Migraine Sessions at CONy 2019

Another intriguing session at CONy 2019 featured a debate on whether the blood–brain barrier (BBB) transiently opens during migraine attacks. Although inflammation and BBB disruption are important contributors to many neurologic disorders, and inflammation has been linked to migraine pathogenesis, it is still unclear whether BBB integrity is disrupted during migraine attacks.

In the session chaired by Dr. José Miguel Laínez (Universidad Católica de Valencia, Spain), Dr. Pablo Irimia Sieria (Clínica Universidad de Navarra, Pamplona, Spain) discussed evidence for BBB disruption as a result of cortical spreading depression (CSD)—an intense wave of neurologic depolarization. CSD is considered to be associated particularly in migraine with aura, and could lead to BBB leakage through disturbance of cerebrovascular reflexes. Dr. Irimia discussed several animal studies, which have shown that CSD can induce transient BBB leakage and associated brain edema 3–6 h after experimental CSD induction. The BBB leakage appears to be transient, recovering approximately 48 h after experimental CSD induction. According to Dr. Irimia, there is strong evidence in favor of BBB disruption during migraine attacks, particularly in migraine with aura.

Prof. Messoud Ashina (Rigshospitalet Glostrup, Copenhagen, Denmark) took the opposing view, stating that there is no evidence for BBB disruption during migraine attacks in humans, and noting that many patients report aura symptoms without headache. He quoted a recent study by Hougaard et al.1 that used contrast-enhanced high-field MRI to investigate BBB permeability and tissue perfusion in migraineurs with and without aura during migraine attacks. There was evidence of increased perfusion in parts of the brain during the phase of migraine with aura, but no evidence of BBB disruption during any phase of migraine, with or without aura. He further emphasized that studies in humans so far have all failed to show a correlation between BBB disruption and migraine.

At the end of the debate, the audience leaned 2:1 towards the position defended by Prof. Ashina, which was that the BBB did not open during a migraine attack. The jury is clearly still out on whether there is a correlation between inflammation, BBB disruption and migraines with and without aura. If there is a correlation between BBB leakage and migraine—and it is currently not possible to detect it due to technical challenges associated with studying this in humans—the next question is whether it is clinically relevant. Uncovering the potential role of BBB leakage in migraine is also extremely important with respect to improving migraine treatments, because transient BBB opening would present opportunities to target the CNS directly with molecules too large to cross an intact BBB.

References

  1. Hougaard A, et al. Increased brainstem perfusion, but no blood-brain barrier disruption, during attacks of migraine with aura. Brain. 2017;140:1633-42.