White matter integrity and cerebral network topology in focal epilepsy

Worldwide more than fifty million people suffer from recurrent spontaneous seizures. Seizures are considered to be harmful to the brain and may have adverse long-term behavioral and cognitive consequences in particular in people with focal epilepsies that do not respond to pharmacotherapy. Characterization of seizure related brain damage may provide knowledge to better comprehend the mechanisms underlying the poorly understood comorbidities often encountered in patients with focal epilepsy. In the studies described in the thesis ‘White matter integrity and cerebral network topology in focal epilepsy’ we focused on the characterization of spatiotemporal changes in brain tissue integrity distant from a focal epileptogenic zone and on concomitant modifications of functional connectivity and network topology. In addition, we studied whether this information could improve diagnostic work-up. We i) systematically reviewed and meta-analyzed existing MRI studies in patients with temporal lobe epilepsy, ii) conducted serial structural and functional MRI in two focal epilepsy rat models, from which we identified the remote cerebral consequences using measures of white matter microstructural integrity, white matter volumetry, hippocampal morphometry and functional connectivity and network configuration and iii) developed and validated a diagnostic prediction model based on EEG network topology in children suspected of focal epilepsy. Our data indicates that recurrent seizures in focal epilepsy causes wide-spread structural pathology both in human and rodent brain white matter and hippocampus. These changes in structural integrity relate to altered functional connectivity and global brain network topology. In addition, we found functional EEG network features to improve the predictive power in focal epilepsy diagnosis. Longitudinal prospective cohort studies with repetitive structural and functional measurements are needed to substantiate our novel experimental findings and to reveal the exact seizure-related mechanisms that underlie cerebral damage in focal epilepsy and its clinical consequences.