Computed tomography and magnetic resonance imaging findings in infants with microcephaly potentially related to congenital Zika virus infection

The recent association between the increase in the number of neonates with microcephaly in northeastern Brazil and the outbreak of infection with the Zika virus, which has been occurring in the Americas, has been declared a public health emergency of international concern. The evidence that implicates the virus as the cause of this public health emergency has been demonstrated ever more consistently. This pictorial essay illustrates the imaging characteristics seen on computed tomography and magnetic resonance imaging scans of infants admitted to a rehabilitation hospital with a diagnosis of microcephaly and a maternal history of rash during pregnancy.

The elucidation of the etiological factor responsible for this most recent outbreak involves, among other factors, the recognition of the relationship between the presence of the virus and the occurrence of microcephaly; verification of the virus crossing the placental barrier; and identification of the Zika virus in stillborn and newborn infants with microcephaly or other malformations of the central nervous system (3) . The virus has been identified in the amniotic fluid of pregnant women following the ultrasound diagnosis of microcephaly (5) , in the brain tissue of a fetus aborted at 32 weeks of gestation in Slovenia (4) , and in a neonate that evolved to death in the northeastern Brazilian state Ceará (3) .
According to the World Health Organization (6) , imaging examinations are necessary for the detection of structural abnormalities in the brains of children born with microcephaly.

EMBRYOLOGY
In brief, the complex embryological process of brain development involves neurulation, followed by neuronal proliferation, neuronal migration, organization (formation of the opercula, sulci, and gyri), and, finally, myelination.

INTRODUCTION
States in several parts of the northeastern region of Brazil have recorded an unusual increase in the number of infants born with microcephaly, an urgent public health problem that affects the quality of life of children and their families. The situation has recently been declared a public health emergency of international concern (1) .
Zika virus infection in humans was first identified in Uganda and Tanzania in 1952, subsequent outbreaks being reported in other parts of Africa, as well as in the Americas, Asia, and the Pacific (2) . However, only recently, in large outbreaks in French Polynesia in 2013 and in Brazil in 2015, neurological and autoimmune complications have been reported, as has the current association with microcephaly (3,4) .
That process begins in the third week of gestation and continues until after birth. The process can be impeded by events of different natures, which, depending on the severity of the insult, can cause microcephaly. Microcephaly can be primary (genetic) or secondary, the most common causes of secondary microcephaly being vascular disorders, maternal diabetes, trauma, and infections (7) .

CLINICAL ASPECTS
The images presented in this study were obtained from the examinations of nine infants admitted to a rehabilitation hospital with microcephaly apparently related to congenital Zika virus infection, according to the criteria established by local authorities (3) .
The infants studied were between 1 and 7 months of age at the time of the examination. All of their mothers had reported having had a cutaneous rash between the second and fourth months of gestation. The serology performed during pregnancy did not identify another infectious factor that could be the cause of the microcephaly. The infants underwent computed tomography (CT) and magnetic resonance imaging (MRI) without sedation, with guidelines related to sleep deprivation.

IMAGING FINDINGS
Various congenital infections, although not pathognomonic, share some imaging characteristics, chief among which are calcifications. Other findings, such as ventriculomegaly, posterior fossa alterations, and malformations of cortical development, have been reported (3) . Below, we describe the main imaging findings among our patients with microcephaly.

Parenchymal calcifications
In all of the patients included, we observed parenchymal calcifications, varying in number and location, that were characterized by hyperattenuating foci on CT scans ( Figure 1) and by areas of low signal intensity in gradientecho MRI sequences (Figure 2). Some of the calcifications also showed high signal intensity in fast spin-echo and fast spoiled gradient echo T1-weighted sequences.
Calcifications were often seen in cortical-subcortical regions, either in a linear arrangement or confluent (Figure 1A). Several calcifications were also identified in the deep white matter, periventricular white matter, and deep gray matter ( Figure 1C).

Alterations in the morphology of the parenchyma and gyri
We identified alterations in the gyral pattern, a simplified pattern, characterized by few gyri and shallow sulci, predominating throughout the parenchyma (Figure 3). We also identified alterations on the lissencephaly spectrum ( Figure 4), with cortical thickening, greater scarcity (or even the absence) of gyri, and a nearly smooth parenchymal surface, seen in a more diffuse or localized form. In other infants, we observed areas of polymicrogyria accompanied by gyral simplification ( Figure 3B). Several patients presented a marked reduction in parenchymal volume, ventriculomegaly being quite common and, in some cases, accompanied by enlargement of the subarachnoid spaces.

Alterations in the corpus callosum
In all of the examinations included in this study, we observed changes in the corpus callosum, characterized by hypogenesis ( Figure 5) or agenesis ( Figure 6), with or without significant hypoplasia. Consequently, in some cases-those in which the agenesis or hypogenesis was more pronounced-there was a predominance of colpocephaly of the lateral ventricles ( Figure 5A).

Other alterations
We identified changes in the posterior fossa ( Figure  7), including hypoplasia of the right cerebellar hemisphere and some changes on the Dandy-Walker continuum. In one of the infants, we observed a subcortical cyst ( Figure  3B). In the cranial vault, we identified occipital protuberance ( Figures 5B and 6A) and narrowing of the frontal bones ( Figure 1A). Figure 7. MRI. A,B: Coronal T2weighted sequence showing discrete hypoplasia of the right cerebellar hemisphere (in A) and relative prominence of the cerebellum in relation to the telencephalon (in B), as well as (in both) ventriculomegaly and a significant reduction in the volume of the white matter. C: Hypoplasia and rotation of the cerebellar vermis, accompanied by a prominent cerebrospinal fluid collection in the posterior fossa, as well as changes on the Dandy-Walker continuum. Note that there is also hypoplasia of the brainstem, notably of the pons.
A B C