Stereo-electroencephalography (SEEG) is an established diagnostic tool in identifying the epileptogenic zone in patients with periventricular nodular heterotopia (PVNH)-related drug-resistant epilepsy. The outcome of seizures after treatment with SEEG-guided radiofrequency thermocoagulation (RFTC) is variable in this patient group and the search for SEEG biomarkers that may improve treatment is ongoing. Our study shows that specific seizure-related SEEG changes in coagulated and non-coagulated contact pairs are associated with seizure outcome after RFTC in PVNH patients. Further prospective validation studies of our findings are indicated, as it could provide a biomarker for the successful targeting of RFTC in this difficult-to-treat patient population.