Progressive lesions of central nervous system in microcephalic fetuses with suspected congenital Zika virus syndrome

Abstract

The majority of cases of congenital ZIKV syndrome have other ultrasonographic findings in addition to microcephaly. ZIKV-related CNS anomalies present mainly as progressive CNS lesions and slowing rate of growth of the fetal head, and this seems to be evident only in the late second trimester, even when maternal infection occurs in the first trimester. Other ultrasound findings, such as ventriculomegaly, brain calcifications and posterior fossa destruction lesions, are also common in this congenital syndrome. Posterior fossa destruction lesions and arthrogryposis are an uncommon finding in other congenital infections, perhaps suggesting a novel severe congenital syndrome associated with fetal ZIKV. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Development of a Zika Virus Infection Model in Cynomolgus Macaques

“…The origin and global spread of ZIKV during the ongoing pandemic is well-documented (Dick et al, 1952; Duffy et al, 2009; Haddow et al, 2012; Musso et al, 2014; Campos et al, 2015; Zanluca et al, 2015; Solomon et al, 2016). The significance of ZIKV is highlighted in the infection associated complications, such as Guillain–Barre syndrome (Oehler et al, 2014; do Rosario et al, 2016) and the risk of vertical transmission of the virus from mother to the fetus, which can result in devastating lifelong neurological complications including microcephaly (Brasil and Nielsen-Saines, 2016; Martines et al, 2016; Mlakar et al, 2016; Sarno et al, 2016). Considering the global health emergency posed by ZIKV, there is an ongoing concerted effort among the scientific community to develop new diagnostics, vaccines and antivirals to stem the pandemic.…”

Characterizing the Pattern of Anomalies in Congenital Zika Syndrome for Pediatric Clinicians

“…In the recent case series, most infants with probable congenital ZIKV infection were noted to have craniofacial disproportion (95.8%) and to a lesser degree biparietal depression (83.3%), prominent occiput (75%) and excess nuchal skin (47.9%). 36 Features supportive of the FBDS phenotype scattered through published reports include redundant scalp, 25,34,37,39 occipital prominence and/or overlapping sutures 12,18,20–22,24,25,36 and typical craniofacial appearance with disproportion. 11,25,31,32,38 The FBDS phenotype is also prevalent in ZIKV-related media (http://www.apimages.com/Collection/Landing/Photographer-Felipe-Dana-Brazil-Zika-Birth-Defects/5437af63923a4384a8b27854132305a5).…”

“…42 Postnatal CT scan and MR imaging have identified a spectrum of abnormalities that include, in decreasing frequency, diffuse, primarily subcortical calcifications; increased fluid spaces–– ventricular and extra-axial; marked cortical thinning with abnormal gyral patterns (most consistent with polymicrogyria); hypoplasia or absence of the corpus callosum; decreased myelination; and cerebellar or cerebellar vermis hypoplasia (Figure 2) 22,24,28,33–39 In addition, calcifications have been identified in the basal ganglion as well as the brainstem in some affected infants. 37 Some of these brain abnormalities can be detected prenatally with ultrasound or MR imaging; 27,33,34,37 however, with severe microcephaly the anterior fontanel is often small or closed 25,34 making tranfontanellar ultrasound in the newborn difficult.…”

“…23,26,31,33,34,39,40,41,52 Case series report chorioretinal atrophy, focal pigmentary mottling of the retina, and optic nerve atrophy/anomalies. 26,32,35,39–41,53 Series of 20 or more infants with presumed ZIKV-associated microcephaly report ocular findings in 24–55% 26,31,40 In one study, testing for ZIKV IgM was performed in 24/40 (60%) of infants with microcephaly and was positive in the cerebrospinal fluid (CSF) in 100% of those tested.…”

“…18,22,34,35,39 The clinical picture of congenital contractures varies among affected infants in regard to type (proximal or distal), laterality, upper or lower limb, and severity, likely reflecting variations in neurologic damage (Figure 4). The three largest case series of infants with microcephaly also reporting congenital contractures found that, among 35, 48 and 52 infants with microcephaly and presumed congenital ZIKV infection, isolated clubfoot occurred in 14%, 10.4% and 3.8% and arthrogryposis in 11%, 10.4 % and 5.7%, respectively.…”