Migraines

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".

The typical migraine headache is unilateral (affecting one half of the head) and pulsating, lasting from 4 to 72 hours; symptoms include nausea, vomiting, photophobia (increased sensitivity to light), and phonophobia (increased sensitivity to sound). 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.

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 unknown; the most common theory is a disorder of the serotonergic control system.

There are migraine headache variants, some originate in the brainstem (featuring intercellular transport dysfunction of calcium and potassium ions) and some are genetically disposed. Studies of twins indicate a 60 to 65 percent genetic influence upon their propensity to develop migraine headache. 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.

Rodents can be grown that suffer from the condition.

Diagnosis

Migraines are underdiagnosed and misdiagnosed. 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.

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

• 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.

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. 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% of migraine sufferers who experience 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.

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 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.

Pain phase

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, 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. 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.

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:

• 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.

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, e.g., 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. 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.
• Aspartame While some people believe that aspartame triggers migraines, and anecdotal evidence is present, this has not been medically proven.
• MSG MSG is frequently reported as a dietary trigger (12%). 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. However another trial found no effect when 3.5g of MSG was given with food.
• Tyramine The National Headache Foundation has a specific list of triggers based on the tyramine theory, detailing allowed, with caution and avoid triggers. However, a 2003 review article concluded that there was no scientific evidence for an effect of tyramine on migraine.
• Other A 2005 literature review 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, 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. 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.

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.

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

Prevention

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. 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.

Many of the preventive treatments are quite effective: Even with a placebo, one-quarter of patients find that their migraine frequency is reduced by half or more, and actual treatments often far exceed this figure. There are many medicines available to prevent or reduce frequency, duration and severity of migraine attacks. They may also prevent complications of migraine. Propranolol, atenolol, metoprolol, flunarizine, sodium valproate, topiramate are some of the commonly used drugs. But they need to be taken for about 3 months or more.

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%.

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.

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.

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.
• Paracetamol (known as acetaminophen in North America) benefited over half of patients with mild or moderate migraines in a randomized controlled trial.
• Simple analgesics combined with caffeine may help. 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. Even by itself, caffeine can be helpful during an attack, despite the fact that in general migraine-sufferers are advised to limit their caffeine intake.
• 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.

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). 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 or other over-the-counter drugs. 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.

Antidepressants

Tricyclic antidepressants have been long established as highly efficacious prophylactic treatments. 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. 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 and 5-HT2C receptors. 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.

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.

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.

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.

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.

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. An open-label study (funded by GelStat) found some tentative evidence of the treatment's effectiveness, 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.

Comparative studies

Regarding comparative effectiveness of these drugs used to abort migraine attacks, a 2004 placebo-controlled trial 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. [Note that 50mg of sumatriptan is not a commonly prescribed full dose (100mg), so would be expected to not be fully comparable.]

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.

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).

Prognosis

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. 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. Migraine sufferers seem to be at risk for both thrombotic and hemorrhagic stroke as well as transient ischemic attacks.[76] 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.