Hippocampal Seizure-Related Burden is Associated with Accelerated Long-Term Forgetting in Focal Epilepsy.
OBJECTIVE Memory impairment is a frequent comorbidity of focal epilepsy, incompletely explained by seizure frequency or structural pathology. Ictal and postictal hippocampal dysfunction disrupt memory processes, but their cumulative impact remains poorly quantified. This study introduces cumulative hippocampal seizure-related burden metrics and examines their association with long-term memory consolidation. METHODS A total of 20 consecutive patients undergoing stereo-electroencephalography in Marseille (2016-2018) were prospectively included. Continuous stereo-electroencephalogram recordings between 2 memory assessments (30 minutes and 1 week postencoding) were analyzed. Hippocampal ictal involvement and durations were assessed using epileptogenicity markers and visual stereo-electroencephalogram analysis. The postictal period was quantified using permutation entropy. Cumulative hippocampal seizure-related burden metrics (ictal, postictal, and combined) were computed across hippocampus-involving ictal events. Verbal and visual memory were assessed using standardized recall and recognition tasks. One-week performance was defined as the percentage score obtained at the 1-week assessment, whereas retention was defined as 1-week performance expressed as a percentage of 30-min performance. Associations were examined using univariate and multivariate analyses. RESULTS Higher dominant-hemisphere hippocampal burden was associated with poorer 1-week verbal memory (performance and retention), independently of most covariates. Higher cumulative hippocampal seizure-related burden was associated with lower total recall performance (free + cued) and total recall retention (β = -25.04 and -23.88; R2 = 0.57 and 0.53; p < 0.05), and accounted for the greatest variance in both outcomes (adjusted R2 = 0.59 and 0.53; β = -25.45 and -24.27; p < 0.01), particularly when adjusting for epilepsy duration. No robust associations were observed between nondominant-hemisphere hippocampal seizure-related burden metrics and visual memory. Effects predominantly involved recall. INTERPRETATION Cumulative ictal-postictal hippocampal dysfunction is a major predictor of impaired long-term verbal memory consolidation in focal epilepsy. ANN NEUROL 2026.