Magnetic resonance imaging ‐negative type II focal cortical dysplasia as a subtle form of bottom‐of‐sulcus dysplasia: Electrophysiological and histopathological evidence and treatment implications

OBJECTIVE: Magnetic resonance imaging (MRI)-negative type II focal cortical dysplasia (FCD) is challenging to localize and treat. Emerging evidence suggests that the sulcal bottom is the critical site of epileptogenicity. This study investigated whether MRI-negative type II FCD represents a subtle form of bottom-of-sulcus dysplasia (BOSD) and evaluated the safety and efficacy of sulcus bottom-targeted minimally invasive therapy. METHODS: Fifty-eight patients (mean age = 18.0 ± 10.0 years, range = 4-41) with drug-resistant epilepsy and MRI-negative scans were clinically diagnosed with FCD type II and included in the study. Of these, 27 met inclusion criteria for stereoelectroencephalographic (SEEG) analysis to compare interictal spike counts, high-frequency oscillation (HFO) counts, and epileptogenicity index (EI) values between sulcal bottom and nonbottom contacts. Histopathological analysis (n = 15) evaluated the spatial distribution of dysmorphic neurons (DNs) and balloon cells (BCs) using nonphosphorylated neurofilament (SMI32), phospho-S6 ribosomal protein (pS6), and Nestin immunoreactivity. An additional 19 patients received magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) targeting the sulcal bottom, with seizure outcomes and ablation coverage systematically evaluated. RESULTS: SEEG demonstrated significantly higher spike counts, HFOs, and EI values at sulcal bottom contacts than at nonbottom regions (all p < .0001), showing strong negative correlations with distance from the sulcal bottom (R = -.85 to -.68). Histopathology revealed a consistent spatial gradient, with DN density and diaminobenzidine intensity significantly enriched at the sulcal bottom across SMI32 and pS6 labeling (all p < .05). BCs, when present, were confined to the sulcal bottom. In the MRgLITT cohort, sulcus bottom-targeted ablation achieved seizure freedom (Engel IA) in 73.7% of patients, with a mean ablation coverage of 28.3% and no permanent neurological deficits. SIGNIFICANCE: MRI-negative type II FCD exhibits sulcus bottom-centered epileptogenicity, consistent with a subtle form of BOSD. These findings support sulcus bottom-targeted MRgLITT as a safe and effective minimally invasive therapy and provide a rationale for sulcus bottom-centered surgical planning in MRI-negative FCD II.