PI: Christine K. Fox

STATUS: Data Analysis
FUNDING: Pediatric Epilepsy Research Foundation

Groundbreaking data from SIPS suggest that acute post-stroke seizures are associated with a higher risk of epilepsy in children. Yet the reason for this relationship remains unclear: Is this a correlation or is there causation? While short seizures are not typically thought to be harmful, prolonged or repeated seizures in the setting of acute stroke could worsen ischemic injury by adding metabolic stress to marginally perfused brain tissue. Despite the frequency of acute post-stroke seizures in children, there is a lack of evidence to guide prophylactic treatment with anti-convulsants. The rationale for our proposed study is that acute seizures are a potentially modifiable risk factor for post-stroke epilepsy. Understanding who is at risk and the relationship of acute seizures to epilepsy could lead to improved management strategies and better patient outcomes.

SIPS provided important early data, but was limited by short follow-up (12 months) and limited sample size for subgroup analyses. Further, though SIPS preliminary data suggests that EEG and MRI studies performed early after the stroke could yield important biomarkers of seizure and epilepsy risk, we lacked the source EEG and MRI data to confirm this. Source MRIs showing the acute stroke are also needed to measure and control for infarct characteristics (such as location and size) in a standardized fashion to determine whether acute seizures are causally related to epilepsy. Therefore, our objectives in SIPS II are to overcome these limitations by increasing our length of follow-up, increasing our cohort size and collecting source EEG and MRI data.

Study Aims and Associated Hypotheses:

Aim 1: Determine the extent to which acute seizures after pediatric stroke are associated with stroke-related death, neurologic recovery and 5-year epilepsy risk. We hypothesize that acute seizures are associated with early stroke complications (malignant MCA syndrome and stroke related death), poorer neurologic recovery, higher epilepsy incidences rates and greater epilepsy severity.

Aim 2: Identify neuroimaging biomarkers associated with acute seizures and epilepsy. We will analyze acute brain infarcts on MRI in a Neuroimaging Core laboratory. We hypothesize that (A) infarct characteristics including size and location will be associated with seizures, and (B) acute seizures predict epilepsy even after controlling for these confounders.

Aim 3: Identify EEG biomarkers associated with severe neurologic outcomes and epilepsy. We will analyze EEGs from stroke hospitalization in an Electrophysiology Core laboratory. We hypothesize that electrographic features on EEG predict malignant MCA syndrome, stroke-related death and epilepsy.