Cortical and etiological determinants of stimulation-induced seizures in children undergoing stereo-EEG

Electrical stimulation during stereo-electroencephalography (SEEG) is used for functional mapping and seizure induction in epilepsy surgery candidates. However, its effects in pediatric populations remain underexplored. The aim of this study is to characterize stimulation-induced seizures (SISs) in children undergoing SEEG and evaluate associations with stimulation parameters, cortical architecture, etiology, and surgical outcome.

We retrospectively analyzed 78 children with drug-resistant focal epilepsy (median age at epilepsy onset=2.8 years ± SD=4.4) who underwent SEEG with low-frequency (1-3 Hz) and/or high-frequency (50 Hz) stimulation. SISs were categorized as low-frequency seizures (LF-ISs) or high-frequency seizures (HF-ISs) and analyzed by anatomic site, cytoarchitectonics, cortical hierarchy, and etiology. Post-surgical outcomes were assessed using Engel classification.

SISs occurred in 43.6% of patients (LF-IS: 21.8%, HF-IS: 32.1%). Focal cortical dysplasia type II (FCD II)-particularly FCD IIb-was significantly associated with SISs (LFS: p = .016; HFS: p = .001). Interictal SEEG biomarkers such as brushes and suppression predicted SISs (p = .002). LF-ISs predominantly involved the orbitofrontal and insular regions, whereas HF-ISs clustered in the cingulate and central areas (p = .029). Stimulation type correlated with cortical hierarchy (p = .005) but not cytoarchitecture. SISs were marginally associated with favorable surgical outcome (Engel class Ia; p = .046).

This is the first study to systematically assess SISs in a pediatric cohort. Findings suggest that SISs-especially in FCD II and heteromodal cortical areas-may serve as biomarkers of epileptogenicity and predictors of surgical outcome. These insights can guide SEEG planning and interpretation in pediatric epilepsy surgery.