Pubmed du 06/05/19

lundi 6 mai 2019

1. Ben-Itzchak E, Zachor DA. Toddlers to teenagers : Long-term follow-up study of outcomes in autism spectrum disorder. Autism. 2019 : 1362361319840226.

This prospective study examined the developmental changes over time of adolescents diagnosed in toddlerhood with autism spectrum disorder and searched for child characteristics at toddlerhood that predict outcome at adolescence. The study included 65 participants who were divided into low cognitive (developmental quotient < 85 ; N = 41) and high cognitive (developmental quotient 85 ; N = 21) groups in adolescence. Participants underwent a comprehensive assessment of cognitive ability, adaptive skills, and autism severity. Significant differences in the current clinical phenotypes and in developmental changes over time were found between the two cognitive groups. At baseline, the high cognitive group had significantly less severe social communication deficits. Only the high cognitive group showed a decrease in social communication deficits over time. Although the two groups did not differ in their adaptive skills at the time of diagnosis, the high cognitive group had better adaptive skills at adolescence. Better adaptive communication skills in toddlerhood were associated with better outcome at adolescence in cognitive ability, adaptive skills, and fewer autism symptoms. Less impaired baseline social affect and better cognitive ability predicted higher cognitive level and adaptive skills at adolescence. Cognitive potential of individuals with autism spectrum disorder plays an important role in long-term outcome and comprehensive evaluations at toddlerhood have strong prognostic value in adolescence.

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2. Cederlund M. Autism Mental Status Examination (AMSE) : A Valid Instrument in the Evaluation of Pre-school Children with Suspected Autism Spectrum Disorders ?. J Autism Dev Disord. 2019.

In this study the Autism Mental Status Exam (AMSE) was validated towards ICD-10 Autism Spectrum Diagnoses (ASD) based on an interview with the Diagnostic Interview for Social and Communication Disorders (DISCO-11) with parent(s)/caregiver(s) in a group of 124 children referred for assessment to a clinical assessment unit for pre-school children. The results from the study indicates a Fair relation across the AMSE score and ICD-10 Autism Spectrum Disorder (ASD). AMSE mean score for children not fulfilling criteria for an ASD at the assessment was significantly lower compared to the AMSE mean score for children who acquired an ASD diagnosis in the study. In addition, Vineland-II Parent/caregiver rating questionnaire GAF standard scores showed a reversed correlation to the AMSE mean scores (i.e. higher AMSE mean scores were related to lower Vineland-II GAF standard scores and vice versa).

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3. Chandrakumar A, t Jong GW. Maternal Exposure to Air Pollution During Pregnancy and Autism Spectrum Disorder in Offspring. JAMA Pediatr. 2019.

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4. Dryburgh E, McKenna S, Rekik I. Predicting full-scale and verbal intelligence scores from functional Connectomic data in individuals with autism Spectrum disorder. Brain Imaging Behav. 2019.

Decoding how intelligence is engrained in the human brain construct is vital in the understanding of particular neurological disorders. While the majority of existing studies focus on characterizing intelligence in neurotypical (NT) brains, investigating how neural correlates of intelligence scores are altered by atypical neurodevelopmental disorders, such as Autism Spectrum Disorders (ASD), is almost absent. To help fill this gap, we use a connectome-based predictive model (CPM) to predict intelligence scores from functional connectome data, derived from resting-state functional magnetic resonance imaging (rsfMRI). The utilized model learns how to select the most significant positive and negative brain connections, independently, to predict the target intelligence scores in NT and ASD populations, respectively. In the first step, using leave-one-out cross-validation we train a linear regressor robust to outliers to identify functional brain connections that best predict the target intelligence score (p - value < 0.01). Next, for each training subject, positive (respectively negative) connections are summed to produce single-subject positive (respectively negative) summary values. These are then paired with the target training scores to train two linear regressors : (a) a positive model which maps each positive summary value to the subject score, and (b) a negative model which maps each negative summary value to the target score. In the testing stage, by selecting the same connections for the left-out testing subject, we compute their positive and negative summary values, which are then fed to the trained negative and positive models for predicting the target score. This framework was applied to NT and ASD populations independently to identify significant functional connections coding for full-scale and verbal intelligence quotients in the brain.

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5. Gaona C, Castro S, Palikara O. The views and aspirations of young people with autism spectrum disorders and their provision in the new Education Health and Care plans in England. Disabil Rehabil. 2019 : 1-12.

BACKGROUND : The new special educational needs and disability legislation in England has introduced Education Health and Care plans as statutory documents for children with special educational needs, and has extended provision beyond compulsory education, placing transition in a compelling position. This policy recognises the need to include the views, wishes and aspirations of children and young people in the development of provision to cater for their needs. For young people with autism spectrum disorders and their families, transition to post-16 education and employment could be challenging. This study aimed to explore how voices of young people with autism spectrum disorders are captured in their Education Health and Care plans. METHODS : These views were collected from the Education Health and Care plans of 12 young people with autism spectrum disorders. These plans were analysed inductively and deductively through content analysis, using the International Classification of Functioning, Disability and Health : Children and Youth Version as a coding framework. RESULTS : Discrepancies were found between plans concerning the ways in which the voices of young people with ASD were elicited. A total of 189 functioning codes were identified, with a prevalence of activities and participation codes to reflect their views, followed by body functions and lastly environmental factors. CONCLUSION : These disparities are discussed in light of the biopsychosocial model of functioning and health, and the new English policy. Implications for adopting the International Classification of Functioning framework to give voice to young people with autism spectrum disorders are also discussed. Implications for rehabilitation Young people with autism spectrum disorders face many challenges in their transition to post-16 education and employment. Engaging young people with autism spectrum disorders in matters that affect their own lives contribute to the development of provision that is aligned with their wishes and aspirations. Practitioners collaborating in the development of Education Health and Care plans should ensure that young people are effectively involved in the development of their own plans. The International Classification of Functioning, Disability and Health, Children and Youth Version provides a systematic framework and language for coding and recording data from different sources with which to capture young people’s views.

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6. Hannant P, Cassidy S, Renshaw D, Joyce A. A double-blind, placebo-controlled, randomised-designed GABA tea study in children diagnosed with autism spectrum conditions : a feasibility study clinical trial registration : ISRCTN 72571312. Nutr Neurosci. 2019 : 1-17.

OBJECTIVE : The research has shown an association with sensorimotor integration and symptomology of Autism Spectrum Conditions (ASC). Specific areas of the brain that are involved in sensorimotor integration, such as the cerebellum and basal ganglia, are pathologically different in individuals with ASC in comparison to typically developing (TD) peers. These brain regions contain GABAergic inhibitory neurons that release an inhibitory neurotransmitter, gamma-Aminobutyric acid (GABA). Brain GABA levels are decreased in ASC. This study explored the effect of introducing a non-invasive GABA substitute, in the form of GABA Oolong tea, on sensorimotor skills, ASC profiles, anxieties and sleep of children with ASC. METHODS : Nine children took part : (5 male, 4 female). Each child participated in three tea conditions : high GABA, high L-Theanine (a compound that increases GABA), placebo with low GABA. A double-blind, repeated measures design was employed. Measures were taken after each tea condition. Sensory and ASC profiles were scored using parental questionnaires. Motor skills were assessed using a gold standard coordination assessment. Sleep was monitored using an actiwatch and anxiety measured through cortisol assays. Subjective views were sought from parents on ’best’ tea. RESULTS : The results showed significant improvement in manual dexterity and some large individual improvements in balance, sensory responsivity, DSM-5 criteria and cortisol levels with GABA tea. Improvements were also seen in the L-Theanine condition although they were more sporadic. CONCLUSIONS : These results suggest that sensorimotor abilities, anxiety levels and DSM-5 symptomology of children with ASC can benefit from the administration of GABA in the form of Oolong tea.

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7. Huberman Samuel M, Meiri G, Dinstein I, Flusser H, Michaelovski A, Bashiri A, Menashe I. Exposure to General Anesthesia May Contribute to the Association between Cesarean Delivery and Autism Spectrum Disorder. J Autism Dev Disord. 2019.

Cesarean section (CS) has been consistently associated with susceptibility to autism spectrum disorder (ASD), however, the underlying mechanism for this association remains vague. Here, we studied various pre-peri-and-neonatal factors among 347 children with ASD, 117 children with other developmental delays (DD), and 2226 age, sex and ethnicity matched controls. We found that CS is significantly associated with an increased risk of ASD but not DD (p = 0.019 and p = 0.540 respectively). Furthermore, we show that only CS performed with general anesthesia (GA) elevated the risk of ASD with no significant difference between indicated and non-indicated surgeries (aOR = 1.537 ; 95% CI 1.026-2.302, and aOR = 1.692 ; 95% CI 1.057-2.709, pdiff = 0.865). We therefore suggest that exposure to GA during CS may explain the association between CS and ASD.

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8. Kishida KT, De Asis-Cruz J, Treadwell-Deering D, Liebenow B, Beauchamp MS, Read Montague P. Diminished single-stimulus response in vmPFC to favorite people in children diagnosed with Autism Spectrum Disorder. Biological psychology. 2019.

From an early age, individuals with autism spectrum disorder (ASD) spend less time engaged in social interaction compared to typically developing peers (TD). One reason behind this behavior may be that the brains of children diagnosed with ASD do not attribute enough value to potential social exchanges as compared to the brains of typically developing children ; thus, potential social exchanges are avoided because other environmental stimuli are more highly valued by default. Neurobiological investigations into the mechanisms underlying value-based decision-making has shown that the ventral medial prefrontal cortex (vmPFC) is critical for encoding the expected outcome value of different actions corresponding to distinct environmental cues. Here, we tested the hypothesis that the responsiveness of the vmPFC in children diagnosed with ASD (compared to TD controls) is diminished for visual cues that represent highly valued social interaction. Using a passive picture viewing task and functional magnetic resonance imaging (fMRI) we measured the response of an a priori defined region of interest in the vmPFC in children diagnosed with ASD and an age-matched TD cohort. We show that the average response of the vmPFC is significantly diminished in the ASD group. Further, we demonstrate that a single-stimulus and less than 30 s of fMRI data are sufficient to differentiate the ASD and TD cohorts. These findings are consistent with the hypothesis that the brains of children with ASD do not encode the value of social exchange in the same manner as TD children. The latter finding suggests the possibility of utilizing single-stimulus fMRI as a potential biologically based diagnostic tool to augment traditional clinical approaches.

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9. Knight VF, Wright J, Wilson K, Hooper A. Teaching Digital, Block-Based Coding of Robots to High School Students with Autism Spectrum Disorder and Challenging Behavior. J Autism Dev Disord. 2019.

The use of robots to teach students with autism spectrum disorder communication skills has basis in the literature ; however, research investigating the effects of teaching coding or programming of robotics to promote learning in STEM to this population has not yet been conducted. The purpose of the current study was to evaluate the effects of teaching one code explicitly, using model-lead-test on the following dependent variables : (a) acquisition of the explicitly-taught code (i.e., robotic movement) ; (b) generalization of the explicitly-taught code to other novel codes (i.e., robotic sounds, light effects, complex movements), and (c) self-generated novel sets of codes. Results of the multiple probe across participants design demonstrate that all three students with ASD and challenging behaviors were able to acquire the initial code, generalize the initial code to novel codes, and self-generate (i.e., create, test, and evaluate) their own coding. Implications for practitioners, study limitations, and recommendations for future research are discussed.

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10. Manohar H, Kandasamy P, Chandrasekaran V, Rajkumar RP. Brief Parent-Mediated Intervention for Children with Autism Spectrum Disorder : A Feasibility Study from South India. J Autism Dev Disord. 2019.

The study assesses the acceptability and feasibility of a brief parent-mediated home-based intervention for children with autism spectrum disorder (ASD), deliverable in resource-limited settings, with an emphasis on addressing parental stress from a socio-cultural perspective. 50 children (2-6 years), with a DSM 5 diagnosis of ASD were randomized to intervention (n = 26) or active control group (n = 24). The intervention based on naturalistic developmental behavioral approach, focusing on joint attention, imitation, social and adaptive skills was structured to be delivered in five outpatient sessions over 12 weeks. All children were followed up at 4, 8 and 12 weeks. Parents of children randomized to the intervention group reported more improvements across parental stress and child outcome measures compared to those in the control group. The intervention was found to be acceptable and feasible, with high fidelity measures and retention rates.

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11. Missig G, McDougle CJ, Carlezon WA, Jr. Sleep as a translationally-relevant endpoint in studies of autism spectrum disorder (ASD). Neuropsychopharmacology. 2019.

Sleep has numerous advantages for aligning clinical and preclinical (basic neuroscience) studies of neuropsychiatric illness. Sleep has high translational relevance, because the same endpoints can be studied in humans and laboratory animals. In addition, sleep experiments are conducive to continuous data collection over long periods (hours/days/weeks) and can be based on highly objective neurophysiological measures. Here, we provide a translationally-oriented review on what is currently known about sleep in the context of autism spectrum disorder (ASD), including ASD-related conditions, thought to have genetic, environmental, or mixed etiologies. In humans, ASD is frequently associated with comorbid medical conditions including sleep disorders. Animal models used in the study of ASD frequently recapitulate dysregulation of sleep and biological (diurnal, circadian) rhythms, suggesting common pathophysiologies across species. As our understanding of the neurobiology of ASD and sleep each become more refined, it is conceivable that sleep-derived metrics may offer more powerful biomarkers of altered neurophysiology in ASD than the behavioral tests currently used in humans or lab animals. As such, the study of sleep in animal models for ASD may enable fundamentally new insights on the condition and represent a basis for strategies that enable the development of more effective therapeutics.

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12. Moran ML, Gomez LE, Alcedo MA, Pedrosa I. Gender Differences in Social Inclusion of Youth with Autism and Intellectual Disability. J Autism Dev Disord. 2019.

The aim of this study was to delve into the role of gender differences in social inclusion of children and youth with autism spectrum disorder (ASD) and intellectual disability (ID). A sample of 420 participants with ASD and ID aged between 4 and 21 years was evaluated using the ASD-KidsLife Scale. Females obtained lower scores in most of the items of social inclusion. These differences remained when the covariables of level of ID, support needs, and age were controlled. None of the items presented differential item functioning as a function of gender. Gender differences, as were found in social inclusion, are discussed and recommendations are given in order to provide equal opportunities to girls and boys with ASD.

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13. Naito N, Kikuchi M, Yoshimura Y, Kumazaki H, Kitagawa S, Ikeda T, Hasegawa C, Saito DN, Tomiyama S, Minabe Y. Atypical body movements during night in young children with autism spectrum disorder : a pilot study. Sci Rep. 2019 ; 9(1) : 6999.

Children with autism spectrum disorder (ASD) reportedly suffer from sleep problems at a higher rate than typically developing (TD) children. Several previous studies have reported differences in sleep indices (e.g., sleep latency) in children with ASD. However, no previous studies have focused specifically on the time course of body movements. In the present study, we investigated the time course of body movements in young TD children and young children with ASD as well as the relationship between body movements during night and social ability. Seventeen TD children and 17 children with ASD participated in this study (5 to 8 years old). We used an accelerometer attached to the waist to record movements during night and measured the average time course of body movements for 3 nights. Our results demonstrated that the rate of body movement 2 to 3 hours after the onset of body stillness was higher in children with ASD than in TD children. In addition, the higher rate of body movement at 0.5 to 1 hour after the onset of body stillness was associated with a lower social ability in the children with ASD. Our results suggested that the time course of body movements is an objective behavioural index for young children with ASD.

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14. Nilsson M, Arnfred S, Carlsson J, Nylander L, Pedersen L, Mortensen EL, Handest P. Self-Disorders in Asperger Syndrome Compared to Schizotypal Disorder : A Clinical Study. Schizophr Bull. 2019.

OBJECTIVE : There are historical and theoretical indications of a difference in subjective experience between autism spectrum disorder (ASD) and the schizophrenia spectrum. However, this difference has not been empirically explored. Therefore, to explore potential differences in subjective experience between the 2 spectra, we examined the presence/absence of self-disorders in Asperger syndrome/autism spectrum disorder (As/ASD) compared to schizotypal disorder (Sd). Self-disorders represent changes in basic self-awareness which have been found to accumulate within the schizophrenia spectrum. METHODS : All participants were recruited from clinical units and interviewed with a focus on the exploration of presence/absence of self-disorders, with the Examination of Anomalous Self-Experience (EASE) scale, and a general assessment of present psychopathology, with Schedules for Clinical Assessment in Neuropsychiatry (SCAN). RESULTS : A total of 51 participants (As/ASD, n = 22 ; Sd, n = 29) were included in the statistical analyses. When controlling for age, gender, years of education, mental problems before the age of 16, and special needs school attendance, there was a clear difference in presence/absence of self-disorders between the 2 groups, with significantly higher levels in the Sd group. Further, there was an overlap in SCAN-rated symptoms between the 2 groups. CONCLUSION : Our results indicate a significant difference between As/ASD and Sd at the level of the basic self, which, in turn, indicates that an exploration of anomalous self-experience is a valuable supplement in the clinical differentiation between As/ASD and Sd.

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15. Pagalan L, Brauer M, Lanphear B. Maternal Exposure to Air Pollution During Pregnancy and Autism Spectrum Disorder in Offspring-Reply. JAMA Pediatr. 2019.

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16. Pagani M, Bertero A, Liska A, Galbusera A, Sabbioni M, Barsotti N, Colenbier N, Marinazzo D, Scattoni ML, Pasqualetti M, Gozzi A. Deletion of autism risk gene Shank3 disrupts prefrontal connectivity. J Neurosci. 2019.

Mutations in the synaptic scaffolding protein Shank3 are a major cause of autism, and are associated with prominent intellectual and language deficits. However, the neural mechanisms whereby SHANK3 deficiency affects higher order socio-communicative functions remain unclear. Using high-resolution functional and structural MRI in adult male mice, here we show that loss of Shank3 (Shank3B (-/-)) results in disrupted local and long-range prefrontal and fronto-striatal functional connectivity. We document that prefrontal hypo-connectivity is associated with reduced short-range cortical projections density, and reduced gray matter volume. Finally, we show that prefrontal disconnectivity is predictive of social communication deficits, as assessed with ultrasound vocalization recordings. Collectively, our results reveal a critical role of SHANK3 in the development of prefrontal anatomy and function, and suggest that SHANK3 deficiency may predispose to intellectual disability and socio-communicative impairments via dysregulation of higher-order cortical connectivity.SignificanceMutations in the synaptic scaffolding protein SHANK3 are commonly associated with autism, intellectual and language deficits. Previous research has linked SHANK3 deficiency to basal ganglia dysfunction, motor stereotypies and social deficits. However, the neural mechanism whereby Shank3 gene mutations affects cortical functional connectivity and higher order socio-communicative functions remain unclear. Here we show that loss of SHANK3 in mice results in largely disrupted functional connectivity and abnormal gray matter anatomy in prefrontal areas. We also show that prefrontal connectivity disruption is tightly linked to socio-communicative deficits. Our findings suggest that SHANK3 is a critical orchestrator of fronto-cortical function, and that disrupted connectivity of prefrontal areas may underpin socio-communicative impairments observed in SHANK3 mutation carriers.

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17. Rodrigues JM, Mestre M, Fredes LI. Qigong in the treatment of children with autism spectrum disorder : A systematic review. Journal of integrative medicine. 2019.

BACKGROUND : Autism spectrum disorder is a condition that affects all races, ethnic and socioeconomic groups. With a high incidence ratio of one in every 68, it has become one of the most discussed psychiatric disorders. For this reason, the need for investigating novel treatments has been emerging. Qigong, a traditional Chinese mind-body technique, has already proven to be able to reduce symptoms of several physical and psychological illnesses. OBJECTIVE : The purpose of this systematic review is to examine and categorize the current scientific evidence regarding the efficacy of Qigong on children suffering from autism spectrum disorders. SEARCH STRATEGY : A systematic literature search of the electronic scientific databases PubMed, Clinical, BioMed Central, PubMed Central and Google Scholar, was performed to identify studies of Qigong in the treatment of children with autism spectrum disorder. INCLUSION CRITERIA : This review included randomized controlled trials, replication studies, retrospective studies and observational follow-up studies of Qigong on children with autism spectrum disorder. Case reports and case series were excluded. DATA EXTRACTION AND ANALYSIS : Two researchers independently evaluated the methodological quality of all included studies. Any discrepancies were solved by discussion until consensus was achieved. RESULTS : Our literature search identified 157 publications, and 10 additional publications from hand search of references. After duplicate removal, 103 records remained. After the title/abstract screening, 19 publications were obtained for detailed evaluation. After detailed evaluation, 10 studies were included. Seven studies were conducted with small children with 2-6years old employing Qigong massage, and three studies were conducted with older children aged 7-17years old applying both Qigong massage (one study) and Neigong (two studies). CONCLUSION : Studies demonstrated that Qigong has interesting and promising applicability and effect on children with autism spectrum disorder and should be tested further. Despite the need for more rigorous controlled studies, Qigong seems to be able to decrease severity of individual sensory, behavioural, and language components of autism, and improve self-control, sociability, sensory and cognitive awareness as well as healthy-physical behaviour. Besides positive effect on children and adolescents, benefits seem to extend to parents and caregivers as well. However, quality of methodology seems to be insufficient to state that Qigong is an alternative to common behavioural therapies. We suggest that, until more investigation is performed, Qigong may only be used as a complement, or when behavioural therapies are not accessible.

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18. Sauer AK, Bockmann J, Steinestel K, Boeckers TM, Grabrucker AM. Altered Intestinal Morphology and Microbiota Composition in the Autism Spectrum Disorders Associated SHANK3 Mouse Model. International journal of molecular sciences. 2019 ; 20(9).

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterized by deficits in social interaction and communication, and repetitive behaviors. In addition, co-morbidities such as gastro-intestinal problems have frequently been reported. Mutations and deletion of proteins of the SH3 and multiple ankyrin repeat domains (SHANK) gene-family were identified in patients with ASD, and Shank knock-out mouse models display autism-like phenotypes. SHANK3 proteins are not only expressed in the central nervous system (CNS). Here, we show expression in gastrointestinal (GI) epithelium and report a significantly different GI morphology in Shank3 knock-out (KO) mice. Further, we detected a significantly altered microbiota composition measured in feces of Shank3 KO mice that may contribute to inflammatory responses affecting brain development. In line with this, we found higher E. coli lipopolysaccharide levels in liver samples of Shank3 KO mice, and detected an increase in Interleukin-6 and activated astrocytes in Shank3 KO mice. We conclude that apart from its well-known role in the CNS, SHANK3 plays a specific role in the GI tract that may contribute to the ASD phenotype by extracerebral mechanisms.

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19. Sharp WG, Burrell TL, Berry RC, Stubbs KH, McCracken CE, Gillespie SE, Scahill L. The Autism Managing Eating Aversions and Limited Variety Plan vs Parent Education : A Randomized Clinical Trial. The Journal of pediatrics. 2019.

OBJECTIVE : To assess the feasibility and initial efficacy of a structured parent training program for children with autism spectrum disorder and moderate food selectivity. STUDY DESIGN : This 16-week randomized trial compared the Managing Eating Aversions and Limited variety (MEAL) Plan with parent education. MEAL Plan (10 core and 3 booster sessions) provided parents with nutrition education and strategies to structure meals and expand the child’s diet. Parent education (10 sessions) provided information about autism without guidance on nutrition, meal structure, or diet. In addition to feasibility outcomes, primary efficacy outcomes included the Clinical Global Impression - Improvement scale and the Brief Autism Mealtime Behaviors Inventory. Grams consumed during a meal observation served as a secondary outcome. RESULTS : There were 38 eligible children (19 per group, 32 males). For MEAL Plan, attrition was <10% and attendance >80%. Therapists achieved >90% fidelity. At week 16, positive response rates on the Clinical Global Impression - Improvement scale were 47.4% for the MEAL Plan and 5.3% for parent education (P < .05). The adjusted mean difference (SE) on Brief Autism Mealtime Behaviors Inventory at week 16 was 7.04 (2.71) points (P = .01) in favor of MEAL Plan. For grams consumed, the adjusted standard mean difference (SE) was 30.76 (6.75), also in favor of MEAL Plan (P = .001). CONCLUSIONS : The MEAL Plan seems to be feasible, and preliminary efficacy results are encouraging. If further study replicates these results, the MEAL Plan could expand treatment options for children with autism spectrum disorder and moderate food selectivity. TRIAL REGISTRATION : : NCT02712281.

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20. Stallworth JL, Dy ME, Buchanan CB, Chen CF, Scott AE, Glaze DG, Lane JB, Lieberman DN, Oberman LM, Skinner SA, Tierney AE, Cutter GR, Percy AK, Neul JL, Kaufmann WE. Hand stereotypies : Lessons from the Rett Syndrome Natural History Study. Neurology. 2019.

OBJECTIVE : To characterize hand stereotypies (HS) in a large cohort of participants with Rett syndrome (RTT). METHODS : Data from 1,123 girls and women enrolled in the RTT Natural History Study were gathered. Standard tests for continuous and categorical variables were used at baseline. For longitudinal data, we used repeated-measures linear and logistic regression models and nonparametric tests. RESULTS : HS were reported in 922 participants with classic RTT (100%), 73 with atypical severe RTT (97.3%), 74 with atypical mild RTT (96.1%), and 17 females with MECP2 mutations without RTT (34.7%). Individuals with RTT who had classic presentation or severe MECP2 mutations had higher frequency and earlier onset of HS. Heterogeneity of HS types was confirmed, but variety decreased over time. At baseline, almost half of the participants with RTT had hand mouthing, which like clapping/tapping, decreased over time. These 2 HS types were more frequently reported than wringing/washing. Increased HS severity (prevalence and frequency) was associated with worsened measures of hand function. Number and type of HS were not related to hand function. Overall clinical severity was worse with decreased hand function but only weakly related to any HS characteristic. While hand function decreased over time, prevalence and frequency of HS remained relatively unchanged and high. CONCLUSIONS : Nearly all individuals with RTT have severe and multiple types of HS, with mouthing and clapping/tapping decreasing over time. Interaction between HS frequency and hand function is complex. Understanding the natural history of HS in RTT could assist in clinical care and evaluation of new interventions.

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21. Strobl MAR, Lipsmeier F, Demenescu LR, Gossens C, Lindemann M, De Vos M. Look me in the eye : evaluating the accuracy of smartphone-based eye tracking for potential application in autism spectrum disorder research. Biomedical engineering online. 2019 ; 18(1) : 51.

BACKGROUND : Avoidance to look others in the eye is a characteristic symptom of Autism Spectrum Disorders (ASD), and it has been hypothesised that quantitative monitoring of gaze patterns could be useful to objectively evaluate treatments. However, tools to measure gaze behaviour on a regular basis at a manageable cost are missing. In this paper, we investigated whether a smartphone-based tool could address this problem. Specifically, we assessed the accuracy with which the phone-based, state-of-the-art eye-tracking algorithm iTracker can distinguish between gaze towards the eyes and the mouth of a face displayed on the smartphone screen. This might allow mobile, longitudinal monitoring of gaze aversion behaviour in ASD patients in the future. RESULTS : We simulated a smartphone application in which subjects were shown an image on the screen and their gaze was analysed using iTracker. We evaluated the accuracy of our set-up across three tasks in a cohort of 17 healthy volunteers. In the first two tasks, subjects were shown different-sized images of a face and asked to alternate their gaze focus between the eyes and the mouth. In the last task, participants were asked to trace out a circle on the screen with their eyes. We confirm that iTracker can recapitulate the true gaze patterns, and capture relative position of gaze correctly, even on a different phone system to what it was trained on. Subject-specific bias can be corrected using an error model informed from the calibration data. We compare two calibration methods and observe that a linear model performs better than a previously proposed support vector regression-based method. CONCLUSIONS : Under controlled conditions it is possible to reliably distinguish between gaze towards the eyes and the mouth with a smartphone-based set-up. However, future research will be required to improve the robustness of the system to roll angle of the phone and distance between the user and the screen to allow deployment in a home setting. We conclude that a smartphone-based gaze-monitoring tool provides promising opportunities for more quantitative monitoring of ASD.

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