Donna S. Murray

The Comprehension of Humorous Materials by Adolescents with High-Functioning Autism and Asperger's Syndrome.

This study investigated the ability of adolescents with Aspergers syndrome or high-functioning autism and an age-matched group of typical adolescents to comprehend humorous materials. The analysis of humor focused on picking funny endings for cartoons and jokes. As expected, the adolescents with autism had significantly poorer comprehension of cartoons and jokes. Both groups had more difficulty with the joke than the cartoon task, but when compared with the typical group, the adolescents with autism performed significantly poorer. Examination of the error patterns revealed that subjects with autism had difficulty handling surprise and coherence within humorous narratives.

The Relationship Between Joint Attention and Language in Children With Autism Spectrum Disorders

The relationship between initiation of and response to joint attention and components of receptive and expressive language in 20 children with autism between the ages of 3 and 5 years were examined. Receptive language skills were assessed using the Mullen Scales of Early Learning (MSEL). Expressive language skills were evaluated by examining Mean Length of Utterance and Type Token Ratio. These variables, along with data on responses to joint attention bids and initiation of joint attention were analyzed using Spearman calculations. The ability to respond to the joint attention bids of others was positively correlated with receptive language scores on the MSEL and mean length of utterance in children with autism. There was no relationship between the ability to initiate joint attention and the selected components of language examined.

Use of the Autism Diagnostic Observation Schedule (ADOS) in a clinical setting

The aim of this study was to examine the Autism Diagnostic Observation Schedule (ADOS) as it is commonly used in clinical practice. ADOS classifications were compared to final diagnoses given by a multidisciplinary team to 584 children referred for evaluation for possible autism spectrum disorder (ASD) at the Cincinnati Children’s Hospital Medical Center. A total of 177 children were evaluated with a Module 1 (87 No Words), 198 with a Module 2 (90 < 5 years) and 209 with a Module 3. Of these, 142 (26%) were diagnosed with autism, 185 (32%) with non-autism ASD, and 257 (44%) with non-spectrum disorders. Sensitivities were moderate to high on both original and revised algorithms, while specificities were substantially lower than those previously reported. This difference is likely attributable to the composition of the sample that included many children with a broad array of developmental and behavioral disorders. The clinical impression of the team member who administered the ADOS was critical to the accuracy of the overall diagnosis. Using numeric scores alone resulted in misclassification from false positive results. The study highlights the importance of the qualitative interactions of the ADOS activities as well as the score in diagnostic decision making.

Autism spectrum disorders in 24 children who are deaf or hard of hearing

OBJECTIVES Approximately 4% of children who are deaf or hard of hearing have co-occurring autism spectrum disorder (ASD). Making an additional diagnosis of ASD in this population can be challenging, given the complexities of determining whether speech/language and social delays can be accounted for by their hearing loss, or whether these delays might be indicative of a comorbid ASD diagnosis. This exploratory study described a population of 24 children with the dual diagnosis of ASD and hearing loss. METHODS Children completed a comprehensive ASD evaluation using standardized autism diagnostic instruments (Autism Diagnostic Observation Schedule, language and psychological testing). Children with permanent hearing loss who had a developmental evaluation between 2001 and 2011 and were diagnosed with an ASD based on the results of that evaluation were included. Information on communication modality, language and cognitive abilities was collected. RESULTS The median age of diagnosis was 14 months (range 1-71) for hearing loss and 66.5 months (range 33-106) for ASD. Only 25% (n=6) children were diagnosed with ASD ≤ 48 months of age and 46% by ≤ 6 years. Twelve (50%) children were diagnosed with ASD, 11 were diagnosed with pervasive developmental disorder not otherwise specified and 1 child had Aspergers. Most (67%) had profound degree of hearing loss. Fourteen (58%) children had received a cochlear implant, while 3 children had no amplification for hearing loss. Nine (38%) of the 24 children used speech as their mode of communication (oral communicators). CONCLUSIONS Communication delays in children who are deaf or hard of hearing are a serious matter and should not be assumed to be a direct consequence of the hearing loss. Children who received cochlear implants completed a multidisciplinary evaluation including a developmental pediatrician, which may have provided closer monitoring of speech and language progression and subsequently an earlier ASD diagnosis. Because children who are deaf or hard of hearing with ASD are challenging to evaluate, they may receive a diagnosis of ASD at older ages.

Influence of seizures on early development in tuberous sclerosis complex

OBJECTIVE Epilepsy is commonly seen in Tuberous Sclerosis Complex (TSC). The relationship between seizures and developmental outcomes has been reported, but few studies have examined this relationship in a prospective, longitudinal manner. The objective of the study was to evaluate the relationship between seizures and early development in TSC. METHODS Analysis of 130 patients ages 0-36months with TSC participating in the TSC Autism Center of Excellence Network, a large multicenter, prospective observational study evaluating biomarkers predictive of autism spectrum disorder (ASD), was performed. Infants were evaluated longitudinally with standardized evaluations, including cognitive, adaptive, and autism-specific measures. Seizure history was collected continuously throughout, including seizure type and frequency. RESULTS Data were analyzed at 6, 12, 18, and 24months of age. Patients without a history of seizures performed better on all developmental assessments at all time points compared to patients with a history of seizures and exhibited normal development at 24months. Patients with a history of seizures not only performed worse, but developmental progress lagged behind the group without seizures. All patients with a history of infantile spasms performed worse on all developmental assessments at 12, 18, and 24months. Higher seizure frequency correlated with poorer outcomes on developmental testing at all time points, but particularly at 12months and beyond. Patients with higher seizure frequency during infancy continued to perform worse developmentally through 24months. A logistic model looking at the individual impact of infantile spasms, seizure frequency, and age of seizure onset as predictors of developmental delay revealed that age of seizure onset was the most important factor in determining developmental outcome. CONCLUSIONS Results of this study further define the relationship between seizures and developmental outcomes in young children with TSC. Early seizure onset in infants with TSC negatively impacts very early neurodevelopment, which persists through 24months of age.

Improving Access to Care at Autism Treatment Centers: A System Analysis Approach.

OBJECTIVE: The prevalence of autism spectrum disorder is steadily increasing and placing more demands on already overburdened diagnostic and treatment systems. A thoughtful, systematic reorganization of autism service delivery may reduce delays and better meet the growing need. METHODS: Two clinical centers in the Autism Intervention Research Network on Physical Health, Cincinnati Children’s Hospital Medical Center (CCHMC) and Nationwide Children’s Hospital (NCH), undertook a year-long access improvement project to reduce delays to care by using system analysis to identify sources of delay and to target changes by using a set of defined access principles. Although both sites addressed access, they focused on slightly different targets (reducing number of patients with autism spectrum disorders waiting for follow-up appointments at NCH and reducing delay to new diagnosis at CCHMC). RESULTS: Both sites achieved dramatic improvements in their complex, multidisciplinary systems. A 94% reduction in number of patients on the waitlist from 99 to 6 patients and a 22% reduction in median delay for a new ongoing care appointment were realized at NCH. A 94% reduction in third next available appointment for new physician visits for children 3 to 5 years old was realized at CCHMC. CONCLUSIONS: This article demonstrates that 2 different clinical systems improved access to care for autism diagnosis and follow-up care by identifying sources of delay and using targeted changes based on a set of access change principles. With appropriate guidance and data analysis, improvements in access can be made.

The Autism Speaks Autism Treatment Network Registry Data: Opportunities for Investigators

OBJECTIVE: Patient registries can effectively collect data over a long period of time to provide a better understanding of the typical presentation of specific conditions. The autism spectrum disorders (ASDs) have experienced a marked increase in reported prevalence over the past 20 years for reasons that are not completely clear. The Autism Treatment Network (ATN) Registry was established to facilitate investigations into a variety of questions critical to expanding our understanding of ASDs. Here we describe the establishment of the registry, its components, some of its findings to date, and opportunities for further use of this data. METHODS: Participants are eligible for enrollment into the ATN registry if they are between the ages of 2.0 and 17.6 years at the time of enrollment and meet criteria for ASD as determined by clinical consensus on the basis of specific diagnostic measures (Autism Diagnostic Observation Schedule/Autism Diagnostic Observation Schedule, Second Edition; Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition/Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition). Baseline measures include demographics, autism assessment, cognitive assessment data, behavioral data, sleep habits, quality of life, sensory data, and treatments. Several of the measures are collected at annual follow-up visits. RESULTS: More than 6800 children with ASD have been enrolled in the Autism Speaks ATN registry. Data from the registry have been reported at numerous scientific meetings and in several publications and have led to new recommendations for best practices in the management of ASD. CONCLUSIONS: A patient registry for children and adolescents with ASD has had and will continue to have a significant impact on care for this population. Investigators are encouraged to query this database to further its impact by testing novel hypotheses and conducting preliminary proof-of-concept analyses.

Everolimus for treatment of tuberous sclerosis complex-associated neuropsychiatric disorders

To evaluate if short‐term treatment with everolimus was safe and could improve neurocognition and behavior in children with TSC.

Multi-frequency localization of aberrant brain activity in autism spectrum disorder

OBJECTIVE The abnormality of intrinsic brain activity in autism spectrum disorders (ASDs) is still inconclusive. Contradictory results have been found pointing towards hyper-activity or hypo-activity in various brain regions. The present research aims to investigate the spatial and spectral signatures of aberrant brain activity in an unprecedented frequency range of 1-2884 Hz at source levels in ASD using newly developed methods. MATERIALS AND METHODS Seven ASD subjects and age- and gender-matched controls were studied using a high-sampling rate magnetoencephalography (MEG) system. Brain activity in delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), low gamma (30-55 Hz), high gamma (65-90 Hz), ripples (90-200 Hz), high-frequency oscillations (HFOs, 200-1000 Hz), and very high-frequency oscillations (VHFOs, 1000-2884 Hz) was volumetrically localized and measured using wavelet and beamforming. RESULTS In comparison to controls, ASD subjects had significantly higher odds of alpha activity (8-12 Hz) in the sensorimotor cortex (mu rhythm), and generally high-frequency activity (90-2884 Hz) in the frontal cortex. The source power of HFOs (200-1000 Hz) in the frontal cortex in ASD was significantly elevated as compared with controls. CONCLUSION The results suggest that ASD has significantly altered intrinsic brain activity in both low- and high-frequency ranges. Increased intrinsic high-frequency activity in the frontal cortex may play a key role in ASD.

The Autism Intervention Research Network on Physical Health and the Autism Speaks Autism Treatment Network.

* Abbreviations: AIR-P — : Autism Intervention Research Network on Physical Health AS — : Autism Speaks ASD — : autism spectrum disorder ATN — : Autism Treatment Network CAA — : Combating Autism Act HRSA — : Health Resources and Services Administration Over 10 years, the Autism Intervention Research Network on Physical Health (AIR-P) and the Autism Speaks Autism Treatment Network (ATN) have collaborated to produce much of the material presented in this supplement and have been pioneers in bringing attention to the medical needs of children and adolescents with autism spectrum disorders (ASDs) and related conditions. Whereas, until recently, medical complaints (eg, abdominal pain, poor sleep, or disruptive behaviors) were typically considered part of the disorder and therefore not requiring specific attention, today clinicians throughout the country directly assess and treat these associated conditions. The combined AIR-P/ATN network has developed systematic ways to assess and treat coexisting conditions, focusing on those for which management was previously highly variable or sporadic and has shared those methods broadly with the larger parent and professional communities. The active involvement of families and young people with ASD has helped the network identify key issues for individuals and families and focus its attention accordingly. Although clinicians may have limited new, evidence-based options for treating autism directly, they now have systematic ways to evaluate and manage coexisting conditions. In turn, families have learned about new ways to help their children and improve their functioning and outcomes. The ATN began a decade ago with key support from private-sector philanthropy. Over the past 7 years, Autism Speaks (AS), the largest parent-led philanthropy in the field of autism, has provided substantial and critical support to the ATN. The ATN maintains a registry of enrolled children at all network sites, collects registry data, and works with sites to improve … Address correspondence to James M. Perrin, MD, Department of Pediatrics, Harvard Medical School, MassGeneral Hospital for Children, 125 Nashua St, Suite 860, Boston, MA 02114