ObjectiveTo investigate the application of stereoelectroencephalography (SEEG) in the refractory epilepsy related to periventricular nodular heterotopia (PNH). MethodsTen patients with drug-resistant epilepsy related to PNHs from Guangdong Sanjiu Brain Hospital and the First Affiliated Hospital of Jinan University from April 2017 to February 2021 were studied. Electrodes were implanted based on non-invasive preoperative evaluation. Then long-term monitoring of SEEG was carried out. The patterns of epileptogenic zone (EZ) were divided into four categories based on the ictal SEEG: A. only the nodules started; B. nodules and cortex synchronous initiation; C. the cortex initiation with early spreading to nodules; D. only cortex initiation. All patients underwent SEEG-guided radiofrequency thermocoagulation (RFTC), with a follow-up of at least 12 months. ResultsAll cases were multiple nodules. Four cases were unilateral and six bilateral. Eight cases were distributed in posterior pattern, and one in anterior pattern and one in diffused pattern, respectively. Seven patients had only PNH (pure PNH) and three patients were associated with other overlying cortex malformations (PNH plus). The EZ patterns of all cases were confirmed by the ictal SEEG: six patients were in pure type A, two patients were in pure type B, one patient in type A+B and one in type A+B+C, respectively. In eight patients SEEG-guided RF-TC was targeted only to PNHs; and in two patients RFTC was directed to both heterotopias and related cortical regions. The mean follow up was (33.4±14.0) months (12 ~ 58 months). Eight patients (in pure type A or type A included) were seizure free. Two patients were effective. None of the patients had significant postoperative complications or sequelae. ConclusionThe epileptic network of Epilepsy associated with nodular heterotopia may be individualized. Not all nodules are always epileptogenic, the role of each nodule in the epileptic network may be different. And multiple epileptic patterns may occur simultaneously in the same patient. SEEG can provide individualized diagnosis and treatment, be helpful to prognosis.