MIGRAINE: A CEREBRAL DISORDER

86

Occasional

Survey

MIGRAINE: A CEREBRAL DISORDER

J. M. S. PEARCE Department of Neurology, Hull Royal Infirmary,

Hull HU3 2JZ

"No anatomical changes are known to underlie the phenomena of migraine, and from the character of the symptoms, and the analogies of the disease, it is unlikely that any will be discovered. Hence the nature ofthe malady is a matter ofinference ..." W. R. GOWERS, 1888.

ALTHOUGH many illustrious predecessors had extensively described and studied the disorder, it was H. G. Wolff who first initiated the clinical and laboratory investigation of migraine by scientific methods. He concluded that preheadache phenomena are due to cerebral vasoconstriction; that the headache is produced by distension of the external carotid arteries, and that pain is enhanced by vasoactive polypeptides in the tissues surrounding the vessels and

exciting a sterile inflammation.I In this paper I attempt to appraise the evidence for vascular and neural (ie, cerebral) factors in the pathogenesis of migraine. VASCULAR HYPOTHESIS

accords with the pulsatile, of the and it explains the varied pain;2 throbbing localisation, which is not confined to the anatomical branches of the trigeminal nerve but better conforms to branches of the external carotid artery in the face and scalp. It is in keeping with Mollendorf’s observation that digital compression of the neck arteries causes the pain to abate while the pressure is maintained. It is consistent with the observations of dilated conjunctival vessels and even of the facial ecchymoses occasionally seen in attacks. The relief of pain by alphaadrenergic drugs (eg, ergot) and the worsening by vasodilators (alcohol, amyl nitrate), the alleged prolongation of the "vasoconstrictive" aura by ergot and its disappearance when nitrites are given-all support the notion of a first phase of cerebral vasoconstriction and a second phase of extracranial vasodilatation. The vascular

hypothesis

nature

J. 1

LA. 1305-07.

Fineberg HV, Pearlman

Surgical

treatment

of peptic

ulcer

Experimentally, reduced cerebral blood flow (rCBF) has been demonstrated in the aura, followed by hyperaemia during headache.3 During induced attacks, hypoperfusion is present, but reactivity to CO2 and to "physiological activation" fails to increase the flow in oligaemic areas. Autoregulation remains normal, and between attacks patients show normal regulation of brain circulation.4 Oligaemia and hypoperfusion are directly related to the symptoms of the aura, but the initiating or causal factors underlying these phenomena are not explained by the vascular hypothesis. Humoral factors have been suggested, the idea being that vasoactive substances might cause vasospasm, thus causing ischaemia. If the blood level of these vasoactive substances fell, a reactive vasodilatation might ensue. This principle implies, in effect, two mechanisms-first intracerebral vasoconstriction and secondly extracerebral vasodilatation, occurring in two vascular territories. It implies more than a biphasic reaction in the cerebral vessels. Biochemical Observations Histamine headache is associated with generalised vasodilatation and was rightly rejected many years ago as a model for migraine, largely because of its widespread vascular effects and the lack of other characteristics of migraine attacks. Vasoactive amines have been isolated from "tissue juice" surrounding superficial temporal arteries during migraine headache and have pain-producing properties when applied to a blister base. Acetylcholine, noradrenaline, bradykinin, histamine, and substance P have been implicated as pain-producing peripheral agents in relation to dilated large scalp arteries. A serotonin (5-HT) releasing factor, demonstrated by Lance and colleagues,5 released serotonin from platelets, causing the vasoconstrictive phase, and in the subsequent painful (dilator) phase low blood levels of serotonin were found and were thought to account for the vasodilatation. Lance thinks this is unlikely to be a major factor, in view of dose-response curves he has observed.6 Reserpine (a 5-HT

releasing factor) is, however, a potent migraine precipitant; and 5-HT-blocking drugs are among the most effective migraine prophylactics. Increased platelet aggregability with a fall in platelet 5-HT and monoamine-oxidase levels have been confirmed in migraine attacks7 and form the basis of

H HANSEN AND U. KNIGGE: REFERENCES

in

the United States.

Lancet 1981; i 2 Wyllie JH, Clark CG, Alexander-Williams J, et al. Effect of cimetidine on surgery for duodenal ulcer Lancet 1981, i: 1307-08. 3. O’Conner PC, Griffiths K, Shanks RG. Trends in peptic ulcer related diseases from 1972-1980. Eur J Clin Pharmacol 1983; 24: 435-40. 4 Gray GR, McWhinnie D, Smith IS, Gillepsie G. Five-year study of cimetidine or surgery for severe duodenal ulcer dyspepsia. Lancet 1982; i: 787-88. 5. Andersen D, Amdrup E, Sørensen FH, Jensen KB. Surgery or cimetidine. I. Comparison of two plans of treatment: operation or repeated cimetidine. World J Surg 1983; 7: 372-77 6. Andersen D, Amdrup E, Sørensen FH, Jensen KB. Surgery or cimetidine. II. Comparison of two plans of treatment. Operation or cimetidine given as low maintenance dose World J Surg 1983; 7: 378-84. 7. Goligher JC, Hill GL, Kenny TE, Nutter E. Proximal gastric vagotomy without drainage for duodenal ulcer: results after 5-8 years Br J Surg 1978, 65: 145-51. 8. Grear MWL. Proximal gastric vagotomy versus long-term maintenance treatment with cimetidine for chronic duodenal ulcer a prospective randomized trial Br Med J 1983; 286: 98-99. 9 Gonzales EM, Arnau BN, Dupont TC, Andolle JF Proximal gastric vagotomy. Acta Chir Scand 1983, 149: 69-76 10 Nyhus LM. Proximal gastric vagotomy. Gold or dross? Arch Surg 1983, 118: 1373-74 11 Kelly KA. Which operation for duodenal ulcer. Mayo Clin Proc 1980, 55: 5-9. 12. Gillespie IE When vagotomy fails Br Med J 1982; 284: 1815-16 13 Amdrup E, Jensen HE Selective vagotomy of the parietal cell mass preserving innervation of the undrained antrum. Gastroenterology 1970; 59: 522-27. 14 De Vries BC, Eeftirck Schattenkerk M, Smith EEJ, et al Prospective randomized multicenter trial of proximal gastric vagotomy or truncal vagotomy and antrectomy for chronic duodenal ulcer results after 5-7 years. Br JSurg 1983; 70: 701-03. 15 Koo J, Lam SK, Chan P, et al. Proximal gastric vagotomy, truncal vagotomy with

and truncal vagotomy with antrectomy for chronic ulcer. Ann Surg 1983, 197: 265-71 16 Kronborg O, Madsen P A controlled, randomized trial for highly selective vagotomy versus selective vagotomy and pyloroplasty in the treatment of duodenal ulcer Gut

drainage

1975, 16: 268-71 17.

Thompson JC, Fender HR, secretion

of five

Watson

current

LC, Villar HV The effects of gastrin and gastric operations for duodenal ulcer. Ann Surg 1976, 183:

599-607. 18. Roland M. Effects of

proximal gastric vagotomy on gastric secretion Scand J Gastroenterol 1976, 11 (suppl 42) 89-91. 19 Gledhill T, Buck M, Paul A, Hunt RH Cimetidine or vagotomy? Comparison of the effects of proximal gastric vagotomy, cimetidine and placebo on nocturnal intragastric acidity and acid secretion in patients with cimetidine resistant duodenal ulcer. Br JSurg 1983, 70: 704-06. 20 Moir JH Psychological, social and surgical factors which influence success or failure after gastric operations. Scand J Gastroenterol 1979; 14: 457-62. 21. Boyd EJS, Wilson JA, Wormsley KG. Smoking impairs therapeutic gastric inhibition Lancet 1983, i: 95-97. 22. Koman MG, Hansky J, Eaves ER, Schmidt GT Influence of cigarette smoking on healing and relapse in duodenal ulcer disease. Gastroenterology 1983, 85: 871-74. 23 Kjaergaard J, Thomsen F, Jensen HE. Cimetidine treatment of patients with duodenal ulcer referred to a surgical clinic Acta Chir Scand 1981, 147: 151-54. 24. Feely J, Wormsley KG H2-receptor antagonists—cimetidine and ranitidine. Br Med J 1983, 286: 695-97. 25 Hubert JP, Kiernan PD, Beahrs OH, ReMine WH Truncal vagotomy and resection in the treatment of duodenal ulcer. Mayo Clin Proc 1980; 55: 19-24. 26 Sawyers JL, Herrington JL, Burney DP Proximal gastric vagotomy compared with vagotomy and antrectomy and selective vagotomy and pyloroplasty Ann Surg 1976, 510: 15.

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vasoconstrictive mechanism. Indeed ifa major arterial trunk was so constricted for several hours, infarction would be the

Hanington’s hypothesis of migraine as a blood disorder due to abnormal platelet function. Thus vascular abnormalities would be secondary to platelet dysfunction in migraine. Unfortunately, this attractive notion is weakened by the very considerable variability of platelet function seen in nonmigrainous subjects in association with age, exercise, emotional stress and drugs. Many other humoral agents have been suggested as causal factors. They include dietary tyramine, phenylethamine, and allergic factors. Genetically determined deficiencies of monoamine oxidase B have been suggested as an explanation for the body’s inability to metabolise various monoamines. In each case, however, the vascular phenomena are seen as being secondary to the humoral factors that may precipitate attacks.

not the exception. A further difficulty is the observation that rCBF is sometimes increased over both sides of the brain during the headache phase, yet the headache itself is most often unilateral. Further, although visual cortical symptoms dominate the aura and are commonly bilateral, the oligaemic phase of rCBF is usually seen mainly in part of one occipital lobe, spreading anteriorly across anatomical arterial territories rather than across the midline. Headache and focal symptoms may occur on the same side. Thus, there are many striking inconsistencies between the distribution of symptoms and the observed changes in rCBF. These suggest that although vascular factors are important, the symptoms are not adequately explained by sequential constriction and dilatation of major arterial trunks. As the initiating event in migraine, vascular instability of large arteries is no longer a tenable hypothesis for several reasons. First, although vascular reactivity is a variable physiological phenomenon, the tendency for migraine attacks to cluster and then to remit for weeks or months at a time is not easy to understand on this basis. Migraine is paroxysmal, and daily or continuous headache is not seen (apart from those cases complicated by ergot habituation or tension headache). What chemical or physiological changes in arterial walls make them refractory to further attacks after a headache has ceased? Vascular reactions or spasm in major arteries tend in general to develop over a matter of minutes; yet in some instances when migraine develops after a visual stimulus it may begin within a few seconds with an expanding scotoma-far too rapid a reaction for an arterial vasospastic event. Gowersil too, rejected the vascular hypothesis,

rule,

Pharmacological Evidence Many workers have trodden the dangerous ground of inferring pathophysiological mechanisms from observations of response to treatment. Aspirin, ergotamine, indomethacin, amitriptyline, beta-blockers, and prostaglandin synthetase inhibitors have all shown significant efficacy in migraine either in relief of symptoms or in prevention of attacks. Similarly, dietary amines may precipitate attacks in a small number of patients, and dietary food sensitivity may trigger attacks in others. However, there are considerable logical objections to accepting these as causal factors. If any of these hypotheses was a complete explanation, even of one type of migraine, one would expect that the subgroup of patients in whom it applied could be separated from the rest and would show a predictable therapeutic response approaching 100% when the agent was withdrawn (or counted by pharmacological means). Nothing of this sort has emerged, and the majority of migraineurs show a pattern of attacks which vary in content and severity; tend to cluster then to remit; and are sensitive to non-specific factors. These include emotional stress8 and hormonal factors which operate at the menarche, in pregnancy, with oral contraceptives, and with the menopause. Responsiveness to treatment is equally variable, placebo reactions are common (30 - 4070), and many effective drugs have several pharmacological actions, each of which could play a part. Amitriptyline, for example, is sedative, antidepressant, weakly anticholinergic, and noradrenergic and has been shown to be a non-specific calcium channel antagonist. Cyproheptadine is antihistanimic, a serotonin antagonist, and a calcium channel antagonist. Thus it is clearly hazardous to deduce an aetiological role for any mechanism because of therapeutic observations. Doubtless, many of the factors referred to will play a part in some types of attacks in some patients. Individually, they are likely to be of importance only as factors contributory to the headache mechanism.

t

Objections to

the Vascular Hypothesis That blood vessels are involved in the production of migraine headache seems inescapable. The headache appears to be mainly a painful dilatation of scalp and facial arteries, but distention of intracranial venous sinuses and Heyck’s theory of shunting from a dilated arteriole into a constricted capillary bed are other possible factors. However, headache is only one of many events in the spectrum of the disorder, and regional cerebral blood flow changes, oedema of arterial walls, and "ischaemic symptoms" are not synonymous with a primary vascular cause. Reduced rCBF long precedes any symptom of the "ischaemic" aura,9,10 often by many hours, and there is no evidence that this oligaemia is caused by a

pointing out: "(i) The same combination occurs in some attacks of epilepsy. (ii) The uniformity of these symptoms in the same case is another factor that

must

be taken into

account

in any

their origin. theory To (iii) explain them on the vasomotor hypothesis we must assume, first, an initial spasm of the arteries in a small region of the brain; secondly, the contraction always begins at the same place and, thirdly, that it can give rise to a definite, uniform, and very peculiar disturbance of as to

function. There is

no

evidence of the truth in any one of these

assumptions." NEURAL HYPOTHESIS

According the neural hypothesis migraine is caused by a primary derangement of function of the brain itself. The neuronal function is disturbed from time to time in a peculiar manner, and the visible vasomotor disturbance is of secondary origin. The periodical derangement of function has been called, by a somewhat dramatic metaphor, a "nervestorm". This theory was ably advocated by Liveing. 12 But, after Liveing and Gowers, the idea ofa primary cerebral cause fell into neglect. In 1969 I wrote, to

"A periodic disturbance of hypothalamic activity could account for the periodicity of migraine attacks, and could also be related to emotional disturbances mediated by pathways from the limbic system to the hypothalamus. An instability of such central control might be inherited in a way similar to the low threshold to epilepsy, which is present in sufferers from the familial idiopathic form of that disorder".2 I drew attention to the curious rhythmicity and pattern of apparently spontaneous attacks, and to the remissions

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following them. Patients’ diary cards show a tendency for grouping or clustering of attacks in many cases; this suggests a basic rhythmicity of a central threshold which falls for a time, allowing a cluster to emerge, then appears to rise with consequent remission. After attacks, patients can be exposed to migraine-provoking stimuli (alcohol, sleeplessness, certain foods, travel) and yet escape the ravages of the migrainous assault: their threshold-whatever its nature-is clearly raised. Genetic, psychological, and hormonal factors are certainly the most common agents provocateurs, and each of these has obvious connections with the hypothalamic region. Further, the sympathetic outflow affecting vasomotor tone originates in the hypothalamus. So much for the notion. What is the clinical and laboratory evidence? First, the old notion that changes in cerebral blood vessels caused altered neuronal metabolism is almost certainly incorrect. Roy and Sherringtonl3 had fathered the modern view that altered neuronal metabolism determines calibre changes in the microcirculation. Stimulation of the cortex increases regional microflow within 1 - 2 s, and Sokoloff 14 showed that a vascular reaction developed within seconds ofa focal metabolic change. This is now accepted, and further evidence is seen in the diminution in rCBF, in Alzheimer’s disease, where neuronal failure causes reduced flow and not vice versa. The second major evidence stems from the computerised blood flow studies of Olesen.9,1O In patients with classical migraine they show that intense oligaemia starts in one occipital lobe. It precedes any symptoms of aura or headache by many hours. Oligaemia spreads slowly forwards but is not confined to the major arterial territories of the posterior or middle cerebral arteries. Oligaemia persists long after the aura and headache phases have ended and continues for several hours after the patient has recovered. EEG changes in migraine include both focal and generalised slow e and activity, which may precede the symptoms of the aura. This could equally be attibuted to a primary vasospasm as to a primary neuronal event. However, the relationship between migraine and epilepsy is of more fundamental importance. The sensory symptoms of both can be qualitatively similar, as are the more subtle psychic phenomena of Hughlings Jackson’s dreamy state, metamorphopsia, language disorders, and vegetative symptoms of mood and appetite. The two distinct disorders co-exist in a greater number of patients than expected by chance.2Rarely epilepsy occurs at the height of a migraine attack, though other disorders of consciousness are much more common-mainly in BickerstafPs basilar artery migraine. The much briefer duration of symptoms in epilepsy and their abrupt onset separate the two attacks clinically, but that epilepsy occurs in 2 -11 /o of migraine patients is of some importance. In some patients epilepsy will cease after many years and be "replaced" by migraine; in others the reverse sequence occurs. An excess of migraine is also seen in the families of

epileptics.

of Attacks Blau 15 has rightly emphasised the importance of sleep as an integral part of the attack and also as a means which patients Content

can cultivate to accelerate termination of the attack. Attacks very often incubate in sleep and declare themselves on awakening; less often they waken the patient during the night. The precipitating role of fatigue, excitement, and stress is well accepted and, like sleep, the factors suggest a cerebral rather than a vascular basis.

Reflex Initiation I have encountered several patients in whom a visual stimulus (2 a match flame, 4 an electric light bulb) will be followed immediately by an exaggerated after-image. This persists and is then perceived as a scotoma which then expands, scintillates with zig-zag coloured edges, and spreads centrifugally. The negative after-image merges into positive teichopsiae within seconds. This is far too rapid a phenomenon to allow us to postulate a vascular disorder of the cerebrum. Leiio 16 spreading electrical depression of the cerebral cortex after the application of electrical tetanic currents at a focal point. This rate of spread of cortical inhibition corresponds closely to the calculated rate of cortical disorder claimed by Lashleyl7 when he plotted his own visual aurae during attacks. These papers provide an understandable basis for a disorder initiated by a focal disturbance of neuronal function with spreading cortical inhibition. Whence this arises is not certain, but it accords well with Olesen’s observation of spreading oligaemia-a secondary phenomenon due to the effect of neuronal disorder on its microcirculation and ultimately on regional blood flow. Neurological prodromata, beginning hours or a day before attacks, consist of repeated and inappropriate yawning, food craving, fatigue, or euphoria. Such symptoms may derive from a hypothalamic vegetative disorder-or from an ascending disorder arising in the brainstem. These essentially neural symptoms are rarely seen in cerebrovascular ischaemic attacks of other origin and therefore are unlikely to be due to major "arterial insufficiency". The occasional reversible oedema of vessel walls shown angiographically is consistent with the observed cerebral blood flow changes and could be induced by secondary disturbances of brainstem nuclei with autonomic efferents or directly via the sympathetic/parasympathetic outflow. As Ross Russell says, "the evolution of a migraine attack which tends to spread from the occipital to the parietal lobe to involve more than one vascular territory is not like the effects of vascular occlusion as generally

reported

understood" .18 Cerebral infarcts have been shown by computed tomographic scanningl9 and rarely at necropsy20 as a consequence of migraine attacks. These too may be explained on the basis of prolonged regional oligaemia with failure of the autoregulatory mechanism. Investigations with positron emission tomography have shown that reduced cerebral perfusion pressure diminishes cerebral metabolic demands.2’ Cerebral blood volume rises with local vasodilatation, and cerebral blood flow (CBF) and volume (CBV) appear to be linked to maintain homoeostasis, so that their ratio, CBF/CBV, remains constant with varying perfusion pressures, within certain limits. At first, when compensation is adequate, CBV rises as CBF remains constant and the ratio again falls so that CBF/CBV is an index of perfusion reserve. When CBF falls the oxygen extraction by tissues is increased from the normal level of 35 - 50% to more than 90%. This threatens incipient failure of autoregulation and parenchymal damage. These findings derive from studies of carotid occlusion but may be pertinent to intracranial vascular disease. Certainly, they support autoregulation of the microcirculation, and this is readily understood if we assume that this is determined by the metabolic activity and needs of neurons. Possible Neural Pathways

Sicuteri22 has argued that headache represents a failure of central (ie, cerebral) adjustment to threatening harmful stimuli-both physical and psychic. He refers to a "central

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biochemical dysnoniception". This is associated with neurotransmitter deficiencies-for example, serotonin and other monamines. Intrinsic cerebral pathways for neurotransmitters provide a pathway for brainstem nuclei to affect the microcirculation of the cortical mantle. Lance and colleagueshave shown that electrode stimulation of the locus caeruleus in macaques produces intracerebral vasoconstriction and extracerebral vasodilatation, the latter mediated by the seventh cranial nerve and a non-cholinergic transmitter. Similarly, in the cat, stimulation of the trigeminal nerves produces vasodilatation of the external carotid artery. Lance postulates that in migraine activation of the locus caeruleus would explain the neurological symptoms, the observed changes in blood flow, and vascular reactivity. These claims suggest that migraine is initiated by a primary disorder activating a neural mechanism in the brainstem. Turning to the microvasculature, experimental work points to regulation of blood flow by purinergic nerves which release adenosine triphosphate and its breakdown product adenosine monophosphate.23 Both are potent cerebral dilators and also stimulate pain in primary afferent ’ nerve terminals such as those found in the adventitia of cerebral vessels traversing the subarachnoid space. CONCLUSION

Thus there is much experimental evidence to support a cerebral basis for the initiation of migraine attacks. Vasoactive neurotransmitters are located in anatomical sites appropriate to the development of a disordered microcirculation and spreading hyperaemia. There is, however, much that we do not understand, not least the asymmetry of both headache and disturbed regional cerebral blood flow. Present evidence favours a primary neural mechanism.24 A varying threshold of neural circuitry can explain the periodicity and variable patterns of attacks, linked to genetic, hormonal,25 and environmental factors in a way comparable to familial idiopathic epilepsy. Vascular and hormonal factors are seen as important- in the production of certain symptoms, especially headache, but are probably dependent on an initial neural mechanism which then causes a secondary disorder of the microcirculation. REFERENCES 1. Wolff HG. Headache and other head pain. New York: Oxford University Press, 1963 227-386. 2. Pearce JMS. Migraine, mechanisms and management. Springfield, Illinois: Charles C Thomas, 1969: 1-9. 3 Skinhoj E. Hemodynamic studies within the brain during migraine. Arch Neurol 1973; 29: 95-98 4 Lauritzen M, Olsen TS, Lassen NA, Poulson OB Regulation of regional cerebral blood flow during and between migraine attacks. Ann Neurol 1983; 14: 569-72. 5 Anthony M, Lance JW Serotonin in migraine. In: Pearce JMS, ed. Topics in migraine. London. Heinemann, 1975. 6 Lance JW, Lambert GA, Goadsby PJ, Duckworth JW. Brainstem influences on the cephalic circulation: experimental data from cat and monkey of relevance to migraine. Headache 1983, 23: 258-65. 7. Hanington E Further observations on platelet behaviour in migraine. In: Rose FC, Zilkha J, eds. Progress in migraine research. I London: Pitman, 1981. 80-84 8. Pearce JMS. Migraine a psychosomatic disorder. Headache 1977; 17: 125-28. 9 Olesen J, Tfelt-Hansen P, Henriksen L, Larsen B. The common migraine attack may not be initiated by cerebral ischaemia. Lancet 1981; ii: 438-40. 10 Olesen J, Larsen B, Lauritzen M. Focal hyperaemia followed by spreading oligaemia and impaired activation of CBF in classic migraine. Ann Neurol 1981, 9: 344-52. 11 Gowers WR. A manual of diseases of the nervous system, vol 2. London Churchill, 1888: 788 et seq 12 Liveing E. Megrim, sick headache and some allied disorders. London: Churchill, 1873. 13 Roy CS, Sherrington CS On the regulation ofthe blood supply of the brain J Physiol 1890; 11: 85-108. 14 Sokoloff L. Local cerebral energy metabolism: its relationship to functional activity and blood flow. Ciba Fdn Symp no 56. Amsterdam: Elsevier, 1978: 171-91. 15. Blau JN Resolution of migraine attacks: sleep and the recovery phase. J Neurol Neurosurg Psychiatry 1982; 45: 223-26.

Private Care CONTRIBUTION OF THE PRIVATE SECTOR TO ELECTIVE SURGERY IN ENGLAND AND WALES

J. P. NICHOLL B. T. WILLIAMS

K. J. THOMAS J. KNOWELDEN

Medical Care Research Unit, Department of Community Medicine, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX a sample of 12 959 records of patients treated in 148 of the 153 independent acute hospitals in England and Wales in 1981, it was estimated that 344 008 patients were admitted during that year. Residents of England and Wales admitted for inpatient elective surgery other than termination of pregnancy represented 162 000 of these cases. From 1980 Hospital Inpatient Enquiry data it was estimated that a

Summary

From

further 57 000 similar elective treatments were undertaken in National Health Service pay-beds. The 219 000 patients treated in the combined private sector represented 13·2% of the total case-load in domestic inpatient elective surgery. For certain operations this proportion rose to 26%, and for some regions the private sector cases represented more than 20% of the total work-load; therefore when assessing the need for, and provision of, acute health care in England and Wales, the contribution of the private sector cannot be ignored. INTRODUCTION

RECENT interest in private-sector health care in Britain has been focused on 2 trends-a rapid growth in the number of people covered by health insurance schemes, and a parallel boom in the development of privately financed hospitals. These new private hospitals may be a response to demand created by changes in the insurance market, but their development was also prompted by the phasing-out of paybeds in NHS hospitals in the late 1970s. By 1981, beds in private hospitals accounted for more than 70% of a total 9314 acute beds available in England and Wales for the treatment of private patients (table I). In 1979 the Royal Commission on the National Health Service considered that, apart from abortions and care of the chronically sick, the scale of private treatment was too small to make a significant impact on the NHS.’ Statistics from health insurance companies seemed to support this. In terms of benefits paid out, the Provident Association’s expenditure

16. Leäo AAP Spreading depression of activity in the cerebral cortex. J Neurophysiol 1944, 7: 359-90. 17. Lashley KS Patterns of cerebral integration indicated by the scotomas of migraine. Arch Neurol Psychiatry 1941; 46: 331-39 18. Ross Russell RW. Vascular diseases of the central nervous system. Edinburgh: Churchill Livingstone, 1983: 393. 19 Hungerford GD, du Boulay GH, Zilkha KJ. Computerized tomography in patients with severe migraine. J Neurol Neurosurg Psychiatry 1976, 39: 990-94. 20. Neligan P, Harriman DGF, Pearce JMS. Respiratory arrest in familial hemiplegic a clinical and neuropathological study Br Med J 1977; ii: 732-34. JM, Wise RJS, Leenders KL, Jones T Evaluation of cerebral perfusion reserve Lancet 1984; i: 182-84. 22 Sicuteri F, Anselmi B, Del Bianco PL. Systemic non-organic central pain. Headache 1978, 18: 133-36. 23. Burnstock G. Pathophysiology of migraine: A new hypothesis. Lancet 1981; i:

migraine:

21 Gibb

1397-98 24. Pearce JMS. Modern topics in

migraine. London: Heinemann, 1975 3-7. NS, Pearce JMS. Hypothalamic-pituitary-adrenal axis studies in migraine, with special reference to insulin sensitivity Brain 1971, 94: 289-98.

25. Rao