AbstractObjectiveTo assess feasibility and efficacy of subtraction ictal SPECT coregistered to MRI (SISCOM) for epilepsy localization in children who are candidates for resective surgery.MethodsWe retrospectively reviewed all patients ≤16 years with drug‐resistant epilepsy screened for epilepsy surgery in the University Hospital of Leuven from January 2009 to January 2018. Fifty‐eight hospitalizations for ictal SPECT and 51 SISCOM analyses in 44 patients were included. Mean age was 9.1 years. Hospitalizations for SISCOM were analyzed in terms of multiple variables affecting feasibility and efficacy. The localization of SISCOM was compared with the localization of the presumed epileptogenic zone (PEZ) as determined by video‐EEG.ResultsSISCOM was feasible in terms of chronic medication management, rescue antiepileptic therapy during hospitalization, and operative timings. Radiotracer injection occurred within 30 seconds from seizure onset in 91.4% of the patients. ictal SPECT imaging was performed within two hours from injection in 100% of the patients (mean: 40 minutes). SISCOM was able to localize the PEZ in 51.0% (26/51) and to additionally lateralize the PEZ in 17.6% (9/51), achieving better localizations than ictal SPECT, FDG‐PET, and MRI (P < .01). SISCOM was useful to localize the PEZ in 25% of patients with poorly localizing video‐EEG and in 27.8% of MRI‐negative cases. The occurrence of habitual seizures during injection for ictal SPECT and the temporal localization of the PEZ both correlated with a better SISCOM localization (P < .05). 36.4% (16/44) patients were finally selected for resective surgery, with a 87.5% seizure‐free rate at 12 months. A localizing SISCOM was associated with seizure freedom in 66.7% and with a Engel I‐II in 75.0% of our patients.SignificanceSISCOM is a reliable tool to localize the epileptogenic zone in clinical practice and is both feasible and useful in children, adding precious presurgical information especially in patients with noninformative MRI or a poorly localizing video‐EEG.