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      Antenatal and Postnatal Diagnosis of Coxsackie B4 Infection: Case Series

      case-report
      , M.D., F.R.C.S.C. 1 , , M.D., F.R.C.S.C. 1 , , M.D., F.R.C.S.C. 1 , , M.D., F.R.C.P.C. 2 , , M.D., Ph.D., F.R.C.P.C. 2
      AJP Reports
      Thieme Medical Publishers
      coxsackie B virus, hydrops, myocarditis, cerebritis, ventriculitis

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          Abstract

          Enteroviruses are a common cause of neonatal infection. In particular, Coxsackie B viruses are often associated with severe, fatal disease. The antenatal diagnosis of Coxsackie B viral infections is uncommon. We present a unique case of Coxsackie B4 virus ventriculitis and myocarditis causing fetal hydrops at 22 weeks gestation. Transmission was inferred by viral isolation from the amniotic fluid and by placental pathology. We also describe two additional cases of fatal neonatal Coxsackie B4 infection complicated by myocarditis and encephalitis with cerebral necrosis in a 4-day-old female and by myocarditis, spinal leptomeningitis, and hepatitis in a 4-day-old male. Transplacental acquisition of infection carries a poor prognosis. We propose that Coxsackie B virus should be considered in the investigation of nonimmune hydrops, particularly in the presence of cardiac dysfunction.

          Most cited references28

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          Coxsackievirus B3 and the neonatal CNS: the roles of stem cells, developing neurons, and apoptosis in infection, viral dissemination, and disease.

          Neonates are particularly susceptible to coxsackievirus infections of the central nervous system (CNS), which can cause meningitis, encephalitis, and long-term neurological deficits. However, viral tropism and mechanism of spread in the CNS have not been examined. Here we investigate coxsackievirus B3 (CVB3) tropism and pathology in the CNS of neonatal mice, using a recombinant virus expressing the enhanced green fluorescent protein (eGFP). Newborn pups were extremely vulnerable to coxsackievirus CNS infection, and this susceptibility decreased dramatically by 7 days of age. Twenty-four hours after intracranial infection of newborn mice, viral genomic RNA and viral protein expression were detected in the choroid plexus, the olfactory bulb, and in cells bordering the cerebral ventricles. Many of the infected cells bore the anatomical characteristics of type B stem cells, which can give rise to neurons and astrocytes, and expressed the intermediate filament protein nestin, a marker for progenitor cells. As the infection progressed, viral protein was identified in the brain parenchyma, first in cells expressing neuron-specific class III beta-tubulin, an early marker of neuronal differentiation, and subsequently in cells expressing NeuN, a marker of mature neurons. At later time points, viral protein expression was restricted to neurons in specific regions of the brain, including the hippocampus, the entorhinal and temporal cortex, and the olfactory bulb. Extensive neuronal death was visible, and appeared to result from virus-induced apoptosis. We propose that the increased susceptibility of the neonatal CNS to CVB infection may be explained by the virus' targeting neonatal stem cells; and that CVB is carried into the brain parenchyma by developing neurons, which continue to migrate and differentiate despite the infection. On full maturation, some or all of the infected neurons undergo apoptosis, and the resulting neuronal loss can explain the longer-term clinical picture.
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            The coxsackievirus-adenovirus receptor protein as a cell adhesion molecule in the developing mouse brain.

            In an attempt to elucidate the molecular mechanisms underlying neuro-network formation in the developing brain, we analyzed 130 proteolytic cleavage peptides of membrane proteins purified from newborn mouse brains. We describe here the characterization of a membrane protein with an apparent molecular mass of 46 kDa, a member of the immunoglobulin superfamily of which the cDNA sequence was recently reported, encoding the mouse homologue of the human coxsackievirus and adenovirus receptor (mCAR). Western and Northern blot analyses demonstrated the abundant expression of mCAR in the mouse brain, the highest level being observed in the newborn mouse brain, and its expression was detected in embryos as early as at 10. 5 days post-coitus (dpc), but decreased rapidly after birth. On in situ hybridization, mCAR mRNA expression was observed throughout the newborn mouse brain. In primary neurons from the hippocampi of mouse embryos the expression of mCAR was observed throughout the cells including those in growth cones on immunohistochemistry. In order to determine whether or not mCAR is involved in cell adhesion, aggregation assays were carried out. C6 cells transfected with mCAR cDNA aggregated homophilically, which was inhibited by specific antibodies against the extracellular domain of mCAR. In addition to its action as a virus receptor, mCAR may function naturally as an adhesion molecule involved in neuro-network formation in the developing nervous system.
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              Prognosis for neonates with enterovirus myocarditis.

              To assess the severity of the disease and the long-term cardiac prognosis for neonates who developed enterovirus (EV) myocarditis within the first weeks of life. Clinical presentation, echocardiographic and ECG findings and the outcome of seven infants with EV myocarditis admitted to the intensive care unit are reported. Additionally, 28 previously reported cases are described. Seven neonates presented with cardiac failure within 17 days after birth requiring respiratory and circulatory support. Echocardiography showed dilatation and severe dysfunction of the left ventricle in all and mitral regurgitation in six. In six patients the echocardiographic pattern resembled myocardial infarction. ECG showed complete loss of the R-wave and a new Q-wave in the left precordial leads in all. Two infants died and five developed long-term cardiac sequelae requiring medication. In all survivors aneurysm formation in the left ventricular wall was found weeks to months later. One patient is awaiting heart transplantation. Coxsackie virus B was detected in blood, cerebrospinal fluid, nasopharyngeal swab or stool by PCR or culture. The mortality of previously described neonates combined with our seven cases was 31% (11/35). Among the survivors 66% (16/24) developed severe cardiac damage. Only 23% (8/35) of the infants fully recovered. EV myocarditis is a rare but severe disease in the neonatal period, which often leads to death or results in serious chronic cardiac sequelae like chronic heart failure, aneurysm formation within the left ventricle and mitral regurgitation. Chronic cardiac drug therapy is necessary in the majority of these patients.
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                Author and article information

                Journal
                AJP Rep
                AJP Rep
                AJP Reports
                Thieme Medical Publishers (333 Seventh Avenue, New York, NY 10001, USA. )
                2157-6998
                2157-7005
                25 November 2011
                November 2012
                : 2
                : 1
                : 1-6
                Affiliations
                [1 ]Department of Obstetrics and Gynaecology
                [2 ]Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada
                Author notes
                Address for correspondence and reprint requests Jennifer C. Hunt, M.D., F.R.C.S.C. Department of Obstetrics and Gynaecology, Women's Hospital Room WS125, 735 Notre Dame Avenue, Winnipeg, Manitoba, R3E 0L8Canada drjenhunt@ 123456gmail.com
                Article
                02001
                10.1055/s-0031-1296027
                3653513
                23946895
                7a9ca84a-c2b0-4db2-b96d-1f9bb652356a
                © Thieme Medical Publishers
                History
                : 28 July 2011
                : 27 August 2011
                Categories
                Article

                coxsackie b virus,hydrops,myocarditis,cerebritis,ventriculitis

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