Roula Choueiri

Early Intervention for Children With Autism Spectrum Disorder Under 3 Years of Age: Recommendations for Practice and Research

This article reviews current evidence for autism spectrum disorder (ASD) interventions for children aged <3 years, based on peer-reviewed articles published up to December 2013. Several groups have adapted treatments initially designed for older, preschool-aged children with ASD, integrating best practice in behavioral teaching methods into a developmental framework based on current scientific understanding of how infants and toddlers learn. The central role of parents has been emphasized, and interventions are designed to incorporate learning opportunities into everyday activities, capitalize on “teachable moments,” and facilitate the generalization of skills beyond the familiar home setting. Our review identified several comprehensive and targeted treatment models with evidence of clear benefits. Although some trials were limited to 8- to 12-week outcome data, enhanced outcomes associated with some interventions were evaluated over periods as long as 2 years. Based on this review, recommendations are proposed for clinical practice and future research.

Early identification of autism spectrum disorder: Recommendations for practice and research

Early identification of autism spectrum disorder (ASD) is essential to ensure that children can access specialized evidence-based interventions that can help to optimize long-term outcomes. Early identification also helps shorten the stressful “diagnostic odyssey” that many families experience before diagnosis. There have been important advances in research into the early development of ASDs, incorporating prospective designs and new technologies aimed at more precisely delineating the early emergence of ASD. Thus, an updated review of the state of the science of early identification of ASD was needed to inform best practice. These issues were the focus of a multidisciplinary panel of clinical practitioners and researchers who completed a literature review and reached consensus on current evidence addressing the question “What are the earliest signs and symptoms of ASD in children aged ≤24 months that can be used for early identification?” Summary statements address current knowledge on early signs of ASD, potential contributions and limitations of prospective research with high-risk infants, and priorities for promoting the incorporation of this knowledge into clinical practice and future research.

Efficacy of intravenous immunoglobulin in Landau-Kleffner syndrome.

We administered 2 gm/kg of intravenous gamma globulin (IVIG) to each of five consecutive patients with Landau-Kleffner syndrome, over 4 days. We compared the 1-month baseline to that following IVIG using a severity score assessing speech, comprehension, behavior, seizures, and electroencephalography. There was a significant drop in this score after IVIG (P = 0.025). Two patients had a dramatic response to IVIG, with complete resolution of symptoms. This finding suggests that IVIG has at least some efficacy for the therapy of Landau-Kleffner syndrome.

Early Screening of Autism Spectrum Disorder: Recommendations for Practice and Research.

This article reviews current evidence for autism spectrum disorder (ASD) screening based on peer-reviewed articles published to December 2013. Screening provides a standardized process to ensure that children are systematically monitored for early signs of ASD to promote earlier diagnosis. The current review indicates that screening in children aged 18 to 24 months can assist in early detection, consistent with current American Academy of Pediatrics’ recommendations. We identify ASD-specific and broadband screening tools that have been ev-aluated in large community samples which show particular promise in terms of accurate classification and clinical utility. We also suggest strategies to help overcome challenges to implementing ASD screening in community practice, as well as priorities for future research.

Potential hepatotoxicity of lamotrigine

Lamotrigine is a new antiepileptic drug that is effective for a broad range of seizures in adults and children. Three children with seizures of different causes who were treated with lamotrigine and developed reversible hepatotoxicity are reported. In one child, this therapy led to relatively severe hepatic failure that required and responded to aggressive therapy. Unlike most of the previously reported six patients with similar severe hepatic involvement, this patients liver function and blood hepatic enzymes became normal. All three patients were on multiple drugs, and two were in epilepsia partialis continua secondary to encephalitis. Two of the patients had relatively rapid medication titration schedules. The close time relationship between the initiation of the lamotrigine therapy and the reversal of the liver abnormalities with lamotrigine discontinuation argues against a cause other than the lamotrigine; however, because of the complexity of the reported cases, the causality remains an assumption. Review of the literature revealed six other previously reported patients (five adults and one child) who had hepatotoxicity during lamotrigine therapy, with or without associated multisystem failure, and similar patient profiles. Lamotrigine is generally a safe and effective medication; however, it should be used with caution in patients on polytherapy and in those with complicated acute systemic and central nervous system conditions, such as fever, status epilepticus, epilepsia partialis, and encephalitis.

Early Identification and Interventions for Autism Spectrum Disorder: Executive Summary

* Abbreviations: ASD — : autism spectrum disorder DSM-5 — : Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition M-CHAT — : Modified Checklist for Autism in Toddlers Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impaired social communication skills and isolated areas of interest.1 The current prevalence of these disorders is estimated to be 1 in 68,2 and recent estimates of the risk of recurrence in families with at least 1 child diagnosed with ASD are 10% to 19%.3–5 Advances have been made in identifying genetic variants that can account for biological vulnerability to ASD,6,7 although recent studies examining patterns of heredity implicate environmental factors and potential gene-by-environment interactions.8 Although the exact etiology remains unknown in most families, some researchers suggest that the pathogenesis of the disorder begins during prenatal life.9,10 It is likely that ASD is heterogeneous in its etiology as well as in its clinical presentation.11 The American Academy of Pediatrics has recommended screening for ASDs at 18 and 24 months of age,12 but recent research suggests that atypical behaviors may be detectable in some children at even younger ages.13,14 However, we are still learning how the timing and developmental course of early ASD symptoms vary across children and how best to detect such symptoms across the continuum of children seen in community practice. In addition, reports15 that early intervention can improve developmental and behavioral outcomes in infants and toddlers have lent urgency to identifying children across the autism spectrum at an earlier age. Advances in genetic, neuroimaging, and other neurobiological research have also raised the potential of biomarker screening. Given the progress in these areas, a review of the current state of the science on early identification, screening, and intervention of ASD was warranted. These issues were the focus of an international, multidisciplinary panel of clinical practitioners and researchers with expertise in ASD and developmental … Address correspondence to Lonnie Zwaigenbaum, MD, Autism Research Center, Glenrose Rehabilitation Hospital, Room E209, 10230 111 Ave, Edmonton, AB, Canada T5G 0B7. E-mail: lonniez{at}ualberta.ca

Classification of epilepsy syndromes and role of genetic factors

In this report the types of epilepsy syndromes seen in children in a tertiary referral center in Beirut, Lebanon were studied and the importance of consanguinity and family history in the occurrence of these syndromes was investigated. Records of 230 pediatric patients evaluated during a 1-year period with the diagnosis of single seizure, febrile seizure, or epilepsy were reviewed. Each patient was classified according to the International League Against Epilepsy classification. The occurrence of consanguinity, of family history of febrile seizures or epilepsy, and of other variables was noted. Thirty-six percent of patients were diagnosed with localization-related epilepsy, 21.7% with generalized epilepsy, 11.7% with undetermined generalized or focal, and 24.3% with special syndromes. Twelve percent of patients were diagnosed with idiopathic, 15.1% with symptomatic, and 30.3% with cryptogenic epilepsies. Consanguinity was more common in patients with symptomatic and cryptogenic epilepsies than in patients with idiopathic epilepsies or with incidental seizures (P < 0.05). Family history of epilepsy was more common in patients with symptomatic, cryptogenic, and idiopathic epilepsies than in patients with incidental seizures (P < 0.05). Family history of febrile seizures but not consanguinity was more common in patients with febrile seizures (P < 0.05). We conclude that genetic factors are important not only in idiopathic epilepsies and febrile seizures but also in cryptogenic and symptomatic epilepsies.

A New Interactive Screening Test for Autism Spectrum Disorders in Toddlers.

OBJECTIVE To develop a clinically valid interactive level 2 screening assessment for autism spectrum disorders (ASD) in toddlers that is brief, easily administered, and scored by clinicians. STUDY DESIGN We describe the development, training, standardization, and validation of the Rapid Interactive Screening Test for Autism in Toddlers (RITA-T) with ASD-specific diagnostic instruments. The RITA-T can be administered and scored in 10 minutes. We studied the validity of the RITA-T to distinguish between toddlers with ASD from toddlers with developmental delay (DD)/non-ASD in an early childhood clinic. We also evaluated the tests performance in toddlers with no developmental concerns. We identified a cutoff score based on sensitivity, specificity, and positive predictive value of the RITA-T that best differentiates between ASD and DD/non-ASD. RESULTS A total of 61 toddlers were enrolled. RITA-T scores were correlated with ASD-specific diagnostic tools (r = 0.79; P < .01) and ASD clinical diagnoses (r = 0.77; P < .01). Mean scores were significantly different in subjects with ASD, those with DD/non-ASD, and those with no developmental concerns (20.8 vs 13 vs 10.6, respectively; P < .0001). At a cutoff score of >14 , the RITA-T had a sensitivity of 1.00, specificity of 0.84, and positive predictive value of 0.88 for identifying ASD risk in a high-risk group. CONCLUSION The RITA-T is a promising new level 2 interactive screening tool for improving the early identification of ASD in toddlers in general pediatric and early intervention settings and allowing access to treatment.

Retrial of Selective Serotonin Reuptake Inhibitors in Children with Pervasive Developmental Disorders: A Retrospective Chart Review

BACKGROUND Youths with pervasive developmental disorders (PDDs) often have symptoms that fail to respond to selective serotonin reuptake inhibitor (SSRI) treatment. These children may be given a subsequent trial of another SSRI. This study reports on the outcome of PDD youths who received a second SSRI trial after an initial treatment failure. METHODS Clinic charts were reviewed for 22 outpatient youths with a DSM-IV diagnosis of a PDD who were treated with an SSRI after an initial failure with a previous SSRI. Response for the second SSRI trial was determined using the Clinical Global Impressions-Improvement Scale (CGI-I). Treatment indications, symptom severity, demographic data, and side effects were recorded. RESULTS For the second SSRI trial, 31.8% of the subjects were rated as much improved on the CGI-I scale and determined to be responders, with 68.2% of the subjects demonstrating activation side effects. 90% of subjects demonstrated activation side effects when data from both SSRI trials were combined. There were no statistically significant associations between outcome of the second SSRI trial and clinical/demographic variables. CONCLUSIONS A second trial of an SSRI after an initial SSRI treatment failure was often unsuccessful in children and adolescents with PDDs. Activation side effects were common. Because alternative treatments in this population are limited, a second trial of an SSRI may still be considered. The study was limited by its retrospective design and by its small sample size.

Feasibility of Conducting Autism Biomarker Research in the Clinical Setting

Objective: Recruitment and completion of research activities during regular clinical care has the potential to increase research participation in complex neurodevelopmental disorders. We evaluated the feasibility, and effect on clinical care, of conducting biomarker research within a subspecialty clinical visit for autism spectrum disorder (ASD). Methods: Children, aged 5 to 10 years, were recruited by providers in ASD clinics at 5 institutions. Biomarkers collected were growth measurements, head circumference, neurologic and dysmorphology examinations, digit ratio (2D:4D) measurement, and platelet serotonin and urinary melatonin sulfate excretion levels. Parents completed the Aberrant Behavior Checklist—Community and a medical/demographic questionnaire. Cognitive level was abstracted from the medical record. Parents and clinicians completed surveys on the effect of the study on the clinical visit. Results: Eighty-three children and their caregivers participated. Factors limiting participation included difficulty reaching families by phone and parent concern about the study blood draw requirement. All children completed at least 4 of 7 planned research activities. Demographic factors, educational placement, and child behavior were not associated with completion of study activities. Lower nonverbal cognitive function was weakly associated with fewer activities completed. Forty-four percent of clinicians reported an effect of the research study on the clinical visit. However, neither parent-reported nor clinician-reported effect was associated with the degree of study activity completion. Conclusion: Recruiting study participants in the context of scheduled ASD clinical visits required significant effort. However, once recruited, participants completed most study activities, regardless of behavioral symptom severity. Research activities did not adversely affect the clinical visit.