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Migraine



Migraine
Classification & external resources
ICD-10 G43.
ICD-9 346
OMIM 157300
DiseasesDB 8207
MedlinePlus 000709
eMedicine neuro/218 
MeSH D008881

Migraine is a neurological disease that can cause a wide range of symptoms during an attack. The most commonly thought of symptom is headache.[1][2][3]

It is widespread in the population. In the U.S., 18% of women and 6% of men report having had at least one migraine episode in the previous year,[4] with seriousness ranging from an annoyance to a life-threatening and/or daily experience. Treatments are expensive in the US and free in most European countries.[citation needed] Periodic or unpredictable disability can cause poverty due to patients' inability to hold down a job.

Contents

Overview

Usually migraine causes episodes of severe or moderate headache (which is often one-sided and pulsating) lasting from several hours to three days, accompanied by gastrointestinal upsets, such as nausea and vomiting, and a heightened sensitivity to bright lights (photophobia) and noise (phonophobia). Approximately one third of people who experience migraine get a preceding aura.[5] The word migraine is French in origin and comes from the Greek hemicrania, as does the Old English term megrim. Literally, hemicrania means "half (the) head".

Migraines' secondary characteristics are inconsistent. Triggers precipitating a particular episode of migraine vary widely. The efficacy of the simplest treatment, applying warmth or coolness to the affected area of the head, varies between persons, sometimes worsening the migraine.[6] A particular migraine rescue drug may sometimes work and sometimes not work in the same patient. Some migraine types don't have pain or may manifest symptoms in parts of the body other than the head.

Available evidence suggests that migraine pain is one symptom of several to many disorders of the serotonergic control system, a dual hormone-neurotransmitter with numerous types of receptors. Two disorders — classic migraine with aura (MA, STG) and common migraine without aura (MO, STG) — have been shown to have a genetic factor.[7] Studies on twins show that genes have a 60 to 65% influence on the development of migraine (PMID 10496258 and PMID 10204850 ). Additional migraine types are suspected and could be proven to be genetic. Migraine understood as several or many disorders could explain the inconsistencies, especially if a single patient has more than one genetic type.

However, still other migraine types might be functionally acquired due to hormone organ disease or injury. Three quarters of adult migraine patients are female, although pre-pubertal migraine affects approximately equal numbers of boys and girls. This reveals the strong correlation to hormonal cycling and hormonal-related causes or triggers.[citation needed] Hormonal migraine is a likely consequence of periodically falling hormone levels causing reduction in protein biosynthesis of metabolic components including intestinal tract serotonin.

Classification

Migraines have been classified by the International Headache Society which periodically revises their classification.[8]

Defining severity of pain

In addition to classifying the type of headache, the International Headache Society defines intensity of pain on a verbal 4 point scale:[9]

  • 0 no pain
  • 1 mild pain 'does not interfere with usual activities'
  • 2 moderate pain 'inhibits, but does not wholly prevent usual activities'
  • 3 severe pain 'prevents all activities'

Migraine without aura

This is the most commonly seen form of migraine; patients who primarily suffer from migraine without aura may also have attacks of migraine with aura. According to the International Classification of Headache Disorders[8] it is a recurrent headache disorder manifesting in attacks lasting 4-72 hours. Typical characteristics of the headache are unilateral location, pulsating quality, moderate or severe intensity, aggravation by routine physical activity and association with nausea and/or photophobia and phonophobia.

In order to diagnose migraine without aura, there must have been at least five attacks not attributable to another cause that fulfill the following criteria:

1. Headache attacks lasting 4-72 hours when untreated
2. At least two of the following characteristics:
  • Unilateral location
  • Pulsating quality
  • Moderate or severe pain intensity
  • Aggravation by or causing avoidance of routine physical activity
3. During the headache there must be at least one of the following associated symptom clusters:
  • Nausea and/or vomiting
  • Photophobia and phonophobia

Where these criteria are not fully met, the problem may be classified as "probable migraine without aura" but other diagnoses such as "episodic tension type headache" must also be excluded.

Migraine with aura

This is the second most commonly seen form of migraine: patients who primarily suffer from migraine with aura may also have attacks of migraine without aura. According to the International Classification of Headache Disorders[8] it is a recurrent disorder manifesting in attacks of reversible focal neurological symptoms that usually develop gradually over 5-20 minutes and last for less than 60 minutes. Headache with the features of "migraine without aura" usually follows the aura symptoms. Less commonly, the aura may occur without a subsequent headache or the headache may be non-migrainous in type.

In order to diagnose migraine with aura, there must have been at least two attacks not attributable to another cause that fulfill the following criteria:

1. Aura consisting of at least one of the following, but no muscle weakness or paralysis:
  • Fully reversible visual symptoms (e.g. flickering lights, spots, lines, loss of vision)
  • Fully reversible sensory symptoms (e.g. pins and needles, numbness)
  • Fully reversible dysphasia (speech disturbance)
2. Aura has at least two of the following characteristics:
  • Visual symptoms affecting just one side of the field of vision and/or sensory symptoms affecting just one side of the body
  • At least one aura symptom develops gradually over more than 5 minutes and/or different aura symptoms occur one after the other over more than 5 minutes
  • Each symptom lasts from 5-60 minutes

Where these criteria are not fully met, a diagnosis of "probable migraine with aura" may be considered, although other neurological causes must also be excluded. If the picture complies with the criteria but includes one-sided muscular weakness or paralysis, a diagnosis of "sporadic hemiplegic migraine" or "familial hemiplegic migraine" should be considered.

Basilar type migraine

Basilar type migraine (BTM), formerly known as basilar artery migraine (BAM) or basilar migraine (BM), is an uncommon type of complicated migraine with symptoms that result from brainstem dysfunction. Serious episodes of BTM can lead to stroke, coma, or even death. The use of triptans and other vasoconstrictors as abortive treatments in BTM is contraindicated. Abortive treatments for BTM often focus on vasodilation and restoration of normal blood flow to the vertebrobasilar territory and subsequent return of normal brainstem function.

Familial hemiplegic migraine

See also the main article on Familial hemiplegic migraine

Familial hemiplegic migraine 'FHM' is a type of migraine with a possible polygenetic component. These migraine attacks may last 4-72 hours[8] and are apparently caused by ion channel mutations, three types of which have been identified to date. Patients who experience this syndrome have relatively typical migraine headaches preceded and/or accompanied by reversible limb weakness on one side as well as visual, sensory or speech difficulties. A non-familial form exists as well, "sporadic hemiplegic migraine" (SHM). It is often difficult to make the diagnosis between basilar-type migraine and hemiplegic migraine. When making the differential diagnosis is difficult, the deciding symptom is often the motor weakness or unilateral paralysis which can occur in FHM or SHM. While basilar-type migraine can present with tingling or numbness, true motor weakness and/or paralysis occur only in hemiplegic migraine.

Abdominal migraine

According to the International Classification of Headache Disorders[8] abdominal migraine is a recurrent disorder of unknown origin which occurs mainly in children. It is characterised by episodes of moderate to severe central abdominal pain lasting 1-72 hours. There is usually associated nausea and vomiting but the child is entirely well between attacks.

In order to diagnose abdominal migraine, there must be at least five attacks, not attributable to another cause, fulfilling the following criteria:

1. Attacks lasting 1-72 hours when untreated
2. Pain must have ALL of the following characteristics:
  • Location in the midline, around the umbilicus or poorly localised
  • Dull or 'just sore' quality
  • Moderate or severe intensity
3. During an attack there must be at least two of the following:
  • Loss of appetite
  • Nausea
  • Vomiting
  • Pallor

Most children with abdominal migraine will develop migraine headache later in life and the two may co-exist during adolescence.

Acephalgic migraine

Acephalgic migraine is a neurological syndrome. It is a variant of migraine in which the patient may experience aura symptoms such as scintillating scotoma, nausea, photophobia, hemiparesis and other migraine symptoms but does not experience headache. Acephalgic migraine is also referred to as amigrainous migraine, ocular migraine, or optical migraine.

Sufferers of acephalgic migraine are more likely than the general population to develop classical migraine with headache.

The prevention and treatment of acephalgic migraine is broadly the same as for classical migraine. However, because of the absence of "headache", diagnosis of acephalgic migraine is apt to be significantly delayed and the risk of misdiagnosis significantly increased.

Visual snow might be a form of acephalgic migraine.

If symptoms are primarily visual, it may be necessary to consult an ophthalmologist to rule out potential eye disease before considering this diagnosis.

Menstrual migraine

Menstrual migraine is distinct from other migraines. Approximately 21 million women in the US suffer from migraines,[10]and about 60% of them suffer from menstrual migraines. [11]


  • There are two types of menstrual migraine – Menstrually Related Migraine (MRM) and Pure Menstrual Migraine (PMM)
  • MRM is a headache of moderate-to-severe pain intensity that happens around the time of a woman’s period and at other times of the month as well.
  • PMM is similar in every respect but only occurs around the time of a woman’s period.[12]
  • The exact causes of menstrual migraine are uncertain but evidence suggest there may be a link between menstruation and migraine due to the drop in estrogen levels that normally occurs right before the period starts.[13]
  • Menstrual migraine has been reported to be more likely to occur during a five-day window, from two days before to two days after menstruation.[14]


When compared with migraines that occur at other times of the month, menstrual migraines have been reported to

  • Last longer—up to 72 hours[15]
  • Occur more often with nausea and vomiting[18]
  • Be more difficult to treat—occur more frequently[19]

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 to 60% of migraineurs. 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 vegetative symptoms. 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%[20][21] of migraineurs 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.[22]

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"). 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 ipsilateral nose-mouth area. 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.

Pain phase

The typical migraine headache is unilateral, throbbing, moderate to severe and can be aggravated by physical activity. Not all of these features are necessary. The pain may be bilateral at the onset or start on one side and become generalized, and usually alternates sides from one attack to the next. The onset is usually gradual. The pain peaks and then subsides, and usually lasts between 4 and 72 hours in adults and 1 and 48 hours in children. The frequency of attacks is extremely variable, from a few in a lifetime to several times a week, and the average migraineur experiences from 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, while vomiting occurs in about one third of patients. Many patients experience sensory hyperexcitability manifested by photophobia, phonophobia, 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. Lightheadedness, rather than true vertigo and a feeling of faintness may occur. The extremities tend to be cold and moist.

Postdrome phase

The patient may feel tired, "washed out", irritable, or listless and may have impaired concentration, scalp tenderness or mood changes. 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.

Diagnosis

Migraines are underdiagnosed[23] and misdiagnosed.[24] 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.[25]

The presence of either disability, nausea or sensitivity, can diagnose migraine with[26]:

Pathophysiology

Migraine was once thought to be initiated by problems with blood vessels. This theory is now largely discredited.[27] Current thinking is that a phenomenon known as cortical spreading depression is responsible for the disorder.[28] 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. 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 report impaired thinking for a few days after the headache has passed.

In 2005, research[29] was published indicating that in some people with a patent foramen ovale (PFO), a hole between the upper chambers of the heart, suffer from migraines which may have been caused by the PFO. The migraines reduce in frequency if the hole is patched. Several clinical trials are currently under way in an effort to determine if a causal link between PFO and migraine can be found. Early speculation as to this relationship has centered on the idea that the lungs detoxify blood as it passes through. The PFO allows uncleaned blood to go directly from the right side of the heart to the left without passing through the lungs.

Migraine headaches can be a symptom of Hypothyroidism.

Epidemiology

Migraine is an extremely common condition which will affect 12-28% of people at some point in their lives.[30] 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.[30] 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.[31] There is then a rapid growth in incidence amongst girls occurring after puberty[32],[33][34] which continues throughout early adult life.[35] By early middle age, around 25% of women experience a migraine at least once a year, compared with fewer than 10% of men.[30][36] 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%.[30][36]

At all ages, migraine without aura is more common than migraine with aura, with a ratio of between 1.5:1 and 2:1.[37][38] Incidence figures show that the excess of migraine seen in women of reproductive age is mainly due to migraine without aura.[39] Thus in pre-pubertal and post-menopausal populations, migraine with aura is somewhat more common than amongst 15-50 year olds[40][41]

  There is a strong relationship between age, gender and type of migraine,[42] illustrated here.


Geographical differences in migraine prevalence are not marked. Studies in Asia and South America suggest that the rates there are relatively low,[43][44] but they do not fall outside the range of values seen in European and North American studies.[30][45]

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.[46]

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.'

According to the National Library of Medicine's Medical Encyclopedia, 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
  • Lack of Water or dehydration
  • Alcohol or caffeine
  • Menstrual cycle fluctuations, birth control pills
  • 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.[47]

Many people report that one or more dietary, physical, hormonal, emotional, or environmental factors precipitate their migraines. The most-often reported triggers include: pesticides (sprayed fruits/vegetables), perfumes or fragrances (30% of sufferers), stress, over-illumination or glare, alcohol, foods, too much or too little sleep, and weather. Some women experience migraines in conjunction with monthly menstrual cycles.

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. Patients are urged to keep a "headache diary" in which to note what they eat and when they get a headache, to look for correlations, and to try to avoid headache by avoiding factors they identify as triggers. Typically this advice is accompanied by a list of trigger factors.

Food

In 2005, authors who reviewed the medical literature[48] found that the available information about dietary trigger factors relies mostly on the subjective assessments of patients. 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. The authors say dehydration deserves more attention, and that some patients report sensitivity to red wine. The authors found little or no demonstrated evidence that notorious suspected triggers chocolate, cheese, or that histamine, tyramine, nitrates, or nitrites normally present in foods trigger headaches. The artificial sweetener aspartame (NutraSweet®) has not been shown to trigger headache, but in a large and definitive study monosodium glutamate (MSG) in large doses (2.5 grams) was associated with adverse symptoms including headache more often than was placebo. 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.

On the other hand, several headache clinics have had good results with individually tailored dietary restriction as a therapy. Dr. Ian Livingstone, director of the Princeton Headache Clinic, recommends eliminating the following common headache triggers from the diet: aged cheese, monosodium glutamate, processed fish and meats containing nitrates (such as hot dogs), dark chocolate, aspartame, certain alcoholic beverages (including red wine), citrus fruits, and caffeine. After a period of one to two months, these foods can be reintroduced one at a time to determine their trigger potential for that individual. Adding large amounts of the suspected trigger in a short time may generate a response that is easy to observe.[citation needed]

Dr. David Buchholz, a neurologist who treats headaches at Johns Hopkins Hospital, has a longer list of suspected migraine triggers. He also recommends eliminating the triggers from the diet altogether, and then reintroducing them slowly after many weeks to measure the effects. His list includes: coffee (including decaf), chocolate, monosodium glutamate, processed meats and fish (aged, canned, preserved, processed with nitrates, and some meats that contain tyramine), cheese and dairy products (the more aged, the worse), nuts, citrus and some other fruits, certain vegetables (especially onions), fresh risen yeast baked goods, dietary sources of tyramine (including the foods listed above), and whatever gives you a headache.

The National Headache Foundation has a more specific list of triggers based on the tyramine theory, which differs slightly from David Buchholz's list. For example, it says that decaffeinated coffee is allowed. The list details "Allowed", "Use with caution", and "Avoid" triggers.[49]

Weather

Several studies have found some migraines are triggered by changes in weather. One study[50](Prince, 2004) noted that 62% of the subjects in the study thought that weather was a factor, in fact 51% were actually sensitive to weather changes. 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 (See Abortive Treatment)

Another study[51](Cooke, 2000) researched whether chinook winds (warm westerly winds occurring along the Front Ranges of the Rocky Mountains) are a migraine trigger. Many patients had 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 is "through increased air positive ion concentrations." (Cooke, 2000; full text web search quote)

Hair wash headache

Another trigger for migraine has been proposed by Dr.K.Ravishankar, a neurologist and headache specialist from India. He reported an unusual trigger for migraine seen among women, Hair Wash Headache. It is described as a migraine headache that originates with a head bath while sitting on the floor, or hanging the head downwards for an extended period of time.[52] (Ravishankar, 2006)

Treatment

Conventional treatment focuses on three areas: trigger avoidance, symptomatic control, and preventive drugs. Patients who experience migraines often find that the recommended treatments are not 100% effective at preventing migraines, and sometimes may not be effective at all.

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[53]


Trigger avoidance

Patients can 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. Beyond an often pronounced placebo effect, general dietary restriction has not been demonstrated to be an effective approach to treating migraine.[2]

Nonetheless, some people fervently claim that they have successfully identified foods that are likely to result in migraines, and by avoiding them, can decrease the likelihood of an episode.

Abortive treatment

Migraine sufferers usually develop their own coping mechanisms for the pain of a migraine attack. A cold or hot shower directed at the head, a hot or cold wet washcloth, a warm bath, or resting in a dark and silent room may be as helpful as medication for many patients, but both should be used when needed.[citation needed]

Some headache sufferers are surprised to learn that a simple cup of coffee is used daily around the world to control minor vascular headaches that are not quite migraines.[citation needed] Minor vascular headaches are frequently associated with the hormonal fluctuations of menstrual periods, irregular eating, and unusually hard work. For migraineurs, a well-timed cup of coffee can prevent outright migraine under the same conditions.

For patients who have been diagnosed with recurring migraines, doctors recommend taking migraine abortive medicines to treat the attack as soon as possible. Migraine without aura presenting without prodrome or nausea can present with sudden onset. Many patients avoid taking their medications when an attack is beginning, hoping that "it will go away". However, in many cases once an attack is underway, it can become intensely painful, last for a long time (sometimes even for several days), and become somewhat resistant to medical treatment. In contrast, treating the attack at the onset can often abort it before it becomes serious, and can reduce the near-term frequency of subsequent attacks.

For sufferers of weather-related migraines there is a simple treatment known as the Valsalva maneuver, which pilots and frequent fliers employ to relieve discomfort from pressure change. By holding your nose and gently pushing the air in your mouth back towards your ears and "popping" them you are opening your eustachian tubes. These normally open and close with regular chewing and talking but in some people may stay closed due to allergies or genetics. Regular opening and closing of the eustachian tubes allows a person to continually equalize to any change in the ambient barometric pressure. When this does not occur regularly the difference in pressure between the head and the environment can cause vascular swelling/constricting and trigger a migraine. Migraines can be stopped by doing the Valsalva maneuver three or four times.[citation needed] During changeable weather patterns doing the maneuver fifteen times per day can eliminate the headaches.

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.[54]
  • Paracetamol, at a dose of 1000 mg, benefited over half of patients with mild or moderate migraines in a randomized controlled trial.[55]
  • Simple analgesics combined with caffeine may help.[56] 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, and probably accounts for its benefit.[citation needed] Excedrin is an example of an aspirin with caffeine product. Caffeine is recognized by the U.S. FDA as an OTC treatment for migraine[citation needed].
  • 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.

Patients themselves often start off with paracetamol (known as acetaminophen in the USA), aspirin, ibuprofen, or other simple analgesics that are useful for tension headaches. Some patients find relief from taking Benadryl[citation needed], an over-the-counter sedative antihistamine, or anti-nausea agents. OTC drugs may provide some relief, although they are typically not effective for most sufferers. It is one of doctors' practical diagnoses of migraine head pain when patients say typical OTC drugs "won't touch it".[citation needed]

Serotonin agonists

Main article: triptans

Sumatriptan and related selective serotonin receptor agonists are excellent for severe migraines or those that do not respond to NSAIDs [54] or other over-the-counter drugs.[55] 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.

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). 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. 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.

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.

Narcotic pain killers (for example, codeine, morphine or other opiates) provide variable relief, but their side effects, the possibility of causing rebound headaches or analgesic overuse headache, and the risk of addiction contraindicates their general use.

Amidrine (a cocktail of a pain reliever, a sedative, and a vasoconstrictor) is sometimes prescribed for migraine headaches.

Anti-emetics by suppository or injection may be needed in cases where vomiting dominates the symptoms. The earlier these drugs are taken in the attack, the better their effect.

Intravenous chlorpromazine has proven very effective in treating status migrainosus — intractable and unremitting migraine.[citation needed]

Status migrainosus is an extremely rare life-threatening condition.[citation needed] In otherwise uncomplicated, non-nauseated cases, it can be treated with 20 mg of prednisone tablets every eight hours until the migraine ends, followed by mandatory tapering off doses (the classic steroid taper). Prednisone is a cortisol-like semi-synthetic adrenal hormone, a non-anabolic steroid, which strongly stimulates biosynthesis of proteins from DNA. The replicated proteins include enzymes that cure the migraine through numerous metabolic boosts, including molecular construction of more natural serotonin to be stored in blood platelets.

Prednisone risks include immune system suppression, adrenal axis suppression, non-addictive dependence, and long-term osteoporosis. Vitamin antioxidants taken with calcium and magnesium may reduce the damage caused by the extra free radicals released, and the bone lost, during long term prednisone use.[citation needed]

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.[59] An open-label study (funded by GelStat) found some tentative evidence of the treatment's effectiveness,[60] but no scientifically sound study has been done.

Comparative studies

Regarding comparative effectiveness of these drugs used to abort migraine attacks, a 2004 placebo-controlled trial[61] 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. Acetylsalicylic acid is OTC aspirin, ibuprofen is OTC Advil, and since migraineurs know they don't provide much relief, the results of this study are unexpected. They may be partly related to the dosage of acetylsalicylic acid used, which was considerably higher than the one or two 300 mg tablets normally recommended for OTC use. High doses of aspirin and ibuprofen may cause ringing of the ears, which is a sign of drug toxicity to the inner ear.

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.[54]

Preventive drugs[62]

Following treatment of an acute migraine, it is important to consider preventive measures. Factors that prompt consideration of such measures include: 1) more than two migraines per month with disabilities lasting three or more days per month; 2) failure of acute treatments; 3) contraindications to acute treatments; 4) adverse reactions from acute treatments; 5) use of acute treatments more than twice a week; or 6) presence of uncommon symptoms such as hemiplegia, prolonged, aura, or migraine infarction.

The main goal of preventive therapy is to reduce the frequency, severity, and durations of migraines, and to increase the effectiveness of abortive therapy. Another reason is to avoid medication overuse headache (MOH), otherwise known as rebound headache, which is an extremely common problem among migraneurs. This occurs in part due to overuse of pain medications. MOH results in the development of chronic daily headache due to "transformed" migraine.

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:

Other drugs:

  • Sansert 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.
  • Namenda, memantine HCI tablets, 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.
  • ASA or Asprin can be taken daily in low doses such as 80 to 81 mg, the blood thinners in ASA has been shown to help some migrainures, especially those who have an aura.

Physical therapy

Many physicians believe that exercise for 15-20 minutes per day is helpful for reducing the frequency of migraines.[69]

Massage therapy and physical therapy are often very effective forms of treatment to reduce the frequency and intensity of migraines. However, it is important to be treated by a well-trained therapist who understands the pathophysiology of migraines. Deep massage can 'trigger' a migraine attack in a person who is not used to such treatments. It is advisable to start sessions as short in duration and then work up to longer treatments.

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]

Prism eyeglasses

At least two British studies have shown a relationship between the use of eyeglasses containing prisms and a reduction in migraine headaches.

Turville, A. E. (1934) "Refraction and migraine". Br. J. Physiol. Opt. 8, 62–89, contains a good review of the literature and theories existing in 1934, and includes the vascular theory of migraine, which is popular today. In that study, Turville suggests that many patients were provided with complete relief from migraine symptoms with proper eyeglass prescriptions, which included prescribed prism.

Wilmut, E. B. (1956) "Migraine". Br. J. Physiol. Opt. 13, 93–97, replicated Turville's work. Both studies are subject to criticism because of sample bias, sample size, and the lack of a control group.

Neither study is available online, but another study that found that precision tinted lenses may be an effective migraine treatment and which references the Turville and Wilmut studies can be found at [3] (PDF).

Turville's and Wilmut's conclusions have largely been ignored since 1956 and it is widely believed that vision problems are not migraine triggers.

Most optometrists avoid prescribing prism because, when incorrectly prescribed, it can cause headaches.

Herbal and nutritional supplements

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.[4]

Cannabis was a standard treatment for migraines from the mid-19th century until it was outlawed in the early 20th century in the USA. 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. There is some indication that semi-regular use may reduce the frequency of attacks. Further studies are being conducted. Some migraine sufferers report that cannabis increases throbbing and pain, especially if smoked. A pharmaceutical company is currently conducting trials of a whole cannabis extract spray for migraine[5]

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,[70] 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.[71]

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.[72] However, since then, more studies have been carried out.[73] As well as its prophylactic properties, feverfew is also touted as a migraine abortative; see above.

Kudzu root (Pueraria lobata) has been demonstrated to help with menstrual migraine headaches and cluster headaches. While the studies on menstrual migraine assumed that kudzu acted by imitating estrogen, it has since been shown that kudzu has significant effects on the serotonin receptors. Kudzu Monograph at Med-Owl.

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.[74]

The supplement Riboflavin (also called Vitamin B2) has been shown (in a placebo-controlled trial)[75] to reduce the number of migraines, when taken at the high dose of 400 mg daily for three months.[76][77]

There is tentative evidence that Vitamin B12 may be effective in preventing migraines.[76] 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.[78] Although the study was not placebo-controlled, this response is larger than the typical placebo effect in migraine prophylaxis.[79]

Non-drug medical treatments

Botox is being used by many headache specialists for patients with frequent or chronic migraines with encouraging results.[80] Spinal cord stimulators are an implanted medical device sometimes used for those who suffer severe migraines several days each month.[81]

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.[6] In about 74% of the migraine headaches, TMS was found to eliminate or reduce nausea and sensitivity to noise and light.[7] 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.[82]

Alternatives

Because the conventional approaches to migraine prevention are not 100% effective and can have unpleasant side effects, many seek alternative treatments.

Some migraine sufferers find relief through acupuncture, which is usually used to help prevent headaches from developing.[83] Sometimes acupuncture is used to relieve the pain of an active migraine headache.[84] 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]

There is evidence to suggest that migraines, "The Bends" and altitude sickness are related and that alcohol brings on attacks through the same mechanism i.e. pressure change within the body.[85] This suggests that sufferers might be treated during an attack with a hyperbaric chamber of some sort, such as a Gamow bag.

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.[86] However, some scents can be a trigger factor.

Biofeedback has been used successfully by some to control migraine symptoms through training and practice.[87]

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.

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.

Sexual activity has been reported by a proportion of male and female migraine sufferers to relieve migraine pain significantly in some cases.[8]

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.

History

9000 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, Spanish-born physician Abulcasis, also known as Abu El Quasim, suggested application of a hot iron to the head or insertion of garlic into an incision made in the temple. In the Medieval 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

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. 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

Recent studies have suggested that migraine sufferers may be at increased risk of stroke in later life. A meta-analysis of several such studies published in the British Medical Journal[88] in 2005 appeared to confirm this association, with young adult sufferers and women using hormonal contraception at particular risk. 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.[89]

References

Migraine triggers

  • Federation of American Societies for Experimental Biology [FASEB] [1995]. Analysis of adverse reactions to monosodium glutamate (MSG). Bethesda, MD: Life Sciences Research Office, FASEB.
  • Ravishankar, K (2006). 'Hair wash' or 'Head bath' triggering migraine - observations in 94 Indian patients". Cephalagia 26 (11): 1330-1334. ISSN 0333-1024.

Treatment

  • Pearce, J.M.S. (1994). Headache. Neurological Management series. Journal of Neurology Neurosurgery and Psychiatry. 57, 134-144.
  • Mayo Clinic Staff. (2005). Migraine Headache. Retrieved August 14, 2005
  • Cathy Wong, ND. (2005). Migraine Elimination Diet Retrieved August 14, 2005
  • Treatment Articles (2005). Butterbur, Co-enzyme Q-10, Melatonin, Folic Acid
  • Buchholz, D. (2002) Heal your headache: The 1-2-3 Program, New York: Workman Publishing, ISBN 0-7611-2566-3
  • Livingstone, I. and Novak, D. (2003) Breaking the Headache Cycle, New York: Henry Holt and Co. ISBN 0-8050-7221-7
  • Izecksohn L, and Izecksohn C. . Fluids' Hypertension Syndromes, ISBN 978-85-906664-0-0.

Triptans

  • Cohen JA, Beall D, Beck A, et al. Sumatriptan treatment for migraine in a health maintenenace organization: economic, humanistic, and clinical outcomes. Clin Ther 1999;21:190-205.
  • Adelman JU, Sharfman M, Johnson R, et al. Impact of oral sumatriptan on workplace productivity, health-related quality of life, healthcare use, and patient satisfaction with medication in nurses with migraine. Am J Manag Care 1996;2:1407-1416.
  • Cohen JA, Beall DG, Miller DW, Beck A, Pait G, Clements BD. Subcutaneous sumatriptan for the treatment of migraine: humanistic, economic, and clinical consequences. Fam Med 1996;28:171-177.
  • Jhingran P, Cady RK, Rubino J, Miller D, Grice RB, Gutterman DL. Improvements in health-related quality of life with sumatriptan treatment for migraine. J Med Econ 1996;42:36-42.
  • Solomon GD, Nielsen K, Miller D. The effects of sumatriptan on migraine: health-related quality of life. Med Interface 1995;June:134-141.
  • Solomon GD, Skobieranda FG, Genzen JR. Quality of life assessment among migraine patients treated with sumatriptan. Headache 1995;35:449-454.
  • Santanello NC, Polis AB, Hartmaier SL, Kramer MS, Block GA, Silberstein SD. Improvement in migrainespecific quality of life in a clinical trial of rizatriptan. Cephalalgia 1997;17:867-872.
  • Caro JJ, Getsios D. Pharmacoeconomic evidence and considerations for triptan treatment of migraine. Expert Opin Pharmacother 2002;3:237-248.
  • Lofland JH, Johnson NE, Batenhorst AS, Nash DB. Changes in resource use and outcomes for patients with migraine treated with sumatriptan: a managed care perspective. Arch Intern Med 1999;159: 857-863.
  • Cady RC, Ryan R, Jhingran P, O’Quinn S, Pait DG. Sumatriptan injection reduces productivity loss during a migraine attack. Arch Intern Med 1998;158: 1013-1018.
  • Litaker DG, Solomon GD, Genzen JR. Impact of sumatriptan on clinic utilization and costs of care in migraineurs. Headache 1996;36:538-541.
  • Greiner DL, Addy SN. Sumatriptan use in a large group-model health maintenance organization. Am J Health Syst Pharm 1996;53:633-638.
  • Lofland JH, Kim SS, Batenhorst AS, et al. Cost-effectiveness and cost-benefit of sumatriptan in patients with migraine. Mayo Clin Proc 2001;76:1093- 1101.
  • Biddle AK, Shih YC, Kwong WJ. Cost-benefit analysis of sumatriptan tablets versus usual therapy for treatment of migraine. Pharmacotherapy 2000;20: 1356-1364.
  • Caro JJ, Getsios D, Raggio G, Caro G, Black L. Treatment of migraine in Canada with naratriptan: a costeffectiveness analysis. Headache 2001;41:456-464.

General

  • Sacks, Oliver (1999) Migraine, Vintage ISBN 0-520-08223-0
  • Relouzat, Raoul & Thiollet, Jean-Pierre, Vaincre la migraine, Anagramme, 2006 ISBN 2-35035046

Economic impact

  • Edmeads J, Mackell JA. The economic impact of migraine: an analysis of direct and indirect costs. Headache 2002;42:501-509.
  • Gerth WC, Carides GW, Dasbach EJ, Visser WH, Santanello NC. The multinational impact of migraine symptoms on healthcare utilisation and work loss. Pharmacoeconomics 2001;19:197-206.
  • Hu XH, Markson LE, Lipton RB, Stewart WF, Berger ML. Burden of migraine in the United States: disability and economic costs. Arch Intern Med 1999;159:813-818.
  • Osterhaus JT, Gutterman DL, Plachetka JR. Healthcare resource and low labour costs of migraine headaches in the US. Pharmacoeconomics 1992;2:2-11.

Clinical picture

  • Blau JN. Classical migraine: symptoms between visual aura and headache onset. Lancet 1992;340:355-6.
  • Silberstein SD: Migraine symptoms: Results of a survey of self-reported migraineurs. Headache 1995;35:387-96.
  • Silberstein SD, Saper JR, Freitag F. Migraine: Diagnosis and treatment. In: Silberstein SD, Lipton RB, Dalessio DJ, eds. Wolff's headache and other head pain. 7th ed. New York: Oxford University Press, 2001:121-237.
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Migraine". A list of authors is available in Wikipedia.
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