Therapeutic approaches targeting seizure networks

Abstract

Epilepsy is one of the most common neurological disorders, affecting over 65 million people worldwide. Despite medical management with anti-seizure medications (ASMs), many patients fail to achieve seizure freedom, with over one-third of patients having drug-resistant epilepsy (DRE). Even with surgical management through resective surgery and/or neuromodulatory interventions, over 50 $\%$ of patients continue to experience refractory seizures within a year of surgery. Over the past 2 decades, studies have increasingly suggested that treatment failure is likely driven by untreated components of a pathological seizure network, a shift in the classical understanding of epilepsy as a focal disorder. However, this shift in thinking has yet to translate to improved treatments and seizure outcomes in patients. Here, we present a narrative review discussing the process of surgical epilepsy management. We explore current surgical interventions and hypothesized mechanisms behind treatment failure, highlighting evidence of pathologic seizure networks. Finally, we conclude by discussing how the network theory may inform surgical management, guiding the identification and targeting of more appropriate surgical regions. Ultimately, we believe that adapting current surgical practices and neuromodulatory interventions towards targeting seizure networks offers new therapeutic strategies that may improve seizure outcomes in patients suffering from DRE.

Keywords: ablation; epilepsy; epilepsy networks; epilepsy surgery; neuromodulation; resection; seizure networks; seizures.

FIGURE 1

Functional (top left) and structural (bottom left) connectivity can identify seizure networks. Combining various imaging modalities can help locate relevant seizure network hubs, central areas of seizure network activity or communication, which can inform pre-surgical epilepsy planning (middle). Modification of current surgical techniques to more precisely target the identified epileptic network, such as through combined resection with neuromodulation, including the use of the Responsive Neurostimulation System (RNS), of additional seizure network foci (right).