Longitudinal Neurocognitive Trajectories In Perinatal Arterial Ischemic Stroke

Perinatal stroke occurs between 20 weeks gestation and 28 days postnatally, with arterial ischemic strokes (AIS) the most common subtype. Research regarding neurocognitive outcomes following perinatal AIS has been primarily cross-sectional with contradictory results given methodological variability (small cohorts, varying age at assessment, differing/non-standardized measures, limited follow-up, mixed populations). No research has characterized neurocognitive trajectories across multiple time points spanning critical developmental periods. Methods: These studies were the first evaluation of neurocognitive trajectories for individuals followed longitudinally at The Hospital for Sick Children across: 1) infancy and early childhood (Study 1; N=40; neonatal AIS), and 2) early and late childhood, adolescence, and early adulthood (Study 2; N=208; perinatal AIS). For Study 1, children underwent developmental assessment(s) at 18- and/or 36-months (Bayley) and neuropsychological assessment(s) from ages 4-13 years (WPPSI/WISC/WASI). For Study 2, individuals underwent neuropsychological assessment(s) from ages 2-25 years (WPPSI/WISC/WASI/WAIS). Predictors included sex, lesion volume, lesion laterality, seizure disorder, neurological diagnoses, medical comorbidities, perinatal AIS type, and early screening. Exploratory multilevel growth curve modelling was used to assess longitudinal neurocognitive trajectories, and to examine main or moderating effects of predictors. Results: Despite age-appropriate functioning statistically extrapolated at stroke occurrence, neurocognitive decline was found across 1) infancy and early childhood and 2) early and late childhood, adolescence, and early adulthood. For neonatal AIS and perinatal AIS, lesion volume moderated neurocognitive change. For neonatal AIS, medical comorbidities (congenital heart disease, genetic conditions) negatively impacted neurocognition at stroke occurrence (main effect) and early screening in infancy positively impacted neurocognition over time. For perinatal AIS, seizure disorder status and perinatal AIS type moderated neurocognitive change. Conclusions: In keeping with the early vulnerability hypothesis, neurocognitive decline was observed across development following perinatal AIS. Lesion volume and seizure disorders had moderating effects on neurocognition whereas medical comorbidities had a main effect; however, differences were apparent for perinatal AIS types. Perinatal AIS type moderated neurocognition such that presumed perinatal AIS involved rapid neurocognitive decline initially followed by improvements relative to neonatal AIS, which demonstrated consistent decline. Understanding neurocognitive trajectories and relevant predictors will inform the early identification of high-risk groups and the implementation of precision-based interventions.