A recent multicenter study (60 patients) shows the efficacy of intralesional therapy with interferon (IFN)-alpha in the treatment of predominantly cystic craniopharyngiomas; tumour size decreased more than 50 % in 78.3 % of patients. The mean follow-up durationwas 44months (range 4–84months). After the treatment, 13 % of patients developed new endocrinological deficits, while other patients developed transient fever, headache or palpebral edema; seizures have not been described [2]. A 48-year-old woman with a cystic craniopharyngioma underwent stereotactic positioning of an intracystic catheter with Rickham reservoir in September 2012. Cyst drainage was performed; the patient suffered from a sudden, sharp, pain at the level of the temple omolateral to the reservoir at the end of the suction of the cyst fluid. No other side-effects occurred. After few days the patient started a protocol of intracystic interferon-alpha injection. Through the Rickham, doses of 3,000 IU of IFN-alpha were administered three times a week, for 4 weeks, following the protocol of Cavalheiro et al. [2]. Beginning from the second week of treatment, the patient did not tolerate the therapy, suffering from nausea, headache, and rare episodes of vomiting; symptoms were partially controlled through medication. A CT scan without contrast injection performed during the treatment excluded complications and showed the shrinkage of the cystic component. After the last administration of interferon, she suffered from a generalized tonico-clonic seizure (GTCS). After the discontinuation of interferon, the patient recovered well and did not present further seizure episode. The last CT scan control (Fig. 1) the complete disappearance of the cyst. According to the study of Cavalheiro, leakage from a craniopharyngioma’s cyst is not considered a contraindication for intralesional IFN-alpha injection, because its lack of neurotoxicity. Cyst shrinkage and the possibility of communication between the cyst and liquoral spaces were considered in our case. The treatment was carried on as suggested by other literature reports [2] with the aim of continuing the antiblastic effects on cyst walls. A previous report [3] describes a patient with a brain– blood barrier (BBB) rupture, due to a previous cranial surgery for a left parietal meningioma. Two weeks after the beginning of subcutaneous IFN-alpha therapy for chronic hepatitis, he suffered from a GTCS, which did not recur after IFN-alpha discontinuation. On this clinical observation a laboratory study on rats was performed; this study concluded that cortical exposure to IFN can generate an epileptic cortex. Our brief report shows that IFN-alpha intrathecal therapy can be associated to a GTCS; other literature reports show that subcutaneous IFN-alpha therapy [1, 4] can be associated with seizure. For this reason, performing a CT scan with iodate contrast into the Rickham, before IFN injection, has to be considered, in order to perform a safer intralesional IFN therapy. Of course, further clinical studies are required in order to confirm our observation. M. Rizzi (*) :G. Messina :M. Castiglione :V. Nazzi : A. Franzini Department of Neurosurgery, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy e-mail: michele.rizzi@live.it