RESUMO
The number of studies published on postnatal microcephaly in children with Congenital Zika Syndrome is small, clinical presentations vary and aspects of the evolution of these children remain unclarified. The present case series examined clinical characteristics and assessed the growth velocity of the head circumference, weight and height Z-scores in 23 children who developed postnatal microcephaly during follow-up in the Microcephaly Epidemic Research Group Pediatric Cohort. To estimate the change in the head circumference, weight and height Z-scores over time and compare the mean difference between sexes, we used multilevel mixed-effects linear regressions with child-specific random effects. Among these children, 60.9% (n = 14/23) presented with craniofacial disproportion, 60.9% (n = 14/23) with strabismus, 47.8% (n = 11/23) with early onset seizures, 47.8% (n = 11/23) with dysphagia and 43.5% (n = 10/23) with arthrogryposis. Of the 82.7% (n = 19/23) children who underwent neuroimaging, 78.9% (n = 15/19) presented with alterations in the central nervous system. Monthly growth velocity, expressed in Z-scores, of the head circumference was - 0.098 (95% CI % - 0.117 to - 0.080), of weight was: - 0.010 (95%-CI - 0.033 to 0.014) and of height was: - 0.023 (95%-CI - 0.046 to 0.0001). Postnatal microcephaly occurred mainly in children who had already presented with signs of severe brain damage at birth; there was variability in weight and height development, with no set pattern.
Assuntos
Microcefalia , Malformações do Sistema Nervoso , Complicações Infecciosas na Gravidez , Infecção por Zika virus , Zika virus , Brasil/epidemiologia , Criança , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Microcefalia/diagnóstico , Microcefalia/epidemiologia , Neuroimagem , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Infecção por Zika virus/complicações , Infecção por Zika virus/congênito , Infecção por Zika virus/epidemiologiaRESUMO
OBJECTIVE: The Bacille Calmette-Guérin (BCG) vaccine is routinely applied in Brazil. Adverse events (AE) may occur in patients with inborn or acquired immunodeficiencies, varying between local (BCGitis) or disseminated (BCGosis) reactions. We evaluated 53 individuals with local or disseminated adverse events to BCG vaccination to assess if they had inborn errors of immunity (IEI). METHODS: Patients diagnosed with an adverse event following BCG vaccination between 2014 and 2017 were included in the study. We collected clinical data, immunophenotyped T and B lymphocytes, and natural killer cells (NK), assessed oxidative function of neutrophils through dihydrorhodamine (DHR) 123 testing, and genotyped 361 genes related to IEI through targeted (panel) sequencing. RESULTS: The median age of the 53 individuals was four months (IQ 1.5-12), and 52.8% were male. Forty-eight (90.6%) individuals presented only locoregional AE and five (9.4%) presented both locoregional and disseminated AE. Nine (16.9%) patients were diagnosed with an IEI. Four of them presented BCGitis and five presented BCGosis after BCG vaccination. Clinically, four presented chronic granulomatous disease (CGD), three Mendelian susceptibility to mycobacterial disease (MSMD), and two severe combined immunodeficiency (SCID). Patients with IEI had a higher frequency of systemic symptomatology (p = 0.002), history of other infections (p < 0.001), parental consanguinity (p = 0.01), familial history of sick siblings (p < 0.001), or early deaths in the family (p < 0.01). CONCLUSION: There is a high frequency of IEI in patients with locoregional and disseminated adverse events to BCG vaccination, revealing the need for the investigation of IEI accompanied by clinical and familial inquiry.
Assuntos
Vacina BCG , Imunodeficiência Combinada Severa , Tuberculose , Pré-Escolar , Feminino , Humanos , Masculino , Vacina BCG/efeitos adversos , Brasil/epidemiologia , Imunodeficiência Combinada Severa/genética , Tuberculose/diagnóstico , Vacinação/efeitos adversosRESUMO
AIMS: Describing the urodynamic parameters of children aged 3 to 5 years with microcephaly related to congenital Zika syndrome and verifying the association with clinical, imaging and neurological characteristics. METHODS: From October 2018 to March 2020, children with Zika-related microcephaly underwent urological, ultrasonographic and urodynamic evaluation. In selected cases, complementary exams such as urethrocystography and scintigraphy were performed. The children also underwent a complete neurological evaluation. To compare frequency between groups, we used Pearson's chi-squared test or Fisher's exact test. RESULTS: This study evaluated 40 children, of whom 85% were 4 years old, and all had abnormalities on the urodynamic study, with low bladder capacity (92.5%) and detrusor overactivity (77.5%) as the most frequent findings. Only three children had ultrasound abnormalities, but no child had cystographic or scintigraphic abnormalities, and the postvoid residual volume was normal in 80% of cases. In spite of a frequency of 67.5% of intestinal constipation, there was no record of febrile urinary tract infection after the first year of life. All children presented severe microcephaly and at least one neurological abnormality in addition to microcephaly. The homogeneity of the children in relation to microcephaly severity and neurological abnormalities limited the study of the association with the urodynamic parameters. CONCLUSIONS: Urodynamic abnormalities in children aged 3 to 5 years with Zika-related microcephaly do not seem to characterize a neurogenic bladder with immediate risks for the upper urinary tract. The satisfactory bladder emptying suggests that the voiding pattern is reflex.
Assuntos
Microcefalia , Sistema Urinário , Infecção por Zika virus , Zika virus , Pré-Escolar , Humanos , Microcefalia/diagnóstico por imagem , Cintilografia , Urodinâmica , Infecção por Zika virus/complicações , Infecção por Zika virus/congênitoRESUMO
This cohort profile aims to describe the ongoing follow-up of children in the Microcephaly Epidemic Research Group Paediatric Cohort (MERG-PC). The profile details the context and aims of the study, study population, methodology including assessments, and key results and publications to date. The children that make up MERG-PC were born in Recife or within 120 km of the city, in Pernambuco/Brazil, the epicentre of the microcephaly epidemic. MERG-PC includes children from four groups recruited at different stages of the ZIKV microcephaly epidemic in Pernambuco, i.e., the Outpatient Group (OG/n = 195), the Microcephaly Case-Control Study (MCCS/n = 80), the MERG Pregnant Women Cohort (MERG-PWC/n = 336), and the Control Group (CG/n = 100). We developed a comprehensive array of clinical, laboratory, and imaging assessments that were undertaken by a 'task force' of clinical specialists in a single day at 3, 6, 12, 18 months of age, and annually from 24 months. Children from MCCS and CG had their baseline assessment at birth and children from the other groups, at the first evaluation by the task force. The baseline cohort includes 711 children born between February 2015 and February 2019. Children's characteristics at baseline, excluding CG, were as follows: 32.6% (184/565) had microcephaly, 47% (263/559) had at least one physical abnormality, 29.5% (160/543) had at least one neurological abnormality, and 46.2% (257/556) had at least one ophthalmological abnormality. This ongoing cohort has contributed to the understanding of the congenital Zika syndrome (CZS) spectrum. The cohort has provided descriptions of paediatric neurodevelopment and early epilepsy, including EEG patterns and treatment response, and information on the frequency and characteristics of oropharyngeal dysphagia; cryptorchidism and its surgical findings; endocrine dysfunction; and adenoid hypertrophy in children with Zika-related microcephaly. The study protocols and questionnaires were shared across Brazilian states to enable harmonization across the different studies investigating microcephaly and CZS, providing the opportunity for the Zika Brazilian Cohorts Consortium to be formed, uniting all the ZIKV clinical cohorts in Brazil.
Assuntos
Epidemias , Microcefalia/epidemiologia , Microcefalia/virologia , Pesquisa , Infecção por Zika virus/epidemiologia , Brasil/epidemiologia , Estudos de Casos e Controles , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Gravidez , Inquéritos e QuestionáriosRESUMO
BACKGROUND: While Zika virus (ZIKV) is now widely recognized as a teratogen, the frequency and full spectrum of adverse outcomes of congenital ZIKV infection remains incompletely understood. METHODS: Participants in the MERG cohort of pregnant women with rash, recruited from the surveillance system from December/2015-June/2017. Exposure definition was based on a combination of longitudinal data from molecular, serologic (IgM and IgG3) and plaque reduction neutralization tests for ZIKV. Children were evaluated by a team of clinical specialists and by transfontanelle ultrasound and were classified as having microcephaly and/or other signs/symptoms consistent with congenital Zika syndrome (CZS). Risks of adverse outcomes were quantified according to the relative evidence of a ZIKV infection in pregnancy. FINDINGS: 376 women had confirmed and suspected exposure to ZIKV. Among evaluable children born to these mothers, 20% presented with an adverse outcome compatible with exposure to ZIKV during pregnancy. The absolute risk of microcephaly was 2.9% (11/376), of calcifications and/or ventriculomegaly was 7.2% (13/180), of additional neurologic alterations was 5.3% (13/245), of ophthalmologic abnormalities was 7% (15/214), and of dysphagia was 1.8% (4/226). Less than 1% of the children experienced abnormalities across all of the domains simultaneously. Interpretation: Although approximately one-fifth of children with confirmed and suspected exposure to ZIKV in pregnancy presented with at least one abnormality compatible with CZS, the manifestations presented more frequently in isolation than in combination. Due to the rare nature of some outcomes and the possibility of later manifestations, large scale individual participant data meta-analysis and the long-term evaluation of children are imperative to identify the full spectrum of this syndrome and to plan actions to reduce damages.
Assuntos
Doenças do Sistema Nervoso Central/virologia , Complicações Infecciosas na Gravidez/virologia , Resultado da Gravidez , Infecção por Zika virus/patologia , Adulto , Brasil/epidemiologia , Doenças do Sistema Nervoso Central/congênito , Feminino , Humanos , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Zika virus , Infecção por Zika virus/congênitoRESUMO
Severe brain damage associated with Zika-related microcephaly (ZRM) have been reported to result in oropharyngeal dysphagia (OPD); however, it is unknown if OPD presents in children with prenatal Zika virus (ZIKV) exposure but only mild or undetectable abnormalities. The aims of this study were: to compare the frequency and characteristics of OPD in children with ZRM and in children without microcephaly born to mothers who tested polymerase chain reaction positive (PCR+) for ZIKV during pregnancy; and to investigate the concordance of caregiver reports of OPD with the diagnosis from the clinical swallowing assessment (CSA). Between Mar/2017 and May/2018, we evaluated 116 children (n = 58 with microcephaly, n = 58 children without microcephaly born to ZIKV PCR + mothers) participating in the Microcephaly Epidemic Research Group (MERG) cohort of children born during the 2015-2016 ZIKV epidemic in Pernambuco, Brazil. To assess OPD we used: a CSA; a clinical assessment of the stomatognathic system; and a questionnaire administered to caregivers. The frequency of OPD was markedly higher in children with ZRM (79.3%) than in the exposed but normocephalic group (8.6%). The children with microcephaly also presented more frequently with anatomic and functional abnormalities in the stomatognathic system. There was a high degree of agreement between the caregiver reports of OPD and the CSA (κ = 0.92). In conclusion, our findings confirm that OPD is a feature of Congenital Zika Syndrome that primarily occurs in children with microcephaly and provide support for policies in which children are referred for rehabilitation with an OPD diagnosis based on caregiver report.
Assuntos
Transtornos de Deglutição , Microcefalia , Complicações Infecciosas na Gravidez , Efeitos Tardios da Exposição Pré-Natal , Infecção por Zika virus , Zika virus , Brasil , Criança , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/etiologia , Feminino , Humanos , Lactente , Microcefalia/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Infecção por Zika virus/complicações , Infecção por Zika virus/epidemiologiaRESUMO
Congenital viral infections and the occurrence of septo-optic dysplasia, which is a combination of optic nerve hypoplasia, abnormal formation of structures along the midline of the brain, and pituitary hypofunction, support the biological plausibility of endocrine dysfunction in Zika-related microcephaly. In this case series we ascertained the presence and describe endocrine dysfunction in 30 children with severe Zika-related microcephaly from the MERG Pediatric Cohort, referred for endocrinological evaluation between February and August 2019. Of the 30 children, 97% had severe microcephaly. The average age at the endocrinological consultation was 41 months and 53% were female. The most frequently observed endocrine dysfunctions comprised short stature, hypothyroidism, obesity and variants early puberty. These dysfunctions occurred alone 57% or in combination 43%. We found optic nerve hypoplasia (6/21) and corpus callosum hypoplasia (20/21). Seizure crises were reported in 86% of the children. The most common-and clinically important-endocrine dysfunctions were pubertal dysfunctions, thyroid disease, growth impairment, and obesity. These dysfunctions require careful monitoring and signal the need for endocrinological evaluation in children with Zika-related microcephaly, in order to make early diagnoses and implement appropriate treatment when necessary.
Assuntos
Doenças do Sistema Endócrino/epidemiologia , Doenças do Sistema Endócrino/etiologia , Microcefalia/epidemiologia , Microcefalia/etiologia , Complicações Infecciosas na Gravidez/epidemiologia , Infecção por Zika virus/complicações , Infecção por Zika virus/epidemiologia , Zika virus , Biomarcadores , Brasil/epidemiologia , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Microcefalia/diagnóstico , Microcefalia/metabolismo , Gravidez , Vigilância em Saúde Pública , Avaliação de Sintomas , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/virologiaRESUMO
The genitourinary tract was recently identified as a potential site of complications related to the congenital Zika syndrome (CZS). We provide the first report of a series of cryptorchidism cases in 3-year-old children with Zika-related microcephaly who underwent consultations between October 2018 and April 2019 as part of the follow-up of the children cohort of the Microcephaly Epidemic Research Group, Pernambuco, Brazil. Of the 22 males examined, eight (36.4%) presented with cryptorchidism. Among 14 undescended testis cases, 11 (78.6%) could be palpated in the inguinal region. Seven of the eight children had severe microcephaly. Conventional risk factors for cryptorchidism were relatively infrequent in these children. We hypothesize that cryptorchidism is an additional manifestation of CZS present in children with severe microcephaly. As in our cases, for most of the children, the testes were located in the inguinal region, and the possible mechanisms for cryptorchidism were gubernaculum disturbance or cremasteric abnormality.
Assuntos
Criptorquidismo/virologia , Microcefalia/virologia , Infecção por Zika virus/complicações , Brasil , Pré-Escolar , Criptorquidismo/etiologia , Humanos , Lactente , Recém-Nascido , Masculino , Microcefalia/etiologia , Fatores de Risco , Infecção por Zika virus/congênitoRESUMO
OBJECTIVE: To estimate the incidence of epilepsy in children with Zika-related microcephaly in the first 24 months of life; to characterize the associated clinical and electrographic findings; and to summarize the treatment responses. METHODS: We followed a cohort of children, born during the 2015-2016 Zika virus (ZIKV) epidemic in Brazil, with congenital microcephaly and evidence of congenital ZIKV infection on neuroimaging and/or laboratory testing. Neurological assessments were performed at ≤3, 6, 12, 15, 18, 21, and 24 months of life. Serial electroencephalograms were performed over the first 24 months. RESULTS: We evaluated 91 children, of whom 48 were female. In this study sample, the cumulative incidence of epilepsy was 71.4% in the first 24 months, and the main type of seizure was infantile spasms (83.1%). The highest incidence of seizures occurred between 3 and 9 months of age, and the risk remained high until 15 months of age. The incidence of infantile spasms peaked between 4 and 7 months and was followed by an increased incidence of focal epilepsy cases after 12 months of age. Neuroimaging results were available for all children, and 100% were abnormal. Cortical abnormalities were identified in 78.4% of the 74 children evaluated by computed tomography and 100% of the 53 children evaluated by magnetic resonance imaging. Overall, only 46.1% of the 65 children with epilepsy responded to treatment. The most commonly used medication was sodium valproate with or without benzodiazepines, levetiracetam, phenobarbital, and vigabatrin. SIGNIFICANCE: Zika-related microcephaly was associated with high risk of early epilepsy. Seizures typically began after the third month of life, usually as infantile spasms, with atypical electroencephalographic abnormalities. The seizure control rate was low. The onset of seizures in the second year was less frequent and, when it occurred, presented as focal epilepsy.
Assuntos
Epilepsias Parciais/fisiopatologia , Malformações do Desenvolvimento Cortical/fisiopatologia , Microcefalia/fisiopatologia , Espasmos Infantis/fisiopatologia , Infecção por Zika virus/fisiopatologia , Anticonvulsivantes/uso terapêutico , Brasil , Córtex Cerebral/diagnóstico por imagem , Pré-Escolar , Eletroencefalografia , Epilepsias Parciais/tratamento farmacológico , Epilepsias Parciais/epidemiologia , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Epilepsia/fisiopatologia , Feminino , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Microcefalia/diagnóstico por imagem , Espasmos Infantis/tratamento farmacológico , Espasmos Infantis/epidemiologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Infecção por Zika virus/congênito , Infecção por Zika virus/diagnóstico por imagemRESUMO
BACKGROUND: In Brazil, in October 2015, an outbreak of Zika virus (ZIKV) infection and an increase in newborns with microcephaly suggested a relationship between maternal infection and microcephaly in children. OBJECTIVE: First, to assess the presence of dental bud sin 13 infants with a confirmed diagnosis of congenital ZIKV syndrome, born to mothers infected with the virus during pregnancy; second, to evaluate the dental development of these children at a 36-month follow-up. DESIGN: Case-based longitudinal study. RESULTS: Dental radiographs in the first semester showed that all children had dental buds. Along with the study, the individuals presented with various dental disturbances. At the end of the evaluation period, some children still had incomplete deciduous dentition. CONCLUSION: The abnormal chronology of dental eruption and dental development disturbances in children with microcephaly infected with ZIKV born to infected mothers indicate a possible role of the virus in odontogenesis.
Assuntos
Odontogênese , Complicações Infecciosas na Gravidez , Infecção por Zika virus , Brasil , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Mães , Gravidez , Síndrome , Infecção por Zika virus/complicações , Infecção por Zika virus/congênitoRESUMO
OBJECTIVES: To describe sleep EEG patterns of neonates, and infants with microcephaly due to congenital Zika virus (ZikV) syndrome. METHODS: A descriptive case series of EEGs performed in a cohort of neonates with microcephaly monitored from October 2015 to February 2016 at a University Hospital in Northeast Brazil. Infants were investigated following an established protocol that includes EEG, neuroimaging studies, PCR and specific antibodies for ZikV detection. RESULTS: EEGs (n=37) from 37 infants were reviewed. Age at investigation varied from 1 to 5months (mean=2.6). Diffuse low voltage (n=7), background asymmetry (n=6) and modified hypsarrhythmia with or without burst-suppression (n=11), were the main background abnormalities identified. Interictal EEG abnormalities were identified in 23 recordings (62%) and localized as focal frontal (n=8) or occipital (n=2) spikes/sharp, multifocal spikes/sharp waves (n=13). Electrographic seizures without clinical manifestation were identified in 4 recordings and characterized as focal pseudo rhythmic pattern. Further findings were focal high amplitude slow waves that were registered in the frontal (n=3) or occipital (n=1) regions. CONCLUSIONS: Different types of EEG abnormalities were encountered with a predominance of interictal epileptogenic activity and hypsarrhythmia. SIGNIFICANCE: Sleep EEGs in congenital Zika virus syndrome are consistently abnormal even in infants who have not yet developed epilepsy.
Assuntos
Eletroencefalografia/métodos , Microcefalia/fisiopatologia , Transtornos do Sono-Vigília/fisiopatologia , Sono , Infecção por Zika virus/fisiopatologia , Zika virus , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Microcefalia/diagnóstico , Microcefalia/etiologia , Sono/fisiologia , Transtornos do Sono-Vigília/diagnóstico , Infecção por Zika virus/complicações , Infecção por Zika virus/diagnósticoRESUMO
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.
Assuntos
Artrogripose/complicações , Microcefalia/complicações , Infecção por Zika virus/congênito , Infecção por Zika virus/complicações , Artrogripose/diagnóstico por imagem , Calcinose/diagnóstico por imagem , Eletromiografia , Humanos , Articulações/anormalidades , Articulações/diagnóstico por imagem , Imageamento por Ressonância Magnética , Microcefalia/diagnóstico por imagem , Estudos Retrospectivos , Medula Espinal/diagnóstico por imagem , Síndrome , Tomografia Computadorizada por Raios X , Ultrassonografia , Infecção por Zika virus/diagnóstico por imagemRESUMO
IMPORTANCE: The Zika virus (ZIKV) might cause microcephaly and ophthalmoscopic findings in infants of mothers infected during pregnancy. OBJECTIVE: To assess and identify possible risk factors for ophthalmoscopic findings in infants born with microcephaly and a presumed clinical diagnosis of ZIKV intrauterine infection. DESIGN, SETTING, AND PARTICIPANTS: We conducted a cross-sectional study at the Altino Ventura Foundation in Recife, Brazil, that included 40 infants with microcephaly born in Pernambuco state, Brazil, between May and December 2015. Toxoplasmosis, rubella, cytomegalovirus, syphilis, and human immunodeficiency virus were ruled out in all of them. Testing of cerebrospinal fluid for ZIKV using IgM antibody-capture enzyme-linked immunosorbent assay was performed in 24 of 40 infants (60.0%). The infants and mothers underwent ocular examinations. The infants were divided into 2 groups, those with and without ophthalmoscopic alterations, for comparison. MAIN OUTCOMES AND MEASURES: Identification of risk factors for ophthalmoscopic findings in infants born with microcephaly and ZIKV intrauterine infection. RESULTS: Among the 40 infants, the mean (SD) age was 2.2 (1.2) months (range, 0.1-7.3 months). Of the 24 infants tested, 100% had positive results for ZIKV infection: 14 of 22 infants (63.6%) from the group with ophthalmoscopic findings and 10 of 18 infants (55.6%) from the group without ophthalmoscopic findings. The major symptoms reported in both groups were rash by 26 mothers (65.0%), fever by 9 mothers (22.5%), headache by 9 mothers (22.5%), and arthralgia by 8 mothers (20.0%). No mothers reported conjunctivitis or other ocular symptoms during pregnancy or presented signs of uveitis at the time of examination. Thirty-seven eyes (46.3%) of 22 infants (55.0%) had ophthalmoscopic alterations. Ten mothers (71.4%) of infants with ocular findings reported symptoms during the first trimester (frequency, 0.48; 95% CI, 0.02-0.67; P = .04). A difference was also observed between the groups of infants with and without ocular findings regarding the cephalic perimeter: mean (SD) of 28.8 (1.7) and 30.3 (1.5), respectively (frequency, -1.50; 95% CI, -2.56 to -0.51; P = .004). CONCLUSIONS AND RELEVANCE: Ocular involvement in infants with presumed ZIKV congenital infection were more often seen in infants with smaller cephalic diameter at birth and in infants whose mothers reported symptoms during the first trimester.
Assuntos
Anticorpos Antivirais/análise , Infecções Oculares Virais/diagnóstico , Oftalmoscopia/métodos , Infecção por Zika virus/diagnóstico , Zika virus/imunologia , Adulto , Brasil/epidemiologia , Estudos Transversais , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Infecções Oculares Virais/congênito , Infecções Oculares Virais/epidemiologia , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/virologia , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Gravidez , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Infecção por Zika virus/congênito , Infecção por Zika virus/epidemiologiaRESUMO
OBJECTIVE: To report radiological findings observed in computed tomography (CT) and magnetic resonance imaging (MRI) scans of the first cases of congenital infection and microcephaly presumably associated with the Zika virus in the current Brazilian epidemic. DESIGN: Retrospective study with a case series. SETTING: Association for Assistance of Disabled Children (AACD), Pernambuco state, Brazil. PARTICIPANTS: 23 children with a diagnosis of congenital infection presumably associated with the Zika virus during the Brazilian microcephaly epidemic. MAIN OUTCOME MEASURES: Types of abnormalities and the radiological pattern of lesions identified on CT and MRI brain scans. RESULTS: Six of the 23 children tested positive for IgM antibodies to Zika virus in cerebrospinal fluid. The other 17 children met the protocol criteria for congenital infection presumably associated with the Zika virus, even without being tested for IgM antibodies to the virus--the test was not yet available on a routine basis. Of the 23 children, 15 underwent CT, seven underwent both CT and MRI, and one underwent MRI. Of the 22 children who underwent CT, all had calcifications in the junction between cortical and subcortical white matter, 21 (95%) had malformations of cortical development, 20 (91%) had a decreased brain volume, 19 (86%) had ventriculomegaly, and 11 (50%) had hypoplasia of the cerebellum or brainstem. Of the eight children who underwent MRI, all had calcifications in the junction between cortical and subcortical white matter, malformations of cortical development occurring predominantly in the frontal lobes, and ventriculomegaly. Seven of the eight (88%) children had enlarged cisterna magna, seven (88%) delayed myelination, and six each (75%) a moderate to severe decrease in brain volume, simplified gyral pattern, and abnormalities of the corpus callosum (38% hypogenesis and 38% hypoplasia). Malformations were symmetrical in 75% of the cases. CONCLUSION: Severe cerebral damage was found on imaging in most of the children in this case series with congenital infection presumably associated with the Zika virus. The features most commonly found were brain calcifications in the junction between cortical and subcortical white matter associated with malformations of cortical development, often with a simplified gyral pattern and predominance of pachygyria or polymicrogyria in the frontal lobes. Additional findings were enlarged cisterna magna, abnormalities of corpus callosum (hypoplasia or hypogenesis), ventriculomegaly, delayed myelination, and hypoplasia of the cerebellum and the brainstem.
Assuntos
Agenesia do Corpo Caloso/diagnóstico , Encéfalo/patologia , Calcinose/diagnóstico , Hidrocefalia/diagnóstico , Malformações do Desenvolvimento Cortical/diagnóstico , Microcefalia/diagnóstico , Complicações Infecciosas na Gravidez , Infecção por Zika virus/diagnóstico , Adulto , Agenesia do Corpo Caloso/complicações , Encéfalo/diagnóstico por imagem , Brasil , Calcinose/complicações , Cisterna Magna/diagnóstico por imagem , Cisterna Magna/patologia , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Feminino , Humanos , Hidrocefalia/complicações , Imunoglobulina M/líquido cefalorraquidiano , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Malformações do Desenvolvimento Cortical/complicações , Microcefalia/complicações , Fibras Nervosas Mielinizadas/diagnóstico por imagem , Fibras Nervosas Mielinizadas/patologia , Tamanho do Órgão , Gravidez , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Adulto Jovem , Zika virus/imunologia , Infecção por Zika virus/complicações , Infecção por Zika virus/congênitoRESUMO
OBJECTIVES: To provide an initial description of the congenital syndrome presumably associated with infection by Zika virus compared with other syndromes including congenital infections of established etiologies. METHODS: We provide an overview of a published case series of 35 cases, a clinical series of 104 cases, and published and unpublished reports of clinical and laboratory findings describing cases diagnosed since the beginning of the epidemic of microcephaly in Brazil. RESULTS: About 60% to 70% of mothers report rash during pregnancy; mainly in the first trimester. Principal features are microcephaly, facial disproportionality, cutis girata, hypertonia/spasticity, hyperreflexia, and irritability; abnormal neuroimages include calcifications, ventriculomegaly, and lissencephaly. Hearing and visual abnormalities may be present. CONCLUSIONS: Preliminary data suggest that severe congenital abnormalities are linked to Zika virus infection. Cases have severe abnormalities, and although sharing many characteristics with congenital abnormalities associated with other viral infections, abnormalities presumably linked to the Zika virus may have distinguishing characteristics. These severe neurologic abnormalities may result in marked mental retardation and motor disabilities for many surviving offspring. POLICY IMPLICATIONS: Affected nations need to prepare to provide complex and costly multidisciplinary care that children diagnosed with this new congenital syndrome will require.
Assuntos
Transmissão Vertical de Doenças Infecciosas , Microcefalia/etiologia , Complicações Infecciosas na Gravidez , Infecção por Zika virus/congênito , Brasil , Exantema , Feminino , Humanos , Recém-Nascido , Deficiência Intelectual/etiologia , Neuroimagem , Gravidez , Síndrome , Zika virus/isolamento & purificação , Infecção por Zika virus/transmissãoRESUMO
PURPOSE: In 2015, a twenty-fold increase in the prevalence of microcephaly in Brazil was reported, and the Ministry of Health associated this abnormal prevalence with the maternal-fetal Zika virus (ZIKV) transmission. METHODS: We assessed the ophthalmological findings of ten mothers and their infants that had been clinically diagnosed with ZIKV-related microcephaly and presented ocular abnormalities, born from May to December 2015. RESULTS: Seven mothers (70.0%) referred symptoms during pregnancy (malaise, rash and arthralgia), of which six (85.7%) were in the first trimester. At the time of exam, no ophthalmological abnormalities were identified in the mothers and they did not report ocular symptoms during pregnancy. Serology was negative in all infants for Toxoplasmosis, Rubella, Cytomegalovirus, Syphilis and Human Immunodeficiency Viruses. Ocular findings included macular alterations (gross pigment mottling and/or chorioretinal atrophy) in fifteen eyes (75.0%), and optic nerve abnormalities (hypoplasia with double-ring sign, pallor, and/or increased cup-to-disk ratio) in nine eyes (45.0%). CONCLUSIONS: Patients presented normal anterior segment and important macular and optic nerve abnormalities. Further studies will assess the visual significance of these alterations.
Assuntos
Anormalidades do Olho/virologia , Microcefalia/virologia , Complicações Infecciosas na Gravidez/virologia , Infecção por Zika virus/complicações , Adulto , Brasil , Anormalidades do Olho/patologia , Feminino , Fundo de Olho , Humanos , Recém-Nascido , Macula Lutea/anormalidades , Masculino , Oftalmoscopia/métodos , Nervo Óptico/anormalidades , GravidezRESUMO
ABSTRACT Purpose: In 2015, a twenty-fold increase in the prevalence of microcephaly in Brazil was reported, and the Ministry of Health associated this abnormal prevalence with the maternal-fetal Zika virus (ZIKV) transmission. Methods: We assessed the ophthalmological findings of ten mothers and their infants that had been clinically diagnosed with ZIKV-related microcephaly and presented ocular abnormalities, born from May to December 2015. Results: Seven mothers (70.0%) referred symptoms during pregnancy (malaise, rash and arthralgia), of which six (85.7%) were in the first trimester. At the time of exam, no ophthalmological abnormalities were identified in the mothers and they did not report ocular symptoms during pregnancy. Serology was negative in all infants for Toxoplasmosis, Rubella, Cytomegalovirus, Syphilis and Human Immunodeficiency Viruses. Ocular findings included macular alterations (gross pigment mottling and/or chorioretinal atrophy) in fifteen eyes (75.0%), and optic nerve abnormalities (hypoplasia with double-ring sign, pallor, and/or increased cup-to-disk ratio) in nine eyes (45.0%). Conclusions: Patients presented normal anterior segment and important macular and optic nerve abnormalities. Further studies will assess the visual significance of these alterations.
RESUMO Introdução: No ano de 2015, foi identificado no Brasil um aumento da prevalência de microcefalia em vinte vezes. Esta malformação foi associada pelo Ministério da Saúde à transmissão vertical do Zika vírus (ZIKV). Método: Investigamos dez lactentes com diagnóstico clínico presumido de microcefalia relacionada à ZIKV, que apresentavam anormalidades oculares, nascidos entre maio e dezembro de 2015. Resultados: Sete mães (70,0%) relataram sintomas (mal-estar, rash e artralgia) durante a gestação, sendo seis (85,7%) no primeiro trimestre. No dia da avaliação nenhuma alteração ocular foi identificada nas mães e elas não relataram sintomas oculares durante a gestação. Sorologia foi negativa para toxoplasmose, rubéola, citomegalovírus, sífilis e vírus da imunodeficiência adquirida (HIV) em todos os lactentes. Os achados oculares incluíram alterações maculares (depósito pigmentar grosseiro e/ou atrofia coriorretiniana) em 15 olhos (75,0%) e alterações do nervo óptico (hipoplasia do disco com sinal do duplo anel, palidez e/ou aumento da escavação papilar) em nove olhos (45,0%). Conclusões: Os pacientes apresentaram segmento anterior normal e importantes e anormalidades maculares e do nervo óptico. Estudos futuros vão avaliar a importância destas alterações visuais.