Relative Entropy is an easy-to-use invasive EEG Biomarker of the Epileptogenic Zone

Travnicek V, Klimes P, Cimbalnik J, Halamek J, Jurak P, Brinkmann B, Balzekas I, Abdallah C, Dubeau F, Frauscher B, Worrell G, Brazdil M.

Epilepsia. 2023 Feb 10. doi: 10.1111/epi.17539. Epub ahead of print. PMID: 36764672.


21 Feb 2023

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Objective: High-frequency oscillations are considered among the most promising interictal biomarkers of the epileptogenic zone in patients suffering from pharmaco-resistant focal epilepsy. However, there is no clear definition of pathological High-frequency oscillations and the existing detectors vary in methodology, performance, and computational costs. This study proposes Relative Entropy as an easy-to-use novel interictal biomarker of the epileptic tissue.

Methods: We evaluated Relative Entropy and High-frequency oscillations biomarkers on intracranial EEG data from 39 patients with seizure-free postoperative outcome (Engel Ia) from three Institutions. We tested their capability to localize the epileptogenic zone, defined as resected contacts located in seizure-onset zone. The performance was compared using areas under the receiver operating curves [AUROC] and precision-recall curves [AUPRC]. Then we tested if a universal threshold can be used to delineate the epileptogenic zone across patients from different institutions.

Results: Relative Entropy in the ripple band (80-250Hz) achieved an average [AUROC] of 0.85. The normalized High-frequency oscillation rate in the ripple band showed an identical [AUROC] of 0.85. In contrast to High-frequency oscillations, Relative Entropy did not require any patient-level normalization and was easy and fast to calculate due to its clear and straightforward definition. One threshold could be set across different patients and Institutions because Relative Entropy is independent of signal amplitude and sampling frequency.

Significance: Although both Relative Entropy and High-frequency oscillations have a similar performance, Relative Entropy has significant advantages such as straightforward definition, computational speed, and universal inter-patient threshold making it an easy-to-use promising biomarker of the epileptogenic zone.

Keywords: SOZ localization; drug-resistant epilepsy; iEEG.

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