Marine Viellard

How do children with autism spectrum disorders express pain? A comparison with developmentally delayed and typically developing children.

Summary Parents and clinicians report difficulties in pain assessment in children with autism because of sociocommunicative deficits. This study shows that children with autism spectrum disorders are at least as reactive to pain during venipuncture as developmentally delayed and typically developing children. Abstract There is a lack of knowledge about pain reactions in children with autism spectrum disorders (ASD), who have often been considered as insensitive to pain. The objective of this study was to describe the facial, behavioral and physiological reactions of children with ASD during venipuncture and to compare them to the reactions of children with an intellectual disability and nonimpaired control children. We also examined the relation between developmental age and pain reactions. The sample included 35 children with ASD, 32 children with an intellectual disability, and 36 nonimpaired children. The children were videotaped during venipuncture and their heart rate was recorded. Facial reactions were assessed using the Child Facial Coding System (CFCS) and behavioral reactions were scored using the Noncommunicating Children’s Pain Checklist (NCCPC). A linear mixed‐effects model showed that children’s reactions increased between baseline and venipuncture and decreased between the end of venipuncture and the recovery period. There was no significant difference between groups regarding the amount of facial, behavioral and physiological reactions. However, behavioral reactions seemed to remain high in children with ASD after the end of the venipuncture, in contrast with children in the 2 other groups. Moreover, we observed a significant decrease in pain expression with age in nonimpaired children, but no such effect was found regarding children with ASD. The data reveal that children with ASD displayed a significant pain reaction in this situation and tend to recover more slowly after the painful experience. Improvement in pain assessment and management in this population is necessary.

Cognitive and adaptive evaluation of 21 consecutive patients with Dravet syndrome.

In order to assess the cognitive and adaptive profiles of school-aged patients with Dravet syndrome (DS), we proposed to evaluate the intelligence and adaptive scores in twenty-one 6- to 10-year-old patients with DS followed in our institution between 1997 and 2013. Fourteen patients were tested using the Wechsler Intelligence Scale for Children (WISC) and the Vineland Adaptive Behavioral Scales (VABS); 6 patients could not be tested with the WISC and were tested with the VABS only, and one was tested with the WISC only. Data regarding the epilepsy were retrospectively collected. Statistical analysis (Spearman rank order and Pearson correlation coefficient) was used to correlate early epilepsy characteristics with the cognitive and adaptive scores. Sodium channel, neuronal alpha-subunit type 1 (SCN1A) was mutated in 19 out of 21 patients. After the age of 6years, none of the DS patients had a normal intelligence quotient (IQ) using WISC (age at the testing period: mean=100±5; median=105months; mean total IQ=47±3; n=15). Only five patients had a verbal and/or a non verbal IQ of more than 60 (points). Their cognitive profile was characterized by an attention deficit, an inability to inhibit impulsive responses, perseverative responses and deficit in planning function. Administering the Vineland Adaptive Behavioral Scales in the same period, we showed that socialization skills were significantly higher than communication and autonomy skills (age at the testing period: mean=100±4; median=100months; n=20). We did not find any significant correlation between the IQ or developmental quotient assessed between 6 and 10years of age and the quantitative and qualitative parameters of epilepsy during the first two years of life in this small group of patients. Despite an overall moderate cognitive deficit in this group of patients, the Vineland Adaptive Behavioral Scales described an adaptive/behavioral profile with low communication and autonomy capacities, whereas the socialization skills were more preserved. This profile was different from the one usually found in young patients with autism and may require specific interventions.

Schizophrénie ou syndrome d'Asperger ?

Patients with Asperger syndrome are often diagnosed late or are wrongly considered to have schizophrenia. Misdiagnosing Asperger syndrome creates serious problems by preventing effective therapy. Several clinical signs described in Asperger syndrome could also be considered as clinical signs of schizophrenia, including impaired social interactions, disabilities in communication, restricted interests, and delusions of persecution. A number of clinical features may facilitate the differential diagnosis: younger age at onset, family history of pervasive developmental disorder, recurring conversations on the same topic, pragmatic aspects of language use, oddities of intonation and pitch, lack of imagination, and incomprehension of social rules are more characteristic of Asperger syndrome. Accurate distinction between Asperger syndrome and schizophrenia would make it possible to offer more treatment appropriate to the patients functioning.

Mise au pointSchizophrénie ou syndrome d’Asperger ?Schizophrenia or Asperger syndrome?

Patients with Asperger syndrome are often diagnosed late or are wrongly considered to have schizophrenia. Misdiagnosing Asperger syndrome creates serious problems by preventing effective therapy. Several clinical signs described in Asperger syndrome could also be considered as clinical signs of schizophrenia, including impaired social interactions, disabilities in communication, restricted interests, and delusions of persecution. A number of clinical features may facilitate the differential diagnosis: younger age at onset, family history of pervasive developmental disorder, recurring conversations on the same topic, pragmatic aspects of language use, oddities of intonation and pitch, lack of imagination, and incomprehension of social rules are more characteristic of Asperger syndrome. Accurate distinction between Asperger syndrome and schizophrenia would make it possible to offer more treatment appropriate to the patients functioning.

Localized Misfolding Within Broca’s Area as a Distinctive Feature of Autistic Disorder

BACKGROUND Recent neuroimaging studies suggest that autism spectrum disorder results from abnormalities in the cortical folding pattern. Usual morphometric measurements have failed to provide reliable neuroanatomic markers. Here, we propose that sulcal pits, which are the deepest points in each fold, are suitable candidates to uncover this atypical cortical folding. METHODS Sulcal pits were extracted from a magnetic resonance imaging database of 102 children (1.5-10 years old) distributed in three groups: children with autistic disorder (n = 59), typically developing children (n = 22), and children with pervasive developmental disorder not otherwise specified (n = 21). The geometrical properties of sulcal pits were compared between these three groups. RESULTS Fold-level analyses revealed a reduced pit depth in the left ascending ramus of the Sylvian fissure in children with autistic disorder only. The depth of this central fold of Brocas area was correlated with the social communication impairments that are characteristic of the pathology. CONCLUSIONS Our findings support an atypical gyrogenesis of this specific fold in autistic disorder that could be used for differential diagnosis. Sulcal pits constitute valuable markers of the cortical folding dynamics and could help for the early detection of atypical brain maturation.

Screening for depression in youth with epilepsy: The NDDI-E-Y

To The Editors: We read with interest the 2016 Epilepsia article by Wagner and colleagues validating the revised 12‐item screening tool for depression in youth with epilepsy: the Neurological Disorders Depression Inventory‐Epilepsy for Youth (NDDI‐E‐Y), and the 2017 Epilepsia article by the same team comparing NDDI‐E‐Y with the Neuro QOL‐SF. We commend the authors for this initiative, which is in line with the International League Against Epilepsy (ILAE) recommendations for routine screening for major depressive disorder (MDD) in epilepsy. Appropriate screening tools are crucial given the symptomatic overlap with the effects of antiepileptic drugs; this diagnostic challenge led to the development of the NDDI‐E for adults with epilepsy, a 6‐item questionnaire with robust psychometric properties across languages and populations. The NDDI‐E was thus a logical basis for the 12‐item NDDI‐E‐Y that aims at screening for MDD in 12‐ to 17‐year‐olds. We wished to validate this instrument in a group of 98 French patients using standard methodology, following our previous experience of validating screening instruments in French 7–9 and using methodology equivalent to that of Wagner et al, comparing NDDI‐E‐Y scores to the Childrens Depression Inventory (CDI). Our group was similar in size and demographics (age range 11‐17 years, mean 15; F 55%). According to the 2016 article of Wagner et al, the 12‐item NDDI‐E‐Y is scored from 0 to 3, giving a maximum possible of 36 if the patient scores 3 for all 12 items. It is therefore surprising that the authors found a cutoff of 32/36 as a suitable screening level, since this represents the highest percentile and would indicate nonnormal distribution of responses, with a possible ceiling effect. For the NDDI‐E in adults, scored from 1 to 4, the maximum possible is 24 and cutoff ranged from 11 to 16 across all studies, and is thus the middle range. For the NDDI‐E‐Y, our study in French youth with epilepsy found a cutoff of 11/ 36 (sensitivity 100% [95% confidence interval (CI) 83.9100.0]; specificity 83.1% [95% CI 72,9-90,7]; positive predictive value 61.8% [95% CI 43,3; -78,1]; negative predictive value 100% [95% CI 94.4; 100.0]), markedly lower than Wagner et als cutoff of 32/36. Indeed, no subject in our cohort reached a score of 32/36. This observed discrepancy in cutoff is difficult to explain by population factors, since prevalence of possible MDD according to CDI scores was similar, or by cultural‐linguistic differences, since previous multilanguage comparisons of NDDI‐E showed only mild variation. We therefore suggest that the NDDI‐E‐Y should be retested rapidly in a separate population to check validity of the proposed cutoff. Testing a new population is essential, as both recent publications on the NDDI‐E‐Y appear to have used the same 99 subjects according to the data provided. In addition, the 2017 paper surprisingly refers to the “11‐item NDDI‐E‐Y,” whereas their 2016 study was based on a 12‐item NDDI‐E‐Y, without explanation for this change. We would be grateful if the authors could present the distribution of responses for the total score and for each item, as is traditional in psychometric validation (Figure S1A,B). Further studies seem essential and urgent: Screening requires reliable and accurate cutoff scores, and an instrument with an overly elevated cutoff score would risk missing cases of MDD.

Troubles bipolaires : continuité enfant-adulte ?

Resume Les troubles bipolaires a debut precoce suscitent encore de nombreuses interrogations en particulier chez l’enfant du fait des nombreuses particularites cliniques des episodes thymiques pour cette tranche d’âge. Il n’existe en effet aucun consensus sur la prevalence de ce trouble pendant la periode pre pubertaire. Ce diagnostic reste donc tres controverse chez l’enfant et le preadolescent, et nous essaierons de comprendre pourquoi. Cette problematique de la continuite entre les troubles bipolaires de l’enfant et de l’adulte, nous interroge egalement sur l’existence de facteurs predictifs des troubles bipolaires chez l’adulte. Nous tenterons a travers des etudes concernant l’enfance des adultes bipolaires mais egalement des etudes sur les enfants de parents bipolaires, d’identifier les troubles psychopathologiques qui precedent le trouble bipolaire.Early onset (pediatric) bipolar disorders are still an issue of much controversy due to several clinical particularities of the thymic episodes at this age. To date, there is indeed no consensus regarding the prevalence of bipolar disorders before puberty. Diagnosis criteria in children and young adolescents remain thus elusive. The purpose of this review is to provide an overview of this issue. The idea of continuity, from childhood to adulthood, in bipolar disorders also raises important questions regarding predictive factors of bipolar disorders in adults. Studies on the childhood of bipolar adults, as well as studies on the children of bipolar parents will be reviewed, in an attempt to identify the psychopathological substrates of bipolar disorders.

Brain structural underpinnings of autism spectrum disorder revealed by sulcus-based morphometry

Autism Spectrum Disorder is associated with an altered early brain development. However, the specific cortical structure abnormalities underlying this disorder remain largely unknown. Here, we designed a multi-modal segmentation pipeline adapted to anatomical MR images acquired in a clinical setting in order to apply state-of-the-art sulcus-based morphometry methods to a large cohort of 73 young children. We computed multiple descriptors of the geometry of each sulcus, hereby separating the folding measurement into distinct factors such as the length and depth of the sulcus. We demonstrated that several sulci showed a significant and consistent pattern of abnormalities across our different geometrical features. These structural abnormalities are confined to regions that are functionally relevant with respect to cognitive disorders in ASD, and might thus represent a set of complementary anatomical markers of this pathology.