- Email: [email protected]
PARVOVIRUS AND IDIOPATHIC THROMBOCYTOPENIC PURPURA
279
(including the pharmaceutical industry) are more likely to behave responsibly. Viewed in this light, the paucity of epidemics reported by registries reflects success rather than failure. Nevertheless, registries must answer the charge that their response to case-reports of possible teratogenesis is generally slow and inadequate. Mounting the investigations needed is hampered by small numbers and the lack of controls but pooled databases such EUROCAT are trying to overcome the first obstacle. The lack of controls tends to be approached inconsistently: perhaps registries should follow the example of Finland3 and simultaneously collect control data routinely along with index cases. as
Social Paediatric and Obstetnc Research Unit, 1 Lilybank Gardens, Glasgow G12 8RZ
DAVID H. STONE
Wals, Bertrand F, De La Mata I, Lechat MF. Chromosomal anomalies and Chernobyl. Int J Epidemiol 1988. 17: 230-31. 2. EUROCAT Working Group. Preliminary evaluation of the impact of the Chernobyl radiological contamination on the frequency of central nervous system malformations in 18 regions of Europe. Paediatr Perinatal Epidemiol 1988: 2: 1 De
253-64. 3. Saxen L, Klemetti A The Finnish Carol Med 1973: 56: 23-30.
register of congenital malformations. Acta Univ
viruses were tested by ELISA (Behring) in 146 individuals: 73 were patients with coronary atherosclerosis proven by arteriography and 73 were healthy controls. No subject had received blood transfusions (which are a risk factor for CMV infection) or had signs of infectious disease or immunosuppression that could alter the results. The atherosclerotic patients were matched with a control by age, sex, and social background. Seropositivity to CMV in the patients was 90% (66/73) and 14% (10/73) of these had high titres; seropositivity in the controls was 86% (63/73) and 21 % (15/73) showed high titres. Seropositivity to HSV was similar in the patients and in the controls (92% and 93%, respectively). No patients with high titres were detected. The lack of association in our study, in contrast with that of Adams et al,’ could be due to several factors such as the time between the performance of both studies (we have detected lower seroprevalences in previous investigations in another control group2,3); the distinct geographical locations (we have seen differences between seroprevalence to HSV in different places of the same country’); and the different sample sizes. The fact that CMV antigen has been detected in plaques of atheromas and that Adams et al did observe a serological relation justifies more extensive and standardised studies to investigate any
association between atherosclerosis and HSV infection. PARVOVIRUS AND IDIOPATHIC THROMBOCYTOPENIC PURPURA
SIR,-Dr Foreman and colleagues (Dec 17, p 1426) report a case of parvovirus-associated thrombocytopenic purpura and suggest that recent parvovirus infection should be looked for in transient
idiopathic thrombocytopenic purpura (ITP). We have studied 61 sera from patients in the Paris area who had recent and typical ITP. We looked for parvovirus antigen (using sera containing total antibodies) and total anti-parvovirus antibodies (using sera containing parvovirus antigen) by counterimmunoelectrophoresis, and we tested for specific IgM by antibody capture radioimmunoassay. No parvovirus antigen was detected. 3 sera had specific anti-parvovirus IgM, suggesting recent infection. Parvovirus causes aplastic crises in patients with chronic haemolytic anaemia. It is also responsible for fifth disease2 and for vascular purpura.3 Thus, besides the moderate and transitory thrombocytopenia of central origin common during aplastic crisis,4 parvovirus infection may trigger ITP (5% in our series). Parvovirus antigen was not isolated in the 3 IgM-positive cases ITP-but it is never isolated in fifth disease2 and only rarely in aplastic crisis’ because viraemia is transient and may even precede clinical expression of the disease. We agree that the parvovirus serology should be included in virological investigations in ITP. Institut National de Transfusion Sanguine, rue
Alexandre-Cabanel,
75015 Paris, France
J. J. LEFRÈRE A. M. COUROUCÉ C. KAPLAN
1
Serjeant GR, Topley JM, Mason K, et al. Outbreak of aplastic crisis in sickle-cell anaemia associated with parvovirus-like agent. Lancet 1981; ii: 595-97 2. Anderson MJ, Jones SDE, Fischer-Hoch SP, et al. Human parvovirus, the cause of erythema infectiosum (fifth disease)? Lancet 1983; i: 1378. 3 Lefrère JJ, Couroucé AM, Muller JY, et al. Human parvovirus and purpura. Lancet 1985; ii: 730. 4. Lefrère JJ, Couroucé AM, Bertrand Y, et al. Human parvovirus and aplastic crisis in chronic hemolytic anemias: study of 24 observations. Am J Hematol 1986; 23: 271-75.
LACK OF SEROLOGICAL ASSOCIATION BETWEEN HERPESVIRUS AND ATHEROSCLEROSIS
SiR,—To verify the possible relation between atherosclerosis and herpesviruses, Adams et aP did a serological study between 1981 and 1984. They tested antibodies to cytomegalovirus (CMV) and herpes simplex virus (HSV) in 157 men undergoing vascular surgery for atherosclerosis and in matched controls (patients with high cholesterol levels). A higher seroprevalence to CMV was detected in the surgical group, and a significantly greater proportion of surgical cases had high titres of CMV antibodies compared with controls. We did a seroepidemiological study for CMV and HSV in Madrid between January and August, 1988. Antibodies to these
Department of Medicine, University Hospital of San Carlos, and Department of Microbiology, School of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain
M. I. COUR F. J. LOPEZ DE ATALAYA L. PALAU E. FDEZ CONTRERAS C. PEREZAGUA
1. Adam E, Melnick JL, Probtsfield JL, et al High levels of cytomegalovirus antibody in patients requiring vascular surgery for atherosclerosis Lancet 1987, ii: 291-93. 2. Artieda P, Cour MI, Ortega P, González-Sinde MC, Giménez M. Citomegalovirus: prevalencia de anticuepos en un grupo control. Rev Clin Esp 1985; 179: 8-11. 3. Cour MI, López Bartolomé O, Ortega P, et al. Citomegalovirus: un estudio en 4.977 mujeres gestantes y no gestantes. Med Clin (Barc)1988; 90: 225-28. 4. Cour MI, Diéguez RA, Mínguez F. Herpes simplex- estudio seroepidemilógico en Madrid (S Sebastián de los Reyes y Amjeuz) y Toledo (Talavera de la Reina). Enf Infect Microbiol Clin 1988, 6: 190-94. 5. Melnick JL, Petrie BL, Dreesman GR, Burek J, McCollum CH, DeBakey ME. Cytomegalovirus antigen within human arterial smooth muscle cells. Lancet 1983; ii: 644-47
EPSTEIN-BARR VIRUS IN BRAIN AND RASMUSSEN’S ENCEPHALITIS
SIR,-Patients with epileptic focal seizures due to chronic encephalitis were first described by Rasmussen and colleagues (Neurology 1958; 8: 435). The clinical course with hemiconvulsions, hemiplegia, and epilepsy resistant to anticonvulsant therapy was documented as HHE syndrome by Gastaut and colleagues (Epilepsia 1960; 1: 418). A viral aetiology has been suspected but to date only electron microscopic findings of "virus crystals resembling those of enteroviruses" have been found in brain cellsSerological tests for viral antibodies and viral culture of brain tissue and cerebrospinal fluid yielded negative or unspecific localised
results. We report
a
4-year-old boy who had intractable focal
motor
seizures, hemiparesis of the left arm, perioral and periorbital dyskinesias of the left side, and dysarthric and dysphagic disorders. A focus within the right insula was confirmed by electrocorticogram intra-operatively and was resected. The second case was a 22-year-old woman who had complex partial seizures for 9 years. More recently additional intractable convulsions of the right perioral region, the right half of the tongue, and the right hand were seen. Invasive electoencephalogram showed three independent foci in the left hippocampal, angular, and insular regions. The angular focus was resected for diagnostic purposes. In both cases, histological investigation revealed encephalitis with perivascular and diffuse lymphocytic infiltrations and a considerable astrogliosis. In-situ hybridisation with biotin-labelled viral DNA probes, followed by detection with avidin-alkaline phosphatase complexes, showed Epstein-Barr virus (EBV) genome in intranuclear central cores within the encephalitic infiltrations in both cases. Other probes for viruses and Mycoplasma pneumoniae gene gave negative results.
(including the pharmaceutical industry) are more likely to behave responsibly. Viewed in this light, the paucity of epidemics reported by registries reflects success rather than failure. Nevertheless, registries must answer the charge that their response to case-reports of possible teratogenesis is generally slow and inadequate. Mounting the investigations needed is hampered by small numbers and the lack of controls but pooled databases such EUROCAT are trying to overcome the first obstacle. The lack of controls tends to be approached inconsistently: perhaps registries should follow the example of Finland3 and simultaneously collect control data routinely along with index cases. as
Social Paediatric and Obstetnc Research Unit, 1 Lilybank Gardens, Glasgow G12 8RZ
DAVID H. STONE
Wals, Bertrand F, De La Mata I, Lechat MF. Chromosomal anomalies and Chernobyl. Int J Epidemiol 1988. 17: 230-31. 2. EUROCAT Working Group. Preliminary evaluation of the impact of the Chernobyl radiological contamination on the frequency of central nervous system malformations in 18 regions of Europe. Paediatr Perinatal Epidemiol 1988: 2: 1 De
253-64. 3. Saxen L, Klemetti A The Finnish Carol Med 1973: 56: 23-30.
register of congenital malformations. Acta Univ
viruses were tested by ELISA (Behring) in 146 individuals: 73 were patients with coronary atherosclerosis proven by arteriography and 73 were healthy controls. No subject had received blood transfusions (which are a risk factor for CMV infection) or had signs of infectious disease or immunosuppression that could alter the results. The atherosclerotic patients were matched with a control by age, sex, and social background. Seropositivity to CMV in the patients was 90% (66/73) and 14% (10/73) of these had high titres; seropositivity in the controls was 86% (63/73) and 21 % (15/73) showed high titres. Seropositivity to HSV was similar in the patients and in the controls (92% and 93%, respectively). No patients with high titres were detected. The lack of association in our study, in contrast with that of Adams et al,’ could be due to several factors such as the time between the performance of both studies (we have detected lower seroprevalences in previous investigations in another control group2,3); the distinct geographical locations (we have seen differences between seroprevalence to HSV in different places of the same country’); and the different sample sizes. The fact that CMV antigen has been detected in plaques of atheromas and that Adams et al did observe a serological relation justifies more extensive and standardised studies to investigate any
association between atherosclerosis and HSV infection. PARVOVIRUS AND IDIOPATHIC THROMBOCYTOPENIC PURPURA
SIR,-Dr Foreman and colleagues (Dec 17, p 1426) report a case of parvovirus-associated thrombocytopenic purpura and suggest that recent parvovirus infection should be looked for in transient
idiopathic thrombocytopenic purpura (ITP). We have studied 61 sera from patients in the Paris area who had recent and typical ITP. We looked for parvovirus antigen (using sera containing total antibodies) and total anti-parvovirus antibodies (using sera containing parvovirus antigen) by counterimmunoelectrophoresis, and we tested for specific IgM by antibody capture radioimmunoassay. No parvovirus antigen was detected. 3 sera had specific anti-parvovirus IgM, suggesting recent infection. Parvovirus causes aplastic crises in patients with chronic haemolytic anaemia. It is also responsible for fifth disease2 and for vascular purpura.3 Thus, besides the moderate and transitory thrombocytopenia of central origin common during aplastic crisis,4 parvovirus infection may trigger ITP (5% in our series). Parvovirus antigen was not isolated in the 3 IgM-positive cases ITP-but it is never isolated in fifth disease2 and only rarely in aplastic crisis’ because viraemia is transient and may even precede clinical expression of the disease. We agree that the parvovirus serology should be included in virological investigations in ITP. Institut National de Transfusion Sanguine, rue
Alexandre-Cabanel,
75015 Paris, France
J. J. LEFRÈRE A. M. COUROUCÉ C. KAPLAN
1
Serjeant GR, Topley JM, Mason K, et al. Outbreak of aplastic crisis in sickle-cell anaemia associated with parvovirus-like agent. Lancet 1981; ii: 595-97 2. Anderson MJ, Jones SDE, Fischer-Hoch SP, et al. Human parvovirus, the cause of erythema infectiosum (fifth disease)? Lancet 1983; i: 1378. 3 Lefrère JJ, Couroucé AM, Muller JY, et al. Human parvovirus and purpura. Lancet 1985; ii: 730. 4. Lefrère JJ, Couroucé AM, Bertrand Y, et al. Human parvovirus and aplastic crisis in chronic hemolytic anemias: study of 24 observations. Am J Hematol 1986; 23: 271-75.
LACK OF SEROLOGICAL ASSOCIATION BETWEEN HERPESVIRUS AND ATHEROSCLEROSIS
SiR,—To verify the possible relation between atherosclerosis and herpesviruses, Adams et aP did a serological study between 1981 and 1984. They tested antibodies to cytomegalovirus (CMV) and herpes simplex virus (HSV) in 157 men undergoing vascular surgery for atherosclerosis and in matched controls (patients with high cholesterol levels). A higher seroprevalence to CMV was detected in the surgical group, and a significantly greater proportion of surgical cases had high titres of CMV antibodies compared with controls. We did a seroepidemiological study for CMV and HSV in Madrid between January and August, 1988. Antibodies to these
Department of Medicine, University Hospital of San Carlos, and Department of Microbiology, School of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain
M. I. COUR F. J. LOPEZ DE ATALAYA L. PALAU E. FDEZ CONTRERAS C. PEREZAGUA
1. Adam E, Melnick JL, Probtsfield JL, et al High levels of cytomegalovirus antibody in patients requiring vascular surgery for atherosclerosis Lancet 1987, ii: 291-93. 2. Artieda P, Cour MI, Ortega P, González-Sinde MC, Giménez M. Citomegalovirus: prevalencia de anticuepos en un grupo control. Rev Clin Esp 1985; 179: 8-11. 3. Cour MI, López Bartolomé O, Ortega P, et al. Citomegalovirus: un estudio en 4.977 mujeres gestantes y no gestantes. Med Clin (Barc)1988; 90: 225-28. 4. Cour MI, Diéguez RA, Mínguez F. Herpes simplex- estudio seroepidemilógico en Madrid (S Sebastián de los Reyes y Amjeuz) y Toledo (Talavera de la Reina). Enf Infect Microbiol Clin 1988, 6: 190-94. 5. Melnick JL, Petrie BL, Dreesman GR, Burek J, McCollum CH, DeBakey ME. Cytomegalovirus antigen within human arterial smooth muscle cells. Lancet 1983; ii: 644-47
EPSTEIN-BARR VIRUS IN BRAIN AND RASMUSSEN’S ENCEPHALITIS
SIR,-Patients with epileptic focal seizures due to chronic encephalitis were first described by Rasmussen and colleagues (Neurology 1958; 8: 435). The clinical course with hemiconvulsions, hemiplegia, and epilepsy resistant to anticonvulsant therapy was documented as HHE syndrome by Gastaut and colleagues (Epilepsia 1960; 1: 418). A viral aetiology has been suspected but to date only electron microscopic findings of "virus crystals resembling those of enteroviruses" have been found in brain cellsSerological tests for viral antibodies and viral culture of brain tissue and cerebrospinal fluid yielded negative or unspecific localised
results. We report
a
4-year-old boy who had intractable focal
motor
seizures, hemiparesis of the left arm, perioral and periorbital dyskinesias of the left side, and dysarthric and dysphagic disorders. A focus within the right insula was confirmed by electrocorticogram intra-operatively and was resected. The second case was a 22-year-old woman who had complex partial seizures for 9 years. More recently additional intractable convulsions of the right perioral region, the right half of the tongue, and the right hand were seen. Invasive electoencephalogram showed three independent foci in the left hippocampal, angular, and insular regions. The angular focus was resected for diagnostic purposes. In both cases, histological investigation revealed encephalitis with perivascular and diffuse lymphocytic infiltrations and a considerable astrogliosis. In-situ hybridisation with biotin-labelled viral DNA probes, followed by detection with avidin-alkaline phosphatase complexes, showed Epstein-Barr virus (EBV) genome in intranuclear central cores within the encephalitic infiltrations in both cases. Other probes for viruses and Mycoplasma pneumoniae gene gave negative results.