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.

Fig 1 (A) Contracture in flexion of knee; (B) hyperextension of knee (knee dislocation); (C) clubfeet; (D) deformities in 2nd, 3rd, and 4th fingers; (E) joint contractures in legs and arms, without involvement of trunk

Fig 2 (A) Magnetic resonance image showing bilateral dislocation of hips, epiphyseal core (small arrow), and dysplastic acetabulum (large arrow); (B) 3D computed tomogram showing bilateral dislocation of hips; (C) anteroposterior radiographs showing features compatible with dislocation of hips: interruption of Shenton’s arc , epiphysis hypoplastic proximal femoral acetabular index of 35 degrees, and right and left proximal femoral epiphysis located laterally on side and bottom quadrant ombredanne; (D) radiograph shows subluxation of knee (arrows)

Fig 3 Spine and brain magnetic resonance imaging of baby with arthrogryposis. Sagittal T2 weighted fast imaging employing steady state acquisition (FIESTA) (A) showing apparently reduced spinal cord thickness (short arrows) and mega cisterna magna (long arrow). Axial reconstruction of T2 weighted FIESTA (B) showing reduction of medullary cone ventral roots (long arrows) compared with dorsal roots (short arrows). Sagittal T2 weighted image (C) showing hypogenesis of corpus callosum (long white arrow), enlarged cisterna magna (long black arrow), enlarged fourth ventricle (short black arrow), and pons hypoplasia (short white arrow). Axial T2 weighted imaging (D) showing pachygyria in frontal lobes (black arrows) and severe ventriculomegaly, mainly at posterior part of lateral ventricles. Axial susceptibility weighted image (E and F) showing some hypointense small dystrophic calcifications (white arrows) in junction between cortical and subcortical white matter (E) and in midbrain (F)

Fig 4 Adductor longus muscle of child with irreducible dislocation of hips before surgery. Colour is characteristic of fibrofatty infiltration, typical of initial phase of neuropathies