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lead poisoning" from material that includes frank toxicity ormajor known exposure. A history of pica was three times ascommon in NEEDLEMAN’s high dentine lead children as inthe low-lead group: later14 this was allowed for statistically,and an important residue was found.Any scientific study in this very difficult area should meet

certain criteria: randomisation, if any, should be pure; follow-up should be reasonably complete; estimates of lead burdenand psychological assessment should be contemporaneous;lead toxicity and pica should be excluded; groups beingcompared should be matched for age; parental IQ and socialbackground should be taken into account and rigorously so.Partialling out after the event is not so satisfactory.Furthermore, when "high" and "low" lead groups are

singled out to the exclusion of the middle ground, doseresponse data are missed. As it is, though there can be littledoubt of an association between clinical disorders and bloodlead levels formerly thought of as safe, proof of cause andeffect remains elusive.NEEDLEMAN and colleagues have also reported15 electro-

encephalographic studies on children in their series, the high-lead ones showing increased low-frequency delta anddecreased alpha activity. These data seem to challenge theconventional wisdom that EEG changes are associated withlead encephalopathy only. What is more, when the best sixEEG and psychological indices were combined NEEDLEMANet al. were able to classify correctly, as high or low dentinelead, two-thirds of the children. Supportive also of the Bostonwork, though not wholly of its conclusions, are WINNEKE’sstudies in two industrial towns in West Germany. TheGerman workers measured tooth lead, and in Duisburg, 16 asin Boston, a low and high lead group of children were studied.The IQ deficit in the high-lead groups was not significant but,at 5-7 points, it accords with the 4 points noted byNEEDLEMAN.13 The matching criteria were sex, age, andfather’s occupational status only. WINNEKE et al. then wentto Stolberg17 and took into account more than fifty potentiallyconfounding social factors. Differences in verbal,performance, and full IQ did not survive multiple regressionanalysis. However, error scores in a Bender-Gestalt type testdid, indicating that "impairment of perceptual-motorintegration may be considered a lead-induced CNS

dysfunction".Since lead is needed for purposes other than petrol

additives and since structures containing it are still

around, circulating concentrations will never bereduced to zero. Is a major shift to the left in thedistribution of blood lead concentrations in the

population, and in children especially, feasible? If it is,how far must we go? And how much of this shift can beachieved by removal of petrol additives alone? There isat least one encouraging trend: average blood levels arefalling. Even in high-risk children the prevalence of

14. Needleman HL, Leviton A Lead and behavioural deficits in children. Lancet 1979; n:104, 743.

15. Burchfiel JL, Duffy FH, Bartels PH, Needleman HL. The combined discriminatingpower of quantitative electroencephalography and neuropsychologic measures inevaluating central nervous system effects of lead at low levels In: Needleman HL,ed. Low level lead exposure: The clinical implications of current research. NewYork: Raven Press, 1980; 75-89,

16. Winneke G Neuropsychological studies in children with elevated tooth-lead levels In:Proceedings of Symposium on Toxic Effects of Environmental Lead. London:Conservation Society, 1979: 33-52

17 Winneke G, Brockhaus A, Kramer U, et al. Neuropsychological comparison ofchildren with tooth-lead levels: Preliminary report. In: Proceedings of InternationalConference on Heavy Metals in the Environment. Amsterdam: WHO, 1981:553-56.

blood lead values above 35 g/dl was only 0-8% in aU.K. survey.7The U.S. National Health and Nutrition

Examination Surveyl8 shows that blood lead levelsabove 30 Ilg/dl are unusual—1*9% in the whole

sample, but 13’ 5% in male Blacks aged six months tofive years. This study spanned four years. When

figures for individual years are analysed separately, adownward trend can be seen.19 This fall was accom-panied by a drop in the amount of lead in petrol in theUnited States, and it is difficult to believe that, evenwith allowance for other environmental activities, theparallel19 is entirely fortuitous. Partly because of theproblem of air lead values and the food chain it is verydifficult to know just how much of an average child’sbody lead burden is due to petrol, other than to agreewith RUTTER that 10% looks too low and 70% may betoo high. IRWIN H. BILLICK showed the CLEARsymposium 12 his regression curves and spoke of theirpower in predicting the fall in the proportion ofchildren with raised (>30 Ilg/dl) blood leads as less leadis added to petrol. Evidence from Frankfurt, thoughcontroversial,20 suggests that blood lead values changelittle when petrol lead is reduced; we must not expectrapid results from a tightening of controls on petrol.Lead is a natural villain, and a ban on tetraethyl-lead

in petrol might seem like a triumph of good over evil.That, however, would be to forget the original purposeof the anti-lead campaign, and the real cause forcelebration would be an unequivocal reduction in therate of neural and intellectual handicap in children.Whether this would happen as a result of an attack onpetrol alone, remains doubtful. Nobody can be greatlyin favour of polluting air, water, and food with thismetal; so let us stop doing so as best we may. But, if weare serious about helping the sort of children who nowhave raised blood concentrations, investment in

housing and education and social services offers morecertain rewards.

Treatment of MigraineIN classical migraine, with its prodromal phase, one

of the early features is a rise in plasma noradrenaline.’In many patients platelet aggregation is persistentlyincreased,2 2 and noradrenaline can intensify the

abnormality, with release of serotonin and adenosinediphosphate (ADP). These substances in turn provokefurther aggregation in cyclical fashion. Serotonin hascomplex vascular effects which result in arterial

18. Annest JL, Mahaffey KR, Cox DH, Roberts J. Blood lead levels for persons 6months-74 years of age: United States, 1976-80. NCHS Advance Data 1982 (May12): no 79.

19. Centers for Disease Control. Blood-lead levels in US population MMWR 1982; 31:132-34

20. Bryce-Smith D, Stephens R. Exposure to lead Lancet 1981, ii 877.

1. Hsu LKG, Crisp AH, Kalucy RS, Koral J, Chen CN, Carruthers M, Zilkha KJ In-

Greene R, ed. Current concepts in migraine research New York Raven Press,1978: 121

2 Deshmukh SU, Meyer JS. Cyclic changes in platelet dynamics and pathogenesis andprophylaxis of migraine. Headache 1977, 17: 101-08.

1339

constriction and capillary dilatation; and in serotonindepletion the reverse takes placed Serotonin is thoughtto increase the permeability of the blood/brain barrier,thus promoting its own entry into brain.4

Consequently arterial vasoconstriction develops alongwith neurological disturbances-typically visual.Blood serotonin now declines and the tonic

constricting effect is lost. This may contribute to theextracranial vasodilatation associated with headache,but a rise in extracranial blood flow is probably not thesole cause of headache: release of neurokinins from

aggregated platelets and mast cells, and of

prostaglandin E1, is thought to sensitise pain receptorsin the extracranial vessel walF—hence the tendernessof scalp and neck vessels commonly observed in anacute attack. Such a provisional model of migraine,based on mechanisms that are not accepted by all,offers enormous scope for therapeutic manipulation,and claims for success abound. Since the placeboresponse in migraine trials is 20-40%, 50%

improvement is probably necessary to substantiate aneffect.6 How should migraine be approached, in thelight of today’s information?A thorough history and examination should never be

omitted: migraine may be precipitated by underlyingdisease; and even if the findings are negative, theanxious or depressed patient will benefit fromreassurance. Treatment of depression alone (byamitriptyline, for example) may substantially reduceattacks.7 Because the initiating event in migraine maybe an increased plasma noradrenaline, it would belogical to prescribe a &bgr;-blocker such as propranolol oratenolol. Apart from their anxiolytic properties(3-blockers may increase vasoconstriction ofextracranial vessels. Such therapy is, of course,prophylactic and should be reserved for those withfrequent attacks-e.g., weekly. Whatever their mode ofaction, moderate success may be expected with thesepreparations.8,9 Stress is often related to migraine andvarious "fringe" techniques have been proposed suchas yoga, biofeedback, and acupuncture. None has yetbeen subjected to stringent trial, but such measuresmay be a useful adjuvant to drugs, especially wheremigraine and tension headache coexist. 7Numerous amines in food-notably, tyramine and

phenylethylamine-stimulate release of serotonin fromplatelets and may induce migraine and headachescommonly begin a few hours after ingestion of

chocolate, cheese, citrus fruits, or alcohol. According3 Roddie IC, Shepherd JT, Whelan RF Action of 5-hydroxytryptamine on the blood

vessels of the human hand and forearm. Br J Pharmacol Chemother 1955; 10:445-50

4 Harper AM. Mackenzie ET, McCulloch J, Pickard JD Migraine and the blood brainbarrier. Lancet 1977; i: 1034-36

5. Fanchamps A. Pharmacodynamic principles of anti-migraine therapy. Headache 1975;15: 79-90

6 O’Neill BP, Mann JD Aspirin prophylaxis in migraine. Lancet 1978; u: 1179-81.7 Mathew NT. Prophylaxis of migraine and mixed headache. A randomized controlled

study. Headache 1981, 21: 105-098 Diamond S, Medina JL. Double blind study of propranolol for migraine prophylaxis.

Headache 1976, 16: 24-279 Stensrud P, Sjaastad O Comparative trial of Tenormin (atenolol) and Inderal

(propranolol) in migraine Headache 1980; 20: 204-07.10. Hanington E Migraine—a blood disorder Lancet 1978; ii: 501-02.

to one report, 11 51 of 60 patients became headache-freewhen they eliminated ten common foodstuffs thoughtto induce headache. Reactions to each food were thenassessed by observation of pulse rate, without coding;indeed, the dietary trial was completely open. In-twocontrolled trials in which tyramine was

administered 12,11 the headache frequency was no

greater than that with placebo. The relation of diet tomigraine is not yet substantiated, even if avoidance ofcertain foodstuffs does help to control attacks.

Certain drugs are best avoided. Rauwolfia alkaloidswhich contain reserpine are still occasionallyprescribed for hypertension; they depress bloodserotonin levels, and an increase in headache frequencyis common. Steroid hormones are claimed to increase

serotonin, adrenaline, and noradrenaline receptors onplatelets and so to promote aggregation. Patients whoget migraine for the first time when on oral

contraceptives (or any steroid) should immediatelystop taking the drug, since there is real danger ofcerebrovascular occlusive episodes. 14 The same applieswhen migraine becomes more frequent during oralcontraception.

Several compounds exist which discourage plateletaggregation and should therefore lessen serotoninrelease from platelets. The simplest is aspirin, which ina small but well controlled trial6 was effective

prophylaxis in doses of 650 mg daily. Dipyridamolealso inhibits platelet aggregation and may be useful inlow dosage (100 mg/day); higher doses may actuallyprovoke migraine. 15 Dipyridamole plus aspirin proveda. useful preventive regimen in another small double-blind trial. 16 If platelets cannot be prevented fromsticking together, at least the harmful effects ofserotonin release may be lessened. For this purposeclonidine has been reported to be particularlybeneficial in "dietary" migraine," but its value nowseems. doubtful.’2,’s Methysergide has powerfulantiserotonin effects and until lately was regarded asthe best prophylactic agent; 19 the dose must be no morethan 6 mg/day and courses should not last more thanthree months for fear of retroperitoneal fibrosis orperipheral vascular constriction.2° Fashion has now

swung to pizotifen-an agent which not only blocksserotonin but also inhibits histamine, tryptamine,

11. Grant ECG. Food allergies in migraine. Lancet 1979; i: 966-68.12 Boisen E, Deth S, Hübbe P, Jansen J, Klee A, Leunbach G. Clonidine in the

prophylaxis of migraine. Acta Neurol Scand 1978; 58: 288-95.13. Forsythe WI, Redmond N Two controlled trials oftyramine in children with migraine

Dev Med Child Neurol 1974; 16: 794-99.14. Bickerstaff ER. Neurological complications of oral contraceptives. Oxford: Oxford

University Press, 1975.15. Hawkes CH. Dipyridamole in migraine. Lancet 1978; ii: 153.16. Masel BG, Chesson AL Jr, Alperin JB, Levin HS, Peters BH. Clinical trial of platelet

inhibition using aspirin and dipyridamole in migraine prophylaxis. Neurology 1978;28: 371.

17 Wilkinson M, Neylan C, Rowsell AR. Clonidine in the treatment of migraine at theCity Migraine Clinic in patients selected with tyramine. Proceedings of

International Headache Symposium, Denmark, 1971, 219-21 abstr.18 Mondrup K, Moller CE Prophylactic treatment of migraine with clonidine: a

controlled clinical trial Acta Neurol Scand 1977, 56: 405-1219. Lance JW, Anthony M, Somerville B Comparative trial of serotonin antagonists in

management of migraine. Br Med J 1970; ii: 327-30.20. Raskin NH, Appenzeller O. In- Smith LH, ed. Major problems in internal medicine.

Philadelphia: W B. Saunders, 1980; 47: 138-45.

1340

acetylcholine, and bradykinin. In several double-blindtrials21,22 it has been effective in about half the cases.Side-effects on daily doses of 1 ’5-3-0 mg consist ofdrowsiness, weight gain, and dry mouth. Pizotifenshould not be used in glaucomatous subjects. Thepreparation may be taken safely for several months at atime and its prophylactic effect seems equal or possiblysuperior to that of methysergide. 21Once the attack has begun, treatment is less effective.

Individuals who experience an aura have time to wardoff headache with ergotamine tartrate 1’ 0-2 - 0 mg bymouth or suppository. Absorption is slow by either ofthese routes. Ergotamine injection has been withdrawnin Britain but some patients are helped by ergotaminespray—0’ 36 mg by metered aerosol. No more than 12mg by mouth or suppository or 6 mg by spray should beadministered in any one week, for fear of ergotism, andsuch preparations are inadvisable in hypertension,ischaemic heart disease, and pregnancy. There is anarrow dividing-line between therapeutic and toxicblood levels, and an early toxic effect in some patients isheadache,24 which the unwary may confuse with

migraine. During the headache phase, ergotpreparations are unlikely to help, and the aim should beto relieve pain and nausea by standard analgesics andantiemetics.25 Prostaglandin release may account inpart for sensitisation of pain receptors. Only a fewprostaglandin inhibitors-mefenamic acid 26 andtolfenamic acid27 -have been tried for acute attacks.Good results are reported, but there has been nocomparison with aspirin, which has a similar mode ofaction and is much cheaper.

MILD ACUTE INFECTIOUS MYOCARDITIS

INFECTIOUS myocarditis poses, many difficulties of

diagnosis and management.’ In flamboyant acute illness withsigns of infectious disease, fever, and cardiac involvementmedical errors should be few, but these cases are the minority.Most infective cardiac muscle disease is mild and easilymisdiagnosed or overlooked. The difficulties have been

highlighted by an appraisal of mild acute infectiousmyocarditis in young military personnel in Finland. Heikkilaand Karjalainen2 have reviewed the cases of 185 patientsbetween 18 and 38 years of age (median 20) admitted_to theCentral Military Hospital, Helsinki, on account of electro-cardiographic abnormalities which were noted in the courseof an acute infectious disease. In about two-thirds of the

patients the ECG was recorded because of clinical symptoms

21. Foster JB. Further experience with pizotifen in the treatment of migraine. Curr TherRes 1976; 19: 66-69.

22. Heathfield KWG, Stone P, Crowder D. Pizotifen in the treatment of migraine.Practitioner 1977; 218: 428-30.

23. Presthus J. BC 105 and methysergide (Deseril) in migraine prophylaxis. Acta NeurolScand 1971; 47: 514-18.

24. Diamond S, Medina JL. Review article: current thoughts on migraine. Headache 1980;20: 208-12.

25. Wilkinson M, Williams K, Leufen M. Observations on the treatment of an acute attackof migraine Res Clin Stud Headache 1978; 6: 141-46.

26. Vardi Y, Rabey IM, Streifler M, Schwartz A, Lindner HR, Zor U. Migraineattacks-alleviation by an inhibitor of prostaglandin synthesis and action. Neurology1976; 26: 447-50.

27. Hakkarainen H, Vapaatalo H, Gothoni G, Parantainen J Tolfenamic acid is as effectiveas ergotamine during migraine attacks. Lancet 1979; ii 326-28.

1. Abelman WH. Virus and the heart. Circulation 1971; 44: 950-56.2. Heikkila J, Karjalainen J. Evaluation of mild acute infectious myocarditis Br Heart J

1982; 47: 381-91

or signs possibly related to acute myocarditis or pericarditis.In the others, an ECG was taken irrespective of any cardiacsymptoms, in individuals admitted with respiratory or

gastrointestinal infection, on the first three days and twoweeks later. The patients were followed up for 12 months ormore.

Since all the patients were on the right side of 40 years, thepopulation is unlikely to have included many with ischaemicdisease. Thus the data provide a "natural history of disease"for infective illness in the younger age category. It has beenheld3 that myopericarditis usually develops one to two weeksafter the onset of an acute respiratory infection-and indeedthis has seemed to be the case when the question ofmyocardial infarct in older patients, preceded by4 andpossibly precipitated by5 virus infection, has arisen. In theHelsinki series, clinical, electrocardiographic, myocardialenzymatic, and echocardiographic signs of myocardialinvolvement were present from the first few days of infectiveillness. Clinically obvious myopericarditis was usuallycaused by vaccinia, mononucleosis, mycoplasma, chlamydia,or Coxsackie B4 infections. Cardiac involvement inadenovirus and influenza infections was most often detected

by serial ECG screening. In most patients, myocardialdamage was local, reflecting a focus of virus-inducedinflammation. There were several important clinical points.The electrocardiogram of "acute pericarditis" seemed torepresent the initial phase of myocarditis, in view of

subsequent clinical progression. The features of pericarditissometimes cause the more important myocarditis to beoverlooked. Similarly, an isolated ECG tracing mightstrongly suggest acute myocardial infarction if the changeswere local. The ease of confusion in patients in an older age-group was obvious. Myocarditis was suggested by the

presence of clinical and echocardiographic ventricular

asynergy, a third heart sound, early cardiac enzyme release,and subsequent local T-wave inversions. Even in mild

myocarditis, serious cardiac arrhythmias, includingatrioventricular block and ventricular tachycardia, are

possible. The lethal possibilities in such cases are much thesame as in ischaemic myocardial infarction. Thus carefulmonitoring and special cardiac care are appropriate. In themilder clinical picture, without overt cardiac signs, theclinician has to be wary of allowing vigorous exercise duringthe acute phase, since there is some evidence that physicalactivity can exacerbate the local disease and lead to seriouscomplications.’

- Nearly all the Finnish patients recovered completely. Thelong-term prognosis seems good, but it is possible that

myocardial scars remain.6 In view of the number of viralinfections which are not assessed by a doctor, post-myocarditis scarring could be very common indeed.

Continuing ECG abnormalities may be a nuisance. Thesimilarity between the ECG changes of infective myocarditisand those associated with coronary atherosclerosis may leadto dilemmas where military and other personnel, such aspilots, are concerned. Some unfortunates do seem prone tofurther attacks, but whether the explanation lies in

3 Burch GE, Giles TD The role of viruses in the production of heart disease Am JCardiol 1972; 29: 231-40.

4 Nicholls AC, Thomas M Coxsackie virus infection in acute myocardial infarctionLancet 1977; i: 883-84

5. Burch GE, Shewey LL Viral coronary arteritis and myocardial infarction Am Heart J1976; 92: 11-14.

6. Mitchell JRA, Schwartz CJ. The relation between myocardial lesions and coronaryartery disease. Br Heart J 1963, 25: 1

7. Gatmaitan BG, Chason JL, Lerner AM Augmentation of the virulence of the murineCoxsackie virus B3 myocardiopathy by exercise J Exp Med 1970; 131: 1121-36