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Congenital Zika Virus Infection: Beyond Neonatal Microcephaly To the Editor In their timely description on the major central nervous system lesions caused by Zika virus (ZIKV) congenital infection, Melo et al1 reported on the neuroimaging, laboratory, and histological findings among 11 children born with ZIKV congenital infection syndrome. Aside from microcephaly and its associated cortical malformations, the authors also described the presence of arthrogryposis among 3 children. In the pathological findings, they observed fewer than expected motor nerve cells in the spinal cord in 1 of the newborns who died after birth. The association of arthrogryposis multiplex congenita with ZIKV congenital infection is a common finding within this spectrum, in which presumably multifaceted pathological mechanisms involving the first and second motor neurons need to be clarified. We have recently published an article on the alarming frequency of arthrogryposis multiplex congenita related to ZIKV congenital infection and the description among animals that contracted other types of Flaviviridae viruses intrauterinely. Interestingly, among these animals, autopsies revealed significant findings in the spinal cord, including the complete loss of motor neurons in the anterior horns.2 Additionally, a recent article published by Martines et al3 demonstrated microcephaly and severe arthrogryposis among 3 newborns who died after birth. Immunohistochemical as well as molecular biology tests performed in 2 of these newborns' brains showed positive results for ZIKV in neural cells and areas of microcalcification. The authors suggested that arthrogryposis multiplex congenita would be a consequence of viral neurotropism, subsequent brain damage, and, as a result, interference in neuromuscular signaling leading to fetal akinesia. Furthermore, van der Linden et al4 highlighted the clinical, radiological, and electromyographic features among 7 children born with congenital infection that was presumably related to ZIKV. Arthrogryposis was present universally and consisted of different types and locations within the upper and lower limbs. Nerve conduction studies showed normal amplitudes and conduction velocity for the sensory nerve action potentials and moderately low amplitudes and normal distal motor latencies and conduction velocities for the obtained compound motor action potentials. Needle electromyography demonstrated moderate signs of remodeling of the motor units and a reduced recruitment pattern. Among 4 children, spinal magnetic resonance imaging results revealed an apparent thinning of the cord and reduced ventral roots. Taking the features from our example of an animal model2 with the recent report from van der Linden et al,4 we suggest that the multifaceted causes of ZIKV arthrogryposis multiplex congenita are possibly more related to a combination of fetal akinesia from an underdevelopment and/or destruction of the motor frontal cortex and anterior horns of the spinal cord rather than a major involvement of the peripheral neurological system.