Introduction: Subacute sclerosing panencephalitis (SSPE) is a progressive and fatal central nervous system disorder that results from a persistent measles virus infection. Long-term data is very scarce with maximum follow-up being 10 years in study. Here we report a patient with SSPE treated with long-term intraventricular IFN-α therapy. Case: A 13-year old boy was transferred to our center with gradual progression of diffuse rigidity, cognitive deterioration, and generalized myoclonic seizures refractory to valproic acid which began several months ago. He had been losing social abilities and living skills such as feeding and dressing himself since the onset of his symptoms. His past medical history revealed that this patient experienced measles at the age of 2 years despite of the scheduled vaccinations. Physical examination revealed spastic quadriplegia with minimal interaction with non-verbal communication at the time of admission. His brain MRI revealed no specific findings but EEG showed anterior dominant periodic lateralized epileptiform discharges on diffuse suppressed backgrounds. Routine blood chemistry, urinalysis and metabolic profiles were normal. The cerebrospinal fluid (CSF) analysis showed normocytosis but positive CSF IgG anti-measles antibody. CSF/serum IgG index was 1.65 and CSF IgG anti-measles antibody titre was 1:160. Based on the clinical symptoms, history, and positive CSF anti-measles antibodies, he was diagnosed as stage III SSPE under Jabbour\'s classification. The patient was treated with oral inosiplex (100 mg/kg/day) and intraventricular one million units of INF-α twice a week via an Ommaya reservoir for initial six months. The intractable myoclonic seizures nearly disappeared and no further neurologic deterioration was noted, in spite of the sustained elevation of CSF/serum IgG index and CSF IgG anti-measles antibody titer. He has been under twice-weekly intraventricular IFN-α for 12 years and remained neurologically stable despite the severe neurological impairment at diagnosis. There are no serious adverse effects by the 12 years treatment of intrathecal IFN-α except one episode of the bacterial meningitis which was successfully treated. Conclusion: Long-term intraventricular treatment with IFN-α brought the neurological stabilization in a patient with SSPE without serious adverse effects.