Does etiology really matter for epilepsy surgery outcome?

Multiple factors influence the outcomes of epilepsy surgery. Prognostic indicators varying from clinical characteristics, imaging findings, ictal, and interictal electrophysiological activity have been linked to surgical outcomes. In this review, we focus on the relatively under-studied role of the underlying epilepsy histopathology in driving post-surgical outcomes, specifically focusing on the broad categories of seizure outcomes and cognitive outcomes. For each of these two outcomes of interest, we answer two questions: 1)- does etiology matter? and 2)- how could it matter? The goal is to review the existing literature on the relationship between etiology and surgical outcomes to provide the best possible judgment as to whether a causal relationship exists between histopathology and the ultimate surgical outcome as an initial step. Then, we delve into the possible mechanisms via which such relationships can be explained. We conclude with a call to action to the epilepsy surgery and histopathology research community to push the mechanistic understanding of the pathology-outcome interaction and identify actionable knowledge and biomarkers that could inform patient care in a timely fashion.