Migraine Headache 

Migraine headache is a complex, recurrent headache disorder that is one of the most common complaints in medicine. In the United States, more than 30 million people have 1 or more migraine headaches per year. Approximately 75% of all persons who experience migraines are women (see Epidemiology).

The term migraine is derived from the Greek word hemikrania. This term was corrupted into low Latin as hemigranea, which eventually was accepted by the French translation as migraine.

Migraine was previously considered a vascular phenomenon that resulted from intracranial vasoconstriction followed by rebound vasodilation. Currently, however, the neurovascular theory describes migraine as primarily a neurogenic process with secondary changes in cerebral perfusion (see Pathophysiology).

Approximately 70% of patients have a first-degree relative with a history of migraine. In addition, a variety of environmental and behavioral factors may precipitate migraine attacks in persons with a predisposition to migraine (see Etiology).

The classic migraine episode is characterized by unilateral head pain preceded by various visual, sensory, motor symptoms, collectively known as an aura. Most commonly, the aura consists of visual manifestations such as scotomas, photophobia, or visual scintillations (eg, bright zigzag lines) (see Clinical Presentation).

In practice, however, migraine headaches may be unilateral or bilateral and may occur with or without an aura. In the current International Headache Society (IHS) categorization, the headache previously described as classic migraine is now known as migraine with aura, and that described as common migraine is now termed migraine without aura. Migraines without aura are the most common, accounting for more than 80% of all migraines.

The diagnosis of migraine is clinical in nature, based on criteria established by the International Headache Society. A full neurologic examination should be performed during the first visit; the findings are usually normal. Neuroimaging is not necessary in a typical case (see Workup).

Migraine treatment involves acute (abortive) and preventive (prophylactic) therapy. Patients with frequent attacks usually require both. Measures directed toward reducing migraine triggers are also generally advisable.

Acute treatment aims to stop or prevent the progression of a headache or reverse a headache that has started. Preventive treatment, which is given even in the absence of a headache, aims to reduce the frequency and severity of the migraine attack, make acute attacks more responsive to abortive therapy, and perhaps also improve the patient's quality of life (see Treatment and Management).

See Migraine in Children for a pediatric perspective on migraine. Also see Migraine Variants.

Migraine classification

The second edition of the International Classification of Headache Disorders^[1] lists the following types of migraine:

• Migraine without aura (formerly common migraine)
• Probable migraine without aura
• Migraine with aura (formerly classic migraine)
• Probable migraine with aura
• Chronic migraine
• Chronic migraine associated with analgesic overuse
• Childhood periodic syndromes that may not be precursors to or associated with migraine
• Complications of migraine
• Migrainous disorder not fulfilling above criteria
• Hemicrania continua

Migraine guidelines

In April 2000, the US Headache Consortium, a multispecialty group that includes the American College of Emergency Physicians, released evidence-based guidelines for the diagnosis, treatment, and prevention of migraine headaches. Guidelines are also available from the American Academy of Neurology, the National Headache Foundation, and the Canadian Association of Emergency Physicians.^{[2, 3, 4]}

The mechanisms of migraine remain incompletely understood. However, new technologies have allowed formulation of current concepts that may explain parts of the migraine syndrome.

Vascular theory

In the 1940s and 1950s, the vascular theory was proposed to explain the pathophysiology of migraine headache. Wolff et al believed that ischemia induced by intracranial vasoconstriction is responsible for the aura of migraine and that the subsequent rebound vasodilation and activation of perivascular nociceptive nerves resulted in headache.

This theory was based on the following 3 observations:

• Extracranial vessels become distended and pulsatile during a migraine attack
• Stimulation of intracranial vessels in an awake person induces headache
• Vasoconstrictors (eg, ergots) improve the headache, whereas vasodilators (eg, nitroglycerin) provoke an attack

However, this theory did not explain the prodrome and associated features, the efficacy of some drugs used to treat migraines that have no effect on blood vessels, and the fact that most patients do not have an aura.

Moreover, with the advent of newer imaging technologies, researchers found that intracranial blood flow patterns were inconsistent with the vascular theory. Intracarotid and single-photon emission computed tomography (SPECT) studies revealed that the headache is dissociated from hyperperfusion at its onset and termination in patients suffering from migraine headache with aura.

SPECT studies also revealed that regional cerebral blood flow (rCBF) decreases in the posterior area of the relevant cerebral hemisphere even before the aura is noted and that headache occurred while rCBF remained decreased; rCBF gradually increased throughout the remainder of the headache phase.

No consistent flow changes have been identified in patients suffering from migraine headache without aura, but rCBF remains normal in the majority. However, bilateral decrease in rCBF beginning at the occipital cortex and spreading anteriorly has been reported. More recently, Perciaccante has shown that migraine is characterized by a cardiac autonomic dysfunction.^[5]

As a result of these anomalous findings, the vascular theory was supplanted by the neurovascular theory.

Neurovascular theory

The neurovascular theory holds that a complex series of neural and vascular events initiates migraine.^[6] According to this theory, migraine is primarily a neurogenic process with secondary changes in cerebral perfusion.^[7]

At baseline, a migraineur who is not having any headache has a state of neuronal hyperexcitability in the cerebral cortex, especially in the occipital cortex.^[8] This finding has been demonstrated in studies of transcranial magnetic stimulation and with functional MRI.

This observation explains the special susceptibility of the migrainous brain to headaches.^[9] One can draw a parallel with the patient with epilepsy who similarly has interictal neuronal irritability.

Cortical spreading depression

In 1944, Leao proposed the theory of cortical spreading depression (CSD) to explain the mechanism of migraine with aura. CSD is a well-defined wave of neuronal excitation in the cortical gray matter that spreads from its site of origin at the rate of 2-6 mm/min.

This cellular depolarization causes the primary cortical phenomenon or aura phase; in turn, it activates trigeminal fibers causing the headache phase. The neurochemical basis of the CSD is the release of potassium or the excitatory amino acid glutamate from neural tissue. This release depolarizes the adjacent tissue, which, in turn, releases more neurotransmitters, propagating the spreading depression.

Positron emission tomography (PET) scanning demonstrates that blood flow is moderately reduced during a migrainous aura, but the spreading oligemia does not correspond to vascular territories. The oligemia itself is insufficient to impair function. Instead, the flow is reduced because the spreading depression reduces metabolism.

Although CSD is the disturbance that presumably results in the clinical manifestation of migraine aura, this spreading oligemia can be clinically silent (ie, migraine without aura). Perhaps a certain threshold is required to produce symptoms in patients having aura but not in those without aura. A study of the novel agent tonabersat, which inhibits CSD, found that the agent helped prevent migraine attacks with aura only, suggesting that CSD may but not be involved in attacks without aura.^[10]

Activation of the trigeminovascular system from CSD stimulates nociceptive neurons on dural blood vessels to release plasma proteins and pain-generating substances such as calcitonin gene-related peptide, substance P, vasoactive intestinal peptide, and neurokinin A. The resultant state of sterile inflammation is accompanied by further vasodilation, producing pain.

The initial cortical hyperperfusion in CSD is partly mediated by the release of trigeminal and parasympathetic neurotransmitters from perivascular nerve fibers, whereas delayed meningeal blood flow increase is mediated by a trigeminal-parasympathetic brainstem connection. According to Moulton et al, altered descending modulation in the brainstem has been postulated to contribute to the headache phase of migraine; this leads to loss of inhibition or enhanced facilitation, resulting in trigeminovascular neuron hyperexcitability.^[11]

In addition, through a variety of molecular mechanisms, cortical spreading depression upregulates genes, such as those encoding cyclo-oxygenase 2 (COX-2), tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta, galanin, and metalloproteinases. The activation of metalloproteinases leads to leakage of the blood-brain barrier, allowing potassium, nitric oxide, adenosine, and other products released by cortical spreading depression to reach and sensitize the dural perivascular trigeminal afferent endings.^[12]

Increased net activity of matrix metalloproteinase–2 (MMP-2) has been demonstrated in migraineurs. Patients who have migraine without aura seem to have an increased ratio of matrix metalloproteinase–9 (MMP-9) to tissue inhibitors of metalloproteinase–1 (TIMP-1), in contrast to a lower MMP-9/TIMP-1 ratio in migraine with aura patients.^[13] MMP-9 when measured alone is the same for migraine patients with or without aura.^[14] .

In an experimental study, acute hypoxia was induced by a single episode of CSD. This was accompanied by dramatic failure of brain ion homeostasis and prolonged impairment of neurovascular and neurometabolic coupling.^[15]

Vasoactive substances and neurotransmitters

Perivascular nerve activity also results in release of substances such as substance P (SP), neurokinin A (NKA), calcitonin gene-related peptide (CGRP), and nitric oxide (NO), which interact with the blood vessel wall to produce dilatation, protein extravasation, and sterile inflammation, stimulating the trigeminocervical complex as shown by induction of c-fos antigen by PET scan. Information then is relayed to the thalamus and cortex for registering of pain. Involvement of other centers may explain the associated autonomic symptoms and affective aspects of this pain.

Is the neurologically mediated sterile plasma extravasation the cause of this pain? Neurogenic plasma extravasation is inhibited by 5-HT1 agonists, gamma aminobutyric acid (GABA) agonists, neurosteroids, prostaglandin inhibitors, SP antagonists, and the endothelin antagonist bosentan; the latter 2 are ineffective as antimigraine drugs, showing that blockade of neurogenic plasma extravasation is not completely predictive of antimigraine efficacy in humans.

Neurogenically induced plasma extravasation may play a role in expression of pain in migraine, but whether this in itself is sufficient to cause pain is not clear; the presence of other stimulators may be required. Also, the pain process requires not only the activation of nociceptors of pain-producing intracranial structures but also reduction in the normal functioning of endogenous pain control pathways that gate the pain.

Migraine center

What generates a migraine episode? A potential "migraine center" in the brain stem has been proposed, based on findings on PET of persistently elevated rCBF in the brain stem (ie, periaqueductal gray, midbrain reticular formation, locus ceruleus) even after sumatriptan-produced resolution of headache and related symptoms in 9 patients who had experienced spontaneous attack of migraine without aura. This increased rCBF was not observed outside of the attack, suggesting that this activation is not due to pain perception or increased activity of the endogenous antinociceptive system.

The fact that sumatriptan reversed the concomitant increased rCBF in the cerebral cortex but not the brainstem centers suggests dysfunction in the regulation involved in antinociception and vascular control of these centers. Thalamic processing of pain is known to be gated by ascending serotonergic fibers from the dorsal raphe nucleus and from aminergic nuclei in the pontine tegmentum and locus ceruleus; the latter can alter brain flow and blood-brain barrier permeability.

Because of the set periodicity of migraine, linkage to the suprachiasmatic nucleus of the hypothalamus that governs circadian rhythm has been proposed. Discovering the central trigger for migraine would help identify better prophylactic agents.

Brainstem activation

PET scanning in patients having an acute migraine headache demonstrates activation of the contralateral pons, even after medications abort the pain. Weiler et al proposed that brainstem activation may be the initiating factor of migraine.

Once the CSD occurs on the surface of the brain, H⁺ and K⁺ ions diffuse to the pia mater and activate C-fiber meningeal nociceptors, which releases a proinflammatory soup of neurochemicals (eg, calcitonin gene–related peptide), and plasma extravasation occurs. Therefore, a sterile, neurogenic inflammation of the trigeminovascular complex is present.

Once the trigeminal system is activated, it stimulates the cranial vessels to dilate. The final common pathway to the throbbing headache is the dilatation of blood vessels.

Cutaneous allodynia

Burstein et al described the phenomenon of cutaneous allodynia, in which secondary pain pathways of the trigeminothalamic system become sensitized during a migrainous episode.^[16]

This observation further demonstrates that sensitization of central pathways in the brain mediates the pain of migraine, in addition to the previously described neurovascular events.

Dopamine pathway

Some authors have proposed a dopaminergic basis for migraine.^[17] In 1977, Sicuteri postulated that a state of dopaminergic hypersensitivity is present in patients with migraine. Interest in this theory has recently been renewed.

Some of the symptoms associated with migraine headaches, such as nausea, vomiting, yawning, irritability, hypotension, and hyperactivity, can be attributed to relative dopaminergic stimulation. Dopamine receptor hypersensitivity has been shown experimentally with dopamine agonists (eg, apomorphine). Dopamine antagonists (eg, prochlorperazine) completely relieve almost 75% of acute migraine attacks.

Magnesium deficiency

Another theory proposes that deficiency of magnesium in the brain triggers a chain of events, starting with platelet aggregation and glutamate release and finally resulting in the release of 5-hydroxytryptamine, which is a vasoconstrictor.

Endothelial dysfunction

Vascular smooth muscle cell dysfunction may involve impaired cyclic guanosine monophosphate and hemodynamic response to nitric oxide.^[18] Nitric oxide released by microglia is a potentially cytotoxic proinflammatory mediator, initiating and maintaining brain inflammation through activation of the trigeminal neuron system, and nitric oxide continues to be increased even in the headache-free period in migraineurs.^[19]

In premenopausal women with migraine, particularly in those with migraine aura, increased endothelial activation, which is a component of endothelial dysfunction, is evident.^[20]

Endothelial function is only one aspect of vascular reactivity, which, in turn, may be affected by many different factors: The most important measurable factors of vascular reactivity in conduit artery function are flow-mediated dilation (FMD), pulse wave velocity (PWV), and the following 4 measures of resistance or microvascular function:

• Forearm reactive hyperemia
• Reactive hyperemia index by finger plethysmography (RHI)
• Skin reactive hyperemia
• Fingertip temperature rebound

These may all provide additional prognostic information in the assessment of cardiovascular risk in postmenopausal women.^[21]

Serotonin and migraine

The serotonin receptor (5-hydroxytryptamine [5-HT]) is believed to be the most important receptor in the headache pathway. To facilitate understanding of the mechanisms of action of the various medications, the relationship between serotonin and migraine is reviewed here briefly, as some of these studies partly define the current understanding of migraine.

Stimulation of the trigeminal nerve releases substance P (SP), calcitonin gene-related peptide (CGRP), and neurokinin A (NKA) from the sensory C-fibers. These substances produce neurogenic inflammation that then interacts with the blood vessel wall, producing dilatation, plasma extravasation, and sterile inflammation.

Plasma extravasation is blocked by ergots, sumatriptan, the newer 5-HT1B/D agonists, indomethacin, acetylsalicylic acid, gamma aminobutyric acid (GABA) agonists such as valproic acid and benzodiazepines, neurosteroids, SP antagonists, and the endothelin antagonist bosentan.

Immunohistochemical studies have detected 5-HT1D receptors in trigeminal sensory neurons, including peripheral projections to the dura and within the trigeminal nucleus caudalis (TNC) and solitary tract, while 5-HT1B receptors are present on smooth muscle cells in meningeal vessels; however, both can be found in both tissues to some extent and even in coronary vessels.

These findings suggest that sumatriptan and other selective 5-HT1 agonists decrease headache by abolishing neuropeptide release in the periphery and blocking neurotransmission by acting on second-order neurons in the trigeminocervical complex.

All the currently available triptans are selective 5-HT1B/D full agonists. The major differences among these agents lie in their pharmacokinetic properties, which may affect onset of action (eg, rizatriptan has a shorter time to maximum plasma concentration [t_max], leading to faster onset), duration of action (eg, naratriptan has a longer half-life, leading to lower recurrence rate), bioavailability (eg, naratriptan has higher oral bioavailability, leading to more consistent response), and CNS penetration (eg, sumatriptan not shown to cross the intact blood-brain barrier).

The GABA-A receptor is suggested to reside on the parasympathetic fibers emanating from the sphenopalatine ganglia, as the effects of valproic acid, benzodiazepines, and steroids are abolished when these projections are sectioned. The possible relationship of dopamine and migraine has been shown by a direct relationship between dopamine concentration and migraine symptomatology and the demonstrated efficacy of dopamine antagonists in the acute treatment of migraine.

Migraine risk factors

Predisposing vascular risk factors include the following:

• Increased levels of C-reactive protein
• Interleukins
• Tumor necrosis factor (TNF)-alpha and adhesion molecules, which are markers of systemic inflammation
• Oxidative stress and thrombosis
• Increased body weight, high blood pressure, hypercholesterolemia
• Impaired insulin sensitivity
• High homocysteine levels, stroke, and coronary heart disease^[22]

Progression to chronic migraine

In some patients, migraine progresses to chronic migraine. Acute overuse of symptomatic medication is considered one of the most important risk factors for migraine progression. Bigal and Lipton identified the following associations of medication with progression to chronic migraine^[23] :

• Opiates - Critical dose of exposure is around 8 days per month; the effect is more pronounced in men
• Barbiturates - Critical dose of exposure is around 5 days per month; the effect is more pronounced in women
• Triptans - Migraine progression is seen only in patients with high frequency of migraine at baseline (10-14 d/mo)

The effect of anti-inflammatory medications varied with headache frequency. These agents were protective in patients with fewer than 10 days of headache at baseline, but induced migraine progression in patients with a high frequency of headaches at baseline.

Approximately 70% of patients have a first-degree relative with a history of migraine. The risk of migraine is increased 4-fold in relatives of people who have migraine with aura.^[24] Although no genetic basis has been identified for common migraine, it generally demonstrates a maternal inheritance pattern.

Familial hemiplegic migraine

Familial hemiplegic migraine (FHM) is a type of migraine with aura that is preceded or followed by hemiplegia, which typically resolves. Three loci have been identified in FHM. FHM type 1, which occurs in approximately 50% of affected families, is linked to band 19p13 or a mutation in the calcium channel gene (CACNA1A4) at the 1q locus.

FHM may be associated with cerebellar ataxia, which is also linked to the 19p locus. Evidence suggests that the 19p locus for FHM may also be involved in patients with nonhemiplegic migraine.

FHM type 2 is due to mutation in the sodium channel gene ATP1A2 on chromosome 1.^[25] FHM3 is a rare subtype of FHM and is caused by mutations in a sodium channel α-subunit coding gene, SCNA1.^[26]

Migraine in other inherited disorders

Migraine occurs with increased frequency in patients with mitochondrial disorders, such as MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes). CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a genetic disorder of the notch 3 gene on chromosome 19 that causes migraine with aura.

Migraine is also a common symptom in other genetic vasculopathies, including RVCL (retinal vasculopathy with cerebral leukodystrophy) and HIHRATL (hereditary infantile hemiparesis; retinal arteriolar tortuosity; and leukoencephalopathy). The mechanisms by which these genetic vasculopathies give rise to migraine is still unclear.^[27]

Migraine precipitants

Various precipitants of migraine events have been identified, as follows:

• Stress
• Excessive or insufficient sleep
• Medications (eg, vasodilators, oral contraceptives^[28] )
• Smoking
• Exposure to bright or fluorescent lighting
• Strong odors (eg, perfumes, colognes, petroleum distillates)
• Hormonal changes, such as menstruation (common),^[29] pregnancy, and ovulation
• Head trauma
• Weather changes
• Metabolic or infectious diseases
• Physical exertion or fatigue
• Motion sickness
• Cold stimulus (eg, ice cream headaches)

Certain foods and food additives can precipitate migraine. These include alcohol, caffeine, chocolates, artificial sweeteners (eg, aspartame, saccharin), monosodium glutamate (MSG), citrus fruits, and meats with nitrites.

Foods containing tyramine may provoke migraine. Such foods include the following:

• Aged cheese
• Yogurt
• Sour cream
• Chicken livers
• Sausages
• Bananas
• Avocados
• Canned figs
• Raisins
• Peanuts
• Soy sauce
• Pickled fish
• Fresh-baked breads
• Pork
• Vinegars
• Beans

Migraine and other vascular disease

People who suffer from migraine headaches are more likely to also have cardiovascular or cerebrovascular disease (ie, stroke and heart attacks).^[30] The physiopathology of the mechanism is still unknown. Reliable evidence comes from the Women's Health Study, which found that migraine with aura raised the risk of myocardial infarction by 91% and ischemic stroke by 108% and that migraine without aura raised both risks by approximately 25%.^[31]

Migraines during pregnancy are also linked to stroke and vascular diseases.^[32]

Migraine with aura for women in midlife has a statistical significant association with late-life vascular disease (infarcts) in the cerebellum. This association is not seen in migraine without aura.^[33]

Other related factors

In a population-based magnetic resonance imaging study by Kruit et al, migraineurs had increased local iron deposits in the putamen, globus pallidus, and red nucleus, compared with controls.^[34] This increase in iron deposits may be explained as a physiological response induced by repeated activation of nuclei involved in central pain processing or by the damage of these structures secondary to formation of free radicals in oxidative stress, possibly the cause of chronification of the disease.^[35]

In the United States, more than 30 million people have 1 or more migraine headaches per year. This roughly corresponds to approximately 18% of females and 6% of males.^[36] Migraine accounts for 64% of severe headaches in females and 43% of severe headaches in males.

Approximately 75% of all persons who experience migraines are women. Currently, 1 in 6 American women has migraine headaches.

The incidence of migraine with aura peaks in boys at around age 5 years and in girls at around age 12-13 years. The incidence of migraine without aura peaks in boys at age 10-11 years and in girls at age 14-17 years.^[37]

Before puberty, both the prevalence and incidence of migraine are higher in boys than in girls. In individuals older than 12 years, the prevalence increases in both males and females, reaching a peak at age 30-40 years. The female-to-male ratio increases from 2.5:1 at puberty to 3.5:1 at age 40 years. Attacks usually decrease in severity and frequency in individuals older than 40 years, except for women in perimenopause. Onset of migraine after age 50 years is rare. A study by Hsu et al suggests that women in aged 40-50 years are also more susceptible to migrainous vertigo.^[38] Onset of migraine after age 50 years is rare.

The reported incidence of migraine in females of reproductive age has increased over the last 20 years. This increase probably reflects greater awareness of the condition.

The prevalence of migraine appears to be lower among African Americans and Asian Americans than among whites. One study showed that among women, 20.4% of whites, 16.2% of African Americans, and only 9.2% of Asian Americans met International Classification of Headache Disorders (ICHD) criteria for migraine. Similarly, in males, 8.6% of whites, 7.2% of African Americans, and 4.8% of Asian Americans were considered to have migraine.

A study by Wilper et al found that insurance status affects migraine care in the United States. After controlling for age, gender, race, and geographic location, patients with migraines with no insurance or with Medicaid were less likely than the privately insured to receive abortive therapy. Thus, uninsured and those with Medicaid receive substandard therapy for migraine because they receive more care in emergency departments and less in the outpatient settings.^[39]

Economic impact of migraine

In the American Migraine Study, more than 85% of women and 82% of men with severe migraine had some headache-related disability. Migraineur males required 3.8 bed-rest days per year, whereas women required 5.6 bed-rest days per year. The loss of productive time from migraine in the US workforce is more than $13 billion per year, most of which is in the form of reduced productivity while at work.^[40]

International statistics

The World Health Organization (WHO) estimates a worldwide prevalence of current migraine of 10% and a lifetime prevalence of 14%. The adjusted prevalence of migraine is highest in North America, followed by South and Central America, Europe, Asia and Africa.

Approximately 3000 migraine attacks occur every day for each million of the general population worldwide. According to the WHO, migraine is 19th among all causes of years lived with disability.

In the United States, migraine prevalence is inversely correlated with household income and level of education. However, this relationship between migraine and socioeconomic status is not present internationally.

Migraine is a chronic condition, but prolonged remissions are common. One study showed that 62% of young adults were migraine free for more than 2 years, but only 40% continued to be migraine free after 30 years.

The severity and frequency of attacks tend to diminish with increasing age. After 15 years, approximately 30% of men and 40% of women no longer have migraine attacks.

Migraine and vascular disorders

Migraine and ischemic strokes reportedly occur in 1.4-3.3 per 100,000 population and account for 0.8% of total strokes. Milhaud et al showed that in young patients (< 45 y) with active migraine who had ischemic stroke, certain risk factors, such as patent foramen ovale, female gender, oral contraceptive use, and posterior circulation stroke, were much more likely to be present.^[41]

Even in patients older than 45 years, women with migraine were more likely to suffer from ischemic stroke. Migraineurs have a 2.5-fold increased risk of subclinical cerebellar stroke and those with migraines with aura and increased headache frequency are at the highest risk.^[42]

Migraineurs also have a higher incidence of adverse cardiovascular profile (including diabetes and hypertension), and they are more likely to be smokers, have a family history of early heart attacks, and have an unfavorable cholesterol profile. The odds of an elevated Framingham risk score of coronary artery disease are doubled with migraine with aura, and females with aura are more likely to be using oral contraceptives.^{[43, 44]}

The Women's Health Study, which included professional women older than 45 years showed that any history of migraine is associated with a higher incidence of major cardiovascular disease and that the highest risk is associated with migraine with aura, with a 2.3-fold risk of cardiovascular death and a 1.3-fold increased risk of coronary vascularization.^[45] However, those with migraine without aura have the same risks as the general population.

These findings have been confirmed in a population-based study by Bigal et al.^[46] According to Gudmundsson et al, both men and women who have migraine with aura are at a higher risk for cardiovascular and all-cause mortality than those without headache.^[47]

Patient education is key to successful long-term management. Migraine is a chronic neurologic disorder that requires a lifestyle change at some level

For patient education information, visit the Headache Center, as well as Causes and Treatments of Migraine and Related Headaches, Migraine Headache, Alternative and Complementary Approaches to Migraine and Cluster Headaches, Migraine Headache FAQs, and Understanding Migraine and Cluster Headache Medications.