Background and objectives: The aim of this study is to propose a methodology that combines non-invasive functional modalities electroencephalography (EEG) and single photon emission computed tomography (SPECT) to estimate the location of the epileptogenic zone (EZ) for the presurgical evaluation of patients with drug-resistant non-lesional epilepsy. Materials and Methods: This methodology consists of: (i) Estimation of ictal EEG source imaging (ESI); (ii) application of the subtraction of ictal and interictal SPECT co-registered with MRI (SISCOM) methodology; and (iii) estimation of ESI but using the output of the SISCOM as a priori information for the estimation of the sources. The methodology was implemented in a case series as an example of the application of this novel approach for the presurgical evaluation. A gold standard and a coincidence analysis based on measures of sensitivity and specificity were used as a preliminary assessment of the proposed methodology to localize EZ. Results: In patients with good postoperative evolution, the estimated EZ presented a spatial coincidence with the resection site represented by high values of sensitivity and specificity. For the patient with poor postoperative evolution, the methodology showed a partial incoherence between the estimated EZ and the resection site. In cases of multifocal epilepsy, the method proposed spatially extensive epileptogenic zones. Conclusions: The results of the case series provide preliminary evidence of the methodology’s potential to epileptogenic zone localization in non-lesion drug-resistant epilepsy. The novelty of the article consists in estimating the sources of ictal EEG using SISCOM result as a prior for the inverse solution. Future studies are necessary in order to validate the described methodology. The results constitute a starting point for further studies in order to support the clinical reliability of the proposed methodology and advocate for their implementation in the presurgical evaluation of patients with intractable non-lesional epilepsy.
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