Background—Data on long-term risk and predictors of recurrent thrombotic events after ischemic stroke at a young age are limited. Methods and Results—We followed 1867 patients with first-ever ischemic stroke who were 18 to 45 years of age (mean age, 36.8±7.1 years; women, 49.0%), as part of the Italian Project on Stroke in Young Adults (IPSYS). Median follow-up was 40 months (25th to 75th percentile, 53). The primary end point was a composite of ischemic stroke, transient ischemic attack, myocardial infarction, or other arterial events. One hundred sixty-three patients had recurrent thrombotic events (average rate, 2.26 per 100 person-years at risk). At 10 years, cumulative risk was 14.7% (95% confidence interval, 12.2%–17.9%) for primary end point, 14.0% (95% confidence interval, 11.4%–17.1%) for brain ischemia, and 0.7% (95% confidence interval, 0.4%–1.3%) for myocardial infarction or other arterial events. Familial history of stroke, migraine with aura, circulating antiphospholipid antibodies, discontinuation of antiplatelet and antihypertensive medications, and any increase of 1 traditional vascular risk factor were independent predictors of the composite end point in multivariable Cox proportional hazards analysis. A point-scoring system for each variable was generated by their β-coefficients, and a predictive score (IPSYS score) was calculated as the sum of the weighted scores. The area under the receiver operating characteristic curve of the 0- to 5-year score was 0.66 (95% confidence interval, 0.61–0.71; mean, 10-fold internally cross-validated area under the receiver operating characteristic curve, 0.65). Conclusions—Among patients with ischemic stroke aged 18 to 45 years, the long-term risk of recurrent thrombotic events is associated with modifiable, age-specific risk factors. The IPSYS score may serve as a simple tool for risk estimation.

Although spontaneous cervical artery dissection (CEAD) is the most frequent cause of ischemic stroke (IS) in young and middle-aged adults, the mechanisms leading to vessel damage are still unclear.¹ A reason for this lack of clarity is the limited number of large epidemiologic studies aimed at investigating this unusual disease that have been conducted thus far. In particular, what is poorly defined is the effect that specific susceptibility factors might have on disease risk. This is especially true for migraine. Scarce reports, mainly derived from case series and case-control studies conducted on small cohorts, have observed a higher prevalence of migraine in patients with spontaneous CEAD compared with patients with an IS due to a cause other than CEAD (non-CEAD IS).² To our knowledge, the international Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) case-control study³ is the only study confirming these findings in a large cohort and providing support for the idea that such an association may vary according to migraine subtype, being stronger for migraine without aura. Apart from the contribution that these findings might have for better understanding the biology of arterial dissection, they also might have potential implications in elucidating the specific pathways underlying the widely accepted association between migraine and IS in young adults. In this regard, any association between this primary headache and spontaneous CEAD deserves to be further substantiated, and the characteristics of migrainous patients with IS caused by CEAD should be better defined. We aimed to evaluate the association between migraine and spontaneous CEAD, as well as the effect of specific migraine subtypes on disease risk, in the Italian Project on Stroke at Young Age (IPSYS), one of the largest registries of patients with early-onset IS that is currently available.