“Neurologists in clinical practice often observe young patients with migraine with aura (MwA) without vascular risk factors who experience stroke,” says Claudia Altamura, MD, PhD. “And we wonder if we could have done something to prevent these strokes. We know that MwA is associated with an increased risk for stroke. However, the high prevalence of MwA and the benign course in most patients do not prompt extensive vascular screening. In this light, understanding if a subgroup of patients requires closer clinical attention based on the clinical features of aura would be of paramount importance on both practical and research grounds. Unfortunately, existing literature has yet to address the characteristics of patients with MwA facing a stroke.”

For a paper published in the Journal of Neurology, Dr. Altamura and colleagues assessed the clinical profile and aura characteristics of patients with MwA having acute cerebral ischemia. They compared stroke phenotype and risk factors in patients with stroke with or without MwA and aura features in patients with MwA with or without stroke.

Phenotypes & Vascular Risk Factors Reviewed

“We had two possibilities to help answer our research question,” Dr. Altamura says. “The first option consisted of following up on patients with MwA to assess who would likely have a stroke (longitudinal design). This approach, however, would have required extensive time and numerous subjects. Another strategy was to investigate the clinical characteristics of patients with MwA with stroke and compare them with patients with MwA without stroke (retrospective design). Since the topic had never been addressed in existing literature, we undertook the second method, as it would offer us meaningful information relatively quickly.”

The study team reviewed stroke phenotypes and vascular risk factors in patients younger than 60 with MwA with and without stroke. They recorded risk factors, aura type, duration, onset age, and the frequency in the previous year in patients matched for age and disease history and investigated them for patent foramen ovale (PFO).

Intrinsic Predisposition to Cerebral Ischemia

“Patients with MwA facing stroke seem to have an intrinsic predisposition to cerebral ischemia, which is likely linked with inadequate energy efficiency,” Dr. Altamura says. “We did not find specific conditions in patients with migraine predisposing them to stroke, however. Although patients with MwA with stroke were more frequently diagnosed with PFO than those with MwA without stroke, PFO with high-risk characteristics had the same frequency. On the other hand, a short visual aura could reflect cortical spreading depression (CSD) triggered by transient ischemia, whereas longer visual or complex aura reflected neurally induced CSD. In practice, long and complex (involvement of multimodal symptoms [eg, language and sensory]) aura or highly frequent episodes should not prompt increased surveillance in patients with MwA.”

In most patients, Dr. Altamura notes, a definitive cause of stroke was not identified. “Indeed, the predisposing factors seem mostly to imply thrombophilic conditions (ie, smoking, estrogen),” she says. “In our hypothesis, local thrombosis in small arterioles or microemboli produced cerebral ischemic damage for inadequate endothelial and energetic compensatory mechanisms (Figure).”

The study team concurs that their findings do not support vascular check-ups in patients with MwA. However, they recommend that physicians educate patients about healthy habits (ie, avoiding smoking and considering a tailored approach for contraception) and reassure patients with MwA that longer, more complex, and frequent aura phenomena do not put them at higher risk for stroke.

“My colleagues and I agree that longitudinal studies are necessary to confirm our findings,” Dr. Altamura says. “There is much more to understand about the complex link between MwA, stroke, and PFO. Is it possible that aura is an epiphenomenon of very different causative substrates? If so, identifying those subjects with a possible ischemic trigger would help focus therapeutic approaches on a subgroup of patients to benefit both aura and vascular prevention.”