Global and Intertuberal Epileptic Networks in Tuberous Sclerosis Based on Stereoelectroencephalographic (sEEG) Findings: A Quantitative EEG Analysis in Pediatric Subjects and Surgical Implications

Abstract

INTRODUCTION Recent evidence favors a network concept in tuberous sclerosis complex (TSC) with seizure generation and propagation related to changes in global and regional connectivity between multiple, anatomically distant tubers. Direct exploration of network dynamics in TSC has been made possible through intracranial sampling with stereoelectroencephalography (sEEG). The objective of this study is to define epileptic networks in TSC using quantitative analysis of sEEG recordings. METHODS Intracranial sEEG recordings were obtained from pediatric patients who presented with medically refractory epilepsy secondary to TSC and subjected to quantitative signal analysis methods. Cortical connectivity was quantified by calculating pairwise coherence between all contacts and constructing an association matrix. The global coherence, defined as the ratio of the largest eigenvalue to the sum of all the eigenvalues, was calculated for each frequency band (delta, theta, alpha, beta, gamma). Spatial distribution of the connectivity was identified by plotting the leading principal component (product of the largest eigenvalue and its corresponding eigenvector). RESULTS Four pediatric subjects with TSC underwent invasive intracranial monitoring with sEEG, comprising 31 depth electrodes and 250 contacts, for localization of the epileptogenic focus and guidance of subsequent surgical intervention. Quantitative connectivity analysis revealed a sustained increase in global coherence during the ictal period in the beta/low gamma (14-30 Hz) and high gamma (31-80 Hz) bands. Our results corroborate findings from existing literature, which implicate higher frequencies as a driver of synchrony and desynchrony. Late delta activity was noted in the postictal period. CONCLUSION Epileptic networks, characterized by coordinated high frequency activity in the beta/low gamma and high gamma bands define the ictal period in TSC. This time-dependent increase in global coherence demonstrates evidence for intratuberal, intertuberal, and perituberal connectivity in TSC. These findings have surgical implications for targeted laser ablation or surgical resection of tubers.