Development and validation of a prediction model for cryptogenic ischemic stroke risk in migraine patients with...

AimLong-term risk stratification for cryptogenic ischemic stroke (CIS) remains uncertain in patients with migraine and contrast-enhanced transcranial Doppler ultrasound-confirmed right-to-left shunting (RLS). Therefore, we aimed to develop and externally validate a simple baseline score for identifying individuals at low risk.MethodsThis 10-year study included 978 and 237 patients in the development and external validation cohorts, respectively. Internal validation involved a five-fold cross-validation strategy. Multivariable Cox proportional hazards modeling was used to develop the Migraine Risk Stratification Score (MRSS). Model performance was comprehensively evaluated using time-dependent receiver operating characteristic (ROC) curves at 3, 5, and 7 years, calibration plots, and decision curve analysis. Model interpretation was based on the Cox regression coefficients, hazard ratios, and integer points assigned to each predictor. Survival divergence was assessed by Kaplan-Meier analysis.ResultsAge ≥50 years (1 point), migraine with aura (2 points), and permanent and large RLS (2 points each) were identified as predictors. Patients were stratified into low- (0-4 points) and high-risk (5-7 points) groups based on total score. The high-risk group exhibited a significantly higher 10-year CIS risk (21.77% vs. 4.68%; hazard ratio: 5.06; 95% confidence interval: 3.31-7.74). The areas under the curve (AUCs) at 3, 5, and 7 years were 0.771, 0.777, and 0.751 in the development cohort; 0.753, 0.768, and 0.744 after five-fold cross-validation; and 0.917, 0.863, and 0.808 in external validation, respectively. The 3-year external AUC was based on only five events; therefore, it should be interpreted cautiously. Across evaluated horizons, the negative-predictive value was high (0.96-0.99), whereas the positive-predictive value (0.05-0.19) and F1 score (0.10-0.30) were low. Kaplan-Meier curves confirmed significant long-term stroke-free survival stratification (log-rank P < 0·001).ConclusionMRSS exhibited characteristics consistent with a rule-out-oriented baseline risk stratification tool rather than a precise individualized absolute risk assessment for treatment selection. Further prospective validation and recalibration are required.