Pubmed du 11/04/18

mercredi 11 avril 2018

1. Ahmad SF, Ansari MA, Nadeem A, Bakheet SA, Alzahrani MZ, Alshammari MA, Alanazi WA, Alasmari AF, Attia SM. Resveratrol attenuates pro-inflammatory cytokines and activation of JAK1-STAT3 in BTBR T(+) Itpr3(tf)/J autistic mice. European journal of pharmacology. 2018.

Autism is a neurodevelopmental disorder characterized by qualitative impairment in communication, social interaction, and repetitive stereotypic behavior. Resveratrol plays a role in several disorders such as neuroimmune, autoimmune, and allergic disorders. BTBR T(+) Itpr3(tf)/J (BTBR) mice, a model for autism, show several behavioral deficits that are physiological characteristics similar to those observed in patients with autism. Previous studies have shown that JAK-STAT signaling pathway is associated with many neurodevelopmental disorders. We investigated the possible role of resveratrol on IL-6(+), TNF-alpha(+), IFN-gamma(+), and STAT3(+) in CD4(+) T spleen cells in BTBR mice as compared to C57BL/6J mice. We also assessed the effect of resveratrol treatment on IL-6, TNF-alpha, IFN-gamma, JAK1, and STAT3 mRNA expression levels in the brain tissue. We further assessed IL-6, IFN-gamma, TNF-alpha, phosphorylated (p) JAK1, and pSTAT3 (Tyr705) protein expression levels in the brain tissue. Resveratrol (20 and 40mg/kg)-treated mice had significantly decreased in IL-6(+), TNF-alpha(+), IFN-gamma(+), and STAT3(+) in CD4(+) spleen cells as compared with BTBR control mice. Resveratrol treatment also decreased IL-6, TNF-alpha, IFN-gamma, JAK1, and STAT3 mRNA expression levels as compared with BTBR control mice in the brain tissue. Moreover, resveratrol treatment resulted in decreased protein expression levels of IL-6, IFN-gamma, TNF-alpha, pJAK1, and pSTAT3 (Tyr705) as compared with BTBR control mice in the brain tissues. Taken together, these results indicate the efficacy of resveratrol in reducing cytokines and JAK-1/STAT3 signaling in BTBR mice, which is a novel and important finding and might be important for future therapies in neuroimmune dysfunction.

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2. Aspiranti KB, Larwin KH, Schade BP. iPads/tablets and students with autism : a meta-analysis of academic effects. Assistive technology : the official journal of RESNA. 2018.

Since the introduction of iPads in 2010, educators have been working to effectively incorporate this technology as a supplement to curriculum and a tool to increase student engagement and student achievement. The current investigation examines the effectiveness of iPad applications in supporting the instruction of students identified on the autism spectrum. Specifically, this investigation provides a meta-analysis of available research that examines the use of iPad technology and its impact on learning outcomes for students with autism. Four studies were found that provided results for groups of students. The findings of this research are based on 12 effect-size measures, representing a synthesized sample size of 99 participants. The results suggest that the use of iPad technology can have a positive, significant effect on student learning outcomes. The moderators of these positive outcomes are presented and discussed.

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3. Broder Fingert S, Carter A, Pierce K, Stone WL, Wetherby A, Scheldrick C, Smith C, Bacon E, James SN, Ibanez L, Feinberg E. Implementing systems-based innovations to improve access to early screening, diagnosis, and treatment services for children with autism spectrum disorder : An Autism Spectrum Disorder Pediatric, Early Detection, Engagement, and Services network study. Autism. 2018 : 1362361318766238.

In 2013, the National Institute of Mental Health funded five trials of unique, multicomponent, systems-based innovations designed to improve access to early screening, diagnosis, and treatment of autism spectrum disorder-collectively known as the Autism Spectrum Disorder Pediatric, Early Detection, Engagement, and Services Network. As part of an ongoing effort to pool data and learn from shared experience, we collected information across all studies about innovation components and implementation strategies. First, each study group completed standardized checklists based on the Template for Intervention Description and Replication and the Expert Recommendation for Implementing Change. Then, we interviewed principal and co-investigators of each study (n = 9) to further explore innovation components and assess barriers and facilitators to implementation. Innovation strategies were diverse (five different autism spectrum disorder screeners were used, 40% included early intervention trainings, 60% involved new technology). Common implementation strategies included developing stakeholder relationships and provider trainings. Barriers included inefficient systems of care, difficulty engaging families in the innovations, provider attitudes, and organizational culture (e.g. difficulty changing clinic processes). These findings suggest that-despite diverse settings and a variety of innovation content-common facilitators and challenges exist in implementing innovations to enhance access to early autism spectrum disorder screening, diagnosis, and treatment.

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4. Churchard A, Ryder M, Greenhill A, Mandy W. The prevalence of autistic traits in a homeless population. Autism. 2018 : 1362361318768484.

Anecdotal evidence suggests that autistic people experience an elevated risk of homelessness, but systematic empirical research on this topic is lacking. As a step towards filling this gap in knowledge, we conducted a preliminary investigation of the prevalence of Diagnostic and Statistical Manual of Mental Disorders (5th ed.) autism symptoms in a group of long-term homeless people. The entire caseload ( N = 106) of a UK homeless outreach team was screened (excluding individuals born outside of the United Kingdom or Republic of Ireland) using an in-depth, semi-structured interview with keyworkers, based on Diagnostic and Statistical Manual of Mental Disorders (5th ed.) diagnostic criteria. This showed adequate inter-rater reliability, as well as evidence of criterion and construct validity. Of the sample, 13 people (12.3%, 95% confidence interval (7.0, 20.4)) screened positive, meeting Diagnostic and Statistical Manual of Mental Disorders (5th ed.) autism criteria by keyworker report. A further nine people (8.5%, 95% confidence interval (4.5, 15.3)) were ’marginal’, having autistic traits that were not quite sufficient to meet Diagnostic and Statistical Manual of Mental Disorders (5th ed.) criteria. Those with elevated autistic traits, compared to those without, tended to be more socially isolated and less likely to use substances. This study has provided initial evidence that autistic traits are over-represented among homeless people and that autistic homeless people may show a distinct pattern of characteristics and needs. Further investigation is required to build upon these provisional findings.

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5. Ciaramelli E, Spoglianti S, Bertossi E, Generali N, Telarucci F, Tancredi R, Muratori F, Igliozzi R. Construction of Past and Future Events in Children and Adolescents with ASD : Role of Self-relatedness and Relevance to Decision-Making. J Autism Dev Disord. 2018.

We studied episodic memory and future thinking for self-relevant and other-relevant events at different levels of retrieval support, theory of mind, and delay discounting in ASD children and adolescents (ASDs). Compared to typically developing controls, ASDs produced fewer internal (episodic) but a similar number of external (semantic) details while remembering past events, imagining future events, and imagining future events happening to others, indicating a general impairment of event construction. This deficit was driven by group differences under high retrieval support, and therefore unlikely to depend on self-initiated retrieval/construction deficits. ASDs’ event construction impairment related to the severity of ASD symptoms, and to theory of mind deficits. ASDs, however, showed normal delay discounting, highlighting preserved forms of future-based decision-making in ASD.

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6. Deliens G, Papastamou F, Ruytenbeek N, Geelhand P, Kissine M. Selective Pragmatic Impairment in Autism Spectrum Disorder : Indirect Requests Versus Irony. J Autism Dev Disord. 2018.

Autism Spectrum Disorder (ASD) is often described as being characterised by a uniform pragmatic impairment. However, recent evidence suggests that some areas of pragmatic functioning are preserved. This study seeks to determine to which extent context-based derivation of non-linguistically encoded meaning is functional in ASD. We compare the performance of 24 adults with ASD, and matched neuro-typical adults in two act-out pragmatic tasks. The first task examines generation of indirect request interpretations, and the second the comprehension of irony. Intact contextual comprehension of indirect requests contrasts with marked difficulties in understanding irony. These results suggest that preserved pragmatics in ASD is limited to egocentric processing of context, which does not rely on assumptions about the speaker’s mental states.

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7. Ehinger Y, Matagne V, Villard L, Roux JC. Rett syndrome from bench to bedside : recent advances. F1000Research. 2018 ; 7 : 398.

Rett Syndrome is a severe neurological disorder mainly due to de novo mutations in the methyl-CpG-binding protein 2 gene ( MECP2). Mecp2 is known to play a role in chromatin organization and transcriptional regulation. In this review, we report the latest advances on the molecular function of Mecp2 and the new animal and cellular models developed to better study Rett syndrome. Finally, we present the latest innovative therapeutic approaches, ranging from classical pharmacology to correct symptoms to more innovative approaches intended to cure the pathology.

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8. Eshraghi AA, Liu G, Kay SS, Eshraghi RS, Mittal J, Moshiree B, Mittal R. Epigenetics and Autism Spectrum Disorder : Is There a Correlation ?. Frontiers in cellular neuroscience. 2018 ; 12 : 78.

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9. Galliver M, Gowling E, Farr W, Gain A, Male I. Cost of assessing a child for possible autism spectrum disorder ? An observational study of current practice in child development centres in the UK. BMJ paediatrics open. 2017 ; 1(1) : e000052.

Objective : UK guidelines recommend that diagnosis of autism in children requires assessment by a multidisciplinary team. With growing numbers of referrals for assessment, diagnostic services have been under increasing pressure to meet the level of need. This study aimed to explore the number of hours of professional time required to complete such an assessment based on current practice in secondary care child development centres across the UK, and from this we calculate the cost of assessment. Design : An online questionnaire, using, was sent to 20 child development centres asking them to retrospectively record team members involved at each stage of assessment and time taken, including report writing and administration for a typical assessment. Costs were estimated based on the hourly rate for each team member, including salary, on-costs and trust overheads. Results : 12 questionnaires (60%) were returned. 10 centres adopted a two-stage approach to assessment with an initial ’screening’ clinic determining whether the child needed to proceed to full multidisciplinary assessment. Median professional time involved was 13 hours (IQR 9.6-15.5 hours). This resulted in a median cost of pound809 ($1213, based on conversion rate pound1 equal to US$1.5 (November 2015)), (IQR pound684- pound925) ($1026-$1388)). Implications : This study confirms that multidisciplinary diagnostic assessment of a child with possible autism requires significant professional time, with staff costs of approximately pound800 ($1200) per child. This does not include costs of intervention, parent psychological education, investigation and assessment and management of comorbidities. If growing waiting times for diagnostic assessment are to be avoided, funding for diagnostic services needs to reflect the human resources required and the resulting costs of that assessment.

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10. Ledbetter-Cho K, O’Reilly M, Lang R, Watkins L, Lim N. Meta-analysis of Tablet-Mediated Interventions for Teaching Academic Skills to Individuals with Autism. J Autism Dev Disord. 2018.

Portable touch-screen devices have been the focus of a notable amount of intervention research involving individuals with autism. Additionally, popular media has widely circulated claims that such devices and academic software applications offer tremendous educational benefits. A systematic search identified 19 studies that targeted academic skills for individuals with autism. Most studies used the device’s built-in video recording or camera function to create customized teaching materials, rather than commercially-available applications. Analysis of potential moderating variables indicated that participants’ age and functioning level did not influence outcomes. However, participant operation of the device, as opposed to operation by an instructor, produced significantly larger effect size estimates. Results are discussed in terms of recommendations for practitioners and future research.

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11. Luo W, Zhang C, Jiang YH, Brouwer CR. Systematic reconstruction of autism biology from massive genetic mutation profiles. Science advances. 2018 ; 4(4) : e1701799.

Autism spectrum disorder (ASD) affects 1% of world population and has become a pressing medical and social problem worldwide. As a paradigmatic complex genetic disease, ASD has been intensively studied and thousands of gene mutations have been reported. Because these mutations rarely recur, it is difficult to (i) pinpoint the fewer disease-causing versus majority random events and (ii) replicate or verify independent studies. A coherent and systematic understanding of autism biology has not been achieved. We analyzed 3392 and 4792 autism-related mutations from two large-scale whole-exome studies across multiple resolution levels, that is, variants (single-nucleotide), genes (protein-coding unit), and pathways (molecular module). These mutations do not recur or replicate at the variant level, but significantly and increasingly do so at gene and pathway levels. Genetic association reveals a novel gene + pathway dual-hit model, where the mutation burden becomes less relevant. In multiple independent analyses, hundreds of variants or genes repeatedly converge to several canonical pathways, either novel or literature-supported. These pathways define recurrent and systematic ASD biology, distinct from previously reported gene groups or networks. They also present a catalog of novel ASD risk factors including 118 variants and 72 genes. At a subpathway level, most variants disrupt the pathway-related gene functions, and in the same gene, they tend to hit residues extremely close to each other and in the same domain. Multiple interacting variants spotlight key modules, including the cAMP (adenosine 3’,5’-monophosphate) second-messenger system and mGluR (metabotropic glutamate receptor) signaling regulation by GRKs (G protein-coupled receptor kinases). At a superpathway level, distinct pathways further interconnect and converge to three biology themes : synaptic function, morphology, and plasticity.

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12. Meng FC, Xu XJ, Song TJ, Shou XJ, Wang XL, Han SP, Han JS, Zhang R. Development of an Autism Subtyping Questionnaire Based on Social Behaviors. Neurosci Bull. 2018.

Autism spectrum disorder can be differentiated into three subtypes (aloof, passive, and active-but-odd) based on social behaviors according to the Wing Subgroups Questionnaire (WSQ). However, the correlations between the scores on some individual items and the total score are poor. In the present study, we translated the WSQ into Chinese, modified it, validated it in autistic and typically-developing Chinese children, and renamed it the Beijing Autism Subtyping Questionnaire (BASQ). Our results demonstrated that the BASQ had improved validity and reliability, and differentiated autistic children into these three subtypes more precisely. We noted that the autistic symptoms tended to be severe in the aloof, moderate in the passive, and mild in the active-but-odd subtypes. The modified questionnaire may facilitate etiological studies and the selection of therapeutic regimes.

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13. Miniscalco C, Fernell E, Thompson L, Sandberg E, Kadesjo B, Gillberg C. Development problems were common five years after positive screening for language disorders and, or, autism at 2.5 years of age. Acta paediatrica (Oslo, Norway : 1992). 2018.

AIM : This study identified whether children who had screened positive for either developmental language disorder (DLD) or autism spectrum disorder (ASD) at the age of 2.5 years had neurodevelopmental assessments five years later. METHODS : Our study cohort were 288 children born from 1 July 2008-20 June 2009 who screened positive for DLD and, or, ASD at 2.5 years. Of these, 237 children were referred to, and assessed, at the Paediatric Speech and Language Pathology clinic (n=176) or the Child Neuropsychiatry Clinic (n=61) at the Queen Silvia Children’s Hospital, Gothenburg, Sweden. Clinical registers covering all relevant outpatient clinics were reviewed five years later with regard to established diagnoses. RESULTS : When the 237 were followed up five years later, 96 (40%) had established neurodevelopmental disorders or problems, often beyond DLD and ASD. Co-existing problems were common in this cohort and multidisciplinary assessments were indicated. The other 60% did not appear in subsequent clinic records. It is likely that this 40% was a minimum rate and that more children will be referred for developmental problems later. CONCLUSION : Five years after they had been screened positive for DLD and, or autism at 2.5 years, 40% of our cohort had remaining or other developmental problems. This article is protected by copyright. All rights reserved.

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14. Mul CL, Stagg SD, Herbelin B, Aspell JE. The Feeling of Me Feeling for You : Interoception, Alexithymia and Empathy in Autism. J Autism Dev Disord. 2018.

Following recent evidence for a link between interoception, emotion and empathy, we investigated relationships between these factors in autism spectrum disorder (ASD). 26 adults with ASD and 26 healthy participants completed tasks measuring interoception, alexithymia and empathy. ASD participants with alexithymia demonstrated lower cognitive and affective empathy than ASD participants without alexithymia. ASD participants showed reduced interoceptive sensitivity (IS), and also reduced interoceptive awareness (IA). IA was correlated with empathy and alexithymia, but IS was related to neither. Alexithymia fulfilled a mediating role between IA and empathy. Our findings are suggestive of an alexithymic subgroup in ASD, with distinct interoceptive processing abilities, and have implications for diagnosis and interventions.

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15. Rigby SN, Stoesz BM, Jakobson LS. Empathy and face processing in adults with and without autism spectrum disorder. Autism Res. 2018.

Many factors contribute to social difficulties in individuals with autism spectrum disorder (ASD). The goal of the present work was to determine whether atypicalities in how individuals with ASD process static, socially engaging faces persist when nonrigid facial motion cues are present. We also sought to explore the relationships between various face processing abilities and individual differences in autism symptom severity and traits such as empathy. Participants included 16 adults with ASD without intellectual impairment and 16 sex- and age-matched controls. Mean Verbal IQ was comparable across groups [t(30) = 0.70, P = 0.49]. The two groups responded similarly to many of the experimental manipulations ; however, relative to controls, participants with ASD responded more slowly to dynamic expressive faces, even when no judgment was required ; were less accurate at identity matching with static and dynamic faces ; and needed more time to make identity and expression judgments [F(1, 30) >/= 6.37, P /= 0.175 in all cases], particularly when the faces were moving [F(1, 30) = 3.40, P = 0.072, etap(2) = 0.104]. In the full sample, as social autistic traits increased and empathic skills declined, participants needed more time to judge static identity, and static or dynamic expressions [0.43 < |rs | < 0.56]. The results suggest that adults with ASD show general impairments in face and motion processing and support the view that an examination of individual variation in particular personality traits and abilities is important for advancing our understanding of face perception. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : Our findings suggest that people with ASD have problems processing expressive faces, especially when seen in motion. It is important to learn who is most at risk for face processing problems, given that in the general population such problems appear to be linked to impaired social skills and empathy. By studying relationships between different abilities and traits, we may be able to find better ways to diagnose and support all people on the autism spectrum.

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16. Rodriguez-Medina J, Rodriguez-Navarro H, Arias V, Arias B, Anguera MT. Non-reciprocal Friendships in a School-Age Boy with Autism : The Ties that Build ?. J Autism Dev Disord. 2018.

This mixed-methods study examined differences in social interaction patterns between a school-age boy with autism and his friends, non-reciprocal friends, and non-friends during recess time at a mainstream school (third grade of elementary school). Through a combination of observational methodology and social network analysis with an idiographic, follow-up and multidimensional design approach, we used lag sequential and polar coordinate analysis to ascertain the associations between various interactive behaviors as a function of type of friendship relation. After 40 sessions, we found that the non-reciprocal friendship relations of the boy with autism could have significantly greater potential than his reciprocal friendships to increase active engagement and reduce the time he spent alone during recess.

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17. Romero V, Fitzpatrick P, Roulier S, Duncan A, Richardson MJ, Schmidt RC. Correction : Evidence of embodied social competence during conversation in high functioning children with autism spectrum disorder. PLoS One. 2018 ; 13(4) : e0195888.

[This corrects the article DOI : 10.1371/journal.pone.0193906.].

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18. Tromans S, Adams C. Brief Report : Autism Spectrum Disorder : A Comprehensive Survey of Randomized Controlled Trials. J Autism Dev Disord. 2018.

We searched the Cochrane Central Register of Controlled Trials to provide an overview of evidence from randomized controlled trials (RCTs) of therapeutic interventions for autism spectrum disorders. From the final survey (529 RCTs), the mean size was 49 participants (standard deviation 50, range 1-479, median 36, mode 40), with a sharp increase in the number of RCTs from 2008. The most frequently evaluated intervention was antipsychotic treatment (n = 44, 3006 participants). The journal with the most RCTs was the Journal of Autism and Developmental Disorders (N = 104). Most trials were small in size, emphasising the need for research groups to collaborate to generate higher quality data with greater applicability to clinical practice.

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19. Wink LK, Adams R, Horn PS, Tessier CR, Bantel AP, Hong M, Shaffer RC, Pedapati EV, Erickson CA. A Randomized Placebo-Controlled Cross-Over Pilot Study of Riluzole for Drug-Refractory Irritability in Autism Spectrum Disorder. J Autism Dev Disord. 2018.

Riluzole is a glutamatergic modulator of particular interest in autism spectrum disorder (ASD). In this 12-week randomized, double-blind, placebo-controlled, crossover pilot study we evaluated the safety and tolerability of 5-week of adjunctive riluzole treatment (vs. 5-week of placebo, with 2-week washout period) targeting ASD-associated drug-refractory irritability in eight individuals age 12-25 years. All participants tolerated riluzole 200 mg per day, however there were no statistically significant findings for the overall treatment effect, the treatment effect by week within period of the study, or a cross-over effect across the periods of the study on the Clinical Global Impression Improvement Scale or the Aberrant Behavior Checklist Irritability subscale. The results of this trial indicate that 5-week of riluzole treatment was well tolerated, but had no significant effect on the target symptoms. Trial Registration Identifier NCT02081027, Registered 5 August 2013, First participant enrolled 19 September 2013.

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20. Yuan H, Li X, Wang Q, Yang W, Song J, Hu X, Shen Y. A de novo 921Kb microdeletion at 11q13.1 including neurexin 2 in a boy with developmental delay, deficits in speech and language without autistic behaviors. European journal of medical genetics. 2018.

Microdeletions at 11q13.1 are very rare. At present only two patients with 11q13.1 deletion involving neurexin 2 (NRXN2) have been reported. Both patients exhibited autistic features, which supported the role of NRXN2 in autism pathogenicity. It is currently unknown whether heterozygous deletion of NRXN2 is of high penetrance or if it is sufficient to result in autism behaviors. Here we reported a 2-year-9-month old boy with developmental delay, short stature, significant language delay and other congenital anomalies. In contrast to previously reported cases, the boy did not present with autistic behaviors and did not meet the clinical diagnosis of autism. A de novo 921kb microdeletion at 11q13.1 was detected by chromosomal microarray analysis (CMA). Whole Exome Sequencing (WES) was also employed for our patient. The deletion was confirmed and no additional pathogenic variants were detected. We compared our patient’s genomic information and clinical features with those of two previously reported individuals. Three patients shared similar deleted intervals and had similar clinical features except for autistic behaviors. This study suggested that NRXN2 gene had incomplete penetrance for autistic behavioral phenotype. The finding is of interest for genetic counseling and clinical management to patients with NRXN2 defects.

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21. Yuen T, Carter MT, Szatmari P, Ungar WJ. Cost-Effectiveness of Universal or High-Risk Screening Compared to Surveillance Monitoring in Autism Spectrum Disorder. J Autism Dev Disord. 2018.

The American Academy of Pediatrics recommends universal screening for autism spectrum disorder at 18 and 24 months. This study compared the cost-effectiveness of universal or high-risk screening to surveillance monitoring. Simulation models estimated the costs and outcomes from birth to age 6 years. The incremental cost per child diagnosed by 36 months was $41,651.6 for high-risk screening and $757,116.9 for universal screening from the societal perspective. Universal screening may not be a cost-effective approach to increase earlier treatment initiation, as most children initiated treatment after age 60 months. Eliminating wait times resulted in more children initiated treatment by 48 months, but at a high initial cost that may be offset by future cost-savings related to better outcomes.

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22. Zarnowska I, Chrapko B, Gwizda G, Nocun A, Mitosek-Szewczyk K, Gasior M. Therapeutic use of carbohydrate-restricted diets in an autistic child ; a case report of clinical and 18FDG PET findings. Metabolic brain disease. 2018.

The ketogenic diet (KD) is a high-fat, adequate-protein, and low-carbohydrate diet that has been used successfully in the treatment of refractory epilepsies for almost 100 years. There has been accumulating evidence to show that the KD may provide a therapeutic benefit in autism spectrum disorders, albeit by a yet-unknown mechanism. We report a case of a 6-year-old patient with high-functioning autism and subclinical epileptic discharges who responded poorly to several behavioural and psychopharmacological treatments. The patient was subsequently placed on the KD due to significant glucose hypometabolism in the brain as revealed by an 18FDG PET. As soon as one month after starting the KD, the patient’s behavior and intellect improved (in regard to hyperactivity, attention span, abnormal reactions to visual and auditory stimuli, usage of objects, adaptability to changes, communication skills, fear, anxiety, and emotional reactions) ; these improvements continued until the end of the observation period at 16 months on the KD. The 18FDG PET, measured at 12 months on the KD, revealed that 18F-FDG uptake decreased markedly and diffusely in the whole cerebral cortex with a relatively low reduction in basal ganglia in comparison to the pre-KD assessment. It warrants further investigation if the 18FDG PET imaging could serve as a biomarker in identifying individuals with autism who might benefit from the KD due to underlying abnormalities related to glucose hypometabolism.

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