Historical aspects of migraine

Journal of Neurology, Neurosurgery, and Psychiatry 1986;49:1097-1103

Occasional review

Historical aspects of migraineJMS PEARCE

From the Department ofNeurology and Headache Clinic, Hull Royal Infirmary, Hull, UK

"Spleen sighs for ever on her pensive bed,Pain at her side and megrim at her head."(Rape of the lock. Alexander Pope, 1688-1744)

The student of medicine first encountering themigraine literature will immediately perceive theextraordinary amount written, and will sense anunspoken frustrated fascination-a sort of blightedcuriosity which pervades many accounts and descrip-tions. Enlightened self interest may explain some ofthe attention shown by physicians, since the incidencein our profession is as high as 30%. It is almostimpossible to do justice to such a vast literature span-ning over 2,000 years, much of which is no longer ofeasy access and is often reproduced by copies of otherauthors' quotations. This account is guilty in part ofthis criticism. In it I select some of the excellentdescriptive writing of the early physicians, and bytaking samples of their scholarship try to outline theirthoughts about the nature of the disorder and itssymptoms which are in no small measure responsiblefor our current insecure concepts.The Shorter Oxford Dictionary (SOED) cites under

MEGRIM, late Mediaeval English:l.b. = vertigo 1595. 2. A whim, fancy, fad 1593. 3.

pi. 'Vapours'; low spirits 1633. 4. pl. The staggers 1639."Hee is troubled with a perpetual migrim; at sea hee

wisheth to bee on land, and on land at sea 1631"The first appearance of "hemicrania" (Greek, half-

skull) is cited by the SOED as 1597; this refers toEnglish texts. Thus even before The Plague and theGreat Fire, it was used to describe a far wider constel-lation of symptoms than headache alone; the associ-ations with disturbed balance and sea-sickness, theemotional changes and depression implied by "thevapours" and "low spirits" were evidently well under-stood. Was it a coincidence that the same wordMegrim was also applied in 1836 to Arnoglossus lat-erna, the scald-fish, or was this some oblique referenceto burning headache or perhaps to facial flushinglater coined under the name "red migraine"?Address for reprint requests: Dr JMS Pearce, Hull Royal Infirmary,Hull, HU3 2JZ, UK.Received 31 December 1985.Accepted 25 January 1986

Hippocrates (c.460-c.370 B.C.)It is said that the earliest description of migraine as aperiodic syndrome appeared 3,000 B.C. in Meso-potamian poems. Hippocrates provided an accountof severe pain in one half of the head associated withdisturbance of sight.1

"he seemed to see something shining before him likea light, usually in part of the right eye; at the end of amoment, a violent pain supervened in the right temple,then in all the head and neck.... vomiting, when itbecame possible, was able to divert the pain and renderit more moderate." The cardinal features of the visualaura, unilaterality and vomiting with relief of painwere clearly understood. Hippocrates was also anearly advocate of drug therapy, mentioning the helle-bore family of plants which may have had a diureticaction. The medical schools of Cos and Cnidas bothbelieved in the "four humours" or chief fluids of thebody advocated by Empedocles (c.490-430 B.C.), butwhereas the Cnidians were empiricists, observers andclassifiers, Hippocrates of the Coan school was dedi-cated to the study of the causes of disease throughdirect observation and inference.

Celsus (A.D. 30)It is sometimes said that there was only one greatRoman book on Medicine: De Re Medicina. Thislarge scale encyclopaedia or "Medical Home Com-panion" was written for rich landowners by A. Cor-nelius Celsus, a friend of the Emperor Tiberius.Celsus was probably not a doctor and like Pliny hada low opinion of physicians. That Celsus recognisedmigraine2 and its precipitating causes is evident:"A long weakness of the head, but neither severe nordangerous, through the whole life. Sometimes the painis more violent, but short, yet not fatal; which is con-tracted either by drinking wine, or crudity, or cold, orheat ofafire, or the sun. And all these pains are some-times accompanied with a fever, and sometimes not;sometimes they afflict the whole head, at other times apart of it;"

Aretaeus (A.D. 81-?)Aretaeus was born in Cappadocia in about A.D. 81.

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First a native of Alexandria he then moved to Rome.His writings refer to cephalagia. headaches lasting afew days, and cephalea. headaches lasting days orweeks without remission.3 "the pain ... remains in thehalf of the head. This is called heterocrania, an illnessby no means mild, even though it intermits, andalthough it appears to be slight ... it sets in acutely, itoccasions unseemly and dreadful symptoms ... nausea,vomiting of bilious matters, collapse of the patient, butif the affect be protracted, the patient will die; or ifmore light and not deadly it becomes chronic; there ismuch torpor, heaviness of the head, anxiety and weari-ness. For theyflee the light; the darkness soothes theirdisease. nor can they bear readily to look upon or hearanything disagreeable; their sense of smell is vitiated".Of this passage, Macdonald Critchley in the first

Sandoz Foundation Lecture, 4 rightly comments thatthe reference to death is foreign to contemporaryexperience, but suggests that Aretaeus might haveobserved a patient with aneurysmal subarachnoidhaemorrhage. Aretaeus used the word "heterocrania"to indicate its location in half of the skull and clearlydescribed headache attacks recognisable as migraine.

Galen (A.D. 131-201)Galen distinguished the nature of migraine fromother common headaches5 and used the term "hemi-crania": "a painful disorder affecting approximatelyone half of the head, either the right or left side, andwhich extends along the length of the longitudinalsuture ... It is caused by the ascent of vapours, eitherexcessive in amount or too hot, or too cold." As everthis famous father figure was preoccupied by the fourhumours: phlegm, blood, bile (choler) and black bile(melancholy). As Critchley observes, this humoralmythopathology was to stultify medical thinking forsome 1400 years.

Caelius Aurelianus (A.D. 400-)In De Capitis Passione, Caelius Aurelianus, born inA.D. 400 in Algeria, described hemicrania and "cro-tophon".6 This term meant a pounding or ham-mering and was accompanied by vertigo with burningof the eyes, nausea or vomiting. He described lachry-mation, noises in the ears and deafness.

In the 7th century, a Greek physician PaulusAeginata of the Alexandrian school of Medicinerecounted the factors which provoked migraine:"... Noises, cries, a brilliant light, drinking of wine andstrong smelling things whichfill the head. Some as ifthewhole head were struck, and some as if one half, inwhich case the complaint is called hemicrania."There was apparently sparse mention of the disor-

der and little to advance the Galenic stance ofhumours as the cause until the 17th century, though itwas appreciated and described in lengthy tracts by the

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distinguished Arabic schools in the 11th, 12th and13th centuries. Surgical techniques applied includedtrephining, incisions into the scalp, the application ofheated irons and of course blood-letting.Thomas WillisPerhaps the greatest forerunner of modern neurology,Willis was familiar with the problems of migraine,both diagnostic and therapeutic. He had a large andthriving practice which counted in its number manytitled and famous contemporary figures. In a section,"De Cephalalgia" in volume I of De anima brutorum(Concerning the souls of brutes) 1672, he dis-tinguished different headache types: "'within orwithout the skull', 'universal or particular', 'short','continuing', or 'intermittent', 'wandering', 'uncertain','before', behind or the side', and 'occasional or habit-ual'. 'The pain of the head' he said 'is wont to beaccounted the chie.fest of the Diseases of the Head ...so common that it is become a Proverb as a sign of amore rare and admirable thing That his head did neverake. "

Willis7 considering aetiology mentioned hereditaryfactors and recorded cases following injury or anemotional upset. It often began in the morning.Causes were "immediate or remote". He alsoobserved that attacks were sometimes induced byhunger and that polyuria might accompany attacks ofmigraine: "I have observed in many, a watery and veryplentiful urine, either to precede or accompany the fitsof the disease".

It was realised by Willis that headaches couldbetoken more ominous disease of the head. His chap-ter ends with eight histories of patients with head-aches of diverse causes, including examples ofmigraine and of fatal brain tumour. C. P. Symonds8recalled Willis's description of a patient with left sidedheadache in whom at necropsy occlusion of the rightcarotid artery was found. He attributed the headacheto a compensatory dilatation of the left carotid circu-lation: an instance supporting his notion of the anas-tamotic function of the circle which now bears hisname. In a previous paper9 I have outlined the historyof cluster headache or migrainous neuralgia and citeRaymond Hierons's suggestion in 1955 that Willis'saccount may have been the first record of this malady.His patient was a lady who began to suffer from head-aches "each afternoon at about 4 o'clock"; this con-tinued daily for some five weeks.

Perhaps the most celebrated migraineur of thisperiod was Anne, Countess of Conway, who had theadded distinction of being attended by both ThomasWillis and William Harvey. His concern about thislady's headaches tells us of his understanding of head-ache mechanisms which was far ahead of his times:"The opening of the skull (trephining) cry'd up by

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Historical aspects of migrainemany, but rarely or never attempted ... This our mostingenious Harvey endeavoured to persuade a NobleLady, labouring with a most grievous inveterate head-ache, promising a cure from thence, but neither she noranm other would admit that administration."He doubted the existence of a tumour which would

have caused "sleepy distempers" or "deadly con-vulsions". He considered the headache might havebeen of meningeal origin according to Spillane"' whoquotes: "beset uwith little whelks, a Schirrous or CallousTumor", although even then, "I think opening of theskull will profit little or nothing".

Plainly, Willis was right and had anticipated theconservatism of modern-day physicians which can onoccasion be so trying to their surgical colleagues,especially so when vindicated by the passage of time.

Willis's description of the migraine of Anne, Coun-tess of Conway4 is a classic: Some twenty years since,I was sent for to visit a most noble lady, for above 20years sick with an almost continual headach, at firstintermitting. she was of a most beautifulform, and agreat wit, so that she was skilled in the liberal arts, andin all forms of literature, beyond the condition of hersex, and as if it were thought too much by nature, forhere to enjoy so great endowment without some detri-ment, she was extremely punished with this disease.Growing well ofa feavour before she was 12 years old,she became obnoxious to pains in the head, which werewont to arise, sometimes of their own accord, and moreoften upon every light occasion. This sickness being lim-ited to no one place of the head, troubled her sometimeson one side, sometimes on the other, and often thorowthe whole encompass of the head. During thefit (whichrarely ended under a day and a night's space, and oftenheld for two, three or four days) she was impatient oflight, speaking, noise, or of any motion, sitting uprightin her bed, the chamber made dark, she would talk to nobody, nor take any sleep, or sustinance. At length aboutthe declination of thefit, she was wont to lye down witha heavy and disturbed sleep, from which awakeing shefound herself better, and so by degrees well, and con-tinued indifferently well till the time of the intermission.Formerly, the fits came not but occasionally, andseldom under 20 days of a month, but afterwards theycame more often: and lately she was seldomfree. More-over, upon sundry occasions, or evident causes (such asthe change of the air, or the year, the great aspects ofthe sun and moon, violent passions, and errors in diet)she was more cruelly tormented with them. Butalthough this distemper, most grievously afflicting thisnoble lady, above 20 years (when I saw her) havingpitched its tents near the confines of the brain, had solong beseiged its regal tower, yet it had not taken it: forthe sick lady, beingfreefrom a vertigo, swimming in thehead, convulsive distempers and any soporiferous symp-toms, found the chief faculties of her soul sound

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enough."This is the richest account to date of the variegated

symptomatology of migraine, and today we can iden-tify many of the characteristics of the natural historyof this affection. Willis did not confine his account ofmigraine to his experience with Lady Conway. Else-where he mentioned a case where a ... "beautiful andyoung woman, indued with a slender habit of body, andan hot blood, being obnoxious to an hereditary head-ach, was wvont to be afflicted with frequent and wander-ingfits of it, to wit, some upon ever' light occasion, andsome of their own accord; that is, arising without anyevident cause. On the day before the coming of thespontaneous fit of this disease, growing very hungry inthe evening, she eat a most plentiful supper, with anhungry, I may say a greed)' appetite, presaging by thissign, that the pain of the head would most certainlyfollow the next morning; and the event never/ailed thisaugury'. For as soon as she awaked, being afflicted by amost sharp torment, thorow the whole forepart of herhead, she was troubled also wvith vomiting, sometimes ofan acid, and as it were a vitriolock, humor, and some-times ofa cholerick and highly bitterish.' hence accord-ing to this sign this headach is thought to arisefrom thevice of the stomach."Of the 17th century Critchley records4 the curious

illusions of Blaise Pascal as possible manifestations ofmigraine. These consisted of the sudden apprehensionof a cavity or yawning precipice sited on his left side;he also produced manuscripts with an extraordinarybroad right margin, and in places he would insertpeculiar zig-zag designs reminiscent of migrainousteichopsiae. These may have been episodes of hom-onymous hemianopia, not uncommon in migraine,but despite their euphonious attribution by his con-temporaries as "l'Abime de Pascal" it is uncertainwhether or not they were of migrainous genesis.Similar in certain respects were the strange visualexperiences of the Abbess Hildegard of Bingen:"I sawv a great star, most splendid and beautiful, andwith it an exceeding multitude offalling sparks withwhich the star followed ... suddenly they were allannihilated, being turned into black coals..."

These images too evoke suspicions of teichopsiaesucceded by a dense scotoma, both migrainous fea-tures; but we have a dearth of description of theirheadaches.

John Fordyce published in 1758 his De Hemicrania,an account of his own, mainly left sided migraineattacks. He was one of the first to observe the poly-uria, prodromal depression and the link with men-struation. Decrying section of the temporal artery, hewas a powerful advocate of large doses of valerianobtained from Valeriana sylvestris. By this time thesyndrome was well known and was described in manytexts and monographs. Fothergill drew attention to

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"fortification figures" in the aura, and was impressedby dietary factors, and was perhaps the first to incrim-inate chocolate as a precipitant of attacks. But, fulldescriptions were few, though many are the anecdotesrelating the migraine of distinguished persons ofthe era.

TissotAn extensive account is found in volume 13 of themonumental text of Tissot in 1790, which has therather impressive title: De la migraine, Oeuvres deMonsieur Tissot, nouvelle edition augment&e etimprimee sous ses yeux. Observing that gastric symp-toms might precede or initiate attacks, and that vom-iting might herald the termination of the headache"he commented: "Afocus ofirritation isformed little bylittle in the stomach, and that when it has reached acertain point the irritation is sufficient to give rise toacute pains in all the ramifications of the supraorbitalnerve...

Interestingly, these fine scholar-physicians of the18th century, who included Whytt, Cheyne, Syn-denham and Willis, made no distinction betweenphysical and emotional symptoms. They recognisedboth, but viewed them as essential manifestations ofnervous disorders. The 19th century saw the terms"organic" and "functional"; the latter implying lite-rally a disordered function or altered physiologicalreaction. This attitude was purveyed in the physicallyorientated descriptions of Abercrombie, Parry,Romberg, Hall, Mollendorff and in the astronomerAiry and his son. Theories of the nature of migrainebegin to embrace the rapidly developing knowledgeof medicine and physiology in the nineteenth century.Inflammations and a variety of vascular disordersranging from cerebral congestion to arterial con-striction or dilatation were popular notions. Pituitaryswelling or menstrual factors were claimed as causes,and masturbation and hereditary taints were cul-pable.

Hughlings Jackson (1834-1911)This Yorkshireman escaped to London from hisnative Green Hammerton via the Medical School ofYork along with his equally distinguished friend Jon-athan Hutchinson. They were both appointed to theLondon Hospital, and Jackson to the -National Hos-pital. So profound was his idiosyncratic scholarship,and so prophetic his clinically founded dicta concern-ing the physiology and integration of the brain, thatwe naturally turn to his writings for clarification.Unfortunately, he had little to say by way of descrip-tion, but his pithy footnotes point the way to conceptswhich are only now finding acceptance. "I believecases ofmigraine to be epilepsies (sensory epilepsies).Dr Latham thinks the paroxysm in migraine to be

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owing to arterial contraction in the region of the poste-rior cerebral artery; Dr Liveing that there is a "nervestorm" traversing the optic thalamus and other centres.I think the sensory symptoms of the paroxysm areowing to a "discharging lesion" ofconvolutions evolvedout of the optic thalamus, i.e. of "sensory middlecentres" analagous to the "motor middle centres".I believe the headache to be post-paroxysmal."'0 Bymiddle centres he referred to the basal nuclei whichwere subservient in his concept to the cortex and asso-ciational areas which were the higher centres in termsof cerebral organisation. Jackson arbitrarily classifiedmigraine as of three types: "(1) Typical: one in whichthere is a "visual projection", the well-known zigzag or'fortification" outline is most common, with in somecases a hemianopic area; then comes headache, mostoften frontal and one-sided, and lastly vomiting. (2)There are subtypical cases, visual projections and noth-ing more, or headache unpreceded by visual projectionsand nothing more, or headache unpreceded by visualprojections, and not followed by vomiting. (3) Thereare supertypical cases deserving very particular consid-eration. In these in addition so to say to the other symp-toms, numbness of one side of the body, and when thenumbness is on the right side there may also be consid-erable aphasia. To the inexperienced these cases lookfar more serious than they are; they do not point to anygross local disease. Some of the symptoms ofmigraine,the headache among others, are, I think, after effects ofthe discharge producing the paroxysm."Here Jackson was making a plea for a particular

approach to advance the philosophy of scientificprogress. He pleaded for the "arbitrary study ofcasesby type (ie classification) which does not prevent usfrom making at other times and for other purposesrational generalisations." He clearly differentiatedmigraine from epilepsy, and used the latter termgenerically to indicate a "discharging lesion" of thecortex; the differences were accounted for by "thedifferent seats of those lesions". He was familiar withthe links between migraine, epilepsy and what hetermed epileptiform seizures and "intermediateforms" of a type which Gowers later referred to as"the borderlands of epilepsy." Jackson was keen toerect hypotheses or suppositions, in the tradition ofNewton, and he decried the Baconian method ofinduction which were limited to observable andalready known facts. As in his work and writings onepilepsy, Jackson's comments on migraine, thoughbrief, heralded an awakening of speculation whichproved invaluable. As he remarked "The use ofhypotheses is the method of science."

Edward LiveingThe best text" is without doubt that of Liveing(1873) which spanned over 500 pages. Liveing was

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Historical aspects of migraine

Registrar to the Royal College of Physicians andAssistant Physician to King's College Hospital. Hisbook gave detailed case histories ofmany migraineursand included those of celebrated doctors' accounts ontheir own sufferings, those drawn from history as wellas his own patients. He provided full descriptions ofthe aura and its protean expressions and consideredthe integral links between migraine and epilepsy,vaso-vagal faints, vertigo, paroxysmal diseases andinsomnia and other nervous diseases. Liveing consid-ered the extant theories of migraine at length, underthe following headings: (1) The Doctrine of Bilious-ness, (2) Sympathetic and Eccentric Theories, (3)Vascular theories: (a) arterial cerebral hyperaemia(b) passive venous congestion of the brain (c) vaso-motor hypotheses, (4) The Theory of "nerve-storms"(his own belief).The first two concepts have been sketched at the

beginning of this paper in the allusions to thehumours emphasised by Galen and his successors.The discovery of a nerve supply governing thecapacity for arteries to dilate or constrict was (andstill is) responsible for the vascular hypothesis. Pleth-ora of the face, and pallor in attacks were of coursewell known and emphasised the idea that similarchanges were occurring in the brain.

E. Du Bois Reymond (1818-1896)This distinguished physician first discovered that theperipheral passage of a nerve impulse was accom-panied by an electrical discharge, the action potential.Writing in 1860 he attributed migraine to "a Tetanustakes place in the muscular coats of the vessels of theaffected half of the head; in other words a Tetanus ofthe cervical portion of the sympathetic". His accountgives us an excellent picture of the art of descriptivewriting at this time: "every three or four weeks I amliable to an attack. I wake with a general feeling ofdisorder, and a slight pain in the region of the righttemple which, without overstepping the midline, reachesits greatest intensity at midday; towards evening it usu-ally passes off. While at rest the pain is bearable, but itis increased by motion to a high degree of violence. . . Itresponds to each beat of the temporal artery. The latterfeels on the affected side, like a hard cord, while the leftis in normal condition. The countenance is pale andsunken, the right eye small and reddened.. . There maybe left behind a slight gastric disorder;frequently, also,the scalp remains tender at one spot thefollowing morn-ing... For a certain period after the attack I can exposemyself with impunity to influences which before wouldinfallably caused an attack."Latham initiated the vascular hypothesis and

explained it thus: "contraction of the blood vessels ofthe brain, and so diminished supply ofblood, producedby the excited action of the sympathetic; and that the

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exhaustion of the sympathetic following on thisexcitement causes the dilatation of the vessels and theheadache". This was to set the foundations for themasterly exposition of Harold Wolff, many yearslater. Liveing accepted that dilatation of the arteriesmight explain the headache, but rejected the vasculartheory as explanation of the varied content of theaura, its bilaterality in certain patients, the vegetativesymptoms throughout the body, and the changes inpatterns of attacks. Liveing regarded it as "a form ofcentrencephalic seizure, the activity of which isprojected rostrally upon the cerebral hemispheres, andperipherally via the ramifications of the autonomicnervous system..." In explaining his "nerve storm"theory he considers migraine along with other"neuroses" to be: a primary and often hereditary ...disposition of the nervous system itself; this consists ina tendency to the irregular accumulation and dischargeof the nerve force ... a gradually increasing instabilityto equilibrium in the nervous parts. when this reaches acertain point, the balance offorces is liable to be upsetand the train ofparoxysmal phenomena determined bycauses in themselves totally inadequate to produce sucheffects-just as a mere scratch will shiver to dust a massof unannealed glass. . .

GowersThe famous two volume work Diseases ofthe NervousSystem published in 1886 is accessible,'2 and thesubstantial chapter on "Migraine: Paroxysmal Head-ache" still provides a surprisingly up to date accountof the clinical expressions, variants, complicationsand aetiology. Here, the reader will find descriptionsand interpretations ofmodel clarity. In respect of cau-sation Gowers refers to the two main theories: vascu-lar and neural. Like Jackson, he was impressed by thesimilarities with epilepsy. But, he stressed: "The pecu-liarity in the disturbance of migraine is its deliberatecharacter and its limitation to sensory structures. Theuniformity of these symptoms in the same case isanother feature that must be taken account of in anytheory as to their origin. To explain them on the vaso-motor hypothesis we must assume, first an initial spasmof the arteries in a small region of the brain; secondly,that the contraction always begins at the same place;and, thirdly, that it can give rise to a definite, uniformand very peculiar disturbance offunction. There is noevidence ofthe truth ofany one ofthese assumptions. . .the vascular changes are the result of a disturbance inthe sensory centre, or are the effect of associatedderangement of vasomotor centres."Gowers agreed with the general tenets of the Live-

ing hypothesis of "ne,rve storms", but favoured thecortex rather than the thalamus as the main site ofderanged neural activity. He anticipated more recentideas'3 '4 by allowinig that "the peculiar disturbance

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might spread to cells of lower centres". This accordswith the current notions1314 which implicate thehypothalamus and brain stem. He found "the causeof the headache obscure", but considered the brainitself, the meninges or a neuralgia referred from thecentral disturbance to the periphery. He could con-ceive that the pain might be the result of a vascularcondition, as had Du Bois Reymond, but wasunhappy with this concept since at that time theoccurrence of arterial pain had not been established.

Treatment was of course primitive, and as it is now,based largely on empirical observation. Gowers mix-ture remained fashionable and enjoyed considerablesuccess for more than half a century, and stillappeared in student texts in the 1950s. It consisted of:

.lq. trinitini minims 1Liq. strychninae minims 3Tinct Gelsemii minims 15Phenazone grains 5Sodium Bromidi grains 5Acid hydrobrom dil minims 10. Aqua Chloroform

ad ozs 1. t.d.s.The use of trinitrine perhaps anticipated the cur-

rent vogue for the calcium channel blockers which arealso vasodilators.

The Twventieth CenturyWhen we come to the present century, research andwritings have sprouted and grown in parallel. Theyare summarised in the well known text of Wolff,'"Sacks,'6 Lance'7 and of the author. 18 19 In the 1920sallergy was a popular new idea supported by the puta-tive links between migraine and asthma and urticaria.Although Lance showed these to be no more than thecoincident coexistence of very common diseases,modern immunologists have attempted to resurrectthis theory in the form of dietary allergy, so far withlittle conviction. Psychosomatic disorders were thefashion of the 1940s and 1950s following the work ofSelye on "Stress diseases". Research has shownabnormalities of serotonin and prostaglandins; cur-rently a defect of endogenous opioids is a popularnotion. But it remains extremely difficult toinvestigate migraine. The fact is that many of theobjective abnormalities on measurement are found inonly small numbers of patients; and, observationsbased on "induced attacks" are nearly always trig-gered by an artefactual stimulus. Likewise, there is noanimal model suitable for experiment. Thus no validor generally applicable "marker" or constant accom-paniment of the disorder has been found.Our current concepts have evolved in Darwinian

fashion from physicians of the past. Migraine can beseen as a reaction or biological adaptation deter-mined by (1) a primary disorder of brain threshold,probably familial, possibly operating at the level of

Pearcethe brain-stem or hypothalamus, in combination with(2) a variety of external precipitating factors whichindividually or collectively lower this threshold to acritical point when an attack will ensue. Thereafter,the "exhausted" nervous system compelled bymigrainous symptoms to rest and retreat from theexternal stresses, recovers and regains its formerthreshold until the cycle is repeated.The primary basal setting of the threshold is a bio-

logical circadian function subject to the individual'sphysiological and emotional resilience. As such, it isprone to fluctuate and to fall, particularly in responseto those complex factors, so difficult of definition,which we recognise as physical and mental stress."A form of centrencephalic seizure, the activit.y oJ

which is projected rostrally upon the cerebral hemi-spheres, and peripherally via the autonomic nervoussystem." Thus wrote Edward Liveing in 1873. We arebut a little wiser in 1986.

I am indebted to Dr Macdonald Critchley for permis-sion to quote from his Sandoz Memorial Lecture,1967.4

References

'Hippocrates. In: Allory AL. Concerning Migraine. Thesis,Paris, 1859.

2 Celsus. In: Thomas L. La Migraine. Paris: Delahaye andLecrosnier, 1887.

Aretaeus. The extant works of Aretaeus the Cappadocian.Francis Adams' translation: printed for the Sydenhamsociety. London: Wertheimer & Co, 1856.

4 Critchley M. Migraine from Cappadocia to Queen Square,First Sandoz Memorial Lecture. In Smith R, ed. Back-ground to Migraine, London: Heinemann, 1967:28-39.

'Galen. Decompositione Medicamentorum SecundumLocos. In: Opera Omnia. Ed. Kuhn. Lipsiae: C. Cno-blochii. Tomus XI 1, Liber 1 1, Capl 1I1 (De hemicrania),1826. cited in: Balyeat RM, ed. Migraine Diagnosis andTreatment. Philadelphia: Lippincot, 1933.

6Aurelianus, Caelius: Liber 1. De Capitis Passione, quamGraeci Cephalaean nominant. In: Medici AntiquiOmnes qui Latinis. Venetius, 1547. cited by BalyeatRM. op cit.

'Willis T. Two Discourses concerning the soul of brutes(De anima brutorum). Part 1. 1672. cited by SpillaneJD. in The Doctrine of the nerves. Oxford: O.U.P.1981.58-61.

8 Symonds CP. The Circle of Willis. Br Med J1955;1: 119-22.

'Pearce JMS. The enigma of cluster headache. J IndianPhysicians 1986. (In press.)

"Jackson JH. In: Taylor J, ed. Selected writing of JHJackson, London: Staples Press. Vol 2. 1958:153, 371and 372.

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l Liveing E. On Megrim, Sick-headache, and some AlliedDisorders: A Contribution to the Pathology of Nerve-storms. London: Churchill. 1873.

12 Gowers WR. Diseases of the Nervous System. Vol 2.776-92. London: Churchill. 1886.

13 Pearce JMS. Migraine: a cerebral disorder. Lancet1984;2:86-89.

Pearce JMS. Is Migraine explained by Leao's Spreadingdepression? Lancet 1985;2:763-6.

5Wolff HG. Headache and other Head Pain. Oxford OUP,

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1963.16Sacks OW. Migruine. Evolution of A Common Disorder.

London, Faber & Faber. 1970.7 Lance JW. Mechanism and Management of Headache. 3rd

edn. London: Butterworths. 1978.Pearce JMS. Modern Topics in Migraine. London: Hei-nemann. 1975.

19 Pearce JMS. Migraine. In: Weatherall DJ. Oxford Text-book of Medicine, 2nd edn Oxford: OUP 1986.

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J M Pearce

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