Malformations attributed to the process of vascular disruption.

BACKGROUND: Several malformations have been attributed to the process of vascular disruption. The central hypothesis for this etiology is that blood flow to a structure has been altered after that structure had formed normally. The decreased blood flow leads to hypoxia, endothelial cell damage, hemorrhage, tissue loss, and repair. After recovery, some structures are normal and others show either tissue loss or structural abnormalities, such as syndactyly and constriction rings. METHODS: The phenotypic features of the 7,020 infants with one or more malformations, who were born to women who had always planned to deliver at Brigham and Women's Hospital (BWH) between, 1972 and 2012, that is, maternal nontransfers, were reviewed. The phenotypes associated with vascular disruption, such as the amniotic band syndrome and terminal transverse limb defects (TTLD), were identified. RESULTS: One hundred and five fetuses and infants had malformations attributed to the process of vascular disruption. Some specific causes of the amniotic band limb deformity were identified. TTLD with associated small digit-like nubbins occurred at three levels: proximal forearm, wrist, and metacarpal-phalangeal joint. Other causes included severe hemoglobinopathies and exposures to misoprostol and to prenatal procedures. CONCLUSIONS: Malformations attributed to the process of vascular disruption were a distinctive entity, among the recognized etiologies. The timing of the causative event in the first trimester was established for infants with exposures to either the prostaglandin misoprostol or the prenatal diagnosis procedure chorionic villus sampling. One challenge is to identify the developmental steps in vascular disruption when no causative exposure can be identified.

Intrauterine fetal death of one of twins, coexisting with hydranencephaly in the surviving co-twin: a case report.

Hydranencephaly, a relatively rare malformation of the brain, is characterised by absence of the cerebral hemispheres and their replacement by sacs filled with cerebrospinal fluid. It is one of the recognised forms of intracranial malformations associated with intrauterine fetal demise of one of twins in monochorionic twin gestation. This report illustrates the development of hydranencephaly in a surviving twin sequel to intrauterine fetal demise of the co-twin.

Maternal systemic lupus erythematosus and hydranencephaly in a neonate: a case report.

Hydranencephaly is characterized by absent cerebral hemispheres replaced by fluid-filled sacs in a normal skull. Herein we report the case of a premature neonate with hydranencephaly born to a mother with systemic lupus erythematosus. Although numerous etiologies have been proposed, an association between maternal systemic lupus erythematosus and neonatal hydranencephaly has not previously been reported.

Vascular etiology of disruptive structural defects in monozygotic twins.

Two infants with structural defects previously undescribed in the survivor of a monozygotic twin pair are reported. One infant had hydranencephaly and a spinal cord transection, with an associated dead monozygotic co-twin of 24 weeks gestation; the other child had complete atresia of the colon and a horseshoe kidney, with a deceased co-twin of approximately six weeks gestation. These defects are presumed to be the result of in utero disruption of previously normally formed structures. They occur secondary to vascular exchange from a dead to a living monozygotic twin through placental vascular anastomoses. As illustrated by the two children described, the nature of the vascular defects seen in the survivor of a monozygotic twin pair depends on the time during gestation at which the co-twin dies. Recognition of the disruptive vascular etiology of the structural defects outlined in this report will allow for appropriate counseling with respect to the negligible recurrence risk for similar vascular accidents.

Congenital hydranencephaly/porencephaly due to vascular disruption in monozygotic twins.

Monozygotic twinning has been associated with a variety of vascular disruptive defects including congenital hydranencephaly/porencephaly. Data involving 24 cases of congenital hydranencephaly/porencephaly associated with twinning are reported. In these cases, the finding of a preponderance of monozygotic twins and the common association of a deceased co-twin support the hypothesis of a vascular disruptive etiology. These defects are presumed to be secondary to embolic phenomena or thromboplastin release from the deceased co-twin to the survivor via the vascular interconnections of a conjoined monochorionic placenta. In all cases of hydranencephaly/porencephaly, a careful examination of the placenta and membranes for evidence of a deceased co-twin is warranted prior to providing recurrence risk counseling.

Decreased maternal age with hydranencephaly.

We studied parental ages of institutionalized children with hydranencephaly. Mothers under age 20 years and under age 18 years were, respectively, 5 and 10 times as frequent as in the general population, and 3 and 4 times more frequent than for institutionalized control patients. Unwed mothers were also common, but may reflect high rates in younger mothers combined with institutionalization bias. Thus, hydranencephaly appears to show a decreased maternal age effect, similar to that seen with other conditions presumably due to prenatal vascular disruptions.

Unexpected disseminated herpes simplex infection in a newborn.

Disseminated herpes simplex virus type 2 was unexpectedly discovered in a baby delivered by primary cesarean section at 36 weeks' gestation prior to rupture of the membranes. The mother was free of orogenital lesions at each prenatal examination. Examination of the placenta revealed chorioamnionitis implicating an ascending infection from the mother's infected genital tract.

Evolution of hydranencephaly following intracerebral hemorrhage.

A circumscribed hyperechoic mass in the mid-portion of the left cerebral hemisphere was the presenting ultrasonographic finding in a 30-week fetus. With repeat ultrasound studies, this echo-dense mass became more sonolucent. In addition, there was an increased fluid accumulation and loss of identifiable cerebral cortex over the left parietal and occipital lobes. The patient underwent induction of labor because of progressive intracranial fluid accumulation with subsequent macrocephaly. The infant died on the fourth day of life. At necropsy, an organizing hematoma with admixtures of fresh and moderately degraded old blood was found in the left hemisphere. There was extensive resorption of the underlying cortex, leaving only a fluid-filled cavity with a meningeal covering. We believe the progressive changes that occurred after fetal intracerebral hemorrhage ultimately resulted in hydranencephaly.

Evidence that Cache Valley virus induces congenital malformations in sheep.

An outbreak of congenital abnormalities occurred in sheep at San Angelo, Texas, between December 1986 and February 1987. Of 360 lambs born, 19.2% had arthrogryposis or other musculo-skeletal problems and hydranencephaly (AGH), and the total neonatal loss was 25.6%. In 1987, all ewes that were tested with AGH lambs had antibody to Cache Valley virus (CVV), whereas 62% of the ewes with normal lambs had CVV-specific antibody. Pre-colostral serum samples from AGH lambs had neutralizing antibody to CVV. An increase in prevalence of CVV-specific antibody, from 5% during the spring of 1986 to 63.4% during the winter of 1987, occurred during a time that included the gestation of these affected lambs, as well as a period of increased rainfall. The isolation of a CVV-related strain from a sentinel sheep in October 1987 confirmed the continued presence of this virus in the pasture where this outbreak occurred and provided a recent field strain for future studies.

Hydranencephaly owing to twin-twin transfusion: serial fetal ultrasonography and magnetic resonance imaging findings.

We report a newborn girl with hydranencephaly. In the setting of a monochorionic twin pregnancy, one twin's demise was detected by ultrasonography at 18 weeks of gestation, apparently the result of a twin-twin transfusion. In the surviving twin, the evolution of ventriculomegaly, first noted at 18 weeks, to hydranencephaly at 27 weeks is documented by serial sonograms. These findings were confirmed with fetal and postnatal magnetic resonance imaging.

Congenital hydranencephalic-hydrocephalic syndrome associated with mitochondrial dysfunction.

We report the case of a 3-year-old girl, the only child of a nonconsanguineous couple without relevant antecedents, who was born with hydranencephalic-hydrocephalic syndrome diagnosed by ultrasonography at gestation week 28, and who was treated during the neonatal period by implantation of a ventriculoperitoneal shunt. She showed severe mental retardation, and died at age 4 years following an acute respiratory infection. Due to persistently high lactic acid levels in blood, muscle and skin biopsies were taken. Analysis of muscle biopsies revealed microscopic and ultrastructural alterations typical of mitochondrial disorders, and low levels of complexes III and IV of the mitochondrial respiratory chain. The enzymes of the pyruvate dehydrogenase complex showed normal activities in cultured skin fibroblasts. These findings raise the possibility that at least some cases of congenital hydranencephalic-hydrocephalic syndrome may be due to alterations in the mitochondrial respiratory chain.

Congenital hydranencephalic-hydrocephalic syndrome with proliferative vasculopathy: a possible relation with mitochondrial dysfunction.

We report the case of a fetus aborted at gestation week 20 because of hydranencephalic-hydrocephalic syndrome. The fetus was the third pregnancy of a nonconsanguineous couple whose first child exhibited congenital hydranencephalic-hydrocephalic syndrome associated with muscle histology findings consistent with mitochondrial cytopathy and deficiency of complexes III and IV of the respiratory chain and whose second pregnancy had terminated in an elective abortion on detection of progressive hydrocephalus at gestation week 19. The third pregnancy had a normal course according to obstetric and ultrasonography examinations performed at gestation weeks 5, 10, and 15, and negative results were obtained in standard serologic and polymerase chain reaction (PCR) tests for prenatal infections of the mother. However, the ultrasonography examination at gestation week 18 revealed hydrocephalus, in response to which the parents requested an abortion, which was performed at gestation week 20; the fetus was male and with no evident external malformations. Histopathologic studies of the brain and medulla oblongata revealed proliferative vasculopathy (glomeruloid vessels, intracytoplasmic inclusions, and microcalcifications) and intracytoplasmic inclusions in the voluntary muscle. Microbiologic and PCR tests of hepatic and spleen tissue were negative for prenatal infections. In view of the precedent of a sister with mitochondrial dysfunction, these findings raise the pos sibility that at least some cases of familial syndrome of congenital hydranencephalic-hydrocephalic syndrome with proliferative vasculopathy can be attributed to alterations in the mitochondrial respiratory chain.

A neonatal case of hydranencephaly caused by atheromatous plaque obstruction of aortic arch: possible association with a congenital cytomegalovirus infection?

A neonate was seen with hydranencephaly and aortic arch obstruction possibly caused by congenital cytomegalovirus infection. At autopsy the aortic arch was occluded by atheromatous plaque between the right brachiocephalic artery and left common carotid artery. Congenital cytomegalovirus infection may have caused cardiovascular disease and hydranencephaly in this case.

Teratogenicity of Aino virus in the chick embryo.

Aino virus (JaNAr 28 strain), a possible agent of a congenital anomaly of calves, was inoculated into the yolk sac of chick embryos at a dose of 10(2), 10(3), 10(4) or 10(5) TCID50 0.2 ml-1 at four, six or eight days of incubation. At 21 days of incubation all the unhatched embryos or hatched chickens in the experimental and control groups were sacrificed for pathological examination. The incidence of hydranencephaly, cerebellar hypoplasia or agenesis and arthrogryposis or scoliosis was highest (85 per cent in the chicks inoculated with 10(3) TCID50 0.2 ml-1 at eight days of incubation. The lesions were very similar to those found in congenital abnormalities in calves suspected of a natural infection with Aino virus.

Serologic evidence for the etiologic role of Chuzan virus in an epizootic of congenital abnormalities with hydranencephaly-cerebellar hypoplasia syndrome of calves in Japan.

An epizootic of congenital abnormalities of calves was observed in the Kyushu district of Japan from November 1985 through April 1986. The main clinical signs of the disease were impairment of mobility and signs of impairment of the nervous system. Opisthotonos was pronounced, and almost all calves were unable to suckle by themselves. The main macroscopic pathologic changes were hydranencephaly and cerebellar hypoplasia. Although an etiologic agent was not isolated from the calves, serotest results of precolostral serum samples indicated that 128 of 139 (92%) abnormal calves had antibody for Chuzan virus, a new virus belonging to the Palyam subgroup of the Orbivirus genus; 34 healthy calves in the epizootiologic area did not have antibody for the virus. The presence of Chuzan virus in Kyushu in 1985 was confirmed serologically.

Bluetongue virus as a cause of hydranencephaly in cattle.

Hydranencephaly was produced in a foetus and a calf by intra-uterine infection with an attenuated Type 10 bluetongue virus. Laparotomy was performed on the respective dams and the foetuses, respectively 126 days and 138 days old, were inoculated intramuscularly through the uterine wall with 1 ml of a virus suspension containing 5 x 103 tissue culture infective doese. The younger feotus was aborted on Day 262, while the other one was born alive on Day 273. Both foetuses showed marked hydranencephaly.

Hydrops amnii in sheep associated with hydranencephaly and arthrogryposis with wesselsbron disease and rift valley fever viruses as aetiological agents.

During the 1974/75 lambing season numerous reports were received from various parts of the Republic of South Africa and South West Africa of severe abdominal distension in ewes after vaccination with the attenuated Rift Valley fever and/or attenuated Wesselsbron disease vaccine. The ewes were vaccinated at different stages of gestation in spite of recommendations to the contrary, the syndrome being especially obvious in ewes immunized with one or both of these vaccines during the first trimester of pregnancy. In some of the flocks hydrops amnii was recorded in as many as 15% of the ewes. Many of the ewes so affected showed a prolonged gestation of up to 6-7 months and, towards the end of gestation, were unable to rise or walk. They eventually died of ketosis, hypostatic pneumonia and complications due to dystocia. The foetuses examined were malformed and larger than normal with a mass of 3,6-6,7 kg. They usually showed arthrogryposis, brachygnathy inferior, hydranencephaly, hypoplasia or segmental aplasia of the spinal cord and neurogenic muscular atrophy. The amnion contained 8,0-18,0 1 of amniotic fluid, the endometrium was oedematous, and cystic tube-like dilatations, 1-10 mm in diameter, filled with a clear fluid, were scattered in the endometrium. No definite conclusions as to the aetiology of the syndrome could be drawn from serological tests performed on the ewes, lambs or foetuses. Preliminary experimental work confirmed previous observations that the attenuated Wesselsbron disease vaccine virus is responsible for this syndrome and that the wild-type virus is also implicated. In addition, the attenuated Rift Valley fever vaccine virus was found to the responsible for arthrogryposis and hydranencephaly without hydrops amnii and for micrencephaly and arthrogryposis associated with hydrops amnii in the ewe.

The development of Akabane virus-induced congenital abnormalities in cattle.

A prospective study of the incidence and severity of congenital deformities of calves, attributable to maternal infection by Akabane virus, was carried out on a population of 174 susceptible animals that were between one and nine months pregnant at the time of infection. The study was carried out in the Hunter Valley of New South Wales during 1983, after an epidemic of Akabane virus infection in late February to early March 1983. The incidence of virus-induced abnormalities in calves and fetuses was 17.8 per cent (31/174). The highest incidence of abnormalities occurred during the third and sixth months of gestation (27 to 29 per cent). The earliest abnormality was observed after infection at 76 days of gestation, and the last after infection at 249 days. The development of the pathological entities of hydranencephaly/porencephaly and arthrogryposis were found to be quite distinct. Cases of hydranencephaly and porencephaly developed after infection between 76 and 104 days of gestation whereas arthrogryposis developed after infection between 103 and 174 days of infection. It was concluded that the type of congenital deformity produced by maternal infection with Akabane virus was dependent on the stage of fetal development at the time of infection. The data suggest that the infection was transplacental and that fetuses of less than two months of age were protected from infection.

[Hydranencephaly: clinicopathological study of 6 cases]. / Hidranencefalia: estudo clinicopatológico de 6 casos.

The study of six patients with hydranencephaly is reported. Clinical and necroscopic findings have been performed in correlation to routine laboratory examination. The Authors have concluded that transilumination is an important procedure for early diagnostic of these cases, especially when the patients have a milder or incomplete form of the syndrome. The necroscopic findings suggest that hydranencephaly may be the result of encephaloclastic lesions (inflammatory, mechanical or vascular) that, either before or after birth, lead to complete destruction of the brain, with sparing of sub-tentorial structures.

Bluetongue: the disease in cattle.

Most researchers in South Africa found that although BT virus could be isolated from apparently healthy cattle and from inoculated cattle the virus did not produce overt clinical disease in cattle. However, when epizootics were reported outside Africa, clinical signs were observed in cattle in Israel, Palestine, Syria, Portugal, and Spain. Most natural BT infections in cattle in the United States do not result in overt clinical signs. However, in certain infected herds, approximately 5% of the cattle show from mild to severe disease. Except for severe cases, spontaneous recovery is usual. The clinical diagnosis of BT in cattle is difficult and requires laboratory assistance. Culicoides variipennis can serve as a vector of BT virus from cattle to cattle, cattle to sheep, sheep to cattle, and sheep to sheep. In utero transmission occurs in cattle and can result in abortion, hydraencephaly, congenital deformity, and birth of viraemic calves which may or may not develop BT antibody. Calves inoculated in utero or those born to infected dams may have a persistent viraemia with or without BT antibody. tone such animal has been held in insect-secure quarters and has continued to harbour virus for 3 years. Bluetongue virus was isolated from the semen of experimentally infected bulls. Calves inoculated with BT virus and also given an immuno-suppressant developed marked clinical disease in 8 to 12 days. Bluetongue virus is very closely associated with the erythrocytes of infected cattle, sheep, and goats. Cattle are considered important and relatively long-term virus reservoirs. In attempts to determine the maximum period of viraemia in cattle it is necessary to inoculate washed erythrocytes, rather than whole blood, and to use susceptible sheep as the assay system rather than embryonated chicken eggs.