Targeting interictal low-entropy zones during epilepsy surgery predicts successful outcomes in pediatric drug-resistant epilepsy.

Objective: Approximately 40% of children undergoing epilepsy surgery have postoperative seizures, underscoring the need for enhanced estimators of the epileptogenic zone (EZ). We hypothesize that visually imperceptible low-entropy activity in the interictal periods, even in the absence of conventional spikes, is a robust signature of the EZ. To test this, we mapped interictal "low-entropy zones" using intracranial electroencephalography (iEEG) in children with drug-resistant epilepsy (DRE) and assessed their value for postsurgical outcome prediction when targeted during surgery, along with their stability over prolonged periods.

Methods: We analyzed iEEG data of 75 DRE children, including brief (5 min) data from patients with known Engel outcome (N = 59; used for outcome prediction) plus prolonged data from a separate recent cohort (N = 16; used for stability assessment). We estimated each contact's entropy across various frequencies (delta to fast-ripple), pinpointed low-entropy zones, and assessed whether their removal predicts outcome (3-fold cross-validation). In addition, the predictive value of entropy during non-epileptiform (spike-free) epochs was also assessed. Furthermore, established interictal estimators (spikes-on-ripple, fast ripples) were tested for outcome prediction. Using the prolonged dataset, we tested whether entropy distribution over brief epochs was similar to prolonged (3 h) data.

Results: High overlap between low-entropy zones and resection correlated with low Engel class (p < 0.0001, R = -0.54, N = 59), also during non-epileptiform epochs (R = -0.52). Low-entropy-zone removal predicted outcomes with F1 score of 87% (p < 0.0001, N = 51; Engel I vs III-IV) outperforming spikes-on-ripple (F1 score = 82%, p = 0.002) or fast ripples (F1 score = 80%, p = 0.01). Low-entropy zones retained high predictive value when non-epileptiform epochs were used (F1 score = 89%, N = 44). Entropy distribution over brief epochs was strongly correlated with prolonged data (R > 0.8, p < 0.0001), and its relationship with seizure-onset zone did not differ (brief vs prolonged data: p > 0.6).

Significance: Surgically targeting low-entropy zones accurately predicts the postoperative seizure outcomes of children with DRE. Mapping low-entropy activity using brief iEEG segments shows consistency with using prolonged data and could enhance surgical planning in pediatric DRE.