Optimization of surgical intervention outside the epileptogenic zone in the Virtual Epileptic Patient (VEP).

Sora An,Maxime Guye,Fabrice Bartolomei,Viktor Jirsa,Daniele Marinazzo

doi:10.1371/journal.pcbi.1007051

Abstract

Studies to improve the efficacy of epilepsy surgery have focused on better refining the localization of the epileptogenic zone (EZ) with the aim of effectively resecting it. However, in a considerable number of patients, EZs are distributed across multiple brain regions and may involve eloquent areas that cannot be removed due to the risk of neurological complications. There is a clear need for developing alternative approaches to induce seizure relief, but minimal impact on normal brain functions. Here, we develop a personalized in-silico network approach, that suggests effective and safe surgical interventions for each patient. Based on the clinically identified EZ, we employ modularity analysis to identify target brain regions and fiber tracts involved in seizure propagation. We then construct and simulate a patient-specific brain network model comprising phenomenological neural mass models at the nodes, and patient-specific structural brain connectivity using the neuroinformatics platform The Virtual Brain (TVB), in order to evaluate effectiveness and safety of the target zones (TZs). In particular, we assess safety via electrical stimulation for pre- and post-surgical condition to quantify the impact on the signal transmission properties of the network. We demonstrate the existence of a large repertoire of efficient surgical interventions resulting in reduction of degree of seizure spread, but only a small subset of them proves safe. The identification of novel surgical interventions through modularity analysis and brain network simulations may provide exciting solutions to the treatment of inoperable epilepsies.

Highlights

Epilepsy is a chronic neurological disorder that is defined by the occurrence of repetitive unexpected seizures
We focus on deriving effective alternative methods for those cases where epileptogenic zone (EZ) are inoperable because of issues related with neurological complications
Surgical intervention is generally accepted as an effective method to control drug-resistant seizures, only about 10% of patients might be considered candidates for surgery [6] because EZs are often located in multiple brain regions simultaneously and involve eloquent areas, which are defined as brain regions where damage causes neurological complications such as language, memory and motor problems [13]

Summary

Introduction

Epilepsy is a chronic neurological disorder that is defined by the occurrence of repetitive unexpected seizures. Surgical intervention is generally accepted as an effective method to control drug-resistant seizures, only about 10% of patients might be considered candidates for surgery [6] because EZs are often located in multiple brain regions simultaneously and involve eloquent areas, which are defined as brain regions where damage causes neurological complications such as language, memory and motor problems [13]. Several alternative methods including multiple subpial transection, which could prevent neuronal synchronization in the EZ without altering normal functions by severing horizontal intracortical fibers while preserving vertical fibers in the eloquent cortex, have been tried for patients who are unsuitable for conventional surgery, but with variable results [13,14,15]. The alternative method must be 1) effective in seizure reduction, 2) able to provide flexible options depending on the inoperable EZ or technically inaccessible region for surgery, and 3) have minimal impact on normal brain functions

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Discussion

Conclusion