Bioenergetic variation is related to autism symptomatology.

Autism spectrum disorder (ASD) has been associated with mitochondrial dysfunction but few studies have examined the relationship between mitochondrial function and ASD symptoms. We measured Complex I and IV and citrate synthase activities in 76 children with ASD who were not receiving vitamin supplementation or medication. We also measured language using the Preschool Language Scales or Clinical Evaluation of Language Fundamentals, adaptive behavior using the Vineland Adaptive Behavioral Scale, social function using the Social Responsiveness Scale and behavior using Aberrant Behavior Checklist, Childhood Behavior Checklist and the Ohio Autism Clinical Impression Scale. Children with ASD demonstrated significantly greater variation in mitochondrial activity compared to controls with more than expected ASD children having enzyme activity outside of the normal range for Citrate Synthase (24%), Complex I (39%) and Complex IV (11%). Poorer adaptive skills were associated with Complex IV activity lower or higher than average and lower Complex I activity. Poorer social function and behavior was associated with relatively higher Citrate Synthase activity. Similar to previous studies we find both mitochondrial underactivity and overactivity in ASD. This study confirms an expanded variation in mitochondrial activity in ASD and demonstrates, for the first time, that such variations are related to ASD symptoms.

Vagus nerve stimulation in children with refractory epilepsy: unusual complications and relationship to sleep-disordered breathing.

BACKGROUND: Vagus nerve stimulation (VNS) is approved for use in patients with refractory epilepsy over the age of 12 years. While this procedure is widely used, there is little data on adverse events in young children. MATERIALS AND METHODS: A retrospective chart review was conducted on 26 children who had VNS implantation for refractory epilepsy from 1998 to 2004. RESULTS: Ages ranged from 3 to 17 years (16 boys and 10 girls). Seventy-seven percent had moderate to severe mental retardation. Sixty-five percent had more than 30 seizures per month. Symptomatic-generalized epilepsy was the predominant epilepsy syndrome seen in 77% of children. The duration of VNS treatment ranged from 1 month to 8 years (mean = 3.5 years). Twenty of 26 patients (77%) were on rapid-cycling mode. More than 50% reduction in seizure frequency was noted in 54% with two patients achieving seizure freedom. Twenty-three percent had less than 50% seizure reduction. Four patients were able to terminate seizures with use of the magnet. VNS was removed from one patient because of intractable cough persisting in spite of stimulation being turned off for 1 month. Another patient had it removed twice for infection. Obstructive sleep apnea (OSA) was observed in four patients (15%) after placement of VNS. CONCLUSION: VNS appears to be an effective treatment for children with refractory epilepsy. Development of intractable cough in one patient in spite of device being turned off and recurrent infection-related removal in another are unusual complications. Polysomnography before implantation of VNS should be considered to identify patients with pre-existing OSA.