Journal of Infection (I982) 5, 93-95
CASE REPORT Cytomegalovirus infection in pregnancy with maternal hepatitis, neurological disease and foetal chondrodysplasia punctata E. Walker, I. W. P i n k e r t o n a n d F. Sharp*
University Department of Infectious Diseases, Ruchill Hospital, Glasgow G2o 9NB Summary A woman in early pregnancy with active cytomegalovirus infection developed hepatitis, a psychiatric illness, and a prolonged peripheral neuropathy with some evidence of upper motor neurone damage. The foetus delivered at 20 weeks gestation showed evidence of chondrodysplasia punctata (Conradi-Hunermann type). The relationship of the infection to the woman's illness and its possible role in the aetiology of chondrodysplasia punctata are discussed.
Case report T h r e e weeks after a m o n t h ' s visit to her h o m e in Central Africa, a 24-year-old primigravida, six weeks pregnant, developed vomiting and recurrent epigastric pain. She was p r e s c r i b e d prochlorperazine and then metoclopramide. She had no previous history of serious illness or k n o w n family history of congenital abnormalities. T w o weeks later she became jaundiced. Investigations s h o w e d a normal white cell, platelet count and blood film, with no malarial parasites, spherocytes or sickling. T h r o m b o t e s t was IO per cent of normal. S e r u m bilirubin was 75 retool/l, A S T I5O i.u./1, A L T Io6o i.u./l. Hepatitis B surface antigen was not detected. Hepatitis A antibody was only of I g G class. T o x o p l a s m a and Paul Bunnell tests were negative. C M V antibody titres are described below. Over four weeks liver function r e t u r n e d to normal b u t she then became agitated, disorientated and confused. She developed horizontal nystagmus, especially to the right, ataxia of left arm, p o w e r loss in arms and legs with rapid loss of muscle bulk, absent knee jerks, ankle jerks and bilateral extensor plantar reflexes. Sensation was r e d u c e d to touch below b o t h mid thighs. Cerebrospinal fluid examination was normal. T r y p a n o s o m e s were not seen. A n electroencephalogram showed m i n o r excess of slow activity b u t no focal or definite diagnostic features. E l e c t r o m y o g r a p h y and nerve conduction studies s u p p o r t e d a diagnosis of peripheral n e u r o p a t h y b u t absent fibrillation potentials suggested i m p r o v e m e n t was likely. T o t a l I g M was raised. Other s e r u m i m m u n o g l o b u l i n s were normal. S e r u m vitamin B I2, folate, and thyroid studies were normal. Serology for syphilis and screening of s e r u m and urine for p o r p h y r i a were negative. R e p e a t e d serology for a wide range of viral and Formerly Senior Lecturer, Department of Midwifery, University of Glasgow. oi63-4453/82/o4oo93 +o4 $o2.oo/o
© I982 The British Society for the Study of Infection
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E. W A L K E R , I. W. P I N K E R T O N
AND F. S H A R P
parasitic infections showed no diagnostic titres other than a rise in c o m p l e m e n t fixation a n t i b o d y to C M V f r o m a titre of ~28 to I024. I g M specific for C M V was present. Cytomegalovirus was isolated from cervix b u t not from C S F , throat or urine. T h e patient's mental state i m p r o v e d sufficiently for the risk of foetal infection to be discussed and pregnancy was terminated at 2o weeks. C o r d blood s h o w e d I g G b u t not I g M antibody to C M V . A u t o p s y on the foetus showed no histological evidence of infection and virus was not cultured from tissues or placenta. H o w e v e r , radiographs showed chondrodysplasia punctata ( C o n r a d i - H u n e r m a n n type), with extensive abnormal calcification of cartilage (Plate I).
F u r t h e r i m p r o v e m e n t in the m o t h e r was slow. T w o years later she was slightly unstable on standing, with absent ankle jerks and diminished vibration sense in the right leg. H o w e v e r intellectual function was satisfactory and she was able to p e r f o r m m o s t normal activities. Discussion
Hepatitis in adults with cytomegalovirus infection is well d o c u m e n t e d . N e r v o u s system involvement is rare (except in the foetus) b u t encephalopathy has been r e p o r t e d in b o t h the immunologically normal and the i m m u n o s u p p r e s s e d . 1 Peripheral n e u r o p a t h y of Guillain Barr6 type occurs 2 b u t central and peripheral nervous system involvement is unusual. T h e s e features which occurred in this patient m a y have been unrelated to the C M V infection b u t extensive tests s h o w e d no other explanation. N o blood was available prior to the maternal illness so as to determine w h e t h e r the C M V infection was p r i m a r y or a reactivation. Rising antibody titres, specific I g M and g r o w t h of C M V from cervix are compatible with both. H o w e v e r the presence of specific I g M w h e n tested for b y immunofluorescence as in this case m a y be m o r e suggestive of p r i m a r y infection. T h e cause of chondrodysplasia punctata is not fully understood. Genetical influences are well established and environmental influences have been postulated. 3 D r u g s such as warfarin m a y be involved 4 and infection remains a possible aetiological factor. In this case prochlorperazine and m e t o c l o p r a m i d e were administered to the m o t h e r at a r o u n d the sixth week of pregnancy. T h e s e drugs do not so far appear to have been associated with this disease. T h e r e is evidence from this c o u n t r y that primary C M V infection is m o r e likely than reactivation to result in foetal abnormality, while the results of studies elsewhere are conflicting. 5 H o w e v e r foetal infection with C M V is usually protracted 6 and here none was d e m o n s t r a t e d I6 weeks after the maternal illness began. A transient foetal infection with foetal damage h o w e v e r remains a possibility. It has been postulated that the teratogenic effect of warfarin resulting in chondrodysplasia punctata m a y be linked to bleeding into cartilage at a critical stage in development. 7 A t h r o m b o test level of IO per cent normal was recorded during the m o t h e r ' s hepatitis w h e n she was approximately eight weeks pregnant, and this is the level r e c o m m e n d e d for satisfactory anticoagulation with warfarin. Foetal bleeding could have occurred.
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95
(We acknowledge with thanks the assistance of the Regional Virus L a b o r a t o r y and Bacteriology D e p a r t m e n t at Ruchill Hospital, D r J. O ' H . T o b i n , former Director, Public Health L a b o r a t o r y , Oxford and D r W. M. Fyfe, Paediatrician at Stobhill Hospital, Glasgow. Also D r A. M. Gibson, D e p a r t m e n t of Pathology, Royal Hospital for Sick Children, Glasgow for examination of the foetus and for the photographs.)
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References Phillips CA, Fanning WL, Gump DW, Phillips CF. Cytomegalovirus encephalitis in immunologically normal adults. 37,434.4 1977; 238: 2299-2300. Arnold AG, Lawrence DS, Corbitt G. Cytomegalovirus infection and the Guillain Barr6 syndrome. Postgrad Med 37, 1978; 54 (628): I I2-I I4. Spranger TW, Opitz JM, Bidder V. Heterogenecity of chondrodysplasia punctata. Humangenetik, 1971; I I : I90--212. Whitfield MF. Chondrodysplasia punctata after warfarin in early pregnancy. Arch Dis Child 198o; 55: 139-142. Grant S, Edmond E, Syme J. A prospective study of cytomegalovirus infection in pregnancy. Laboratory evidence of congenital infection following maternal primary and reactivated infection. 37 Infect 1981 ; 3 : 24-3 i. MacDonald H, Tobin J O'H. Congenital cytomegalovirus infection, a collaborative study on epidemiological, clinical and laboratory findings. Devl 34ed Child Neur 1978; 2o (4): 471-482. ShaulWL, EmeryH, HallJG. Chondrodysplasia punctata and maternal warfarin use during pregnancy. Am 37 Dis Child 1975; 129: 360-362.