Pre-treatment seizures and cognition at the time of focal epilepsy diagnosis

People with focal epilepsy experience one or more seizures prior to diagnosis. The Human Epilepsy Project (HEP) was a prospective study enrolling people with newly diagnosed focal epilepsy. It collected information including cognitive testing at the time of enrollment. This was completed utilizing a computerized test battery called the Cogstate Brief Battery (CBB). A prior analysis found that enrollment CBB test scores were below that of age matched controls and that performance on testing was not independently associated with the longer-term development of treatment resistance over the course of the HEP study. The present study assesses the impact of pretreatment seizures on cognition at time of diagnosis, considering time-to-treatment initiation in relation to seizure onset, pre-treatment seizure frequency, and pretreatment seizure classification.

Participants with newly diagnosed focal epilepsy and no other major medical comorbidities or intellectual disability (estimated IQ > 70) were enrolled between June 29, 2012, and September 1, 2019. A subset of the 448 enrolled participants (N = 183) were over 18 years old, had complete HEP enrollment data that included pre-treatment seizure histories, and complete enrollment CBB testing for analysis in this study. Performance on enrollment CBB testing was modeled using multiple linear regression with pre-treatment seizure characteristics including seizure type and duration between seizure onset and treatment initiation, controlling for other key baseline participant characteristics.

There were no independent associations between cognitive measures on the CBB at the time of enrollment and pre-treatment seizures after correcting for potentially confounding variables. Z-scores for the attention composite on CBB (an average of Identification and Detection tests) were not associated with a global pre-treatment seizure score that quantified time with seizures (days) and seizure count by seizure type (motor, non-motor, bilateral tonic clonic) (p = 0.29). Similarly, z-scores for the memory composite (an average of the One Card Learning test and One Back tests) were not associated with the pre-treatment seizure score (p = 0.1). No additional independent associations were found to be significant between z-scores for attention or memory composites and other potential explanatory variables.

This study highlights an important finding for people who develop focal epilepsy and otherwise are in good health: pre-treatment time-limited seizures do not have an independent impact on cognition early on, as measured by a brief validated cognitive screening test. This suggests that that cognition at the time of epilepsy diagnosis may be more strongly related to underlying etiology, chronic disease, and comorbidities.