- Email: [email protected]
Current aspects of migraine headache
LEE KUDROW, M.D.
Current aspects of migraine headache The introduction of psychopharmacological agents has: brought a new appreciation of the role of cerebral biogenic amines in emotional disorders. The study of biogenic amines in headache disorders has led to a better understanding of the etiological aspects and mechanisms of head pain and the possible role of psychological and personality influences. Current understanding of the role of these various factors is reviewed. ABSTllACT:
Psychiatrists have recently become mor:e involved in evaluation and treatment of chronic pain syndromes, while the headache researcher has becOme more interested in the emotional aspects of primary headache disorders. Efforts to understand the psychophysiology of migraine have increased in both disciplines, following the introduction of psychopharmacological agents. With tbese agents, a new appreciation of the role of cerebral biogenic amines in emotional disorders has evolved. We now believe that neurotransmitters (such as serotonin, norepinephrine, and dopamine) are in some way alte-red by these psychotropic agents. They may with some de48
gree of predictability allay anxiety, relieve depression, and organiZe rational thought processes; or, as in the case of hallucinogens, these agents may serve to disrupt such organization. The activity of these neurohumoral chemicals is also the basis of autonomic nervous system function and it is likely that alteration of this biochemical activity would produce either psychological or somatic symptoms, or both. This concept is the rationale for the study of biogenic amines in headache disorders. It has led to a better understanding of the etiological aspects and mechanisms of head pain and the possible role of psychological and personality influences.
This article summarizes the current findings of one headache type, migraine, characterized by autonomic nervous system dysfunction and specific psychological and personality traits. Classification Migraine is considered a primary headache disorder, since it is a physiological condition having headache as the outstanding clinical feature-as opposed to a pathological process in which the headache symptom is secondary. Another distinction between primary and secondary headache is that the pain of secondary headache originates intracranially. It is mediated by increased intracranial pressure or tissue displacement causing traction of pain-sensitive structures. A more common mechanism is dilation of cerebral blood vessels.) The pain of primary headache disorders originates extracranially, involving the cranial arteries and scalp muscles. Migraine headache pain comes from vasodilation and, probably, increased JANUARY 1978
scalp muscle reactIvIty. A 1962 classification of headache disorders in general lists these six kinds of migraine: 1. Common, classical (including menstrual, hormonal, menopausal, and tyramine) 2. Ophthalmic 3. Ophthalmoplegic 4. Hemiplegic 5. Basilar artery 6. Equivalent. 2 Clinical description
About 25% of women and 10% of men have migraine. 3 Numerous reports suggest that it is a genetic disorder, primarily affecting the vasomotor system.4.S
Goodell and associates 6 concluded that the gene associated with this disorder is probably autosomal dominant, having an 80% penetrance. In one study of monozygotic and dizygotic twin populations, however, significant concordance for migraine was lacking. 7 Vasomotor instability is the basis for the headache attack. An increased reactivity of arteries thus occurs under certain circumstances and the patient may complain of cold hands and feet in the presence of only minimal stress. This tendency of peripheral vasoconstriction has been documented. 8
The migraine attack has three phases. 9 In the first, diminished cerebrovascular flow occurs, resulting in ischemic changes. If the occipital lobes are affected, a visual aura is experienced, usually lasting from 10 to 30 minutes and beginning with a pericentral field defect. For example, if the headache victim is reading, first a portion of a word, then greater areas of the written page will disappear. After a few minutes, fortification lines, bright points of light, or bursts of color may appear, further obscuring the reader's vision and stimulating considerable anxiety. Involvement of the parietotemporal lobes may pro-
Phase III Intractable headache
0(0
Phase II Reversible headache
00 ©O
Phase I Prodrome
Resting
00 Asymptomatic
Scotoma Visual field defects Fatigue Euphoria Excitement
FIGURE 1- Vasomotor changes in relation to headache stage and symptoms of migraine. Each pair of circles
PSYCHOSOMATICS
Headache Vomiting Photophobia Ph onophobia
Intractable headache
I
represents a cross section of the internal (left) and external (right) carotid arteries. 49
Migraine
duce visual distortion of size and shape-and "Alice in Wonderland" perceptual distortion. (Lewis Carroll was reported to have suffered from the symptoms of classical migraine.) The second stage of migraine is heralded by pain mediated by extracranial vessel dilation. During this phase, the cerebral circulation has normalized. Edema of the scalp arteries and perivascular tissues marks the third phase (Figure 1). The migraine attack may be described in terms of periodicity, symptoms, and signs. Characteristically, attacks occur from one to three times each month, frequently associated with menstrual periods. Each attack may last from one to three days, with some variation. Pain develops slowly over a period of several hours, with its peak lasting for a day or longer. In 80% of all cases the headache is unilateral, involving the temporal artery region and extending over the hemicrania1 area. Often the pain is described as throbbing and is associated with nausea, vomiting, photophobia, and phonophobia. Not infrequently, strong odors are poorly tolerated during the heada<;he phase. Paresthesias, hot and cold sensations, orthostatic lightheadedness, and anorexia may also be experienced during the occurrence of these episodes. Types of migraine
Classical migraine is generally considered typical, but its comparative incidence is only one tenth that of common or ordinary migraine. Common migraine is the most frequently occurring of the primary headache 4isorders. In contrast to other types, the patient
with common migraine does not experience an obvious prodrome. Qualitatively, the headache phase is similar in all forms, while the frequency of attacks is highest among patients who are suffering from common migraine. Ophthalmic migraine is the second most frequently occurring form. As previously noted, classical migraine is distinguished by a visual prodrome followed by headache. In certain cases, however, headache does not follow the visual episode, presumably due to the absence of an extracranial vascular response. When this occurs, the headache type is known as ophthalmic migraine. Alvarez,1O himself a victim of frequent recurring attacks of this type of migraine, has written extensively on this subject. Hemiplegic migraine is an infrequently occurring headache resembling classical migraine, with these added characteristicsunilateral extremity and facial n um bness, weakness, and paresthesias, usually associated with dysphasia. This condition is strongly familial, as first noted by Clarke l1 as early as 1910 and reviewed by Whitt y l2 in 1953. Ophthalmoplegic migraine, first named in 1882 by Saundby,13 most often begins in early childhood and may recur throughout the lifetime, though infrequently. Third nerve paresis usually occurs three to five days following onset of headache and may last for as long as two to three months. Friedman and associates l4 reported that of eight patients with ophthalmoplegic migraine from a population of 5,000 migraine patients, only one had involvement of both the third and fourth cranial nerves; in another, perma-
nent (partial) damage of the oculomotor nerve resulted. Basi/ar artery migraine is another example of a rare and complicated form of migraine. It was first defined by Bickerstaff'S in 1961. It most often affects young girls with a positive family history of migraine. Vertigo, ataxia, dysarthria, and tinnitus may be experienced following or associated with the pre-headache visual aura. In approximately 30% of the cases, syncope may result and last as long as 30 minutes. Following this period, as in classical migraine, the headache phase begins. It is believed that the cerebellar symptoms result from involvement of the basilar-vertebral arteries. We will exclude discussion of the questionable "equivalent" type of migraine. Causative factors The increased frequency of migraine attacks among users of oral contraceptives is well established. 16•17 The cyclic use of moderately high doses of estrogen preparations for replacement or supplemental therapy has also been shqwn to increase migraine frequency. In a recent study of 239 women with migraine, the frequency of attacks was significantly greater in 60 women who used oral contracept~v~s and 87 who received estrogen replacement or supplementatipn therapy than in 92 women not using hormones. Moreover, upon discontinuation of the oral contraceptives in the first group and following reduction and "decycling" of estrogen in the second group, the headache frequency rate decreased by 70% and 80%, respectively. 18 Sommerville l9 concluded JANUARY 1978
that prolonged, elevated levels of plasma estrogen may prime cranial blood vessels, resulting in vessel dilation and consequent headache upon withdrawal. This helps to explain why, in the absence of extrinsic estrogen use, attacks occur in association with menstruation, and it may account for the higher incidence of migraine in women. In regard to this, it has been reported that although the female-to-male ratio of migraine in childhood is I: 1,20 it changes following menarche to favor women 2: I.J In headache clinics, this ratio is 4: I or greater. Numerous factors have been reported to induce the acute migraine attack. In an effort to identify these factors and establish their frequency of migraine induction, 400 patients at the California Medical Clinic for Headache were followed over a sixmonth period. In order of decreasing frequency, the factors apparently inducing attacks were found to be: extrinsic estrogen; premenstrual and menstrual times; anticipatory anxiety; vacation periods; alcohol; weekends; post-crisis events; and chocolate. There was no significant influence of cigarette smoke, smog, weather change, season, monosodium glutamate, sodium nitrate, or foods containing tyramine. Ryan 21 and Shaw and associates 22 have also reported similar negative results regarding tyramine induction of migraine. This is in disagreement with the original studies of Hanington,23 published in 1967. A major factor in migraine production appears to be stress, either resulting from anticipation or arising from adaptation effort. Clearly, migraine sufferers experience headaches as a result of PSYCHOSOMATICS
environmental change, which may involve moving, job changes, and even vacations and weekends. Vacations and weekends are generally unstructured and may tax the adaptive abilities of rigid, intolerant, perfectionist individuals. For these reasons, migraine
I • Epinephrine release ~ MAO deficiency I
may well be considered a maladaptation syndrome affecting the psychological, biochemical, and vasomotor functions. Biochemistry Specific biochemical events have been identified in associa-
~
Estrogen
Menstrually related Oral contraceptives Cyclic supplements
I
Stress
I
Dietary
I
Phenylethylamine Tyramine
Platelet aggregation
Serotonin release
I
Prostaglandin release Prodromal phase (Cerebral vasoconstriction)
I
Serotonin depletion
FIGURE
I
Headache phase (Cranial vasodilation)
2-Proposed scheme o(migraine pathogenesis (Part 1). 51
Migraine
tion with migraine and involve histamines, platelet serotonin, kinin, intrinsic heparin, monoamine oxidase (MAO), y-aminobutyric acid (GABA), prostaglandins, and tyramine. In 1961, Sicuteri and associates 24 found that the urinary turnover rate of 5-hydroxyindoleacetic acid, the major catabolic product of serotonin, was increased during the migraine attack. In 1967, Anthony and associates 25 demonstrated that levels of platelet serotonin were elevated during the pre-headache phase and were decreased during the headache period. During attacks, ThonnardNeumann 26 observed an increased basophilic heparin level. Blood basophils and tissue mast cells store heparin, which lends
importance to this observation, since heparin may affect platelet integrity. Also, during the migraine attack, alteration in neurotransmitter metabolism was inferred by the findings of Welch and associates,27 who were able to demonstrate the presence of GABA in the spinal fluid of one group of patients with acute migraine and in another group of patients with cerebrovascular ~is ease and ischemia. Control groups consisting of non-migraine headache sufferers and migraine sufferers in remission showed no elevation of cerebral spinal fluid GABA levels. Other biochemical characteristics of migraine include: MAO deficiency and phenylethylamine oxidizing defects, as re-
I Mast cells I
I
Serotonin I
: Histamine
I + I Proteolytic enzymes I
I Plasmakinin release
j
Increased capillary permeability
Lowered levels
! I - - - Reduced
pain threshold
FIGURE
Incre~sed pain sensitivity of vessel walls and perivascular tissue
3-Proposed scheme o(migraine pathogenesis (Part 2).
PSYCHOSOMATICS
ported by Sandler and associates 28; prostaglandin activity, described by Carlson 29; and the elicitation of histamine 30 and kinin increases. 31 As noted earlier, estrogen changes, stress, and dietary factors may precipitate the headache attack in genetically predisposed individuals. It is believed that these factors may induce platelet aggregability, as first reported by Kalendovsky and Austin. 32 This makes possible the construction of a reasonable scheme of migraine pathogenesis that incorporates most of the biochemical changes observed in migraine. Induced platelet aggregation leads to serotonin release, causing cerebrovascular constriction responsible for the pre-headache stage of an attack. Circulating serotonin induces prostaglandin release from lung tissue, which is in part responsible for the profound extracranial arterial dilation of the headache phase. Breakdown of circulating serotonin allows for an unopposed vasodilation, contributing to a sustained painful period (Figure 2). To this scheme Fanch amps 33 suggests an additional step: as the platelets release serotonin, mast cells liberate histamine and proteolytic enzymes. Histamine and serotonin increase capillary permeability while proteolytic enzymes act on plasmakininogen, producing plasmakinin. Transudation of this substance causes vascular and perivascular pain and, with the combined action of reduced serotonin levels, reduces the pain threshold (Figure 3). Psychological aspects Personality studies by Wolff,34 Friedman and asso55
Migraine
ciates,35 and more recently Henryk-Gutt and Rees 36 have characterized the migraine sufferer as tense, obsessive, overcontrolled, perfectionistic, orderly, and rigid. Clearly, individuals with such personality characteristics would be expected to have difficulty in adjusting to even minor environmental variations. Indeed, using psychometric scales for maladjustment, Rogado and associates37 reported that migraine victims scored worse than controls. Neuroticism was also found to be more prevalent among migraine sufferers than controls in a study that utilized the Eysenck-Maudsley test. 36 Rogado and associates37 reported that patients with migraine scored higher on the hysteria and hypochondriasis scales of the MMPI than did controls. In fact, they indicated that a "conversion V" configuration (a configuration commonly seen in conversion neurosis) was typical of the migraine population. In our own study of 50 migraine patients, only those who also suffered chronic scalp-muscle contraction headache showed these results, whereas migraine patients free from scalp-muscle contraction headache did not score higher on these scales than controls or those with combination headache. In addition, only 10% of this migraine population had significant depression. This observation is in agreement with data of Couch and associates38 concerning depression in migraine. Neurophysiological aspects Unusual personality and psychological aspects of migraine are not the only conditions reflective of maladaptive behavior. We
have already reviewed the biochemically related vasomotor instability, which may be seen as maladaptive mechanisms. Nor are the affected systems limited to vascular function. Pozniak-Patewicz39 reported that muscular reactivity was greater in migraine patients than in patients with other types of headache, even when headache free. In a study of autonomic nervous system response patterns, Rickles and associates40 concluded that migraineurs exhibit significantly greater reactivity of three psychophysiological functions when compared
with their non-migraine cohorts: forehead and hand temperature, finger-pulse amplitude, and frontalis EM G changes. Thus, migraine appears to be a strongly familial disorder characterized by psychophysiological, biochemical, and vasomotor dysfunction, causing difficulty in adaptation to environmental changes. One can appreciate the trepidation exhibited by migraine sufferers when faced with circumstances considered pleasurable to others, such as vacations, travel, weekends, or even an evening out with friends. 0
REFERENCES I. Kudrow L: Systemic causes of headache. Postgrad Med 56: lOS-III, 1974. 2. Ad Hoc Committee on the Classification of Headache. JAMA 179:717-718, 1962. 3. Waters WE. O'Connor PJ: Prevalence of migraine. J Neurol Neurosurg PsychiaJry 30:613-616, 1975. 4. Refsum S: Genetic aspects of migraine, in Vinken PJ, Bruyn GW (eds): Handbook of Clinical Neurology. Amsterdam, North-Holland Publishing Co, 1968, vol 5, chap 25. 5. Barolin GS, Sperlich D: Migraine familien. Fortsch Neurol Psychiat 37:521-554. 1969. 6. Goodell H, Lewontin R, Wolff HG: Familial occurrence of migraine headache. Arch Neurol PsychiaJ 72:325-334, 1954. 7. Ziegler DK, Hassanein RS, Harris D, et al: Headache in a non-clinic twin population. Headache 13:213-218, 1975. 8. Price KP, Tursky B: Vascular reactivity ofmigraineurs and nonmigraineurs: A comparison of responses to self-control procedures. Headache 16:210-217, 1976. 9. Dalessio D: Classification of headache. Internat Ophtha/mol C/in 10:647-665, 1970. 10. Alvarez WC: The migrainous scotoma as studied in 618 persons. Amer J Ophtha/mol49:489-504, 1960.
11. Clarke JM: On recurrent motor paraI· ysis in migraine; with report of a family in which recurrent hemiplegia accompanied the attacks. Br Med J 1: 15341538, 1910. 12. Whitty CMW: Familial hemiplegic migraine. J Neuro/ Neurosurg Psychiatry 16:172-177, 1953. 13. Saundby R: A case of megrim, with paralysis of the third nerve. Lancet 2:345-346, 1882. 14. Friedman AP, Harter DH, Merritt HH: Ophthalmoplegic migraine. Arch Neuro/7:82-87, 1962. 15. Bickerstaff ER: Basilar artery migraine. Lancet 1:15-17, 1961. 16. Grant ECG: Relation between headaches from oral contraceptives and development of endometrial arterioles. Br MedJ 3:402-405,1968. 17. Whitty CWM, Hockaday JM, Whitty MM: The effect of oral contraceptives on migraine. Lancet 1:856-859, 1966. 18. Kudrow L: The relationship of headache frequency to hormone use in migraine. Headache 15:36-40, 1975. 19. Sommerville BW: The role of estradiol withdrawal in the etiology of menstrual migraine. Neurology 22:355-365, 1972. 20. Krupp GR, Friedman AP: Migraine in children, A report of fifty children. Read before the Section on Pediatrics, IOlst Annual Session of AMA, Chicago, June 1950. 21. Ryan RE: A clinical study of tyramine
JANUARY 1978
as an etiological factor in migraine. Headache 14:43-48. 1974. 22. Shaw SWJ. Johnson RH. Keogh HJ: Oral tyramine in dietary migraine sufferers. Read before the Migraine Trust International Symposium. London. Sept 1976. 23. Hanington E: Preliminary report on tyramine headache. Sr Med J 2:550551. 1967. 24. Sicuteri F. Testi A. Anselmi B: Biochemical investigations in headache: increase in the hydroxyindoleacetic acid excretion during migraine allacks. Internat Arch A lIer~ 19:55-58. 1961. 25. Anthony M. Hinterberger H. Lance JW: Plasma serotonin in migraine and stress. Arch Neurol (Chicago) 16:544552. 1967. 26. Thonnard-Neumann E: Heparin in migraine headache. Headache 13:4964. 1973. 27. Welch KMA. Chabi E. Nell JH. et al: Biochemical comparLson of migraine and stroke. Headache 16: 160-167. 1976. 28. Sandler M. Youdim MBH. Hanington
E: A phenylethylamine oxidizing defect in migraine. Nature 250:335-341. 1974. 29. Carlson LA: Metabolic and cardiovascular effects in vivo of prostaglandins. in Bergstrom S. Samuelson B (cds): Prostaglandins. Nohel Srmposium 2. New York. Interscience. 1967. pp 123161. 30. Sjaastad O. Sjaastad OV: The histaminuria in vascular headache. Acta Neurol Scand 46:331-342. 1970. 31. Chapman LF. Ramos AO. Goodell H. et al: Humoral agent implicated in vascular headache of the migraine type. Arch Neurol (Chicago) 3:223-229. 1960. 32. Kalendovsky Z. Austin JH: "Complicated migraine:' its association with increased platelet aggregability and abnormal plasma coagulation factors. Headache IS: 18-35. 1975. 33. Fanchamps A: The role of humoral mediators in migraine headache. Call J Neurol Sci I: 189-195. 1974. 34. Wolff HG: Personality factors and re-
Dr. Kudrow is director of the Ca/~rornia Medical Clinic for Headache. in Encino, and associate editor of the journal, Headache. Reprint requests 10 Dr. Kudrow, 16542 Ventura Blvd.. Encino. CA 91436.
actions of subjects with migraine. Arch Neurol P.ITchiatrr 37:895-903. 1937. 35. Friedman AP. Von Storch Jc. Houston MH: Migraine and tension headaches: A clinical study of 2000 cases. Neurolo?r 4:773-788. 1954. 36. Henryk-Gull R. Rees WL: Psychological aspects of migraine. J Pwchmomatic ReJ 17: 141-153. 1973. 37. Rogado1\, Harrison RH. Graham JR: Personality profiles in cluster headache. migraine and normal controls. Read before the 10th International Congress of World Federation of Neurology. Amsterdam. Sept 1973. 38. Couch JR. Ziegler DK. Hassanein RS: Evaluation of the relationship between migraine headache and depression. Headache 15:41-50. 1975. 39. Pozniak-Patewicz E: "Cephalgic" spasm of head and neck muscles. Headache 15:261-266. 1976. 40. Rickles WHo Cohen MJ. McArthur DL: A psychophysiology study of ANS response pallerns in migraine headache patients and their headache-free friends. Read before the 19th annual meeting of the American Association for the SlUdy of Headache. San Francisco. June 1977.
CALL FOR PAPERS "Psychosomatic Medicine-Tempo of the Times" 25th Anniversary Meeting November 15-19, 1978, Atlanta, Georgia Contributions in each of the following emphasis areas are invited: EDUCATION-With particular emphasis on training of primary care physicians by psychiatrists and behavioral scientists. TREATMENT-Preventive and therapeutic
RESEARCH-Recent advances of relevance and utility to the practitioner. Psychosomatic problems in children, adolescents and families With special emphasis on diagnostic treatment and research methods.
Abstracts, papers and ideas for the program should be submitted to: William L. Webb, Jr., MD Departmenl of Psychialry University of Tennessee 865 Poplar Avenue, Memphis, TN 38105
PSYCHOSOMATICS
I
57
Current aspects of migraine headache The introduction of psychopharmacological agents has: brought a new appreciation of the role of cerebral biogenic amines in emotional disorders. The study of biogenic amines in headache disorders has led to a better understanding of the etiological aspects and mechanisms of head pain and the possible role of psychological and personality influences. Current understanding of the role of these various factors is reviewed. ABSTllACT:
Psychiatrists have recently become mor:e involved in evaluation and treatment of chronic pain syndromes, while the headache researcher has becOme more interested in the emotional aspects of primary headache disorders. Efforts to understand the psychophysiology of migraine have increased in both disciplines, following the introduction of psychopharmacological agents. With tbese agents, a new appreciation of the role of cerebral biogenic amines in emotional disorders has evolved. We now believe that neurotransmitters (such as serotonin, norepinephrine, and dopamine) are in some way alte-red by these psychotropic agents. They may with some de48
gree of predictability allay anxiety, relieve depression, and organiZe rational thought processes; or, as in the case of hallucinogens, these agents may serve to disrupt such organization. The activity of these neurohumoral chemicals is also the basis of autonomic nervous system function and it is likely that alteration of this biochemical activity would produce either psychological or somatic symptoms, or both. This concept is the rationale for the study of biogenic amines in headache disorders. It has led to a better understanding of the etiological aspects and mechanisms of head pain and the possible role of psychological and personality influences.
This article summarizes the current findings of one headache type, migraine, characterized by autonomic nervous system dysfunction and specific psychological and personality traits. Classification Migraine is considered a primary headache disorder, since it is a physiological condition having headache as the outstanding clinical feature-as opposed to a pathological process in which the headache symptom is secondary. Another distinction between primary and secondary headache is that the pain of secondary headache originates intracranially. It is mediated by increased intracranial pressure or tissue displacement causing traction of pain-sensitive structures. A more common mechanism is dilation of cerebral blood vessels.) The pain of primary headache disorders originates extracranially, involving the cranial arteries and scalp muscles. Migraine headache pain comes from vasodilation and, probably, increased JANUARY 1978
scalp muscle reactIvIty. A 1962 classification of headache disorders in general lists these six kinds of migraine: 1. Common, classical (including menstrual, hormonal, menopausal, and tyramine) 2. Ophthalmic 3. Ophthalmoplegic 4. Hemiplegic 5. Basilar artery 6. Equivalent. 2 Clinical description
About 25% of women and 10% of men have migraine. 3 Numerous reports suggest that it is a genetic disorder, primarily affecting the vasomotor system.4.S
Goodell and associates 6 concluded that the gene associated with this disorder is probably autosomal dominant, having an 80% penetrance. In one study of monozygotic and dizygotic twin populations, however, significant concordance for migraine was lacking. 7 Vasomotor instability is the basis for the headache attack. An increased reactivity of arteries thus occurs under certain circumstances and the patient may complain of cold hands and feet in the presence of only minimal stress. This tendency of peripheral vasoconstriction has been documented. 8
The migraine attack has three phases. 9 In the first, diminished cerebrovascular flow occurs, resulting in ischemic changes. If the occipital lobes are affected, a visual aura is experienced, usually lasting from 10 to 30 minutes and beginning with a pericentral field defect. For example, if the headache victim is reading, first a portion of a word, then greater areas of the written page will disappear. After a few minutes, fortification lines, bright points of light, or bursts of color may appear, further obscuring the reader's vision and stimulating considerable anxiety. Involvement of the parietotemporal lobes may pro-
Phase III Intractable headache
0(0
Phase II Reversible headache
00 ©O
Phase I Prodrome
Resting
00 Asymptomatic
Scotoma Visual field defects Fatigue Euphoria Excitement
FIGURE 1- Vasomotor changes in relation to headache stage and symptoms of migraine. Each pair of circles
PSYCHOSOMATICS
Headache Vomiting Photophobia Ph onophobia
Intractable headache
I
represents a cross section of the internal (left) and external (right) carotid arteries. 49
Migraine
duce visual distortion of size and shape-and "Alice in Wonderland" perceptual distortion. (Lewis Carroll was reported to have suffered from the symptoms of classical migraine.) The second stage of migraine is heralded by pain mediated by extracranial vessel dilation. During this phase, the cerebral circulation has normalized. Edema of the scalp arteries and perivascular tissues marks the third phase (Figure 1). The migraine attack may be described in terms of periodicity, symptoms, and signs. Characteristically, attacks occur from one to three times each month, frequently associated with menstrual periods. Each attack may last from one to three days, with some variation. Pain develops slowly over a period of several hours, with its peak lasting for a day or longer. In 80% of all cases the headache is unilateral, involving the temporal artery region and extending over the hemicrania1 area. Often the pain is described as throbbing and is associated with nausea, vomiting, photophobia, and phonophobia. Not infrequently, strong odors are poorly tolerated during the heada<;he phase. Paresthesias, hot and cold sensations, orthostatic lightheadedness, and anorexia may also be experienced during the occurrence of these episodes. Types of migraine
Classical migraine is generally considered typical, but its comparative incidence is only one tenth that of common or ordinary migraine. Common migraine is the most frequently occurring of the primary headache 4isorders. In contrast to other types, the patient
with common migraine does not experience an obvious prodrome. Qualitatively, the headache phase is similar in all forms, while the frequency of attacks is highest among patients who are suffering from common migraine. Ophthalmic migraine is the second most frequently occurring form. As previously noted, classical migraine is distinguished by a visual prodrome followed by headache. In certain cases, however, headache does not follow the visual episode, presumably due to the absence of an extracranial vascular response. When this occurs, the headache type is known as ophthalmic migraine. Alvarez,1O himself a victim of frequent recurring attacks of this type of migraine, has written extensively on this subject. Hemiplegic migraine is an infrequently occurring headache resembling classical migraine, with these added characteristicsunilateral extremity and facial n um bness, weakness, and paresthesias, usually associated with dysphasia. This condition is strongly familial, as first noted by Clarke l1 as early as 1910 and reviewed by Whitt y l2 in 1953. Ophthalmoplegic migraine, first named in 1882 by Saundby,13 most often begins in early childhood and may recur throughout the lifetime, though infrequently. Third nerve paresis usually occurs three to five days following onset of headache and may last for as long as two to three months. Friedman and associates l4 reported that of eight patients with ophthalmoplegic migraine from a population of 5,000 migraine patients, only one had involvement of both the third and fourth cranial nerves; in another, perma-
nent (partial) damage of the oculomotor nerve resulted. Basi/ar artery migraine is another example of a rare and complicated form of migraine. It was first defined by Bickerstaff'S in 1961. It most often affects young girls with a positive family history of migraine. Vertigo, ataxia, dysarthria, and tinnitus may be experienced following or associated with the pre-headache visual aura. In approximately 30% of the cases, syncope may result and last as long as 30 minutes. Following this period, as in classical migraine, the headache phase begins. It is believed that the cerebellar symptoms result from involvement of the basilar-vertebral arteries. We will exclude discussion of the questionable "equivalent" type of migraine. Causative factors The increased frequency of migraine attacks among users of oral contraceptives is well established. 16•17 The cyclic use of moderately high doses of estrogen preparations for replacement or supplemental therapy has also been shqwn to increase migraine frequency. In a recent study of 239 women with migraine, the frequency of attacks was significantly greater in 60 women who used oral contracept~v~s and 87 who received estrogen replacement or supplementatipn therapy than in 92 women not using hormones. Moreover, upon discontinuation of the oral contraceptives in the first group and following reduction and "decycling" of estrogen in the second group, the headache frequency rate decreased by 70% and 80%, respectively. 18 Sommerville l9 concluded JANUARY 1978
that prolonged, elevated levels of plasma estrogen may prime cranial blood vessels, resulting in vessel dilation and consequent headache upon withdrawal. This helps to explain why, in the absence of extrinsic estrogen use, attacks occur in association with menstruation, and it may account for the higher incidence of migraine in women. In regard to this, it has been reported that although the female-to-male ratio of migraine in childhood is I: 1,20 it changes following menarche to favor women 2: I.J In headache clinics, this ratio is 4: I or greater. Numerous factors have been reported to induce the acute migraine attack. In an effort to identify these factors and establish their frequency of migraine induction, 400 patients at the California Medical Clinic for Headache were followed over a sixmonth period. In order of decreasing frequency, the factors apparently inducing attacks were found to be: extrinsic estrogen; premenstrual and menstrual times; anticipatory anxiety; vacation periods; alcohol; weekends; post-crisis events; and chocolate. There was no significant influence of cigarette smoke, smog, weather change, season, monosodium glutamate, sodium nitrate, or foods containing tyramine. Ryan 21 and Shaw and associates 22 have also reported similar negative results regarding tyramine induction of migraine. This is in disagreement with the original studies of Hanington,23 published in 1967. A major factor in migraine production appears to be stress, either resulting from anticipation or arising from adaptation effort. Clearly, migraine sufferers experience headaches as a result of PSYCHOSOMATICS
environmental change, which may involve moving, job changes, and even vacations and weekends. Vacations and weekends are generally unstructured and may tax the adaptive abilities of rigid, intolerant, perfectionist individuals. For these reasons, migraine
I • Epinephrine release ~ MAO deficiency I
may well be considered a maladaptation syndrome affecting the psychological, biochemical, and vasomotor functions. Biochemistry Specific biochemical events have been identified in associa-
~
Estrogen
Menstrually related Oral contraceptives Cyclic supplements
I
Stress
I
Dietary
I
Phenylethylamine Tyramine
Platelet aggregation
Serotonin release
I
Prostaglandin release Prodromal phase (Cerebral vasoconstriction)
I
Serotonin depletion
FIGURE
I
Headache phase (Cranial vasodilation)
2-Proposed scheme o(migraine pathogenesis (Part 1). 51
Migraine
tion with migraine and involve histamines, platelet serotonin, kinin, intrinsic heparin, monoamine oxidase (MAO), y-aminobutyric acid (GABA), prostaglandins, and tyramine. In 1961, Sicuteri and associates 24 found that the urinary turnover rate of 5-hydroxyindoleacetic acid, the major catabolic product of serotonin, was increased during the migraine attack. In 1967, Anthony and associates 25 demonstrated that levels of platelet serotonin were elevated during the pre-headache phase and were decreased during the headache period. During attacks, ThonnardNeumann 26 observed an increased basophilic heparin level. Blood basophils and tissue mast cells store heparin, which lends
importance to this observation, since heparin may affect platelet integrity. Also, during the migraine attack, alteration in neurotransmitter metabolism was inferred by the findings of Welch and associates,27 who were able to demonstrate the presence of GABA in the spinal fluid of one group of patients with acute migraine and in another group of patients with cerebrovascular ~is ease and ischemia. Control groups consisting of non-migraine headache sufferers and migraine sufferers in remission showed no elevation of cerebral spinal fluid GABA levels. Other biochemical characteristics of migraine include: MAO deficiency and phenylethylamine oxidizing defects, as re-
I Mast cells I
I
Serotonin I
: Histamine
I + I Proteolytic enzymes I
I Plasmakinin release
j
Increased capillary permeability
Lowered levels
! I - - - Reduced
pain threshold
FIGURE
Incre~sed pain sensitivity of vessel walls and perivascular tissue
3-Proposed scheme o(migraine pathogenesis (Part 2).
PSYCHOSOMATICS
ported by Sandler and associates 28; prostaglandin activity, described by Carlson 29; and the elicitation of histamine 30 and kinin increases. 31 As noted earlier, estrogen changes, stress, and dietary factors may precipitate the headache attack in genetically predisposed individuals. It is believed that these factors may induce platelet aggregability, as first reported by Kalendovsky and Austin. 32 This makes possible the construction of a reasonable scheme of migraine pathogenesis that incorporates most of the biochemical changes observed in migraine. Induced platelet aggregation leads to serotonin release, causing cerebrovascular constriction responsible for the pre-headache stage of an attack. Circulating serotonin induces prostaglandin release from lung tissue, which is in part responsible for the profound extracranial arterial dilation of the headache phase. Breakdown of circulating serotonin allows for an unopposed vasodilation, contributing to a sustained painful period (Figure 2). To this scheme Fanch amps 33 suggests an additional step: as the platelets release serotonin, mast cells liberate histamine and proteolytic enzymes. Histamine and serotonin increase capillary permeability while proteolytic enzymes act on plasmakininogen, producing plasmakinin. Transudation of this substance causes vascular and perivascular pain and, with the combined action of reduced serotonin levels, reduces the pain threshold (Figure 3). Psychological aspects Personality studies by Wolff,34 Friedman and asso55
Migraine
ciates,35 and more recently Henryk-Gutt and Rees 36 have characterized the migraine sufferer as tense, obsessive, overcontrolled, perfectionistic, orderly, and rigid. Clearly, individuals with such personality characteristics would be expected to have difficulty in adjusting to even minor environmental variations. Indeed, using psychometric scales for maladjustment, Rogado and associates37 reported that migraine victims scored worse than controls. Neuroticism was also found to be more prevalent among migraine sufferers than controls in a study that utilized the Eysenck-Maudsley test. 36 Rogado and associates37 reported that patients with migraine scored higher on the hysteria and hypochondriasis scales of the MMPI than did controls. In fact, they indicated that a "conversion V" configuration (a configuration commonly seen in conversion neurosis) was typical of the migraine population. In our own study of 50 migraine patients, only those who also suffered chronic scalp-muscle contraction headache showed these results, whereas migraine patients free from scalp-muscle contraction headache did not score higher on these scales than controls or those with combination headache. In addition, only 10% of this migraine population had significant depression. This observation is in agreement with data of Couch and associates38 concerning depression in migraine. Neurophysiological aspects Unusual personality and psychological aspects of migraine are not the only conditions reflective of maladaptive behavior. We
have already reviewed the biochemically related vasomotor instability, which may be seen as maladaptive mechanisms. Nor are the affected systems limited to vascular function. Pozniak-Patewicz39 reported that muscular reactivity was greater in migraine patients than in patients with other types of headache, even when headache free. In a study of autonomic nervous system response patterns, Rickles and associates40 concluded that migraineurs exhibit significantly greater reactivity of three psychophysiological functions when compared
with their non-migraine cohorts: forehead and hand temperature, finger-pulse amplitude, and frontalis EM G changes. Thus, migraine appears to be a strongly familial disorder characterized by psychophysiological, biochemical, and vasomotor dysfunction, causing difficulty in adaptation to environmental changes. One can appreciate the trepidation exhibited by migraine sufferers when faced with circumstances considered pleasurable to others, such as vacations, travel, weekends, or even an evening out with friends. 0
REFERENCES I. Kudrow L: Systemic causes of headache. Postgrad Med 56: lOS-III, 1974. 2. Ad Hoc Committee on the Classification of Headache. JAMA 179:717-718, 1962. 3. Waters WE. O'Connor PJ: Prevalence of migraine. J Neurol Neurosurg PsychiaJry 30:613-616, 1975. 4. Refsum S: Genetic aspects of migraine, in Vinken PJ, Bruyn GW (eds): Handbook of Clinical Neurology. Amsterdam, North-Holland Publishing Co, 1968, vol 5, chap 25. 5. Barolin GS, Sperlich D: Migraine familien. Fortsch Neurol Psychiat 37:521-554. 1969. 6. Goodell H, Lewontin R, Wolff HG: Familial occurrence of migraine headache. Arch Neurol PsychiaJ 72:325-334, 1954. 7. Ziegler DK, Hassanein RS, Harris D, et al: Headache in a non-clinic twin population. Headache 13:213-218, 1975. 8. Price KP, Tursky B: Vascular reactivity ofmigraineurs and nonmigraineurs: A comparison of responses to self-control procedures. Headache 16:210-217, 1976. 9. Dalessio D: Classification of headache. Internat Ophtha/mol C/in 10:647-665, 1970. 10. Alvarez WC: The migrainous scotoma as studied in 618 persons. Amer J Ophtha/mol49:489-504, 1960.
11. Clarke JM: On recurrent motor paraI· ysis in migraine; with report of a family in which recurrent hemiplegia accompanied the attacks. Br Med J 1: 15341538, 1910. 12. Whitty CMW: Familial hemiplegic migraine. J Neuro/ Neurosurg Psychiatry 16:172-177, 1953. 13. Saundby R: A case of megrim, with paralysis of the third nerve. Lancet 2:345-346, 1882. 14. Friedman AP, Harter DH, Merritt HH: Ophthalmoplegic migraine. Arch Neuro/7:82-87, 1962. 15. Bickerstaff ER: Basilar artery migraine. Lancet 1:15-17, 1961. 16. Grant ECG: Relation between headaches from oral contraceptives and development of endometrial arterioles. Br MedJ 3:402-405,1968. 17. Whitty CWM, Hockaday JM, Whitty MM: The effect of oral contraceptives on migraine. Lancet 1:856-859, 1966. 18. Kudrow L: The relationship of headache frequency to hormone use in migraine. Headache 15:36-40, 1975. 19. Sommerville BW: The role of estradiol withdrawal in the etiology of menstrual migraine. Neurology 22:355-365, 1972. 20. Krupp GR, Friedman AP: Migraine in children, A report of fifty children. Read before the Section on Pediatrics, IOlst Annual Session of AMA, Chicago, June 1950. 21. Ryan RE: A clinical study of tyramine
JANUARY 1978
as an etiological factor in migraine. Headache 14:43-48. 1974. 22. Shaw SWJ. Johnson RH. Keogh HJ: Oral tyramine in dietary migraine sufferers. Read before the Migraine Trust International Symposium. London. Sept 1976. 23. Hanington E: Preliminary report on tyramine headache. Sr Med J 2:550551. 1967. 24. Sicuteri F. Testi A. Anselmi B: Biochemical investigations in headache: increase in the hydroxyindoleacetic acid excretion during migraine allacks. Internat Arch A lIer~ 19:55-58. 1961. 25. Anthony M. Hinterberger H. Lance JW: Plasma serotonin in migraine and stress. Arch Neurol (Chicago) 16:544552. 1967. 26. Thonnard-Neumann E: Heparin in migraine headache. Headache 13:4964. 1973. 27. Welch KMA. Chabi E. Nell JH. et al: Biochemical comparLson of migraine and stroke. Headache 16: 160-167. 1976. 28. Sandler M. Youdim MBH. Hanington
E: A phenylethylamine oxidizing defect in migraine. Nature 250:335-341. 1974. 29. Carlson LA: Metabolic and cardiovascular effects in vivo of prostaglandins. in Bergstrom S. Samuelson B (cds): Prostaglandins. Nohel Srmposium 2. New York. Interscience. 1967. pp 123161. 30. Sjaastad O. Sjaastad OV: The histaminuria in vascular headache. Acta Neurol Scand 46:331-342. 1970. 31. Chapman LF. Ramos AO. Goodell H. et al: Humoral agent implicated in vascular headache of the migraine type. Arch Neurol (Chicago) 3:223-229. 1960. 32. Kalendovsky Z. Austin JH: "Complicated migraine:' its association with increased platelet aggregability and abnormal plasma coagulation factors. Headache IS: 18-35. 1975. 33. Fanchamps A: The role of humoral mediators in migraine headache. Call J Neurol Sci I: 189-195. 1974. 34. Wolff HG: Personality factors and re-
Dr. Kudrow is director of the Ca/~rornia Medical Clinic for Headache. in Encino, and associate editor of the journal, Headache. Reprint requests 10 Dr. Kudrow, 16542 Ventura Blvd.. Encino. CA 91436.
actions of subjects with migraine. Arch Neurol P.ITchiatrr 37:895-903. 1937. 35. Friedman AP. Von Storch Jc. Houston MH: Migraine and tension headaches: A clinical study of 2000 cases. Neurolo?r 4:773-788. 1954. 36. Henryk-Gull R. Rees WL: Psychological aspects of migraine. J Pwchmomatic ReJ 17: 141-153. 1973. 37. Rogado1\, Harrison RH. Graham JR: Personality profiles in cluster headache. migraine and normal controls. Read before the 10th International Congress of World Federation of Neurology. Amsterdam. Sept 1973. 38. Couch JR. Ziegler DK. Hassanein RS: Evaluation of the relationship between migraine headache and depression. Headache 15:41-50. 1975. 39. Pozniak-Patewicz E: "Cephalgic" spasm of head and neck muscles. Headache 15:261-266. 1976. 40. Rickles WHo Cohen MJ. McArthur DL: A psychophysiology study of ANS response pallerns in migraine headache patients and their headache-free friends. Read before the 19th annual meeting of the American Association for the SlUdy of Headache. San Francisco. June 1977.
CALL FOR PAPERS "Psychosomatic Medicine-Tempo of the Times" 25th Anniversary Meeting November 15-19, 1978, Atlanta, Georgia Contributions in each of the following emphasis areas are invited: EDUCATION-With particular emphasis on training of primary care physicians by psychiatrists and behavioral scientists. TREATMENT-Preventive and therapeutic
RESEARCH-Recent advances of relevance and utility to the practitioner. Psychosomatic problems in children, adolescents and families With special emphasis on diagnostic treatment and research methods.
Abstracts, papers and ideas for the program should be submitted to: William L. Webb, Jr., MD Departmenl of Psychialry University of Tennessee 865 Poplar Avenue, Memphis, TN 38105
PSYCHOSOMATICS
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