Mutations in Eml1 lead to ectopic progenitors and neuronal heterotopia in mouse and human.

Neuronal migration disorders such as lissencephaly and subcortical band heterotopia are associated with epilepsy and intellectual disability. DCX, PAFAH1B1 and TUBA1A are mutated in these disorders; however, corresponding mouse mutants do not show heterotopic neurons in the neocortex. In contrast, spontaneously arisen HeCo mice display this phenotype, and our study revealed that misplaced apical progenitors contribute to heterotopia formation. While HeCo neurons migrated at the same speed as wild type, abnormally distributed dividing progenitors were found throughout the cortical wall from embryonic day 13. We identified Eml1, encoding a microtubule-associated protein, as the gene mutated in HeCo mice. Full-length transcripts were lacking as a result of a retrotransposon insertion in an intron. Eml1 knockdown mimicked the HeCo progenitor phenotype and reexpression rescued it. We further found EML1 to be mutated in ribbon-like heterotopia in humans. Our data link abnormal spindle orientations, ectopic progenitors and severe heterotopia in mouse and human

Hématomes sous-duraux chez l'enfant (étude rétrospective chez 86 sujets clinique, paraclinique, étiologies, prise en charge et devenir)

Introduction : Les hématomes sous-duraux (HSD) sont fréquents dans la population pédiatrique et sont une cause de morbi-mortalité importante notamment dans le cadre des traumatismes crâniens non accidentels. L objectif de cette étude est de décrire la présentation clinique, les caractéristiques TDM et IRM, les examens complémentaires notamment ophtalmologiques, la prise en charge thérapeutique, le devenir médical et socio-judiciaire chez les enfants âgés de 0 à 18 ans souffrant d un HSD. Matériel et méthodes : dans le cadre de cette revue rétrospective, les quatre-vingt huit dossiers de cas d HSD survenus entre 1998 et 2012 au CHU d Amiens ont été étudiés. Résultats : 72% des enfants avaient moins de 12 mois. Les motifs de consultation et les signes cliniques constatés à l entrée étaient multiples et non spécifiques. Il n y avait pas de caractéristique radiologique significative (localisation, latéralisation, lésions parenchymateuses associées) permettant d affirmer avec certitude l étiologie de l HSD (notamment le diagnostic de syndrome du bébé secoué). Dans 51% des cas il était également retrouvé des hémorragies rétiniennes au fond œil. 49% des HSD étaient dus à un traumatisme crânien accidentel, 36% à un syndrome du bébé secoué et 15% à une pathologie identifiée ou non. 46% souffraient à posteriori de séquelles cliniques de sévérité variable. Discussion - Conclusion : Nos résultats étaient concordants avec ceux retrouvés dans la littérature en particulier concernant les différentes caractéristiques des HSD selon l étiologie en cause. Chaque acteur de santé a un rôle primordial face à un enfant consultant pour HSD et notamment afin de ne pas méconnaître une situation de maltraitance.Objective : Subdural hematoma (SDH) are common in the pediatric population and are a major cause of morbidity and mortality, particularly in the context of non-accidental head injury. The aim of this study was to describe clinical presentations, imaging findings (CT and MRI), additional exams including eye examination, therapeutic care, and medical and socio-legal outcomes, in children aged 0-18 years suffering from HSD. Methods : In this retrospective review, eighty-eight cases files HSD occurred between 1998 and 2012 at the University Hospital in Amiens were studied. Results : 72% of the children had less than 12 months. The consultation s reasons and clinical signs observed at the admission were various and non-specific. There was no significant radiological characteristics (localization, lateralization, parenchymal lesions) to determine exactly the etiology of HSD (including the diagnosis of shaken baby syndrome). In 51% of cases it was also found retinal hemorrhages at the eye fundus. 49% of HSD were caused by an accidental head injury, 36% to shaken baby syndrome and 15% a disease identified or not. 46% had neurological injury of variable severity. Conclusions : Our results were similar with the data in the literature, in particular concerning the different characteristics of HSD in the etiology involved. Each health professional must have a key role face to a child patient with HSD and in particular to avoid missing an abusive situation.AMIENS-BU Santé (800212102) / SudocSudocFranceF

Marche digitigrade chez l'enfant (les entités étiologiques)

INTRODUCTION : La marche digitigrade ou Toe-walking est un motif fréquent de consultation en pédiatrie. Elle est définie sur le plan biomécanique par une absence de premier pivot lors du cycle de la marche, ce qui a pour conséquence une attaque du sol par la pointe des pieds et non par le talon. Décrite par certains auteurs comme une étape physiologique du schéma d acquisition de la locomotion, elle est pourtant associée à de nombreuses pathologies neurologiques. L objectif de notre travail était, après avoir redéfini les mécanismes physiopathologiques de la marche, de mettre en évidence les entités étiologiques de la marche digitigrade. PATIENTS ET METHODE : Etude rétrospective observationnelle des caractéristiques de la marche digitigrade chez 64 enfants qui ont consulté au CHU d Amiens en neurologie pédiatrique ou orthopédie pédiatrique de janvier à décembre 2011. RESULTATS : Les enfants avaient présenté un âge moyen d acquisition de la marche de 15,2 mois. L âge moyen des 64 patients était de 4 ans et 7 mois. L âge moyen du diagnostic était de 4,2 ans. Les différents diagnostics évoqués étaient une marche digitigrade idiopathique (45%), des séquelles de paralysie cérébrale (23%), une myopathie (8 %), un retard d acquisition psychomotrice d origine indéterminée (5%), un trouble envahissant du développement (5%) et une neuropathie sensitivomotrice (3%). Il n a pas été retrouvé d étiologie dans 11% des cas. CONCLUSION : La marche digitigrade pathologique de l enfant est de diagnostic facile lorsqu elle est associée à d autres signes cliniques d une pathologie neurologique connue (la paralysie cérébrale ou les pathologies neuromusculaires). Cependant lorsqu elle est débutante et isolée, elle peut être un signe précurseur d une pathologie neuromusculaire ou d une anomalie développementale. Toute marche digitigrade chez l enfant nécessite donc un suivi spécialisé en neurologie ou orthopédie pédiatrique dès son diagnostic.AMIENS-BU Santé (800212102) / SudocSudocFranceF

Pertinence d'un dossier informatisé partagé pour favoriser la coordination interprofessionnelle autour de l'enfant handicapé (enquête auprès de 700 professionnels en Picardie)

La prise en charge de l enfant handicapé est multidimensionnelle et implique de nombreux professionnels. Une meilleure coopération interprofessionnelle favorise coordination et continuité des prises en charge. Une bonne circulation de l information facilite cette coopération. Les Dossiers Informatisés Partagés (DIP) sont de nouveaux moyens d échanges d informations. Un tel dossier permettrait-il d améliorer la qualité de la prise en charge de l enfant handicapé ? Nous avons interrogé à ce sujet les professionnels concernés. Nous avons réalisé courant 2011 une enquête auprès de 659 professionnels libéraux et 50 structures médicosociales (SMS) de Picardie, sous la forme de questionnaires postaux ou sur internet. La qualité de la circulation de l information était jugée insuffisante ou mauvaise par 77,3% des répondants (IC95%=+-5,2), et 80,1% des répondants (IC95%=+-4,9) estimaient que la mise en place d un DIP permettrait d améliorer la qualité de la prise en charge de l enfant handicapé. 70,9% des répondants (IC95%=+-5,6) estimaient essentielle la mise en place de ce dossier. L idée d un DIP autour de l enfant handicapé nous semble pertinente. Cependant les résultats ne sont généralisables qu en Picardie et aux catégories de professionnels libéraux interrogés. Il serait utile de consulter les infirmiers libéraux, les parents, et de réaliser auprès des SMS une enquête plus étendue. Pour juger véritablement de la pertinence d un DIP il faudrait un retour sur expérience, et il reste à déterminer quelle forme ce dossier devrait prendre et comment le mettre en place. On se réfèrera utilement aux DIP expérimentés ailleurs.The management of disabled children is multidimensional and involves many professionals. Better collaboration promotes interprofessional coordination and continuity of care. A good flow of information facilitates this collaboration. Shared electronic health records (EHRs) are new ways of information exchange. Would such records allow to improve the quality of care of disabled children? We asked the involved professionals about it. We conducted in 2011 a survey of 659 liberal professionals and 50 medical-social structures (MSS) from Picardie, France, in the form of postal or online questionnaires.The quality of the flow of information was deemed insufficient or poor in 77.3% of respondents (95% CI = +- 5.2), and 80.1% of respondents (95% CI = +- 4.9) considered that the introduction of a shared EHR would improve the quality of care of disabled children. 70.9% of respondents (95% CI = +- 5.6) considered it essential to set up such a record.The idea of a shared EHR concerning disabled children seems relevant. The results can be generalized in Picardy and among categories of liberal professionals interviewed. It would be useful to consult independent nurses, parents, and to conduct in MSS a larger survey. To properly evaluate the relevance of shared EHRs should be a feedback process, and it is unclear what form this record should take and how to set it up. It may be useful to refer to experienced shared EHRs.AMIENS-BU Santé (800212102) / SudocSudocFranceF

Should isolated fetal ventriculomegaly measured below 12 mm be viewed as a variant of the norm? Results of a 5-year experience in a prenatal referral center

International audienceBackground: Fetal ventriculomegaly (VM) is defined as lateral ventricles measured above 10mm. Some authors believe VM <12mm are variants of the norm and need not be addressed for referral ultrasound.Methods: A retrospective continuous cohort study of 127 confirmed fetal VM was divided into three groups after initial referral sonographic assessment: isolated VM <12mm (group A), isolated VM 12mm (group B), and VM associated with other malformations (group C). We reviewed obstetric outcome and neonate evolution after 1 month with the aim of defining a pertinent prenatal workup.Results: We reported fetal infections in all groups (p=.24) and chromosomal abnormalities only in group C (p=.41). Fetal magnetic resonance imaging (MRI) found initially undiagnosed brain abnormalities in groups B and C (12.5 and 14.1%, p<.05). Ratios of healthy children after 1 month stemming, respectively, from groups A, B, and C were 66.7, 62.5, and 20.2% (p<.05).Conclusions: Our results are in favor of a systematic referral ultrasound for every fetal VM, regardless of size, as soon as definition criterion is met. Additional paraclinical assessment (maternal serologic status for toxoplasmosis and cytomegalovirus, amniocentesis, fetal cerebral MRI) should be discussed depending on the situation

A Movement Monitor Based on Magneto-Inertial Sensors for Non-Ambulant Patients with Duchenne Muscular Dystrophy: A Pilot Study in Controlled Environment.

UNLABELLED:Measurement of muscle strength and activity of upper limbs of non-ambulant patients with neuromuscular diseases is a major challenge. ActiMyo® is an innovative device that uses magneto-inertial sensors to record angular velocities and linear accelerations that can be used over long periods of time in the home environment. The device was designed to insure long-term stability and good signal to noise ratio, even for very weak movements. In order to determine relevant and pertinent clinical variables with potential for use as outcome measures in clinical trials or to guide therapy decisions, we performed a pilot study in non-ambulant neuromuscular patients. We report here data from seven Duchenne Muscular Dystrophy (DMD) patients (mean age 18.5 ± 5.5 years) collected in a clinical setting. Patients were assessed while wearing the device during performance of validated tasks (MoviPlate, Box and Block test and Minnesota test) and tasks mimicking daily living. The ActiMyo® sensors were placed on the wrists during all the tests. Software designed for use with the device computed several variables to qualify and quantify muscular activity in the non-ambulant subjects. Four variables representative of upper limb activity were studied: the rotation rate, the ratio of the vertical component in the overall acceleration, the hand elevation rate, and an estimate of the power of the upper limb. The correlations between clinical data and physical activity and the ActiMyo® movement parameters were analyzed. The mean of the rotation rate and mean of the elevation rate appeared promising since these variables had the best reliability scores and correlations with task scores. Parameters could be computed even in a patient with a Brooke functional score of 6. The variables chosen are good candidates as potential outcome measures in non-ambulant patients with Duchenne Muscular Dystrophy and use of the ActiMyo® is currently being explored in home environment. TRIAL REGISTRATION:ClinicalTrials.gov NCT01611597

Effects of Methylphenidate on Default-Mode Network/Task-Positive Network Synchronization in Children With ADHD

OBJECTIVE: A failure of the anti-phase synchronization between default-mode (DMN) and task-positive networks (TPN) may be involved in a main manifestation of ADHD: moment-to-moment variability. The study investigated whereby methylphenidate may improve TPN/DMN synchronization in ADHD. METHOD: Eleven drug-naive ADHD children and 11 typically developing (TD) children performed a flanker task during functional magnetic resonance imaging. The ADHD group was scanned without and 1 month later with methylphenidate. The signal was analyzed by independent component analysis. RESULTS: The TD group showed anti-phase DMN/TPN synchronization. The unmedicated ADHD group showed synchronous activity in the posterior DMN only, which was positively correlated with response time variability for the flanker task. Methylphenidate initiated a partial anti-phase TPN/DMN synchronization, reduced variability, and abolished the variability/DMN correlation. CONCLUSION: Although results should be interpreted cautiously because the sample size is small, they suggest that a failure of the TPN/DMN synchronization could be involved in the moment-to-moment variability in ADHD. Methylphenidate initiated TPN/DMN synchronization, which in turn appeared to reduce variability

Patient flow-chart.

<p>Patient flow-chart.</p

Clinical features of the DMD patients ordered by increasing age.

<p>Clinical features of the DMD patients ordered by increasing age.</p