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Startseite Background to Migraine: Fourth Migraine Symposium September 11th, 1970
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BACKGROUND TO MIGRAINE FOURTH MIGRAJNE SYMPOSIUM September 11th, 1970 BACKGROUND TO MIGRAINE FOURTH MIGRAINE SYMPOSIUM September 11th, 1970 Sponsored by The Migraine Trust 23 Queen Square, London, W.C.l Edited by Professor J. N. Cumings, M.D., F.R.C.P., F.R.C.Path. Department of Chemical Pathology, The National Hospital, Queen Square, London, W.C.l Symposium Committee: Chairman: Dr Raymond Greene, M.A., D.M., F.R.C.P. Dr Macdonald Critchley, C.B.E., M.D., F.R.C.P., F.A.C.P. Professor J. N. Cumings, M.D., F.R.C.P., F.R.C.Path. Dr Marcia Wilkinson, M.A., D.M., F.R.C.P. Hon. Secretary: Dr K. J. Zilkha, M.D., F.R.C.P. SPRINGER SCIENCE+BUSINESS MEDIA, LLC © Springer Science+Business Media New York 1971 Originally published by The Migraine Trust, 1971 Softcoverreprint ofthe bardeover Istedition 1971 ISBN 978-1-4757-4579-5 ISBN 978-1-4757-4577-1 (eBook) DOI 10.1007/978-1-4757-4577-1 CONTENTS Chapter Page Preface vm Opening remarks by Sir John Richardson, Bart MVO MA MD FRCP xi Generalreview of migraine J. M. S. Pearce 2 Migraine as seen in The London City Clinic Marcia Wilkinson 3 Diagnostic problems in a migraine clinic J. D. Carroll 14 4 Migraine in General Practice K. M. Hay 25 5 Epidemiological aspects of migraine W. E. Waters 36 6 Psychiatrie and psychological factors in migraine W. Linford Rees 45 7 Migraine and the Pill B. M. Phillips 55 8 Migraine and flying P. J. O'Connor 62 9 New sturlies on the circulatory effects of ergot compounds with implications to migraine B. Berde 66 I0 SANDOZ LECTURE: Migraine, a biochemical disorder? J. N. Cumings 76 Index 91 V 8 CONTRIBUTORS AND THEIR ADDRESSES B. Berde, M.D., Biological and Medical Research Division, Sandoz Limited, Basle, 13, Switzerland J. D. Carrol/, M.D., M.R.C.P., F.R.C.P.Ed., Regional Neurological Unit, Royal Surrey County Hospital, Guildford, Surrey Professor J. N. Cumings, M.D., F.R.C.P., F.R.C.Path., Department of Chemical Pathology, Institute of Neurology, The National Hospital, Queen Square, London,; W.C.l K. M. Hay, M.B.E., M.A., M.D., M.R.C.G.P., 35 Sherbourne Road, Birmingham, 27 Air Commodore P. J. O'Connor, O.B.E., M.D., D.P.M., F.R.C.P.Ed., M.R.C.P., Division of Neurology & Psychiatry, R.A.F. Central Medical Establishment, Kelvin Hause, Cleveland Street, London, W.l J. M. S. Pearce, M.D., M.R.C.P., Combined Neurological Service, Hull Royal Infirmary, Hull B. M. Phi/lips, M.B., B.S., M.R.C.P., Morriston Hospital, Morriston, Glam. Professor W. Linford Rees, M.D., F.R.C.P., D.P.M., Department of Psychiatry, St Bartholomew's Hospital, E.C.l W. E. Waters, M.B., B.S., D.l.H., M.R.C. Epidemiology Unit (South Wales), Cardiff Marcia Wilkinson, M.A., D.M., F.R.C.P., Elizabeth Garreit Anderson Hospital, Euston Road, London, N. W.l vii PREFACE The Fourth Migraine Symposiumheldon September 11th, 1970 was deliberately slanted towards a different audience from the earlier meetings. An attempt was made to interest General Practitioners rather than Scientists in some of the problems associated with diagnosis and therapy in migraine. Yet the volume does include two papers of a more scientific nature and these may be of some interest to those physiologists and biochemists interested in this common disorder. References are those given by each author, but as far as possible they have been checked and are presented here in as uniform a manner as possible. Dr Raymond Greene most kindly acted throughout the entirc meeting as a most excellent Chairman. Our thanks are also due and are given to The Migraine Trust for their part in the organizing of the meeting, to Miss S. Barkwell, my secretary, for her painstaking assistance, and to the Department of Medical Illustration for preparing the figures in Chapters I, 3, 4 and I 0. November, I970 J. N. CUMINGS Editor viii Chairman: DR RA YMOND GREENE OPENING ADDRESS Sir John Richardson As a generat physician, I am naturally very greatly honoured at being invited tobe the first speaker at this Fourth Symposium of the Migraine Trust. Migraine certainly deserves special study because of the enormous morbidity that it causes throughout the world. I understand that it has been estimated that there are seven million sufferers in this country alone. The condition was recognized in the times of antiquity, and I have read that an account of it is given in a Sumerian poem written some 5000 years ago. Our profession has-as you yourself have pointed out, Mr Chairman-identified and studied this condition for over 2000 years, and therefore there is no need for any opener to justify the study of migraine, but rather to congratulate you on having formed a body to do so. The importance of this came home to me forcibly when, after reading recent accounts of migraine in the lay as weil as in the medical press, I took stock of the present situation, comparing it in my mind with the state of affairs when I first was aware of migraine as a medical problern nearly 40 years ago. I must confess to you that I found little to suggest to me that we understand its underlying mechanism notably better now than then, and certainly I do not find that any great advances have been added to its classical clinical description. In the field of therapeutics there also seems to be no major breakthrough since the first use of ergotamine, if indeed that can be described as a major breakthrough, although we naturally have hopes of methysergide and clonidine which are under trial at present but clearly have their own difficulties, such as the fascinating but intimidating methysergide fibrosis. I was, therefore, after experiencing these rather negative thoughts, in some personal difficulty about choosing what to say. However, after looking through the very attractive programme that lies before us I feit that I might be allowed to mention some of the less clinical manifestations of migraine, although nothing that I shall say is likely to be new to anyone here. This, I fear, is often the fate of the general physician. Because of the sophistication of this audience I am not going to follow the common practice of giving a description of the classical type of migraine before discussing some of the less usual manifestations. I wish, nevertheless, to stress two points which recur consistently when a diagnosis of a migrainous equivalent is under consideration. They are the periodicity of the attacks, and the frequency of a family history of migraine. xi Xll Background to Migraine A common variant of migraine which we have all met is vertiginous or vestibular migraine. Periodic giddiness of varying intensity, first coming on quite frequently in the forties, may accompany or actually replace classical attacks. Such vertigo can, on the other hand, be a variant which is the only symptom of migraine to be recognized in the patient. It is here that exclusion, together with the periodicity of the lesion and possibly a family history may of necessity have to be the basis for this clinical diagnosis. The severity of the symptoms may vary from a sense of unsteadiness to a state of affairs where, without care, a Meniere's syndrome might be suspected. Periodic attacks of drowsiness which occasionally seem to overwhelm the patient are also not uncommon in middle-aged sufferers from migraine, and may be definite enough to compel a driver, for instance, to stop his car and possibly to sleep for a short period in a lay-by. This state of affairs is, of course, not by any means always migrainous or due to narcolepsy, but is sometimes associated with rapidly developing obesity and disappears when a significant reduction in weight is achieved. Another and very disconcerting manifestation of migraine is the inability to remember, either from the spoken or written word, the beginning of a long sentence by the time the end is reached. A question may have been asked, and the questioner or the one questioned, if in a migrainous state, may forget the beginning of the question before the end is reached, so that only very short sentences can be properly comprehended. Together with this may be a failure to add up pieces of evidence because some are immediately forgotten, or to change from an initial impression to a further conclusion due to additional information, because this has been lost. An incongruous example of this was when a very eminent, careful and senior obstetrician sent a young woman to a physician with the request that he should reduce her weight. She was, in fact, very pregnant. The unfortunate and deeply chagrined obstetrician had recognized later in the day that he was suffering from migraine but had not realized this during the time he was struggling through a long gynrecological clinic. A variant of migraine that presents notable difficulty in diagnosis and can be dangerous if such a diagnosis is incorrectly made is abdominal migraine. Again, careful exclusion and a periodic symptomatology, coupled with a family history, may be the basis of the diagnosis if previous manifestations of migraine are absent. Periodic bouts of abdominal pain may emulate an acute abdomen. Severe nausea with upper abdominal tenderness may Iead to a mistaken diagnosis of cholecystitis. Severe vomiting and diarrhcea can be mistaken for infective gastro-enteritis. Apparently in patients with migraine on whom a barium meal has been carried out, there is pretty well complete loss of gastric peristalsis and the stomach is an inert bag, and the late Professor John Ryle records a patient who had been diagnosedas suffering from pyloric stenosis and operation advised, but was, in fact, suffering from Opening Address xiii migraine. I personally have rarely made a diagnosis of abdominal migraine, and only in patients who have other migrainous manifestations. I have on the other band often, after exclusion, as have all of us, regarded as migrainous a patient whose complaint is recurrent nausea accompanied by a slowing of the mental processes, sometimes of an incapacitating degree. Here a bile salt preparation may turn a life previously almost intolerable into a satisfactory one, and even save a threatened career. This is the commonest variant that has come my way. I do not know whether you, Sir, will consider that I am stepping beyond the confines of migraine if I mention a condition that has many names but is often called in this country the migrainous neuralgia of Harris. I think this is the same thing as Americans call cluster or paroxysmal headaches. The characteristics of this condition are the grouping of attacks of extremely severe pain, which is unilateral and usually on the same side, and their tendency to come on at the same time of the day or night. The severity of the attacks can be so great that the patient can think of nothing eise but the pain in his head. They last usually, and fortunately, for a short period-an hour or so-only to recur about the sametime possibly the next night, and nightly for, say, a week. Such was the case in a man of 65 who suffered from diabetes mellitus for which he was under my care. One day he told me that he bad for three successive nights awoken at I a.m. with a pain just over his left eye. This only Iasted for an hour but was extremely agonizing, and although he bad had much to put up with during his life from the medical point of view, he had never experienced anything like it. Cafergot, as seems to be the case not infrequently in this condition, relieved bis pain completely, and as soon as he had a recurrence he would use a suppository, thus abolishing clusters and only experiencing one bout. A very similar story was told me by a man of about the same age, a regular and gallant soldier with a cheerful spirit, who nevertheless claimed that he had never experienced comparable pain. He was equally promptly relieved of bis symptoms by ergotamine, an observation that has been known for a long time. My last example was again in a man. This conditions appears, unlike migraine, to be more frequent in men than in women. He was aged 46 and had suffered from migraine in the past, particularly in his 42nd year. He had also had two bouts of unsteadiness of gait in the last few weeks. He was found to be suffering from hypertension and was admitted because of very severe headaches which were attributed to his raised B.P. On enquiry his recent story was this. Eight days before admission he had had a first attack of extreme pain of a throbbing nature behind his right eye. It had awoken him from his sleep and had Iasted for five hours, totally absorbing his attention. He had noticed no difference in vision but, as is not uncommon in migraine attacks, his right eye watered profusely and became red during the attack. Two nights XIV Background to Migraine Iater and four nights later he had had similar attacks Iasting about the same number of hours. He thought that standing up relieved his pain for a matter of two minutes, and it was certainly worse when he lay down. The cluster of attacks did not continue so I do not know whether he would have responded to ergotamine. You will have perceived that all the features I have mentioned as variants, and others I have not, such as isolated ocular disturbances, are found in many people with a classical clinical picture of migraine. It is only their occurrence without any, or with only very faint or blurred features of the weil recognized picture, that justifies their classification as variants. Their recognition as such may greatly relieve a patient's anxiety and Iead to a new therapeutic line of approach. Knowing about them is thus weil worth while. Mr Chairman, I Iook forward to the rest of the programme with very great interest. Although I said earlier on that I am not as yet persuaded that any really great advance in treatment has been made in my medical lifetime, I nevertheless feel that every patient can be helped and usually to a considerable extent by a persistent and sustained interest and effort by the doctor. I hope to learn more in support ofthisbelief today. CHAPTER 1 GENERAL REVIEW SOME .tETIOLOGICAL FACTORS IN MIGRAINE John Pearce This review of migraine is based on observations stemming from the author's interest in migraine over the last eight years, and in particular from the Headache Clinic at the Hull Royal Infirmary which has been active since 1967. I will not attempt yet another definition of the syndrome; the classical case poses no diagnostic problerns, the difficult case rnay provoke differing opinions arnong experts. Gowers' definition (1893) has not been excelled: "an affection characterised by paroxysrnal nervous disturbance, of which headache is the rnost constant elernent. The pain is seldorn absent and rnay exist alone, but is comrnonly accornpanied by nausea and vorniting, and it is often preceded by sorne sensory disturbance, especially by sorne disorder of the sense of sight.... " Our observations on the problern of the diagnosis and rnanagernent of rnigraine, and its cornplications have been previously reported (Pearce and F oster, 1965; Pearce, 1968, 1969) and I shall not discuss these today, in the belief that these will be dealt with elsewhere in this Symposium. My efforts here are directed to describing the background, hereditary and environrnental, and the precipitating factors present in rnigrainous patients, and to speculate on sorne of the retiological factors. Since there is no panacea for the treatrnent of migraine, the rnagnitude of the problern viewed epiderniologically, and the identification of precipitating factors which may be correctable are of irnportance. Some of the cornplex data on the epidemiology are summarized in Table I. This rnakes it clear that the prevalence rate is high, that wornen attend clinics rnore frequently than rnen, and that there is a strong hereditary cornponent in the genesis of the syndrorne. TABLEI The Migraine Profile in 450 Clinic Patients Prevalence . Sex . Age of onset Family history lnheritance . 5-10% population 66% females 5-30 in 85% cases Positive in 65 % ?Dominant 2 Background to Migraine TABLE II Precipitating Factors Anxiety or worry Relaxation . . . Fatigue or sleeplessness Menstruation Bright light Specific foods Alcohol Hunger % 73 45 43 39 30 13 10 7 The frequency of some of the more common factors which patients are able to identify as precipitants are summarized in Table II, where it will be seen that anxiety, relaxation after stress (weekend headache) and menstruation figure prominently. In my experience specific foodstuffs, especially those containing tyramine are uncommon provocative agents though doubtless important to the susceptible subject (Hanington, 1969). Hunger, alcohol, excess or loss of sleep are occasional factors of importance, though their biochemical mechanisms remain obscure. Mechanical factors, such as head injury, neckinjury andcervical spondylosis are occasional aggravating agents, but more often important in the mind of the patient than in the mind of the physician. These observations as a whole are important, but only as precipitating, not causative factors. Hormonal changes related to migraine include: I. the secretion of restradial at ovulation and before the menstrual period when attacks occur in 60 per cent of female migraine subjects (de Wit, 1950) is common; 2. secretion of vasopressin induced by anxiety; 3. the increased frequency andfor severity of migraine in women taking the contraceptive pill, especially its occurrence in the days of the cycle when the progestogen present is withdrawn (Greene, 1967; Phillips, 1968; Whitty, Hockaday and Whitty, 1966); 4. the remission of migraine in pregnancy. These factors are of considerable interest, but the ways in which these changes in hormonal Ievels can effect the widespread vascular and autonomic disturbances characteristic of migraine, remain obscure. A study of associated disorders (Table 111) shows a high incidence of travel sickness and bilious attacks in childhood; and if the term "migraine equivalent" has any significance it probably lies in disorders such as these. There is undoubtedly a high frequency of neurotic illness past or present in migraine subjects. Similarly, shy and sensitive, retiring personalities with obsessional traits such as excessive tidiness, perfectionistic outlook and over-conscientiousness figure prominently. These factors are, however, only apart of the background-the type of soil in which the migrainous seed is more easily germinated. They are 3 General Review of Migraine by no means exclusive to migraine, they vary widely, andin generat they bear little identifiable relationship with the individual migraine attack. TABLE III Associated Disorders Travel sickness . Bilious attacks . Obsessional traits Shy or sensitive . Psychoneurotic illness Fear of tumour Hypertension Epilepsy % 60 47 53 50 30 17 4 2 The prime challenge in the study of the problems of migraine seems not to be in these secondary aggravating or precipitating factors, but in the pursuit of the primary migraine diathesis. Little is known of this, and the only feature of note clinically is the strong but still debated role of hereditary (Dalsgaard-Nielsen, 1965; Goodell, Lewontin and Wolff, 1954; Pearce, 1969). The only !>;>eculations about what is inherited are: I. Graham's (1967) suggestion of deficiency of the ability of the cranial neuro-vasculature to adjust to various stimuli, and 2. the suggestion (Pearce, 1969) of an inherited anomaly of threshold of the central mechanisms in the hypothalamus. Considerations of centrat mechanisms seem cogent for a number of reasons: I. What controls the resistant periods in a migraine patient's life history, during which almost any stress or self-abuse fail to produce an attack; similarly what altered mechanism underlies the vulnerable spells in which factors as varied as sunlight, special foods, relaxation after stress, and alcohol may easily precipitate an attack? (Pearce, 1968) 2. What governs the frequency of attacks so that one subject has two or three episodes in a lifetime, another one a week? 3. Why do attacks often occur in clusters of two or three, as is so common in epilepsy? 4. After an attack (or cluster) what causes the increased resistance, the raised threshold which may last for days or many weeks? These unanswered questions suggest the theory that some mechanism exists with a variable threshold; and that the mechanism is susceptible to the effects of both humoral and neural (including emotional) processes. Such a mechanism may lie in the hypothalamus. This structure receives neural impulses governed by extrinsic emotional disorders via the limbic system of the temporal Iobes and fornix; it can influence vegetative visceral and vascular functions via the sympathetic and parasympathetic nervous systems whose cells of origin lie within it. The hypothalamus via its portal system of vessels in the pituitary stalk B.M. 2 4 Background to Migraine secretes releasing factors for the hormones of the adenohypophysis, which in turn regulate endocrine function via feed-back mechanisms. This structure is of unquestioned importance in its varying and dynamic function in regulating temperature, urine secretion, cortisol, blood sugar, restrus and so forth. These basic functions work as if set by a biological clock, the spring of which is the hypothalamus. Investigating the hypothalamo-pituitary-adrenal axis by means of cortisol assays, metyrapone tests and insulin-hypoglycremia tests, little was found wrong with the integrity of the component parts of this axis (Rao and Pearce, 1971). However, a highly significant (see Figs. 1, 2) tendency to prolonged hypoglycremia-unresponsiveness in migraine subjects was observed which was not present in matched controls. This finding coincides with the clinical observations that migraine may be induced by starvation (Critchley and Ferguson, 1933; Blau and Cumings, 1966), but in our experience is not directly related to hypoglycremia per se. Our results exclude deficiences of ACTH, corticotrophin releasing factor (CRF) and adrenal cortisol, but abnormalities of secretion of growth hormone, and the liver glycogenolytic mechanisms require further investigation as contenders for the cause of this prolonged hypoglycremia unresponsiveness or increased insulin sensitivity. There is a possible analogy here with the syndrome of "functional hypoglycremia", and though we have no evidence ofthis in our patients, further study might be fruitful. The roJe of tissue kinins, plasma serotonin changes (Curran, Hinterberger and Lance, 1965) are of obvious importance in the production of certain symptoms of the migraine syndrome. So too are changes in arterial stores of catecholamines (Adams, Orton and Zilkha, 1968). Vaso-neuroactive substances (Sicuteri, 1967) have been shown to be factors central to the production of pain around dilated scalp vessels, and probably are also important in relation to distension of intracranial venous sinuses which certainly contribute to the pain of migraine. The complex actions of drugs in the syndrome have not yet been defined, but it is becoming increasingly clear that drugs such as methysergide, the tricyclic antidepressants and MAO inhibitors act to as great an extent on the central pathways as they do on the peripheral humoral mechanisms. These points are to a !arge extent speculative, but both clinical and experimental evidence have been cited which call attention to the central mechanisms which I believe tobe of importance in the basic retiology of migraine. Further experimental and clinical endeavours in this field are needed. 5 General Review of Migraine go . INSULIN HYPOGLYCAEMIA TEST 80 L-50 0 Cl' ::J V') ""0 0 0 40 ..0 ."30 ::J 0 c:: / Cl) / / / ,x: / / / / / X / / / / / > 2.0 10 + Controls o--o (lo) Patients *--X (20) o~--~----~----~--~~--~~--~ 30 - o ~ i.v. Insulin 30 bo go minutes 120 0·15 unitsjkg. FIG. 1. Blood sugar ranges in insulin hypoglycremia tests in control andin patients with migraine. Background to Migraine 6 INSULIN Q HYPOGLYCAEMIA "TEST 30 / / / / u I 0 25 20 0 VI ...__ .... c; 15 0 ~ 10 0 a... 5 Controls o--o (10) Patients x---x (20) 0~~--~----~----~--~----~----~ 120 go 60 Midnight 30 - o + 30 t I. V. lnsu Iin minutes 0· 15 units/ kg. FIG. 2. Plasma cortisol variations in insulin hypoglycremia tests in control andin patients with migraine. General Review of Migraine 7 REFERENCES Adams, C. W. M., Orton, C. C. and Zilkha, K. J. (1968). Arterial catecholamine and enzyme histochemistry in migraine. J. Neuro!. Neurosurg. Psychiat. 31, 50. Blau, J. N. and Cumings, J. N. (1966). A method of precipitating and preventing some migraine attacks. Brit. med. J. 2, 1242. Critchley, M. and Ferguson, F. R. (1933). Migraine. Lancet i, 123 and 182. Curran, D. A., Hinterberger, H. and Lance, J. W. (1965). Total plasma serotonin, 5-hydroxyindoleacetic acid and p-hydroxymethoxymandelic acid excretion in normal and migrainous subjects. Brain 88, 997. Dalsgaard-Nielsen, T. (1965). Migraine and heredity. Acta neuro!. scand. 41, 287. Goodell, H., Lewontin, R. and Wolff, H. G. (1954). The familial occurrence of migraine headache: A study of heredity. Res. Pub!. Ass. Res. Nerv. Ment. Dis. 33, 346. Gowers, W. (1893). Diseases of the Nervous System. Philadelphia, Blakiston, Vol. 2, p. 836. Graham, J. R. (1967). Methysergide. Practitioner, 198, 302. Greene, R. (1967). Menstrual headache. In Res. Clin. Stud. Headache (ed. Friedman, A. P.) 1, 62, Basel/New York, Karger. Hanington, E. (1969). The effect of tyraminein inducing migrainous headache. In Background to Migraine, London, William Reinemann Medical Books. Pearce, J. (1968). The ophthalmological complications of migraine. J. Neuro/. Sei. 6, 73. Pearce, J. (1969). Migraine: Clinical Features, Mechanisms and Management. Springfield, Ill.: Thomas. Pearce, J. and Foster, J. B. (1965). An investigation of complicated migraine. Neurology, Minneap. 15, 333. Phillips, B. M. (1968). Oral contraceptive drugs and migraine. Brit. med. J. 2, 99. Rao, N. S. and Pearce, J. (1971). In preparation. Sicuteri, F. (1967): Vasoneuroactive substances and their implications in vascular pain. In Res. Clin. Stud. Headache (ed. Friedman, A. P.) 1, 6--45, Basel/New York, Karger. Whitty, C. W. M., Hockaday, J. M. and Whitty, M. M. (1966). The effect of oral contraceptives on migraine. Lancet i, 856. de Wit, J. C. (1950). Allergy to restrone in cases of migraine. Acta endocrin. 5, 173. CHAPTER 2 THE CITY MIGRAINE CLINIC Marcia Wilkinson The City Migraine Clinic was founded by the Migraine Trust and formally operred by H.R.H. the Princess Margaret on May 19th, 1970. The Clinic has two main aims, firstly to provide treatment for those suffering from migraine, and secondly to act as a centre for research into migraine. The City Clinic is the financial responsibility of the Migraine Trust which not only has to meet all the costs of upkeep but also has to pay to the N.H.S. the cost of any investigations carried out by the ancillary departments and of any prescription. Treatment is free for all U.K. residents but a small charge is made to overseas patients. The Clinic is, however, very fortunateinthat it is under the regis of St Bartholomew's Hospital, without whose kind co-operation and help it would have been impossible to start it. The medical staff is appointed by Bart's, but in consultation with the Trust, and the nurse is also a member of the hospital staff. We are fortunateinthat the Physicians and Surgeons of the Hospital have kindly consented to see any patients who attend the Clinic with medical or surgical problems in addition to their headaches. We are also very much indebted to the various drug companies who have kindly given us sn many of the drugs we have used. The City Clinic was the idea of Mr Derek Mullis, Chairman of the Management Committee of the Migraine Trust and himself, at that time, a City worker. He thought that a centre for treatment of migraine should be set up in the City as over half a million people come in to work there every day. If between 5 and 10 per cent of the population suffer from migraine, somewhere between 25,000 and 50,000 people in the City suffer from this disorder. The Clinic is staffed by one full-time and two part-time doctors, a staff nurse and a secretary. Patient referral The majority of patients coming to the Clinic are referred by their own family doctor as to an ordinary out-patient clinic. A special service is provided for those who develop a severe headache during working hours. The Clinic is open five days a week from 10 a.m. to 4 p.m. and emergency treatment is given to any patient coming in with a headache. Usually patients can be made better within two or three hours, but if they have not recovered sufficiently to go home by public transport, 8 Migraine as seen in The London City Clinic 9 arrangements are made for them to be taken home. Barclays Bank Limited have very kindly made their ambulance available to the Clinic either for fetehing patients whose headaches are so severe that they are unable to reach the Clinic on their own or to take patients back again. If for any reason the ambulance is not available, a minicah is used. In either case there is no charge to the patient. Number of patients Since the opening over 650 new patients have come to the Clinic and in addition there have been over 400 second or subsequent visits, a total of over 1000 out-patient attendances. About two-thirds of those coming suffer from migraine either classical or non-classical. In the other third the headaches are due to a variety of causes including tension and general medical conditions. All patients attending the Clinic are seen by a doctor and given a full medical examination. In all cases the general practitioner is sent a full report with recommendations as to treatment. The City Migraine Clinic offers unique opportunities for research into migraine as it seems probable that the biochemical and other changes which may take place only occur, or are maximal, in the hour before and the first two or three hours of the headache and since the opening, we have seen over 200 patients in an acute attack of headache. The present projects being carried out at the Clinic are: 1. A statistical analysis of some of the clinical and sociological aspects of migraine. 2. Clinical trials. At the moment trials on clonidine (Boehringer Ingelheim) are continuing as is the investigation of the roJe of tyramine in the production of headaches. Laterit is hoped that trials will be done on other new substances. 3. An evaluation of ergotarnirre tartrate, cyclizine (Valoid) and Torecan as treatment for acute attacks. 4. In conjunction with Professor J. N. Cumings and Miss B. Hilton, a study is being carried out on 5-HT Ievels and variation in platelet aggregation in patients with migraine. 5. A study of blood 5-HT Ievels in normal patients, in patients with migraine over a 24-hour period, and before and after tyramine has been given, bothin a control group and a group oftyramine positive patients. It is also hoped that after consultation with the Medical Research Committee, we will be able to provide material for other groups who are studying the biochemical changes in migraine. An analysis of the first 500 patients attending the City Migraine Clinic Classification of headaches Following a simplified form of the international classification patients attending have been put into the following groups: Background to Migraine 10 (a) Classical migraine, including dietary migraine, focal migraine, etc. (b) Non-classical migraine. (c) Tension or anxiety headaches. (d) Other. The criteria for classical migraine have been taken as (a) severe bilateral or unilateral headache, (b) nausea and/or vomiting and (c) disturbances of vision or other focal signs. Using this classification it has been possible to draw certain conclusions from the figures obtained: (a) 362 (72 per cent) of the patients have migraine, either classical or non-classical, and there is, therefore, a considerable demand for a clinic which specializes in treatment of this condition. (See Table I.) (b) Headaches as a whole occur more frequently in women, approximately 2:1 even in the Citypopulation (64 per cent:36 per cent). The sex distribution is more or less constant for both groups of migraine, classical and non-classical, but tension headaches are relatively more common in men, i.e. 44 per cent of those with tension headaches are men (56 per cent:44 per cent). (c) We are dealing with a relatively young age group, the average age being approximately 38 for all groups. (See Table II.) TABLEI Diagnosis in 500 Cases Type Classical migraine Non-classical migraine Nurobers % of type 186} 362 176 51 % of total } 49 72 Tension headaches 84 17 Other 54 11 II Sex Differences in Migraine TABLE - F=ID< Classical migraine . Non-classical migraine Tension headache 116 (62%) 114 (65%) 47 (56%) ·~·· Mol< 70 (38%) 62 (35%) 37 (44%) Average age Fernale Male 37 41 39 39 35 39 Migraine as seen in The London City Clinic 11 Social group The patients were considered in relation to their various social groups as can be seen in Table 111. TABLE III Social Groups of the 500 Patients Executive and professional Clerical and administrative Skilied workers . Manual workers . Schoolchildren/students Housewives Others 82 (16%) 222 (44%) 51 (10%) ll (2%) 24 (5%) 79 (16%) 31 (6%) As the Migraine Clinic is situated in the City, it was expected to provide a service mainly for those working there and this is reflected in the high nurober of those doing clerical and administrative work, 222 or 44 per cent. There is also a relatively high proportion of those doing executive or professional work, 82 (16 per cent). Manual workers form a very small proportion of this total, 11 or 2 per cent. This may be due either to the fact that there are few manual workers in the City or that those doing this type of job are less often subject to headache or take less notice of the headache when it occurs. Treatment of acute attacks An analysis of the results of treatment of the first 100 patients attending the City Clinic has been done. Fifty-nine of these were women, and 41 men, their ages ranging from 12 to 85, 44 had classical migraine, 37 common migraine and 12 tension headaches. In 4 the headaches were thought to be due to other causes. Of the 44 patients with classical migraine, 18 were men and of the non-classical migraine patients, 16 out of 37 were men. The analysis of this group is as follows: Classical Non-classical Tension headaches Other Men: 18 16 3 1 Women: 26 21 9 3 The main types of treatment given for classical migraine were: (a) Paragesic (Sandoz) tabs. (Panadol 550 mg., pseudo-ephedrine and caffeine 10 mg.)-an effervescent tablet. (b) Intramuscular Fernergin (Sandoz) 0·5 mg. (ergotamine tartrate). (c) Intramuscular Fernergin 0·5 mg. + intramuscular cyclizine 50 mg. (Valoid, Burroughs Wellcome) if the patient is nauseated or vomiting. The main forms of treatment for non-classical migraine were: (a) Paragesic tabs. and (b) Intramuscu1ar ergotamine tartrate 0·5 mg. 12 Background to M igraine For both forms of migraine other treatments were tried but no satisfactory conclusions could be drawn as the number of patients treated was too small. The evaluation of the success of each form of treatment was based on the degree ofreliefwithin a four-hour period after the initiation of treatment. Hourly observations of the patient, as to severity of headache and change in pulse and blood pressure were recorded after the start ofthe treatment. Table IV shows the results oftreatment in classical migraine. TABLE IV Treatment of Classical Migraine I Number of cases No improvement after 4 hours. . Some improvement after 4 hours . No symptoms after 4 hours. Attack aborted Effect unknown ~ I I i Paragesic Fernergin 14 9 0 6 (42·9%) 4 (28·6%) 0 4 F<=<g;n I and Miscelcyclizine laneous 9 I 12 I i I I 1 1 0 (11·1 %) (11·1 ~~) 3 4 4 I (33-3 %) (44·5%) (33-3%) 3 3 2 (33-3 %) (33-3 %) (16·7%) 2 0 2 (22·2%) I (16·7%) I 0 1 4 ! I Total 44 2 (4·8%) 17 II (40·5%) 12 (28·6%) 4 (9-6%) 9 On the evidence thus shown in Table IV the treatment of choice for the acute attack of classical migraine appears to be intramuscular ergotamine tartrate 0·5 mg. However, when the symptoms included vomiting, intramuscular cyclizine was found to be necessary in addition to ergotamine tartrate to alleviate all the symptoms. Only in one case was it found necessary to give a !arger dose of ergotamine tartrate. Table V shows the results obtained in non-classical migraine. TABLE V Treatment of Non-classical Migraine . I E rgotamme ~· tartrate Miscel- 1 [ Paragesic 0·5mg Ianeous Total 4 1_ _ 1_2_ 21 Number of cases 37 . . 1 I 0 No improvement after 4 hours . 0 1 Some improvement after 4 hours. 11 20 1 I 8 No symptoms after 4 hours 1 4 0 Attack aborted 1 I Effect unknown 9 11 o I 2 ~ ~ 13 Migraine as seen in The London City Clinic These results indicate that Paragesic is the most effective singleform of treatment used in the City Clinic in an acute attack of non-classical migraine. Other simple analgesics such as aspirin or other forms of paracetamol may be equally effective but Paragesic was used because it is readily absorbed. The use of intramuscular ergotamine tartrate 0·5 mg. in this respect is difficult to assess as only four cases received Fernergin as a form of treatment. These resul ts can be illustrated by the figures shown in Table VI. VI Ejfect o.f Treatment in M igraine TABLE Im_pr_o_v_ed-~ercentage . _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _T_ot_a_l_ 1__ 67 Migraine treated with Paragesic only . Tension headaches treated with Paragesic only . . . . . Migraine treated with i/m ergotamine tartrate only . . . Classical migraine treated with i/m ergotamine + antiemetic 52 , I' 11 9 17 12 16 15 I 78% 0 82% 71% [ 94% CHAPTER 3 DTAGNOSTIC PROBLEMS IN A MIGRAINE CLINIC J. D. Carroll The Migraine Clinic is a comparatively new idea in this country and the question is often asked, especially by those of us who are engaged in general practice, as to whether such specialized clinics serve any useful function to the community. My feelings on this, although it could be said that I was somewhat biased in view of my special interest in the subject, is that they have a very important part to play in clinical medicine. In the first place, the management of a patient with migraine is very often time-consuming and may make great demands on the family doctor. The fact that his patients are seen at a clinic by a specialist who is interested and sympathetic and can spend some little time listening to their problems can be a distinct advantage to the patient, for it is a wellknown fact that spontaneous remission, even without change of treatment, may occur under such circumstances. The patient is studied in a systematic and energetic manner and the best possible advice and treatment can be instituted for him. It is also worthy of note that the occasional patient may require special neurological investigations when their particular migraine is suggestive of an underlying intracranial lesion. Secondly, and you might say that it is of greater importance, is that research both from the clinical and biochemical aspects on the basic cause of migraine can be more easily facilitated when there is a viable clinic in operation. It may be of some interest that all patients who are referred to a migraine clinic are not necessarily suffering from typical migraine as will be seen from an analysis of 200 consecutive cases referred to my clinic at Guildford in 1969 and illustrated in Table I. I do not intend to discuss the salient points in the diagnosis of the conditions which are listed, but should Iike to draw attention to the influence of depression and anxiety on the migrainous subject and to refer to the conditions of cervical spondylosis and temporal arteritis which can easily be mistakenly Iabelied as migraine. A sound appreciation of the former is essential if the management and treatment of the patient with migraine is to be at all effective. The familiar phenomenon of absolutely continuous headache for weeks or months should not be readily accepted as a case of migraine; it suggests that the headaches are due to underlying tension and anxiety. In these cases, the headache is often described as being Iike a weight on 14 15 Diagnostic Problems in a Migraine Clinic TABLE 1 The Diagnosis of 200 Consecutive Headache Patients Referred to a Migraine Clinic in 1969 Number of patients . . . Migraine Migraine and depression Depression . Tension headaches Migrainous neuralgia . Post-concussional syndrome Ocular conditions . Cerebra! tumour . Cervical spondylosis Temporal arteritis Sinusitis 58 31 29 23 16 16 10 6 5 4 2 Percentage 29 15·5 14·5 11·5 8 8 5 3 2·5 2 1 the head, a tight band around the forehead or a feeling that the head is being split open. There are usually associated symptoms of depression consisting of insomnia, loss of appetite or weight, Iack of concentration, fatigue and inability to cope with work. However, there may be simultaneous true migrainous and psychoneurotic headache and this can only be ascertained by a careful and detailed history from the patient. The migraine when associated with depression and anxiety is very often more frequent and severe and so treatment has to be directed at both disorders if progress is to be made in the management of these patients. Cervical spondylosis may cause headaches not unlike migraine in the older subject. Both conditions may co-exist and so produce problems in diagnosis and management. The headaches are invariably occipital and are due to encroachment by osteophytes on the upper cervical roots as they come through the intervertebral foramina to supply the back of the head (see Fig. 1). The history in these patients should be carefully studied with special reference to the site of the headache and its aggravating factors if mistakes are to be avoided. Unilateral headache is associated with temporal arteritis but this condition affects elderly patients over sixty and should cause little diagnostic difficulty. The headache is severe and continuous and the superficial temporal arteries are intensely tender and may thrombose along part of their length. Visual disturbances may occur which can Iead to loss of vision due to involvement of the retinal arteries by the disease process. The condition runs a self-limiting course of several months and the blood Sedimentation rate is invariably raised in the acute stage of the illness. Migraine in its usual form is characteristic but it can produce a number of atypical clinical manifestations which fit into a disti~t pattern 16 Background to Migraine FIG. 1. Radiograph of the cervical spine (oblique view) showing encroachment of the exit foramina by osteophytes. of symptomatology and such are often referred to as migraine variants or equivalents. Time only allows me to mention a few of the more common varieties. Diagnostic Problems in a Migraine Clinic 17 The concept of basilar artery migraine was introduced by Bickerstaff (1961). It seems tobe mainly confined to young women. In this form of the disorder, the symptoms reflect a functional disturbance in the areas supplied by the basilar and posterior cerebral arteries. The first prodromal symptom is a visual one consisting of total Ioss of vision in both eyes or positive ill-formed hallucinations of hemianopic distribution through both visual fields. The visual disturbance is then followed by some or all of the following symptoms: vertigo, unsteadiness of gait, dysarthria and parresthesire in the peripheral parts of the limbs and sometimes around the lips and on the sides of the tongue. These premonitory symptoms are then followed after a variable short period by severe occipital headache and vomiting. Loss of consciousness at the height of the attack is an occasional feature. Such an unusual presentation will, of course, raise a thought in the practitioner's mind as to whether his patient has sustained a subarachnoid hremorrhage or a brain stem vascular accident. Recurrent attacks of unilateral headache associated with partial or complete paralysis of one or more of the ocular nerves has been termed ophthalmoplegic migraine. The paralysis and headache is always on the same side, the former appearing some hours after the headache or in some cases when the actual attack abates. The paralysis seems to occur only in those patients whose headache lasts Ionger than 24 hours and it is usually transient. However, in patients with repeated attacks recovery takes place rapidly at first, but in later attacks the paralysis may persist for weeks or months and in some instances may remain permanent. How very difficult, therefore, it can be to distinguish this variant of migraine from an aneurysm which may be situated either on the carotid bifurcation or on its posterior cerebral branch. A clinical point of value in these cases is the fact that if the palsies have occurred on previous occasions over a number of years and each of them has been comparatively short-Iived then a migrainous basis is very likely. It is, of course, very difficult to avoid not doing a carotid arteriogram as a precautionary measure, especially when the patient is seen after the first attack. Table II shows my experience of this form of migraine over a threeyear period. A case history of one such variant of migraine is that presented by Case 1, a woman D.D. aged 29 who was admitted to the Unitin May, 1970 with an eight-day history of pain around the Ieft eye associated with double vision. The pain was severe for two days and when it began to settle down she was aware of the double vision especially when she looked upwards. The headache was associated with nausea, vomiting and photophobia. She gave a history of three previous attacks over a five-year period and on each occasion the double vision took about four to six weeks to clear up completely. Clinical examination showed that she had a partial third nerve palsy. A lumbar puncture produced fluid under normal pressure with a normal protein content. Serology of Background to Migraine 18 TABLE li Ophthalmoplegie Migraine (1966-1969) Number of patients . Permanent ocular palsies Jllrd nerve IVth nerve Vlth nerve Fixed pupil Transient ocular palsies Illrd nerve IVth nerve Vlth nerve 12 4 (>9 attacks) 3 0 0 I 8 5 2 I the fluid was negative. A left carotid angiogram was also normal. She made an uneventful recovery from this attack but the double vision did not clear up for three months. lt is really surprising how often the diagnosis of migrainous neuralgia or duster headache is missed in general and hospital practice for it has a most distinct clinical pattern. There is more or less general agreement that the condition is a variant of migraine. The patient, who is usually a male, complains of attacks of severe throbbing pain in or around one eye which wakes him up from sleep in the early hours of the morning. The pain may last from 15 minutes to 4 hours and it is accompanied by some or all of the following symptoms: vomiting, watering and redness of the same eye and a feeling of congestion in the ipsilateral nostril. Drooping ofthe eyelid and a small pupil may also be additional features in an attack. The attacks occur in bouts which may last 6-8 weeks and it is customary for the patient to have one or two bouts each year. Specific treatment can be very effective in this condition but it should be noted that the approach differs to some extent from that employed in the more common varieties of migraine. There is one other clinical presentation in a migraine clinic which deserves attention and it is often a difficult diagnostic problem. This is the condition known as Lower-Half Headache or Sphenopalatine Neuralgia. lt is allied, as regards the mechanism of the pain, to migraine headache. The pain is episodic and recurrent. It is confined to the lower half of the face and never extends above the Ievel of the eye. lt is usually situated either in the region of the orbit or around the base of the nose and may spread to the ear, the side ofthe neck and even into the shoulder and arm. The pain may be associated with tenderness of the eyeball. Less commonly, the pain may originate around the mastoid process and cause a sensation of fullness in the ear. The duration of a bout of 19 Diagnostic Problems in a Migraine Clinic pain varies from minutes to days. Visual disturbances and vomhing may occur especially when the pain is particularly severe. It is of paramount importance to draw attention to the fact that migraine must be distinguished from somewhat similar symptoms which arise from disease of the brain. An intracranial neoplasm situated in the occipitallobe gives rise to headache, vomiting and visual hallucinations which can simulate migraine closely. Clinical examinations of the visual fields, however, will reveal a persistent field defect between attacks while sooner or later signs and symptoms of raised intracranial pressure inevitably make their appearance. Arteriovenous malformations or angiomas which are situated in the substance or on the surface of the brain may also cause difficulty in diagnosis as suchpatientsoften develop periodic headaches which come on in early life and closely resemble true migraine. The possibility of such a lesion has to be kept in mind when the headache is persistently unilateral in the absence of a family history, and auscultation ofthe skull should never be omitted as it may reveal the presence of an intracranial bruit. Cerebra! angiomas may cause focal epilepsy, subarachnoid hremorrhage and signs of motor or sensory dysfunction referable to the contralateral limbs at any time during their history and these features in conjunction with a history of migrainous type headaches make this diagnosis much more likely. Angiomas in the posterior fossa may produce clinical evidence of brainstem dysfunction and closely resemble the basilar artery type of migraine. However, in the former the symptoms are persistent whereas in the latter they are transient and are followed by a severe headache. When the angioma is in this situation the bruit is heard much more easily over one or other mastoid process. As examples of two such cases brief details are recorded here. Case 2 V.W., aged 52, was admitted to the Unh in August, 1969 with a history of typical migrainous headaches for four years. These occurred about once a month and could last for up to four days. The headaches were invariably associated with nausea, vomhing and photophobia. However, for about two years her attacks had become morefrequent and had been associated with tingling of her left hand and a similar sensation around the left side of her mouth. For about six months she had tended to drop objects from her left hand when she had one of her attacks, and for a week prior to admission she had more regular vomhing and had tended to drag her left foot. Clinical examination showed slight swelling of both optic discs and minimal weakness of her left arm and leg. The left plantarresponsewas weakly extensor. Ultrasound examination revealed a slight right to left shift and radiographs of the skull indicated evidence of early raised intracranial pressure. A brain scan showed an abnormality in the right posterior frontal region, B.M. 3 FIG. 2. Radiograph of skull showing demineralization of the inner Iamina dura of the pituitary fossa, consistent with early raised intracranial pressure. ~-" . .....". ~ ~ o. @ "'P> hl :::s !:l P> G "0 .§ G 00 G :::s- !"' >-l @ "'P> 2: 5' :::s ."""(p' s·"' :::s P> o..- ~ Wt:h "' s:: N"' "' (Jq :!!~» :::s...., '""'0 P,.G aG <p-. (') ~e: ..... ..., P> ::::::::t:S <::> ~ s· i$ ~ oq· c $:.)... § ~ ""' ~ ..., N 0 Diagnostic Problems in a Migraine Clinic 21 At operation by Sir Wylie McKissock, a meningioma was encountered at the site indicated by the scan and was totally excised. She made a very satisfactory post-operative recovery and has been symptom free since that time. Fig. 3. 3 and 4. Brain scintigram showing an area of increased uptake in the right posterior frontal low convexity region indicative of a superficial lesion in this area. FIGS. Case 3 A.H., aged 18, was admitted to the Unitin June, 1966, with a history of typical migrainous headaches for four years. The headaches were associated with vomiting, photophobia and fortification spectra in his right visual field, and had increased in severity over the previous year. For about six months he had noticed some difficulty in looking to his 22 Background to Migraine right even in the absence of an attack. Clinical examination showed that he had a complete right homonymaus hemianopia. Auscultation of his head revealed a loud bruit which was most easily heard over both eyes and over his left mastoid process. On investigation a left carotid angiogram showed a )arge arteriovenous malformation in his left cerebral FIG. 4. hemisphere, seen in Figs. 5 and 6. The vascular lesion was not amenable to surgery but he was given a course of radiotherapy to minimize the risk of a subarachnoid hremorrhage. He has continued to have periodic attacks of migraine since that time. Summary These are just some of the problems the neurologist or physician meets within a migraine clinic. It is a relatively common condition in general practice and it poses some very great difficulties in diagnosis, management and treatment for us all. Diagnostic Problems in a Migraine Clinic 23 Fig. 5. 5 and 6. Carotid angiogram showing a !arge arterio-venous malformation in the left cerebral hemisphere. FIGS. 24 Background to Migraine FIG. 6. REFERENCE Bickerstaff, E. R. (1961). Basilar artery migraine. Lancet i, 15. CHAPTER 4 MIGRAINE IN GENERAL PRACTICE K. M. Hay The late Lord Brain, the first Chairman of the Migraine Trust, wrote in 1964 in one of his essays these words: "Many of the important things that happen in the body can no Ionger be explained simply as the result of the interaction of two or more organs, but require the conception of a dynamic transaction which itselfintegrates the activities ofthe organs." Later, he says: "In other words, though physiology and pathology have to take account of what is happening in individual organs, the transaction as a whole is the more important and unifying factor." This concept is important to the study of migraine and allied disorders, and helps to define the field of research which properly belongs to General Practice. This was recognized by Lord Brain in the same essay in the words-" ... The General Practitioner above all deals with the patient as a whole man in relation to the environment in which his life is lived, his upbringing, his family life and his pastimes." lt follows from this that the General Practitioner is like the field naturalist who studies and observes what is happening within various environments, and how the necessities for change and adaption affect his subjects, and how they meet the complex internal and external demands that are made on them from day to day. The medical practitioner's chief tools are his clinical notes, and his developed powers of observation and understanding of what he hears. He needs to pass on his findings to specialists working in laboratories and hospitals where science can analyse and answer some of the questions he has raised. He is in the direct line of field naturalists such as Gilbert White, and like him, need not be afraid to be anecdotal and discursive. N or need he be afraid to be wrong. Gilbert White was wrong when he believed that swallows hibernated in winter but in putting right this error we have learned much about the astanishing abilities of birds to navigate over the world on migration. In our day the discoveries of Tinbergen and Konrad Lorenz on birds, and Jane Goodall and G. Schaller on primates, with many others have become almost as well known to the public as were the discoveries of Freud, Darwin and Mendel in former times. As field researchers we have the advantages-and sometimes disadvantages-of being part of the scene ourselves and sharing a language and environment with our patients. 25 26 Background to Migraine When we Iook at our migraine patients we find that there is an obvious genetic factor. Of 67 male migraine patients of a recent series, there was a history of recurrent headaches in the father in 11 cases, and the mother in 19, while in 34 neither parent was subject to headaches. In women, out of 177 patients the father had recurrent headaches in 20 cases, and the mother in 41, but in 84 neither had recurrent headaches. Allergy is thought to be associated with migraine, and active allergy is certainly a factor which will reduce the threshold to attacks, but it is not known what the incidence of active allergy is in the population. Of 67 men, 26 had a history of asthma, allergic rhinitis including hayfever, eczema or urticaria. The figures for women were 39 out of 177. Frequently family trees can be compiled such as the one seen in Fig. I. The incidence in this family of rheumatic fever, now a rare disease, is of interest if it is accepted as being a form of allergic reaction to the streptococcus, but we need to know much more about the family relationships of these disorders through field research. Fourteen men out of 67 gave a history of periodic vomhing in childhood, and 47 out of 177 women. Jf it can be established that there is a relationship between some of these disorders, then the insight gained into one, will be of value in research into others. This is not the occasion to dilate on this largely uncharted field of study, and we can go on to ask our patients what it is like to have a bad attack of migraine. Unless we have the literary skills of Lady Snow, it is difficult for any of us to describe a pain, Iet alone an attack of migraine. Some peopie, however, can draw and paint what they feeland we can gather from these illustrations something of what they suffer. The following points can be noted (photographs of some examples were shown): I. The distortion of the body image. The head, and the cranium in particular, is Iarge compared to the rest of the body. 2. The red throbbing pulses along the temporal artery, the tight bands around the head, and the occipital pain. In some pictures one gains a better understanding of the expression "a splitting headache". 3. Some of the areas which are illustrated so vividly by the patient are where one can find localized tender spots which are often slightly boggy to touch. These places are hyperresthetic and painful to pressure. They were investigated by Wolff (I963) who found pain-causing polypeptides of the kinin family, and when sensory nerves to the skin were stimulated anti-dromically these substances accumulated. He found that the concentration of these substances in fluid taken from patients at the height of attacks of migraine was eight or more times that obtained from controls. These tender areas occur also in the trapezius and pectoralis musdes and can be found in patients between frequent migraine attacks. It seems that vascular and muscle tension headaches often merge into migraine proper, when the vascular disturbances produce the pallor !II . =ro 1 n=~ "'" '1 o-6 side ?J ~~· • ' others • l sode Fernale 0Mole 0 ==;===0 FIG. 1. Pedigree of patient P.M.B. showing frequency of migraine, rheumatic fever and asthma in many members of the family. 4th. GEN. 3rd. GEN. 2nd. GEN. ht. GEN. Fothers ~ -...,J IV !II ;:;· l:l -'"' ~ i ~ s· !II s· ~ aq· 28 Background to Migraine (occasionally flushing) and throbbing symptoms and signs. The pain in a true migraine has several components: (a) The localized tender areas. (b) The vascular throbbing as when the temporal artery is dilated and painful. (c) Referred pain from structures inside the skull and sometimes from the neck, particularly in the upper cervical region. In the writer's opinion anything which can cause chronic tension of the trapezius and other shoulder musdes can exacerbate migraine. The commonest of these is spondylosis and cervical arthritis in the middleaged or elderly subject, when the condition is sufficiently severe to cause pressure on nerve roots. It can also occur following a whiplash injury as is shown in the X-ray of a 23 year-old nurse who had an exacerbation of her migraine following a motor accident. (See Figs. 2 and 3.) (d) Possibly a psychogenic pain. This is pain easily precipitated by certain stimuli and circumstances from conditioned learning. Rarely spontaneaus bruising in the body can be seen. For example, one patient said: "Finger pricked during evening and while I was clearing things away preparatory to going to bed ... I looked at my finger and the lowest joint had a black knobble standing out on it and was red and swollen all round. The finger subsided in about an hour but still feit sore and bruised." Apre-menstrual migraine attack started the next day. This patient has severe migraine and is one of the few to have suffered some permanent darnage from localized retinal vein thrombosis for which no other cause was found on full investigation in hospital. The visual disturbances in migraine are interesting and alarming to the patients. Lewis Carroll, who suffered from migraine, must have used them as inspiration for scenes in the "Alice" books; such items as the Cheshire Cat and the distortions of size together with word jumbles and games are alllikely to have been derived from his personal experiences. Types of visual disturbances which may occur are: 1. Blurring or visual field defects. 2. Diplopia. 3. Scintillating scotomata. 4. An increased sensitivity to light and colours leading to photophobia. 5. Distortions of visual percepts. Objects may appear to be bigger or smaller than they should be. Spatial discrimination may be upset and objects appear tobe elsewhere than they really are (the so-called autokinetic sensory illusions). Sometimes the body imagery is disturbed and limbs appear as objects detached from the person. 6. On rare occasions there are true hallucinations. These kinds of visual disturbances occur in many circumstances apart from migraine, and have been induced by: Migraine in General Practice 29 FIG. 2 2 and 3. X-ray of neck of 23-year-old nurse to show whiplash injury following a motor accident. FIGS. Hallucinogenic drugs Aldous Huxley (1959) describes his experience under the influence of mescalin in these words: "Half an hour after swallowing the drug r 30 Background to Migraine FIG. 3 became aware of a slow dance of golden lights. A Iittle Iater there were sumptuous red surfaces swelling and expanding from bright nodes of energy that vibrated with a constantly changing patterned life. At another time the closing of my eyes revealed a complex of grey structures within Migraine in General Practice 31 which pale bluish spheres kept ernerging into intense solidity, and, having emerged would slide noiselessly upwards out of sighto" Extremes of stress and exhaustion William Sargant (1959) quotes Weissenberg on his experiences when being brain-washed: "My eyes were two balls of pain in the head that feit as though it would split open but for the iron band drawn tighter and tighter round ito o ooRed rings whirled before my eyes and my brain no Ionger functionedo" Sleep deprivation experiments Luce and Segal (1969) say this: "They (the volunteers) stopped making unnecessary movements and began to complain of unpleasant sensations-burning or itching eyes, blurred vision and a tight band round the heado Somewhere between thirty and sixty hours they began to notice changes in depth of perceptiono Small objects seemed to dart out of placeo Chairs seemed to change sizeo Many saw a halo of fog around lightso" Similar phenomena have been noted in volunteers subject to sensory deprivation experimentso If these phenomena are due to an artificial breakdown of the integration of cerebral brain function, we can consider whether they might have anything in common with migraineo lf there are biochemical disturbances in localized areas these might be the cause rather than the effect of the known vascular changes in migraineo It may well be that many ofthe symptoms ofmigraine could be experienced by the majority of people if they be subject to sufficient stress, and perhaps migrainous patients have a Iow threshold in this regard compared to other peopleo The breakdown of the integration of cerebral function has been expressed in these lines, by a patient: "MIGRAINE I am invaded by sounds and the presence of things: Not through expanding Iove and delight in their co-existence For confusion and multiplicity overwhelm my understanding, Crowd the Iabyrinth of mind, paralyse its networks of meaningo Sounds are embodied in contours, advance in relentless succession; Sounds touch and explode to expand within my foreheado Colours throb and resound like trumpets and gongs in madness, Hover over their boundaries and quiver, beat wings round the edges of visiono Touch bums with vibration as the atoms leap under my fingerso Traffic drives in and roars on the roadway of my nerves, Y our footsteps march on my brain, my footsteps shudder its shelter. Voices rattle and echo in the corridors of the mindo 32 Background to Migraine Around me, faces grimace; their words tumble forth in thousands of meaningless fragments ejected, to batter me, uncomprehending, Like hail-stones that rebound or shatter in fragments of ice, unreflecting, A broken bead-string of hail words scatters on the floor of my mind. I seek a cocoon of quietness, of darkness and stillness concealing; Oblivion in which to hide until movement and clamour recede; Until the fragmented meaning of the heckled world of the senses re-forms, each returns to its place, and their schism unites me again." lt seems that there is a failure of the "gating mechanisms" which control how much of the sensory input should reach the higher centres of the brain, and many migraine patients are particularly sensitive to sensory stimuli, be they glare, flicker, noise, smells or stuffy atmospheres. The modern entertainments centred around "pop" with rhythmic noise of up to 120 decibels, flashing lights and excitement, can precipitate migraine in some instances. The common precipitants of migraine are listed in Table I. TABLEI Precipitating Factors in Migraine Fatigue Menstruation and endocrine factors Allergy Excessive sensory stimulation Functional hypoglycremia Infections and debilitating illness Food sensitivities Various, e.g. climatic Considering the first of these, migraine occurs in a rhythmic pattern, the best known being week-end migraine where we are tempted tothink there might be an over-activity followed by an exhaustion cycle based on the week's work, the migraine occurring at the exhaustion phase. There is also a tendency for attacks to start in the early morning, and this was reported in 82 cases out of 244. This is difficult to explain but it may be related to the cerebral circulation changes and autonomic activities of R.E.M. type sleep; and the sleep laboratories might enlighten us over this problem. But migraine itself is the final stage of a state which has been slowly developing over days or weeks. lt is likely that the enormous development of the human cortex has brought about a tendency for fatigue to follow long continued states of "high arousal". The ability to become obsessed with problems in the Migraine in General Practice 33 "minds eye" distant in time and space means that arousal stimuli can be more complex and sustained than is the case with animals living in narrower dimensions of "here and now". The types of stimuli deriving from the brain's powers of conceptual thought and imagery are many and complex, but they give rise to chronic states of tension in many migraine patients. Clinically, 121 out of 244 patients were thought to have evidence of chronic tension. This must be a subjective estimate on the part of the clinician who notices a variety of small signs to suggest this. It is difficult to measure, but some evidence in support of this theory has been obtained by subjecting patients to a validated questionnaire, in this case the I.P.A.T. Anxiety Scale. Admittedly anxiety is only one form of long sustained arousal stimulus, but it has been extensively examined in the literature. The components ofthis scale are given by Cattell and Scheier (1967) as being five in number: 1. A Iack of self-sentiment development. 2. Ego weakness. This is taken to mean an insecure ego with many ego defences. 3. Suspiciousness. Paranoid type insecurity. 4. Guilt proneness which may include feelings of unworthiness. 5. Frustration. Id pressure. It is quoted as appearing: "to represent the degree to which anxiety is generated by id pressure-by excited drives and unsatisfied needs of all kinds. Sex drive, excitations, need for recognition and situational fears are among the drives positively reIated to this component. It shows itself descriptively in proneness to emotionality, irritability and jitteriness." A pilot study was carried out on 12 migraine patients who had been selected for group relaxation therapy, and the following results on their "raw scores" were obtained as compared to those found in the general population: Generalpopulation raw score mean = 27·1 Standard deviation = 11-4 sample mean of 12 values are 20·5 to 33·7 (ii) sample mean of 13 values are 20·8 to 33·4 (sample size = 13) just within Control group mean = 33 95 per cent limits (sample size = 12) which lies Migraine group mean = 42 well outside. 95 per cent confidence Iimits for (i) Thus the control group mean exceeds the published general population mean, but the excess just fails to be of statistical significance. On the other hand, the difference between the migraine group and the population mean is highly significant. 34 Background to Migraine When a comparison is made of total anxiety raw scores in control and migraine groups the following results are obtained: Mean S. Dev. S. Error 42 10·25 Migraine group 3·1 33 8·7 2·4 Control group Difference between means = 9 Standard error of difference = 3·87 Ratio of difference:standard error = 2·3 P < 0·05. lt is seen from these figures that there is a significant difference between means. A further unselected group of 22 patients answered a questionnaire before being seen clinically, and the same general tendency was confirmed. A more detailed analysis of these results is now being carried out. In some cases migraine can become an established pattern of response to environmental pressures, and changes in the environment can cause a remission of symptoms. In one case a boy of the "Billy Bunter" type required a Iot of treatment to control his migraine until he left school to train for skilled work which interested him and which freed him from what he found disagreeable. He now does not require any treatment. A Iady who had unpleasant experiences in her house was free after she had moved. Another lost her migraine when her divorce proceedings had been successfully concluded. A housewife Iabelied as "verging on a psychotic depression" lost her migraine when away from her flat situated on the top of a tall block, where she had found family life impossibly difficult. Animals and birds are susceptible to small changes in their environment. Birds whose reactions are stereotyped relative to human ones, may fail to settle and thrive in long narrow aviaries when they will do so in reetangular ones of the same dimensions, the latter providing several alternative routes of escape for the bird in the face of what it considers to be a threat. Finally one can end with a further quotation from Lord Brain who writes: "Medicine alone takes as its province the whole man. lt is not concerned only with his needs for nursing or with inquiries into his home circumstances or his difficulty in getting a job when disabled ... it is concerned with all these, but how much more. With man in all the complexity of his body and mind from his conception to his last breath: and its concern extends increasingly beyond his sickness to conditions which make it possible for him to Iead a healthy and happy life." Acknowledgements I would like to thank those patients who have contributed their art which is the basis of this paper. They prefer to remain anonymous. Dr Kenneth Cross, Medical Statistician to the Birmingham United Hos- Migraine in General Practice 35 pitals has prepared the statistics. Miss Branw.en Williams has dorre much of the work on the I.T.A.P. tests, and her help has been invaluable. REFERENCES Brain, Lord (1964). Doctors Past and Present. Pitman Medical. Cattell, R. B. and Scheier, I. H. (1967). Handbook for the l.P.A.T. Anxiety Scale Questionnaire. Institute for Personality and Ability Testing. Huxley, Aldous (1959). The Doors ofPerception and Heaven and Hell. Penguin Books. Luce, G. G. and Segal, J. (1969). Sleep and Dreams. Panther Science. Sargant, W. W. (1959). Battle for the Mind. Pan Books. Wolff, H. G. (1963). Headache and Other Head Pain. Oxford University Press. 8.M. CHAPTER 5 EPIDEMIOLOGICAL ASPECTS OF MIGRAINE W. E. Waters The extensive Iiterature on rnigraine often rnentions its epiderniology. However, alrnost all these references refer to inforrnation derived frorn selected series of patients with rnigraine who are seen by doctors with a particular interest in the condition. Whether they are representative of all rnigraine sufferers is not known. It is likely that patients in such series have rnore severe, or rnore frequent, attacks than other individuals with rnigraine and it rnay be that they are also different in other respects. One of the difficulties, in elucidating the epiderniology of rnigraine in a series of patients attending a clinic, is to get suitable "controls". It is of little help to find out the distribution ofblood pressure, or the percentage with a farnily history of rnigraine, in rnigraine patients unless these can be cornpared with sirnilar data frorn controls. But who, it rnay be asked, is a suitable control for such a rnigraine patient? Is it sorneone without rnigraine who attends a doctor? If so, should it be the sarne doctor? Is it sorneone without rnigraine who does not attend a doctor? It can be seen that the problern of selecting suitable controls is difficult as the controls are likely to be different with each of these rnethods. In fact, a satisfactory study of the epiderniology of rnigraine is even rnore elusive than this, for not all rnigraine sufferers consult a doctor. In a recent survey, in a Welshindustrial valley, about half the wornen with clinically diagnosed rnigraine had never consulted a doctor for their headaches (Waters and O'Connor, 1970). Such individuals rnay differ frorn those rnigraine sufferers who seek attention frorn their own general practitioners. Patients who attend a neurological or rnigraine clinic are rnore highly selected again. Having briefly outlined the difficulties of a clinician interested in epiderniology, Iet us now consider the problern of an epiderniologist trying to investigate rnigraine in his defined populations. Here the rnain difficulty is in defining rnigraine. This is not to say that typical cases present any problerns. But in cornrnunity surveys there are large nurnbers of individuals with headache and who have at least sorne of the features of rnigraine (Waters, 1970a). Most definitions of rnigraine are really descriptions of characteristic attacks and sirnply Iist features that are "usually" or "often" present (Ad Hoc Cornrnittee on Classification of Headache, 1962; World Federation of Neurology, 1970). For this reason, in cornrnunity studies, it is difficult to give the prevalence of rnigraine. Indeed, cornrnunity studies do raise the possibility that 36 Epidemiological Aspects of Migraine 37 migraine may not be a distinct clinical entity but that it may be an extreme in a continuous distribution of headache severity. This, probably controversial, view will not be considered further here but it does show the difficulty in separating some of the milder migraine from other headaches, in community studies. At the M.R.C. Epidemiology Unit, we have developed a questionnaire and the correlation between this and a neurologist's clinical 50 ERGOTAMINE 40 30 20 D 10 0 50 PLACEBO 40 30 20 10 0 Worse No change Slight benefit D Consideroble benefit Fm. 1. Response to treatment with ergotamine tartrate and placebo in 79 women who completed the eross-over clinical trial. diagnosis has been published (Waters and O'Connor, 1970). In an attempt to validate further this questionnaire, a double-blind clinical 38 Background to Migraine Order Colour Content Number of subjects No preference 33 35 31 37 First Second Green White 31 37 Ergot- Placebo amine FIG. 2. Tablet preference for 79 women in relation to order of treatment, colour of tablets, and content of tablets. trial of oral ergotamine tartrate and placebo was carried out in 88 women, identified during a community survey, with at least some of the features of migraine (Waters, 1970b). The clinical trial was of erossover design, each woman receiving ergotamine and placebo, each of which was either green or white, in random order. The results were most surprising; 79 women completed the trial and their response to the treatment is shown in Fig. 1. The only statistically significant difference was the larger proportion with adverse side-effects on ergotamine. When the women were asked which tablet they preferred, there were no significant differences between ergotamine or placebo, nor between first and second treatments, nor between green and white tablets (Fig. 2). There are a number of possible reasons for this unexpected result. In particular it may be important that the trial used ergotamine tartrate on its own, but other drugs are added in most proprietary preparations. There is now evidence that caffeine may influence the absorption of ergotamine (Berde, Cerletti, Dengier and Zoglio, 1970) and further clinical trials are obviously required. The trial did not help in identifying individuals with migraine and this had been one of its objectives. When random samples of adults in the general population in the Pontypridd area of Glamorgan completed the headache questionnaire, it was found that significantly more women than men had had headache in the preceding year (Fig. 3). In both sexes, the proportion with headache in the preceding year declined with increasing age. The prevalence of headache therefore varies with both age and sex. However, among those who did have a headache in the previous year, the proportion with the three migraine features, a unilateral distribution, a warning that the headache is coming, and accompanying nausea, is surprisingly similar at all ages. Fig. 4 shows that each of these three migraine features had occurred, at some time in the previous year, in a high pro- 39 Epidemiological Aspects of Migraine portion of all individuals with headache. The severity of the headache was assessed as indicated in Table 1 on a seven-point scale determined by asking each individual to select the statement nearest to the truth for their severe headaches. Formen, and for women, as the severity of the headache increased so did the proportion with unilateral distribution (Fig. 5), with a warning (Fig. 6) and with accompanying nausea (Fig. 7). TABLEI Scale of Severity of Headache 1. 2. 3. 4. 5. 6. 7. My headaches are very mild. My headaches are mild. My headaches are not usually severe. My headaches are quite severe. My headaches are very severe. My headaches are terribly severe. My headaches are almost unbearable. 100 80 60 40 20 0 AgeZI-34 Age 35-54 Age 55-74 Age 75 + Fio. 3. Prevalence of individuals with "headaches" in the previous year in the Pontypridd area of Glamorgan. These were the three features from the questionnaire that correlated best with the neurologist's clinical diagnosis of migraine, and nearly 90 per cent of women with all three were so diagnosed (Waters and O'Connor, 1970). 40 % Background to Migraine 60 40 Unilateral distribution 20 0 % % Warning 60 Nausea AgeZI-34 Age35-54 Age55-74 Age 75+ FIG. 4. Prevalence of unilateral distribution of headache, warning before headache, and nausea with headache, in the previous year in individuals with headache in the Pontypridd area of Glamorgan. The "migraine group", with the three migraine features, has been compared with those having unilateral headache, those having headache and none of the three features, and those without headache in the year immediately preceding the survey. Measurements of blood pressure, intelligence, social dass, visual acuity and ocular-muscle imbalance have been made on over 400 individuals selected at random, on the basis of their headaches, from the defined population. In all cases the observers making these measurements have been unaware of the headache histories of each individual. It is important that such measurements are done "blindly" to avoid the possibility of bias. In several analyses age has to be taken into account as most of these variables are agedependent. We found no evidence that the distributions of either systolic or diastolic blood pressures were different in the migraine group. Using the AH4 Group Test of General Intelligence (National Foundation for Educational Research) no evidence was found that individuals with migraine were more intelligent, nor did they predominate in any one of the General Register Office's social classes. There was no evidence of any difference in visual acuity, or in the proportion wearing spectacles, between migraine sufferers and others (Waters, 1970c). Epidemiologica/ Aspects of Migraine 41 100 80 ,... 60 I I ,,.e-----...... ,-, _ _.' 40 I I I I I \ I \ \ \ Women Men \ ' I ~' 20 2 4 3 5 Severity of headache 6 7 FIG. 5. Relation of severity of headache to unilateral distribution of headache in 491 men and 741 women Iiving in the Pontypridd area of Glamorgan. When the subjects were examined for latent squint, hyperphoria with near vision was found to be significantly commoner in those with migraine. In general, however, there was little evidence to support the widely held belief that headaches are often due to defects in visual acuity or ocular-muscle imbalance. Our latest survey has involved the tracing of first-degree relatives of the randomly selected probands with migraine, headache, and without headache. A short headache questionnaire has been completed by 519 relatives of these three groups of probands and this number represents over 99 per cent of all parents, siblings and children, over 21 years of age, living in South Wales. Although first-degree relatives of the probands of migraine did have slightly more migraine, this difference was not statistically significant. Migraine is usually considered to have a strong family tendency. Most of the studies on which this view is based can be criticized on several grounds. In particular none was based on an unbiased assessment of the headaches of relatives of representative migraine sufferers, and of relatives of others without migraine selected at random from amongst those living in the same defined population. A study of headaches and migraine in children and their parents has 42 Background to Migraine just been completed by Mr D. Deubner working at the M.R.C. Epidemiology Unit and again there is remarkably little evidence that migraine has a pronounced familial trait. Women __ .. Men ~----....--/ 2 / / / 5 Severity of headache 3 4 6 7 Fra. 6. Relation of severity of headache to warning before the onset of headache in 491 men and 741 women living in the Pontypridd area of Glamorgan. In conclusion, the epidemiological studies described briefly here do not support and indeed conflict with much that is frequently quoted in medical textbooks. lt is suggested that this may be due to the selection of the cases previously investigated and that it is only by community studies that a true picture of the epidemiology of migraine can be elucidated. Epidemiological Aspects of Migraine 43 100 Women 80 60 , 40 ...... v---.o,./ 20 0 .... ", ........ 2 / / / ... . /" " ,. I I I I I I I I I ' )I I I I I I I tt Men I / 4 3 5 Severity of headache 6 7 FIG. 7. Relation of severity of headache to nausea accompanying the headache in 491 men and 741 women Iiving in the Pontypridd area of Glamorgan. Acknowledgements I am grateful to Professor A. L. Cochrane, Director of the M.R.C. Epidemiology Unit (South Wales) for advice and encouragement during all the various studies mentioned in this paper. I thank the other Unit members for their help and the Migraine Trust for a grant which aided this research. REFERENCES Ad Hoc Committee on Classification of Headache (1962). Classification of Headache. J. Amer. med. Ass. 179, 717. Berde, B., Cerletti, A., Dengler, H. J. and Zoglio, M. A. (1970). Studies of the interaction between ergot alkaloids and scanthine derivatives. In Background to Migraine. London: William Reinemann Medical Books. Waters, W. E. (1970a). Community studies of the prevalence of headache. Headache 9, 178. Waters, W. E. (1970b). Controlled clinical trial of ergotamine tartrate. Brit. med. J. 2, 325. Waters, W. E. (1970c). Headache and the eye. Lancet ii, 1. 44 Background to Migraine Waters, W. E. and O'Connor, P. J. (1970). The clinical validation of a headache questionnaire. In Background to Migraine. London, William Reinemann Medical Books. World Federation of Neurology (1970). Definition of migraine. In Background to Migraine. London: William Reinemann Medical Books. CHAPTER 6 PSYCHIATRie AND PSYCHOLOGICAL ASPECTS OF MIGRAINE W. Linford Rees Migraine has been known from the time of ancient Greco-Roman medicine. lt has been studied by physicians throughout the ages, and many eminent physicians and scientists have themselves suffered from it. Despite the fact that it is a common disorder which has been extensively studied, it remains a subject of controversy regarding many aspects including retiology, natural history, treatment and management. Among matters which continue to be controversial are the relative importance of psychological factors in relationship with other retiological factors and, in general, the relevance of psychiatric and psychological correlates of the disorder. The available evidence indicates that migraine is a complex disorder with multiple retiological factors . .tEtiological factors in migraine may be described as Essential and Sufficient, the Essential causes being the ones without which the disease cannot develop, and the Sufficient causes being those which enable the Essential causes to be manifested in an attack of migraine. We may also consider which factors have predisposing action in retiology and which are responsible for the precipitation of attacks. A number of psychological and psychiatric features in migraine have been described as having a predisposing function including personality, intelligence Ievel, the co-existence of neurosis and other psychiatric disorders. Possible precipitating factors include emotional changes, psycho-social stresses, certain times of the day or part of the week. Such predisposing and precipitating factors have been claimed to play an retiological role in migraine, involving what one may term a psychosomatic sequence, i.e. a psychological event being followed by a physical event, viz. an attack of migraine. A somatopsychic sequence of events can also occur in migraine. During an attack of migraine, mood changes are common, with alterations in energy output, concentration and ability to work. Furthermore, various emotional reactions to an attack of migraine can occur just as may occur with any illness. In some patients vicious circles can develop by the interaction of psychosomatic with somatopsychic sequences. Personality Characteristics A number of the pioneer workers in the study of psychosomatic 45 46 Background to Migraine relationships have put forward the theory that there is a specific relationship between personality types or constellations of personality traits with individual disorders, including migraine. The outstanding work in this field has been that of Harold Wolffwho, in 1937, published a paper based on a study of 46 patients with severe migraine. He found that his migraine patients had, during childhood, been shy and withdrawn and very obedient to parental wishes, being extremely polite and conscientious. However, at times they were stubborn andinflexible and exhibited contrasting qualities, being mainly courteous, gracious, polite and accommodating, and in certain situations being obstinate, openly defiant or even rebellious. Their tendency to be very sensitive was associated with restraint in social relationships. In general, they were energetic and trusted by their elders, often being given responsibility at an early age. Other traits were tidiness and being very clean. As adults their personalities were characterized by a tendency to be markedly efficient and preoccupied by achieving success. They tended to drive themselves on even when they were feeling unwell or tired and characteristically conscientious, perfectionistic, persistent and exacting in trying to achieve order wherever possible. Although they themselves were usually efficient, they usually had great difficulty in delegating tasks to other people. In addition to the above they exhibited marked orderliness in their work. In their private lives they were careful collectors and meticulously classified their material. Many exhibited doubts and a tendency to repeat certain actions. They were very inflexible and resented having their plans altered in any way. Many of the subjects harboured strong feelings of resentment which appeared to be linked with their Iack of elasticity. They tended to be cautious and parsimonious. The above traits are those which comprise the typical obsessional personality. In social relationships migraine patients tended to be cautious, avoiding personal relationships. They tended to be cautious and conservative in their sexual adjustments. Many had difficulties in sexual adjustment and a !arge proportion of the women were frigid (Wolff, 1937, 1963). Friedman, Von Storch and Merritt (1954) studied a series of 2000 migraine sufferers and patients with tension headache, and later Friedman (1964) described a ten-year follow-up of 5000 such patients. Although he does not assert that there is a specific migraine personality, he considers that, in general, migraine patients are intelligent, sensitive, methodical and perfectionistic. During childhood they show inability to express aggressive feelings constructively and he considers that rigid parental attitudes have contributed to this. When confronted with stressful situations they often develop anxiety which may result in headaches. The obsessional patient may often feel depressed when he releases hostility. Similar findings have been reported with the use of projective Psychiatrie and Psychological Factars in Migraine 47 personality tests such as the Rorschach test and with other well standardized tests such as the Minnesota Multiple Personality Inventory (MMPI). Ross and McNaughton (1945), using the Rorschach projective method of assessing personality, reported their results on a group of 50 migraine subjects compared with various control groups, including ten with psychogenic headaches, 15 with headaches of unknown origin, 50 normal individuals of superior intelligence, 50 neurotic patients and 24 patients with brain tumour or injury. The results indicated that migraine patients showed obsessive-compulsive perfectionistic traits. In general, they were persistent, inflexible, intolerant and had sexual difficulties. Martin, Rome and Swenson (1967) studied a series of 25 patients with long-standing severe tension headaches by means of the MMPI. They described their patients as rigid, perfectionistic and worriers, with problems related to control of hostility and to dependency, and difficulties in sexual adjustment. Dalsgaard-Nielsen (1965), in a genetic study of migraine, found that one-third of a series of migraine patients had a normal personality, one-third showed certain traits of personality such as being sensitive, perfectionistic and with a tendency to bottle-up emotions but within normal Iimits, and another third with traits of personality which were regarded as being outside the normal range. Conclusion on the Present Stage of Our Knowledge on the Relevance of Personality in Migraine It is clear from many studies that persons suffering from migraine are not necessarily unstable or neurotic in the usual sense and are frequently very successful well-adjusted people. However, a varying proportion of patients are described as having personality characteristics which are conducive to the development of states of emotional tension which in turn can precipitate migraine. They are described as being tense, anxious, self-driving persons who are rigid, ambitious, perfectionistic, and who tend to be highly competitive in their outlook, always trying to excel over their fellows. They are reliable, conscientious persons, responsibilities and duties tend tobe thrust upon them and, as a rule, they have great difficulty in keeping up to their own expectations ofwhat the world in general may expect of them. The inevitable outcome is the development of resentment, frustration, tension, fatigue and exhaustion (Rees, 1965). In conclusion, one may say that there is no specific personality type which is applicable to migraine in general. Many of the characteristics described by the above workers relate to traits of personality which in various ways are conducive to development of tension: sensitiveness, over-anxiety and obsessionality and all traits which make the person 48 Background to Migraine respond to the environment and tend to produce emotional reactions which, if bottled-up or mounting in severity, can act as precipitants of psychosomatic disorders. The author found these traits to be common in asthma in all age groups and in both sexes, in vasomotor rhinitis, chronic urticaria, peptic ulcer and thyrotoxicosis. Therefore, in my opinion, there is no evidence of any specificity of personality type. One of the problems in evaluating reports of the personality correlates of migraine is that most studies have been on selected groups of patients; for instance, patients either attending clinics for psychotherapy or attending special clinics in a hospital which inevitably involves an element of selection. What is needed is the investigation of a random and representative sample of migraine sufferers from the community using reliable methods for assessing personality, in migraine groups and appropriate control groups. Control groups may be taken from the healthy general population and also groups of patients suffering from other disorders (HenrykGutt, 1964). Until such a study is carried out, controversy will continue on the relevance of personality attributes in migraine. Relationships Between Migraine and Psychiatrie Illness Neurosis: There is a variety of hypotheses about the relationships between migraine and other psychosomatic disorders and neurosis. First of all, it is claimed that neurotic symptoms are more common in psychosomatic disorders, whereas others put forward the view that there may be a reciprocal relationship between the manifestations of neurotic symptoms and the manifestations of a psychosomatic disorder, in this instance, attacks of migraine, may show an alternation with each other. Maxwell (1966), in a study of the Maudsley Personality Inventory scores on 60 migraine sufferers, concluded that the neuroticism score was increased but that the extraversion score was within the normal range. Martin et al. (1967) at the Mayo Clinic give results of studies on 25 patients with long-standing severe tension headaches who had been tested by the Minnesota Multiple Personality Inventory. It was found that 16 out of 22 women and 1 out of 3 men showed neurotic patterns. Hunterand Ross (1960) reported that women sufferers from migraine showed more psychiatric disability than men. Sainsbury (1960) using the Maudsley Personality Inventory in a variety of psychosomatic disorders and control groups of various kinds, concluded that the psychosomatic groups as a whole were significantly higher in scores of neuroticism and that they tended to be more introverted than control groups. The evidence suggests that the various samples of patients having migraine and other psychosomatic disorders studied at hospital clinics Psychiatrie and Psychological Factors in Migraine 49 tend to show a higher incidence of neurotic symptoms than normal control groups, but there is nothing specific in this relationship between neurotic symptoms or neuroticism as measured by tests and migraine. One of the difficulties in accepting these findings as being conclusive isthat they have all been carried out in samples which are to some extent selected as they have been attending hospitals or special clinics. Again, in ordertobe able to elucidate this problem, it will be necessary to take a random representative sample of migraine sufferers from the community and study it by objective methods of neurosis and neuroticism and compare it with control groups. Psychosis: Literature on psychomatic disorders contains many reports of various relationships between psychosomatic disorders, including migraine, and the severe psychiatric disorders (psychoses) such as schizophrenia and manic depressive illness, and migraine. Some observers report a negative relationship, stating that the incidence of psychosomatic disorders is less than would be expected by chance. Others have claimed a positive correlation with some psychiatric disorders, particularly affective disorders; some authorities have suggested a reciprocal relationship and that the psychoses, such as schizophrenia and manic depressive illness, may alternate in the same patient with a psychosomatic disorder. In a recent study by Pedder (1969) in a series of 1034 inpatients admitted to the Bethlem Royal and Maudsley Hospital it was found that schizophrenia appeared to be less frequent among psychosomatic patients than in the control group. He found a high incidence of phobic symptoms in the psychosomatic group. Some psychoanalytic investigators have put forward the view that psychosomatic illness serves as a defence against a psychosis and that when one clears up the other tends to appear. But, in general, careful studies have failed to support any reciprocal relationship between psychosomatic disorders, including migraine, and psychotic illnesses except in a very small minority of patients who may show alternation between psychosis and psychosomatic illness. Intelligence: It is frequently asserted in the literature that migraine sufferers are above average intelligence. In my opinion this is a myth which has been passed on from one authority to another throughout the years. Very often migraine sufferers, because of their conscientious, alert, reliable characteristics, give the impression of being intelligent. In the author's experience, migraine can occur in patients of all ranges of intelligence, from the very superior intelligence, from above average to average, and evm in patients who are below average intelligence. I suspect that if a random sample of migraine patients were taken and intelligence tests carried out, the intelligence score would be distributed along a normal frequency distribution curve and may not differ significantly in central tendency or in dispersion from that of normal population. 50 Background to Migraine Precipitating Factors in Migraine Emotional reactions: It is generally accepted that emotional reactions can precipitate some attacks of migraine in some patients. Opinion varies with regard to the frequency with which emotional factors precipitate attacks and their relative importance with regard to other possible precipitating agents. A variety of emotional reactions have been reported to precipitate attacks of migraine-anxiety and apprehension are particularly common; the next most frequent are feelings of frustration and resentment -whereas anger and rage which are expressed are relatively infrequent precipitants. What is probably more important than the variety of emotion experienced is its severity, the degree to which it is sustained and inadequately expressed, and the tendency to bottle-up emotions with the development of mounting tension and a gradual build-up of feelings of anxious apprehension, frustration and resentment. Development of Attacks of Migraine During Let-down Periods Some sufferers from migraine tend to develop attacks mainly at week-ends or during the first few days of a holiday, others sometimes in the evenings, following any period of hard work or stress. This occurrence often puzzles patients and makes them believe that their attacks are not related to stress, but patients who are self-driving, obsessional and meticulous or who are addicted to work may often find it difficult to adjust to periods of relaxation, and these periods for them are really let-down periods. Many of these patients, not having work and other activities to absorb their energies, become more tense and anxious and accordingly develop attacks during these let-down periods. It is also known that headaches, including migraine, were less frequent

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