Efficacy of Low-Dose Buspirone for Restricted and Repetitive Behavior in Young Children with Autism Spectrum Disorder: A Randomized Trial.

OBJECTIVES: To determine safety and efficacy of the 5HT1A serotonin partial agonist buspirone on core autism and associated features in children with autism spectrum disorder (ASD). STUDY DESIGN: Children 2-6 years of age with ASD (N = 166) were randomized to receive placebo or 2.5 or 5.0 mg of buspirone twice daily. The primary objective was to evaluate the effects of 24 weeks of buspirone on the Autism Diagnostic Observation Schedule (ADOS) Composite Total Score. Secondary objectives included evaluating the effects of buspirone on social competence, repetitive behaviors, language, sensory dysfunction, and anxiety and to assess side effects. Positron emission tomography measures of tryptophan metabolism and blood serotonin concentrations were assessed as predictors of buspirone efficacy. RESULTS: There was no difference in the ADOS Composite Total Score between baseline and 24 weeks among the 3 treatment groups (P = .400); however, the ADOS Restricted and Repetitive Behavior score showed a time-by-treatment effect (P = .006); the 2.5-mg buspirone group showed significant improvement (P = .003), whereas placebo and 5.0-mg buspirone groups showed no change. Children in the 2.5-mg buspirone group were more likely to improve if they had fewer foci of increased brain tryptophan metabolism on positron emission tomography (P = .018) or if they showed normal levels of blood serotonin (P = .044). Adverse events did not differ significantly among treatment groups. CONCLUSIONS: Treatment with 2.5 mg of buspirone in young children with ASD might be a useful adjunct therapy to target restrictive and repetitive behaviors in conjunction with behavioral interventions. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00873509.

Arterial ischemic stroke risk factors: the International Pediatric Stroke Study.

OBJECTIVE: To describe presumptive risk factors (RFs) for childhood arterial ischemic stroke (AIS) and explore their relationship with presentation, age, geography, and infarct characteristics. METHODS: Children (29 days-18 years) were prospectively enrolled in the International Pediatric Stroke Study. Risk factors, defined conditions thought to be associated with childhood AIS, were divided into 10 categories. Chi-square tests were used to compare RFs prevalence across regions and age; logistic regression was used to determine whether RFs were associated with particular features at presentation or infarct characteristics. RESULTS: A total of 676 children were included. No identifiable RFs was present in 54 (9%). RFs in others included arteriopathies (53%), cardiac disorders (CDs) (31%), infection (24%), acute head and neck disorders (AHNDs) (23%), acute systemic conditions (ASCs) (22%), chronic systemic conditions (CSCs) (19%), prothrombotic states (PTSs) (13%), chronic head and neck disorders (CHNDs) (10%), atherosclerosis-related RFs (2%), and other (22%). Fifty-two percent had multiple RFs. There was lower prevalence of arteriopathy in Asia, lower prevalence of CSCs in Europe and Australia, higher prevalence of PTSs in Europe, and higher prevalence of ASCs in Asia and South America. Prevalence of CDs and ASCs was highest in preschoolers, arteriopathies in children 5 to 9 years old, and CHNDs were highest in children aged 10 to 14 years. Arteriopathies were associated with focal signs and ASCs, CHNDs, and AHNDs with diffuse signs. Arteriopathies, CSCs, and ASCs were associated with multiple infarcts and CDs with hemorrhagic conversion. INTERPRETATION: RFs, especially arteriopathy, are common in childhood AIS. Variations in RFs by age or geography may inform prioritization of investigations and targeted preventative strategies.