Thank you to Gretchen E. Tietjen, MD for her contribution to this spotlight!
Migraine and Stroke
Both migraine and stroke are common disorders, but they usually occur in quite different populations. Stroke most commonly affects elderly men, and migraine, young women, but over the past 40 years study after study has shown an independent link between migraine and stroke. Despite much exploration, the complex relationship of migraine and stroke is still unfolding. The following is list of ways in which the two conditions may be connected:
- Migraine causes of stroke (migrainous infarction)—stroke occurs during the migraine attack
- Migraine is a risk factor for stroke—stroke occurs more frequently in person who have or have had migraine, but not during an attack
- Migraine mimics stroke, and stroke mimics migraine
- Migraine is caused by stroke (symptomatic migraine)—ischemia or hemorrhage trigger a migraine-like, or aura-like event
- Migraine and stroke share a common cause—such as cardiac shunt (known as patent foramen ovale), or an abnormality of blood vessels (known as vasculopathy) due to a genetic condition, such as CADASIL
- Migraine is associated with silent stroke—stroke-like lesions seen on MRI without symptoms of stroke
What is the risk of stroke with migraine?
Fortunately, the absolute risk of migraine-related stroke is low. In the U.S. the yearly number of strokes from all causes is about 800,000 (split fairly evenly between the sexes) in a population of over 322 million persons. The yearly risk of stroke in women with migraine is about 3 times what it is for women without migraine, with an estimated 13 strokes per 100,000 women that are tied to migraine rather than to another diagnosis. This means that out of 28 million women in the U.S. with migraine, the number of stroke per year related to that diagnosis is about 3600, which is less than 1 percent of the total strokes affecting women.
Who is at risk?
The main type of migraine associated with stroke is migraine with aura, a subtype affecting about 25% of persons with migraine. The main type of stroke associated with migraine is ischemic stroke (resulting from decreased blood flow to a portion of the brain) but persons with migraine also have an increased risk of hemorrhagic stroke (resulting from bleeding into or around the brain). Women with aura are 2 to 3 times more likely to have stroke than women without migraine, all other things being equal. Women with aura are also at higher risk of stroke than men with aura. Interestingly, young persons (below the age of 45 years old) are at greater risk for migraine-related stroke than are older individuals, and the strongest association of migraine and stroke is in persons without traditional stroke risk factors such as high blood pressure, diabetes mellitus and high cholesterol.
Migraine Aura or TIA?
Due to an overlap of clinical features it is sometimes difficult to tell a typical migraine aura from a transient ischemic attack (TIA), an event often referred to as a “mini-stroke”. Both aura and TIA involve brief (usually 60 minutes or less), focal neurological symptoms, which may or may not be followed by headache. Symptoms in aura are typically “positive” and expanding, such as a growing bright, crescent with jagged edges obscuring part of the vision, or a 5-minute long march of tingling from finger tips on one side up to the face. Symptoms of TIA are, in contrast, often “negative” and of sudden onset, such one-sided visual loss (eye or field of vision), and numbness. Some aura symptoms, including visual loss in one eye (retinal migraine), one-sided weakness (hemiplegic migraine), vertigo (basilar migraine), and migraine with prolonged aura are difficult to clinically differentiate from TIA. In both conditions labs and MRI may be normal. An additional wrinkle in the complex relationship of migraine aura and brain ischemia is the fact that ischemia may trigger an electrical brain phenomenon known as cortical spreading depression, which manifests itself aura. This phenomenon is referred to as symptomatic migraine. This means that in some cases aura symptoms may be due to a TIA-like event.
The ABCs of migraine-stroke linking mechanisms
A is for Arteries
Atherosclerosis, the most common cause of stroke in the general population is not enhanced in persons with migraine. Stroke occurring during the migraine with aura attack may be due to vasospasm, which is a reversible constriction of one or more arteries. The rare condition is known as migrainous infarction. Cervical artery dissection, another vascular cause of stroke, refers to a tear within the inner lining of an artery carrying blood to the brain. This may be due to quick movement of the neck traumatizing the artery. Arterial dissection is more likely to occur in young persons with a history of migraine, and the most common presenting symptoms of head and neck pain may not be initially recognized as having another cause. The rare genetic condition, CADASIL, shows abnormalities of the small and medium sized arteries and clinical features of migraine with aura, TIAs, strokes, and eventually, vascular dementia. Even under normal circumstances, there is growing evidence that migraine attacks perturb or activate the inner cell lining (endothelium) of the arteries, leading to release of substances involved in inflammation, and coagulation, and decreasing the ability of the vessel to fully dilate.
B is for Blood
Blockage of an artery from a clot may cause stroke, but if the blockage is temporary the result may be a TIA or aura-like episode. When blood clots more than normal, this is referred to hypercoagulability. It may be caused by genetic, acquired, or lifestyle factors, such as cigarette smoking or use of estrogen containing contraceptives (risk varies with dose). One study of young persons with stroke showed that those with migraine with aura were over twice as likely to have at least one factor causing hypercoagulability as those with migraine without aura, or no migraine at all. For some persons use of daily aspirin prevents aura.
C is for Cardiac
About 15-25% of persons are born with a passageway between the right and left upper chambers (atria) of the heart, and this is known as a patent foramen ovale (PFO). Clots forming in or shunting through the PFO may be pumped to the brain and result in stroke, TIA, or aura-like episodes. Wide variation of results from studies investigating the frequency of PFO in persons with migraine (range: 15 to 90%), and of migraine in persons with PFO (range: 16 to 64%) have clouded the potential role of PFO as a link between migraine and stroke. Clinical trials of PFO closure have not proven that this is an effective way to prevent migraine.
Migraine and Heart Disease
Most of the studies examining migraine and vascular disease have naturally focused on stroke, another brain condition. There is, however, also strong evidence that migraine increases the risk of heart disease, such as myocardial infarction (heart attacks) and angina. The link between migraine and heart disease has been uncovered in men and women over a vast range of ages and across the globe. Most recently the large (23,000 women) Nurses’ Health Study, which enrolled persons, ages 25 to 42 years old, about 20 years earlier, showed that migraine increases the risk of stroke, coronary events, and related death by about 50%. In several other study populations the risk of ischemic heart disease was doubled. The mechanisms are unknown but likely involve inflammation, coagulation, and dysfunction of endothelial lining of the arteries.
Tips for lowering risk of stroke and heart disease:
- Maintain a healthful diet, drink plenty of water, and get regular exercise and at least 8 hours of sleep
- Be evaluated and treated for conditions known to cause stroke and heart disease such as high blood pressure, high cholesterol and diabetes
- No cigarette smoking
- Use migraine preventive strategies. In addition to decreasing attacks of migraine aura and headache, this may also prevent stroke. In addition to the traditional migraine preventives, ask your doctor whether meds, which in addition to decreasing inflammation, decrease clotting (such as daily aspirin), or repair the endothelium (such as a statin with Vitamin D) are right for you
- Avoid use of estrogen containing contraceptives, especially if you smoke or have a personal or family history of blood clots. Progestogen-contraception has less risk.
- Avoid chiropractic manipulation of the neck, in order to decrease risk of cervical artery dissection
- Do not use triptans or other medications that constrict blood vessels if you have a history of heart disease or stroke, or if you have attacks weakness on one side (possible hemiplegic migraine) vertigo and gait imbalance (possible basilar migraine).
- Spalice A, Del Balzo F, Papetti L, et al. Stroke and migraine is there a possible comorbidity? Ital J Pediatr. 2016; Apr 26;42:41. doi:10.1186/s13052-016-0253-8.
- Lee MJ, Lee C, Chung CS. The migraine-stroke connection. J Stroke 2016; 18:146-56.
- Mawet J, Kurth T, Ayata C. Migraine and stroke: in search of shared mechanisms. Cephalalgia 2015; 35:165-81.
- Kurth T, Chabriat H, Bousser M-G. Migraine and stroke: a complex association with clinical implications. Lancet Neurol 2012;11:92-100.
- Sacco S, Ornello R, Ripa P, Pistoia F, Carolei A. Migraine and hemorrhagic stroke: a meta-analysis. Stroke 2013;44:3032-8.
- Mawet J, Debette S, Bousser MG, Ducros A. The Link Between Migraine, Reversible Cerebral Vasoconstriction Syndrome and Cervical Artery Dissection. Headache. 2016 Apr;56(4):645-56.
- Stam AH, Haan J, van den Maagdenberg AM, Ferrari MD, Terwindt GM. Migraine and genetic and acquired vasculopathies. Cephalalgia. 2009;29(9):1006-17.
- Pezzini A, Grassi M, Lodigiani C, et al. Italian Project on Stroke in Young Adults Investigators. Predictors of migraine subtypes in young adults with ischemic stroke: the italian project on stroke in young adults. Stroke. 2011 Jan;42(1):17-21.
- Tepper NK, Whiteman MK, Zapata LB, et al. Safety of hormonal contraceptives among women with migraine: A systematic review. Contraception. 2016 May 3. pii: S0010-7824(16)30051-8. doi: 10.1016/j.contraception.2016.04.016
- Tariq N, Tepper SJ, Kriegler JS. Patent Foramen Ovale and Migraine: Closing the Debate-A Review. Headache. 2016 Mar;56(3):462-78.
- Kurth T, Gaziano JM, Cook NR, et al. Migraine and risk of cardiovascular disease in men. Arch Intern Med 2007;167:795-801.
- Kurth T, Winter AC, Eliassen AH, et al. Migraine and risk of cardiovascular disease in women: prospective cohort study. BMJ. 2016 May 31;353:i2610. doi: 10.1136/bmj.i2610.
- Bousser MG, Conrad J, Kittner S, et al. Recommendations on the risk if ischaemic stroke associated with use of combined oral contraceptives and hormone replacement therapy in women with migraine. The International Headache Society Task Force on Combined Oral Contraceptives and Hormone Replacement Therapy. Cephalalgia 2000; 20:155-6.
- ACOG Committee on Practice Bulletins-Gynecology. ACOG practice bulletin. No. 73: Use of hormonal contraception in women with coexisting medical conditions.Obstet Gynecol. 2006 Jun;107(6):1453-72.
- Roberto G, Raschi E, Piccinni C, et al. Adverse cardiovascular events associated with triptans and ergotamines for treatment of migraine: systematic review of observational studies. Cephalalgia. 2015;35:118-31.