Advanced Invasive Neurophysiological Methods to Aid Decision Making in Paediatric Epilepsy Surgery

Abstract

For patients with drug-resistant focal epilepsy, surgery is the most effective treatment to attain seizure freedom. Intracranial electroencephalogram investigations succeed in defining the seizure onset zone (SOZ) where non-invasive methods fail to identify a single seizure generator. However, resection of the SOZ does not always lead to a surgical benefit and, in addition, eloquent functions like language might be compromised. The aim of this thesis was to use advanced invasive neurophysiological methods to improve pre-surgical planning in two ways. The first aim was to improve delineation of the pathological tissue, the SOZ using novel quantitative neurophysiological biomarkers: high gamma activity (80–150Hz) phase-locked to low frequency iEEG discharges (phase-locked high gamma, PLHG) and high frequency oscillations called fast ripples (FR, 250–500Hz). Resection of contacts containing these markers were recently reported to lead to an improved seizure outcome. The current work shows the first replication of the PLHG metric in a small adult pilot study and a larger paediatric cohort. Furthermore, I tested whether surgical removal of PLHG- and/or FR-generating brain areas resulted in better outcome compared to the current clinical SOZ delineation. The second aim of this work was to aid delineation of eloquent language cortex. Invasive event-related potentials (iERP) and spectral changes in the beta and gamma frequency bands were used to determine cortical dynamics during speech perception and production across widespread brain regions. Furthermore, the relationship between these cortical dynamics and the relationship to electrical stimulation responses was explored. For delineation of pathological tissue, the combination of FRs and SOZ proved to be a promising biomarker. Localising language cortex showed the highest level of activity around the perisylvian brain regions with a significantly higher occurrence rate of iERPs compared to spectral changes. Concerning electrical stimulation mapping beta and high gamma frequency bands represented the most promising markers

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