Description of 13 Infants Born During October 2015-January 2016 With Congenital Zika Virus Infection Without Microcephaly at Birth - Brazil.

Congenital Zika virus infection can cause microcephaly and severe brain abnormalities (1). Congenital Zika syndrome comprises a spectrum of clinical features (2); however, as is the case with most newly recognized teratogens, the earliest documented clinical presentation is expected to be the most severe. Initial descriptions of the effects of in utero Zika virus infection centered prominently on the finding of congenital microcephaly (3). To assess the possibility of clinical presentations that do not include congenital microcephaly, a retrospective assessment of 13 infants from the Brazilian states of Pernambuco and Ceará with normal head size at birth and laboratory evidence of congenital Zika virus infection was conducted. All infants had brain abnormalities on neuroimaging consistent with congenital Zika syndrome, including decreased brain volume, ventriculomegaly, subcortical calcifications, and cortical malformations. The earliest evaluation occurred on the second day of life. Among all infants, head growth was documented to have decelerated as early as 5 months of age, and 11 infants had microcephaly. These findings provide evidence that among infants with prenatal exposure to Zika virus, the absence of microcephaly at birth does not exclude congenital Zika virus infection or the presence of Zika-related brain and other abnormalities. These findings support the recommendation for comprehensive medical and developmental follow-up of infants exposed to Zika virus prenatally. Early neuroimaging might identify brain abnormalities related to congenital Zika infection even among infants with a normal head circumference (4).

Discordant clinical outcomes of congenital Zika virus infection in twin pregnancies.

Congenital Zika syndrome is an emergent cause of a congenital infectious disorder, resulting in severe damage to the central nervous system and microcephaly. Despite advances in understanding the pathophysiology of the disease, we still do not know all the mechanisms enrolled in the vertical transmission of the virus. As has already been reported in other types of congenital infectious disorders in dizygotic twin pregnancies, it is possible that the virus affects only one of the fetuses. In this article, we report on two cases of twin pregnancies exposed to the Zika virus, but with only one of the fetuses affected with microcephaly and brain damage. This indicates the urgent need for more studies regarding the pathophysiology of viral infection and the mechanisms involved in the natural protection against the virus.

Congenital Zika syndrome with arthrogryposis: retrospective case series study.

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.

Discordant clinical outcomes of congenital Zika virus infection in twin pregnancies / Evolução clínica discordante da infecção congénita do vírus Zika em gestação gemelar

ABSTRACT Congenital Zika syndrome is an emergent cause of a congenital infectious disorder, resulting in severe damage to the central nervous system and microcephaly. Despite advances in understanding the pathophysiology of the disease, we still do not know all the mechanisms enrolled in the vertical transmission of the virus. As has already been reported in other types of congenital infectious disorders in dizygotic twin pregnancies, it is possible that the virus affects only one of the fetuses. In this article, we report on two cases of twin pregnancies exposed to the Zika virus, but with only one of the fetuses affected with microcephaly and brain damage. This indicates the urgent need for more studies regarding the pathophysiology of viral infection and the mechanisms involved in the natural protection against the virus.

RESUMO A síndrome congênita do Zika vírus é uma causa de infecção congênita emergente, resultando em graves danos ao sistema nervoso central e microcefalia. Apesar dos avanços na compreensão da fisiopatologia da doença, ainda não conhecemos todo o mecanismo envolvido na transmissão vertical do vírus. Como já foi relatado em outros tipos de infecções congênitas em gestações gemelares dizigóticas, é possível que apenas um dos fetos seja afetado pelo vírus. Este artigo descreve 2 casos de gestações gemelares expostas ao vírus Zika, onde apenas um dos fetos foi afetado, com microcefalia associado a graves danos no sistema nervoso central. Isso indica a necessidade urgente de mais estudos sobre a fisiopatologia da infecção viral e os mecanismo envolvidos na proteção natural contra o vírus.

Epileptic seizures in children with congenital Zika virus syndrome / Crises epilépticas em crianças com síndrome congênita do Zika vírus

Abstract Objectives: to describe preliminary data referred to epileptic seizures and the probability of occurring these epileptic seizures in the infants' first months of life with congenital Zika virus (ZIKV) syndrome. Methods: concurrent cohort study including newborns and infants with congenital Zika virus syndrome attended at the specialized outpatient clinic at IMIP, Recife, Pernambuco, from October 2015 to May 2016. Results: data on 106 infants were analyzed with confirmed or suspected association to ZIKV infection. Forty children (38.7%) presented an epileptic seizure, classified at 43.3% of the cases as being spasms, 22.7% as generalized tonic seizures, 20.5% as partial and 4.5% other types of seizures. The median of days until the first report on the occurrence of epileptic seizure was 192 days of life. Conclusions: children with congenital Zika virus syndrome presented a high incidence of epileptic seizures before the end of the first semester of life, and spasm was the epileptic seizure mostly observed.

Resumo Objetivos: descrever dados preliminares referentes às crises epilépticas e à probabilidade de ocorrência dessas crises nos primeiros meses de vida em crianças com síndrome congênita do Zika vírus (ZIKV). Métodos: estudo de coorte concorrente incluindo recém-nascidos e lactentes com síndrome congênita do Zika vírus, atendidos no ambulatório especializado do IMIP, Recife, Pernambuco durante o período de outubro 2015 a maio 2016. Resultados: foram analisados dados de 106 lactentes com diagnóstico confirmado ou provável associação da infecção pelo ZIKV. Quarenta crianças (38,7%) apresentaram crise epiléptica, classificada em 43,3% dos casos como sendo espasmo, 22,7% como crise generalizada tônica, 20,5% parcial e 4,5% crises epilépticas de outros tipos. A mediana dos dias até o primeiro relato de ocorrência de crise epiléptica foi 192 dias de vida. Conclusões: crianças com síndrome congênita do Zika vírus apresentaram elevada incidência de crises epilépticas de aparecimento precoce, antes do final do primeiro semestre de vida, sendo o espasmo o tipo de crise mais observado.