Early diagnosis of pyridoxine-dependent epilepsy: Video-EEG monitoring and biochemical and genetic investigation

International audiencePyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive metabolic disease. A delay of treatment may affect outcome and early initiation of pyridoxine based on effective diagnosis is crucial to ensure good cognitive outcome in neonates. A consensus for the diagnosis of PDE is based on refractive seizures and responsiveness to pyridoxine, however, a growing body of evidence suggests that additional elements should be considered which include biochemical data, genetic screening, and EEG monitoring. We present a case study of a neonate with PDE, who presented with misleading clinical presentation and a novel mutation in the antiquitin (ALDH7A1) gene (A294V), and highlight important aspects in order to consider the definition of diagnosis and management of PDE in the light of more recent data. (C) 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved

Les nouvelles technologies comme outils pédagogiques pour l'autisme (table ronde)

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Childhood apraxia of speech without intellectual deficit in a patient with cri du chat syndrome.

International audienceWe report an 11-year-old girl for whom the diagnosis of cri du chat syndrome (CdCS) was made during a genetic investigation of childhood apraxia of speech. The patient presented with the classic chromosome 5 short arm deletion found in CdCS. The microdeletion, characterised using aCGH (array Comparative Genomic Hybridisation), was 12.85 Mb, overlapping the 5p15.2 and 5p15.3 critical regions. CdCS is typically associated with severe mental retardation while this patient had normal intellectual performance, confirmed by normal results from categorisation tasks. This mild phenotype was assessed using a comprehensive cognitive battery. Language evaluation showed normal receptive vocabulary scores, in contrast with obvious oro-facial dyspraxia. Disabled fine motor skills were confirmed as well as weak visuo-spatial reasoning abilities. In conclusion, fine cognitive assessment may be worthwhile for patients with CdCS since good intellectual functioning may be masked by severe speech and gestural dyspraxia, thus requiring specific teaching and rehabilitation strategies

Early screening of Autism Spectrum Disorder in primary care using parental questionnaires: The Kitcat French study protocol

Early screening of children with Autism Spectrum Disorder (ASD) needs to be improved to propose early interventions. Parental questionnaires are useful to help primary care professionals and nurseries to detect children’s autism signs. Our primary objective is to estimate the positive predictive value of an early detection kit composed of 2 parental questionnaires M-CHAT-R/F™ (Modified-CHecklist for Autism in Toddlers-Revised/Follow-up) and CSBS DP™-ITC (Communication and Symbolic Behavior Scales Developmental Profile-Infant Toddler Checklist) followed by a psychologist’s confirmation. Methods and Analysis: Boys and girls aged 16 to 30 months, seen at their general or paediatric practice or attending nurseries or early childcare centers, never diagnosed ASD, are eligible. We plan to have a cohort of 1700 children filling the screening kit and expect to detect about 81 children confirmed positive . We also expect to detect other neurodevelopmental disorders than ASD. Discussion: The use of 2 questionnaires and the intervention of trained psychologists should optimize the access to early detection of ASD near home and links between childhood professionals. Our study is coherent with the French organization and existing tools

History of multiple sclerosis in 2 successive pregnancies: A French and Italian cohort

Objective: To evaluate the risk of relapses during pregnancy and in the first 3 months after delivery in 2 successive pregnancies in a cohort of French and Italian women with multiple sclerosis (MS). Methods: A total of 93 women were included if they had had 2 pregnancies followed prospectively after MS onset between January 1993 and 2013. The association of a relapse during pregnancy or the first postpartum trimester in pregnancy 1 and pregnancy 2 was evaluated by univariate logistic regression. Results: A majority of women did not experience any exacerbation in the 3 months after delivery (31.2% and 23.7%, respectively, relapsed after pregnancy 1 and 2; p 0.32). A total of 7.6% had a relapse after both pregnancies. The risk of relapse after pregnancy 2 was not associated with the number of relapses in the prepregnancy year (odds ratio [OR] 1.52 [0.57-4.05]) or during pregnancy (OR 1.57 [0.52-4.79]) or with the occurrence of a relapse after pregnancy 1 (OR 0.86 [0.29-2.50]). Conclusions: Our work provides original data on the evolution of successive pregnancies in MS, showing a similar (and even lower) disease activity in the second pregnancy. There was no correlation of activity in successive pregnancies. Therefore, counseling of women with MS who consider having a second baby should be the same as for the first one

A Novel Analog Reasoning Paradigm: New Insights in Intellectually Disabled Patients

International audienceBackgroundIntellectual Disability (ID) is characterized by deficits in intellectual functions such as reasoning, problem-solving, planning, abstract thinking, judgment, and learning. As new avenues are emerging for treatment of genetically determined ID (such as Down’s syndrome or Fragile X syndrome), it is necessary to identify objective reliable and sensitive outcome measures for use in clinical trials.ObjectiveWe developed a novel visual analogical reasoning paradigm, inspired by the Progressive Raven’s Matrices, but appropriate for Intellectually Disabled patients. This new paradigm assesses reasoning and inhibition abilities in ID patients.MethodsWe performed behavioural analyses for this task (with a reaction time and error rate analysis, Study 1) in 96 healthy controls (adults and typically developed children older than 4) and 41 genetically determined ID patients (Fragile X syndrome, Down syndrome and ARX mutated patients). In order to establish and quantify the cognitive strategies used to solve the task, we also performed an eye-tracking analysis (Study 2).ResultsDown syndrome, ARX and Fragile X patients were significantly slower and made significantly more errors than chronological age-matched healthy controls. The effect of inhibition on error rate was greater than the matrix complexity effect in ID patients, opposite to findings in adult healthy controls. Interestingly, ID patients were more impaired by inhibition than mental age-matched healthy controls, but not by the matrix complexity. Eye-tracking analysis made it possible to identify the strategy used by the participants to solve the task. Adult healthy controls used a matrix-based strategy, whereas ID patients used a response-based strategy. Furthermore, etiologic-specific reasoning differences were evidenced between ID patients groups.ConclusionWe suggest that this paradigm, appropriate for ID patients and developmental populations as well as adult healthy controls, provides an objective and quantitative assessment of visual analogical reasoning and cognitive inhibition, enabling testing for the effect of pharmacological or behavioural intervention in these specific populations

Epileptic patients with de novo STXBP1 mutations: Key clinical features based on 24 cases

International audienceObjective: Mutations in the syntaxin binding protein 1 gene (STXBP1) have been associated mostly with early onset epileptic encephalopathies (EOEEs) and Ohtahara syndrome , with a mutation detection rate of approximately 10%, depending on the criteria of selection of patients. The aim of this study was to retrospectively describe clinical and electroencephalography (EEG) features associated with STXBP1-related epilepsies to orient molecular screening. Methods: We screened STXBP1 in a cohort of 284 patients with epilepsy associated with a developmental delay/intellectual disability and brain magnetic resonance imaging (MRI) without any obvious structural abnormality. We reported on patients with a mutation and a microdeletion involving STXBP1 found using array comparative geno-mic hybridization (CGH). Results: We found a mutation of STXBP1 in 22 patients and included 2 additional patients with a deletion including STXBP1. In 22 of them, epilepsy onset was before 3 months of age. EEG at onset was abnormal in all patients, suppression-burst and multifocal abnormalities being the most common patterns. The rate of patients carrying a mutation ranged from 25% in Ohtahara syndrome to <5% in patients with an epilepsy beginning after 3 months of age. Epilepsy improved over time for most patients, with an evolution to West syndrome in half. Patients had moderate to severe developmental delay with normal head growth. Cerebellar syndrome with ataxic gait and/or tremor was present in 60%