1. Glaze DG, Neul JL, Percy A, Feyma T, Beisang A, Yaroshinsky A, Stoms G, Zuchero D, Horrigan J, Glass L, Jones NE. {{A Double-Blind, Randomized, Placebo-Controlled Clinical Study of Trofinetide in the Treatment of Rett Syndrome}}. {Pediatr Neurol}. 2017.
BACKGROUND: This study aimed to determine the safety and tolerability of trofinetide and to evaluate efficacy measures in adolescent and adult females with Rett syndrome, a serious and debilitating neurodevelopmental condition for which no therapies are available for its core features. METHODS: This was an exploratory, phase 2, multicenter, double-blind, placebo-controlled, dose-escalation study of the safety and tolerability of trofinetide in 56 adolescent and adult females with Rett syndrome. Subjects were randomly assigned in a 2:1 ratio to 35 mg/kg twice daily of trofinetide or placebo for 14 days; 35 mg/kg twice daily or placebo for 28 days; or 70 mg/kg twice daily or placebo for 28 days. Safety assessments included adverse events, clinical laboratory tests, vital signs, electrocardiograms, physical examinations, and concomitant medications. Efficacy measurements were categorized into four efficacy domains, which related to clinically relevant, phenotypic dimensions of impairment associated with Rett syndrome. RESULTS: Both 35 mg/kg and 70 mg/kg dose levels of trofinetide were well tolerated and generally safe. Trofinetide at 70 mg/kg demonstrated efficacy compared with placebo based on prespecified criteria. CONCLUSION: Trofinetide was well tolerated in adolescent and adult females with Rett syndrome. Although this study had a relatively short duration in a small number of subjects with an advanced stage of disease, consistent efficacy trends at the higher dose were observed in several outcome measures that assess important dimensions of Rett syndrome. These results represented clinically meaningful improvement from the perspective of the clinicians as well as the caregivers.
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2. Hong ER, Gong LY, Ninci J, Morin K, Davis JL, Kawaminami S, Shi YQ, Noro F. {{A meta-analysis of single-case research on the use of tablet-mediated interventions for persons with ASD}}. {Res Dev Disabil}. 2017.
BACKGROUND: There is a growing amount of single-case research literature on the benefits of tablet-mediated interventions for individuals with autism spectrum disorder (ASD). With the development of tablet-based computers, tablet-mediated interventions have been widely utilized for education and treatment purposes; however, the overall quality and evidence of this literature-base are unknown. AIMS: This article aims to present a quality review of the single-case experimental literature and aggregate results across studies involving the use of tablet-mediated interventions for individuals with ASD. METHODS AND PROCEDURES: Using the Tau nonoverlap effect size measure, the authors extracted data from single-case experimental studies and calculated effect sizes differentiated by moderator variables. The moderator variables included the ages of participants, participants’ diagnoses, interventions, outcome measures, settings, and contexts. OUTCOMES AND RESULTS: Results indicate that tablet-mediated interventions for individuals with ASD have moderate to large effect sizes across the variables evaluated. The majority of research in this review used tablets for video modeling and augmentative and alternative communication. CONCLUSIONS AND IMPLICATIONS: To promote the usability of tablet-mediated interventions for individuals with ASD, this review indicates that more single-case experimental studies should be conducted with this population in naturalistic home, community, and employment settings.
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3. Kang MS, Choi TY, Ryu HG, Lee D, Lee SH, Choi SY, Kim KT. {{Autism-like behavior caused by deletion of vaccinia-related kinase 3 is improved by TrkB stimulation}}. {J Exp Med}. 2017; 214(10): 2947-66.
Vaccinia-related kinases (VRKs) are multifaceted serine/threonine kinases that play essential roles in various aspects of cell signaling, cell cycle progression, apoptosis, and neuronal development and differentiation. However, the neuronal function of VRK3 is still unknown despite its etiological potential in human autism spectrum disorder (ASD). Here, we report that VRK3-deficient mice exhibit typical symptoms of autism-like behavior, including hyperactivity, stereotyped behaviors, reduced social interaction, and impaired context-dependent spatial memory. A significant decrease in dendritic spine number and arborization were identified in the hippocampus CA1 of VRK3-deficient mice. These mice also exhibited a reduced rectification of AMPA receptor-mediated current and changes in expression of synaptic and signaling proteins, including tyrosine receptor kinase B (TrkB), Arc, and CaMKIIalpha. Notably, TrkB stimulation with 7,8-dihydroxyflavone reversed the altered synaptic structure and function and successfully restored autism-like behavior in VRK3-deficient mice. These results reveal that VRK3 plays a critical role in neurodevelopmental disorders and suggest a potential therapeutic strategy for ASD.
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4. Ribeiro SH, Paula CS, Bordini D, Mari JJ, Caetano SC. {{Barriers to early identification of autism in Brazil}}. {Rev Bras Psiquiatr}. 2017: 0.
OBJECTIVE: Parents of children with autism spectrum disorders (ASD) seem to perceive that their child’s development is not following the normal pattern as early as the first year of life. However, ASD children may not receive a diagnosis until they are of preschool age, especially in low- and middle-income countries. The objective of this study was to evaluate the pathway between initial parental concerns about atypical child development and ASD diagnosis in Brazil. METHODS: Nineteen mothers whose children had been diagnosed with ASD participated and were interviewed. The ASD group consisted of two girls and 17 boys, with a mean age of 93.0 months (SD 48.4 months; range 39-197 months). RESULTS: Mothers had their first concerns regarding ASD when children were 23.6+/-11.6 months old, but formal diagnosis occurred at a mean +/- SD age of 59.6+/-40.5 months, corresponding to a 3-year delay. Most mothers felt discouraged to address their concerns due to negative experiences with health professionals. CONCLUSION: In Brazil, mothers perceived the first signs of ASD in their children at an age similar to that reported in other countries, but the diagnosis of ASD seemed to be delayed. Consistent with the literature, mothers reported negative experiences with health professionals during the pathway to achieving ASD diagnosis.
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5. Stahlhut M, Downs J, Aadahl M, Leonard H, Bisgaard AM, Nordmark E. {{Patterns of sedentary time and ambulatory physical activity in a Danish population of girls and women with Rett syndrome}}. {Disabil Rehabil}. 2017: 1-9.
BACKGROUND: Rett syndrome (RTT) is a rare neurodevelopmental disorder leading to multiple disabilities and high dependency on caregivers. This study aimed to: (1) describe the patterns of sedentary time and daily steps and (2) identify the association of individual and environmental characteristics with sedentary time. METHODS: All Danish females with RTT older than 5 years of age and with a MECP2 mutation were invited to participate. The activPAL and StepWatch Activity Monitor (SAM) were worn by participants for at least four days. Sedentary time and step counts were plotted by time to examine daily activity patterns. Associations between sedentary time and individual and environmental covariates were assessed with linear regression models. RESULTS: The median (interquartile range) age of participants was 22.0 (14.3-36.5) years. On average 83.3% (standard deviation 13.9%) of waking hours were spent in sedentary behaviours (n = 48) and the median (interquartile range) daily step count was 5128 (2829-7704) (n = 28). Females older than 33.5 years, and those unable to walk independently were more sedentary. CONCLUSIONS: This study demonstrated high levels of sedentary time and low daily step counts in a Danish population of females with RTT. Advancing age and lower walking skills were associated with higher levels of sedentary time. Implications for Rehabilitation Sedentary lifestyles in individuals with disabilities have a negative impact on health and quality of life. High levels of sedentary time and low daily step counts were demonstrated in a Danish population of females with Rett syndrome. Advancing age and inability to walk independently were strongly associated with higher levels of sedentary time in females with Rett syndrome. Understanding patterns of sedentary behaviour and physical activity can aid health care professionals in developing health-promoting physical activity interventions.
