1209

DRUG TREATMENT OF EPILEPSY

S!R,—I wish to point out an important omission in DrReynolds’ excellent review (Sept. 30, p. 721). Besides the toxi-city of anticonvulsants to the individual patient with epilepsy,the question of teratogenicity of antiepileptic therapy has to beconsidered. Structural malformations and functional anoma-lies have been amply documented in infants whose epilepticmothers received anticonvulsant treatment during pregnancy:phenytoin,’-3 phenobarbitone,4 trimethadione,s 6 and diaze-pam are among the drugs incriminated. Many women areneedlessly kept on such drugs because the necessity for con-tinued treatment has not been evaluated before their pregnan-cies, while others are not advised of the potential risk to theirunborn fetuses from exposure to these teratogenic agents inutero.

,

The need for periodic assessment of young female epileptics(especially in respect of drugs and their continued use); the re-placement of known teratogens by drugs of no, or less, fetaltoxicity, and the provision of genetic counselling to those pa-tients who contemplate pregnancy cannot be overemphasised.Unfortunately, achievement of the above goals is hampered byinadequate information about the relative safety to the fetusor toxicity of anticonvulsant agents, the nature and extent ofthe possible genetic contribution to an interactive aetiology ofthe fetal anomalies observed, and the role of maternal epilepsyper se in causing congenital malformations.8 It is, however,gratifying to note a recent upsurge in monitoring and record-ing specific fetal abnormalities among neonates of epilepticmothers.9

Division of Medical Genetics,Department of Pediatrics,University of Saskatchewan,Saskatoon, Canada S7N 0W8 M. H. K. SHOKEIR

A.C.T.H. IN GUILLAIN-BARRÉ SYNDROMESIR,-The report of Dr Hughes and his colleagues (Oct.

7, p. 750), on a controlled trial of prednisolone in acutepolyneuropathy, was of great interest to us. We embarked onour prospective, randomised, double-blind study of A.C.T.H. inthis disorder’" for many reasons-among them, to see if wecould document an effect on a measurable disease, and, if wecould, then to compare the effect of A.C.T.H. with prednisoneor one of its analogues (to address the age-old question ofwhether A.C.T.H. does something that prednisone does not).One interpretation of a comparison between these two studiesis that A.C.T.H. does have a reparative effect on demyelinatedperipheral nerves that prednisone does not.

Leaving aside detailed comments on the methodology ofHughes’ study (e.g., was bias introduced by excluding patientswho had started to improve before being seen, or by leavingthe decision to ask for patient consent to the physician incharge of each case and how did the withdrawls or irregularretention affect each group?), the point that struck us was thedifference between times of entry in the two studies. Statistical,significance against prednisolone was observed only in patientswho entered Hughes’ study within one week of onset of illness;the mean time to entry of patients receiving A.T.C.H. in our

1. Hanson, J. W., Smith, D. W.J. Pediat. 1975, 87, 285.2. Hanson, J. W., and others ibid. 1976, 89, 662.3. Corcoran, R., Rizk, M. W. Lancet, 1976, ii, 960.4. Seip, M. Acta pædiat. scand. 1976, 65, 617.5. German, J., Kowal, A., Ehlers, K. L. Teratology, 1970, 3, 349.6. Feldman, G. L., Weaver, D. M., Lovrien, E. W. Am. J. Dis. Child. 1977,

131, 1389.7. Czeizel, A. Lancet, 1976, i, 810.8. Shapiro, S., Hartz, S. C., Siskine, V., Mitchell, A. A., Slone, D., Rosenberg,

L., Monson, R. R., Heinonen, O. P. Idänpään-Heikklia, J., Härö, S.,Sazén, L. ibid. p. 272.

9. Smith, D. W. Am. J. Dis. Child. 1977, 131, 1337.10. Swick, H. M., McQuillen, M. P. Neurology, Minneap. 1976, 26, 205.

double-blind trial was 18.4 days, and no patient entered earlierthan 10 days after onset.We concluded that A.C.T.H. had little effect on the acute

(?immune-active) phase of idiopathic polyneuropathy, butseems to promote healing of damaged nerves. Perhaps it ismore correct to hypothesise that steroids are bad for the im-mune system that is trying to do battle with the cause of theillness." Others have started to present data that support a

reparative effect of steroids on chronic inflammatory polyradi-culoneuropathy.12Department of Neurology,Medical College of WisconsinMilwaukee, Wisconsin 53226, U.S.A.

MICHAEL P. MCQUILLENHERBERT M. SWICK

SHOULD ASTHMATIC PATIENTS LAUGH?

SIR,-Dr Gayrard (Nov. 18, p. 1105) may give his patientspermission to laugh, but only on the condition that they do notlaugh too long, thus causing hyperventilation, excess loss ofCO2 and a fall of Paco.. In a 1946 paper on hyperventilationasthma I described this condition and its prevention by experi-mental inhalation of CO2, A little laugh, of course, does noharm, but continuous giggling often does, as can happen inyoung women watching a funny film in a cinema. Similar over-breathing may happen in smaller children with mild asthma,who, for days, do nothing but look forward to a big event likea birthday party. Experienced mothers never tell such childrenof such feasts in advance.2A similar transient loss of CO2 with a resulting low Paco2

may occur during the recovery from a short, sharp exercisesuch as a sprint. This is one type of the so-called exerciseasthma, when the body has lost CO2 by being swamped withlactic acid and the blood requires time to retain again suffi-cient CO2,

I have explained this elsewhere.3-5 If a clinician wants to seeit for himself he should let a patient prone to this disorderrebreathe his own breath through a wide, open rubber tube.This will prevent him losing excess CO2 and thus his hyperven-tilation asthma. But, of course, this experiment is not reallysuitable for girls giggling at the cinema.9 Park CrescentLondon N3 2NL H. HERXHEIMER

PROLACTIN SECRETION IN XYY MALES

SiR,—Dr Benezech and Dr Noel (Oct. 21, p. 899) reportthat two out of six institutionalised XYY males had prolactinlevels substantially higher than normal These increases werenot related to drug therapy and have not been satisfactorilyexplained. It would be interesting to know the nature of anycrimes these men may have committed. In our experience XYYmales in institutions whose prolactin levels have been highhave all committed serious crimes against the person, whereasin XYY males with no criminal convictions the prolactin levelshave not been increased (unpublished).

Benezech and colleagues have also described a fall in serum-prolactin after an injection of T.R.H. in one of their patients.This is remarkable because the normal response is a brisk rise.This finding again raises the possibility that XYY males underdetention have some disturbance of prolactin secretion.M.R.C. Clinical and Population

Cytogenetics Unit,and Department of Medicine,

Western General Hospital,Edinburgh EH4 2XU

W. H. PRICEW. A. CAMPBELL

11. Asbury, A. K., Arnason, B. G., Adams, R. D. Medicine, 1969, 48, 173.12. Dyck, P. J., O’Brien, P. C., Oviatt, K. F., Bastron, J. A., Daube, J. R., Dina-

poli, R. P., Groover, R. V., Stephens, J. C. Ann. Neurol. 1978, 4, 165.1. Herxheimer, H. Lancet, 1946, i, 83.2. Herxheimer, H. Guide to Bronchial Asthma; p. 47. New York, 1975.3. Herxheimer, H. Lancet, 1972, i, 436.4. Herxheimer, H. ibid. i, 906.5. Herxheimer, H. Br. med. J. 1977, ii, 767.6. Benezech, M., Croizet, M., Belabas, M., Mathieu, C., Mathieu, P., Noël, B.,

Ferret-Bouin, P. Ann. Endocr, 1978, 39, 89.