Background: Selective amygdalohippocampectomy (SA) is an effective treatment for drug-resistant cases of epilepsy due to hippocampal sclerosis (HS). However, its neurocognitive outcomes are inconsistent across the previous studies, pointing to potential location-specific confounders. Here, we investigated the neurocognitive outcomes of SA in an Iranian center recently adopting this approach. Methods: Thirty adults (53.3% of females, age 31.4 ± 6.2 years) with drug-resistant epilepsy due to HS were included in the study. Patients were stratified into surgical (n = 15) and medical (n = 15) treatment groups based on their preferences. Neurocognitive function was assessed before and 6 months after intervention using Wisconsin Card Sorting Test (WCST), Wechsler Adult Intelligence Scale-Revised, and Wechsler Memory Scale- Third Edition (WMS-III). Postintervention performance changes were compared between the two groups, and predictors of worse postoperative outcomes were investigated. Results: Longitudinal changes of performance in WMS-III and WCST were significantly different between the surgically and medically treated patients. Postoperative WMS-III performance showed an average 25% decline (mean ∆T2-T1 = –25.1%, T = –6.6, P < 0.001), and WCST performance improved by an average of 49% (mean ∆T2-T1 = +49.1%, T = 4.6, P < 0.001). The decline in memory performance was more severe in the left-sided surgery and in patients with higher baseline education (mean ∆T2-T1 = –31.1%, T = –8.9, P < 0.001). Conclusion: In our center, executive functioning improved or remained stable after SA, but memory functions declined moderately. The left-sided SA and higher education were associated with more severe decline in memory functions, highlighting the need for special considerations for these groups.

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