migraine

This article may be too long to read and navigate comfortably. Please consider splitting content into sub-articles and using this article for a summary of the key points of the subject. (March 2009)

This article needs additional citations for verification. Please help improve this article by adding reliable references. Unsourced material may be challenged and removed. (May 2009)

Migraine is a neurological syndrome characterized by altered bodily perceptions, severe headaches, and nausea. Physiologically, the migraine headache is a neurological condition more common to women than to men. The word migraine was borrowed from Old French migraigne (originally as "megrim", but respelled in 1777 on a contemporary French model). The French term derived from a vulgar pronunciation of the Late Latin word hemicrania, itself based on Greek hemikrania, from Greek roots for "half" and "skull".^[1]

The typical migraine headache is unilateral and pulsating, lasting from 4 to 72 hours;^[2] symptoms include nausea, vomiting, photophobia (increased sensitivity to light), and phonophobia (increased sensitivity to sound).^[3][4][5] Approximately one-third of people who suffer migraine headache perceive an aura—unusual visual, olfactory, or other sensory experiences that are a sign that the migraine will soon occur.^[6]

Initial treatment is with analgesics for the headache, an antiemetic for the nausea, and the avoidance of triggering conditions. The cause of migraine headache is idiopathic; the accepted theory is a disorder of the serotonergic control system, as PET scan has demonstrated the aura coincides with diffusion of cortical depression consequent to increased blood flow (up to 300% greater than baseline).

There are migraine headache variants, some originate in the brainstem (featuring intercellular transport dysfunction of calcium and potassium ions) and some are genetically disposed.^[7] Studies of twins indicate a 60 to 65 percent genetic influence upon their propensity to develop migraine headache.^[8][9] Moreover, fluctuating hormone levels indicate a migraine relation: 75 percent of adult patients are women, although migraine affects approximately equal numbers of prepubescent boys and girls; propensity to migraine headache is known to disappear during pregnancy, although in some women migraines may become more frequent during pregnancy.^{[citation needed]}

Classification

The International Headache Society (IHS) classifies migraine headache.^[10]

Defining pain severity

The IHS defines the intensity of pain with a verbal, four-point scale:^[11]

Signs and symptoms

The signs and symptoms of migraine vary among patients. Therefore, what a patient experiences before, during and after an attack cannot be defined exactly. The four phases of a migraine attack listed below are common but not necessarily experienced by all migraine sufferers. Additionally, the phases experienced and the symptoms experienced during them can vary from one migraine attack to another in the same migraineur:

1. The prodrome, which occurs hours or days before the headache.
2. The aura, which immediately precedes the headache.
3. The pain phase, also known as headache phase.
4. The postdrome.

Prodrome phase

Prodromal symptoms occur in 40–60% of migraineurs (migraine sufferers). This phase may consist of altered mood, irritability, depression or euphoria, fatigue, yawning, excessive sleepiness, craving for certain food (e.g. chocolate), stiff muscles (especially in the neck), constipation or diarrhea, increased urination, and other visceral symptoms.^[12] These symptoms usually precede the headache phase of the migraine attack by several hours or days, and experience teaches the patient or observant family how to detect that a migraine attack is near.

Aura phase

For the 20–30%^[13][14] of individuals who suffer migraine with aura, this aura comprises focal neurological phenomena that precede or accompany the attack. They appear gradually over 5 to 20 minutes and generally last fewer than 60 minutes. The headache phase of the migraine attack usually begins within 60 minutes of the end of the aura phase, but it is sometimes delayed up to several hours, and it can be missing entirely. Symptoms of migraine aura can be visual, sensory, or motor in nature.^[15]

Visual aura is the most common of the neurological events. There is a disturbance of vision consisting usually of unformed flashes of white and/or black or rarely of multicolored lights (photopsia) or forma­tions of dazzling zigzag lines (scintillating scotoma; often arranged like the battlements of a castle, hence the alternative terms "fortification spectra" or "teichopsia"^{[citation needed]}). Some patients complain of blurred or shimmering or cloudy vision, as though they were look­ing through thick or smoked glass, or, in some cases, tunnel vision and hemianopsia. The somatosensory aura of migraine consists of digitolingual or cheiro-oral paresthesias, a feeling of pins-and-needles experienced in the hand and arm as well as in the nose-mouth area on the same side. Paresthesia migrate up the arm and then extend to involve the face, lips and tongue.

Other symptoms of the aura phase can include auditory or olfactory hallucinations, temporary dysphasia, vertigo, tingling or numbness of the face and extremities, and hypersensitivity to touch.

Visual symptoms of migraine aura

Enhancements reminiscent of a zigzag fort structure

Negative scotoma, loss of awareness of local structures

Positive scotoma, local perception of additional structures

Mostly one-sided loss of perception

Pain phase

This section does not cite any references or sources. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (September 2009)

The typical migraine headache is unilateral, throbbing, and moderate to severe and can be aggravated by physical activity. Not all these features are necessary. The pain may be bilateral at the onset or start on one side and become generalized, and usually it alternates sides from one attack to the next. The onset is usually gradual. The pain peaks and then subsides and usually lasts 4 to 72 hours in adults and 1 to 48 hours in children. The frequency of attacks is extremely variable, from a few in a lifetime to several a week, and the average migraineur experiences one to three headaches a month. The head pain varies greatly in intensity.

The pain of migraine is invariably accompanied by other features. Nausea occurs in almost 90 percent of patients, and vomiting occurs in about one third of patients. Many patients experience sensory hyperexcitability manifested by photophobia, phonophobia, and osmophobia and seek a dark and quiet room. Blurred vision, nasal stuffiness, diarrhea, polyuria, pallor, or sweating may be noted during the headache phase. There may be localized edema of the scalp or face, scalp tenderness, prominence of a vein or artery in the temple, or stiffness and tenderness of the neck. Impairment of concentration and mood are common. The extremities tend to feel cold and moist. Vertigo may be experienced; a variation of the typical migraine, called vestibular migraine, has also been described. Lightheadedness, rather than true vertigo,^{[citation needed]} and a feeling of faintness may occur.

Postdrome phase

The patient may feel tired or "hungover" and have head pain, cognitive difficulties, gastrointestinal symptoms, mood changes, and weakness.^[16] Some people feel unusually refreshed or euphoric after an attack, whereas others note depression and malaise. Often, some of the minor headache phase symptoms may continue, such as loss of appetite, photophobia, and lightheadedness. For some patients, a 5- to 6-hour nap may reduce the pain, but slight headaches may still occur when the patient stands or sits quickly. These symptoms may go away after a good night's rest, although there is no guarantee. Some people may suffer and recover differently than others.

Diagnosis

Migraines are underdiagnosed^[17] and misdiagnosed.^[18] The diagnosis of migraine without aura, according to the International Headache Society, can be made according to the following criteria, the "5, 4, 3, 2, 1 criteria":

• 5 or more attacks
• 4 hours to 3 days in duration
• 2 or more of - unilateral location, pulsating quality, moderate to severe pain, aggravation by or avoidance of routine physical activity
• 1 or more accompanying symptoms - nausea and/or vomiting, photophobia, phonophobia

For migraine with aura, only two attacks are required to justify the diagnosis.

The mnemonic POUNDing (Pulsating, duration of 4–72 hOurs, Unilateral, Nausea, Disabling) can help diagnose migraine. If 4 of the 5 criteria are met, then the positive likelihood ratio for diagnosing migraine is 24.^[19]

The presence of either disability, nausea or sensitivity, can diagnose migraine with:^[20]

• sensitivity of 81%
• specificity of 75%

Migraine should be differentiated from other causes of headaches such as cluster headaches. These are extremely painful, unilateral headaches of a piercing quality. The duration of the common attack is 15 minutes to three hours. Onset of an attack is rapid, and most often without the preliminary signs that are characteristic of a migraine.^{[citation needed]}

Pathophysiology

Migraines were once thought to be initiated exclusively by problems with blood vessels. The vascular theory of migraines is now considered secondary to brain dysfunction^[21] and claimed to have been discredited by others.^[22] Trigger points can be at least part of the cause, and perpetuate most kinds of headaches.^[23]

The effects of migraine may persist for some days after the main headache has ended. Many sufferers report a sore feeling in the area where the migraine was, and some^[who?] report impaired thinking for a few days after the headache has passed.

Migraine headaches can be a symptom of Hypothyroidism.^{[24][citation needed]}

Depolarization theory

Animation of cortical spreading depression

A phenomenon known as cortical spreading depression can cause migraines.^[25] In cortical spreading depression, neurological activity is depressed over an area of the cortex of the brain. This situation results in the release of inflammatory mediators leading to irritation of cranial nerve roots, most particularly the trigeminal nerve, which conveys the sensory information for the face and much of the head.

This view is supported by neuroimaging techniques, which appear to show that migraine is primarily a disorder of the brain (neurological), not of the blood vessels (vascular). A spreading depolarization (electrical change) may begin 24 hours before the attack, with onset of the headache occurring around the time when the largest area of the brain is depolarized. A French study in 2007, using the Positron Emission Tomography (PET) technique identified the hypothalamus as being critically involved in the early stages.^[26]

Vascular theory

Migraines can begin when blood vessels in the brain contract and expand inappropriately. This may start in the occipital lobe, in the back of the brain, as arteries spasm. The reduced flow of blood from the occipital lobe triggers the aura that some individuals who have migraines experience because the visual cortex is in the occipital area.^{[21][unreliable source?]}

When the constriction stops and the blood vessels dilate, they become too wide. The once solid walls of the blood vessels become permeable and some fluid leaks out. This leakage is recognized by pain receptors in the blood vessels of surrounding tissue. In response, the body supplies the area with chemicals which cause inflammation. With each heart beat, blood passes through this sensitive area causing a throb of pain.^{[21][unreliable source?]}

The vascular theory of migraines is now seen as secondary to brain dysfunction.^{[21][unreliable source?][27]}

Serotonin theory

Serotonin is a type of neurotransmitter, or "communication chemical" which passes messages between nerve cells. It helps to control mood, pain sensation, sexual behaviour, sleep, as well as dilation and constriction of the blood vessels among other things. Low serotonin levels in the brain may lead to a process of constriction and dilation of the blood vessels which trigger a migraine.^[21] Triptans activate serotonin receptors to stop a migraine attack.^[21]

Neural theory

When certain nerves or an area in the brain stem become irritated, a migraine begins. In response to the irritation, the body releases chemicals which cause inflammation of the blood vessels. These chemicals cause further irritation of the nerves and blood vessels and results in pain. Substance P is one of the substances released with first irritation. Pain then increases because substance P aids in sending pain signals to the brain.^[21]

Unifying theory

Both vascular and neural influences cause migraines.

1. stress triggers changes in the brain
2. these changes cause serotonin to be released
3. blood vessels constrict and dilate
4. chemicals including substance P irritate nerves and blood vessels causing pain^[21]

Triggers

A migraine trigger is any factor that, on exposure or withdrawal, leads to the development of an acute migraine headache. Triggers may be categorized as behavioral, environmental, infectious, dietary, chemical, or hormonal. In the medical literature, these factors are known as 'precipitants.'

The MedlinePlus Medical Encyclopedia, for example, offers the following list of migraine triggers:

Migraine attacks may be triggered by:

• Allergic reactions
• Bright lights, loud noises, and certain odors or perfumes
• Physical or emotional stress
• Changes in sleep patterns
• Smoking or exposure to smoke
• Skipping meals
• Alcohol
• Menstrual cycle fluctuations, birth control pills, hormone fluctuations during the menopause transition
• Tension headaches
• Foods containing tyramine (red wine, aged cheese, smoked fish, chicken livers, figs, and some beans), monosodium glutamate (MSG) or nitrates (like bacon, hot dogs, and salami)
• Other foods such as chocolate, nuts, peanut butter, avocado, banana, citrus, onions, dairy products, and fermented or pickled foods.

– MedlinePlus medical encyclopedia^[28]

Sometimes the migraine occurs with no apparent "cause". The trigger theory supposes that exposure to various environmental factors precipitates, or triggers, individual migraine episodes. Migraine patients have long been advised to try to identify personal headache triggers by looking for associations between their headaches and various suspected trigger factors and keeping a "headache diary" recording migraine incidents and diet to look for correlations in order to avoid trigger foods. It must be mentioned, that some trigger factors are quantitative in nature, i.e., a small block of dark chocolate may not cause a migraine, but half a slab of dark chocolate almost definitely will, in a susceptible person. In addition, being exposed to more than one trigger factor simultaneously will more likely cause a migraine, than a single trigger factor in isolation, e.g., drinking and eating various known dietary trigger factors on a hot, humid day, when feeling stressed and having had little sleep will probably result in a migraine in a susceptible person, but consuming a single trigger factor on a cool day, after a good night's rest with minimal environmental stress may mean that the sufferer will not develop a migraine after all. Migraines can be complex to avoid, but keeping an accurate migraine diary and making suitable lifestyle changes can have a very positive effect on the sufferer's quality of life. Some trigger factors are virtually impossible to avoid, e.g. the weather or emotions, but by limiting the avoidable trigger factors, the unavoidable ones may have less of an impact on the sufferer.

Food

Many migraine sufferers report reduced incidence of migraines due to identifying and avoiding their individual food triggers. However, more studies are needed.

Gluten One food elimination that has proven to reduce or eliminate migraines in a percentage of patients is gluten. For those with (often undiagnosed) celiac disease or other forms of gluten sensitivity, migraines may be a symptom of gluten intolerance. One study found that migraine sufferers were ten times more likely than the general population to have celiac disease, and that a gluten-free diet eliminated or reduced migraines in these patients.^[29] Another study of 10 patients with a long history of chronic headaches that had recently worsened or were resistant to treatment found that all 10 patients were sensitive to gluten. MRI scans determined that each had inflammation in their central nervous systems caused by gluten-sensitivity. Seven out of nine of these patients that went on a gluten-free diet stopped having headaches completely.^[30]

Aspartame While some people believe that aspartame triggers migraines, and anecdotal evidence is present, this has not been medically proven.^[31]

MSG In a placebo-controlled trial, monosodium glutamate (MSG) in large doses (2.5 grams) taken on an empty stomach was associated with adverse symptoms including headache more often than was placebo.^[32] However another trial found no effect when 3.5g of MSG was given with food.^[33]

Tyramine The National Headache Foundation has a specific list of triggers based on the tyramine theory, detailing allowed, with caution and avoid triggers.^[34] However, a 2003 review article concluded that there was no scientific evidence for an effect of tyramine on migraine.^[35]

Other A 2005 literature review found that the available information about dietary trigger factors relies mostly on the subjective assessments of patients.^[31] Some suspected dietary trigger factors appear to genuinely promote or precipitate migraine episodes, but many other suspected dietary triggers have never been demonstrated to trigger migraines. The review authors found that alcohol, caffeine withdrawal, and missing meals are the most important dietary migraine precipitants, that dehydration deserved more attention, and that some patients report sensitivity to red wine. Little or no evidence associated notorious suspected triggers like chocolate, cheese, histamine, tyramine, nitrates, or nitrites with migraines. However, the review authors also note that while general dietary restriction has not been demonstrated to be an effective migraine therapy, it is beneficial for the individual to avoid what has been a definite cause of the migraine.

Weather

Several studies have found some migraines are triggered by changes in weather. One study noted 62% of the subjects thought weather was a factor but only 51% were sensitive to weather changes.^[36] Among those whose migraines did occur during a change in weather, the subjects often picked a weather change other than the actual weather data recorded. Most likely to trigger a migraine were, in order:

1. Temperature mixed with humidity. High humidity plus high or low temperature was the biggest cause.
2. Significant changes in weather
3. Changes in barometric pressure

Another study examined the effects of warm chinook winds on migraines, with many patients reporting increased incidence of migraines immediately before and/or during the chinook winds. The number of people reporting migrainous episodes during the chinook winds was higher on high-wind chinook days. The probable cause was thought to be an increase in positive ions in the air.^[37]

Other

One study found that for some migraineurs in India, washing hair in a bath was a migraine trigger. The triggering effect also had to do with how the hair was later dried.^[38]

Strong fragrances have also been identified as potential triggers, and some sufferers report an increased sensitivity to scent as an aura effect.^[39]

Management

Conventional treatment focuses on three areas: trigger avoidance, symptomatic control, and prophylactic pharmacological drugs. Patients who experience migraines often find that the recommended migraine treatments are not 100% effective at preventing migraines, and sometimes may not be effective at all. Pharmacological treatments are considered effective if they reduce the frequency or severity of migraine attacks by 50%.^[40]

Children and adolescents are often first given drug treatment, but the value of diet modification should not be overlooked. The simple task of starting a diet journal to help modify the intake of trigger foods like hot dogs, chocolate, cheese and ice cream could help alleviate symptoms.^[41]

For patients who have been diagnosed with recurring migraines, migraine abortive medications can be used to treat the attack, and may be more effective if taken early, losing effectiveness once the attack has begun. Treating the attack at the onset can often abort it before it becomes serious, and can reduce the near-term frequency of subsequent attacks.^{[citation needed]}

Paracetamol or non-steroidal anti-inflammatory drug (NSAIDs)

The first line of treatment is over-the-counter abortive medication.

• Regarding non-steroidal anti-inflammatory drugs, a randomized controlled trial found that naproxen can abort about one third of migraine attacks, which was 5% less than the benefit of sumatriptan.^[42]
• Paracetamol (known as acetaminophen in North America) benefited over half of patients with mild or moderate migraines in a randomized controlled trial.^[43]
• Simple analgesics combined with caffeine may help.^[44] During a migraine attack, emptying of the stomach is slowed, resulting in nausea and a delay in absorbing medication. Caffeine has been shown to partially reverse this effect. Excedrin is an example of an aspirin with caffeine product. Caffeine is recognized by the U.S. Food and Drug Administration as an Over The Counter Drug (OTC) treatment for migraine when compounded with aspirin and paracetamol.^[45] Even by itself, caffeine can be helpful during an attack,^[46][47] despite the fact that in general migraine-sufferers are advised to limit their caffeine intake.^[47]

Patients themselves often start off with paracetamol, aspirin, ibuprofen, or other simple analgesics that are useful for tension headaches. OTC drugs may provide some relief, although they are typically not effective for most sufferers.

In all, the U.S. Food and Drug Administration has approved three OTC products specifically for migraine: Excedrin Migraine, Advil Migraine, and Motrin Migraine Pain. Excedrin Migraine, as mentioned above, is a combination of aspirin, acetaminophen, and caffeine. Both Advil Migraine and Motrin Migraine Pain are straight NSAIDs, with ibuprofen as the only active ingredient.^[48]

Analgesics combined with antiemetics

Antiemetics by mouth may help relieve symtoms of nausea and help prevent vomiting, which can diminish the effectiveness of orally taken analgesia. In addition some antiemetics such as metoclopramide are prokinetics and help gastric emptying which is often impaired during episodes of migraine. In the UK there are three combination antiemetic and analgesic preparations available: MigraMax (aspirin with metoclopramide), Migraleve (paracetamol/codeine for analgesia, with buclizine as the antiemetic) and paracetamol/metoclopramide (Paramax in UK).^[49] The earlier these drugs are taken in the attack, the better their effect.

Some patients find relief from taking other sedative antihistamines which have anti-nausea properties, such as Benadryl which in the US contains diphenhydramine (but a different non-sedative product in the UK).

Serotonin agonists

Sumatriptan and related selective serotonin receptor agonists are excellent for severe migraines or those that do not respond to NSAIDs^[42] or other over-the-counter drugs.^[43] Triptans are a mid-line treatment suitable for many migraineurs with typical migraines. They may not work for atypical or unusually severe migraines, transformed migraines, or status (continuous) migraines.

Serotonin specific reuptake inhibitors (SSRIs) are not approved by the U.S. Food and Drug Administration (FDA) for treatment of migraines, but have been found to be effective by clinical consensus.^[40]

Antidepressants

Tricyclic antidepressants have been long established as highly efficacious prophylactic treatments.^[40] These drugs, however, may give rise to undesirable side effects, such as insomnia, sedation or sexual dysfunction. SSRIs antidepressants are less established than tricyclics for migraines prophylaxis. Despite the absence of FDA approval for migraine treatment, antidepressants are widely prescribed.^[40] In addition to tricyclics and SSRIs, the anti-depressant nefazodone may also be beneficial in the prophylaxis of migraines due to its antagonistic effects on the 5-HT2A^[50] and 5-HT2C receptors^[51][52] It has a more favorable side effect profile than amitriptyline, a tricyclic antidepressant commonly used for migraine prophylaxis. Anti-depressants offer advantages for treating migraine patients with comorbid depression.^[40]

Ergot alkaloids

Until the introduction of sumatriptan in 1991, ergot derivatives (see ergoline) were the primary oral drugs available to abort a migraine once it is established.

Ergot drugs can be used either as a preventive or abortive therapy, though their relative expense and cumulative side effects suggest reserving them as an abortive rescue medicine. However, ergotamine tartrate tablets (usually with caffeine), though highly effective, and long lasting (unlike triptans), have fallen out of favour due to the problem of ergotism. Oral ergotamine tablet absorption is reliable unless the patient is nauseated. Anti-nausea administration is available by ergotamine suppository (or Ergostat sublingual tablets made until circa 1992). Ergot drugs themselves can be so nauseating it is advisable for the sufferer to have something at hand to counteract this effect when first using this drug. Ergotamine-caffeine 1/100 mg fixed ratio tablets (like Cafergot, Ercaf, etc.) are much less expensive per headache than triptans, and are commonly available in Asia and Romania (Cofedol). They are difficult to obtain in the USA. Ergotamine-caffeine can't be regularly used to abort evening or night onset migraines due to debilitating caffeine interference with sleep. Pure ergotamine tartrate is highly effective for evening-night migraines, but is rarely or never available in the USA. Dihydroergotamine (DHE), which must be injected or inhaled, can be as effective as ergotamine tartrate, but is much more expensive than $2 USD Cafergot tablets.

Steroids

Based on a recent meta analysis a single dose of IV dexamethasone, when added to standard treatment, is associated with a 26% decrease in headache recurrence.^[53]

Other agents

If over-the-counter medications do not work, or if triptans are unaffordable, the next step for many doctors is to prescribe Fioricet or Fiorinal, which is a combination of butalbital (a barbiturate), paracetamol (in Fioricet) or acetylsalicylic acid (more commonly known as aspirin and present in Fiorinal), and caffeine. While the risk of addiction is low, butalbital can be habit-forming if used daily, and it can also lead to rebound headaches. Barbiturate-containing medications are not available in many European countries.

Amidrine, Duradrin, and Midrin is a combination of acetaminophen, dichloralphenazone, and isometheptene often prescribed for migraine headaches. Some studies have recently shown that these drugs may work better than sumatriptan for treating migraines.^[54]

Antiemetics may need to be given by suppository or injection where vomiting dominates the symptoms.

Recently it has been found that calcitonin gene related peptides (CGRPs) play a role in the pathogenesis of the pain associated with migraine as triptans also decrease its release and action. CGRP receptor antagonists such as olcegepant and telcagepant are being investigated both in vitro and in clinical studies for the treatment of migraine.^[55]

Status migrainosus

Status migrainosus is characterized by migraine lasting more than 72 hours, with not more than four hours of relief during that period. It is generally understood that status migrainosus has been refractory to usual outpatient management upon presentation.

Treatment of status migrainosus consists of managing comorbidities (i. e. correcting fluid and electrolyte abnormalities resulting from anorexia and nausea/vomiting often accompanying status migr.), and usually administering parenteral medication to "break" (abort) the headache.

Although the literature is full of many case reports concerning treatment of status migrainosus, first line therapy consists of intravenous fluids, metoclopramide, and triptans or DHE.^[56]

Herbal treatment

The herbal supplement feverfew (more commonly used for migraine prevention, see below) is marketed by the GelStat Corporation as an OTC migraine abortive, administered sublingually (under the tongue) in a mixture with ginger.^[57] An open-label study (funded by GelStat) found some tentative evidence of the treatment's effectiveness,^[58] but no scientifically sound study has been done. Cannabis, in addition to prevention, is also known to relieve pain during the onset of a migraine.^[59]

Comparative studies

Regarding comparative effectiveness of these drugs used to abort migraine attacks, a 2004 placebo-controlled trial^[60] reveals that high dose acetylsalicylic acid (1000 mg), sumatriptan 50 mg and ibuprofen 400 mg are equally effective at providing relief from pain, although sumatriptan was superior in terms of the more demanding outcome of rendering patients entirely free of pain and all other migraine-related symptoms.

Another randomized controlled trial, funded by the manufacturer of the study drug, found that a combination of sumatriptan 85 mg and naproxen sodium 200 mg was better than either drug alone.^[42]

Recently the combination of sumatriptan 85 mg and naproxen sodium 500 mg was demonstrated to be effective and well tolerated in an early intervention paradigm for the acute treatment of migraine. Significant pain-free responses in favor of sumatriptan/naproxen were demonstrated as early as 30 minutes, maintained at 1 hour, and sustained from 2 to 24 hours. At 2 and 4 hours, sumatriptan/naproxen provided significantly lower rates of traditional migraine-associated symptoms (nausea, photophobia, and phonophobia) and nontraditional migraine-associated symptoms (neck pain/discomfort and sinus pain/pressure).^[61]

Epidemiology

Age-Gender Incidence

Migraine is an extremely common condition which will affect 12–28% of people at some point in their lives.^[62] However this figure — the lifetime prevalence — does not provide a very clear picture of how many patients there are with active migraine at any one time. Typically, therefore, the burden of migraine in a population is assessed by looking at the one-year prevalence — a figure that defines the number of patients who have had one or more attacks in the previous year. The third figure, which helps to clarify the picture, is the incidence — this relates to the number of first attacks occurring at any given age and helps understanding of how the disease grows and shrinks over time.

Based on the results of a number of studies, one year prevalence of migraine ranges from 6–15% in adult men and from 14–35% in adult women.^[62] These figures vary substantially with age: approximately 4–5% of children aged under 12 suffer from migraine, with little apparent difference between boys and girls.^[63] There is then a rapid growth in incidence amongst girls occurring after puberty,^[64][65][66] which continues throughout early adult life.^[67] By early middle age, around 25% of women experience a migraine at least once a year, compared with fewer than 10% of men.^[62][68] After menopause, attacks in women tend to decline dramatically, so that in the over 70s there are approximately equal numbers of male and female sufferers, with prevalence returning to around 5%.^[62][68]

At all ages, migraine without aura is more common than migraine with aura, with a ratio of between 1.5:1 and 2:1.^[69][70] Incidence figures show that the excess of migraine seen in women of reproductive age is mainly due to migraine without aura.^[69] Thus in pre-pubertal and post-menopausal populations, migraine with aura is somewhat more common than amongst 15–50 year olds.^[67][71]

There is a strong relationship between age, gender and type of migraine.^[72]

Geographical differences in migraine prevalence are not marked. Studies in Asia and South America suggest that the rates there are relatively low,^[73][74] but they do not fall outside the range of values seen in European and North American studies.^[62][68]

The incidence of migraine is related to the incidence of epilepsy in families, with migraine twice as prevalent in family members of epilepsy sufferers, and more common in epilepsy sufferers themselves.^[75]

Preventive treatment

Preventive (also called prophylactic) treatment of migraines can be an important component of migraine management. Such treatments can take many forms, including everything from taking certain drugs or nutritional supplements, to lifestyle alterations such as increased exercise and avoidance of migraine triggers.

The goals of preventive therapy are to reduce the frequency, painfulness, and/or duration of migraines, and to increase the effectiveness of abortive therapy.^[76] Another reason to pursue these goals is to avoid medication overuse headache (MOH), otherwise known as rebound headache, which is a common problem among migraneurs. This is believed to occur in part due to overuse of pain medications, and can result in chronic daily headache.^[77][78]

Many of the preventive treatments described below are quite effective: Even with a placebo (sham treatment), one-quarter of patients find that their migraine frequency is reduced by half or more, and actual treatments often far exceed this figure.^[79]

Trigger avoidance

Patients should attempt to identify and avoid factors that promote or precipitate migraine episodes. Moderation in alcohol and caffeine intake, consistency in sleep habits, and regular meals may be helpful. General dietary restriction has not been demonstrated to be an effective approach to treating migraine.^[80] However, eliminating particular foods that are known to trigger migraines in an individual can be very effective.

Gluten-Free Diet

Some individuals have a condition called celiac disease (or "gluten intolerance") that results in the body incorrectly processing gluten. Studies have suggested that many migraine sufferers have celiac disease, and for those who do, decreasing gluten intake may significantly reduce migraine frequency.^[81] Celiac disease and gluten sensitivity may be an underlying cause of migraines in some patients, and a gluten-free diet has been demonstrated to reduce, if not completely eliminate, migraines in these individuals. A study of 10 patients with a long history of chronic headaches that had recently worsened or were resistant to treatment found that all 10 patients were sensitive to gluten. MRI scans determined that each had inflammation in their central nervous systems caused by gluten-sensitivity. Seven out of nine of these patients that went on a gluten-free diet stopped having headaches completely.^[30] Another study showed that migraneurs were 10 times more likely than the general population to have celiac disease, and that for migraneurs with celiac disease, a gluten-free diet improved blood-flow to the brain and either eliminated migraines or reduced migraine frequency, duration, and intensity.^[81]

Prescription drugs

A 2006 review article by S. Modi and D. Lowder offers some general guidelines on when a physician should consider prescribing drugs for migraine prevention:

Following appropriate management of acute migraine, patients should be evaluated for initiation of preventive therapy. Factors that should prompt consideration of preventive therapy include the occurrence of two or more migraines per month with disability lasting three or more days per month; failure of, contraindication for, or adverse events from acute treatments; use of abortive medication more than twice per week; and uncommon migraine conditions (e.g., hemiplegic migraine, migraine with prolonged aura, migrainous infarction). Patient preference and cost also should be considered.

...Therapy should be initiated with medications that have the highest levels of effectiveness and the lowest potential for adverse reactions; these should be started at low dosages and titrated slowly. A full therapeutic trial may take two to six months. After successful therapy (e.g., reduction of migraine frequency by approximately 50 percent or more) has been maintained for six to 12 months, discontinuation of preventive therapy can be considered.

—^[76]

Preventive medication has to be taken on a daily basis, usually for a few weeks, before the effectiveness can be determined. Supervision by a neurologist is advisable. A large number of medications with varying modes of action can be used. Selection of a suitable medication for any particular patient is a matter of trial and error, since the effectiveness of individual medications varies widely from one patient to the next. Often preventive medications do not have to be taken indefinitely. Sometimes as little as six months of preventive therapy is enough to "break the headache cycle" and then they can be discontinued.

The most effective prescription medications include several drug classes:

• beta blockers such as propranolol and atenolol. A meta-analysis by the Cochrane Collaboration of nine randomized controlled trials or crossover studies, which together included 668 patients, found that propranolol had an "overall relative risk of response to treatment (here called the 'responder ratio')" was 1.94.^[82]
• anticonvulsants such as valproic acid and topiramate. A meta-analysis by the Cochrane Collaboration of ten randomized controlled trials or crossover studies, which together included 1341 patients, found anticonvulsants had an "2.4 times more likely to experience a 50% or greater reduction in frequency with anticonvulsants than with placebo" and a number needed to treat of 3.8.^[83] However, concerns have been raised about the marketing of gabapentin.^[84]
• antidepressants include tricyclic antidepressants (TCAs) such as amitriptyline and the newer selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine. A meta-analysis by the Cochrane Collaboration found selective serotonin reuptake inhibitors are no more effective than placebo.^[85] Another meta-analysis found benefit from SSRIs among patients with migraine or tension headache; however, the effect of SSRIs on only migraines was not separately reported.^[86] A randomized controlled trial found that amitriptyline was better than placebo and similar to propranolol.^[87]

A wide range of pharmacological drugs have been evaluated to determine their efficacy in reducing the frequency or severity of migraine attacks.^[40] These drugs include beta-blockers, calcium antagonists, neurostabalizers, nonsteroidal anti-inflammatory drugs (NSAIDs),tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), other antidepressants, and other specialized drug therapies.^[40] The US Headache Consortium lists five drugs as having medium to high efficacy: amitriptyline, divalproex, timolol, propranolol and topiramate.^[40] Lower efficacy drugs listed include aspirin, atenolol, fenoprofen, flurbiprofen, fluoxetine, gabapentin, ketoprofen, metoprolol, nadolol, naproxen, nimodipine, verapamil and Botulinum A.^[40] Additionally, most antidepressants (tricyclic, SSRIs and others such as Bupropion) are listed as "clinically efficacious based on consensus of experience" without scientific support.^[40] Many of these drugs may give rise to undesirable side-effects, or may be efficacious in treating comorbid conditions, such as depression.

Other drugs:

• Methysergide was withdrawn from the US market by Novartis, but is available in Canadian pharmacies. Although highly effective, it has rare but serious side effects, including retroperitoneal fibrosis.
• Memantine, which is used in the treatment of Alzheimer's Disease, is beginning to be used off label for the treatment of migraines. It has not yet been approved by the FDA for the treatment of migraines.
• Aspirin can be taken daily in low doses such as 80 mg, the blood thinners in ASA have been shown to help some migrainures, especially those who have an aura.

Herbal and nutritional supplements

Butterbur

50 mg or 75 mg/day of butterbur (Petasites hybridus) rhizome extract was shown in a controlled trial to provide 50% or more reduction in the number of migraines to 68% of participants in the 75 mg dose group, 56% in the 50 mg dose group and 49% in the placebo group after four months. Native butterbur contains some carcinogenic compounds, but a purified version, Petadolex, does not.^[88]

Cannabis

Cannabis was a standard treatment for migraines from 1874 to 1942.^[89] It has been reported to help people through an attack by relieving the nausea and dulling the head pain, as well as possibly preventing the headache completely when used as soon as possible after the onset of pre-migraine symptoms, such as aura.^[89]

Coenzyme Q10

Supplementation of coenzyme Q10 has been found to have a beneficial effect on the condition of some sufferers of migraines. In an open-label trial,^[90] Young and Silberstein found that 61.3% of patients treated with 100 mg/day had a greater than 50% reduction in number of days with migraine, making it more effective than most prescription prophylactics. Fewer than 1% reported any side effects. A double-blind placebo-controlled trial has also found positive results.^[91]

Feverfew

The plant feverfew (Tanacetum parthenium) is a traditional herbal remedy believed to reduce the frequency of migraine attacks. A number of clinical trials have been carried out to test this claim, but a 2004 review article concluded that the results have been contradictory and inconclusive.^[92] However, since then, more studies have been carried out.^[93] As well as its prophylactic properties, feverfew is also touted as a migraine abortative.

Magnesium citrate

Magnesium citrate has reduced the frequency of migraine in an experiment in which the magnesium citrate group received 600 mg per day oral of trimagnesium dicitrate. In weeks 9–12, the frequency of attacks was reduced by 41.6% in the magnesium citrate group and by 15.8% in the placebo group.^[94]

Omega-3 fatty acids

Omega 3 fatty acids have been studied as a method of controlling frequency and intensity of migraines, with a Danish study showing 2/3 of participants who took Omega 3 supplements seeing a decline in intensity and duration of migraines of roughly 30%^[95], however another study found Omega 3 treatment to be non-effective^[96]

Riboflavin

The supplement Riboflavin (also called Vitamin B₂) has been shown (in a placebo-controlled trial)^[97] to reduce the number of migraines, when taken at the high dose of 400 mg daily for three months.^[98][99]

Vitamin B12

There is tentative evidence that Vitamin B₁₂ may be effective in preventing migraines.^[98] In particular, in an open-label pilot study, 1 mg of intranasal hydroxocobalamin (a form of Vitamin B12), taken daily for three months, was shown to reduce migraine frequency by 50% or more in 10 of 19 participants.^[100] Although the study was not placebo-controlled, this response is larger than the typical placebo effect in migraine prophylaxis.^[79]

Melatonin

Melatonin has been studied in migraine and other headache disorders. In an open label study, migraine patients taking melatonin 3 mg before bedtime with a good headache response and tolerability. Melatonin has multiple mechanisms affecting migraine pathophysiology.^[101]

Surgical treatments

Surgical options for reducing or preventing migraines is an active area of research. Treatment of chronic migraines with botulinum neurotoxin (Botox) injections appears to be effective, but the Botox injections do not appear to work for episodic migraines.^[102] Several invasive surgical procedures are currently under investigation. One involves the surgical removal of specific muscles or the transection of specific cranial nerve branches in the area of one or more of four identified trigger points.^[103] There also appears to be a causal link between the presence of a patent foramen ovale and migraines.^[104][105]

Noninvasive medical treatments

Transcranial Magnetic Stimulation (TMS): At the 49th Annual meeting of the American Headache Society in June 2006, scientists from Ohio State University Medical Center presented medical research on 47 candidates that demonstrated that TMS — a medically non-invasive technology for treating depression, obsessive compulsive disorder and tinnitus, among other ailments — helped to prevent and even reduce the severity of migraines among its patients. This treatment essentially disrupts the aura phase of migraines before patients develop full-blown migraines.^[106] In about 74% of the migraine headaches, TMS was found to eliminate or reduce nausea and sensitivity to noise and light.[3] Their research suggests that there is a strong neurological component to migraines. A larger study will be conducted soon to better assess TMS's complete effectiveness.^[107] In June 2008, a hand-held apparatus designed to apply TMS as a preemptive therapy to avert a migraine attack at the onset of the aura phase was introduced in California.^[108]

Biofeedback has been used successfully by some to control migraine symptoms through training and practice.^[109]

Hyperbaric oxygen therapy has been used successfully in treating migraines.^{[110][111][112]} This suggests that sufferers might be treated during an attack with a hyperbaric chamber of some sort, such as a Gamow bag (as is done in the treatment of "The Bends" and altitude sickness).

Bruxism, clenching or grinding of teeth, especially at night, is a trigger for many migraineurs. A device called a nociceptive trigeminal inhibitor (NTI) takes advantage of a reflex limiting the force of clenching. It can be fitted by dentists and clips over the front teeth at night, preventing contact between the back teeth. It has a success rate similar to butterbur and co-enzyme Q10, although it has not been subjected to the same rigorous testing as the supplements. Massage therapy of the jaw area can also reduce such pain.

There is a speculative connection between vision correction (particular with prism eyeglasses) and migraines. Two British studies, one from 1934^[113] and another from 1956^[114] claimed that many patients were provided with complete relief from migraine symptoms with proper eyeglass prescriptions, which included prescribed prism. However, both studies are subject to criticism because of sample bias, sample size, and the lack of a control group. A more recent study^[115] found that precision tinted lenses may be an effective migraine treatment. (Most optometrists avoid prescribing prism because, when incorrectly prescribed, it can cause headaches.)

Behavioral treatments

Many physicians believe that exercise for 15–20 minutes per day is helpful for reducing the frequency of migraines.^[116]

Sleep is often a good solution if a migraine is not so severe as to prevent it, as when a person awakes the symptoms will have most likely subsided.

Diet, visualization, and self-hypnosis are also alternative treatments and prevention approaches.

Sexual activity has been reported by a proportion of male and female migraine sufferers to relieve migraine pain significantly in some cases.^[117]

In many cases where a migraine follows a particular cycle, attempting to interrupt the cycle may prolong the symptoms. Letting a headache "run its course" by not using painkillers can sometimes decrease the length of an episode. This is especially true of cases where vomiting is common, as often the headache will subside immediately after vomiting. Curbing the pain may delay vomiting, and prolong the headache.^{[citation needed]}

Alternative medicine

A number of forms of alternative medicine, particularly bodywork, are used in preventing migraines.

Clinical trials have suggested that chiropractic care may be an efficacious treatment for migraine headaches^[118][119] Likewise, Massage therapy, physical therapy, and Bowen Technique^[120] are often very effective forms of treatment to reduce the frequency and intensity of migraines.^{[citation needed]} These initial studies are limited by lack of control subjects, poor control subjects, lack of blind study design, small sample sizes, and other methodological flaws.^[121] Chiropractic researchers have argued that the current evidence for chiropractic treatment of migraines indicates that "evidence is steadily increasing to the point where there is now seen to be a moderate level of efficacy for chiropractic SMT in the treatment of headaches or migraines".^[121] The effect of chiropractic treatment may be mediated by stress release,^[121] and may be more efficacious for tension-type headaches than migraines^[122] A review of the literature until 2004 found that "Chiropractic manipulation demonstrated a trend toward benefit in the treatment of TTH, but evidence is weak. ... In the absence of clear evidence regarding their role in treatment, physicians and patients are advised to make cautious and individualized judgments about the utility of physical treatments for headache management; in most cases, the use of these modalities should complement rather than supplant better-validated forms of therapy."^[122]

Frequent migraines can leave the sufferer with a stiff neck which can cause stress headaches that can then exacerbate the migraines. Claims have been made that Myofascial Release can relieve this tension and in doing so reduce or eliminate the stress headache element.^{[citation needed]}

Some migraine sufferers find relief through acupuncture, which is usually used to help prevent headaches from developing.^[123] Sometimes acupuncture is used to relieve the pain of an active migraine headache.^[124] In one controlled trial of acupuncture with a sham control in migraine, the acupuncture was not more effective than the sham acupuncture but was more effective than delayed acupuncture.^{[citation needed]}

Additionally acupressure is used by some for relief. For instance pressure between the thumbs and index finger to help subside headaches if the headache or migraine isn't too severe.^{[citation needed]}

Incense and scents are shown to help. The smell and incense of peppermint and lavender have been proven to help with migraines and headaches more so than most other scents.^[125] However, some scents can be a trigger factor.

Large anecdotal evidence suggests that serotonergic psychedelic drugs such as LSD or psilocybin can prevent migraine headaches.

History

The Head Ache. George Cruikshank (1819)

9,000 year old skulls exist with evidence of trepanation. It is hypothesized that this drastic step was taken in response to headaches, though there is no clear evidence proving this.^{[citation needed]}. Headache with neuralgia was recorded in the medical documents of the ancient Egyptians as early as 1200 BC.

In 400 BC Hippocrates described the visual aura that can precede the migraine headache and the relief which can occur through vomiting. Aretaeus of Cappadocia is credited as the "discoverer" of migraines because of his second century description of the symptoms of a unilateral headache associated with vomiting, with headache-free intervals in between attacks.

Galenus of Pergamon used the term "hemicrania" (half-head), from which the word "migraine" was derived. He thought there was a connection between the stomach and the brain because of the nausea and vomiting that often accompany an attack. For relief of migraine, Andalusian-born physician Abulcasis, also known as Abu El Qasim, suggested application of a hot iron to the head or insertion of garlic into an incision made in the temple.

In the Middle Ages migraine was recognized as a discrete medical disorder with treatment ranging from hot irons to blood letting and even witchcraft^{[citation needed]}. Followers of Galenus explained migraine as caused by aggressive yellow bile. Ebn Sina (Avicenna) described migraine in his textbook "El Qanoon fel teb" as "... small movements, drinking and eating, and sounds provoke the pain... the patient cannot tolerate the sound of speaking and light. He would like to rest in darkness alone." Abu Bakr Mohamed Ibn Zakariya Râzi noted the association of headache with different events in the lives of women, "...And such a headache may be observed after delivery and abortion or during menopause and dysmenorrhea."

In Bibliotheca Anatomica, Medic, Chirurgica, published in London in 1712, five major types of headaches are described, including the "Megrim", recognizable as classic migraine. Graham and Wolff (1938) published their paper advocating ergotamine tart for relieving migraine. Later in the 20th century, Harold Wolff (1950) developed the experimental approach to the study of headache and elaborated the vascular theory of migraine, which has come under attack as the pendulum again swings to the neurogenic theory.

Economic impact

This section does not cite any references or sources. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (August 2008)

In addition to being a major cause of pain and suffering, chronic migraine attacks are a significant source of both medical costs and lost productivity. It has been estimated to be the most costly neurological disorder in the European Community, costing more than €27 billion per year^[126]. Medical costs per migraine sufferer (mostly physician and emergency room visits) averaged $107 USD over six months in one 1988 study,^{[citation needed]} with total costs including lost productivity averaging $313. Annual employer cost of lost productivity due to migraines was estimated at $3,309 per sufferer. Total medical costs associated with migraines in the United States amounted to one billion dollars in 1994, in addition to lost productivity estimated at thirteen to seventeen billion dollars per year. Employers may benefit from educating themselves on the effects of migraines in order to facilitate a better understanding in the workplace. The workplace model of 9–5, 5 days a week may not be viable for a migraine sufferer. With education and understanding an employer could compromise with an employee to create a workable solution for both.

Migraine and cardiovascular risks

The risk of stroke may be increased two- to threefold in migraine sufferers. Young adult sufferers and women using hormonal contraception appear to be at particular risk.^[127] The mechanism of any association is unclear, but chronic abnormalities of cerebral blood vessel tone may be involved. Women who experience auras have been found to have twice the risk of strokes and heart attacks over non-aura migraine sufferers and women who do not have migraines.^[127][128] Migraine sufferers seem to be at risk for both thrombotic and hemorrhagic stroke as well as transient ischemic attacks.^[129] Death from cardiovascular causes was higher in people with migraine with aura in a Women's Health Initiative study, but more research is needed to confirm this.^[130][128]

See also

Footnotes

References

External links

• Migraine at the Open Directory Project
• Migraine Headache Information
• Migraine Triggers and Treatment

General information

• Migraine Information from the US National Institute of Neurological Disorders and Stroke
• Diagnostic criteriaPDF (1.21 MB)
• Alternative and Complementary Approaches to Migraine and Cluster Headaches

Organizations

• World Headache Alliance
• Headache, a medical journal