Effect of pioglitazone treatment on behavioral symptoms in autistic children.

INTRODUCTION: Autism is complex neuro-developmental disorder which has a symptomatic diagnosis in patients characterized by disorders in language/communication, behavior, and social interactions. The exact causes for autism are largely unknown, but is has been speculated that immune and inflammatory responses, particularly those of Th2 type, may be involved. Thiazolidinediones (TZDs) are agonists of the peroxisome proliferator activated receptor gamma (PPARgamma), a nuclear hormone receptor which modulates insulin sensitivity, and have been shown to induce apoptosis in activated T-lymphocytes and exert anti-inflammatory effects in glial cells. The TZD pioglitazone (Actos) is an FDA-approved PPARgamma agonist used to treat type 2 diabetes, with a good safety profile, currently being tested in clinical trials of other neurological diseases including AD and MS. We therefore tested the safety and therapeutic potential of oral pioglitazone in a small cohort of children with diagnosed autism. CASE DESCRIPTION: The rationale and risks of taking pioglitazone were explained to the parents, consent was obtained, and treatment was initiated at either 30 or 60 mg per day p.o. A total of 25 children (average age 7.9 +/- 0.7 year old) were enrolled. Safety was assessed by measurements of metabolic profiles and blood pressure; effects on behavioral symptoms were assessed by the Aberrant Behavior Checklist (ABC), which measures hyperactivity, inappropriate speech, irritability, lethargy, and stereotypy, done at baseline and after 3-4 months of treatment. DISCUSSION AND EVALUATION: In a small cohort of autistic children, daily treatment with 30 or 60 mg p.o. pioglitazone for 3-4 months induced apparent clinical improvement without adverse events. There were no adverse effects noted and behavioral measurements revealed a significant decrease in 4 out of 5 subcategories (irritability, lethargy, stereotypy, and hyperactivity). Improved behaviors were inversely correlated with patient age, indicating stronger effects on the younger patients. CONCLUSION: Pioglitazone should be considered for further testing of therapeutic potential in autistic patients.

Laryngeal dysfunction: a common cause of respiratory distress, often misdiagnosed as asthma and responsive to antireflux therapy.

Asthma is diagnosed frequently in patients with respiratory distress. However, laryngeal dysfunction, a common cause of dyspnea, may masquerade as asthma. This study investigated 158 consecutive patients referred to an allergy practice with a diagnosis of asthma. Pulmonary function testing with flow volume loops were used to separate the patients into four groups. These groups consisted of patients with asthma alone in 32%, asthma and laryngeal dysfunction in 16%, laryngeal dysfunction in 26%, and another group not meeting these criteria in 25%. Thirty patients, 10 each from the first three groups, were treated with antireflux medication and reevaluated. Symptom evaluation observed inspiratory difficulties in 73% of the laryngeal dysfunction group compared with 2% of the asthma group (p < 0.0001). Expiratory problems were present in 7% of the laryngeal dysfunction group and 71% of the asthma group (p < 0.0001). The laryngeal dysfunction group only had a 29% beneficial response to Albuterol inhalation compared with a 92% response in the asthma group (p < 0.0001). The laryngeal dysfunction group responded significantly less to both inhaled and oral steroids (p = 0.002). Among the 30 patients treated with antireflux medications, the peak flows improved by 38.7% in the laryngeal dysfunction group compared with 14.8% in the asthma group (p = 0.01).