Wednesday, August 24, 2016

Prenatal and postnatal findings with Zika virus

Soares de Oliveira-Szejnfeld P, Levine D, Melo AS, Amorim MM, Batista AG,
Chimelli L, Tanuri A, Aguiar RS, Malinger G, Ximenes R, Robertson R, Szejnfeld J,
Tovar-Moll F. Congenital Brain Abnormalities and Zika Virus: What the Radiologist
Can Expect to See Prenatally and Postnatally. Radiology. 2016 Aug 23:161584.
[Epub ahead of print]


Purpose To document the imaging findings associated with congenital Zika virus infection as found in the Instituto de Pesquisa in Campina Grande State Paraiba (IPESQ) in northeastern Brazil, where the congenital infection has been particularly severe.

Materials and Methods From June 2015 to May 2016, 438 patients were referred to the IPESQ for rash occurring during pregnancy or for suspected fetal central nervous system abnormality. Patients who underwent imaging at IPESQ were included, as well as those with documented Zika virus infection in fluid or tissue (n = 17, confirmed infection cohort) or those with brain findings suspicious for Zika virus infection, with intracranial calcifications (n = 28, presumed infection cohort). Imaging examinations included 12 fetal magnetic resonance (MR) examinations, 42 postnatal brain computed tomographic examinations, and 11 postnatal brain MR examinations. Images were reviewed by four radiologists, with final opinion achieved by means of consensus.

Results Brain abnormalities seen in confirmed (n = 17) and presumed (n = 28) congenital Zika virus infections were similar, with ventriculomegaly in 16 of 17 (94%) and 27 of 28 (96%) infections, respectively; abnormalities of the corpus callosum in 16 of 17 (94%) and 22 of 28 (78%) infections, respectively; and cortical migrational abnormalities in 16 of 17 (94%) and 28 of 28 (100%) infections, respectively. Although most fetuses underwent at least one examination that showed head circumference below the 5th percentile, head circumference could be normal in the presence of severe ventriculomegaly (seen in three fetuses). Intracranial calcifications were most commonly seen at the gray matter-white matter junction, in 15 of 17 (88%) and 28 of 28 (100%) confirmed and presumed infections, respectively. The basal ganglia and/or thalamus were also commonly involved with calcifications in 11 of 17 (65%) and 18 of 28 (64%) infections, respectively. The skull frequently had a collapsed appearance with overlapping sutures and redundant skin folds and, occasionally, intracranial herniation of orbital fat and clot in the confluence of sinuses.

Conclusion The spectrum of findings associated with congenital Zika virus infection in the IPESQ in northeastern Brazil is illustrated to aid the radiologist in identifying Zika virus infection at imaging.

Courtesy of a colleague


  1. van der Linden V, Filho EL, Lins OG, van der Linden A, Aragão Mde F, Brainer-Lima AM, Cruz DD, Rocha MA, Sobral da Silva PF, Carvalho MD, do Amaral FJ, Gomes JA, Ribeiro de Medeiros IC, Ventura CV, Ramos RC. Congenital Zika syndrome with arthrogryposis: retrospective case series study. BMJ. 2016 Aug 9;354:i3899.

    To describe the clinical, radiological, and electromyographic features in a series of children with joint contractures (arthrogryposis) associated with congenital infection presumably caused by Zika virus.
    Retrospective case series study.
    Association for Assistance of Disabled Children, Pernambuco state, Brazil.
    Seven children with arthrogryposis and a diagnosis of congenital infection presumably caused by Zika virus during the Brazilian microcephaly epidemic.
    Main clinical, radiological, and electromyographic findings, and likely correlation between clinical and primary neurological abnormalities.
    The brain images of all seven children were characteristic of congenital infection and arthrogryposis. Two children tested positive for IgM to Zika virus in the cerebrospinal fluid. Arthrogryposis was present in the arms and legs of six children (86%) and the legs of one child (14%). Hip radiographs showed bilateral dislocation in seven children, subluxation of the knee associated with genu valgus in three children (43%), which was bilateral in two (29%). All the children underwent high definition ultrasonography of the joints, and there was no evidence of abnormalities. Moderate signs of remodeling of the motor units and a reduced recruitment pattern were found on needle electromyography (monopolar). Five of the children underwent brain computed tomography (CT) and magnetic resonance imaging (MRI) and the remaining two CT only. All presented malformations of cortical development, calcifications predominantly in the cortex and subcortical white matter (especially in the junction between the cortex and white matter), reduction in brain volume, ventriculomegaly, and hypoplasia of the brainstem and cerebellum. MRI of the spine in four children showed apparent thinning of the cord and reduced ventral roots.
    Congenital Zika syndrome should be added to the differential diagnosis of congenital infections and arthrogryposis. The arthrogryposis was unrelated to the abnormalities of the joints themselves, but was possibly of neurogenic origin, with chronic involvement of central and peripheral motor neurones leading to deformities as a result of fixed postures in utero. Based on the neurophysiological observations, we suggest two possible mechanisms: tropism of neurones, with involvement of peripheral and central motor neurones, or a relation with vascular disorders.

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  2. Babies born to mothers infected with Zika during pregnancy may have the virus in their systems for more than 2 months after birth, according to a case report published in the New England Journal of Medicine.

    Physicians at the Universidade de São Paulo and the Irmandade da Santa Casa de Misericórdia de São Paulo in São Paulo, Brazil monitored the health of a male child born with microcephaly at 40 weeks of gestation to a mother who had reported having Zika-like symptoms during the 26th week of pregnancy. The mother had presented with fever, pruritic maculopapular rash, headache, conjunctival hyperemia, and swelling and pain in the joints of the hands and feet during her third trimester, and all the symptoms had resolved spontaneously. She had not left São Paulo during her pregnancy; the physicians treating her suspect that she could have been infected via sexual transmission from the baby’s father, who had traveled to the northeast region of Brazil, where there have been multiple outbreaks of the virus. Samples obtained from the mother and father at days 59 and 67 after birth were positive for Zika-specific IgG and negative for IgM.

    The child, who was born on January 2, 2016, was 6.8 pounds at birth; he was 18.9 inches long and had a head circumference of 12.8 inches. Microcephaly was not detected during an initial physical examination. At birth, the physicians analyzed the baby’s cerebrospinal fluid and performed ophthalmologic and optoacoustic exams; findings on all were normal. However, an MRI revealed “reduced brain parenchyma, notably in the frontal and parietal lobes, foci of calcification in the subcortical area, and compensatory dilatation of the infratentorial supraventricular system,” they wrote.

    The baby’s serum, saliva, and urine were tested for Zika using qRT-PCR assay at day 54, and all 3 were positive for Zika RNA, with 1.4×105 copies per milliliter in the serum, 4.1×104 in the saliva, and 5.4×103 in the urine, respectively. RNA sequencing of a urine sample obtained from the infant showed a high degree of similarity with samples isolated in the Americas with 98.5% bootstrap support. According to the authors, virus-specific IgM and IgG were positive as well. On day 67, the baby still had detectable levels of Zika RNA in his blood (2.8×104 copies per milliliter) and, on day 216, although virus RNA was no longer detectable, virus-specific IgG titer remained high (>320).

    “When the infant was examined on day 54, he had no obvious illness or evidence of any immunocompromising condition,” the authors wrote in their report. “However, by 6 months of age, he showed neuropsychomotor developmental delay, with global hypertonia and spastic hemiplegia, with the right dominant side more severely affected.”

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  3. Oliveira DB, Almeida FJ, Durigon EL, Mendes ÉA, Braconi CT, Marchetti I, Andreata-Santos R, Cunha MP, Alves RP, Pereira LR, Melo SR, Neto DF, Mesquita FS, Araujo DB, Favoretto SR, Sáfadi MA, Ferreira LC, Zanotto PM, Botosso VF, Berezin EN. Prolonged Shedding of Zika Virus Associated with Congenital Infection. N Engl J Med. 2016 Sep 22;375(12):1202