Spectrum of Spinal Cord,Spinal Root,and Brain MRI Abnormalities in Congenital Zika Syndrome with and without Arthrogryposis

BACKGROUND AND PURPOSE:Arthrogryposis is among the malformations of congenital Zika syndrome. Similar to the brain, there might exist a spectrum of spinal cord abnormalities. The purpose of this study was to explore and describe in detail the MR imaging features found in the spinal cords, nerve roots, and brains of children with congenital Zika syndrome with and without arthrogryposis.MATERIALS AND METHODS:Twelve infants with congenital Zika syndrome (4 with arthrogryposis and 8 without) who had undergone brain and spinal cord MR imaging were retrospectively selected. Qualitative and quantitative analyses were performed and compared between groups.RESULTS:At visual inspection, both groups showed reduced thoracic spinal cord thickness: 75% (6/8) of the group without arthrogryposis and 100% (4/4) of the arthrogryposis group. However, the latter had the entire spinal cord reduced and more severely reduced conus medullaris anterior roots (respectively, P = .002 and .007). Quantitative differences were found for conus medullaris base and cervical and lumbar intumescences diameters (respectively, P = .008, .048, .008), with more prominent reduction in arthrogryposis. Periventricular calcifications were more frequent in infants with arthrogryposis (P = .018).CONCLUSIONS:Most infants had some degree of spinal cord thickness reduction, predominant in the thoracic segment (without arthrogryposis) or in the entire spinal cord (with arthrogryposis). The conus medullaris anterior roots were reduced in both groups (thinner in arthrogryposis). A prominent anterior median fissure of the spinal cord was absent in infants without arthrogryposis. Brain stem hypoplasia was present in all infants with arthrogryposis, periventricular calcifications, in the majority, and polymicrogyria was absent.

The Zika virus infection is transmitted by a bite from an infected mosquito, with Aedes aegypti being the main vector.¹ Zika virus was first discovered in 1947 in monkeys in the Zika forest in Uganda,² and human infection was identified in 1952.³ The first epidemic of Zika virus occurred only in 2007 in Micronesia and the Yap Islands.⁴ The second epidemic was found in 2013, in French Polynesia,⁵ and the third began in Brazil,^6,7 where it was initially detected in Bahia, Northeast Brazil, in March 2015.^6,8In September 2015, a substantial increase in the incidence of infants with microcephaly was detected in northeast Brazil.⁸ For the first time, a strong increase of evidence suggested the association between the Zika virus infection outbreak and microcephaly by congenital infection.⁹ In Brazil, on December 31, 2016, there were 2366 cases of microcephaly and other central nervous system malformations suggestive of congenital Zika syndrome.¹⁰ There are 2 major lineages of Zika virus, the African, reported recently in Guinea-Bissau, and the Asian, reported from Asia and the West Pacific region to the Americas and Cabo Verde, which is the strain currently in Brazil.¹⁰ Neurologic complications have been related only to the Asian strains after 2007.¹⁰ The explanation as to why and how the Brazilian Zika virus strain could have developed this neurotropism for the central nervous system is still unknown.The disease has already spread and, according to the World Health Organization, 76 countries and territories, particularly in Latin America, have reported evidence of transmission of the Zika virus by mosquitoes. Cases of microcephalic infants have been reported in 29 countries.¹⁰In addition to microcephaly, other serious brain abnormalities were observed, especially brain calcifications, predominantly in the cortical and subcortical white matter junction, associated with malformations of cortical development (often polymicrogyria or pachygyria with predominant frontal lobe involvement) and a simplified cortical gyral pattern. Other frequent imaging findings are ventriculomegaly; decrease in brain, brain stem, and cerebellar volumes; enlargement of the cisterna magna and the extra-axial subarachnoid space; corpus callosum abnormalities (hypogenesis and hypoplasia); and delayed myelination.¹¹The congenital Zika syndrome is an entity without a well-known clinical spectrum, probably with only the most severe cases of the spectrum recognized. Other malformations have been described in some infants, such as ophthalmologic alterations^12,13 and arthrogryposis.^11,13,14 Currently, 8% of the children with presumed congenital Zika virus infection followed by the Association for Assistance of Disabled Children (AACD) in Recife, Brazil have arthrogryposis. Among the children with CSF immunoglobulin M (IgM) who tested positive for Zika virus, 6.6% have arthrogryposis.Arthrogryposis multiplex congenita, often known simply as arthrogryposis, is a syndrome characterized by joint contractures, present since birth, affecting ≥2 areas of the body.^15–20 These joint malformations can be attributed to different disorders, such as defects of uterine environment, disorders of connective tissues, muscular dystrophies, and other abnormalities or conditions that affect the central or peripheral nervous systems in at least one of the components of the motor pathways from the spinal cord to muscles.^16,18 Regardless of the cause, children affected by arthrogryposis have onset and severe weakness early in intrauterine life, with immobilization of joints at different developmental stages.¹⁶No study has yet analyzed qualitatively and quantitatively MR imaging of the spinal cord of children with congenital Zika syndrome, to our knowledge. Because there is a spectrum of congenital Zika syndrome for brain abnormalities, a similar spectrum might occur in the spinal cord. Therefore, the aim of this study was to explore and describe in detail the MR imaging features found in the spinal cord and nerve roots of infants with congenital Zika syndrome with or without arthrogryposis.