Congenital Zika syndrome with arthrogryposis: retrospective case series study

Abstract

Objective 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.Design Retrospective case series study.Setting Association for Assistance of Disabled Children, Pernambuco state, Brazil.Participants Seven children with arthrogryposis and a diagnosis of congenital infection presumably caused by Zika virus during the Brazilian microcephaly epidemic.Main outcome measures Main clinical, radiological, and electromyographic findings, and likely correlation between clinical and primary neurological abnormalities.Results 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.Conclusions 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.

Lessons Learned at the Epicenter of Brazil’s Congenital Zika Epidemic: Evidence From 87 Confirmed Cases

“…Our results suggest that head ultrasound should be performed initially in suspected or probable cases of CZS. Some studies have associated ZIKV infection with developmental abnormalities, such as arthrogryposis and microphthalmia [25][26][27]. Eighteen infants (21%) in our series had associated malformations, manifested as arthrogryposis involving >1 joint contractures of upper and lower limbs, clubfoot, and knee flexion contracture.…”

Serial Head and Brain Imaging of 17 Fetuses With Confirmed Zika Virus Infection in Colombia, South America

“…Talipes equinovarus, the first sign for two patients, has been seen in previously reported Zika cases and might be due to damage to the corticospinal tract or to the central or peripheral motor neurons (20). Other ultrasound findings included arthrogryposis, ventriculomegaly, intracranial calcifications, dysgenesis or agenesis of the corpus callosum, dysgenesis of the cerebellar vermis and reduction in brain volume, which are consistent with a literature review of congenital Zika syndrome (6).…”

Visual and Motor Deficits in Grown-up Mice with Congenital Zika Virus Infection

“…One recently published retrospective study summarized the clinical and radiological features of arthrogryposis in presumed ZIKV-infected children including the presence of arthrogryposis in all the four limbs of 86% of children, but only the lower limbs of 14% (van der Linden et al, 2016). It is possible that previous animal model studies found no such similar phenomenon because arthrogryposis is not remarkable at birth and, in contrast to our study, these studies did not rear neonatal mice to the age when mice learn to walk.…”