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Anti-epilepsy and anti-psychosis drugs have traditionally been used in the clinic to treat epilepsy complicated by mental disorders. However, there is still no effective therapy for refractory epilepsy patients suffering from persistent mental disorders.To explore the therapeutic effects of stereotactic multi-element localization and multi-target radiofrequency ablation on patients with refractory primary epilepsy and mental disorders.A retrospective case analysis.Department of Neurosurgery, the 454 Hospital of Chinese PLA.Between June and November 2004, 13 patients with refractory primary epilepsy complicated by persistent mental disorders were admitted to the Department of Neurosurgery, the 454 Hospital of Chinese PLA. The patient group consisted of nine males and four females, with an average age of 25 years (range 18–39 years), and a course of disease ranging 3–11 years. Diagnosis of mental disorders was in accordance with Chinese Classification of Mental Disorders. Written informed consent was obtained from all patients and their families, and the treatment protocol was approved by the Ethics Committee of the Hospital.Under venous inhalation anesthesia, the disease targets, including bilateral corpus callosum, bilateral amygdala, and bilateral medial septal area, as well as unilateral Forel-H area, were coagulated by RFG–3CF radiofrequency thermocoagulation at 75–80 °C for 60–70 seconds. During thermocoagulation, the targets were identified using deep-brain microelectrodes and localized according to electrophysiology and electric resistance values.One year post-surgery, epileptic seizures were assessed on the basis of the Tan classification, and psychogenic (non-epileptic) seizures were evaluated using a 5-grade system.All enrolled 13 epileptic patients were included in the final analysis. The results of follow-up evaluations demonstrated that epilepsy was well-controlled. In total, nine patients did not experience relapse, and the frequency of seizures was reduced by 75% in two patients, and 50%–74% in another two patients. Psychogenic seizures were ameliorated in 11 cases (class 1, recovery) and improved significantly in two cases (class 2, significant improvement).Radiofrequency ablation of bilateral corpus callosum, bilateral amygdala, bilateral medial septal area, and unilateral Forel-H area exhibits certain efficacy in treating epileptic patients suffering from persistent mental disorders.