Natural medicine 172

Diagnostic summary
Migraine headache
General considerations
Therapeutic considerations
Therapeutic approach
DIAGNOSTIC SUMMARY
¥ Recurrent, paroxysmal attacks of headache¥ Headache is typically pounding and unilateral, but ¥ Attacks often preceded by psychological or visual disturbances; accompanied by anorexia, nausea, andgastrointestinal upset; and followed by drowsiness.
GENERAL CONSIDERATIONS
Migraine headaches are caused by excessive dilation of a blood vessel in the head. Migraines are a surprisinglycommon disorder, at some time in their life affecting15Ð20% of men and 25Ð30% of women.1 More than halfof the patients have a family history of the illness.
Although many migraines come without warning, many migraine sufferers have warning symptoms (auras)before the onset of pain. Typical auras last a few minutesand include: ¥ blurring or bright spots in the vision¥ anxiety¥ fatigue¥ disturbed thinking¥ numbness or tingling on one side of the body.
In vascular headaches, like migraine headaches, the pain is characterized by a throbbing or pounding sharppain. In non-vascular headaches, like tension headaches,the pain is characterized as a steady, constant, dull painthat starts at the back of the head or in the forehead andspreads over the entire head, giving the sensation ofpressure or as if a vise grip has been applied to the skull(see Table 172.1 for primary classifications of headaches).
The pain of a headache comes from outside the brain because the brain tissue itself does not have sensorynerves. Pain arises from the meninges and from the scalpand its blood vessels and muscles when these structuresare stretched or tensed.
The most common non-vascular headache is the Table 172.1
it is now separately classified. Also referred to as hista-mine cephalgia, HortonÕs headache, or atypical facial neuralgia, it is much less common than migraine.
Another headache to be considered in this chapter is chronic daily headache (CDH). Approximately 40% of —complicated migraine—variant migraine patients seen in headache clinics suffer from CDH. Other terms used to describe CDH by doctors include: ¥ migraine with interparoxysmal headache To simplify matters, CDH has now been divided into —common tension headache—temporomandibular joint (TMJ) dysfunction • Increased or decreased intracranial pressure Pathophysiology
Considerable evidence supports an association between migraine headache and vasomotor instability, but the mechanisms are not yet known. Although most cliniciansand researchers believe that the sequence of events isexcessive intracranial arterial constriction (causing brain tension headache. This headache is usually caused by ischemia) followed by rebound dilation of the extra- tightening in the muscles of the face, neck, or scalp as cranial vessels (the headache phase), sophisticated studies a result of stress or poor posture. The tightening of the of sequential cerebral blood flow before, during, and after muscles results in pinching of the nerve or its blood are inconsistent in their support of this hypothesis.2,3 supply which results in the sensation of pain and pres-sure. Relaxation of the muscle usually brings about It is a well-known clinical observation that superficial Classification and diagnosis
temporal vessels are visibly dilated and local compres-sion of these vessels or the carotid artery temporarily Migraine headache has been subdivided into several relieves migraine pain.4 However, other types of extra- types, based on the presence or absence of preceding or cranial vasodilation (e.g. heat- or exercise-induced) are concomitant neurological manifestations and the nature not associated with migraine. Despite the extracranial of the manifestations. Although there are several subtypes, vasodilation, the patient appears pale during the headache, the three most common (common, classic, and complicated) suggesting constriction of the small vessels. This is sup- comprise the vast majority of patients, and differen- ported by the observation of lower skin temperature on tiation, while important, does not at this time have any therapeutic significance. The differentiation and diagnosis The clinical manifestations of focal or diffuse cerebral of these types are summarized in Table 172.2.
or brain stem dysfunction have been attributed to intra- Cluster headache was once considered a migraine-type cranial vasoconstriction. A majority, but not all, of the headache, since vasodilation is a key component, but studies measuring cerebral blood flow have confirmed Table 172.2
Neurological aura, vertigo, syncope, diplopia, hemiparesis Mild neurological signs, speech disorder, hemiparesis, unsteadiness, cranial nerve III palsy Table 172.3
the quantity of serotonin released by the platelets of themigraine patient in response to serotonin stimulation, while normal (or even subnormal) immediately after an attack, becomes progressively higher as the next attack • New daily persistent headache• Post-traumatic headache The platelet hypothesis is strengthened by the ob- servation that patients with classic migraine have atwofold increase in incidence of mitral valve prolapse.7 a reduction of blood flow, sometimes to very low and Using careful clinical and echocardiographic criteria and critical levels, during the prodromal stage. This is fol- matched controls, the researchers found in the migraine lowed by a stage of increased blood flow that can persist patients definite mitral prolapse in 16% and possible for more than 48 hours. There is significant decrease in prolapse in 15%. The controls had 7 and 8%, respectively.
regional cerebral blood flow in classic, but not common, This is of significance, since the prolapsing mitral valve migraine.5 The abnormal blood flow appears confined to is known to damage platelets and increase their aggre- the cerebral cortex, while deeper structures are perfused gation. This work has been confirmed in several studies.8,9 There is some evidence that migraine patients have an inherited abnormality of vasomotor control. Migrainepatients suffer from orthostatic symptoms more often A third major hypothesis is that the nervous system plays than normal people, and they seem to be abnormally a role in initiating the vascular events in migraine.1 It sensitive to the vasodilatory effects of physical and has been suggested that the trigeminovascular neurons, which innervate the pial arteries, release peptide sub-stance P either in direct response to the various initiatorsor secondarily to changes in the central nervous system.10 Substance P is an important mediator of pain, and its The migraine platelet shows significant differences from release into the arteries is associated with vasodilation, the normal platelet both during and between headaches.6 mast cell degranulation, and increased vascular per- These differences include a significant increase in sponta- meability. It is thought that the endothelial cells of the neous aggregation, highly significant differences in the arteries respond to substance P by releasing vasoactive manner of serotonin release, and significant differences substances, such as arachidonic acid metabolites, purine compounds, or molecules containing carbonyl groups.
The major proponent of the platelet hypothesis is This theory suggests that functional changes within Hanington,6 who starts with the observation that the most the noradrenergic system constitute the threshold for common precipitant of migraine is some type of stressor.
migraine activation, and it is through modulation of This results in a rise in plasma catecholamine levels which sympathetic activity that potentiators exert their effect.10 triggers the release of serotonin and resultant platelet Chronic stress is thought to be an important potentiator The platelets of migraine sufferers aggregate more readily than normal platelets, both spontaneously and Migraine as a “serotonin deficiency” syndrome when exposed to serotonin (and to adenosine diphos-phate and catecholamines). The increase in spontaneous The final hypothesis is that migraine headache represents aggregation is similar to that reported in patients a serotonin deficiency state. The story of serotonin and suffering from transient cerebral ischemic attacks (TIAs).
headaches began in the 1960s when researchers found This is significant, considering the close resemblance of that there was an increase in the serotonin breakdown the symptomatology of TIAs and the prodromal phase product 5-hydroxyindoleacetic acid (5-HIAA) in the urine during a migraine.11 Initially it was thought that The onset of an attack is accompanied by a significant serotonin excess was the culprit; however, newer infor- rise in plasma serotonin levels, followed by an increase mation indicates that the factor responsible for the in- in urinary 5-hydroxyindoleacetic acid, the breakdown crease in 5-HIAA is more likely the increased breakdown product of serotonin metabolism. All of the serotonin of serotonin as a result of increased activity of mono- normally in the blood is stored in the platelets and is amine oxidase (MAO).12,13 Because migraine sufferers released by platelet aggregation and in response to actually have low levels of serotonin in their tissues, it various stimuli, such as catecholamines. There is no led researchers to refer to migraine as a Òlow serotonin difference in total serotonin content between normal platelets and the platelets of migraine patients. However, Low serotonin levels are thought to lead to a decrease in the pain threshold in patients with chronic headaches.
Table 172.4
This contention is strongly supported by over 35 years of research, including positive clinical results in double- blind studies with the serotonin precursor 5-hydroxy- —shunting of tryptophan into other pathways tryptophan (5-HTP). For more information on the • Foods clinical studies with 5-HTP in migraine headaches, see The link between low serotonin levels and headache • Alcohol, especially red wine• Chemicals is the basis of many prescription drugs for the treatment and prevention of migraine headaches. For example, the serotonin agonist drug sumatriptan (Imitrex) is • Withdrawal from caffeine or other drugs which constrict blood now among the most popular migraine prescriptions. In addition to sumatriptan, monoamine oxidase inhibitors (which increase serotonin levels) have also been shown • Emotional changes, especially let-down after stress, and intense to prevent headaches. The bottom line is that there • Hormonal changes, e.g. menstruation, ovulation, birth control pills is considerable evidence that increasing serotonin levels leads to relief from chronic migraine headaches.
The effects that 5-HTP, sumatriptan, and other drugs exert on the serotonin system are extremely complex • Weather changes, e.g. barometric pressure changes, exposure to because of the multiple types of serotonin receptors. The manner in which many substances produce theireffects on cells is by first binding to receptor sites on thecell membrane. Some serotonin receptors are involved in triggering migraines and others prevent them. This Although a particular stressor may be associated with situation is quite clear by looking at the different effects the onset of a specific attack, it appears that initiation that various drugs exert when binding to these different is dependent on the accumulation over time of several serotonin receptors. Drugs which bind to serotonin re- stressors. These stressors ultimately affect serotonin ceptors designated as 5-HT1c trigger migraines, while metabolism (see Table 172.4). Once a critical point of drugs like methysergide that inhibit 5-HT1c are used to susceptibility (or threshold) is reached, a cascade event prevent migraines.15 In addition, the serotonin receptor is initiated. This susceptibility is probably a combination 5-HT1d may prevent migraine headaches since drugs like of decreased tissue serotonin levels, changes in the sumatriptan which bind to these receptors and mimic platelet, alteration in the responsiveness of key cerebro- the effects of serotonin are quite effective in the acute vascular end-organs, increased sensitivity of the intrinsic noradrenergic system of the brain, and the build-up 5-HTP supplementation affects these different receptors of histamine, arachidonic acid metabolites, or other in several ways. For example, some serotonin receptors mediators of inflammation. The platelet changes include appear to undergo desensitization when exposed to increased adhesiveness, enhanced tendency to release higher levels of serotonin. It is thought that by increasing serotonin, and increased levels of arachidonic acid in the serotonin levels, 5-HT1c lose their ability or affinity to membranes. Once the platelet is stimulated to secrete bind serotonin, resulting in more serotonin binding to serotonin, platelet aggregation, vasospasm, and inflam- the 5-HT1d receptor. In other words, it is thought that matory processes result in local cerebral ischemia. This what is occurring with 5-HTP in the preventive treatment is followed by rebound vasodilation and the release of of migraine headache is that the higher levels of serotonin peptide substance P and other mediators of pain. These produced over time result in a decrease in the sensitivity events are summarized in Figure 172.1.
of the 5-HT1c receptors and an increased sensitivity for 5-HT1d receptors.17 As a result, there would be a lowered THERAPEUTIC CONSIDERATIONS
tendency to experience headache. One of the key piecesof evidence to support this concept is the fact that 5-HTP Modern pharmacological treatment of headache, whether is more effective over time (better results are seen after migraine or tension, is ultimately doomed because it fails to address the underlying cause. The first step intreating migraine headache is identifying the precipi-tating factor. Although food intolerance/allergy is the most important, many other factors must be considered The mechanism of migraine can be described as a as either primary causes or contributors to the migraine three-stage process: initiation, prodrome, and headache.
process. In particular, it is very important to assess the Initiation
Prodrome
Headache
Figure 172.1
role that headache medications may be playing, especially Withdrawal of medication results in prompt clinical im- provement in most cases. In one study (summarized inTable 172.5) of 200 patients suffering from analgesic- Drug reaction
rebound headache, discontinuation of these symptomaticmedications resulted in 52% improvement in the total Several clinical studies have estimated that approximately headache index, improvements in headache frequency 70% of patients with chronic daily headaches suffer from and severity, general well-being, sleep patterns, and a drug-induced headaches.18 There are two main forms reduction in irritability, depression, and lethargy.19 of drug-induced chronic daily headaches: analgesic These 200 patients were typical in that they sought rebound headache and ergotamine rebound headache.19 relief from a variety of drugs. Table 172.6 lists the types Table 172.5
Profile of 200 patients with chronic daily headache Butalbital/aspirin, acetaminophen/caffeine with or without codeine Table 172.6
Commonly used drugs to prevent migraine headaches Fatigue, lassitude, depression, insomnia, nausea, vomiting, constipation Drowsiness, dry mouth, constipation, weight gain, blurred vision, water retention Anxiety, insomnia, sweating, tremor, gastrointestinal disturbances Nausea, vomiting, abdominal pain, diarrhea Sedation, dry mouth, gastrointestinal disturbances Dry mouth, drowsiness, sedation, headache, constipation Nausea, vomiting, diarrhea, abdominal pain, cramps, weight gain, insomnia, edema, decreased blood flow to extremities, heart and lung fibrosis Headache, low blood pressure, flushing, water retention, constipation of drugs used for symptomatic relief. Most of these patients took at least three of these preparations at the ¥ dyspnea¥ convulsions¥ loss of consciousness.
Symptoms of chronic poisoning include two types In the early 1980s, it began to be quite apparent in the of manifestations: those resulting from blood vessel medical literature that headache medications increase the contraction and reduced circulation Ð numbness and tendency for headache and perpetuate chronic headache.
coldness of the extremities, tingling, pain in the chest, Early reports were labeled ÒparadoxicalÓ in that heavy heart valve lesions, hair loss, decreased urination, and analgesic users experienced headaches of much greater gangrene of the fingers and toes Ð and those resulting frequency and intensity. For example, in one study it from nervous system disturbances Ð vomiting, diarrhea, was found that sufferers of migraine headaches who took headache, tremors, contractions of the facial muscles, and more than 30 analgesic tablets per month had twice as many headache days per month as those who took fewer Regular use of ergotamine in migraine headaches than 30 tablets.20 This finding led to the recommendation is also associated with a dependency syndrome charac- that analgesic use should be restricted in patients with terized by severe chronic headache with an increase in headache intensity upon cessation of medication. Because In another study, 70 patients with daily headaches who most migraine headaches rarely occur more than once were consuming 14 or more analgesic tablets per week or twice a week, the presence of an almost daily migraine- were told to discontinue their use.21 One month later, type headache in individuals taking ergotamine is a 66% of the patients were improved. At the end of the good clue for ergotamine-rebound headache. Dosage second month, this percentage had grown to 81%.
of ergotamine can also be a clue. In most cases of Analgesic-rebound headaches should be suspected in ergotamine-rebound headache, individuals take weekly any patient with chronic headaches who is taking large dosages in excess of 10 mg. In some cases, patients may quantities of analgesics and who is experiencing daily be taking dosages as high as 10Ð15 mg daily.
predictable headache. The critical dosage which can Stopping ergotamine causes predictable, protracted, lead to analgesic-rebound headache is estimated to be and extremely debilitating headache usually accom- 1,000 mg of either acetaminophen or aspirin.
panied by nausea and vomiting. These symptoms usually Analgesic medications typically contain substances in appear within 72 hours and may last for another 72 hours.
addition to the analgesic such as caffeine or a sedative Improvement after stopping the medication is very like butabarbital. These substances further contribute to common. Ginger (discussed below) may lessen ergotamine the problem and may lead to withdrawal headache and related symptoms such as nausea, abdominal cramps,diarrhea, restlessness, sleeplessness, and anxiety. With-drawal symptoms typically start at 24Ð48 hours, and in There is little doubt that food allergy/intolerance plays a role in many cases of migraine headache. Many double-blind, placebo-controlled studies have demonstrated that Ergotamine is the most widely used drug in the treat- the detection and removal of allergic/intolerant foods ment of severe acute migraine and cluster headaches.
will eliminate or greatly reduce migraine symptoms in Ergotamine works by constricting the blood vessels of the majority of patients. What is unclear is the percentage the head, thereby preventing or relieving the excessive of migraine patients for whom food control is the most dilation of the blood vessels that is responsible for important factor. Table 172.7 summarizes the results of the pain of migraine and cluster headaches. Ergotamine several clinical studies. As can be seen, success ranges is administered intramuscularly, by inhalation or by from 30 to 93%, with the majority of studies showing suppository since it is poorly absorbed when given orally.
a remarkably high degree of success.21Ð27 Although usually quite effective, ergotamine is also A possible explanation for the large difference between associated with some significant side-effects. Symptoms the results of Mansfield et al21 and the others is that the Mansfield design was carefully selected for food allergy only, while the others included food intolerance. These studies found the incidence of food allergy to be similar for the three major types of migraine. The foods most Table 172.7
Food allergy/intolerance and migraine headache Egger et al24 suggested that migraine headache may result from chronic alteration of the non-specific respon- siveness of cerebral vascular end-organ as a result of long-term antigenic stimulation. This mechanism would be analogous to the response in asthma of the bronchioles to exercise or cold after antigen contact. Allergic reactions to foods are known to cause platelet degranulation, with There are several methods which can be used to detect food allergies, most of which are described in Chapter 15.
Although laboratory procedures are probably the most commonly found to induce migraine headaches are listed convenient for the patient, challenge testing is thought to be the most reliable. Unfortunately, challenge testing The mechanism by which food allergy/intolerance has limitations: some foods evoke a delayed response, induces a migraine attack is still unknown. Several theories which may require several days of repeated challenge to elicit recognizable symptoms; also, ingestion of large ¥ idiopathic response to a pharmacologically active amounts of several foods may be necessary to detect those that are marginally reactive. The recommended proce- dure for the diagnosis and management of food allergy/ ¥ platelet phenolsulfotransferase deficiency; intolerance is described in the section on ÒTherapeutic Table 172.8
Foods which most commonly induce migraine headaches Foods such as chocolate, cheese, beer and wine precipitate migraine attacks in many people because they containhistamine and/or other vasoactive compounds which can trigger migraines in sensitive individuals by causing blood vessels to expand (see Table 172.9).28Ð30 Red wine is much more likely than white wine to cause a headache because it contains 20Ð200 times the amount of histamine and also stimulates the release of vasoactive compounds by platelets.6,29,31 It is also much higher in flavonoids Ð the antioxidant components shown to help prevent heart disease. These compounds can also inhibit the enzyme (phenolsulfotransferase) which normally breaks down Table 172.9
Factors involved with histamine-induced headaches • Histamine in alcoholic beverages (particularly red wine) —food additives (e.g. yellow dye #5, monosodium glutamate) • Antioxidants (e.g. vitamin C, vitamin E, selenium, etc.) serotonin and other vasoactive amines in platelets. Many studies with 5-HTP in migraine headaches are discussed migraine sufferers have been found to have significantly lower levels of this enzyme.32 Since red wine containssubstances which are potent inhibitors of this enzyme, it often triggers migraines in these individuals, especiallyif consumed along with high vasoactive amine foods like The role of essential fatty acids in the pathogenesis of cheese or chocolate. The standard treatment of histamine- migraine may be quite important but does not appear induced headache is the histamine-free diet along with to have received much research attention. Considering the significance of platelet aggregation and arachidonic The activity of the enzyme diamine oxidase, which acid metabolites in the mediation of the events leading breaks down histamine in the lining of the small intestine to the prodromal cerebral ischemia of migraine, mani- before it is absorbed into the circulation, appears to play pulation of dietary EFAs may be very useful. It has a major role in determining whether or not a person is been well demonstrated that reducing the consumption going to react to dietary histamine. Individuals sensitive of animal fats and increasing the consumption of fish will to dietary histamine have lower levels (about half) of this significantly change platelet and membrane EFA ratios enzyme in their tissues compared with control subjects.29 Diamine oxidase is a vitamin B6-dependent enzyme. Not surprisingly, compounds which inhibit vitamin B6 also inhibit diamine oxidase.29 These inhibiting factorsinclude food coloring agents (specifically the hydrazine Another hypothesis for explaining migraine headaches dyes like FD&C yellow #5), some drugs (isoniazid, is that they are caused by a reduction of energy produc- hydralazine, dopamine, and penicillamine), birth control tion within the mitochondria of cerebral blood vessels. pills, alcohol, and excessive protein intake. Yellow dye #5 If this hypothesis is true, riboflavin, which has the (tartrazine) is often consumed in greater quantities (per potential of increasing mitochondrial energy efficiency, capita intake of 15 g/day) than the RDA for vitamin B6 might have preventive effects against migraine. To test of 2.0 mg for males and 1.6 mg for females.
this hypothesis, 49 patients suffering from migraine were Vitamin B6 supplementation (usually 1 mg/kg body treated with a very large dose (400 mg daily) of riboflavin weight) has been shown to improve histamine tolerance, for at least 3 months.38 Overall improvement after therapy presumably by increasing diamine oxidase activity.29,32 was 68.2% in the riboflavin group as determined by the Women have lower levels of diamine oxidase which migraine severity score used in the study. No side-effects may explain their higher indicence of histamine-induced were reported. The results from this preliminary study headaches. Women are also much more frequently suggest high-dose riboflavin could be an effective, low- unable to tolerate red wine.29 Interestingly, the level of cost preventive treatment of migraine.
diamine oxidase in a woman increases by over 500 timesduring pregnancy.33,34 It is very common for women with histamine-induced headaches to experience completeremission of their headaches during pregnancy.
Low magnesium levels may also play a significant role in many cases of headaches as several researchers have Nutritional supplements
provided substantial links between low magnesiumlevels and both migraine and tension headaches based on both theory and clinical observations.39Ð41 A magne- The role of 5-HTP in preventing migraine headaches by sium deficiency is known to set the stage for the events increasing serotonin levels was discussed above. In addi- that can cause a migraine attack as well as a tension tion to this mechanism of action, 5-HTP also increases headache. Low brain and tissue magnesium concentra- endorphin levels. The use of 5-HTP in the prevention tions have been found in patients with migraines, of migraine headache offers considerable advantages indicating a need for supplementation since one of over drug therapy. Although a number of drugs have magnesiumÕs key functions is to maintain the tone of been shown to be useful in the prevention of migraine the blood vessels as well as preventing overexcitability headaches, all of these currently used drugs carry with them significant side-effects. 5-HTP is at least as effective Unfortunately, two recent double-blind studies have as other pharmacological agents used in the prevention given conflicting results in the prevention of migraines of migraine headaches and is certainly much safer and in people prone to recurrent migraine headaches. In the better tolerated. While some studies have used a dosage first study, 250 mg of magnesium or placebo was given of 600 mg/day, equally impressive results have been twice daily to 69 patients (35 received magnesium, 34 the achieved at a dosage as low as 200 mg/day. The clinical placebo) for 12 weeks.43 The number of responders was 10 in each group (28.6% under magnesium and 29.4% period) typically resulted in a nearly 90% success rate in under placebo). There was no benefit with magnesium patients with low ionized magnesium levels.48Ð50 compared with placebo in the number of migraine days In the first study, the efficacy of intravenous infusion of 1 g of magnesium sulfate (MgSO4) was evaluated in In the other double-blind study, 81 patients suffering 40 patients (16 patients had migraines without aura, from recurrent migraines were given either 600 mg of nine had cluster headaches, four had chronic tension-type oral magnesium daily for 12 weeks or placebo.44 By the headaches, and 11 had chronic migraine headaches).48 ninth week, the attack frequency was reduced by 41.6% Complete elimination of pain was observed in 32 (80%) in the magnesium group compared with only 15.8% in patients within 15 minutes of infusion of MgSO4. No the placebo group. The number of days with migraine recurrence or worsening of pain was observed within 24 and the drug consumption for symptomatic treatment hours in 56% of the patients. Patients treated with MgSO4 per patient also decreased significantly in the magnesium observed complete elimination of migraine-associated group. Side-effects with magnesium supplementation symptoms such as sensitivity to light and sound as well included diarrhea (18.6%) and gastric irritation (4.7%).
as nausea. No side-effects were observed, except for a It appears that magnesium supplementation may only brief flushed feeling. The eight non-responders exhibited be effective in those individuals with low tissue or significantly elevated serum ionized magnesium levels low ionized levels of magnesium. Low tissue levels of compared with responders prior to the infusion of magnesium are common in patients with migraine, but most cases go unnoticed because most physicians rely In a study of migraine sufferers only, the hypothesis on serum magnesium levels to indicate magnesium that patients with an acute attack of migraine headache levels, a very unreliable indicator as most of the bodyÕs and low serum levels (< 0.54 mmol/L) of ionized magne- store of magnesium lies within cells, not in the serum. A sium are more likely to respond to an intravenous infu- low magnesium level in the serum reflects end-stage sion of magnesium sulfate (MgSO4) than patients with deficiency. More sensitive tests of magnesium status higher serum ionized magnesium levels was tested.49 are the level of magnesium within the red blood cell Serum ionized magnesium levels were drawn immedi- (erythrocyte magnesium level) and the level of ionized ately before infusion of 1 g of MgSO4 in 40 consecutive magnesium (the most biologically active form) in serum.
patients with an acute migraine headache. Pain reduction Another possible benefit of magnesium in migraine of 50% or more, as measured on a headache intensity sufferers may be its ability to improve mitral valve pro- verbal scale of 1Ð10, occurred within 15 min of infusion lapse. Mitral valve prolapse is linked to migraines because in 35 patients. In 21 patients, at least this degree of it leads to damage to blood platelets, causing them to improvement or complete relief persisted for 24 hours release vasoactive substances like histamine, platelet- or more. Pain relief lasted at least 24 hours in 18 of 21 activating factor, and serotonin.7Ð9 Since research has patients (86%) with serum ionized magnesium levels shown that 85% of patients with mitral valve prolapse below 0.54 mmol/L, and in three of 19 patients (16%) have chronic magnesium deficiency, magnesium supple- with ionized magnesium levels at or above 0.54 mmol/L.
mentation is indicated.45 This recommendation is further The average ionized magnesium level in patients with supported by several studies showing that oral magne- relief lasting for at least 24 hours was significantly lower sium supplementation improves mitral valve prolapse.
than that in patients with no relief or brief relief.
Magnesium bound to citrate, malate, aspartate, or some The final study involved patients with cluster head- other Krebs cycle compound is better absorbed and better aches.50 Because previous studies reported that low tolerated than inorganic forms, such as magnesium serum ionized magnesium levels are common in patients sulfate, hydroxide, or oxide, which tend to produce a with cluster headaches, researchers examined the pos- laxative effect.46 If magnesium produces a loose stool sibility that patients with cluster headaches and low or diarrhea, advise the patient to cut back to a level that ionized magnesium levels may respond to an intravenous is tolerable. Also, it is a good idea to prescribe at least infusion of magnesium sulfate. Infusions of magnesium 50 mg of vitamin B6 daily as this B vitamin has been sulfate given to 22 patients with cluster headaches pro- shown to increase the intracellular accumulation of duced meaningful improvement in nine (41%) of them Ð not great numbers, but certainly worth the effort andcertainly much safer than the drugs used in the treatmentof acute cluster headaches such as ergotamine.
Intravenous magnesium for acute migraine headaches Intravenous magnesium has been shown to be an extre- Physical medicine
mely effective treatment in some cases of acute migraine,tension, and cluster headaches in three studies. A dosage Many forms of physical medicine have been used in the of 1Ð3 g of intravenous magnesium (over a 10 minute treatment of migraine headache. Although most have been shown to be effective in shortening the duration It is interesting to note that the mechanism of relief and decreasing the intensity of an attack, they appear is apparently not endorphin-mediated. One study found relatively ineffective in actually curing this disorder.
that the injection of saline or naloxone did not affect the Although very effective for headaches which have a signi- efficacy of the therapy,57 and another found that, while ficant muscular contraction component, these methods acupuncture increased endorphin levels in controls, the appear to have more limited success in reducing the low levels of serum endorphins found in migraine frequency of attacks of true migraine.
patients did not increase with treatment.58 The mecha-nism of action may instead be through normalization of serotonin levels. One study found that acupuncturewas effective in relieving pain when it normalized In a 6 month trial in Australia, 85 patients were studied serotonin levels, but was ineffective in relieving pain and to determine the efficacy of manipulation of the cervical in raising serotonin levels in those patients with very low spine by a chiropractor in the treatment of migraine headache. The study was controlled by comparing chiro- Acupuncture appears to have some success in reducing practic manipulation with manipulation by a medical the frequency of migraine attacks, although, as men- practitioner or physiotherapist and with simple cervical tioned above, limitations in experimental design make mobilization. Although the study found no difference interpretation difficult. One study found that 40% of the in frequency of recurrence, duration, or disability, the subjects experienced a 50Ð100% reduction in severity and chiropractic patients reported greater reduction in the frequency.57 Although the authors used a double-blind, cross-over design, the patients were only followed for 2 months. Another (uncontrolled) study found that five Temporomandibular joint dysfunction syndrome treatments (over a period of 1 month) decreased recur-rence in 45% of the patients over a period of 6 months.60 Some researchers and clinicians have claimed that asubstantial portion of headaches diagnosed as classic or common migraine are in reality the symptoms of temporomandibular joint dysfunction syndrome (TMJ).
The most widely used non-drug therapy for migraine However, a careful investigation found that the incidence headaches is thermal biofeedback and relaxation training.
of migraine in patients with TMJ is similar to that in Thermal biofeedback utilizes a feedback gauge to monitor the general population, while the incidence of headache the temperature of the hands. The patient is then taught due to muscle tension is much higher.52 These results how to raise (or lower) the temperature of the hand suggest that, while correction of TMJ dysfunction may by the device providing feedback as to what is affecting be of use in the treatment of migraine headaches, it is far the temperature. Relaxation training involves teaching more important in muscle tension headaches.
patients techniques designed to produce the ÒrelaxationresponseÓ Ð a term used to describe the physiological state that is the opposite of the stress response. This term Transcutaneous electrical stimulation (TENS) has been was originally coined by Harvard professor and cardio- shown in a placebo-controlled trial to be effective in logist Herbert Benson MD in his best-selling book, The the treatment of patients with migraine and muscle relaxation response (William Morrow 1975). tension headaches (55% responded to treatment vs. an The effectiveness in reducing the frequency and severity 18% placebo response).53 However, the study also found of recurrent migraine headaches with biofeedback and that inappropriately applied TENS, i.e. TENS applied relaxation training has been the subject of over 35 clinical below perception threshold, was ineffective.
studies.61 When the results from these studies were com-pared with studies using the beta-blocking drug Inderal(propranolol), it was apparent that the non-drug approach was as effective as the drug approach, but was without The use of acupuncture in the treatment of migraine headache has received considerable research attention.
However, assessing its efficacy is difficult since thestudies have not been blind, migraine patients were Table 172.10
Biofeedback/relaxation compared with propranolol – seldom studied separately, and most of the research has average percentage improvement per patient been reported in foreign languages, with only summaries Despite these limitations, sufficient evidence exists to support use of acupuncture to relieve migraine pain.54Ð56 Botanical medicines
migraines who discontinued all medications for a 3-month period prior to a trial of ginger.68 For the trial, Botanical medicines have a long history of use as folk 500Ð600 mg of dried ginger was taken mixed with water cures for migraine headache. Although many botanicals at the onset of the migraine and repeated every 4 hours have been used, few have received careful evaluation.
for 4 days. Improvement was evident within 30 minutes Feverfew (Tanacetum parthenium) and ginger (Zingiber and there were no side-effects. The woman subsequently officinalis) are discussed here, as they have the most began to use uncooked fresh ginger in her daily diet.
Migraines became less frequent and, when they did occur,they were at a Òmuch lower intensityÓ than previously.
There remain many questions concerning the best form of ginger and the proper dosage. The most active Perhaps the most popular preventive treatment of anti-inflammatory components of ginger are found in migraine headaches is the herb feverfew. Scientific interest in feverfew began when a 1983 survey found that70% of 270 migraine sufferers who had eaten feverfewdaily for prolonged periods claimed that the herb de- THERAPEUTIC APPROACH
creased the frequency and/or intensity of their attacks.62 Migraine headache is a multifaceted disease, and indeed Many of these patients had been unresponsive to orthodox could be accurately described as a symptom rather than medicines. This survey prompted several clinical investi- as a disease. The challenge for the clinician is to determine gations of the therapeutic and preventive effects of which of the several factors discussed here are respon- feverfew in the treatment of migraine.62Ð65 sible for each patientÕs migraine process. Identification The first double-blind study was done at the London of the precipitating factors, and their avoidance, is impor- Migraine Clinic, using patients who reported being tant in reducing the frequency of headaches. Avoidance helped by feverfew.62 Those patients who received the of initiators is particularly significant, considering that placebo (and as a result stopped using feverfew) had a significant increase in the frequency and severity of Due to the high incidence (80Ð90%) of food allergy/ headache, nausea, and vomiting during the 6 months intolerance in patients with migraine headache, diagnosis of the study, while patients taking feverfew showed no and management begins with 1 week of careful avoidance change in the frequency or severity of their symptoms.
of all foods to which the patient may be allergic or Two patients in the placebo group who had been in intolerant. This can be accomplished through either a complete remission during self-treatment with feverfew pure water fast or the use of an elemental diet (an leaves developed a recurrence of incapacitating migraine oligoantigenic diet may be used but is less desirable, since and had to withdraw from the study. The resumption significant allergens may be inadvertently included). of self-treatment led to renewed remission of symptoms All other possible allergens, e.g. vitamins, unnecessary in both patients. The second double-blind study, per- drugs, herbs, etc., should also be avoided. During this formed at the University of Nottingham, demonstrated procedure, food-sensitive patients will exhibit a strong that feverfew was effective in reducing the number and exacerbation of symptoms early in the week, followed by almost total relief by the end of the fast/modified diet.
Follow-up studies to the clinical results have shown This sequence is due to the addictive characteristic of that feverfew works in the treatment and prevention of the reactive foods. Once the patient is symptom-free, migraine headaches by inhibiting the release of blood one new food is reintroduced (and eaten several times) vessel-dilating substances from platelets, inhibiting the each day while symptoms are carefully recorded. Some production of inflammatory substances, and re-establishing authors recommend reintroduction on a 4 day cycle.
proper blood vessel tone.64 The effectiveness of feverfew Suspected foods (symptom onset ranges from 20 minutes is dependent upon adequate levels of parthenolide, the to 2 weeks) are eliminated, and apparently safe foods are rotated through a 4 day cycle (see Ch. 58). Once asymptom-free period of at least 6 months has been established, the 4 day rotation diet should no longer be The common ginger root has been shown to exert significant effects against inflammation and platelet aggregation.66,67 Unfortunately, in relation to migraineheadache, there is much anecdotal information but little As discussed above, all food allergens must be eliminated clinical evidence. For example, a 1990 article described and a 4 day rotation diet utilized until the patient is a 42-year-old woman with a long history of recurrent symptom-free for at least 6 months. Foods containing vasoactive amines should initially be eliminated. After symptoms have been controlled they can be carefully re- Ñ extract standardized to contain 20% of gingerol introduced. The primary foods to eliminate are alcoholic and shogaol 100Ð200 mg three times/day for beverages, cheese, chocolate, citrus fruits, and shellfish.
prevention and 200 mg every 2 hours (up to six The diet should be low in sources of arachidonic acid times daily) in the treatment of an acute migraine.
(land animal fats) and high in foods which inhibit plateletaggregation, e.g. vegetable oils, fish oils, garlic, and ¥ TENS to control secondary muscle spasm¥ Acupuncture to balance meridians ¥ Magnesium: 250Ð400 mg three times/day The Association for Applied Psychophysiology and ¥ 5-HTP: 100Ð200 mg three times/day.
10200 West 44th Avenue, Suite 304Wheat Ridge, CO 80033(303) 422-8436 ¥ Tanacetum parthenium: 0.25Ð0.5 mg parthenolide twice Ñ fresh ginger: approximately 10 g/day (6 mm slice) 1. Rubenstein E, Federman DD. Scientific American medicine. New 19. Mathew NT. Transformed migraine. Cephalalgia 1993; 13: 78Ð83 York, NY: Scientific American. 1987: p 11: XI: 1Ð3, CTM: II: 10 20. Isler H. Migraine treatment as a cause of chronic migraine. In: 2. Rose FC. The pathogenesis of a migraine attack. TINS 1983; 6: 247 Rose FC, ed. Advances in migraine research and therapy. New 3. Shinhoj E. Hemodynamic studies within the brain during 21. Mansfield LE, Vaughan TR, Waller ST et al. Food allergy and 4. Blacklow RS. MacbrydeÕs signs and symptoms. 6th edn. New adult migraine. Double-blind and mediator confirmation of an allergic etiology. Ann Allergy 1985; 55: 126Ð129 5. Olesen J. The ischemic hypothesis of migraine. Arch Neurol 1987; 22. Carter CM, Egger J, Soothill JF. A dietary management of severe childhood migraine. Hum Nutr Appl Nutr 1985; 39A: 294Ð303 6. Hanington E. The platelet and migraine. Headache 1986; 26: 411Ð415 23. Hughes EC, Gott PS, Weinstein RC, Binggeli R. Migraine. A 7. Spence JD, Wong DG, Melendez LJ et al. Increased incidence of diagnostic test for etiology of food sensitivity by a nutritionally mitral valve prolapse in patients with migraine. Can Med Assoc supported fast and confirmed by long-term report. Ann Allergy 8. Gamberini G, DÕAlessandro R, Labriola E et al. Further evidence 24. Egger J, Carter CM, Wilson J et al. Is migraine food allergy? on the association of mitral valve prolapse and migraine.
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