IntroductionPeriventricular nodular heterotopias (PVNH) are developmental abnormalities with neurons abnormally clustered around the cerebral ventricles. Patients frequently present with focal drug-resistant epilepsy (DRE). However, the relationship between PVNH and the seizure onset zone (SOZ) is complex.Stereo-electroencephalography (SEEG) is an invasive diagnostic procedure for patients with DRE. In selected patients, the SEEG may be converted into a therapeutic procedure, lesioning the probable (SOZ) with pulsed radiofrequency thermocoagulation (RFTC). The aim of our study was to evaluate the efficacy and safety of SEEG-RFTC in a series of DRE patients with PVNH. MethodsTwenty-four patients with focal DRE related to PVNH and treated with SEEG-guided-RFTC restricted to nodules were prospectively collected between 2016 and 2023 and retrospectively analyzed after a follow-up of at least 12 months. ResultsSeventeen patients (71 %) responded (ILAE class 1–4) after SEEG-guided RFTC of whom eleven (46 %) became seizure-free (class 1) at last follow up, nine (45 %) despite residual PVNH tissue on MRI. SEEG seizure onset was restricted to PVNH in eleven patients (class 1 in 45 %) and simultaneously in PVNH and other cortical areas in thirteen patients (class 1 in 46 %). Out of 31 SEEG-RFTC procedures in twenty-four patients, adverse events, related to RFTC, were recorded in eight (26 %), of which two patients (8 %) had predicted permanent visual complaints whilst the other five had transient complaints. SignificanceThis study demonstrates that a considerable percentage of patients, even with bilateral, multiple PVNH and involvement of adjacent cortical regions can be rendered seizure-free with SEEG-guided-RFTC restricted to the nodules. Furthermore, this study delivers evidence that the complete destruction of the entire nodule is not necessary to render a patient seizure free. This justifies the use of SEEG in patients with single, multiple or bilateral PVNHs to provide insight into the epileptogenic organization in and around these lesions.