Behavioral training and mirroring techniques to prepare elective anesthesia in severe autistic spectrum disorder patients: An illustrative case and review.

Children with autistic spectrum disorder are more likely to become distressed during induction of anesthesia. Inhalational induction is almost always the preferred route with acceptance of the face mask often presenting a considerable challenge. Tempering measures to facilitate gas induction such as forced premedication and physical restraint are no longer viable options except in extenuating circumstances. Recent research interest has focused on the need for advanced planning in collaboration with the caregiver to tailor an individualized perioperative plan. This plan may include both pharmacological and non-pharmacological interventions. Applied behavior analysis strategies have a well-documented efficacy in this unique population to systematically change an individual's usual behavior. These can be used, as a non-pharmacological strategy, to ensure a smooth perioperative course. We present a successful case of preoperative desensitization of a child with severe autistic spectrum disorder using a mirror demonstration technique associated with positive reinforcement to prepare him for general anesthesia. We discuss the potential application of applied behavior analysis strategies for anesthesia in this unique population. From a practical point of view, early communication with carers is required to establish who may benefit from this behavioral training. Planned individual preparation for general anesthesia must be provided by trained multidisciplinary staff.

Case report: an unexpected link between partial deletion of the SHANK3 gene and Heller's dementia infantilis, a rare subtype of autism spectrum disorder.

BACKGROUND: Deletions and mutations involving the SHANK3 gene lead to a nonspecific clinical presentation with moderate to profound intellectual disability, severely delayed or absent speech, and autism spectrum disorders (ASD). Better knowledge of the clinical spectrum of SHANK3 haploinsufficiency is useful to facilitate clinical care monitoring and to guide molecular diagnosis, essential for genetic counselling. CASE PRESENTATION: Here, we report a detailed clinical description of a 10-year-old girl carrying a pathogenic interstitial 22q13.3 deletion encompassing only the first 17 exons of SHANK3. The clinical features displayed by the girl strongly suggested the diagnosis of dementia infantilis, described by Heller in 1908, also known as childhood disintegrative disorder. CONCLUSION: Our present case confirms several observations according to which regression may be part of the clinical phenotype of SHANK3 haploinsufficiency. Therefore, we think it is crucial to look for mutations in the gene SHANK3 in patients diagnosed for childhood disintegrative disorder or any developmental disorder with a regressive pattern involving social and communicative skills as well as cognitive and instinctual functions, with onset around 3 years.

Subthreshold traits of the broad autistic spectrum are distributed across different subgroups in parents, but not siblings, of probands with autism.

Autism is a categorical developmental disorder characterized by impairment in socialization, communication, and by restricted and circumscribed interests. Several authors have described the presence of subthreshold autistic traits in the general population, pervasive developmental disorders representing the extreme end of their distribution. In this study, we explored the presence of autistic traits in siblings and parents of a proband with autism, and in siblings and parents of a normally developing child, using the previously validated self-report French Autism Quotient, an adaptation of the AQ developed by S. Baron-Cohen. Scores were distributed between two main factors, F1 corresponding to socialization and communication, F2 to imagination and rigidity. Here, we show that both parents and siblings of a child with autism have more symptomatic scores in the domains of communication and socialization. In addition, we show that in these families the parents, but not the siblings, are distributed across different subcategories, according to their scores for the F1 and F2 domains. We hypothesize that these different subgroups may correspond to different underlying genetic mechanisms.

Infant's engagement and emotion as predictors of autism or intellectual disability in West syndrome.

West syndrome (WS) is a rare epileptic encephalopathy with early onset and a high risk of autistic outcome. The PréAut grid assesses this risk following WS onset by taking into account synchrony and emotion in interactions and by evaluating the baby's active desire to engage in pleasant interactions (especially the infant's early active behaviors that encourage being gazed at or kissed by the mother or to share joy with her). We followed a sample of 25 WS patients prospectively from disease onset and assessed whether the PréAut grid before 9 months, and the checklist for autism in toddlers (CHAT) at 18 and 24 months predicted autism or intellectual disability (ID) outcomes at 4 years. We found that the PréAut grid at 9 months (sensitivity = 0.83; specificity = 1) had similar prediction parameters as the CHAT at 18 months (sensitivity = 0.90; specificity = 0.83) and 24 months (sensitivity = 0.92; specificity = 1). WS patients with a positive PréAut screening at 9 months had a risk of having autism or ID at 4 years, which is 38 times that of children with a negative PréAut grid [OR = 38.6 (95 % CI 2.2-2961); p = 0.006]. We conclude that the PréAut grid could be a useful tool for the early detection of autism or ID risk in the context of WS. Further research is needed to assess the PréAut grid in other contexts (e.g. infants at high-risk for non-syndromic autism).

Observational Cohort Study Dedicated to Autism Spectrum Disorder: Milestone Steps, Results Updates, Perspectives.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by persistent difficulties in two domains: social communication and interaction, alongside with restricted, repetitive pattern of behaviors. It affects children and persists into adolescence and adulthood. Its causes and underlying psychopathological mechanisms are unknown and remain to be discovered. TEDIS cohort study developed over the decade 2010-2022, in Ile-de-France region, includes 1300 patients' files up to date, with valuable health information drawn from ASD evaluation. It provides researchers and decision makers with reliable data source to improve knowledge and practice in the context of ASD patients.

Early-onset catatonia associated with SHANK3 mutations: looking at the autism spectrum through the prism of psychomotor phenomena.

Background: Individuals with Phelan-McDermid syndrome (PMS) present with a wide range of diagnoses: autism spectrum disorder, intellectual disability, or schizophrenia. Differences in the genetic background could explain these different neurodevelopmental trajectories. However, a more parsimonious hypothesis is to consider that they may be the same phenotypic entity. Catatonic disturbances occasionally reported from adolescence onwards in PMS prompts exploration of the hypothesis that this clinical entity may be an early-onset form of catatonia. The largest cohort of children with childhood catatonia was studied by the Wernicke-Kleist-Leonhard school (WKL school), which regards catatonia as a collection of qualitative abnormalities of psychomotricity that predominantly affecting involuntary motricity (reactive and expressive). The aim of this study was to investigate the presence of psychomotor signs in three young adults carrying a mutation or intragenic deletion of the SHANK3 gene through the prism of the WKL school conception of catatonia. Methods: This study was designed as an exploratory case study. Current and childhood psychomotor phenomena were investigated through semi-structured interviews with the parents, direct interaction with the participants, and the study of documents reporting observations of the participants at school or by other healthcare professionals. Results: The findings show catatonic manifestations from childhood that evolved into a chronic form, with possible phases of sub-acute exacerbations starting from adolescence. Conclusion: The presence of catatonic symptoms from childhood associated with autistic traits leads us to consider that this singular entity fundamentally related to SHANK3 mutations could be a form of early-onset catatonia. Further case studies are needed to confirm our observations.

TEDIS, Pervasive Developmental Disorder' patients information system, preliminary results.

TEDIS, an information system dedicated to patients with Pervasive Developmental Disorder (PDD) was tested. Results focused on the process of behavioural changes among physicians and health professionals with regard to structured organized patient information.The experiment encouraged changes in professionals' habits for further documenting and systematizing patient information collection. TEDIS' project federated professionals for developing methods for a systematic and exhaustive patient data management, in a longitudinal and cross-domain perspective, for improving knowledge and health care management.

Implementation and experimentation of TEDIS: an information system dedicated to patients with pervasive developmental disorders.

This article aims at describing the implementation and experimentation of TEDIS, an information system dedicated to patients with Pervasive Developmental Disorder. The experiment included 30 prospective patient records aged from 3.2 to 7.5 with an average of 6.3. Preliminary patient data analysis highlighted the need of improving the data collection process, by making relevant data systematically and accurately documented. Despite a small study ample size, data analysis also showed the interest of such information system in making evident improvements in patient care and resources allocation after medical and clinical expert assessment.

TEDIS: an information system dedicated to patients with pervasive developmental disorders.

Pervasive Development Disorders (PDD) represent a life disorder which significantly affects individuals and families. It requires long term specialized institutions health care, education and social accompaniment. In France, 350,000 to 600,000 patients are estimated to be affected and 5,000 to 8,000 newborns will develop the disorder every year. In 2005, Autism Resource Centres were created in each of the 23 regions in France, to support the PDD hospital reference centres in providing formal clinical assessment for each patient. Such assessments will support the prescription of health care measures, educative and intuitional orientation and accompaniment. An information system called TEDIS was designed to assist the psychiatrists and multidisciplinary medical experts at Necker child-psychiatry hospital, in organizing PDD patient's information and providing ground for improving knowledge about the disorder, its epidemiology and underlying biological mechanisms. The professionals' involvement from the beginning in the development process facilitated TEDIS design and implementation. The results of first experimentations are encouraging. They are described as well as the short term and mid-term deployment planning.

[Evolution of the concept of autism]. / Evolutions du concept d'autisme.

Since it was originally described in 1943 by L. Kanner, the concept of autism has changed. Autistic disorder is now recognized as a pervasive developmental disorder diagnosed on the basis of three behaviorally altered domains: social deficits, impaired language and communication, and stereotyped and repetitive behaviors. The prevalence of the autistic disorder according to these criteria has raised to about 0.3%, and the prevalence of the pervasive developmental disorders is estimated between 0.3 and 0.6%. Autism is now considered as an heterogeneous neurodevelopmental syndrome, with genetic and environmental factors contribution.

[Early recognition of autistic features]. / Comment reconnaître l'autisme?

Autism is a neurodevelopmental disorder diagnosed on the basis of three behaviorally altered domains: social deficits, impaired language and communication, and stereotyped and repetitive behaviors. The early recognition of the disorder, as early as two years, is an important challenge, because early treatments are more efficient in helping children to develop their adaptation skills, allowing their better integration in the society, with less suffering and a lower level of handicap. Therefore are described the symptoms that may lead first degree practioners to suspect autistic disorders as early as possible, and how they can help the children and their parents to be directed to the appropriate services for diagnostic and treatment.

Behavior and interaction imaging at 9 months of age predict autism/intellectual disability in high-risk infants with West syndrome.

Automated behavior analysis are promising tools to overcome current assessment limitations in psychiatry. At 9 months of age, we recorded 32 infants with West syndrome (WS) and 19 typically developing (TD) controls during a standardized mother-infant interaction. We computed infant hand movements (HM), speech turn taking of both partners (vocalization, pause, silences, overlap) and motherese. Then, we assessed whether multimodal social signals and interactional synchrony at 9 months could predict outcomes (autism spectrum disorder (ASD) and intellectual disability (ID)) of infants with WS at 4 years. At follow-up, 10 infants developed ASD/ID (WS+). The best machine learning reached 76.47% accuracy classifying WS vs. TD and 81.25% accuracy classifying WS+ vs. WS-. The 10 best features to distinguish WS+ and WS- included a combination of infant vocalizations and HM features combined with synchrony vocalization features. These data indicate that behavioral and interaction imaging was able to predict ASD/ID in high-risk children with WS.

TEDIS, a Comprehensive Data Model for In-Depth Clinical Assessment of Patients Affected with Neuro-Developmental Disorders Including Autism.

TEDIS, an information system dedicated to patients affected with neuro-developmental disorders including autism, focuses on patient data generated during in-depth clinical assessment in nine expert centers in Ile-de-France region. Long term partnership involving methodologists and domain experts is necessary to support quality data production and analyses and to guarantee quality data and information governance in a domain characterized by frequent evolutions in clinical assessment instruments and in diagnostic criteria and classification.

The Impact of Atypical Sensory Processing on Adaptive Functioning and Maladaptive Behaviors in Autism Spectrum Disorder During Childhood: Results From the ELENA Cohort.

Atypical sensory processing is common in autism spectrum disorders (ASD), but their role in adaptive difficulties and problem behaviors is poorly understood. Our aim was to determine the prevalence and type of atypical sensory processing in children with ASD and investigate its impact on their adaptive functioning and maladaptive behaviors. We studied a subsample of 197 children rigorously diagnosed with ASD from the ELENA cohort. Children were divided into atypical and typical sensory processing groups and several independent variables were compared, including adaptive functioning and maladaptive behaviors. Overall, 86.8% of the children had at least one atypical sensory pattern and all sensory modalities were disturbed. Atypical sensory processing explained a significant part of the variance of behavioral problems.

[Towards an integrated approach to infantile autism: the superior temporal lobe between neurosciences and psychoanalysis]. / Pour une approche intégrative de i'autisme infantile: le lobe temporal supérieur entre neurosciences et psychanalyse.

The superior temporal lobe is currently at the focus of intensive research in infantile autism, a psychopathologic disorder apparently representing the severest failure of access to intersubjectivity, i.e. the ability to accept that others exist independently of oneself. Access to intersubjectivity seems to involve the superior temporal lobe, which is the seat of several relevant functions such as face and voice recognition and perception of others' movements, and coordinates the different sensory inputs that identify an object as being "external". The psychoanalytic approach to infantile autism and recent cognitive data are now converging, and intersubjectivity is considered to result from "mantling" or comodalization of sensory inputs from external objects. Recent brain neuroimaging studies point to anatomic and functional abnormalities of the superior temporal lobe in autistic children. Dialogue is therefore possible between these different disciplines, opening the way to an integrated view of infantile autism in which the superior temporal lobe holds a central place--not necessarily as a primary cause of autism but rather as an intermediary or a reflection of autistic functioning

Investigating the natural history and prognostic factors of ASD in children: the multicEntric Longitudinal study of childrEN with ASD - the ELENA study protocol.

INTRODUCTION: There is global concern about the increasing prevalence of autism spectrum disorders (ASDs), which are early-onset and long-lasting disorders. Although ASDs are considered to comprise a unique syndrome, their clinical presentation and outcome vary widely. Large-scale and long-term cohort studies of well-phenotyped samples are needed to better understand the course of ASDs and their determinants. The primary objective of the multicEntric Longitudinal study of childrEN with ASD (ELENA) study is to understand the natural history of ASD in children and identify the risk and prognostic factors that affect their health and development. METHODS AND ANALYSIS: This is a multicentric, longitudinal, prospective, observational cohort in which 1000 children with ASD diagnosed between 2 and 16 years of age will be recruited by 2020 and followed over 6 years. The baseline follow-up starts with the clinical examination to establish the ASD diagnosis. A battery of clinical tools consisting of the Autism Diagnostic Observation Schedule, the revised version of the Autism Diagnostic Interview, measures of intellectual functioning, as well as large-scale behavioural and developmental measurements will allow us to study the heterogeneity of the clinical presentation of ASD subtypes. Subsequent follow-up at 18 months and at 3, 4.5 and 6 years after the baseline examination will allow us to explore the developmental trajectories and variables associated with the severity of ASD. In addition to the children's clinical and developmental examinations, parents are invited to complete self-reported questionnaires concerning perinatal and early postnatal history, congenital anomalies, genetic factors, lifestyle factors, medical and psychiatric comorbidities, and the socioeconomic environment. As of 1 November 2018, a total of 766 participants have been included. ETHICS AND DISSEMINATION: Ethical approval was obtained through the Marseille Mediterranean Ethics Committee (ID RCB: 2014-A01423-44), France. We aim to disseminate the findings through national and international conferences, international peer-reviewed journals, and social media. TRIAL REGISTRATION NUMBER: NCT02625116; Pre-results.

Clinical, cellular, and neuropathological consequences of AP1S2 mutations: further delineation of a recognizable X-linked mental retardation syndrome.

Mutations in the AP1S2 gene, encoding the sigma1B subunit of the clathrin-associated adaptor protein complex (AP)-1, have been recently identified in five X-linked mental retardation (XLMR) families, including the original family with Fried syndrome. Studying four patients in two unrelated families in which AP1S2 nonsense and splice-site mutations segregated, we found that affected individuals presented, in addition to previously described features, with elevated protein levels in cerebrospinal fluid (CSF). Moreover, computed tomography scans demonstrated that the basal ganglia calcifications associated with AP1S2 mutations appeared during childhood and might be progressive. Based on these observations, we propose that AP1S2 mutations are responsible for a clinically recognizable XLMR and autism syndrome associating hypotonia, delayed walking, speech delay, aggressive behavior, brain calcifications, and elevated CSF protein levels. Using the AP-2 complex, in which the sigma subunit is encoded by one single gene, as a model system, we demonstrated that sigma subunits are essential for the stability of human AP complexes. By contrast, no major alteration of the stability, subcellular localization, and function of the AP-1 complex was observed in fibroblasts derived from a patient carrying an AP1S2 mutation. Similarly, neither macro- nor microscopic defects were observed in the brain of an affected fetus. Altogether, these data suggest that the absence of an AP-1 defect in peripheral tissues is due to functional redundancy among AP-1 sigma subunits (sigma1A, sigma1B, and sigma1C) and that the phenotype observed in our patients results from a subtle and brain-specific defect of the AP-1-dependent intracellular protein traffic.

Children with mixed language disorder do not discriminate accurately facial identity when expressions change.

We investigated the recognition of pairs of faces (same or different facial identities and expressions) in two groups of 14 children aged 6-10 years, with either an expressive language disorder (ELD), or a mixed language disorder (MLD), and two groups of 14 matched healthy controls. When looking at their global performances, children with either expressive (ELD) or MLD have few differences from controls in either face or emotional recognition. At contrary, we found that children with MLD, but not those with ELD, take identical faces to be different if their expressions change. Since children with mixed language disorders are socially more impaired than children with ELD, we think that these features may partly underpin the social difficulties of these children.

Children with mixed developmental language disorder have more insecure patterns of attachment.

BACKGROUND: Developmental Language disorders (DLD) are developmental disorders that can affect both expressive and receptive language. When severe and persistent, they are often associated with psychiatric comorbidities and poor social outcome. The development of language involves early parent-infant interactions. The quality of these interactions is reflected in the quality of the child's attachment patterns. We hypothesized that children with DLD are at greater risk of insecure attachment, making them more vulnerable to psychiatric comorbidities. Therefore, we investigated the patterns of attachment of children with expressive and mixed expressive- receptive DLD. METHODS: Forty-six participants, from 4 years 6 months to 7 years 5 months old, 12 with expressive Specific Language Impairment (DLD), and 35 with mixed DLD, were recruited through our learning disorder clinic, and compared to 23 normally developing children aged 3 years and a half. The quality of attachment was measured using the Attachment Stories Completion Task (ASCT) developed by Bretherton. RESULTS: Children with developmental mixed language disorders were significantly less secure and more disorganized than normally developing children. CONCLUSIONS: Investigating the quality of attachment in children with DLD in the early stages could be important to adapt therapeutic strategies and to improve their social and psychiatric outcomes later in life.

Strengthening Data Confidentiality and Integrity Protection in the Context of a Multi-Centric Information System Dedicated to Autism Spectrum Disorder.

Autism spectrum disorders (ASD) are complex neuro-developmental disorders affecting children in early age. Diagnosis relies on multidisciplinary investigations, in psychiatry, neurology, genetics, electrophysiology, neuro-imagery, audiology, and ophthalmology. To support clinicians, researchers, and public health decision makers, we developed an information system dedicated to ASD, called TEDIS. It was designed to manage systematic, exhaustive and continuous multi-centric patient data collection via secured internet connections. TEDIS will be deployed in nine ASD expert assessment centers in Ile-DeFrance district. We present security policy and infrastructure developed in context of TEDIS to protect patient privacy and clinical information. TEDIS security policy was organized around governance, ethical and organisational chart-agreement, patients consents, controlled user access, patients' privacy protection, constrained patients' data access. Security infrastructure was enriched by further technical solutions to reinforce ASD patients' privacy protection. Solutions were tested on local secured intranet environment and showed fluid functionality with consistent, transparent and safe encrypting-decrypting results.