Influence of Catechol-O-methyltransferase on Executive Functioning Longitudinally After Early Childhood Traumatic Brain Injury: Preliminary Findings.

OBJECTIVE: To elucidate the association of a functional catechol-O-methyltransferase (COMT) genotype (rs4680) with recovery of executive functions up to 18 months after early childhood traumatic brain injury (TBI) compared with an orthopedic injury (OI) group. SETTING: Outpatient. PARTICIPANTS: A total of 134 children with a moderate to severe TBI (n = 63) or OI (n = 71) between the ages of 3 and 6 years who were followed 18 months postinjury. DESIGN: Case-comparison, longitudinal cohort MAIN MEASURES: : The Behavior Rating Inventory of Executive Function, developmental NEuroPSYchological Assessment (NEPSY) of Verbal Fluency, and a modified Stroop Test for young children (Shape School). RESULTS: The low-activity COMT enzyme genotype (AA) was associated with better scores on the developmental NEPSY of Verbal Fluency (F = 3.80; P = .02) and the Shape School (F = 2.89; P = .06) in all participants when controlling for injury type (TBI vs OI) over the first 18 months after injury. Injury type (TBI vs OI) did not significantly moderate the effect of the COMT genotypes on executive function recovery. CONCLUSION: This study provides preliminary evidence for a role of COMT genotypes in long-term recovery of executive function after pediatric TBI and OI. Larger studies are needed to determine the exact link between genetic variation in the COMT gene and TBI recovery in children.

Cognition and Brain Structure Following Early Childhood Surgery With Anesthesia.

BACKGROUND: Anesthetics induce widespread cell death, permanent neuronal deletion, and neurocognitive impairment in immature animals, raising substantial concerns about similar effects occurring in young children. Epidemiologic studies have been unable to sufficiently address this concern, in part due to reliance on group-administered achievement tests, inability to assess brain structure, and limited control for confounders. METHODS: We compared healthy participants of a language development study at age 5 to 18 years who had undergone surgery with anesthesia before 4 years of age (n = 53) with unexposed peers (n = 53) who were matched for age, gender, handedness, and socioeconomic status. Neurocognitive assessments included the Oral and Written Language Scales and the Wechsler Intelligence Scales (WAIS) or WISC, as appropriate for age. Brain structural comparisons were conducted by using T1-weighted MRI scans. RESULTS: Average test scores were within population norms, regardless of surgical history. However, compared with control subjects, previously exposed children scored significantly lower in listening comprehension and performance IQ. Exposure did not lead to gross elimination of gray matter in regions previously identified as vulnerable in animals. Decreased performance IQ and language comprehension, however, were associated with lower gray matter density in the occipital cortex and cerebellum. CONCLUSIONS: The present findings suggest that general anesthesia for a surgical procedure in early childhood may be associated with long-term diminution of language abilities and cognition, as well as regional volumetric alterations in brain structure. Although causation remains unresolved, these findings nonetheless warrant additional research into the phenomenon's mechanism and mitigating strategies.

Interventions for attention problems after pediatric traumatic brain injury: what is the evidence?

OBJECTIVE: To gain an understanding of the current state of the evidence for management of attention problems after traumatic brain injury (TBI) in children, determine gaps in the literature, and make recommendations for future research. TYPE: Focused systematic review. LITERATURE SURVEY: PubMed/Medline and PsychINFO databases were searched for relevant articles published in English during the last 20 years. Keywords included "attention" "attention deficit and disruptive behavior disorders," and "brain injuries." Studies were limited to children. METHODOLOGY: Titles were examined first and eliminated based on lack of relevancy to attention problems after brain injury in children. This was followed by an abstract and full text review. Article quality was determined based on the US Preventative Services Task Force recommendations for evidence grading. SYNTHESIS: Four pharmacologic and 10 cognitive therapy intervention studies were identified. These studies varied in level of evidence quality but were primarily nonrandomized or cohort studies. CONCLUSIONS: There are studies that demonstrate benefits of varying pharmacologic and cognitive therapies for the management of attention problems after TBI. However, there is a paucity of evidence available to definitively guide management of attention problems after pediatric TBI. Larger randomized, controlled trials and multicenter studies are needed to elucidate optimal treatment strategies in this population.