The etiological classification of the epilepsies: A brain network underpinning?

Objective: the current epilepsy classification is primarily clinical driven and lacks a mechanistic basis. A mechanistic basis of the classification, and within the classification especially the etiology layer, may help to better understand epilepsy and the associated comorbidities. It may also be helpful in guiding epilepsy treatment. With this study we aimed to investigate if there is a modelled mechanistic underpinning for the etiological epilepsy classification by assessing the association between epilepsy etiology and brain network topology. Methods: to that aim we assessed the association between epilepsy etiology and brain network topology. We included children referred to our outpatient first seizure clinic with suspected epilepsy who had a standard interictal EEG recording. From these EEGs, functional networks were constructed based on eyes-closed resting state time-series. Networks were characterized using measures of segregation, integration, centrality, and network strength. Principal component analyses were used to assess whether patients with epilepsy of similar etiology cluster together based on their functional brain network topology. Results: in total, 228 children with epilepsy were included. Another 402 children served as control subjects. We were not able to detect a correlation between epilepsy etiology and functional brain network topology. We also did not find a difference in brain network topology between the controls and patients with epilepsy. Conclusions: our results do not support the presence of a brain network underpinning for the etiological epilepsy classification. This may support the hypothesis that brain network abnormalities in epilepsy are a result of ongoing seizure activity rather than the epilepsy etiology itself. Further in-depth analyses of network measures and longitudinal studies are needed to confirm this hypothesis.