Recent advances in the understanding of neuropathogenesis associated with Zika virus (ZIKV) infection has led to descriptions of neonatal microcephaly cases. However, none of these reports have ...evaluated the humoral response during ZIKV infection. We report here polyfunctional immune activation associated with increased interferon‐gamma‐inducible protein 10, interleukin (IL)‐6, IL‐8, vascular endothelial growth factor (VEGF), monocyte chemoattractive protein 1 (MCP‐1), and granulocyte colony‐stimulating factor (G‐CSF) levels in the amniotic fluid of ZIKV‐positive pregnant women with neonatal microcephaly. These cytokines have been associated not only with neuronal damage, but also with differentiation and proliferation of neural progenitor cells. Our results suggested that the immune activation caused by ZIKV infection in the uterine environment could also interfere with fetal development. ANN NEUROL 2017;81:152–156
Objective
To describe obstetric and perinatal outcomes in cases of congenital Zika syndrome (CZS).
Methods
A dual prospective and retrospective cohort study involving 102 pairs of mothers and ...fetuses/children with CZS whose infection was confirmed by testing for the Zika virus in amniotic fluid, umbilical cord blood, and fragments from the placenta of the newborn infant (confirmed CZS), or by intrauterine imaging tests (neurosonography), and/or postnatal computed tomography (presumed CZS).
Results
Suspicion of CZS was investigated by ultrasonography during pregnancy in 52.9% of cases. The principal prenatal imaging findings were ventriculomegaly (43.1%) and microcephaly (42.2%). Median gestational age at delivery was 39 weeks, with 15.7% being premature. Mean head circumference at birth was 30.0 ± 2.3 cm, with 66% of cases being classified as having microcephaly. Arthrogryposis was found in 10 cases (9.8%). There were no fetal deaths; however, nine neonatal deaths were recorded, and three autopsies were performed.
Conclusion
Neonatal mortality was high, almost 10%. Regarding the abnormalities of CZS, microcephaly, although common, was not present in all cases and intracranial findings need to be taken into consideration for diagnosis. Therefore, ultrasound screening during pregnancy should be systematized and expanded in endemic zones.
A major concern associated with ZIKV infection is the increased incidence of microcephaly with frequent calcifications in infants born from infected mothers. To date, postmortem analysis of the ...central nervous system (CNS) in congenital infection is limited to individual reports or small series. We report a comprehensive neuropathological study in ten newborn babies infected with ZIKV during pregnancy, including the spinal cords and dorsal root ganglia (DRG), and also muscle, pituitaries, eye, systemic organs, and placentas. Using in situ hybridization (ISH) and electron microscopy, we investigated the role of direct viral infection in the pathogenesis of the lesions. Nine women had Zika symptoms between the 4th and 18th and one in the 28th gestational week. Two babies were born at 32, one at 34 and 36 weeks each and six at term. The cephalic perimeter was reduced in four, and normal or enlarged in six patients, although the brain weights were lower than expected. All had arthrogryposis, except the patient infected at 28 weeks gestation. We defined three patterns of CNS lesions, with different patterns of destructive, calcification, hypoplasia, and migration disturbances. Ventriculomegaly was severe in the first pattern due to midbrain damage with aqueduct stenosis/distortion. The second pattern had small brains and mild/moderate (ex-vacuo) ventriculomegaly. The third pattern, a well-formed brain with mild calcification, coincided with late infection. The absence of descending fibres resulted in hypoplastic basis pontis, pyramids, and cortico-spinal tracts. Spinal motor cell loss explained the intrauterine akinesia, arthrogryposis, and neurogenic muscle atrophy. DRG, dorsal nerve roots, and columns were normal. Lympho-histiocytic inflammation was mild. ISH showed meningeal, germinal matrix, and neocortical infection, consistent with neural progenitors death leading to proliferation and migration disorders. A secondary ischemic process may explain the destructive lesions. In conclusion, we characterized the destructive and malformative consequences of ZIKV in the nervous system, as reflected in the topography and severity of lesions, anatomic localization of the virus, and timing of infection during gestation. Our findings indicate a developmental vulnerability of the immature CNS, and shed light on possible mechanisms of brain injury of this newly recognized public health threat.
Neither microcephaly nor neurological damage was found in children born from pregnancies subsequent to one resulting in an infant with congenital Zika syndrome.
Abstract
Developmental malformations (dysgenesis) of the corpus callosum lead to neurological conditions with a broad range of clinical presentations. Investigating the altered brain connectivity ...patterns is crucial to understanding both adaptive and maladaptive neuroplasticity in corpus callosum dysgenesis patients. Here, we acquired structural diffusion-weighted and resting-state functional MRI data from a cohort of 11 corpus callosum dysgenesis patients (five with agenesis and six with hypoplasia) and compared their structural and functional connectivity patterns to healthy subjects selected from the Human Connectome Project. We found that these patients have fewer structural inter- and intra-hemispheric brain connections relative to healthy controls. Interestingly, the patients with callosal agenesis have a scant number of inter-hemispheric connections but manage to maintain the full integrity of functional connectivity between the same cortical regions as the healthy subjects. On the other hand, the hypoplasic group presented abnormal structural and functional connectivity patterns relative to healthy controls while maintaining the same total amount of functional connections. These results demonstrate that acallosal patients can compensate for having fewer structural brain connections and present functional adaptation. However, hypoplasics present atypical structural connections to different brain regions, leading to entirely new and abnormal functional brain connectivity patterns.
Szczupak et al. report that patients born with developmental corpus callosum malformations have abnormal structural brain connections. While acallosal patients have a scant number of inter-hemispheric connections, they preserve functional integrity and have a better prognosis than hypoplasic patients, which have atypical structural connections leading to abnormal functional connectivity patterns.
Graphical Abstract
Graphical Abstract
SARS-CoV-2 infection during pregnancy is not usually associated with significant adverse effects. However, in this study, we report a fetal death associated with mild COVID-19 in a 34-week-pregnant ...woman. The virus was detected in the placenta and in an unprecedented way in several fetal tissues. Placental abnormalities (MRI and anatomopathological study) were consistent with intense vascular malperfusion, probably the cause of fetal death. Lung histopathology also showed signs of inflammation, which could have been a contributory factor. Monitoring inflammatory response and coagulation in high-risk pregnant women with COVID-19 may prevent unfavorable outcomes, as shown in this case.
IMPORTANCE: Recent studies have reported an increase in the number of fetuses and neonates with microcephaly whose mothers were infected with the Zika virus (ZIKV) during pregnancy. To our knowledge, ...most reports to date have focused on select aspects of the maternal or fetal infection and fetal effects. OBJECTIVE: To describe the prenatal evolution and perinatal outcomes of 11 neonates who had developmental abnormalities and neurological damage associated with ZIKV infection in Brazil. DESIGN, SETTING, AND PARTICIPANTS: We observed 11 infants with congenital ZIKV infection from gestation to 6 months in the state of Paraíba, Brazil. Ten of 11 women included in this study presented with symptoms of ZIKV infection during the first half of pregnancy, and all 11 had laboratory evidence of the infection in several tissues by serology or polymerase chain reaction. Brain damage was confirmed through intrauterine ultrasonography and was complemented by magnetic resonance imaging. Histopathological analysis was performed on the placenta and brain tissue from infants who died. The ZIKV genome was investigated in several tissues and sequenced for further phylogenetic analysis. MAIN OUTCOMES AND MEASURES: Description of the major lesions caused by ZIKV congenital infection. RESULTS: Of the 11 infants, 7 (63.6%) were female, and the median (SD) maternal age at delivery was 25 (6) years. Three of 11 neonates died, giving a perinatal mortality rate of 27.3%. The median (SD) cephalic perimeter at birth was 31 (3) cm, a value lower than the limit to consider a microcephaly case. In all patients, neurological impairments were identified, including microcephaly, a reduction in cerebral volume, ventriculomegaly, cerebellar hypoplasia, lissencephaly with hydrocephalus, and fetal akinesia deformation sequence (ie, arthrogryposis). Results of limited testing for other causes of microcephaly, such as genetic disorders and viral and bacterial infections, were negative, and the ZIKV genome was found in both maternal and neonatal tissues (eg, amniotic fluid, cord blood, placenta, and brain). Phylogenetic analyses showed an intrahost virus variation with some polymorphisms in envelope genes associated with different tissues. CONCLUSIONS AND RELEVANCE: Combined findings from clinical, laboratory, imaging, and pathological examinations provided a more complete picture of the severe damage and developmental abnormalities caused by ZIKV infection than has been previously reported. The term congenital Zika syndrome is preferable to refer to these cases, as microcephaly is just one of the clinical signs of this congenital malformation disorder.
Abstract Purpose To review our experience with prenatal diagnosis of bladder exstrophy by fetal magnetic resonance imaging (MRI). Bladder exstrophy can be diagnosed by ultrasonography (US) evaluation ...of the fetus based on absence of bladder filling, low-set umbilicus, small genitalia and lower abdominal mass, although in some instances more accurate anatomical information is desired. Material and methods We studied three patients at mean gestational age of 27.3 weeks. The fetal MRI exam was performed on axial, sagittal, coronal planes and echo gradient in the best plan for acquisition of fetus. Images were analyzed by a group of three radiologists with experience in fetal MRI. Results The MRI defined a lower abdominal mass prolapsing below the umbilical vessels, having the ureters ending on it in an anterior position. A cloacal malformation or a cloacal exstrophy could be excluded, as well as other accompanying spinal abnormalities. The renal system and oligohydramnios could be well documented. Conclusions The MRI showed a detailed scenario of the abnormality with advantages over the US evaluation in regard to excluding cloacal anomalies. MRI allowed accurate sexual differentiation and may be indicated after suspected bladder exstrophy on US evaluation.
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