Ventriculitis in congenital rubella: ultrasound demonstration

A female infant with proven congenital rubella infection was referred for cranial ultrasound examination. Intraventricular strands and debris with periventricular echogenic foci were demonstrated. These findings, typical of ventriculitis, have not previously been reported in congenital rubella. Mental retardation is the rule in symptomatic cases and therefore early recognition of central nervous system involvement is of benefit in assessing the long-term neurodevelopmental outcome.     

Sonography of subependymal cysts in congenital rubella syndrome

Two newborns with congenital rubella syndrome are reported. Cranial sonography demonstrated bilateral cystic lesions in the subependymal germinal matrix. Congenital rubella and cytomegalovirus (CMV) infections are the most common proven causes of subependymal cysts of nonhaemorrhagic origin in the newborn. The sonographic detection of these cysts should prompt an intensive search for congenital viral infectionsAbbreviations ABR auditory brainstem response - CMV cytomegalovirus - CT computed tomography - HAI Haemagglutination inhibition test - RV rubella virus - SEH subependymal haemorrhage     

Congenital cytomegalovirus infection with osteolytic lesions: use of DNA hybridization in diagnosis

A case of congenital cytomegalovirus (CMV) infection with long-bone lesions is presented. The bone lesions consisted of broad regions of generalized osteopenia with irregular fragmentation and spiculization at the zone of provisional calcification. Diagnosis of CMV infection was made by DNA spot hybridization of the urine sediment to DNA from the Towne strain of CMV, demonstrating the usefulness of DNA hybridization for identification of CMV in clinical specimens. Bone lesions associated with congenital CMV infection are useful early clues to diagnosis but can be indistinguishable from those of congenital rubella syndrome.     

Prevalence of rubella virus and cytomegalovirus infections in suspected cases of congenital infections

Although rubella virus and cytomegalovirus (CMV) are important causes of congenital infections, information on their prevalence in our country is scarce. We studied a total of 249 infants suspected of having congenital infections from January 1988 to September 1989. Serum samples of these infants were tested for rubella and cytomegalovirus specific IgM antibodies by mucapture ELISA. Thirty (12%) infants were positive for rubella IgM antibody, and 50 (20%) had CMV specific IgM antibody. In the group presenting with hepatosplenomegaly (n=56) rubella and CMV specific IgM antibodies were detected in 1 (1.7%) and 25 (44.6%) infants respectively. In the group presenting with congenital malformations (n=90), 23 (25.5%) were positive for rubella, and only 9 (10%) had CMV IgM antibodies. Of the infants presenting with mental retardation (n=39), only CMV infection was detected in 3 (7.7%) infants, whereas amongst the group showing intrauterine growth retardation (n=16), 5 (31.25%) had CMV specific IgM antibodies and 2 (12.5%) had rubella specific IgM antibodies. In the miscellaneous group (n=48), 4 (8.3%) and 8 (16.6%) infants had rubella and CMV IgM antibodies respectively. CMV infection was prevalent in a significantly higher number of children with hepatosplenomegaly than rubella while in infants with congential malformations a significantly higher number had rubella infection. It is concluded that rubella and CMV infections are commonly seen in children with intrauterine infections in our population.     

Rubella and cytomegalovirus (CMV) infections: laboratory aspects of investigation of antenatal, congenital, persistent, and subclinical infections

Rubella specific IgM tests carried out on pregnant women with history of rubella contact or rubella-like rash indicated the presence of rubella-IgM by the second week after contact, persistence to 3-4 weeks followed by a decline and non-detectability around 8-9 weeks and at delivery. Laboratory investigation of cases of rubella infection in infants and children, including clinically proven and suspected congenital rubella revealed distinct patterns of combinations of positivity and negativity of IgM and IgG antibodies. Three cases of persistence of rubella specific IgM antibodies with one even up to 3 years in congenital rubella and a case of CMV-IgM persistence in congenital CMV are described. Rubella-IgM and CMV-IgM were detected in the serum of two patients aged 12 years and 24 years with CMV mononucleosis. Utilization of rubella-IgM/CMV-IgM tests enabled the identification of four cases of subclinical rubella and one of subclinical CMV in a pediatric population.     

Non calcific vasculopathy in the basal ganglia.

Stripes of high echogenicity in the basal ganglia of infants have been rarely observed on cerebral ultrasound. These lesions, which appear to be due to a non calcific vasculopathy, are caused, in the majority of cases, by congenital infections and trisomy 13. We describe four infants with the characteristic ultrasonic appearance of this vasculopathy. Two children had cytomegalovirus (CMV) infection, one a human immunodeficiency virus (HIV) infection. The fourth child who presented a malformation of the skull and eye anomalies had no definitive diagnosis. Of the three surviving children one was developing normally. One had mild and one severe psychomotor retardation.     

Sonographic follow-up studies in purulent meningitis and its complications in infancy

In 29 newborns and 18 infants ill with meningitis the following characteristic signs visible by sonographic examination of the brain mostly indicated complications: increase of the leptomeningeal echogenicity, increase of the periventricular echogenicity in ventriculitis, alterations of the configuration of the ventricles, typical echos in the CNS-fluid by increased cell and protein content, alterations of the Plexus chorioideus caused by inflammation, membranes in the enlarged ventricular system. In the first year of life the sonographic examination of the brain is ideal for early diagnosis of possible complications in meningitis to change the therapeutic management without any loss of time.     

A practical guide to the diagnosis of congenital infections in the newborn infant

Every attempt should be made to identify an etiologic agent in infants with suspected congenital infection. Some of the infections are treatable, such as herpes simplex, syphilis, and toxoplasmosis. For other infectious agents (i.e., CMV and rubella), close follow-up will enable early detection of hearing impairment and permit early educational intervention. In addition, appropriate isolation measures will reduce the risk of nosocomial infections due to herpes simplex, rubella, hepatitis B, and CMV. Rational use of the available diagnostic tools will enable detection of most symptomatic congenitally infected neonates at a reasonable cost.     

Relation between neuroradiological findings and upper limb function in hemiplegic cerebral palsy

The relation between neuroradiological findings and upper limb function was examined in 53 children with hemiplegic cerebral palsy (CP). CT and MRI images of the children were classified into four groups (malformations, periventricular lesions, congenital cortical–subcortical lesions and postnatally acquired lesions). Additionally, each single affected neuroanatomical structure was noted. Clinical assessments included measures of activity (Melbourne Assessment of Unilateral Upper Limb Function and House Classification) and body functions (motor and sensory impairments). Comparative statistics and correlation analysis were used. Three children had a malformation, 28 a periventricular lesion, 14 a cortical–subcortical lesion and eight a postnatally acquired lesion. Children with periventricular lesions obtained the best motor functioning. Within this group, children with pure periventricular lesions performed significantly better compared to mixed lesions. The differences between congenital cortical–subcortical lesions and acquired lesions were not significant. Results further showed that middle cerebral artery infarctions and basal ganglia/thalamic lesions were significantly correlated to a worse performance. The type of lesion determined by the timing of the brain insult, and the location of the lesion distinguish children with hemiplegic CP regarding upper limb function. These insights are valuable for prognosis and may contribute to a better delineation of therapeutic interventions.     

先天性巨细胞病毒感染抗病毒治疗的效果和安全性观察

目的：观察更昔洛韦（GCV）和（或）缬更昔洛韦（VGCV）治疗先天性巨细胞病毒（ CMV）感染患儿的疗效和不良反应。 方法：回顾性纳入2012年3月1日至2017年5月31日在复旦大学附属儿科医院（我院）新生儿科住院、确诊为先天性CMV感染的患儿,随访至2017年12月31日。从病史资料中提取患儿的一般资料,抗CMV治疗的药物和疗程,新生儿期及1、 3和6月龄的肝脾触诊检查结果、胆红素和肝功能检查指标、CMV抗体和DNA检测结果、颅脑MRI、眼底检查结果和听力检测结果,治疗期间药物的不良反应。根据抗病毒治疗与否以及疗程长短分组,比较各组的临床特征和治疗反应。 结果：28例先天性CMV感染患儿进入本文分析,其中早产儿11例,男17例;无症状/轻度症状9例,未予抗病毒治疗;中重度症状19例,GCV和（或）VGCV治疗≤6周组11例,治疗6个月组8例。①6月龄时,除1例胆汁酸轻度升高外27例中枢神经系统以外的症状和体征、胆红素、肝功能和血常规均恢复正常。②无症状／轻度症状组1例在6月龄时出现左侧听力中度损失。治疗≤6周组中,2例CMV相关眼底病变于1月龄时消失; 颅脑MRI异常信号和听力损失者各5例,6月龄时分别有3例和2例无改善。治疗6个月组中,4例先天性CMV感染相关视网膜病变在随访中均消失;3例头颅MRI异常信号者和7例有听力损失者,6月龄时分别有2例和1例无改善。③治疗≤6周组和治疗6个月组在6月龄时中枢神经系统病变改善情况差异无统计学意义。④治疗过程中未发现与GCV和VGCV应用相关的粒细胞减少和肝功能异常。 结论：抗病毒治疗能改善感音神经性耳聋和脉络膜视网膜炎,GCV和（或）VGCV≤6周与6个月的治疗效果相近;建议对无临床症状先天性CMV感染患儿行眼底检查、脑干诱发电位和头颅MRI检查。     

Congenital rubella syndrome in a child born to Liberian refugees: clinical and public health perspectives

We describe a case of congenital rubella syndrome with typical stigmata in an infant born in New Hampshire to Liberian refugees. The infant's clinical specimens were tested for rubella. Rubella immunity status was sought for contacts. The infant's specimen cultures grew wild-type rubella virus; serum immunoglobulin M and G were positive. Eighteen of 20 contacts were rubella-immune. Family's transit history, mother's vaccination history, and infant's estimated gestational age supported congenital infection acquired overseas. Clinicians should maintain vigilance for congenital rubella syndrome in infants with relevant stigmata, particularly those whose mothers are from countries with nonexistent or recently implemented rubella vaccination programs.     

Congenital rubella infection after previous immunity of the mother

A newborn boy was admitted with a congenital rubella infection. Seven years previously his mother had been vaccinated against rubella; 3 years previously rubella immunity had been confirmed. Therefore, intrauterine transmission must have occurred after maternal reinfection during pregnancy. Prenatal diagnosis of rubella embryopathy with serological methods after subclinical maternal reinfection is nearly impossible.Abbreviations ABR auditory brainstem response - CMV cytomegalovirus - CSF cerebrospinal fluid - EBV Epstein-Barr virus - EIA enzyme-linked immunoassay - HAI haemagglutination inhibition test - WBC white blood cell count     

Generation of periventricular leukomalacia by repeated umbilical cord occlusion in near-term fetal sheep and its possible pathogenetical mechanisms

Periventricular leukomalacia (PVL) is a major cause of cerebral palsy. However, pathogenetic mechanisms of PVL have not been fully understood. Although it has been postulated that umbilical cord compression is related to the development of PVL, no animal experiments clearly demonstrated an association of umbilical cord occlusion with 'periventricular' white matter lesions. The purpose of this study is to determine whether umbilical cord occlusions could produce periventricular white matter lesions in fetal sheep and to examine how changes in fetal cardiovascular and metabolic variables are related to the induction of brain damage. Fourteen near-term fetal sheep underwent umbilical cord occlusion (3-min total cord occlusions 5 times at 5-min intervals). Dissections performed 24 h after cord occlusion revealed that periventricular white matter lesions were produced in 7 out of 14 sheep fetuses. According to the pattern of brain damage, we classified the fetal sheep into three groups: 5 fetuses with dominant lesions in the periventricular white matter (group I), 4 fetuses with brain lesions in the cerebral cortex and thalamus (group II) and 5 fetuses with no or minimal brain lesions (group III). Group I showed higher blood pressure and higher plasma lipid peroxide levels before cord occlusion compared to the other groups, while group II showed systemic hypotension during cord occlusion. No significant differences in changes in pH, PaCO2, PaO2 and heart rate were found between the three groups. It is speculated that PVL might be produced by an association of preexisting chronic circulatory instability with an acute episode of severe repetitive cord occlusion.     

Neuroimaging findings (ultrasonography,CT, MRI) in 3 infants with congenital rubella syndrome

Neuroimaging observations of three infants with congenital rubella syndrome are reported. We have observed congenital rubella syndrome lesions in the subependymal area, the basal ganglia and the deep white matter. Cranial ultrasonography defines subependymal cysts, calcification and possible vascular changes in the basal ganglia while MRI is the most sensitive to minor atrophic changes and white matter lesions. Although CT defines calcification, it is less sensitive than MRI to white matter changes and does not demonstrate subependymal cysts.     

Progressive hearing loss in infants with asymptomatic congenital cytomegalovirus infection.

Congenital cytomegalovirus (CMV) infection is a major public health problem because 30,000 to 40,000 neonates with the infection are born each year in the United States. Although 90% of the congenitally infected infants are asymptomatic at birth, evidence is accumulating that these infants are at risk for audiologic, neurologic, and developmental sequelae. The current study describes the audiologic outcome of 59 infants with asymptomatic congenital CMV infection compared with 26 control infants. Eight of 59 infected infants had congenital sensorineural hearing loss (SNHL) but none of the control subjects did. Longitudinal audiologic assessments revealed that 5 of the 8 infants had further deterioration of their SNHL; a ninth infant with initially normal hearing experienced a unilateral SNHL during the first year of life, with further deterioration subsequently. The frequency of SNHL was similar for infected infants born to mothers with recurrent CMV infections during pregnancy (2 of 9) and for those born to mothers who experienced primary CMV infections (5 of 26). There was a significant difference between the occurrence of hearing loss in infected infants with normal computed tomographic scans (2 of 40) compared with those with either periventricular radiolucencies (4 of 13) or calcifications (1 of 3). Children with SNHL often have no identified cause of the loss; thus, it is likely that many of these children had asymptomatic congenital CMV infection. Given the progressive nature of SNHL associated with asymptomatic congenital CMV infection, longitudinal audiologic assessments are mandatory.     

小鼠巨细胞病毒抑制神经干细胞分化及其机制研究

目的探讨小鼠巨细胞病毒(MCMV)对体外培养的神经干细胞(NSCs)分化的影响及其机制。方法体外分离、培养BABL／c胎鼠NSCs,利用NSCs向神经细胞分化模型,用感染复数(MOI)为1的含Lacz报告基因的重组MCMV毒株RM461进行感染,通过免疫组化、流式细胞术和RT-PCR检测MCMV感染后Nestin、GFAP和NSE阳性细胞比率及对神经干细胞分化相关信号分子Wnt-1和neurogenin 1(Ngn1)基因表达的影响。结果体外分离培养的NSCs,神经干细胞特异性标志Nestin表达强阳性,并可进一步分化为GFAP阳性的星形胶质细胞和NF-200、NSE阳性的神经元。当NSCs分化培养2 d,感染组和未感染组Nestin阳性细胞分别为(62．2±1．8)％和(37．2±2．4)％(t= 4．62,P<0．01),差异有统计学意义;而GFAP阳性细胞的比例分别为(37．4±1．6)％和(50．3±1．8)％(t=9．89,P<0．01),NSE阳性细胞的比例分别为(8．9±0．8)％和(23．4±1．3)％(t=5．09, P<0．01),差异均有统计学意义。感染组和未感染组Wnt-1基因的相对表达量分别为0．14±0．03和0．32±0．04(t=7．21,P<0．01),Ngn1基因的相对表达量分别为0．09±0．01和0．21±0．02(t= 10．73,P<0．01),差异均有统计学意义。结论(1)CMV可抑制NSCs分化,这可能是CMV致脑发育异常的重要机制;(2)CMV感染可抑制Wnt-1和Ngn-1的基因表达而影响NSCs分化,人为调控这两条通路可能为探寻防治CMV感染致脑发育异常的方法提供新策略。     

Herpes simplex virus infections in neonates and early childhood

Of the commonly considered congenital infections, those caused by cytomegalovirus (CMV), syphilis, and herpes simplex virus (HSV) are frequently (CMV, HSV) or exclusively (syphilis) acquired sexually by the mother, with subsequent transmission to the developing fetus. Of the other commonly considered congenital infections, including rubella and toxoplasma infections, the mother is exposed to the infectious agent via interpersonal or environmental contacts. Unlike each of these other pathogens, which are transmitted transplacentally to the developing fetus following maternal infection though, HSV usually is transmitted perinatally as the neonate is exposed to the virus during passage through an infected birth canal. This difference in timing of acquisition of infection has had important consequence in the therapeutic advances achieved during the last 30 years in the management of neonatal HSV infections. Because the time period between the acquisition of infection and initiation of effective antiviral therapy is shorter in neonatal herpes than in congenital toxoplasmosis or CMV infections, the outcomes of therapy have the potential to be markedly different. This article will summarize the current state of neonatal HSV disease presentation, diagnosis, and management.     

Congenital ocular blindness in children, 1945 to 1984

A total of 676 children born in British Columbia with congenital ocular blindness during the years 1945 through 1984 were studied. The birth prevalence rate of congenital blindness has decreased from eight per 10,000 live births in the late 1940s to three per 10,000 live births. Retinopathy of prematurity was replaced by genetic ocular disorders as the leading cause of congenital blindness, although the former is reemerging. The rate of congenital rubella infection also declined. There has been a significant increase in the rate of births with optic nerve lesions during the past 15 years, while the rate of births with lesions of the lens fell, reflecting the decline in the rate of maternal rubella infection. There are fewer children with congenital ocular legal blindness who have no light perception today, and they also have fewer associated handicaps.     

Cranial sonography in term and near-term infants

Sonographic patterns of brain injury in the term and near-term infant are quite different from those in the premature infant. Although periventricular leukomalacia and germinal matrix hemorrhage are rarely seen in term infants, selective neuronal injury, parasagittal infarction, focal stroke, diffuse hypoxic-ischemic injury, and deep parenchymal hemorrhages are more common lesions. In addition, congenital brain tumors, hamartomatous lesions, such as hemimegalencephaly, and tuberous sclerosis can mimic ischemic and hemorrhagic injury. Sonography remains an important tool in the initial evaluation of intracranial abnormalities in critically ill term and near-term infants. An understanding of the differences in etiology, sonographic patterns, and limitations of sonography in the term infant is essential for accurate and effective diagnoses in this age group.     

Clinical features of infants with subependymalgerminolysis and choroid plexus cysts

BACKGROUND: Periventricular cysts are not rare findings in neonates. However, they are sometimes associated with serious clinical complications, such as congenital viral infections and anomalies. METHODS: We performed a retrospective follow-up study on newborns who had periventricular cysts on routine cranial ultrasound examination. RESULTS: We followed 13 infants (three preterm) with periventricular cysts. Ten had single or multiple germinolysis cysts and the remaining three had choroid plexus cysts. All infants had various kinds of underlying complications, including congenital viral infection (two with cytomegalovirus and one with rubella),Sotos syndrome (n = 4), intrauterine growth retardation (n = 5), large-for-dates(n = 4), congenital heart disease (n = 1),myelomeningocele (n = 1) and other minor anomalies. All cases of germinolysis except for one developed a neurodevelopmental abnormality and/or delay. In contrast,all three cases with choroid plexus cysts appeared to develop well,despite the underlying complications. CONCLUSIONS: Germinolysis cysts seem to be associated with systemic diseases and should be treated as a high-risk sign for impaired neurological development.