Cerebral Sinovenous Thrombosis in Children: Clinical Presentation and Extension, Localization and Recanalization of Thrombosis

Many important questions regarding pathophysiology and treatment of cerebral sinovenous thrombosis need clarification and may depend on further knowledge on the etiology, site, extension and recanalization of the thrombosis. We studied these variables in a cohort of children and adolescents from seven Portuguese Centers. We conclude from our results that the deep venous system and the superior longitudinal sinus are less frequently affected with thrombosis but have a greater potential for serious neurologic disease and for major sequelae. Non-recanalization, at least in the long term, is not an adverse prognostic factor. Extensive propagation of the thrombus from the initial site of origin seems to be common. The early identification of risk factors and their treatment coupled with an aggressive attitude towards diagnosis and treatment for thrombosis involving the deep venous system would be warranted.

Cerebral sinus venous thrombosis in Swiss children

AIMo describe the characteristics of paediatric cerebral sinus venous thrombosis (CSVT) in Switzerland.

Neurological consequences of diabetic ketoacidosis at initial presentation of type 1 diabetes in a prospective cohort study of children

OBJECTIVE To investigate the impact of new-onset diabetic ketoacidosis (DKA) during child- hood on brain morphology and function. RESEARCH DESIGN AND METHODS Patients aged 6–18 years with and without DKA at diagnosis were studied at four time points: <48 h, 5 days, 28 days, and 6 months postdiagnosis. Patients under- went magnetic resonance imaging (MRI) and spectroscopy with cognitive assess- ment at each time point. Relationships between clinical characteristics at presentation and MRI and neurologic outcomes were examined using multiple linear regression, repeated-measures, and ANCOVA analyses. RESULTS Thirty-six DKA and 59 non-DKA patients were recruited between 2004 and 2009. With DKA, cerebral white matter showed the greatest alterations with increased total white matter volume and higher mean diffusivity in the frontal, temporal, and parietal white matter. Total white matter volume decreased over the first 6 months. For gray matter in DKA patients, total volume was lower at baseline and increased over 6 months. Lower levels of N-acetylaspartate were noted at base- line in the frontal gray matter and basal ganglia. Mental state scores were lower at baseline and at 5 days. Of note, although changes in total and regional brain volumes over the first 5 days resolved, they were associated with poorer delayed memory recall and poorer sustained and divided attention at 6 months. Age at time of presentation and pH level were predictors of neuroimaging and functional outcomes. CONCLUSIONS DKA at type 1 diabetes diagnosis results in morphologic and functional brain changes. These changes are associated with adverse neurocognitive outcomes in the medium term.

Multi-site study of additive genetic effects on fractional anisotropy of cerebral white matter: Comparing meta and megaanalytical approaches for data pooling

Combining datasets across independent studies can boost statistical power by increasing the numbers of observations and can achieve more accurate estimates of effect sizes. This is especially important for genetic studies where a large number of observations are required to obtain sufficient power to detect and replicate genetic effects. There is a need to develop and evaluate methods for joint-analytical analyses of rich datasets collected in imaging genetics studies. The ENIGMA-DTI consortium is developing and evaluating approaches for obtaining pooled estimates of heritability through meta-and mega-genetic analytical approaches, to estimate the general additive genetic contributions to the intersubject variance in fractional anisotropy (FA) measured from diffusion tensor imaging (DTI). We used the ENIGMA-DTI data harmonization protocol for uniform processing of DTI data from multiple sites. We evaluated this protocol in five family-based cohorts providing data from a total of 2248 children and adults (ages: 9-85) collected with various imaging protocols. We used the imaging genetics analysis tool, SOLAR-Eclipse, to combine twin and family data from Dutch, Australian and Mexican-American cohorts into one large "mega-family". We showed that heritability estimates may vary from one cohort to another. We used two meta-analytical (the sample-size and standard-error weighted) approaches and a mega-genetic analysis to calculate heritability estimates across-population. We performed leave-one-out analysis of the joint estimates of heritability, removing a different cohort each time to understand the estimate variability. Overall, meta- and mega-genetic analyses of heritability produced robust estimates of heritability.

Acute liver failure in children : a regional experience

Objective: To review the outcome of acute liver failure (ALF) and the effect of liver transplantation in children in Australia. Methodology: A retrospective review was conducted of all paediatric patients referred with acute liver failure between 1985 and 2000 to the Queensland Liver Transplant Service, a paediatric liver transplant centre based at the Royal Children's Hospital, Brisbane, that is one of three paediatric transplant centres in Australia. Results: Twenty-six patients were referred with ALF. Four patients did not require transplantation and recovered with medical therapy while two were excluded because of irreversible neurological changes and died. Of the 20 patients considered for transplant, three refused for social and/or religious reasons, with 17 patients listed for transplantation. One patient recovered spontaneously and one died before receiving a transplant. There were 15 transplants of which 40% (6/15) were < 2 years old. Sixty-seven per cent (10/15) survived > 1 month after transplantation. Forty per cent (6/15) survived more than 6 months after transplant. There were only four long term survivors after transplant for ALF (27%). Overall, 27% (6/22) of patients referred with ALF survived. Of the 16 patients that died, 44% (7/16) were from neurological causes. Most of these were from cerebral oedema but two patients transplanted for valproate hepatotoxicity died from neurological disease despite good graft function. Conclusions: Irreversible neurological disease remains a major cause of death in children with ALF. We recommend better patient selection and early referral and transfer to a transplant centre before onset of irreversible neurological disease to optimize outcome of children transplanted for ALF.

Children and adolescents in full-time special education : an epidemiological and magnetic resonance imaging study

The need for special education (SE) is increasing. The majority of those whose problems are due to neurodevelopmental disorders have no specific aetiology. The aim of this study was to evaluate the contribution of prenatal and perinatal factors and factors associated with growth and development to later need for full-time SE and to assess joint structural and volumetric brain alterations among subjects with unexplained, familial need for SE. A random sample of 900 subjects in full-time SE allocated into three levels of neurodevelopmental problems and 301 controls in mainstream education (ME) provided data on socioeconomic factors, pregnancy, delivery, growth, and development. Of those, 119 subjects belonging to a sibling-pair in full-time SE with unexplained aetiology and 43 controls in ME underwent brain magnetic resonance imaging (MRI). Analyses of structural brain alterations and midsagittal area and diameter measurements were made. Voxel-based morphometry (VBM) analysis provided detailed information on regional grey matter, white matter, and cerebrospinal fluid (CSF) volume differences. Father’s age ≥ 40 years, low birth weight, male sex, and lower socio-economic status all increased the probability of SE placement. At age 1 year, one standard deviation score decrease in height raised the probability of SE placement by 40% and in head circumference by 28%. At infancy, the gross motor milestones differentiated the children. From age 18 months, the fine motor milestones and those related to speech and social skills became more important. Brain MRI revealed no specific aetiology for subjects in SE. However, they had more often ≥ 3 abnormal findings in MRIs (thin corpus callosum and enlarged cerebral and cerebellar CSF spaces). In VBM, subjects in full-time SE had smaller global white matter, CSF, and total brain volumes than controls. Compared with controls, subjects with intellectual disabilities had regional volume alterations (greater grey matter volumes in the anterior cingulate cortex bilaterally, smaller grey matter volume in left thalamus and left cerebellar hemisphere, greater white matter volume in the left fronto-parietal region, and smaller white matter volumes bilaterally in the posterior limbs of the internal capsules). In conclusion, the epidemiological studies emphasized several factors that increased the probability of SE placement, useful as a framework for interventional studies. The global and regional brain MRI findings provide an interesting basis for future investigations of learning-related brain structures in young subjects with cognitive impairments or intellectual disabilities of unexplained, familial aetiology.

Visual Impairment in Finnish Children : Prevalence, causes and morbidity of full-term and preterm children with visual impairment born from 1972 through 1989

The prevalence and the causes of childhood visual impairment in Finland during the 1970s and the 1980s were investigated, with special attention to risk factors and further prevention of visual impairment in children. The primary data on children with visual impairment were obtained from the Finnish Register of Visual Impairment, one of the patient registers kept up by the National Research and Development Centre for Welfare and Health (Stakes). The data were supplemented from other registers in Stakes and from patient records of the children in Finnish central hospitals. Visual impairment had been registered in 556 children from a population of 1,138,326 children between ages 0-17, born from 1972 through 1989. The age-specific prevalence of registered visual impairment was 49/100,000 in total. Of them, 23/100,000 were blind children and 11/100,000 were children born prematurely. Boys were impaired more often and more severely than girls. Congenital malformations (52%), systemic diseases (48%), and multiple impairments (50%) were common. The main ophthalmic groups of visual impairment were retinal diseases (35%), ocular malformations (29%), and neuro-ophthalmological disorders (29%). Optic nerve atrophy was the most common diagnosis of visual impairment (22%), followed by congenital cataract (11%), retinopathy of prematurity (10%), and cerebral visual impairment (8%). Genetic factors (42%) were the most common etiologies of visual impairment, followed by prenatal (30%) and perinatal (21%) factors. The highest rates of blindness were seen in cerebral visual impairment (83%) and retinopathy of prematurity (82%). Retinopathy of prematurity had developed in the children born at a gestational age of 32 weeks or earlier. Significant risks for visual impairment were found in the association with preterm births, prenatal infections, birth asphyxia, neonatal respiratory difficulties, mechanical ventilation lasting over two weeks, and hyperbilirubinemia. A rise in blind and multi-impaired children was seen during the study period, associating with increases in the survival of preterm infants with extremely low birth weight. The incidence of visual impairment in children born prematurely was seven times higher than in children born at full term. A reliable profile of childhood visual impairment was obtained. The importance of highly qualified antenatal, neonatal, and ophthalmological care was clearly proved. The risks associated with pre- and perinatal disorders during pregnancy must be emphasized, e.g. the risks associated with maternal infections and the use of tobacco, alcohol, and drugs during pregnancy. Obvious needs for gene therapies and other new treatments for hereditary diseases were also proved.

Efeitos da exposição à nicotina e à fumaça de cigarro durante a lactação sobre o sistema de recompensa cerebral em ratos

Crianças de mães fumantes são mais suscetíveis a se tornarem adultos obesos e se viciarem em drogas ou alimentos palatáveis. Drogas e alimentos ativam a via mesolímbica de recompensa, causando sensação de prazer que induz ainda mais o consumo. Assim, avaliamos a relação entre a exposição apenas à nicotina ou à fumaça do cigarro durante a lactação com a preferência alimentar e sistema dopaminérgico de recompensa cerebral das proles, em dois modelos de programação: Modelo I: no 2o dia pós-natal (PN), lactantes receberam implante de minibombas osmóticas que liberam nicotina (NIC) ou salina (C), durante 14 dias. Em PN150 e novamente em PN160, as proles foram divididas em 4 grupos para um desafio alimentar: N-SC e C-SC que receberam ração padrão; N-SSD e C-SSD que podiam escolher livremente entre as dietas hiperlipídica e hiperglicídica. A ingestão alimentar foi avaliada após 12 h. As mães foram sacrificadas apenas na 21 da lactação (desmame) e as proles em PN15 (com nicotina), PN21 e PN170 (ausência da NIC). Ao desmame, as ratas lactantes NIC apresentaram menor conteúdo de tirosina hidroxilase (TH), maior OBRb e SOCS3 na area tegmentar ventral (VTA); menor TH, maior receptor de dopamina 1 (D1R), receptor de dopamina 2 (D2R) e transportador de dopamina (DAT) no núcleo accumbens (NAc); maior conteúdo de TH no estriado dorsal (DS); e maior D2R e SOCS3 no núcleo arqueado (ARC). Em PN15, os filhotes NIC apresentaram maior conteúdo de D1R, D2R e menor DAT no NAc, enquanto em PN21, apresentaram apenas menor DAT no DS, e menor conteúdo de pSTAT3 em ARC. Aos 170 dias, as proles SSD demonstraram maior preferência para a ração hiperlipídica. No entanto, os animais N-SSD consumiram mais ração hiperglicidica do que as proles C-SSD. A prole N apresentou menor conteúdo de D2R e DAT no NAc e menor D2R no ARC. Modelo II: as mães e suas proles foram divididas em: expostos à fumaça do cigarro (grupo S: 4 vezes / dia, do 3 ao 21 dia de lactação), e expostos ao ar filtrado (grupo C). Em PN175, as proles foram divididas em 4 grupos para o desafio alimentar S-SC, C-SC, S-SSD e C-SSD. A ingestão alimentar foi avaliada após 30 min e 12 h. Em PN180, as proles foram sacrificadas. O grupo S-SSD ingeriu mais das rações palatáveis do que o grupo C-SSD em 30 min e 12 h. Ambos os grupos preferiram a ração hiperlipídica. No entanto, os animais S-SSD consumiram mais ração hiperlipídica do que C-SSD em 30 min. A prole S apresentou menor conteúdo de TH no VTA, menor conteúdo de TH, D2R e maior conteúdo de D1R no NAc e menor OBRb no ARC. Demonstramos que tanto a nicotina isolada como a exposição à fumaça do cigarro durante a lactação resultaram em mudanças no sistema dopaminérgico das proles, programando o comportamento alimentar devido à diminuição da dopamina no NAc.

Dopaminergic genotype biases spatial attention in healthy children

In everyday life, our sensory system is bombarded with visual input and we rely upon attention to select only those inputs that are relevant to behavioural goals. Typically, humans can shift their attention from one visual field to the other with little cost to perception. In cases of, unilateral neglect', however, there is a persistent bias of spatial attention towards the same side as the damaged cerebral hemisphere. We used a visual orienting task to examine the influence of functional polymorphisms of the dopamine transporter gene (DAT1) on individual differences in spatial attention in normally developing children. DAT1 genotype significantly influenced spatial bias. Healthy children who were homozygous for alleles that influence the expression of dopamine transporters in the brain displayed inattention for left-sided stimuli, whereas heterozygotes did not. Our data provide the first evidence in healthy individuals of a genetically mediated bias in spatial attention that is related to dopamine signalling.

Persistent endothelial activation and inflammation after Plasmodium falciparum Infection in Malawian children

Endothelial dysregulation is central to the pathogenesis of acute Plasmodium falciparum infection. It has been assumed that this dysregulation resolves rapidly after treatment, but this return to normality has been neither demonstrated nor quantified. We therefore measured a panel of plasma endothelial markers acutely and in convalescence in Malawian children with uncomplicated or cerebral malaria. Evidence of persistent endothelial activation and inflammation, indicated by increased plasma levels of soluble intracellular adhesion molecule 1, angiopoetin 2, and C-reactive protein, were observed at 1 month follow-up visits. These vascular changes may represent a previously unrecognized contributor to ongoing malaria-associated morbidity and mortality.

Cerebral perfusion CT: Current state of the art : P44

Purpose: The aim of this educational poster is to introduce the technical principles of cerebral perfusion CT and to provide examples of its clinical applications and potential limitations in the everyday emergency practice. Methods and materials: Cerebral perfusion CT is a well established investigatory tool for many vascular and parenchymal brain dysfunctions. CT perfusion maps allow a semiquantitative assessment of cerebral perfusion. Results: Currently, cerebral perfusion CT has a pivotal role in differentiating reversible from irreversible ischemic parenchymal insult besides its integral role in grading vasospasm after subarachnoid hemorrhage. Furthermore, cerebral perfusion CT can be coupled to acetazolamide administration in order to assess the cerebrovascular reserve capacity before performing extra-/intra-cranial bypass surgery in patients with cerebral vascular insufficiency. Cerebral perfusion CT can also identify diffuse abnormalities of cerebral perfusion in children with traumatic brain injury showing a low initial GCS in order to predict the final outcome regarding the late occurrence of irreversible parenchymal damage. Cerebral Perfusion CT is also able to detect focal parenchymal perfusion abnormalities in acute epileptic seizures. Conclusion: Cerebral perfusion CT can be integrated in the management of many vascular, traumatic and functional disorders of the brain.

Executive functions in school-aged children: age and socioeconomic status effects

Lately, the study of prefrontal executive functions in grade scholars has noticeably increased. The aim of this study is to investigate the influence of age and socioeconomic status (sEs) on executive tasks performance and to analyze those socioeconomic variables that predict a better execution. A sample of 254 children aged between 7 and 12 years from the city of santa Fe, Argentina and belonging to different socioeconomic status were tested. A bat- tery of executive functions sensitive to prefrontal function was used to obtain the results. These in- dicate a significant influence of age and SES on executive functions. The cognitive patterns follow a different path according to the development and sEs effect. Besides, it is revealed a pattern of low cognitive functioning in low-sEs children in all executive functions. Finally, from the variables included in this study, it was found that only the educational level of the mother and the housing conditions are associated to the children’s executive function. The results are discussed in terms of the influence of the cerebral maturation and the envi- ronmental variables in the executive functioning.

Comunicação suplementar e alternativa no discurso narrativo do aluno com paralisia cerebral

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Caracterização da resposta inflamatória e alterações neuroquímicas e eletrofisiológicas do tecido retiniano em modelo murino de malária cerebral induzido pela infecção por Plasmodium Berghei ANKA

A malária cerebral (MC) é uma das complicações mais graves resultante da infecção por P. falciparum e a principal causa de morte em crianças. O quadro de MC apresenta uma patogênese complexa, associado a complicações neurológicas provenientes de uma resposta imunológica exacerbada, bem como eventos hemorrágicos. Estudos descrevem uma retinopatia associada ao quadro, juntamente com um intenso processo de astrogliose nas proximidades de vasos que nutrem o tecido retiniano. O presente trabalho buscou caracterizar o processo inflamatório e as possíveis alterações neuroquímicas e eletrofisiológicas no tecido retiniano de camundongos albino suíço, quando inoculados com a cepa ANKA de Plasmodium berghei (PbA). Camundongos albino suíço foram infectados com cepa PbA. Para caracterização do quadro de malária cerebral experimental (MCE) foram avaliados diversos parâmetros, como surgimento dos sinais clínicos, curva de sobrevivência, parasitemia (%), ganho de massa corpórea, permeabilidade vascular e quantificação de citocinas (TNF-α, IL-6 e IL-10) no tecido cortical. Para avaliarmos alterações na funcionalidade do tecido retiniano, utilizamos eletrorretinograma de campo total. Para a avaliação dos sistemas de neurotransmissão foi realizado ensaio de liberação e captação de glutamato e GABA que, posteriormente foi quantificado por Cromatografia Líquida de Alta Eficiência. Para análise da resposta inflamatória foi realizada a quantificação de citocinas (TNF-α, IL-6 e IL-10) no tecido retiniano. Após a caracterização do quadro de MCE nós observamos a diminuição da amplitude de onda-b de cones e bastonetes, bem como aumento do tempo implícito de bastonetes, respostas mistas em diferentes intensidades e potencial oscilatório. Observamos aumento na liberação e captação de glutamato e, ainda, a ativação de uma via antiinflamatória no tecido retiniano. Este trabalho nos permitiu validar o modelo murino de MCE e caracterizar, pela primeira vez, alterações na funcionalidade do tecido retiniano, acompanhada de alterações no sistema glutamatérgico, bem como ativação de uma via antiinflamatória no tecido retiniano.

Dental development of children and adolescents with cleft lip and palate

Aim: To evaluate the dental development of Brazilian children and adolescents with cleft lip and palate. Methods: The sample consisted of 107 panoramic radiographs of children and adolescents with cleft lip and/or palate (cleft group) and 107 panoramic radiographs of children and adolescents without cleft lip and/or palate (control group), with chronological ages ranging from 6 to 15 years, matched in gender and chronological age within 60 days. Radiographs were digitized and masked and dental age was assessed using the method described by Demirjian et al. (1973). Three trained examiners conducted the assessments. Each examiner evaluated the radiographs three times. Data were statistically analyzed using non-parametric tests and univariate linear regression (p<0.05). Results: The dental age was overestimated in relation to the chronological age in both groups (p<0.0001). Compared to the control group, there was a delay in the dental age in the cleft group of 0.17 years (2.1 months). However, no statistically significant difference in the dental age between the cleft and the control group was found even when considering the different cleft types (p=0.152). Conclusions: There was no statistically significant difference in the dental age between the cleft and the control groups. The evaluation of dental development in individuals with cleft lip and palate should be approached in the same way as in individuals without clefts, with a focus on the individualization of diagnosis and treatment planning.