectivity patterns differ among patients at various stages of epilepsy, both among themselves and compared to healthy controls. These findings pave the way for further research into the potential use of brain functional connectivity and diffusion changes as biomarkers for epilepsy development.
Keywords: first seizure; epilepsy; functional connectivity; electroencephalography; diffusion tensor imaging