We conducted a descriptive, retrospective, case series study by reviewing the medical records of 9 children in Brazil with dysphagia and CZS microcephaly diagnosed during the 2015 epidemic of microcephaly.
Neck hyperextension was associated with irritability, a frequent symptom in children with CZS (6/9 children in this series), and was a contributing factor to dysphagia.
The severe form of CZS with microcephaly usually causes severe encephalopathy with cerebral palsy secondary to brain injury, including involvement of cortical and subcortical areas, the basal ganglia, and, in some cases, the brainstem.
As of this writing, children with microcephaly resulting from CZS have only been followed for up to a maximum of 18 months after onset, but it is known that they have multiple disabilities affecting motor function, cognition, sight, and hearing.
21) In a report of 40 infants with microcephaly and presumed CZS from Pernambuco, Brazil, Ventura et al (22) described ophthalmoscopic alterations in 55% (n = 22) of the infants.
The spectrum of ocular abnormalities reported in CZS includes maculopathies, such as a particular pattern of macular chorioretinal atrophy with a hyperpigmented ring that resembles torpedo maculopathy, abnormalities of the optic nerve (hypoplasia and severe cupping of the optic disk), microcornea, microphthalmia, falciform folds, pigmentary and hemorrhagic retinopathy, circumscribed chorioretinal atrophy, abnormal vascular development (tortuosity, early termination, absence), coloboma, lens subluxation, cataracts, and retinal dysplasia.
Musculoskeletal abnormalities are frequently described in published reports of CZS, but their actual prevalence among infants of women infected during pregnancy remains unknown.
The musculoskeletal findings and malformations present in CZS are probably not the result of direct cytopathic effect of the virus on the affected tissues, but instead are likely secondary to ZIKV-induced brain injury.
24,64) Transmission electron microscopy showed spherical 40-nm enveloped viral particles and viral factories within neurons in the brain of an aborted 22-week-gestation fetus with CZS, indicating active viral replication in these cells (Martines, 2016, manuscript in preparation).
Placental pathologic lesions in CZS are frequently absent, and documented to date predominantly for maternal infection in the first trimester.
87-90) Infection of immunodeficient pregnant dams results in viral detection in placenta and fetal brain, sometimes with reduced brain size and cortical thinning, similar to CZS.
The timing of maternal infection (first trimester) associated with CZS and the preferential susceptibility of neural progenitor cells in vitro and the CNS of young and fetal animals in vivo suggest that the overall mechanism of neural damage relates to arrest of brain growth, rather than damage and collapse of preformed neural structures.