Migraine and stroke are neurological disorders that are often found in the community. The association between them has been studied since 40 years ago. Based on the 2016 Global Burden of Disease, Injuries, and Risk Factors studies, 1.04 billion individuals suffer from migraines. Measuring the impact of migraine using the YLDs (years of life lived with disability), measured from the disease prevalence and the average time of headache multiplied by the severity of the headache disability. The impact of migraines is 45.1 million YLDs, of which 20.3 million YLDs (45%) occur in women aged 15-49 years.

Migraine related to stroke

The same study found 13.7 million new stroke cases and 80.1 million cases of stroke globally in 2016. Measurement of stroke's impact using the DALYs (disability-adjusted life-years), which is the number of years of life lost and years of living with a disability. In 2016, there were 116.4 million DALYs due to stroke. Besides being a major cause of disability, stroke is also a major cause of mortality. In 2016 there were 5.5 million deaths due to stroke.

Association Between Migraine and Ischemic Stroke

Several studies have shown that migraine is associated with ischemic stroke. Migraine and stroke can have similar clinical presentations, especially in the basilar type of migraine and ocular migraine.

Ischemic strokes in migraine sufferers can be grouped into migraine-related stroke and migrainous infarction. Migraine-related stroke is cerebral infarction that occurs together with migraines. Migrainous infarction is cerebral infarction that occurs during migraine attacks with aura.

Migraine Related Stroke

Migraine-related stroke is a stroke that occurs in migraine sufferers. The incidence is 1.44 / 100,000 to 1.7 / 100,000 individuals per year. The risk of ischemic stroke increases twice in migraine sufferers. Risk factors for ischemic stroke in migraine sufferers include migraine with aura, female, age under 45 years, smoking, and use of oral contraceptives. The risk of ischemic stroke increases with increasing migraines frequency. Specific drugs for migraine, namely triptans and ergot derivatives, are also risk factors because they are strong vasoconstrictors.

Migrainous Infarction

Migrainous infarction is an ischemic stroke that occurs during a migraine attack with aura. The criteria for the diagnosis of migrainous infarction are as follows:

1. Migraine attacks that meet the criteria B and C
2. Occurs in migraine sufferers with an aura like the previous attack, but one or more aura lasts more than 60 minutes
3. Imaging examination shows infarction in the relevant area
4. Not better described by other diagnoses

The incidence of migrainous infarction is infrequent, i.e., 1.4-3.4 / 100,000 individuals per year, and 0.2-0.5% of all ischemic stroke incidents. Migrainous infarction often occurs in young women and affects the posterior circulation (70.6-82.0%). Visual aura is the most frequent aura (82.3%), followed by sensory dysfunction and aphasia. Symptoms of migrainous infarction are visual field disorders, sensory disorders, hemiparesis, aphasia, and tetraparesis.

Frequent imaging findings are small and multiple lesions, which are limited to certain areas of vascularization. Most cases of migrainous infarction are recovered with minor sequelae or without sequelae.

Association Between Migraine and Hemorrhagic Stroke

The risk of hemorrhagic stroke, both Intracerebral hemorrhage (ICH) and Subarachnoid hemorrhage (SAH), also increases in migraine sufferers. However, the results of various related studies are still not consistent. Several studies have shown that risk factors for hemorrhagic stroke in migraine sufferers include migraines with aura, females, and age under 45 years. However, other studies have shown that hemorrhagic stroke's increased risk does not depend on gender or age. The incidence of hemorrhagic stroke in migraine sufferers is also reported is very low.

The mechanism underlying the association between migraine and stroke

The mechanism that causes a stroke in migraine is still not known. However, there are several theories put forward, such as cortical spreading depression and vascular factors.

a. Cortical Spreading Depression
Cortical spreading depression (CSD) is a wave of activity that occurs slowly on the brain's surface, in the form of depolarization followed by suppression of brain activity. CSD is suspected to be a mechanism underlying migraine with aura based on studies in animals.

There is a slow decline in cerebral blood flow from the posterior to the anterior in the aura phase, followed by an increase in cerebral blood flow at the time of the attack. Decreased cerebral blood flow that occurs in CSD can trigger an ischemic stroke. CSD is also associated with excretion of glutamic excitatory amino acids associated with ischemic neuron injury, blood-brain barrier weakness, and endothelial damage.

b. Vascular Factors
In both migraine and ischemic stroke, the generalized blood vessel abnormalities in the form of endothelial dysfunction and decreased endothelial repairability can be found. Young women with migraine also have higher estradiol levels, thrombocytosis, erythrocytosis, and levels of von Willebrand factors, fibrinogen, tissue plasminogen activator antigens, and higher endothelial microparticles. All of these things cause hypercoagulability. Additionally, the incidence of spontaneous cervical artery dissection is also found to be higher in migraine sufferers.

c. Genetic Factors
Some genetic disorders have a clinical presentation in migraines and cause vascular damage, thereby increasing the risk of ischemic stroke. The most known genetic disease related to this is cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy due to mutations in the NOTCH3 gene.

Besides, patent foramen ovale (PFO), a congenital defect of the heart, is often found in migraine sufferers with aura and is thought to be associated with ischemic stroke. The larger of PFO shunt, the higher the level of hypoxia that can occur. It is suspected to be related to the incidence of cerebral infarction.

d. White Matter Hyperintensities
White matter hyperintensities (WMH) are often found in radiological examinations of migraine sufferers. Several studies have shown that WMH results from subclinical cerebral infarction (silent strokes) and is associated with lower cerebral blood flow. These lesions are commonly found in the frontal lobe, parietal lobe, or limbic system. The increase in WMH occurs with an increase in the frequency of migraine attacks and patients taking ergotamine.

Clinical Implications

At present, there are no recommendations or guidelines for the prevention of ischemic stroke in migraine sufferers. However, because there is an association between them, if there are clinical indications, the selection of drugs reduces migraine attacks, and the risk of cardiovascular disease can be done. The drugs in question are:

Antihypertensives such as beta-blockers, angiotensin II receptor blockers, and ACE inhibitors. These medicines that can be chosen are lisinopril and candesartan. These antihypertensives have shown to reduce the frequency, severity, and disability caused by migraine, also effective in migraine prophylaxis.
Statins, both single and with vitamin D, are reported to be useful in migraine prophylaxis. Examples of statin drugs are simvastatin, atorvastatin, and rosuvastatin.

Because there is an increased risk of stroke in young women with migraines with aura, identifying and modifying cardiovascular risk factors is important in this population. Risk factors that need to be identified and modified include hypertension, smoking, oral contraceptive consumption, and sedentary lifestyle. Specific medicines for migraine therapy, namely triptans and ergot derivatives, should be avoided in patients with migraine with risk factors cardiovascular disease.

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