Poststroke epilepsy is associated with vascular cognitive disorder in young stroke patients: The ODYSSEY study

Objective: Cognitive disorder is common after stroke at a young age, especially in patients with poststroke epilepsy (PSE). Whether the causative mechanism is direct (due to epilepsy-related network alterations) or indirect (due to effect-modifiers such as stroke severity) is not fully understood. We assessed the role of PSE in cognitive disorder in young stroke patients by investigating the association between vascular cognitive disorder (VCD) and PSE in young stroke patients, and by investigating the association between cognitive impairment per cognitive domain and PSE. Methods: In this multicenter prospective cohort study, we investigated the occurrence of PSE in patients aged 18–49 years presenting with a first-ever transient ischemic attack, ischemic stroke, or primary intracerebral hemorrhage between 2013 and 2021 and assessed the cognitive function 1 year after the event. We calculated composite z-scores for seven cognitive domains. VCD was categorized as a composite z-score in any domain between −2.0 SD and −1.5 SD (mild) and <−2.0 SD (major). We performed multivariable regression analyses to examine the association between PSE and VCD and between PSE and cognitive impairment per domain. Results: Eight (median age = 38.6 years, median NIHSS score = 2, 30% male) of 20 patients with PSE (40.0%) had major VCD, compared to 93 (median age = 44.2 years, median NIHSS = 2, 50% male) of 426 patients (20.1%) without PSE (adjusted odds ratio [OR] = 3.96, 95% confidence interval [CI] = 1.24–12.65). Additionally, PSE was independently associated with cognitive impairment in the domain attention and working memory (adjusted OR = 5.09, 95% CI = 1.15–22.59). Significance: We found independent associations between PSE and major VCD, and between PSE and cognitive impairment in the attention and working memory domain. This could support the “second-hit hypothesis,” in which epilepsy following a primary injury relates directly to increased cognitive impairment with a subcortical neuropsychological profile.