Dual-outcome Prediction of Post-Ischemic Stroke Epilepsy and Mortality Using Multimodal Quantitative Biomarkers
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Background and Objectives
Post-ischemic stroke epilepsy (PISE) reduces quality of life, and early risk prediction can guide prevention strategies and anti-epileptogenesis treatment trials. Stroke severity predicts both PISE and mortality, and ignoring mortality can overestimate epilepsy risk. We sought to enhance PISE risk stratification by modeling death as a competing outcome, integrating quantitative clinical, neuroimaging, and electroencephalography (EEG) biomarkers to distinguish shared and distinct predictors of epilepsy and mortality.
Methods
We developed a PISE prediction model using retrospective data from Yale-New Haven Hospital. The training cohort included patients from 2014–2020; the testing cohort from 2021–2022. Eligible patients were adults with acute ischemic stroke who underwent neuroimaging and EEG monitoring <7 days post-stroke and had follow-up >7 days.
Results
Of 280 patients, 53 developed PISE first, 104 died first, and the rest were censored. Quantitative PISE biomarkers included greater 72h stroke severity (HR Δ3 [95%CI], 1.2 [1.1-1.4]), infarct volume (HR Δ10mL , 1.06 [1.04-1.08]), EEG epileptiform abnormality burden (HR Δ10% , 1.2 [1.1-1.3]), and EEG power asymmetries (HR Δ10% , 2.0 [1.4-2.9]). Death predictors included older age (HR Δ10years , 1.7 [1.4-2.0]), worse pre-stroke functional status (HR, 1.4 [1.2-1.7]), atrial fibrillation history (HR, 2.4 [1.6-3.7]), cardioembolism etiology (HR, 1.9 [1.2-3.0]), anterior cerebral artery involvement (HR, 2.2 [1.2-3.7]), and greater EEG global theta-band powers (HR Δ10µV , 6.2 [2.3-17]). Our model, CRIME PISE , integrating these features, allows prediction of PISE-first and death-first risk scores with AUC of 0.72 (95%CI, 0.60-0.83) and 0.79 (0.72-0.85), respectively. Compared with the benchmark SeLECT model, CRIME PISE better predicted PISE in patients with ≥4 SeLECT points (AUC, 0.72 vs 0.58) but not those with <4 points (AUC, 0.33 vs 0.52). In the testing cohort, CRIME PISE identified a more selective group (n=18 vs 44 per SeLECT) with a higher PISE rate (39% vs 20%) and a lower mortality rate (22% vs 45%).
Discussion
CRIME PISE enhances PISE prediction by accounting for mortality as a competing outcome and incorporating multimodal quantitative biomarkers. Because its benefits over SeLECT are most pronounced in high-risk patients, a two-stage approach—SeLECT screening followed by CRIME PISE in SeLECT-positive cases—may better target candidates for anti-epileptogenesis trials by prioritizing patients likely to survive long-term and develop epilepsy.
