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Many centers have reported that ictal single photon emission computed tomography (SPECT) localizes regions of seizure onset with greater sensitivity and specificity than interictal SPECT. Here we report interictal and ictal SPECT scan results in both lesional and nonlesional cases. Using technetium hexamethyl propylamenamine oxide (HMPAO) or ethyl cysteinate dimer (ECD), these scans were done in 52 patients with partial and secondarily generalized seizures. Twenty-five had normal MRI and 27 showed structural lesions. None had mesial temporal sclerosis clearly identified on MRI. All 52 subsequently had interictal and ictal intracranial EEG studies that appeared to localize the seizure focus. Thirty-nine patients had surgery and have been followed for 2 or more years. Interictal SPECT scans showed focal hypoperfusion consistent with intracranial EEG localization of the seizure focus in 29% of patients. In another 13%, there was correct lateralization but not localization. Ictal SPECT scans showed focal hyperperfusion consistent with intracranial EEG localization of the seizure focus in 52% of patients. In another 25%, there was correct lateralization but not localization. The presence or absence of structural lesions on MRI did not affect ictal hyperperfusion or its correlation with intracranial EEG. Thirty-nine patients had resective surgery, of whom 62% had class I outcomes. There was a trend towards better outcome when ictal SPECT data were concordant with intracranial EEG data. The presence or absence of structural lesions on MRI did not affect the likelihood of class I outcome. Ictal SPECT is superior to interictal SPECT in localizing and lateralizing seizure foci. Its results correlate well with intracranial EEG, but in more than one third of cases, the latter shows focal seizure onset in areas that do not show focal hyperperfusion. Surgical outcome tends to be better when the two modalities give concordant results. [ABSTRACT FROM AUTHOR]