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We hope you will enjoy getting to know the Fellows who participate in the 2019 interview series and thank them in advance for taking the time to share with our readers. The series began with Alastair Webb, University of Oxford, UK, next we interviewed Anita Arsovska, University Ss Cyril and Methodius, Skopje, Republic of North Macedonia. In March we featured Francesco Corea, Stroke and Neurology Units, Ospedale San Giovanni Battista Foligno, Italy. In April, we got to know Prof. Hanne Christensen, MD, PhD, DMSC, University of Copenhagen, Stroke Consultant at Bispebjerg & Frederiksberg Hospitals.
In May, we took advantage of the ESOC to interview 3 YSPR members: Francisco Moniche, Caroline M.J. Moos, Georgia Fischer. For June,introduced Christine Kremer, assoc professor, Neurology Department, Skåne University Hospital, Department of Clinical Sciences Lund University. For July, we have asked Simona Sacco, Professor of Neurology – Department of Applied Clinical Sciences and Biotechnology – University of L’Aquila, Director – Neurology Clinical Unit Avezzano Hospital and an active member of the ESO Guidelines Board. We deviated from our standard line of questions to ask her about stroke and migraine in recognition of World Brain Day focused on the topic of migraine.
Migraine and Stroke: what’s new in an old association?
I have to admit that after more than 40 years from the first study showing an association between migraine and stroke there is still a lot to understand. We know that migraine carries some vascular risk, that this risk is not only for ischemic stroke but also for other cardiovascular events including cardiac ischemic disease and that the risk is clearly evident for migraine with aura and is very controversial for migraine without aura. However we miss a lot of information which may be relevant from a clinical perspective. Migraine is common the young and usually improves with aging; some evidences indicate that active migraine with aura carries an increased risk while past history of migraine does not. Additional data indicate that subjects with migraine at a young age develop stroke later in life and other data indicate that migraine with aura starting after 50 years of age is associated with increased risk of ischemic stroke while migraine with aura starting at an earlier age and migraine without aura are not. Consequently the role of aging and migraine activity remains to be elucidated. There is also some evidence suggesting that the burden of migraine may impact on the stroke risk. High frequency of attacks of migraine with aura was associated with increased ischemic stroke risk while low frequency was not. But this information needs to be further supported also taking into account that subjects with chronic migraine (headache days for more than 15 days per month) are not suspected to have higher stroke risk. Additionally, migraine is a condition involving more women than men but gender differences in the risk are not entirely clear.
How can migraine affect stroke risk?
Mechanisms which are responsible for the increased stroke risk in subjects with migraine are yet to be elucidated. Experimental data indicate that there is a peculiar mechanism associated with migraine which lowers the threshold for ischemia. This is also indirectly supported by evidence in humans during the acute stroke phase showing that brain tissue in migraineurs suffers more quickly the ischemic damage as compared to the tissue of non-migraineurs. Taking together the experimental and clinical evidence, it is possible that in the cascade of events leading to ischemic stroke, migraine might act as a susceptibility factor by rendering the brain more sensitive to ischemic depolarizations. In this view some mechanisms may contribute to the association including hypercoagulability (e.g., antiphospholipid antibodies, protein C and protein S deficiency); hyperviscosity (polycythemia); hyperhomocysteinemia; hormonal dysregulation; paradoxical embolism from patent foramen ovale; and dissection of carotid, vertebral, or cerebral arteries. Moreover, recent data supported a specific association between migraine with visual aura and elevated risk of cardioembolic ischemic stroke; atrial fibrillation is supposed to be a mediator of migraine with visual aura-related ischemic stroke risk. This is line with experimental data on the mouse model showing that injection of microemboli in the carotid circulation may trigger cortical spreading depression which is the pathophysiological substrate of migraine with aura. In summary, clinical and experimental data suggest that some cases of migraine with visual aura are the clinical expression of microembolism to the brain originating in the heart after a paroxysm of atrial fibrillation and that at least a subset of migraine with visual auras be regarded as atrial fibrillation-related transient ischemic attacks.
Migraine, hormonal therapy and risk of stroke. Is there any connection?
Migraine, especially with aura, and the use of combined hormonal contraceptives are both independent risk factors for ischemic stroke in young women. Available studies indicate that the risk of ischemic stroke in women with migraine using low-dose combined hormonal contraceptives compared with those without migraine not using combined hormonal contraceptives is increase by 2 to 14-fold. The increased odds of ischemic stroke in young women with migraine using low-dose combined hormonal contraceptives compared with those without migraine not using combined hormonal contraceptives might result from several migraine characteristics, including aura and frequency of episodes, that are not adequately considered by the included studies. One recent study, using administrative coding data, found that both migraine with and without aura were associated with an increased risk of ischemic stroke. However, the use of combined hormonal contraceptives increased the risk of ischemic stroke in women with migraine with aura but not in women with migraine without aura. More robust data from studies with adequate selection criteria and validated migraine diagnosis are needed to assess whether combined hormonal contraceptives are a safe contraceptive option for women with migraine without aura.
How we can manage contraceptives strategies in women with migraine?
A consensus statement from the European Headache Federation (EHF) and the European Society of Hormonal Contraception and Reproductive Health (ESCRH) did not suggest the use of combined hormonal contraceptives in all the available formulations (pills, patches, vaginal ring) in women with migraine with aura. In those women safer contraceptives options such as non-hormonal contraception of progestogen-only contraceptives should be preferred. In women with migraine without aura, the evidence is much more controversial as I told you before, and combined hormonal contraceptives are not strictly to be avoided unless the woman has other concurrent vascular risk factors. For women with migraine who need to use estrogens for medical reason, such as endometriosis or polycystic ovary syndrome, the balance between benefits and risk is much more complex and the use of estrogens not contraindicated.
The issue of use of hormonal contraceptives in women with migraine is very common. The problem is that migraine is often underrecognized and aura can be misinterpreted. This may mostly happen in the gynecological or general practice settings where hormonal contraceptives are mostly prescribed. On the other hand, headache specialist and neurologist are not extremely confident with the contraceptive options. For this reason there is the need to improve the recognition of migraine and to improve the knowledge of contraceptives strategies among those who deal with migraine.