Migraine

DESCRIPTION

Migraine is a neurological and often hereditary disease in which the most prominent symptom is an intense, pounding headache. The headache, itself called a migraine, is usually felt on one side of the head and is accompanied by other symptoms including nausea, vomiting, and visual disturbances. During a migraine attack, blood vessels in the head become hyperreactive and enter into a repetitive cycle of extreme constriction followed by rapid dilation. While a full understanding of the process that produces a migraine headache has not yet been reached, most scientists believe in the following basic scenario: a variety of triggers, which differ from individual to individual, imbalance brain chemistry causing nerve pathway changes, specifically in a major nerve pathway in the brain called the trigeminal system. The trigeminal nerve releases neuropeptides, which inflame blood vessels causing them to constrict and then dilate. These blood vessel changes then restimulate trigeminal nerve endings to release more neuropeptides, initiating a vicious cycle. The result is a severe throbbing headache that may last anywhere from 2–72 hours.

Migraine headaches are generally classified as either “common” or “classic”. Common migraines come on without warning, while classic migraines, which are more typical, are preceded by auras before the onset of pain. Auras usually last a few minutes and include blurring or bright spots in the vision, anxiety, fatigue, disturbed thinking, and numbness or tingling on one side of the body.

A surprisingly common disorder, migraines affect between 18 and 26 million Americans, 15–20% of men and 25–30% of women. Initial onset is often during the teen years, but migraines also commonly occur for the first time between the ages of 20 and 40. Frequency varies dramatically. In some people, migraines occur weekly, in others, less than once a year. Among female migraineurs (migraine sufferers), about 65% experience migraines immediately before, during, or immediately after their monthly period.

 
FREQUENT SIGNS AND SYMPTOMS

Classic migraine

Although the signs and symptoms of a migraine attack vary among individuals and even in the same individual over time, the symptoms of a “classic” migraine typically occur in the following sequence.

• An aura that may affect vision, hearing or smell precedes the headache.
• The most common aura symptom is an inability to see clearly, followed by seeing bright spots and zigzag patterns. Visual disturbances may last several minutes to several hours, but disappear once the headache begins.
• Other common preceding symptoms include a feeling of anxiety, fatigue, disturbed thinking, and/or numbness or tingling on one side of the body.
• Dull, boring pain begins in one temple and spreads to that entire side of the head, becoming intense, pounding or throbbing.
• Nausea, vomiting.

Common migraine

In a “common” migraine, the headache may occur without preceding aura symptoms. In either classic or common migraine, the following symptoms may be present:

• Pale skin
• Bloodshot eyes
• Runny nose or eyes (in some individuals)
• Gastrointestinal upset, nausea and anorexia accompanying the headache
• Drowsiness following the headache.

CAUSES

The proximate cause of migraine is a hyperreactivity of nerves in the head (the trigeminal system), which triggers constriction and then rebound dilation of blood vessels that go to the scalp and brain. Headache begins when these blood vessels dilate (widen) again. Several hypotheses have been advanced as to the why these nerves become hyperreactive including the following:

• Inherited vascular instability: migraine patients may have an inherited abnormality in their control of blood vessel constriction and dilation and/or may be abnormally sensitive to the effects of physical and chemical factors that cause these changes in blood vessels.
• Platelet disorder: platelets are small blood cells involved in the formation of blood clots. Migraine sufferers’ platelets act differently from normal platelets:
• Migraineurs’ platelets spontaneously clump together (aggregate) much more often than normal platelets.
• Migraineurs’ platelets release serotonin differently from normal platelets:
• Serotonin is a compound used in the chemical transfer of information from one cell to another and also plays a role in vascular tone – the state of relaxation or constriction of blood vessels.
• Normal platelets release only a set amount of serotonin when they are stimulated.
• Platelets of migraineurs, in response to stimulation (such as from exposure to a chemical or food allergen), release higher and higher amounts of serotonin until a migraine is produced.
• Mitral valve prolapse: patients with classic migraine are twice as likely as normal individuals to have mitral valve prolapse, i.e., a leaky heart valve. With each beat of the heart, this leaky valve can damage platelets as they surge through, thus leading to the platelet disorder described above.
• Excessive levels of estrogen: estrogen contributes to migraines by increasing the uptake of magnesium into bone and soft tissues, thus decreasing the amount of magnesium available to stabilize brain cell membranes:
• One of magnesium’s most important jobs is stabilizing cellular membranes, thus regulating molecular traffic into and out of cells. When magnesium levels are low, brain cell membranes become much more permeable, rendering them hyperreactive and prone to a special kind of neuronal depression termed “spreading depression” that is the first phase of a migraine attack.
• When estrogen levels are too high, too much magnesium is shunted into bone and soft tissue, leaving both brain and blood vessel cell membranes unstable, and prone to hyperreactivity.
• Estrogen may rise to abnormally high levels during a woman’s menstrual cycle, particularly immediately before, during or immediately after menstruation:
• High estrogen levels are a primary cause of premenstrual syndrome (PMS).
• Estrogen levels fluctuate widely during perimenopause, frequently spiking to higher than optimal levels.
• Supplemental estrogen from oral contraceptive use or hormone replacement therapy can also raise estrogen to problematic levels.
• When estrogen is prescribed to help prevent osteoporosis, high doses of calcium are also typically given, which exacerbates any magnesium inadequacy:
• Calcium and magnesium are usually maintained in a delicate balance necessary for the many enzymatic reactions that occur during normal cellular metabolism. Not only are these reactions disrupted, but excessive amounts of calcium, which competes with magnesium for entry into the cells, blocks magnesium’s absorption.
• In addition, the influx of calcium into blood vessel cells causes blood vessels to constrict.
• Nerve disorder: nerve cells in the blood vessels of migraineurs are more prone to release a compound termed “substance P”, which triggers pain, dilates blood vessels, and signals the immune system’s white blood cells, called mast cells, to release histamine and other allergic compounds. Chronic stress is thought to play an important role in hypersensitizing nerve cells.
• Serotonin deficiency: migraineurs have been found to have low levels of the neurotransmitter serotonin in their tissues. Low serotonin levels lead to a decrease in the pain threshold in patients with chronic headaches:
• Low serotonin is most likely due to higher than normal activity of MAO (monoamine oxidase).MAO, an enzyme found in the gut as well as in the brain, breaks down chemicals in foods that affect the tone of blood vessels, thus preventing the absorption of these chemicals into the bloodstream. Because serotonin, which acts as a neurotransmitter in the brain, is also a potent vasoconstrictor and stimulator of smooth muscle contraction in the gut, it is broken down by MAO.
• Many prescription drugs for migraine (e.g., sumatriptan) work by inhibiting MAO, thus increasing serotonin levels.
• The serotonin system is, however, very complicated. Some serotonin receptors actually trigger migraines while others prevent them:
• Drugs that bind to serotonin 5-HT1c receptors trigger migraines, while drugs that inhibit 5-HT1c receptors or bind to 5-HT1d receptors may prevent migraines.
• The serotonin precursor 5-HTP (5-hydroxytryptophan)prevents migraines by gradually decreasing the sensitivity of 5-HT1c receptors
  while increasing the sensitivity of 5-HT1d receptors, the reason why 5-HTP becomes more effective over time (better results are seen after 60 days than after 30 days)
• Low levels of phenol-sulfotransferase (PST): the enzyme PST normally breaks down serotonin and other chemicals in platelets that affect blood vessel tone. In addition to being in platelets, these chemicals, called amines, are found in certain foods such as red wine, chocolate, and cheese:
• Many migraineurs have been found to have significantly lower levels of PST, so they are more susceptible to the accumulation of amines, such as histamine. Histamine, an inflammatory amine known for its production of cold-like allergy symptoms, also causes blood vessels to expand, thus acting as a migraine trigger.
• Low levels of diamine oxidase: this enzyme breaks down histamine found in the lining of the small intestine before it can be absorbed into the circulation, travel to the head and cause blood vessel dilation:
• Diamine oxidase is a vitamin B6-dependent enzyme. If a person is deficient in B6 or ingests compounds that inhibit B6, diamine oxidase activity is inhibited. Factors that inhibit B6 include food coloring agents (specifically the hydrazine dyes such tartrazine, also called FD&C yellow #5), some drugs (isoniazid, hydralazine, dopamine, and penicillamine), birth control pills, alcohol, and excessive protein intake.
• Women have lower levels of diamine oxidase than men, which may explain their higher incidence of migraine.
• During pregnancy, a woman’s diamine oxidase levels increase by over 500% – one reason why remission of headaches is common during pregnancy.
• A combination of causes: migraines are most likely initiated when a combination of triggers builds to a threshold, after which the next stressor sets off the series of physiological reactions that produce a headache. Reaching this critical threshold is probably the result of a combination of decreased tissue serotonin levels, low levels of magnesium, changes in platelets, increased sensitivity to compounds such as substance P, and the buildup of histamine and other chemicals that cause inflammation.

Triggering factors

As explained above, in most cases, a single trigger will not cause a migraine, but when combined with other potential stressors will produce sufficient stimulus to provoke an attack. An individual’s triggers are often complex. To identify them, a daily diary should be kept recording foods eaten, weather conditions, medications taken, and any other potential triggers. Particular combinations of triggers may also increase the severity of a migraine.

Common triggers include the following:

• Tension: prolonged tension or stress causes an increase in the secretion of stress hormones and a shift of magnesium from inside of cells to the bloodstream:
• Sress hormones constrict blood vessels and stimulate platelets to aggregate more easily.
• A lowering of the level of magnesium within cells renders them more permeable, thus more likely to become hyperreactive.
• Drug reaction: several clinical studies have estimated that 70% of patients with chronic headaches suffer from drug-induced headaches, of which there are two basic types: analgesic rebound and ergotamine rebound:
• Analgesic-rebound headaches: analgesic medications such as aspirin or acetaminophen constrict blood vessels. Rebound dilation may occur as their effects wear off:
• In one study, migraineurs who took more than 30 analgesic tablets per month were found to have twice as many headaches as those who took fewer analgesics.
• In another study, when 70 patients consuming 14 or more analgesic tablets per week discontinued their use, 66% were improved within 1 month, and 81% were improved within 2 months.
• Dosage that typically leads to rebound headache is 1,000 mg of either acetaminophen or aspirin.
• Withdrawal symptoms – nausea, abdominal cramps, diarrhea, restlessness, sleeplessness, anxiety – typically start within 24–48 hours and subside in 5–7 days.
• Ergotamine-rebound headaches: ergotamine is the most widely used drug for treatment of severe migraine and cluster headaches. Administered by IM injection, inhalation or suppository since it is poorly absorbed orally, ergotamine works by constricting blood vessels in the head:
• Although effective, ergotamine, even at prescribed doses, is associated with serious side effects including acute poisoning in about 10% of patients.
• Regular use is associated with dependency syndrome characterized by severe chronic headache.
• Migraines rarely occur more than once or twice a week, so an almost daily migraine headache in individuals taking ergotamine is a strong indicator of an ergotamine-rebound headache.
• Withdrawal symptoms – protracted, debilitating headache accompanied by nausea/vomiting – usually appear within 72 hours and may last another 72 hours.
• Food allergy/intolerance: the immune response that is activated by consumption of foods to which an individual is intolerant results in platelets releasing serotonin and histamine, thus triggering a migraine:
• Foods most commonly found to induce migraine include cow’s milk, wheat, chocolate, egg, orange.
• Foods high in amines:
• Foods such as chocolate, cheese, beer, and wine (especially red wine) contain histamine and/or other compounds that cause blood vessels to expand:
• Red wine contains 20–200 times more histamine than white wine.
• Histamine stimulates platelets to release vasoactive compounds (compounds that affect blood vessel tone).
• Red wine also contains high amounts of flavonoids that inhibit PST, an enzyme that breaks down vasoactive amines and serotonin in platelets, before these substances can be released into the bloodstream where they cause blood vessel dilation.
• Red wine, citrus fruits, aged cheese, and chocolate all inhibit PST.
• Factors that inhibit vitamin B6:
• FD&C yellow dye #5 (tartrazine), drugs (isoniazid, hydralazine, dopamine, penicillamine), birth control pills, alcohol, and excessive protein intake inhibit vitamin B6.
• Vitamin B6 is necessary for the activity of diamine oxidase, an enzyme that breaks down histamine.
• Foods containing certain additives:
• Meats such as hot dogs and hams that contain nitrates; beer and red wines which contain nitrites; the chemicals used in pickled or marinated foods; foods prepared with monosodium glutamate; foods containing the artificial sweetener, aspartame.
• In susceptible individuals, these chemicals trigger brain cell hyperreactivity.
• Foods containing caffeine such as chocolate, coffee and other caffeinated beverages:
• Caffeine causes blood vessels to constrict.
• In susceptible individuals, a rebound blood vessel dilation occurs when caffeine is withdrawn from the system
• Missing meals: the brain, the body’s hungriest organ, relies on glucose for fuel. Missing meals may result in a less than optimal supply of glucose, a significant stressor for brain cells prone to hyperreactivity.
• Light: the stress caused by bright sunlight, fluorescent lights that cause glare, or eyestrain may act as the final straw for hyperreactive brain cells.
• Chemical fumes: chemicals in perfumes, cleaning products, gasoline, etc. may be a source of significant stress in susceptible individuals:
• Individuals’ liver detoxification capabilities, which are composed of numerous enzyme systems, vary widely. Individuals with lesser amounts of various enzymes will not be able to clear these chemicals rapidly, which may then act as migraine triggers.
• Fatigue: a stressor that, in susceptible individuals, may increase the tendency of platelets to aggregate and release serotonin.
• Menstrual cycles: high levels of estrogen result in too much magnesium being shunted into bone and soft tissue, leaving both brain and blood vessel cell membranes unstable, and prone to hyperreactivity.

RISK INCREASES WITH

• Stress: increases secretion of stress hormones and depletes the amount of magnesium within cells:
• Stressors include intense emotions, such as grief or anger, exhaustion, muscle tension, poor posture.
• Weather changes (barometric pressure changes, sun exposure) may be physiological stressors in sensitive individuals.
• Family history of migraines:
• Possible inherited low production of enzymes that break down histamine.
• Food allergy and/or increased sensitivity to various triggers.
• Learned styles of coping with stress that are ineffective.
• Food allergies or intolerances: consumption of foods to which an individual reacts causes an immune response that involves the release of serotonin and histamine from platelets.
• Smoking: smoking causes blood vessel constriction and promotes platelet aggregation.
• Use of oral contraceptives:
• Oral contraceptives prevent conception by increasing estrogen levels.
• Birth control pills are known to increase the adverse effects of smoking and to decrease cellular levels of numerous nutrients including vitamin B6, riboflavin, and magnesium. A deficiency in any of these nutrients can trigger a migraine in susceptible individuals.
• Estrogen replacement therapy: increases estrogen levels.
• PMS: often due to high levels of estrogen.
• Perimenopause: during menopause, estrogen levels fluctuate widely and may spike irregularly before subsiding.
• Menstruation: estrogen may rise to excessively high levels at various times during a woman’s monthly cycle, e.g., immediately before, during or after menstruation.
• Use of many prescription and non-prescription drugs:
• Many commonly used drugs, antihistamines for example, constrict blood vessels; a rebound dilation may occur when these drugs are discontinued.
• Diuretics, often prescribed to lower blood pressure, do so by increasing urination, thus increasing the loss of minerals, including magnesium.
• Numerous commonly used drugs inhibit histamine breakdown. Histamine can trigger migraines in sensitive individuals by causing blood vessels to expand.
• Alcohol consumption: alcohol, especially red wine, inhibits histamine breakdown.

PREVENTIVE MEASURES

• Reduce stress where possible: exercise regularly, develop your spirituality, take regular vacations.
• Keep a “trigger diary” to identify factors that precede attacks, so that these can be avoided.
• Minimize drug use, especially oral contraceptives,antihistamines, diuretics, and analgesics (aspirin, acetaminophen).
• Don’t smoke.
• Avoid alcohol consumption, especially red wine.
• Get adequate rest – 8 hours sleep per night.
• Ensure adequate intake of riboflavin, vitamin B6 and magnesium. Good food sources include:
  ¦ riboflavin: liver, brewer’s yeast, almonds, wheat germ
  ¦ vitamin B6: brewer’s yeast, sunflower seeds, wheat germ, soybeans, salmon, liver, walnuts
  ¦ magnesium: kelp, wheat bran, wheat germ, almonds, cashews, blackstrap molasses, brewer’s yeast, buckwheat, brazil nuts, dulse, filberts, peanuts.
• If high estrogen levels are suspect, refer to the chapters on the appropriate issue: Menopause, Menorrhagia, Premenstrual syndrome.

Expected outcomes

Headache frequency should begin to decrease within 2 weeks. Although this process may take several months, complete resolution of migraines can be expected after triggers have been identified and controlled.

 

TREATMENT

Diet

• Eliminate all food allergens and utilize a 4-day rotation diet.
• Initially, all foods containing vasoactive amines should be totally eliminated from the diet:
• Primary foods to eliminate are alcoholic beverages, cheese, chocolate, citrus fruits, and shellfish.
• After symptoms have been controlled, these foods can be carefully reintroduced, one at a time. If, after 3 days, no reactions to the reintroduced food have occurred, this food may be eaten every fourth day, and another food may be reintroduced.
• The diet should be low in meat and dairy products since these contain animal fats:
• Domestically grown animal fats are our primary source of arachidonic acid, a fatty acid that is metabolized in the body to produce series 2 prostaglandins, which promote inflammation.
• Increase intake of flaxseed oil, and cold-water fish such as salmon, garlic and onion
• Flaxseed oil and cold-water fish are excellent sources of omega-3 essential fatty acids. These fats are metabolized in the body to produce series 1 and 3 prostaglandins, both of which are antiinflammatory. (Flaxseed oil, which is highly susceptible to oxidation, should be stored in an opaque container, refrigerated, and never heated.)
• Onions and garlic inhibit platelet aggregation, as they contain compounds that inhibit the enzymes responsible for metabolizing arachidonic acid into the pro-inflammatory prostaglandins and thromboxanes that promote platelet aggregation.
• Use fresh ginger liberally. Ginger can be added to juices, used as a spice in cooking, or steeped in hot water for tea:
• Ginger is a potent anti-inflammatory agent, which has also been shown to inhibit platelet aggregation.

Nutritional supplements

• Magnesium: one of magnesium’s key functions is to stabilize cell membranes, thus preventing  overexcitability of nerve cells and changes in blood vessel tone:
• Low tissue levels of magnesium are common in persons with migraine.
• The tests which best indicate low tissue levels of magnesium are those for the level of magnesium in red blood cells (erythrocyte magnesium level), and the level of ionized magnesium (the most biologically active form) in serum:
• Serum (the blood minus all blood cells) magnesium is a very poor indicator of tissue levels of magnesium since most of the body’s store of magnesium is within cells. Low serum magnesium reflects only end-stage deficiency
• Mmagnesium also improves mitral valve prolapse, which is linked to migraines since it leads to damage to blood platelets, which then release histamine, platelet-activating factor, and serotonin:
• Research shows that 85% of patients with mitral valve prolapse have chronic magnesium deficiency and that oral magnesium supplementation improves mitral valve prolapse.
• Dosage: magnesium bound to citrate, malate or aspartate. 250–400 mg t.i.d.:
• These forms are better absorbed and better tolerated than inorganic forms such as magnesium sulfate, hydroxide, or oxide, which tend to have a laxative effect.
• If a loose stool results, cut back to a level that is tolerable.
• IV magnesium for acute migraine: in several studies,a dosage of 1–3 g of IV magnesium, given over a 10-min period, resulted in a nearly 90% resolution of headache in patients with low ionized magnesium levels.
• Vitamin B6: B6 increases the cellular accumulation of magnesium and is necessary for the activity of the enzyme diamine oxidase, which breaks down histamine in the lining of the small intestine, thus helping to prevent a migraine induced by foods containing histamine; dosage: 25 mg t.i.d.
• Riboflavin: in the mitochondria, the energy factories in every cell, riboflavin (vitamin B2) acts as a coenzyme in the production of energy from fatty acids. When the amount of available riboflavin is inadequate, mitochondrial energy production drops. Decreased energy production in brain cells activates the trigeminal nerve, which then releases neuropeptides that cause blood vessel inflammation
  and dilation, triggering a migraine attack; dosage: 50 mg q.d.
• 5-Hydroxytryptophan (5-HTP): 5-HTP increases levels of both serotonin (discussed under Causes above) and endorphins:
• Levels of endorphins, the body’s own pain-relieving and mood-elevating substances, are typically low in migraineurs.
• 5-HTP has been found to be as effective as drugs used to prevent migraines (methysergide, pizotifen, propranolol), but unlike these drugs, 5-HTP has no unpleasant side effects, plus it improves mood and helps alleviate, sleep disorders and feelings of depression.
• 5-HTP is so safe, it has been used with excellent results to treat chronic headaches in children.
• Dosage: 100–200 mg t.i.d.

Botanical medicines

• Tanacetum parthenium (feverfew): feverfew has been shown in a number of clinical trials to reduce both frequency and intensity of migraine attacks:
• Feverfew works by inhibiting the release of blood vessel dilating substances from platelets, inhibiting the production of inflammatory substances, and re-establishing proper blood vessel tone.
• Effectiveness is dependent upon the presence of adequate levels of parthenolide, the active component in feverfew.
• Dosage: 0.25–0.5 mg of parthenolide b.i.d.
• Zingiber officinale (ginger): although evidence for ginger’s effectiveness against migraine is in the form of case reports rather than full clinical trials, ginger has been shown in numerous studies to exert significant effects against inflammation and platelet aggregation:
• A typical example was reported in 1990 of a 42-year-old woman with a long history of recurrent migraine. She discontinued all medications for 3 months, then took 500–600mg of dried ginger mixed with water at the onset of the migraine and repeated that dosage every 4 hours for 4 days. Improvement was evident in 30 min, and there were no side effects. She then began to use uncooked fresh ginger in her daily diet. Migraines became less frequent, and when they did occur, were significantly less severe.
• The active components of ginger are found in fresh preparations and the oil.
• Dosage: choose one of the following forms:
• Fresh ginger: approximately 6 mm slice (10 g) q.d.
• Dried ginger: 500mg q.i.d.
• Extract: standardized to contain 20% gingerol and shogaol, 100–200 mg t.i.d. for prevention. Up to 200 mg every 2 hours, up to six times a day, in the treatment of acute migraine.

Drug–herb interaction cautions

• Zingiber officinale (ginger):
• plus oral drugs: in rats, ginger increases absorption of oral drugs, such as extract with sulphaguanidine, in the small intestine.

Physical medicine

Several forms of physical medicine have been shown to be effective in shortening the duration and decreasing the intensity of a migraine attack, but they do not appear to reduce the frequency of attacks of true migraine.

• Chiropractic manipulation: in a 6-month trial of 85 patients in Australia, manipulation of the cervical
  spine by a chiropractor found no difference in frequency of recurrence, duration or disability, but patients reported greater reduction in pain associated with migraine attacks.
• Temporomandibular joint (TMJ) dysfunction syndrome: correction of dysfunction in the TMJ, the jaw joint, may be of help in treating migraines, although it has been shown to be more likely and of more importance in muscle tension headaches.
• Transcutaneous electrical nerve stimulation (TENS): TENS involves stimulation of muscles with very low levels of electricity to cause them to contract and then relax:
• TENS has been shown to be effective in both migraine and muscle tension headaches (55% of patients responded to TENS versus an 18% response to placebo).
• Home TENS units are available through doctors.
• Acupuncture: sufficient positive studies exist to suggest that acupuncture may be successful in reducing the frequency of migraine attacks:
• In one study, 40% of subjects experienced a 50–100% reduction in severity and frequency, although the patients were only followed for 2 months.
• In another study, five treatments over a period of 1 month decreased recurrence in 45% of patients over a period of 6 months.
• Acupuncture appears to relieve pain by normalizing serotonin levels; however, it was ineffective in those patients with very low levels of serotonin.
• Biofeedback and relaxation therapy: the effectiveness of biofeedback and relaxation training on reducing frequency and severity of migraines has been the subject of more than 35 clinical studies. The results showed that these non-drug approaches are as effective as the beta-blocking drug Inderal (propranolol), but unlike the drug, these mind–body therapies have no negative side effects:
• Thermal biofeedback utilizes a feedback gauge to monitor the temperature of the hands. The patient learns how to raise (or lower) hand temperature, with the device providing feedback as to what is effective.
• Relaxation training involves teaching patients how to produce the “relaxation response”, a physiological state that is the opposite of the stress response.

This article is not meant to be used for treatment but for information purposes only. If you feel that this approach is appropriate for you please contact ICIM Medics on 045 844 819 or www.icim.ie e-mail : info@icim.ie  An appointment can be arranged for you.

Tags: Headache, Migraine