<h3>Objective:</h3> To determine the factors which predict the occurrence of preoperative seizures (PRS) and post-operative seizures (POS) among patients with glioblastoma (GBM). <h3>Background:</h3> Seizures have been well described in patients with GBM, albeit at a lower frequency than low grade gliomas. Although recent studies suggest epileptogenesis has more to do with genetic molecular markers in low grade glioma-related seizure, information on factors that influence the development of of GBM-related PRS and POS is lacking. <h3>Design/Methods:</h3> We performed a single-center retrospective cohort study of patients with GBM evaluated at Mayo Clinic Florida, between 2018 and 2022. Clinical factors including, tumor molecular markers, neurophysiological and imaging findings were analyzed according to the status of PRS and POS. <h3>Results:</h3> One hundred thirty-two adult patients (median age=61.5 years), 79 (59.85%) females) were included. The most common locations were the temporal (n=50, 42.02%) and frontal (n=47, 39.50%) lobes. All patients underwent GBM resection, with 17.1% undergoing total resection (n=22). Sixty-two patients (46.27%) underwent intra-operative electrocorticography during GBM resection. Isocitrate dehydrogenase 1 (IDH1) wildtype was present in 121 patients (90.3%), 61 patients had O<sup>6</sup>-methylguanine-DNA methyltransferase (<i>MGMT</i>)-methylated GBM (46.21%). Forty patients (33.9%) had PRS, and 39 patients (38.24%) had POS (median follow-up=17.27 months; IQR=10.6–30.1). IDH1 wildtype and MGMT methylation status were not associated with PRS or POS. Patients with PRS were younger (59 years vs. 64 years, <b><i>p=0.021</i></b>) and experienced a longer survival time (16.1 months vs. 8.3 months, <b><i>p=0.044</i></b>) compared to patients without PRS. Occipital lobe GBM was associated with a lower likelihood of PRS (<b><i>p=0.043</i></b>) and POS (<b><i>p=0.001</i></b>). <h3>Conclusions:</h3> PRS is associated with younger age and longer survival time. PRS and POS are less likely to occur with occipital lobe tumors. Further studies are needed to confirm our findings and elucidate the influence of other tumor molecular markers in the development of PRS and POS in patients with GBM. <b>Disclosure:</b> Dr. Sánchez Boluarte has nothing to disclose. Dr. Garcia has nothing to disclose. Dr. Gunasekera has nothing to disclose. Dr. Tatum has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Bioserenity. Dr. Tatum has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Tatum has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Defense Law Firm on behalf of a patient with epilepsy with funds donated to the Epilepsy Foundation of America. The institution of Dr. Tatum has received research support from Esai. The institution of Dr. Tatum has received research support from Mayo Clinic. The institution of Dr. Tatum has received research support from Liva Nova. The institution of Dr. Tatum has received research support from Engage Pharmaceuticals. The institution of Dr. Tatum has received research support from Xenon. Dr. Tatum has received publishing royalties from a publication relating to health care. Dr. Tatum has received publishing royalties from a publication relating to health care. Dr. Sirven has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Sirven has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Medtronic. Dr. Sirven has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neurelis. Dr. Sirven has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medtronic. Dr. Sirven has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN. Dr. Sirven has stock in Doximity. Dr. Sirven has received publishing royalties from a publication relating to health care. Dr. Sirven has a non-compensated relationship as a Host with WJCT Public Media/ NPR that is relevant to AAN interests or activities. Dr. Freund has nothing to disclose. The institution of Dr. Ritaccio has received research support from NIH. Dr. Ritaccio has received intellectual property interests from a discovery or technology relating to health care. Kaisorn Chaichana has nothing to disclose. Alfredo Quiñones-Hinojosa has nothing to disclose. Dr. Feyissa has nothing to disclose.
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