594

Case 3.-This 2-year-boy was admitted with a 4-day historyof fever, upper respiratory infection, and vomiting. A few hoursbefore admission he became unconscious. There was a historyof recurring focal fits. Haemogram, total and differential, blood-proteins, blood-sugar, and complete spinal-fluid examinationwere normal. Blood-urea and S.G.O.T. were significantly raised.At necropsy there was massive fatty change in liver and kidneysassociated with cerebral cedema (1225 g.). The right temporallobe contained 3 necrotising granulomas (negative for fungi andacid-fast bacilli) histologically compatible with cerebral cysticer-cosis, which is an endemic disease in this part of India. Clinically,a possibility of Reye’s syndrome was considered but excludedbecause of uncharacteristic focal neurological signs. At necropsythese related to the focal lesions in the right temporal lobe. Whileit is debatable whether this was a case of Reye’s syndrome therewas an association of fatty viscera and neurological lesions.

All three cases had several interesting common features.They were in the same age-group, had a short history offatal illness, massive fatty change in liver and kidneys inabsence of gross malnutrition and structural or functionalneurological lesions. Whether they were Reye’s syndromeor not is probably a matter of semantics, but in our opinionthe alternative possibility of pathogenesis of Reye’s syn-drome (neurologic lesions primary and visceral fatty changesecondary) deserves at least equal consideration.

Departments of Pediatrics andPathology,

Postgraduate Institute of MedicalEducation and Research,

Chandigarh, India.

ARVIND G. BHAGWATR. CHANDRASEKHARANC. K. BANERJIV. KUMAR.

FENFLURAMINE AND DREAMING

SIR,-An association between fenfluramine and dreaminghas previously been reported,l.2 and we now have furtherevidence of this, which was obtained during the course of aweight-reducing investigation.

Eight obese patients (age range 22-26 years) were treatedwith fenfluramine in daily doses varying from 20 mg. to60 mg. during a period of from 1 to 20 weeks. Five of the

patients complained of unpleasant dreams which weredescribed as being especially vivid. Two described theirdreams as " nightmares ", and the other patients statedthat their dreams were terrifying. The frequency of dream-ing varied from three to seven times per week. Previousto fenfluramine therapy the patients rarely dreamed. Whenfenfluramine was withdrawn dreaming ceased in all thepatients. The effect of fenfluramine on dreaming may bedose related. Of three patients on 20 mg. fenfluraminedaily, only one reported dreaming, whereas of four patientson 60 mg. daily, three complained of dreaming. Fourother patients, who were on a weight-reducing diet alone,did not report any change in their dreaming pattern.Dreaming occurs during the paradoxical phase of

sleep.3 The proportion of time spent in paradoxical sleepvaries at different ages, from 50% at birth, decreasing to20-25% of total sleeping-time in adults. 4,5 5 Lewis et al. 8

have shown that administration of 40 mg. of fenfluraminedid not alter the proportion of time spent as paradoxicalsleep, throughout the night. However, paradoxical sleepwas reduced when the patients were receiving 80 mg. daily.They noted that more frequent spontaneous shifts to

stage-1 sleep or to wakefulness, described as intra-sleeprestlessness, occurred when 80 mg. of fenfluramine werebeing administered daily. It therefore seems that althoughpatients may not spend more time in paradoxical sleep

1. Hooper, A. C. Br. med. J. 1971, iii, 305.2. Oswald, I. ibid. 1971, iii, 70.3. Dewent, W., Kleitman, N. J. J. exp. Psychol. 1957, 53, 339.4. Fisher, C. J. Am. Psychoanal. Ass. 1965, 13, 197.5. Roffwerg, H. P., Muzio, J. N., Dewent, W. C. Science, 1966, 152,

604.6. Lewis, S. A., Oswald, I. Br. med. J. 1971, iii, 67.

while on fenfluramine, they are more aware of their dreamsdue to the intra-sleep restlessness. This is supported bythe observation that dreaming seems predominantly to beassociated with daily doses of fenfluramine in the region of60 mg.Department of Pharmacology,

University of Dublin,Trinity College,Dublin 2, Ireland.

ANN MULLENC. W. M. WILSON.

WEATHER AND MYASTHENIC FATIGUE

Sir share Professor Simpson’s view (Aug. 24, p. 458)that Dr Borenstein and Professor Desmedt are surelymistaken in thinking " that temperature and weathercorrelates of myasthenic weakness have not been recog-nised previously ".

In keeping with his own observations, I particularlyrecollect an airman who was brought into hospital duringthe 1939-45 war, suffering from very severe sunburn.He was a myasthenic who had been lying sunbathing andhad become so weak that he was unable to get up and moveinto the shade.

152 Harley Street,London W1N 1HH. ERIC C. O. JEWESBURY.

LITHIUM, EBSTEIN’S ANOMALY, AND OTHERCONGENITAL HEART DEFECTS

SiR,-Studies on the possible teratogenicity of lithiumhave yielded conflicting results. Animal studies 1,2 revealteratogenic effects in mice and rats. Johansen suggestedthat not all rat strains are susceptible. The Register ofLithium Babies has been reviewed, revealing 9 childrenin 118 with major malformations.4 4 This was not con-sidered conclusive evidence of teratogenicity.We have encountered the improbable occurrence of 2

infants who presented in the first hours of life with severecyanosis, cardiomegaly, and a quadruple rhythm. Both ofthese infants were demonstrated to have Ebstein’s anomalyat cardiac catheterisation, and both mothers had takenlithium throughout the first trimester of their pregnancies.The frequency of Ebstein’s anomaly is approximately

1 in 20,000 total births in our population. Lithium exposureduring the two years in which these 2 patients were ascer-tained was recorded only in these 2 instances out of 733teratogenic histories obtained. Although the chance occur-rence of the only 2 patients among 733 who took lithiumhaving infants with such a rare cardiac anomaly is remote, itdoes remain an alternative explanation of our finding.What was not emphasised in the report from the register,4

was the finding that 6 of the 118 lithium babies had con-genital cardiovascular diseases, including ventricular

septal defect, mitral atresia, coarctation of the aorta,

tricuspid atresia, and 2 cases of Ebstein’s anomaly. Thisis a five-fold increase over the expected frequency for

congenital heart-disease. More striking is the recognitionthat 3 infants had tricuspid malformations, 2 of whichwere Ebstein’s anomaly (which represents a 400-foldincrease over the expected frequency).Thus 8 of 120 patients in whom there was exposure to

lithium in the first trimester produced infants with con-genital heart-disease. 4 of these infants had the rare

Ebstein’s anomaly. Although lithium exposure may notbe attended by the high risk of a drug such as thalidomide,our data, taken with that of the register, makes it difficultto deny an setiological relationship in susceptible indi-

1. Szabo, K. T. Lancet, 1969, ii, 849.2. Wright, T. L., Hoffman, L. H., Davies, J. ibid. 1970, ii, 876.3. Johansen, K. T. ibid. 1971, i, 1026.4. Schou, M., Goldfield, M. D., Weinstein, M. R., Villeneuve, A

Br. med. J. 1973, ii, 135.