Hippocampal FosB expression is associated with cognitive impairment in a subgroup of patients with childhood epilepsies

Epilepsy is a chronic neurological disorder characterized by recurrent seizures, and is often comorbid with other neurological and neurodegenerative diseases, such as Alzheimer's disease (AD). Patients with recurrent seizures often present with cognitive impairment. However, it is unclear how seizures, even when infrequent, produce long-lasting deficits in cognition. One mechanism may be seizure-induced expression of Delta FosB, a long-lived transcription factor that persistently regulates expression of plasticity-related genes and drives cognitive dysfunction. We previously found that, compared with cognitively-intact subjects, the activity-dependent expression of Delta FosB in the hippocampal dentate gyrus (DG) was increased in individuals with mild cognitive impairment (MCI) and in individuals with AD. In MCI patients, higher Delta FosB expression corresponded to lower Mini-Mental State Examination scores. Surgically resected DG tissue from patients with temporal lobe epilepsy also showed robust Delta FosB expression; however, it is unclear whether Delta FosB expression also corresponds to cognitive dysfunction in non-AD-related epilepsy. To test whether DG Delta FosB expression is indicative of cognitive impairment in epilepsies with different etiologies, we assessed Delta FosB expression in surgically-resected hippocampal tissue from 33 patients with childhood epilepsies who had undergone Wechsler Intelligence Scale for Children (WISC) testing prior to surgery. We found that Delta FosB expression is inversely correlated with Full-Scale Intelligence Quotient (FSIQ) in patients with mild to severe intellectual disability (FSIQ < 85). Our data indicate that Delta FosB expression corresponds to cognitive impairment in epilepsies with different etiologies, supporting the hypothesis that Delta FosB may epigenetically regulate gene expression and impair cognition across a wide range of epilepsy syndromes.