MIGRAINE

Migraine is a neurologic disease, of which the most common symptom is an intense and disabling headache. Migraine is the most common type of vascular headache. Migraine headaches are usually characterized by severe pain on one or both sides of the head, an upset stomach, and at times disturbed vision. The word "Migraine" comes from the Greek construction "hemikranion" (ημικρανίον, pain affecting one side of the head)
Signs & Symptoms

Migraine with aura is a neurological disease characterized by flare-ups generally referred to as "Migraine attacks." "Aura" refers to the non-headache features of Migraine that often happen before, or in the place of, the actual headache.

It is possible to have a Migraine attack marked by other symptoms and no headache at all, which is called acephalgic Migraine. The aura symptoms associated with these Migraines are very similar to the symptoms of Chronic Fatigue Syndrome, and thus it is possible that the two may be related, or even the same.

Many Migraine sufferers have headache without aura. Such headaches are commonly misdiagnosed as sinusitis or chronic sinus infections. The error can be revealed by a CT scan of the sinuses, which will show inflammation in the sinuses if a sinus infection is present. Migraine had been thought to be caused by vasodilation in the head and neck; however, newer research suggests that vascular dilation associated with Migraine is a symptom of Migraine, not the cause of Migraine symptoms.

Blood vessel diameter is under neurochemical control; in other words, blood vessels dilate during a Migraine episode because the nervous system tells them to. The cause of the pain itself is from activation of the trigeminal nerve. This theory is still being examined though. The trigger of the Migraine may be overactivity of nerve cells in certain areas of the brain (for example, the raphe nucleus). Often a Migraine episode is associated with strong emotional expression or psychic tension, but those may be Migraine symptoms rather than Migraine triggers.

The pain from a Migraine is typically one-sided, though it may encompass the whole head, or move from side-to-side as the Migraine progresses. Additionally, the pain from a Migraine is usually described as throbbing and moderate to severe in intensity. Migraines are frequently accompanied by nausea/vomiting and either photophobia (excessive sensitivity to light) or phonophobia (excessive sensitivity to sound), causing the sufferer to seek a dark, quiet room for recovery. If the predominant feature is vomiting or nausea cyclic vomiting syndrome should be considered as a possible cause.

In Migraine with aura, formerly called classical Migraine, the headache phase is preceded or accompanied by a group of specific symptoms called aura, most commonly experienced as a visual disturbance prior to the attack. Aura usually lasts less than 60 minutes, and in those who suffer Migraine with aura there is generally little time between the onset of aura and the onset of the attack. Migraine without aura, formerly called common Migraine, in contrast to Migraine with aura, lacks any manifestations associated with headache. Some experience aura without Migraine, a condition formerly called amigrainous Migraine or optical Migraine, now usually called acephalgic Migraine. Although sometimes comparable in severity, the symptoms of Migraine differ from those of cluster headache.

Visual aura can include castellated scotoma or fortification spectra, multicolored zig-zag patterns which can cover a large part of the visual field of one eye (sometimes both). Other types of visual aura involve distortions in perception of color, such as color bleeding or the appearance of halos, or as a white spot in the visual field, similar to when a camera flash temporarily "blinds" your vision.

While the most common type of aura is visual, it can manifest as any specific neurological symptom complex. Some experience tingling sensations called paresthesias or disturbances of other regions of the brain (such as language ability or smell) instead of a visual aura, either as an occasional alternate or as their normal aura. Some experience unusual odors that are not actually present, fatigue, nausea, balance problems, and vertigo.

Aura need not be related to the five senses: many Migraineurs experience a prodrome, a vague feeling that things are just not right. While the types and severity of aura can be extremely diverse, a given sufferer will generally experience similar manifestations of aura with each Migraine attack. Many people experience difficulty in speaking and/or forming cohesive syntax.

Migraine can accompany, in many cases, another type of headache called tension headache. Studies have demonstrated that, in patients who get both Migraines and tension headaches, their tension headaches will respond to their usual Migraine treatment. This is in contrast to patients who get only tension headaches.

Because chronic tension headaches are sometimes caused by the same triggers as Migraine and can often be remedied using the same treatments used for Migraine, and because Migraine itself presents with different symptoms for different people, there are some who believe that chronic tension headaches are just another symptom of Migraine.

Migraines can be associated with seizures. Stroke symptoms are seen in some patients and are known as complicated Migraine; these symptoms should not be permanent.

Migraine often runs in families and starts in adolescence, although evidence indicates that it starts also in childhood (including infants) or even in utero. In children, Migraine has some distinct features: headache is more often bilateral or difficult to localize, the patient is unable to describe the symptoms with significant accuracy; in infants, Migraine attacks may be manifested by periods of somnolence or irritability.

Because their symptoms vary, an intense headache may be misdiagnosed as a Migraine by a layperson. Indeed, many other headaches, some of them caused by very serious diseases (like a brain tumour, hydrocephalus, brain vascular disorders) may have a great resemblance to the clinical picture of Migraine and can lead to misdiagnosis. Where possible, see a doctor to determine if the headaches are a symptom of something else.

Hemiplegic Migraine may have periods of one-sided paralysis. This is one of the few types with a known etimology, a defect in atomic-size pores in the cell membranes of nerves that admit calcium into the cell. It may be associated with loss of conscioiusness and is often misdiagnosed as epilepsy. It can often be effectively prevented with medicines called calcium channel blockers.

A less frequently seen type of Migraine is the Basilar Type Migraine, which, until recently had also been referred to as a Basilary Artery Migraine. These Migraines have many of the same symptoms as Migraine with aura or Migraine without aura, but affect a different part of the brain, and are oftentimes accompanied by difficulty walking, speaking, or use of other motor skills. Other symptoms of Basilar Type Migraine may include depersonalization, auditory and visual hallucinations, and a distorted time sense.


Pathophysiology

Research scientists are unclear about the precise cause of Migraine headaches. There seems to be general agreement, however, that a key element is blood flow changes in the brain. People who get Migraine headaches appear to have blood vessels that overreact to various triggers.

Scientists have devised one theory of Migraine which explains these blood flow changes and also certain biochemical changes that may be involved in the headache process. According to this theory, the nervous system responds to a trigger such as stress by causing a spasm of the nerve-rich arteries at the base of the brain. The spasm closes down or constricts several arteries supplying blood to the brain, including the scalp artery and the carotid or neck arteries.

As these arteries constrict, the flow of blood to the brain is reduced. At the same time, blood-clotting particles called platelets clump together-a process which is believed to release a chemical called serotonin. Serotonin acts as a powerful constrictor of arteries, further reducing the blood supply to the brain.

Reduced blood flow decreases the brain's supply of oxygen. Symptoms (neurological symptoms) signaling a headache, such as distorted vision or speech, may then result, similar to symptoms of stroke.

Reacting to the reduced oxygen supply, certain arteries within the brain open wider to meet the brain's energy needs. This widening or dilation spreads, finally affecting the neck and scalp arteries. The dilation of these arteries triggers the release of pain-producing substances called prostaglandins from various tissues and blood cells. Chemicals which cause inflammation and swelling, and substances which increase sensitivity to pain, are also released. The circulation of these chemicals and the dilation of the scalp arteries stimulate the pain-sensitive nociceptors. The result, according to this theory: a throbbing pain in the head.

More recent imaging techniques seem to show that Migraine is primarily a disorder of the brain (neurological), not of the blood vessels (vascular). A spreading depolarization (electrical changes) may begin 24 hours before the attack, with onset of the headache occurring at about the time of maximum brain coverage. 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 was published indicating that in some people with a patent foramen ovale (PFO), a hole between the upper chambers of the heart, Migraine might result and that the Migraine ended if the hole were blocked. That procedure is hazardous enough that it may not be wise to treat solely to prevent Migraine, but if there is evidence of small strokes on magnetic resonance imaging, the procedure could be worthwhile. Early speculation as to the cause of the relationship has centered on the idea that the lungs detoxify blood as it passes through. The PFO allows blood to go directly from the right side of the heart to the left without passing through the lungs.


Migraine triggers

Migraine is irregularly episodic, so there needs to be some explanation for why a particular Migraine episode occurs at a particular time and not at another time.

The trigger theory supposes that exposure to various environmental factors precipitates, or triggers, individual Migraine episodes. Many people report that one or more dietary, physical, hormonal, emotional, or environmental factors precipitate their Migraines. The most-often reported triggers include stress, alcohol, foods, too much or too little sleep, and weather. Sometimes the Migraine occurs with no apparent "cause".

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.

Authors who in 2005 reviewed the medical literature 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 are sensitive 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 general dietary restriction has not been demonstrated to be an effective Migraine therapy.


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.


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.


Symptomatic control to abort attacks

Migraine sufferers usually develop their own coping mechanisms for intractable pain. A cold or hot shower directed at the head, a wet washcloth, less often 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.

For patients who have been diagnosed with recurring Migraines, doctors recommend taking painkillers to treat the attack as soon as possible. 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 frequency of subsequent attacks in the near-term.

The first line of treatment is over-the-counter abortive medication. Doctors start patients off with simple analgesics, such as paracetamol (acetaminophen), aspirin and caffeine. They may provide some relief, although they are not effective for most sufferers. Some patients find relief from taking Benadryl or other anti-nausea agents.

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.

If over-the-counter medications do not work, the next step for many doctors is to prescribe fioricet or fiorinal, which is a combination of butalbital (a barbiturate), acetaminophen (in fioricet) or acetylsalicylic acid (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.

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.

Until the introduction of sumatriptan (Imitrex®/Imigran®) around 1985, ergot derivatives (see ergoline) were the primary oral drugs available to abort a Migraine once it is underway. However, ergotamine tablets (usually with caffeine), though sometimes effective, have fallen out of favour. Absorption is erratic unless taken by suppository or injection. Dihydroergotamine (DHE), which must be injected or inhaled, can also be effective. These drugs can be used either as a preventive or abortive therapy.

Sumatriptan and related selective serotonin receptor agonists are now the therapy of choice for severe Migraine attacks that cannot be controlled by other means. They are highly effective, reducing the symptoms or aborting the attack within 30 to 90 minutes in 70-80% of patients. Some patients have a recurrent Migraine later in the day, and only one such recurrence in a day can be treated with a second dose of a triptan. They have few side effects if used in correct dosage and frequency. Some members of this family of drugs are:
Sumatriptan (Imitrex®, Imigran®)
Zolmitriptan (Zomig®)
Naratriptan (Amerge®, Naramig®)
Rizatriptan (Maxalt®)
Eletriptan (Relpax®)
Frovatriptan (Frova®)
Almotriptan (Almogran®)

Evidence is accumulating that these drugs are effective because they act on serotonin receptors in nerve endings as well as the blood vessels. This leads to a decrease in the release of several peptides, including CGRP and Substance P.

These drugs are available only by prescription (US and UK). Many Migraine sufferers do not use them only because they have not sought treatment from a physician.

Regarding comparative effectiveness of these drugs used to abort Migraine atacks, a 2004 placebo-controlled trial (Cephalalgia. 2004 Nov;24(11):947-54) reveals that acetylsalicylic acid, sumatriptan and ibuprofen are equally effective.

Triptan therapy has been shown to result in a reduction in lost productivity. Sumatriptan has been shown to result in an average of 0.5 fewer missed workdays during the first three months of therapy and 0.7 fewer missed workdays within the first six months, as well as a reduction in the number of days spent working while symptomatic. The average reduction in lost productivity has been estimated at $1,249, at a cost of $25 per day of disability avoided. The annual net savings in reduced health care costs and lost productivity, over the increased cost of triptan therapy, has been estimated at between $114 and $540 per patient; thus the use of these pharmaceuticals represents a cost savings as well as an improvement in the patients’ quality of life.


Preventive drugs

Patients who have more than two headache days per week are usually recommended to use preventatives and avoid overuse of acute pain medications.

Preventive medication has to be taken on a daily basis, usually for a few weeks, before the effectiveness can be determined. It is used only if attacks occur more often than every two weeks. 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.

The most effective prescription medications include several classes of medications including beta blockers such as propranolol and atenolol, antidepressants such as amitriptyline, and anticonvulsants such as valproic acid and topiramate.

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