Epilepsy beyond seizures: predicting enduring cognitive dysfunction in genetic generalized epilepsies

Reduced cognitive functioning has been documented in the genetic generalized epilepsies (GGE). Among a number of hypothesized causal mechanisms, some evidence from other epilepsy syndromes suggests the impact of epileptiform discharges. This study investigates the relationship between cognitive function in GGE and burden of epileptiform discharges within a 24-hour EEG recording, controlling for variables relevant to cognitive function in epilepsy. As part of a larger prospective cohort study, 69 patients with EEG-confirmed GGE (11-58years) underwent 24-hour EEG and detailed neuropsychological assessment using the Woodcock Johnson III Tests. Ten-second pages of the EEG were marked manually page-by-page on longitudinal bipolar montage with 0.5 to 70Hz bandwidth by an experienced EEG reader. Multiple regression analyses were conducted. Epileptiform discharges were detected in 90% of patients. Less than 0.01% of electrophysiological events of two or more seconds were recognized by patients. Regression analysis demonstrated that the cumulative duration of epileptiform discharges over a 24-hour period predicted overall cognitive ability and memory function, accounting for 9.6% and 11.8% of adjusted variance, respectively. None of the epilepsy covariates included in multiple regression analysis added significantly to the model. Duration of epileptiform discharges negatively predicts overall cognitive ability and memory function, even after accounting for other known determinants of cognition. Prolonged epileptiform discharges are common and remain unreported by patients, raising important questions regarding the management of GGE syndromes and their associated comorbidities. Further research is required to investigate causal mechanisms if we are to improve cognitive outcomes in this common group of epilepsies.