A new insight into the definition of microcephaly in Zika congenital syndrome era / Uma nova visão da definição de microcefalia na era da síndrome congênita do vírus Zika / Una nueva perspectiva en la definición de microcefalia durante la era del síndrome congénito Zika

Abstract: This study aimed to compare the anthropometric measurements and body proportionalities of neonates born before the Zika virus epidemic with those born during this period. We compared 958 neonates born during the pre-Zika epidemic with 264 neonates born during the epidemic period. The newborns had their head circumference, weight, and length classified according to the Fenton & Kim growth chart. We considered disproportionate those individuals that presented microcephaly and adequate weight or length for sex and gestational age, and those whose head circumferences were lower than the ratio ((length / 2) + 9.5) - 2.5cm. We estimated the frequencies of Zika positivity and brain imaging findings among neonates with microcephaly born during the epidemic period, concerning the anthropometric and body proportionality parameters. Low weight and proportionate microcephaly were similar among newborns from both periods. However, the frequencies of newborns with microcephaly with a very low length and disproportionate microcephaly were higher among the neonates of the epidemic period with brain abnormalities and positive for Zika virus. We conclude that, at birth, the disproportion between head circumference and length can be an indicator of the severity of microcephaly caused by congenital Zika.

Resumo: O estudo buscou comparar as medidas antropométricas e proporções corporais de recém-nascidos do período pré-Zika com os nascidos durante a epidemia de microcefalia congênita pelo vírus Zika. Comparamos 958 recém-nascidos do período pré-Zika com 264 nascidos durante o período epidêmico. Foram classificados o perímetro cefálico, peso e comprimento dos neonatos de acordo com a escala de crescimento de Fenton & Kim. Consideramos desproporcionais aqueles neonatos que apresentaram microcefalia e peso ou comprimento adequado para sexo e idade gestacional, além daqueles cujo perímetros cefálicos eram menores que a razão ((comprimento / 2) + 9,5) -2,5cm. Estimamos as frequências de positividade para Zika e resultados de imagens de cerebrais entre bebês com microcefalia nascidos no período epidêmico, em relação aos parâmetros antropométricos e de proporcionalidade corporal. Baixo peso e microcefalia proporcional foram semelhantes entre recém-nascidos de ambos os períodos. Entretanto, as frequências de neonatos com microcefalia e com comprimento muito curto e microcefalia desproporcional foram muito maiores entre os nascidos no período epidêmico com anomalias cerebrais e positivos para Zika. Concluímos que a desproporção entre perímetro cefálico e comprimento ao nascer pode ser um indicador da gravidade da microcefalia causada pela síndrome congênita do Zika vírus.

Resumen: El objetivo del estudio fue comparar las medidas antropométricas y de proporcionalidad corporal en neonatos nacidos durante un período pre-Zika, con quienes nacieron durante la epidemia de microcefalia por el síndrome congénito Zika. Comparamos a 958 neonatos nacidos durante la epidemia pre-Zika, con 264 neonatos nacidos durante el período epidémico. A los recién nacidos se les clasificó su circunferencia de la cabeza, peso y longitud según la tabla de crecimiento Fenton & Kim. Consideramos desproporcionados a quienes presentaron microcefalia y peso o longitud adecuada para sexo y edad gestacional, y quienes tenían unas circunferencias de cabeza cuyo ratio era menor que ((longitud / 2) + 9.5) - 2.5cm. Estimamos las frecuencias de positividad para Zika, así como los resultados de imágenes cerebrales entre neonatos nacidos con microcefalia durante el período epidémico, en relación con parámetros antropométricos y de proporcionalidad corporal. Bajo peso y microcefalia proporcional fueron similares entre los recién nacidos de ambos períodos. No obstante, las frecuencias de recién nacidos con microcefalia con una longitud muy baja y microcefalia desproporcionada fueron mayores entre los neonatos del período epidémico, con anormalidades cerebrales y positivos para Zika. Concluimos que la desproporción entre la circunferencia de cabeza y longitud al nacer puede ser un indicador de la gravedad de la microcefalia, causada por el Zika congénito.

Radiographic evaluation of dental anomalies in patients with congenital Zika virus syndrome

Abstract: Numerous studies have reported abnormalities in the development of oral structures in congenital infections that also involve microcephaly. In this context, it is necessary to identify possible dental anomalies of shape and/or number in patients with Zika virus syndrome using radiography. The study population consisted of 35 children born with congenital ZIKV who underwent intraoral radiographic examinations for 24 consecutive months. A modified periapical technique was performed in an occlusal position for the maxilla and mandible. Categorical data were expressed as absolute and percentage frequencies and compared using Pearson's Chi-square test, with a 95% confidence interval. Of the entire sample, eight children (22.8%) had dental anomalies of shape and/or number, and four children (11.4%) presented with both anomalies, with agenesis of the upper and lower deciduous/permanent incisors and dental form modifications, such as microdontia and anomalous cusps. When we considered age and sex, there was no statistically significant difference between patients who presented with agenesis and those who presented with modifications. Children with congenital Zika virus syndrome were more likely to have dental modifications in the number and shape of their teeth, and it is essential to implement medium- to long-term monitoring to diagnose other possible alterations throughout the development of the mixed and permanent dentition, favoring their treatment.

Caracterização inovadora da morfologia da cabeça de bebês nascidos com o vírus zika: uma inovação metodológica para amplas aplicações clínicas / Novel characterization of head morphology of infants born with Zika Virus: a methodological innovation for broad clinical applications

Introdução: A epidemia do vírus Zika em 2016 constituiu uma emergência de saúde pública, com o chamando da OMS para vigilância reforçada na detecção precoce de microcefalia relacionada às condições neurológicas. Métodos: Quarenta e quatro crianças infectadas pelo vírus Zika foram avaliadas e comparadas com crianças saudáveis com o objetivo de identificar as medidas mais confiáveis do formato e tamanho da cabeça, explorando o relacionamento entre fenótipo craniofacial e anormalidades cerebrais. A análise de componentes principais (ACP) foi utilizada para identificar padrões de variação na morfologia craniofacial. As seguintes medições adicionais da abóboda craniana foram realizadas; altura cefálica (AC), comprimento cefálico (ComC), circunferência cefálica (CC) e ângulo naso-frontal (ANF). O nível de anormalidade cerebral presente nas tomografias, a gravidade da perda de volume do parênquima cerebral e ventriculomegalia foram classificadas como leve, moderada ou grave. Resultados: Os 12 primeiros componentes principais das abóbodas analisadas explicaram 91% da variação da abóboda craniana. Correlações significativas foram detectadas entre a pontuação do segundo CP da abóbada craniana e CC (+0,66), AC (+0,87), ComC (+0,80) e ANF (-0,48). Conclusão: Este estudo recomenda mensurar a AC em pacientes com infecção pelo vírus Zika, em vez de CC como recomendado pela OMS, para melhorar a sensibilidade e especificidade da detecção precoce(AU)

Background: The 2016 Zika virus epidemic constituted a public health emergency, with the WHO calling for strengthened surveillance for the early detection of related microcephaly and associated neurological conditions. Methods: We analysed 44 Zika infected infants and matched controls to identify the most reliable measurements of head shape and size and explore the relationship between craniofacial phenotype and brain abnormalities. Principal component analysis (PCA) was applied to identify patterns of variation in the craniofacial morphology of Zika cases relative to controls. We carried out the following additional measurements of the cranial vault, the head circumference (HC), head height (HH), head length (HL) and naso-frontal-angle (NFA). The level of brain abnormality present in the CT scans, mainly the severity of parenchymal volume loss and ventriculomegaly, was classified as being mild, moderate or severe. Results: The first 12 PCs of the vaults we analysed explained 91% of the variation of the cranial vault between Zika cases and controls. Significant correlations were detected between the score of the 2nd PC of the cranial vault and HC (+0.66); HH (+0.87); HL (+0.80) and NFA (-0.48). Conclusion: We recommend measuring HH in Zika patients, rather than HC as recommended by WHO, to improve the sensitivity and specificity of early detection(AU)

Evaluation of the frequency of neuroimaging findings in congenital infection by Zika virus and differences between computed tomography and magnetic resonance imaging in the detection of alterations

Abstract INTRODUCTION: Congenital infection by the Zika virus (ZIKV) is responsible for severe abnormalities in the development of the central nervous system. The aim of this study was to evaluate and compare the ability of computed tomography (CT) and magnetic resonance (MR) to detect patterns of involvement of the central nervous system in congenital ZIKV syndrome. METHODS: We retrospectively analyzed CT and MR images from 34 patients with congenital ZIKV syndrome and evaluated the differences between the two methods in detecting alterations. RESULTS: The predominant radiographic finding was a simplified gyral pattern, present in 97% of cases. The second most common finding was the presence of calcifications (94.1%), followed by ventriculomegaly (85.3%), dysgenesis of the corpus callosum (85.3%), craniofacial disproportion and redundant scalp (79.4%), complete opercular opening (79.4%), occipital prominence (44.1%), cerebellar hypoplasia (14.7%), and pontine hypoplasia (11.8%). The gyral pattern was extensively simplified in most cases, and calcifications were located predominantly at the cortical-subcortical junction. CT was able to better identify calcifications (94.1% × 88.2%), while MRI presented better spatial resolution for the characterization of gyral pattern (97% × 94.1%) and corpus callosum dysgenesis (85.3% × 79.4%). CONCLUSIONS: Although congenital ZIKV syndrome does not present pathognomonic neuroimaging findings, some aspects, such as calcifications at the cortical-subcortical junction, especially when associated with compatible clinical and laboratory findings, are suggestive of intrauterine ZIKV infection.

Características epidemiológicas, clínicas e imagenológicas en pacientes con microcefalia y sospecha de infección por el virus del zika. Servicio Desconcentrado Hospital Pediátrico Dr. Agustín Zubillaga / Epidemiological, clinical and imaging features of patients with microcephaly and suspected infection by zika virus. Servicio Desconcentrado Hospital Pediátrico Dr. Agustín Zubillaga

La infección por virus Zika es transmitida por la picadura del Aedes sp, aunque también se ha descrito la transmisión transplacentaria a los fetos. La microcefalia congénita es el primer hallazgo relacionado con la enfermedad y se asocia a defectos en la proliferación neuronal y muerte de las células progenitoras corticales que tiene como consecuencia una disminución de la producción neuronal y que resulta en una serie de trastornos cerebrales que comprometen la motricidad, visión, audición y funciones cognitivas. La presente investigación describió las características epidemiológicas, clínicas e imagenológicas en pacientes pediátricos con microcefalia secundario a la sospecha de infección por el virus Zika, que acudieron a la consulta de Neuropediatría del Servicio Desconcentrado Hospital Pediátrico Dr. Agustín Zubillaga de la ciudad de Barquisimeto, estado Lara durante el lapso diciembre 2016- septiembre 2017(AU)

Zika virus infection is transmitted by the bite of Aedes sp, although transplacental transmission to the fetuse has also been described. Congenital microcephaly is the first finding related to the disease and is associated with defects in neuronal proliferation and death of cortical progenitor cells, which result in a decrease in neuronal production and a group of brain disorders which compromise motor skills, vision, hearing and cognitive functions. The present study describes the epidemiological, clinical and imaging characteristics in pediatric patients with microcephaly secondary to suspected Zika virus infection who attended the Neuropediatric consultation of the Servicio Desconcentrado Hospital Pediátrico Dr. Agustín Zubillaga during the December 2016-September 2017 period(AU)

Epidemiological profile of 39 cases of microcephaly caused by congenital infections diagnosed in the state of Rio Grande do Sul between 2015-2017

Introduction: Microcephaly is a clinical finding that can arise from congenital anomalies or emerge after childbirth. Maternal infections acquired during pregnancy can result in characteristic brain damage in the newborn (NB), which may be visible even in the fetal stage. To describe the epidemiological profile of newborns with reported microcephaly and diagnosed with congenital infections in the state of Rio Grande do Sul between 2015 and 2017. Methods: A cross-sectional study was carried out on data collected from the Public Health Event Registry as well as from medical records. The investigation included serologies for toxoplasmosis and rubella; polymerase chain reaction (PCR) for Zika virus (ZIKV) in the blood and cytomegalovirus in the urine; non-treponemal tests for syphilis; and brain imaging tests. Results: Of the 257 reported cases of microcephaly, 39 were diagnosed with congenital infections. Severe microcephaly was identified in 13 patients (33.3%) and 51.3% of the cases showed alterations in brain imaging tests. In relation to the diagnosis of congenital infections, three patients (7.7%) were diagnosed with ZIKV, nine (23.1%) with cytomegalovirus, nine (23.1%) with toxoplasmosis, and 18 (46.1%) with congenital syphilis. The three cases of ZIKV showed calcification in brain imaging tests, signs of arthrogryposis, excess occipital skin and irritability, characterizing the typical phenotype of ZIKV infection. Conclusions: Most cases of congenital infection had severe neurological lesions, particularly the cases of ZIKV, which can cause neurodevelopmental delays and sequelae in these infants throughout early childhood.

Zika Vírus na gestação / Zika Virus in pregnancy

A infecção congênita pelo zika vírus (ZIKV) tornou-se uma pandemia em meados de 2015 e é considerada uma emergência em saúde pública de interesse mundial, no que tange à prevalência, transmissão e possíveis sequelas neurológicas fetais. O artigo busca realizar uma revisão sobre a infecção do ZIKV na gestação e suas consequências para o feto. Realizada revisão a partir de estudos qualitativo, retrospectivo e documental, baseando-se em levantamento de produções científicas publicadas entre 2016 e 2018. Por meio da estratégia de busca, localizou-se 194 artigos, dos quais 28 foram selecionados para redação final. Conclui-se que as alterações ultrassonográficas, advindas de infecção no primeiro e segundo trimestre, são devidas à ação viral direta, efeito de imunoglobulinas e alterações na placentação. As alterações fetais são sobretudo as neurológicas, cardíacas e oftalmológicas. Gestantes com infecção comprovada, ou suspeitada, devem ser acompanhadas até o parto. Os investimentos em medicamentos e vacinas devem ser continuados.(AU)

Congenital zika virus (ZIKV) infection has become pandemic by mid-2015 and is considered a public health emergency of global concern with regard to prevalence, transmission and possible fetal neurological sequelae. The article aims to review the ZIKV infection in pregnancy and its consequences for the fetus. A review was carried out based on a qualitative, retrospective and documental studies, based on a survey of scientific productions published between 2016 and 2018. Through the search strategy, 194 articles were found, of which 28 were selected for final writing. It is concluded that ultrasonographic changes, due to infection in the first and second trimester, are due to direct viral action, immunoglobulins effect and changes in placentation. Fetal alterations are especially those neurological, cardiac and ophthalmologic. Pregnant women with proven or suspected infection should be followed up until delivery. Investments in drugs and vaccines should be continued.(AU)

Microcephaly caused by congenital Zika virus infection and viral detection in maternal urine during pregnancy / Microcefalia causada por infecção congênita pelo Zika virus e detecção viral na urina materna durante a gestação

Summary Currently Latin America is undergoing a major epidemic of Zika virus, which is transmitted by Aedes mosquitoes. Concern for Zika virus infection has been increasing as it is suspected of causing brain defects in newborns such as microcephaly and, more recently, potential neurological and autoimmune complications including Guillian-Barré syndrome and acute disseminated encephalomyelitis. We describe a case of virus infection in a 25-year-old woman during the first trimester of her pregnancy, confirmed by laboratory tests only for the detection of viral particles in maternal urine, with imaging studies demonstrating the progression of cranial and encephalic changes in the fetus and later in the newborn, such as head circumference reduction, cerebral calcifications and ventriculomegaly.

Resumo Atualmente, a América Latina está passando por uma grande epidemia de Zika vírus, transmitido por mosquitos Aedes. A preocupação pela infecção pelo Zika vírus vem aumentando, uma vez que é suspeita de causar defeitos cerebrais em recém-nascidos, como a microcefalia e, mais recentemente, potenciais complicações neurológicas e autoimunes, como síndrome de Guillian-Barré e encefalomielite disseminada aguda. Descrevemos um caso de infecção pelo vírus em uma mulher de 25 anos durante o primeiro trimestre de gestação, confirmado dentre os exames laboratoriais apenas pela detecção de partículas virais na urina materna, com estudos de imagens demonstrando a evolução das alterações cranianas e encefálicas no feto e no recém-nascido, como redução do perímetro cefálico, calcificações cerebrais e ventriculomegalia.

Presumed Zika virus-related congenital brain malformations: the spectrum of CT and MRI findings in fetuses and newborns / Malformações congênitas do encéfalo presumivelmente relacionadas ao Zika vírus: espectro de achados de RM e TC em fetos e neonatos

ABSTRACT The new epidemic of Zika virus infection raises grave concerns, especially with the increasingly-recognized link between emerging cases of microcephaly and this infectious disease. Besides small cranial dimensions, there are striking morphologic anomalies in the fetal brain. Key anomalies include cortical developmental malformations and a peculiar distribution of pathologic calcifications. These potentially indicate a new pattern of congenital central nervous system infection. Methods: Eight women underwent fetal MRI. Four infants also underwent postnatal CT. Five of the women underwent amniocentesis. Results: All neonates were born with microcephaly. On fetal MRI, ventriculomegaly, marked reduction of white matter thickness, severe sylvian fissure simplification, abnormal sulcation, and diffuse volumetric loss of cerebellar hemispheres were consistently seen. On postnatal CT, diffuse subcortical and basal ganglia calcifications were observed. The Zika virus was detected in two amniocenteses by polymerase chain reaction assays. Conclusion: We hope to assist the medical community in recognizing the spectrum of encephalic changes related to congenital Zika virus infection.

RESUMO Os novos casos epidêmicos de infecção pelo vírus Zika suscitam grande preocupação, sobretudo com o crescente reconhecimento da ligação entre casos emergentes de microcefalia e esta doença infecciosa. Além da cabeça de pequenas dimensões, existem profundas alterações morfológicas no encéfalo fetal. Anomalias mais típicas incluem malformações do desenvolvimento cortical e uma distribuição peculiar de calcificações patológicas. Estes dados potencialmente indicam um novo padrão de infecção congênita do sistema nervoso central. Métodos: Oito mulheres foram submetidas a RM fetal. Quatro crianças também realizaram TC pós-natal. Cinco mulheres foram submetidas a amniocentese. Resultados: Todos os neonatos nasceram com microcefalia. Na RM fetal, ventriculomegalia, acentuada redução da espessura da substância branca, acentuada simplificação da fissura sylviana, sulcação anormal e redução volumétrica difusa dos hemisférios cerebelares foram constantes. Na TC pós-natal, calcificações difusas subcorticais e nos núcleos da base foram observadas. O vírus Zika foi detectado por PCR em duas amniocenteses. Conclusão: Esperamos dar suporte à comunidade médica em reconhecer este padrão de imagem potencialmente específico.

Altered intrauterine ultrasound, fetal head circumference growth and neonatal outcomes among suspected cases of congenital Zika syndrome in Brazil / Alterações ultrassonográficas intraútero, crescimento da circunferência cefálica fetal e desfechos neonatais entre casos presumíveis de síndrome da Zika congênita no Brasil

Abstract Objectives: to describe altered intrauterine ultrasound, analyze fetal head circumference (HC) growth and neonates' outcomes among presumed cases of congenital Zika syndrome in Brazil. Methods: 30 women were included in the study with suspected history of Zika virus (ZIKV) infection during pregnancy and fetal's brain altered on ultrasound diagnosis. Sociodemographic and obstetric characteristics, prenatal altered ultrasounds, HC and other perinatal outcomes have been described. The relation between HC and gestational age was analyzed by using random regression effects based on polynomials fractions. The Z test was calculated to determine an instant variant mean rate of the HC for each gestational age. Results: the mean gestational age of the ultrasound diagnosis was 33.3 + 4.7 weeks and HC at birth was 28.9 + 1.6 cm. The main altered brain ultrasound was microcephaly (96.7%). The analysis of the fetal head circumference showed an estimated increase of the average HC, as to gestational age, it did not occur in a linear form. The instant HC variation rate increased according to gestational age (p<0,001). Conclusions: Fetal's main morphological alteration was microcephaly, observing an increase in the head circumference according to gestational age in a non-linear form and the variation decreased with gestational age.

Resumo Objetivos: descrever alterações ultrassonográficas intraútero, analisar o crescimento da circunferência cefálica (CC) fetal e desfechos neonatais entre casos presumíveis de síndrome da Zika congênita no Brasil. Métodos: foram incluídas 30 mulheres com história sugestiva de infecção por Zikavirus (ZIKV) na gestação e diagnóstico ultrassonográfico de alteração cerebral fetal. Foram descritas as características sociodemográficas e obstétricas, alterações ultrassonográficas pré-natal, CC e os resultados perinatais. A relação entre a CC e a idade gestacional foi analisada utilizando-se modelos de regressão de efeitos aleatórios baseados em polinômios fracionais. O teste Z foi calculado para determinar a taxa de variação instantânea da CC média de cada idade gestacional. Resultados: a média da idade gestacional do diagnóstico ultrassonográfico foi de 33,3 + 4,7 semanas e da CC ao nascer foi de 28,9 + 1,6 cm. A principal alteração ultrassonográfica cerebral foi a microcefalia (96,7%). A análise da circunferência cefálica fetal demonstrou que o aumento da estimativa da CC média segundo a idade gestacional ocorreu de forma não linear. Observou-se ainda que a taxa de variação instantânea da CC aumentou segundo a idade gestacional (p<0,001). Conclusões: a principal alteração morfológica fetal foi a microcefalia, observando um crescimento da circunferência cefálica segundo a idade gestacional de forma não linear e que a variação diminui com a idade gestacional.

MICrocephaly, disproportionate pontine and cerebellar hypoplasia syndrome: A clinico-radiologic phenotype linked to calcium/calmodulin-dependent serine protein kinase gene mutation.

MICrocephaly, disproportionate pontine and cerebellar hypoplasia (MICPCH) syndrome, a rare X-linked disorder, generally seen in girls, is characterized by neurodevelopmental delay, microcephaly, and disproportionate pontine and cerebellar hypoplasia. It is caused by inactivating calcium/calmodulin-dependent serine protein kinase (CASK) gene mutations. We report a 2-year-old girl with severe neurodevelopmental delay, microcephaly, minimal pontine hypoplasia, cerebellar hypoplasia, and normal looking corpus callosum, with whom the conventional cytogenetic studies turned out to be normal, and an array-comparative genomic hybridization (a-CGH) analysis showed CASK gene duplication at Xp11.4. Our case highlights the importance of using clinico-radiologic phenotype to guide genetic investigation and it also confirms the role of a-CGH analysis in establishing the genetic diagnosis of MICPCH syndrome, when conventional cytogenetic studies are inconclusive.

Recent experience with Rett syndrome at a tertiary care center.

Rett syndrome (RS), a neurological developmental disorder, is one of the commonest causes of cognitive impairment in girls and women. These patients are often initially misdiagnosed as idiopathic mental retardation, cerebral palsy, or autism. Despite several reports from the West, there are very few reports from the Indian population. We present four female children with RS and emphasize the importance of early diagnosis.