To resect or not to resect? Unbiased performances of single and combined biomarkers in intra-operative corticography for tailoring during epilepsy surgery

Abstract

Objective:Signal analysis biomarkers, in an intra-operative setting, may be complementary tools to guide and tailor the resection in drug-resistant epilepsy patients. Unbiased assessment of biomarker performances are needed to evaluate their clinical usefulness and translation. We defined a realistic ground-truth scenario and compared the effectiveness of different biomarkers alone and combined to localize epileptogenic tissue. Methods:We investigated the performances of univariate, bivariate and multivariate signal biomarkers applied to 1 minute inter-ictal intra-operative electrocorticography to discriminate between electrodes covering normal or pathologic activity in 47 drug-resistant people with epilepsy (temporal and extra-temporal) who had been seizure-free one year after the operation. Results:The best result using a single biomarker was obtained using the phase-amplitude coupling measure for which the epileptogenic tissue was localized in 16 out of 47 patients. Combining the whole set of biomarkers provided an improvement of the performances: 20 out of 47 patients. Repeating the analysis only on the temporal-lobe resections we reached a sensitivity of 93% (28 out of 30) combining all the biomarkers. Conclusion:We suggest that the assessment of biomarker performances on a ground-truth scenario is required to have a proper estimate on how biomarkers translate into clinical use. Phase-amplitude coupling seems the best performing single biomarker and combining biomarkers improves localization of epileptogenic tissue. However, sensitivity achieved is not adequate for the usage as a tool in the operation theater, but it can improve the understanding of pathophysiological process.

Relative entropy is an easy‐to‐use invasive electroencephalographic biomarker of the epileptogenic zone

“…18,19 To date, none of the proposed connectivity measures reached the sensitivity and specificity of HFOs on a systematic and representative data sample. 20,21 Another approach is to quantify the level of complexity of physiological signals, because disease degrades the physiological function and therefore decreases signal complexity. 22 Costa et al 23 suggest a multiscale entropy measure, which was successfully used to localize the seizure onset zone (SOZ) in the dataset of 13 pediatric patients with focal cortical dysplasia.…”

“…More recently, multiple studies reported altered connectivity patterns inside the EZ compared to the non‐EZ, suggesting functional connectivity as a promising new interictal biomarker 18,19 . To date, none of the proposed connectivity measures reached the sensitivity and specificity of HFOs on a systematic and representative data sample 20,21 …”