Urological outcomes in children with congenital Zika syndrome: The experience of a cohort in Campina Grande, Brazil.

OBJECTIVE: To describe the urological outcomes in children with congenital Zika syndrome (CZS) and investigate the relationship between clinical and urological findings in this population. METHODS: This cross-sectional study involved children with CZS followed up by a referral centre for children with microcephaly in the state of Paraiba in northeast Brazil. The urological evaluation included clinical history, urine culture results, ultrasonography of the urinary tract, and urodynamic evaluation, following the protocol proposed by Costa Monteiro et al. (2017). Descriptive statistical analysis was performed in addition to association and correlation tests, considering clinical and urodynamic variables. RESULTS: Among the 88 children with CZS (35.5 ± 5.5 months), 97.7% had microcephaly, and 51% presented urinary tract infection (UTI) confirmed with clinical history and lab tests. The number of confirmed UTI episodes varied from one to 14 per child. The urodynamic evaluation confirmed the presence of an overactive bladder in 78 children and incomplete voiding in 50. Urodynamic findings were associated with the number of confirmed UTI episodes, child's sex, and actual weight, in addition to the use of anticonvulsant and myorelaxant drugs. CONCLUSIONS: UTIs were confirmed in most children. Other urological outcomes observed were overactive bladder and low bladder capacity, which were associated with the number of confirmed UTI episodes, use of anticonvulsants and myorelaxants, and the child's sex and weight. These are treatable conditions, and it is paramount that paediatricians, neonatologists, and infectious disease specialists are aware of them to make clinical decisions and help reduce the risk of renal damage and other morbidities.

My child is growing and now? Exploring the environmental needs of children with congenital Zika syndrome according to their caregivers' perceptions.

INTRODUCTION: Promoting social inclusion of children with congenital Zika virus syndrome (CZS) is challenging, mostly, when there is a transport problem, low access to information and a long distance between the house and health services. Participation can be understood as involvement in a life situation and is strongly influenced by physical, social and attitudinal environmental factors; however, was still little explored in the case of children with CZS. In this sense, this study aimed to explore the perception of caregivers about the environmental needs of children with CZS, differentiating barriers and facilitators. METHODS: This is qualitative research. Thematic analysis was used to identify the environmental needs perceived by caregivers of children with CZS. The patient public involvement (PPI) approach was incorporated with the purpose of validating the data analysis performed by the researchers. After this step, the data were categorized in terms of barriers and facilitators and validated by the group of researchers. RESULTS: A relevant environmental need reported by caregivers as a barrier was social support for children with CZS. Ableism was also evidenced as an important attitudinal barrier. Health services were essential for the lives of children with CZS and the availability of auxiliary devices as facilitators of participation. Environmental factors related to medication and food routines were, for the most part, facilitators. CONCLUSION: This study contributes to critical approaches to the impacts linked to environmental factors of children with CZS, recognition of these children is an evolving process and fundamental to basic rights for adequate living in society. The data point to the need to implement public policies aimed at children with CZS, as well as the availability of qualified professionals to apply family-centred care and skills-focused management. Building friendly environments that promote broad social participation will contribute to the healthy growth of children with CZS. PATIENT OR PUBLIC CONTRIBUTION: Six caregivers (20% of the caregivers) as part of the PPI approach were contacted and participated in individual virtual meetings to discuss the results of the thematic analysis regarding the environmental needs of children with CZS.

Eating contexts at breakfast, lunch, and dinner: Associations with ultra-processed foods consumption and overweight in Brazilian adolescents (EVA-JF Study).

This cross-sectional study estimated associations of eating contexts (including regularity of meals, places where they occur, and if they take place with attention and in company) with food consumption by degree of industrial processing and overweight indicators in a sample of Brazilian adolescents (14-19 years old) enrolled in 29 public schools in Juiz de Fora, MG (n = 805). We used an exploratory questionnaire, which was submitted to cluster analysis. Three clusters were identified: cluster 1 (n = 572), "appropriate eating contexts at breakfast, lunch, and dinner"; cluster 2 (n = 139), "inappropriate eating context at breakfast"; and cluster 3 (n = 94) "inappropriate eating context at dinner". The evaluation of food consumption involved two 24-h dietary recalls, whose items were analyzed according to the NOVA classification system. Linear regression models were performed, using cluster 1 as reference. Clusters 2 and 3 were associated with an increase in the energy fraction from ultra-processed foods [respectively, ß = 2.55% (IC 95%: 0.50; 5.05) and ß = 4.18% (IC 95%: 1.21; 7.14)]; and cluster 2 was associated with a reduction in the energy fraction from unprocessed or minimally processed foods and processed culinary ingredients [ß = -3.61% (IC 95%: -6.40; -0.82)]. Additionally, clusters 2 and 3 were associated with an increase of body mass index for age [respectively, ß = 0.23 z-score (IC 95%: 0.01; 0.46) and ß = 0.27 z-score (IC 95%: 0.02; 0.54)]; and cluster 2 was associated with an increase of body fat [ß = 1.21% (IC 95%: 0.23; 2.64)]. In conclusion, inappropriate eating contexts at breakfast and dinner were associated with higher ultra-processed food intake, higher body mass index and higher body fat percentage.

Effect of neurodevelopmental treatment in children with congenital Zika syndrome: A pilot study.

AIM: To evaluate the effects of neurodevelopmental treatment (NDT) in children with congenital Zika syndrome (CZS). METHODS: This prospective, interventional cohort study involved children with CZS undergoing follow-up at a specialist centre in northeastern Brazil. The duration of the proposed NDT protocol was 1 year, with 45-min sessions delivered one to five times weekly. Motor function, weight, height, head circumference and the incidence of comorbidities were evaluated in children before protocol initiation and then at 3, 6 and 12 months of treatment. RESULTS: Thirty children were evaluated (age mean 30.1 ± 3 months). Motor function improved from baseline to 6 months (P = 0.001). No difference in weight and head circumference z-score (P = 0.51 and P = 0.29, respectively), but an increase in height z-score (P < 0.001) was observed over the evaluation period. There was a reduction in the incidence of upper respiratory tract infections, pneumonia and urinary tract infections over the follow-up period. CONCLUSIONS: NDT proved to be a viable treatment approach that can improve motor function and reduce the incidence of comorbidities in children with CZS, while having no harmful effects on their growth.

Identification and characterisation of SARS-CoV-2 and Human alphaherpesvirus 1 from a productive coinfection in a fatal COVID-19 case.

BACKGROUND: During routine Coronavirus disease 2019 (COVID-19) diagnosis, an unusually high viral load was detected by reverse transcription real-time polymerase chain reaction (RT-qPCR) in a nasopharyngeal swab sample collected from a patient with respiratory and neurological symptoms who rapidly succumbed to the disease. Therefore we sought to characterise the infection. OBJECTIVES: We aimed to determine and characterise the etiological agent responsible for the poor outcome. METHODS: Classical virological methods, such as plaque assay and plaque reduction neutralisation test combined with amplicon-based sequencing, as well as a viral metagenomic approach, were performed to characterise the etiological agents of the infection. FINDINGS: Plaque assay revealed two distinct plaque phenotypes, suggesting either the presence of two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains or a productive coinfection of two different species of virus. Amplicon-based sequencing did not support the presence of any SARS-CoV-2 genetic variants that would explain the high viral load and suggested the presence of a single SARS-CoV-2 strain. Nonetheless, the viral metagenomic analysis revealed that Coronaviridae and Herpesviridae were the predominant virus families within the sample. This finding was confirmed by a plaque reduction neutralisation test and PCR. MAIN CONCLUSIONS: We characterised a productive coinfection of SARS-CoV-2 and Herpes simplex virus 1 (HSV-1) in a patient with severe symptoms that succumbed to the disease. Although we cannot establish the causal relationship between the coinfection and the severity of the clinical case, this work serves as a warning for future studies focused on the interplay between SARS-CoV-2 and HSV-1 coinfection and COVID-19 severity.

Microbial inoculation and fertilizer application on growth of cowpea and spore-based assemblages of arbuscular mycorrhizal fungi in its rhizophere.

In this study, the effect of microbial inoculants and fertilizer application on cowpea (BRS Pujante) growth and on the structure and composition of arbuscular mycorrhizal fungi (AMF) assemblages were evaluated. A completely randomized experiment was set up involving 17 treatments: four with AMF, three with nodulating bacteria, six with AMF + nodulating bacteria, two with phosphorus, one with nitrogen and one control (reference) in five replicates. Plant growth and nutritional content, mycorrhizal colonization, glomerospores number, spore-based AMF assemblages and ecological indices were evaluated. Mycorrhizal inoculants associated with Bradyrhizobium BR3267 strain were more effective than the Microvirga BR3296 strain. Multidimensional scaling analysis showed that Acaulospora longula treatments were more similar among themselves, and distinct from the other treatments. A difference was observed in the structure of AMF community assemblage between treatments with G. albida + Bradyrhizobium BR 3267 and A. longula, with greater Shannon diversity and Pielou equitability indices in the first treatment and greater dominance in the treatment with A. longula only. Long-term studies are required to determine if the successful establishment of A. longula among indigenous species persists over time and if its dominant behavior is not deleterious to the AMF native community.

Arbuscular Mycorrhizal Fungal Assemblages in Conservation Unit of Atlantic Forest Areas Under Native Vegetation and Natural Regeneration.

Arbuscular mycorrhizal fungi (AMF) play an important role in the dynamic of plant community in the south American Atlantic Rainforest biome. Even in protected areas, this biome is under several anthropic impacts, which can cause shifts in the soil microbiota, including AMF. This study aimed to determine the structure and composition of AMF community in areas of native Atlantic Forest and in natural regeneration and to identify which abiotic factors are influencing this community in these areas. Soil samples were collected at Monte Pascoal National and Historical Park, in Southern Bahia, in native and natural regeneration areas of Atlantic Forest in two seasons (rainy and dry). Greater number of glomerospores and richness and diversity of AMF were found in the area under regeneration, with differences between seasons being observed only for the number of glomerospores. Seventy-seven species of AMF were recorded, considering all areas and seasons, with Acaulospora and Glomus being the most representative genera. Greater abundance of species of the genera Acaulospora, Claroideoglomus, and Septoglomus was found in the regeneration area. The AMF community differed between the study areas, but not between seasons, with soil attributes (pH, K, Al, Mg, m, and clay) structuring factors for this difference in the AMF community. Atlantic Forest areas in natural regeneration and the soil edaphic factors provide changes in the structure and composition of the AMF community, increasing the richness and diversity of these fungi in conservation units.

Percentage of energy contribution according to the degree of industrial food processing and associated factors in adolescents (EVA-JF study, Brazil).

OBJECTIVE: To evaluate energetic contribution according to the degree of industrial food processing and its association with sociodemographic, anthropometric, biochemical, clinical and behavioural characteristics in adolescents. DESIGN: Cross-sectional study (Adolescent Lifestyle Study). Food consumption was assessed using 24-h dietary recalls, with foods classified by degree of industrial progressing. The usual diet was estimated using the Multiple Source Method. In a linear regression model, the energy percentage (E %) was associated with sociodemographic, anthropometric, biochemical, clinical and behavioural characteristics, after adjustment for sex and age. SETTING: Juiz de Fora, Brazil. PARTICIPANTS: Eight hundred and four adolescents, of both sexes, 14-19 years of age, enrolled in public schools. RESULTS: The E % of unprocessed or minimally processed foods corresponded to 43·1 %, processed foods to 11·0 % and the ultraprocessed foods to 45·9 %. E % of unprocessed foods was associated with socio-economic stratum (adjusted ß = -0·093; P = 0·032), neck circumference (adjusted ß = 0·017; P = 0·049), screen time (adjusted ß = -0·247; P = 0·036) and HDL-cholesterol (adjusted ß = -0·156; P = 0·003). E % of ultraprocessed foods was associated with socio-economic stratum (adjusted ß = 0·118; P = 0·011), screen time (adjusted ß = 0·375; P = 0·003), BMI (adjusted ß = -0·029; P = 0·025), neck circumference (adjusted ß = -0·017; P = 0·028) and HDL-cholesterol (adjusted ß = 0·150; P = 0·002). CONCLUSIONS: There was a high E % of ultraprocessed foods in the diet of the adolescents. Actions are needed to raise the awareness of adopting healthy eating habits.

Effect of Intensive Physiotherapy Training for Children With Congenital Zika Syndrome: A Retrospective Cohort Study.

OBJECTIVE: To investigate the effect of intensive physiotherapy training on the motor function of children with congenital Zika syndrome (CZS). DESIGN: A retrospective cohort study. SETTING: A support center for children with microcephaly. PARTICIPANTS: Children (N=7) aged 14 to 18 months old who were diagnosed with CZS and previously monitored more than 1 year. INTERVENTIONS: A 2-stage protocol repeated uninterruptedly for 1 year. In the first stage, the children were submitted to 1 hour of conventional physiotherapy and 1 hour of suit therapy 5 times a week for 4 weeks. The second stage consisted of 1 hour of suit therapy 3 times a week for 2 weeks. MAIN OUTCOME MEASURES: Gross motor function measure (GMFM) and body weight. RESULTS: Six evaluations were conducted approximately 3 months apart. An increase in the overall GMFM score was observed between the first and second (P=.046), first and third (P=.018), first and fourth (P=.018), first and fifth (P=.043), and first and sixth evaluations (P=.018). Differences in the scores of the individual GMFM dimensions were found only for dimension A (lying and rolling) between the first and fourth evaluations (P=.027) and for dimension B (sitting) between the first and third (P=.018), first and fourth (P=.046), and first and sixth evaluations (P=.027). No difference was found in body weight between the first and sixth evaluations (P=.009). During follow-up, only 1 child required hospitalization, and another had increased irritability. CONCLUSIONS: Children with CZS were able to perform 2 hours of motor physiotherapy daily with no serious complications, resulting in an increase or stabilization in GMFM scores.

Motor function in children with congenital Zika syndrome.

AIM: To evaluate gross motor function and associated factors in children with congenital Zika syndrome (CZS). METHOD: Fifty-nine children (30 males, 29 females) with CZS at a mean (SD) age of 14.7 (3.9), months (range 5-29mo) were evaluated using the Gross Motor Function Measure (GMFM) and classified according to the Gross Motor Function Classification System (GMFCS). Neurological damage was evaluated by neuroimaging. The mothers' sociodemographic characteristics and general data on the children were obtained from interviews with the mothers and from the children's medical records. Correlational and multiple regression analyses were performed to identify factors associated with these children's motor function. RESULTS: In 81% of the children, motor function impairment was severe, classified as GMFCS level V. The overall GMFM score ranged from 5 to 210 (median 18; interquartile range 11), with only four children receiving scores in the D and E dimensions. The factors found to affect motor function were the presence of severe malformations of cortical development and small head circumference at birth. INTERPRETATION: Although motor impairment may be mild in some children, it is generally severe. Severe malformations of cortical development and small head circumference at birth were factors associated with poorer motor function, reflecting the greater severity of brain damage. WHAT THIS PAPER ADDS: Motor impairment is severe in most children with congenital Zika syndrome (CZS). Motor skills are adequate or close to adequate for age in 7% of children with CZS. Severe malformations of cortical development are associated with poor motor control. Small head circumference at birth is also associated with poor motor control.

FUNCIÓN MOTORA EN NIÑOS CON SÍNDROME DE ZIKA CONGÉNITO: OBJETIVO: Evaluar la función motora gruesa y los factores asociados en niños con síndrome de Zika congénito (CZS). MÉTODO: Cincuenta y nueve niños (30 varones, 29 mujeres) con CZS a una edad media (DE) de 14,7 (3,9), meses (rango 5-29 meses) se evaluaron utilizando la Medida de la función motora gruesa (GMFM) y se clasificaron de acuerdo con el Sistema de Clasificación de la Función Motora Gruesa (GMFCS). El impacto estructural neurológico se evaluó mediante neuroimagen. Las características sociodemográficas de las madres y los datos generales de los niños se obtuvieron en entrevistas con las madres y de los registros médicos de los niños. Se realizaron análisis de regresión correlacional y múltiple para identificar los factores asociados con la función motora de estos niños. RESULTADOS: En el 81% de los niños, el deterioro de la función motora fue grave, clasificado como nivel V de GMFCS. El puntaje general de GMFM varió de 5 a 210 (mediana 18; rango intercuartil 11), y solo cuatro niños recibieron puntajes en las dimensiones D y E. Los factores que afectaron la función motora fueron la presencia de malformaciones graves del desarrollo cortical y la circunferencia de la cabeza (microcefalia) al nacer. INTERPRETACIÓN: Aunque el deterioro motor puede ser leve en algunos niños, generalmente el impacto de CZS es grave. Las malformaciones graves del desarrollo cortical y la microcefalia al nacer fueron factores asociados con una función motora más limitada, lo que refleja la mayor gravedad del daño cerebral.

FUNÇÃO MOTORA EM CRIANÇAS COM SÍNDROME CONGÊNITA DE ZIKA: OBJETIVO: Avaliar a função motora grossa e fatores associados em crianças com síndrome congênita de Zika (SCZ). MÉTODO: Cinquenta e nove crianas (30 do sexo masculino, 29 do sexo feminino) com SCZ com uma média (DP) de idade de 14,7 (3,9) meses (variação 5-29m) foram avaliadas usando a Medida da Função Motora Grossa (GMFM) e classificadas de acordo com o Sistema de Classificação da Função Motora Grossa (GMFCS). O dano neurológico foi avaliado por neuroimagem. As características sócio-demográficas da mãe e dados gerais sobre as crianças foram obtidos em entrevistas com as mães e a partir dos prontuários medicos. Análises de correlação e de regressão múltipla foram realizadas para identificar fatores associados com a função motora destas crianças. RESULTADOS: Em 81% das crianças, o comprometimento da função motora era severo, classificao como nível GMFCS V. O escore geral da GMFM various de 5 a 210 (mediana 18; intervalo interquartil 11), com apenas quatro crianças recebendo pontuações nas dimensões D e E. Os fatores que afetaram a função motora grossa foram a presença de malformações severas no desenvolvimento cortical, e o pequeno perímetro cefálico ao nascimento. INTERPRETAÇÃO: Embora a deficiência motora possa ser leve em algumas crianças, em geral ela é severa. Malformações severas no desenvolvimento cortical e o pequeno perímetro cefálico foram fatores associados com pior função motora, refletindo a maior severidade do dano cerebral.

Obstetric and perinatal outcomes in cases of congenital Zika syndrome.

OBJECTIVE: To describe obstetric and perinatal outcomes in cases of congenital Zika syndrome (CZS). METHODS: A dual prospective and retrospective cohort study involving 102 pairs of mothers and fetuses/children with CZS whose infection was confirmed by testing for the Zika virus in amniotic fluid, umbilical cord blood, and fragments from the placenta of the newborn infant (confirmed CZS), or by intrauterine imaging tests (neurosonography), and/or postnatal computed tomography (presumed CZS). RESULTS: Suspicion of CZS was investigated by ultrasonography during pregnancy in 52.9% of cases. The principal prenatal imaging findings were ventriculomegaly (43.1%) and microcephaly (42.2%). Median gestational age at delivery was 39 weeks, with 15.7% being premature. Mean head circumference at birth was 30.0 ± 2.3 cm, with 66% of cases being classified as having microcephaly. Arthrogryposis was found in 10 cases (9.8%). There were no fetal deaths; however, nine neonatal deaths were recorded, and three autopsies were performed. CONCLUSION: Neonatal mortality was high, almost 10%. Regarding the abnormalities of CZS, microcephaly, although common, was not present in all cases and intracranial findings need to be taken into consideration for diagnosis. Therefore, ultrasound screening during pregnancy should be systematized and expanded in endemic zones.

Ecological and social determinants of association and proximity patterns in the fission-fusion society of spider monkeys (Ateles geoffroyi).

Some social species exhibit high levels of fission-fusion dynamics (FFD) that improve foraging efficiency. In this study, we shed light on the way that FFD allows animal groups to cope with fluctuations in fruit availability. We explore the relative contribution of fruit availability and social factors like sex in determining association and proximity patterns in spider monkeys. We tested the influence of fruit availability and social factors on the association and proximity patterns using three-year data from a group of spider monkeys in the Yucatan Peninsula of Mexico. We identified subgroup members and estimated their Interindividual distances through instantaneous scan sampling. We evaluated fruit availability by monitoring the phenology of the 10 most important food tree species for spider monkeys in the study site. Social network analyses allowed us to evaluate association and proximity patterns in subgroups. We showed that association patterns vary between seasons, respond to changes in fruit availability, and are influenced by the sex of individuals, likely reflecting biological and behavioral differences between sexes and the interplay between ecological and social factors. In contrast, proximity patterns were minimally affected by changes in fruit availability, suggesting that social factors are more important than food availability in determining cohesion within subgroups.

Wide dispersion of B chromosomes in Rhammatocerus brasiliensis (Orthoptera, Acrididae).

The grasshopper Rhammatocerus brasiliensis shows polymorphism of B chromosomes, but the magnitude of B-chromosome occurrence and the factors that may contribute to their dispersion in the species remain unknown thus far. The present study analyzed the occurrence and dispersion of B chromosomes in R. brasiliensis individuals from 21 populations widely distributed in the Brazilian Northeast. The genetic connectivity between 10 populations was verified through analysis of ISSR markers from 200 individuals. Of the 21 populations, 19 presented individuals with one B chromosome, three with two, and one with three B chromosomes. The B chromosome is of medium size and constitutive heterochromatin (CH) located in the pericentromeric region. A variant B chromosome was observed in three populations, similar in size to that of chromosome X, gap and CH, and located in the terminal region. B chromosome frequencies in different populations varied from 0% to 18,8%, mean 8,5%. The wide distribution of the B chromosome is likely a consequence of the positive gene flow among the analyzed populations. B-chromosome occurrence in populations of R. brasiliensis possibly follows the population genetic structure of the species and, owing to the existence of a variant, its origin may not be recent.

Teething symptoms in children with congenital Zika syndrome: A 2-year follow-up.

BACKGROUND: The eruption of primary teeth represents a stage of many challenges for parents. AIM: To investigate the occurrence of signs and symptoms related to the eruption of the primary dentition in children with congenital Zika syndrome. DESIGN: Longitudinal study developed with 79 children followed up for a period of 24 months. Data on sex, gestational age, low birthweight, microcephaly, signs and symptoms related to the dental eruption phase, and use and type of medication were collected. Data were presented by descriptive and inferential statistics (chi-square test). RESULTS: The majority (94.9%) exhibited simultaneously two or more signs and symptoms related to dental eruption. Increased salivation (91.1%), irritability (86.1%), and gingival itching (83.5%) were the most commonly reported signs and symptoms. Bivariate analysis showed association between elevation of body temperature and sex (P < 0.05). Almost two-thirds of mothers (63.3%) reported using medication to relieve symptoms presented by the child; however, the use of topical medication prevailed (57.1%). CONCLUSION: All children with congenital Zika syndrome presented manifestations related to the eruption of primary teeth, with increased salivation, irritability, and gingival pruritus. The use of ointments and gels was the option of mothers in the treatment of the oral discomfort presented by infants.

Immune activation in amniotic fluid from Zika virus-associated microcephaly.

Recent advances in the understanding of neuropathogenesis associated with Zika virus (ZIKV) infection has led to descriptions of neonatal microcephaly cases. However, none of these reports have evaluated the humoral response during ZIKV infection. We report here polyfunctional immune activation associated with increased interferon-gamma-inducible protein 10, interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), monocyte chemoattractive protein 1 (MCP-1), and granulocyte colony-stimulating factor (G-CSF) levels in the amniotic fluid of ZIKV-positive pregnant women with neonatal microcephaly. These cytokines have been associated not only with neuronal damage, but also with differentiation and proliferation of neural progenitor cells. Our results suggested that the immune activation caused by ZIKV infection in the uterine environment could also interfere with fetal development. ANN NEUROL 2017;81:152-156.

Imaging findings in congenital Zika virus infection syndrome: an update.

BACKGROUND: Zika virus (ZIKV) is a neurotropic and neurotoxic RNA Flavivirus prompt to cause severe fetal brain dysmorphisms during pregnancy, a period of rapid and critical central nervous system development. A wide range of clinico-radiological findings of congenital ZIKV infections were reported in the literature, such as microcephaly, overlapping sutures, cortical migrational and corpus callosum abnormalities, intracranial calcifications, ventriculomegaly, brain stem and cerebellar malformations, spinal cord involvement, and joint contractures. ZIKV is also related to other severe neurological manifestations in grown-up individuals such as Guillain-Barré syndrome and encephalomyelitis. PURPOSE: Our purpose is to review the radiological central nervous system abnormalities of congenital ZIKV infection syndrome on different imaging modalities.

The spectrum of neuropathological changes associated with congenital Zika virus infection.

A major concern associated with ZIKV infection is the increased incidence of microcephaly with frequent calcifications in infants born from infected mothers. To date, postmortem analysis of the central nervous system (CNS) in congenital infection is limited to individual reports or small series. We report a comprehensive neuropathological study in ten newborn babies infected with ZIKV during pregnancy, including the spinal cords and dorsal root ganglia (DRG), and also muscle, pituitaries, eye, systemic organs, and placentas. Using in situ hybridization (ISH) and electron microscopy, we investigated the role of direct viral infection in the pathogenesis of the lesions. Nine women had Zika symptoms between the 4th and 18th and one in the 28th gestational week. Two babies were born at 32, one at 34 and 36 weeks each and six at term. The cephalic perimeter was reduced in four, and normal or enlarged in six patients, although the brain weights were lower than expected. All had arthrogryposis, except the patient infected at 28 weeks gestation. We defined three patterns of CNS lesions, with different patterns of destructive, calcification, hypoplasia, and migration disturbances. Ventriculomegaly was severe in the first pattern due to midbrain damage with aqueduct stenosis/distortion. The second pattern had small brains and mild/moderate (ex-vacuo) ventriculomegaly. The third pattern, a well-formed brain with mild calcification, coincided with late infection. The absence of descending fibres resulted in hypoplastic basis pontis, pyramids, and cortico-spinal tracts. Spinal motor cell loss explained the intrauterine akinesia, arthrogryposis, and neurogenic muscle atrophy. DRG, dorsal nerve roots, and columns were normal. Lympho-histiocytic inflammation was mild. ISH showed meningeal, germinal matrix, and neocortical infection, consistent with neural progenitors death leading to proliferation and migration disorders. A secondary ischemic process may explain the destructive lesions. In conclusion, we characterized the destructive and malformative consequences of ZIKV in the nervous system, as reflected in the topography and severity of lesions, anatomic localization of the virus, and timing of infection during gestation. Our findings indicate a developmental vulnerability of the immature CNS, and shed light on possible mechanisms of brain injury of this newly recognized public health threat.

Congenital Brain Abnormalities and Zika Virus: What the Radiologist Can Expect to See Prenatally and Postnatally.

Purpose To document the imaging findings associated with congenital Zika virus infection as found in the Instituto de Pesquisa in Campina Grande State Paraiba (IPESQ) in northeastern Brazil, where the congenital infection has been particularly severe. Materials and Methods From June 2015 to May 2016, 438 patients were referred to the IPESQ for rash occurring during pregnancy or for suspected fetal central nervous system abnormality. Patients who underwent imaging at IPESQ were included, as well as those with documented Zika virus infection in fluid or tissue (n = 17, confirmed infection cohort) or those with brain findings suspicious for Zika virus infection, with intracranial calcifications (n = 28, presumed infection cohort). Imaging examinations included 12 fetal magnetic resonance (MR) examinations, 42 postnatal brain computed tomographic examinations, and 11 postnatal brain MR examinations. Images were reviewed by four radiologists, with final opinion achieved by means of consensus. Results Brain abnormalities seen in confirmed (n = 17) and presumed (n = 28) congenital Zika virus infections were similar, with ventriculomegaly in 16 of 17 (94%) and 27 of 28 (96%) infections, respectively; abnormalities of the corpus callosum in 16 of 17 (94%) and 22 of 28 (78%) infections, respectively; and cortical migrational abnormalities in 16 of 17 (94%) and 28 of 28 (100%) infections, respectively. Although most fetuses underwent at least one examination that showed head circumference below the 5th percentile, head circumference could be normal in the presence of severe ventriculomegaly (seen in three fetuses). Intracranial calcifications were most commonly seen at the gray matter-white matter junction, in 15 of 17 (88%) and 28 of 28 (100%) confirmed and presumed infections, respectively. The basal ganglia and/or thalamus were also commonly involved with calcifications in 11 of 17 (65%) and 18 of 28 (64%) infections, respectively. The skull frequently had a collapsed appearance with overlapping sutures and redundant skin folds and, occasionally, intracranial herniation of orbital fat and clot in the confluence of sinuses. Conclusion The spectrum of findings associated with congenital Zika virus infection in the IPESQ in northeastern Brazil is illustrated to aid the radiologist in identifying Zika virus infection at imaging. (©) RSNA, 2016 Online supplemental material is available for this article.

Gray matter volume in left rostral middle frontal and left cerebellar cortices predicts frontal executive performance in alcoholic subjects.

BACKGROUND: Alcoholic subjects manifest important deficits in frontal executive function, yet maintain cognitive mental status within normal range. METHODS: This study searched for volumetric measurements of segmented brain structures obtained from magnetic resonance imaging (MRI) that would predict executive functions and cognitive mental status in alcoholic subjects. The frontal assessment battery (FAB) and the Mini-Mental State Examination (MMSE) were applied to alcoholic subjects who underwent MRI. Cortical and subcortical segmentation and corrections were performed using FreeSurfer. Multiple linear regressions analyses having volumetric measures of segmented brain structures as predictors for FAB or MMSE scores as dependent measures were conducted. Sixty alcoholic subjects, 52 males, mean age of 47.2 ± SD 10.4 years, with heavy use of alcohol (mean 284.4 ± SD 275.9 g of alcohol/d) over a long time (mean 32.4 ± SD 11.1 years), showed FAB 11.1 ± SD 3.2 and MMSE of 25.2 ± SD 4.1. RESULTS: Multiple regression analyses having left and right side of each segment as predictors showed that gray matter volumes of rostral middle frontal cortex and cerebellar cortex (p < 0.001), in which only the left side of these structures showed significant partial effects in the full model (p < 0.05), showed to predict FAB performance. They were even more predictive when considered together (p < 0.001), in which both left rostral middle frontal cortex (p < 0.05) and left cerebellar cortex (p < 0.01) predictors had significant partial effects in the full model. None of brain structures was predictive of MMSE performance. CONCLUSIONS: We have concluded that volumetric measurements of left rostral middle frontal and cerebellar cortices seem to be able to predict the frontal executive performance but not the cognitive mental status in alcoholic subjects.