The role of quantitative markers in surgical prognostication after stereoelectroencephalography

Abstract

Objective: Stereoelectroencephalography (SEEG) is the reference method in the presurgical exploration of drug-resistant focal epilepsy. However, prognosticating surgery on an individual level is difficult. A quantified estimation of the most epileptogenic regions by searching for relevant biomarkers can be proposed for this purpose. We investigated the performances of ictal (Epileptogenicity Index, EI; Connectivity EI, cEI), interictal (spikes, high-frequency oscillations, HFO [80-300 Hz]; Spikes × HFO), and combined (Spikes × EI; Spikes × cEI) biomarkers in predicting surgical outcome and searched for prognostic factors based on SEEG-signal quantification.

Methods: Fifty-three patients operated on following SEEG were included. We compared, using precision-recall, the epileptogenic zone quantified using different biomarkers (EZ_q ) against the visual analysis (EZ_C ). Correlations between the EZ resection rates or the EZ extent and surgical prognosis were analyzed.

Results: EI and Spikes × EI showed the best precision against EZ_c (0.74; 0.70), followed by Spikes × cEI and cEI, whereas interictal markers showed lower precision. The EZ resection rates were greater in seizure-free than in non-seizure-free patients for the EZ defined by ictal biomarkers and were correlated with the outcome for EI and Spikes × EI. No such correlation was found for interictal markers. The extent of the quantified EZ did not correlate with the prognosis.

Interpretation: Ictal or combined ictal-interictal markers overperformed the interictal markers both for detecting the EZ and predicting seizure freedom. Combining ictal and interictal epileptogenicity markers improves detection accuracy. Resection rates of the quantified EZ using ictal markers were the only statistically significant determinants for surgical prognosis.

Figure 1

Example of the epileptogenic zone quantification using ictal and interictal epileptogenicity markers. Quantified ictal and interictal stereoelectroencephalography (SEEG) data of a patient suffering from drug‐resistant epilepsy associated with a left temporal lateral ganglioglioma are shown. The epileptogenic zone (EZ) defined by visual analysis included the left anterior T1 (perilesional cortex sampled by the electrode T′, just posteriorly to the lesion) up to Heschl gyrus, the temporal pole, the amygdala, and the anterior hippocampus. The resection of these structures sparing the hippocampus led to seizure freedom (Engel class I). (A) Ictal markers. The maximal Epileptogenicity Index (EI, left panel) and Connectivity EI (cEI, middle panel) values quantified from two spontaneous seizures are represented as spheres on the patient's 3D brain mesh with implanted electrodes. Right panel: Graph showing epileptogenicity values quantified for each contact within the gray matter using EI (blue) and cEI (yellow); EI energy ratio is shown in red. The EZ defined by EI (EI ≥0.41) includes the left anterior T1 (T′1‐3) and the left anterior hippocampus (TB′1‐2). The EZ defined by cEI (cEI ≥0.65) includes the left anterior T1 (T′1‐3) and the left posterior T1 with adjacent superior temporal sulcus (H′14‐16). B. Interictal markers. Left and middle panels: the maximal normalized Spike‐ and high‐frequency oscillations HFO (HFO, 80–300 Hz) rates quantified using Delphos detector are shown on the patient's 3D brain mesh. Right panel: Graph showing the spike– (black) and the ripple (orange) rates/min quantified for each contact from a 5‐min period of NREM sleep. The EZ defined by Spikes (Spikes ≥0.48) includes the left anterior T1 (T′1‐4), the left posterior T1 and superior temporal sulcus (H′12‐16), the left anterior hippocampus (TB′1‐3) and the right rhinal cortex (TB1‐2). The EZ defined by HFO (HFO ≥0.38) includes the left anterior hippocampus, the left anterior T2 (TB′10‐11), the left F3 pars opercularis (OF′11‐12) and the right rhinal cortex (TB1‐2).

Figure 2

Performances of SEEG biomarkers as compared to clinical gold standard. Precision (A) and Recall (B) for the quantified EZ using Spikes, HFO, cEI, EI, Spikes × HFO, Spikes × EI, and Spikes × cEI versus clinically defined EZ in the whole cohort of 53 operated patients. Spikes × EI showed the best precision against the clinical analysis. The cEI and spike × EI demonstrated the best sensitivity.

Figure 3

The extent of EZ resection in seizure‐free versus non‐seizure‐free patients. Percentage of resected epileptogenic contacts as defined by ictal (EZ_EI; EZ_cEI), interictal (EZ_Spikes, EZ_HFO, EZ_spikes × HFO), and combined ictal–interictal (EZ_spikes × EI, EZ_spikes × cEI) markers as well as by visual analysis (EZc) comparing the seizure‐free and the non‐seizure‐free group. The EZ resection rates were significantly higher in seizure‐free than in non‐seizure‐free patients for the EZ quantified by ictal markers; the same trend was present for the combined markers and the EZc, while the resection rates of EZ quantified using interictal markers did not differ depending on surgical outcome.

Figure 4

Correlation between the EZ resection rate and surgical prognosis according to Engel class. The EZ resection rate was significantly correlated with prognosis according to Engel class for the EZ quantified using EI (A) and Spike × EI (B). The same trend was observed for the EZ quantified by cEI (C) but not for the EZ quantified by spikes (D), nor for the HFO or visual analysis (not shown).