Abstracts

Rationale: Temporal lobe epilepsy (TLE) with hippocampal sclerosis affects widespread structural and functional connectivity and often entails cognitive dysfunction. EEG is mandatory to disentangle the interaction of epileptic and physiological networks at the core of cognitive comorbidity. Here we evaluate the role of interictal epileptic discharges (IED) in cognitive performance. Methods: Thirty-four patients (right TLE=17, left TLE=17) were examined with 24-hour video-EEG and a large battery of neuropsychological tests spanning intelligence quotient, frontal and temporal lobe functions during their presurgical evaluation. High-resolution T1-weighted imaging was used to segment the hippocampus with FreeSurfer. The number and topography of interictal spikes and sharp waves were clinically determined and confronted to the test performance in partial correlations. Twenty-five patients had later epilepsy surgery with excellent outcome in the majority of cases (68% seizure free). Results: We found negative correlations between the amount of IED and executive functions, including verbal fluency, and intelligence quotient (IQ). Topography of IED affected left and right TLE differentially, with verbal fluency being strongly related to spiking over Broca's area. Importantly, partial correlations were corrected for age, age at disease onset, disease duration and hippocampal volume, lending particular strength to the genuine role of IED. At the opposite, effects on memory functions were not robust to correction for clinical factors and hippocampal sclerosis. As a general rule, patients with abundant IED performed poorly in most of the test delivered. Preliminary analysis of the groups of patients with favorable and unfavorable post-operative seizure outcome showed that pre-operative IED was comparable between groups. Post-operative neuropsychological testing revealed stable results: Patients with a high frequency of pre-operative IED remained comparably poor performers. Conclusions: TLE patients with longstanding disease showed a strong relationship between IED and cognitive deficits, most pronounced for frontal lobe functions. We suggest that IED is an independent risk factor for cognitive comorbidity, probably as a hallmark of the underlying network disease. The fact that patients with abundant IED were generally poor performers and did not recover despite surgery and seizure freedom is a further argument that IED is related to structural and functional network disease at distance of the sclerotic hippocampus. We propose that IED is a biomarker of cognitive curtailing in TLE. Funding: This work was supported by a grant from INSERM and the "Fondation Française pour la Recherche sur l'Epilepsie" to Vera Dinkelacker and by the "Institut Universitaire de France" to Séverine Samson. The research leading to these results has received funding from the program "Investissements d’avenir" ANR-10-IAIHU-06.