Le diagnostic précoce des troubles du comportement externalisé est-il fiable ? Mise à l’épreuve d’une procédure multi informateurs et multi méthodes

peer reviewedCette contribution questionne la fiabilité du diagnostic précoce des troubles du comportement externalisé chez l’enfant. Les données concernant le comportement de 118 enfants ont été collectées par questionnaires et observation auprès de leurs parents, leurs enseignants et les cliniciens lors du recrutement et après 12 mois. Les résultats montrent des variations importantes dans le nombre d’enfants atteignant un seuil clinique selon l’informateur et la méthode considérés. Une méthode combinant les évaluations des informateurs pour obtenir un diagnostic valide est éprouvée. Les résultats plaident en faveur d’une procédure multi-informateurs et multiméthodes dont les implications sont discutées sur le plan clinique et de la recherche.H2M childre

Eight further individuals with intellectual disability and epilepsy carrying bi-allelic CNTNAP2 aberrations allow delineation of the mutational and phenotypic spectrum

Background Heterozygous copy number variants (CNVs) or sequence variants in the contactin-associated protein 2 gene CNTNAP2 have been discussed as risk factors for a wide spectrum of neurodevelopmental and neuropsychiatric disorders. Bi-allelic aberrations in this gene are causative for an autosomal-recessive disorder with epilepsy, severe intellectual disability (ID) and cortical dysplasia (CDFES). As the number of reported individuals is still limited, we aimed at a further characterisation of the full mutational and clinical spectrum. Methods Targeted sequencing, chromosomal microarray analysis or multigene panel sequencing was performed in individuals with severe ID and epilepsy. Results We identified homozygous mutations, compound heterozygous CNVs or CNVs and mutations in CNTNAP2 in eight individuals from six unrelated families. All aberrations were inherited from healthy, heterozygous parents and are predicted to be deleterious for protein function. Epilepsy occurred in all affected individuals with onset in the first 3.5 years of life. Further common aspects were ID (severe in 6/8), regression of speech development (5/8) and behavioural anomalies (7/8). Interestingly, cognitive impairment in one of two affected brothers was, in comparison, relatively mild with good speech and simple writing abilities. Cortical dysplasia that was previously reported in CDFES was not present in MRIs of six individuals and only suspected in one. Conclusions By identifying novel homozygous or compound heterozygous, deleterious CNVs and mutations in eight individuals from six unrelated families with moderate-to-severe ID, early onset epilepsy and behavioural anomalies, we considerably broaden the mutational and clinical spectrum associated with bi-allelic aberrations in CNTNAP2

Pandemic A/H1N1v influenza 2009 in hospitalized children: a multicenter Belgian survey

<p>Abstract</p> <p>Background</p> <p>During the 2009 influenza A/H1N1v pandemic, children were identified as a specific "at risk" group. We conducted a multicentric study to describe pattern of influenza A/H1N1v infection among hospitalized children in Brussels, Belgium.</p> <p>Methods</p> <p>From July 1, 2009, to January 31, 2010, we collected epidemiological and clinical data of all proven (positive H1N1v PCR) and probable (positive influenza A antigen or culture) pediatric cases of influenza A/H1N1v infections, hospitalized in four tertiary centers.</p> <p>Results</p> <p>During the epidemic period, an excess of 18% of pediatric outpatients and emergency department visits was registered. 215 children were hospitalized with proven/probable influenza A/H1N1v infection. Median age was 31 months. 47% had ≥ 1 comorbid conditions. Febrile respiratory illness was the most common presentation. 36% presented with initial gastrointestinal symptoms and 10% with neurological manifestations. 34% had pneumonia. Only 24% of the patients received oseltamivir but 57% received antibiotics. 10% of children were admitted to PICU, seven of whom with ARDS. Case fatality-rate was 5/215 (2%), concerning only children suffering from chronic neurological disorders. Children over 2 years of age showed a higher propensity to be admitted to PICU (16% vs 1%, p = 0.002) and a higher mortality rate (4% vs 0%, p = 0.06). Infants less than 3 months old showed a milder course of infection, with few respiratory and neurological complications.</p> <p>Conclusion</p> <p>Although influenza A/H1N1v infections were generally self-limited, pediatric burden of disease was significant. Compared to other countries experiencing different health care systems, our Belgian cohort was younger and received less frequently antiviral therapy; disease course and mortality were however similar.</p

The role of short-term memory and visuo-spatial skills in numerical magnitude processing: evidence from Turner syndrome

Peer reviewe

De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome.

Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes1. Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here we identify the non-coding RNA RNU4-2 as a syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome2. We identify an 18 base pair region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 115 individuals with NDD. Most individuals (77.4%) have the same highly recurrent single base insertion (n.64_65insT). In 54 individuals in whom it could be determined, the de novo variants were all on the maternal allele. We demonstrate that RNU4-2 is highly expressed in the developing human brain, in contrast to RNU4-1 and other U4 homologues. Using RNA sequencing, we show how 5 splice-site use is systematically disrupted in individuals with RNU4-2 variants, consistent with the known role of this region during spliceosome activation. Finally, we estimate that variants in this 18 base pair region explain 0.4% of individuals with NDD. This work underscores the importance of non-coding genes in rare disorders and will provide a diagnosis to thousands of individuals with NDD worldwide

Cocaine induces apoptosis in embryonic mouse neurons : teratogenic implications

The developing central nervous system appears particularly vulnerable to cocaine exposure. However, whether the effects of cocaine on the developing brain are the consequences of prolonged episodes of hypoxia induced by this drug or result from a direct toxicity is still a matter of debate. The purpose of this work was to investigate direct effects of cocaine on cerebral cells. We have used the embryonic mouse coculture system of neuronal and glial cells, which maintains communication between these two major populations of cerebral cells, to test for direct neurotoxicity of cocaine concentrations that can be expected in the fetal brain upon severe maternal abuse, on developing brain cells, without intervening structures, including placental, maternal and/or fetal systemic effects. In particular, the system of cultures cells eliminates the most important presynaptic sites of cocaine action, namely the re-uptake of neurotransmitters and the metabolic and degradative pathways present in systemic and brain parenchymal compartments. We are aware that the exposure of our coculture system to cocaine does not reflect exactly the “in vivo” pharmacokinetics of fetal exposure. Results from animal studies suggests that cocaine concentrations peak in the fetal brain 20-30 minutes after administering cocaine to the pregnant dam, and fall progressively, with no detectable cocaine after 6 hours (Sandberg et al., 1991, 1995; Spear et al, 1989). In our coculture system, cocaine hydrolyzed with t1/2 of 17.5 hr, involving a different pattern of exposure. neurons and glial cells were obtained from brain hemispheres of 15-day-old mouse embryos, and were co-cultures for up ti 6 days with Minimum Essential Medium supplemented by heat-inactivated fetal calf serum. After 2 days, and daily thereafter, freshly dissolved cocaine was added to the culture at various concentrations, and medium was renewed daily. Once such cultures were established (after 2 days), neurons lay and extended neuritis on a flat layer of glial cells. The effects of cocaine were first examined by immuno-fluorescence. After 6 days of coculture, control preparations showed neurons with extensive neuritis and prominent MAP2 labeling, well spread over a flat layer of glial cell, labelled for GFAP. After 4 days of exposure to 100µM cocaine, neuritis became scantly and less branched. At 250µM, the number of neuritis par cells had largely decreased, producing an aspect of bi-and unipolar cells. At 500µM, neuritis had almost completely vanished and very few scattered MAP2-labaled round cell bodies persisted. In contrast the number of glial cells remained unchanged in control and treated cultures, although the drug caused some cell flattening and a discrete alteration in their fibrillar structure. When cells were exposed only for 2 days to cocaine and were then cultured for 2 additional days on cocaine-free medium, the remaining cells reextended neuritis although a definitive loss of cells is evidentThèse de doctorat en sciences biomédicales (neurobiologie) -- UCL, 199

Coma postopératoire chez une jeune fille

n/

Coma postopératoire chez une jeune fille [quiz question]

n/