Association between Migraine and Cryptogenic Ischemic Stroke in Young Adults

Objective To assess the association between migraine and cryptogenic ischemic stroke (CIS) in young adults, with subgroup analyses stratified by sex and presence of patent foramen ovale (PFO). Methods We prospectively enrolled 347 consecutive patients aged 18 to 49 years with a recent CIS and 347 age‐ and sex‐matched (±5 years) stroke‐free controls. Any migraine and migraine with (MA) and migraine without aura (MO) were identified by a screener, which we validated against a headache neurologist. We used conditional logistic regression adjusting for age, education, hypertension, diabetes, waist‐to‐hip ratio, physical inactivity, current smoking, heavy drinking, and oral estrogen use to assess independent association between migraine and CIS. The effect of PFO on the association between migraine and CIS was analyzed with logistic regression in a subgroup investigated with transcranial Doppler bubble screen. Results The screener performance was excellent (Cohen kappa > 0.75) in patients and controls. Compared with nonmigraineurs, any migraine (odds ratio [OR] = 2.48, 95% confidence interval [CI] = 1.63–3.76) and MA (OR = 3.50, 95% CI = 2.19–5.61) were associated with CIS, whereas MO was not. The association emerged in both women (OR = 2.97 for any migraine, 95% CI = 1.61–5.47; OR = 4.32 for MA, 95% CI = 2.16–8.65) and men (OR = 2.47 for any migraine, 95% CI = 1.32–4.61; OR = 3.61 for MA, 95% CI = 1.75–7.45). Specifically for MA, the association with CIS remained significant irrespective of PFO. MA prevalence increased with increasing magnitude of the right‐to‐left shunt in patients with PFO. Interpretation MA has a strong association with CIS in young patients, independent of vascular risk factors and presence of PFO. ANN NEUROL 2021;89:242–253