Interictal epileptiform discharges as the most significant confounding factor underlying memory impairment in focal...

Cognitive disturbances are highly prevalent in focal epilepsy and are often attributed to multifactorial causes, though the specific contributions of various predictors remain poorly understood. This study aimed to identify and prioritize factors contributing to memory deficits in temporal lobe epilepsy, with a particular emphasis on interictal epileptiform discharges (IED).

In a cohort of 48 patients with temporal lobe epilepsy undergoing presurgical evaluation with invasive foramen ovale electrodes, we examined offline memory performance alongside language and attention as controls. Cognitive performance was correlated with mesial temporal IED rates recorded over 24 h and additional factors, including seizure characteristics, age at onset, epilepsy duration, temporal lobe lesions, and antiseizure medication use.

A robust negative correlation emerged between mesial temporal IED rates and hippocampal-dependent cognitive scores (r = -0.43 - -0.29, p < 0.05), suggesting a direct impact of IEDs on memory consolidation processes. Epilepsy duration, antiseizure medication use and generalized seizures showed limited associations, but other variables including seizure frequency did not significantly correlate with cognitive performance.

Our findings suggest that IEDs may be the most relevant confounding factor contributing to sustained cognitive deficits in focal epilepsy. While IEDs are recognized markers of transient cognitive disruption, they have not yet demonstrated sufficient sensitivity or specificity as biomarkers of long-term cognitive dysfunction. Our study highlights the potential of IED frequency as a practical, clinically accessible biomarker for predicting chronic cognitive decline. These results emphasize the importance of developing targeted therapeutic strategies aimed at reducing interictal activity to improve cognitive outcomes.