Reduced frontal white matter volume in long-term childhood leukemia survivors: a voxel-based morphometry study.

BACKGROUND AND PURPOSE: To our knowledge, no published studies have examined whole-brain regional differences to identify more discrete volumetric changes in the brains of childhood leukemia survivors. We used voxel-based morphometry (VBM) to examine regional gray and white matter differences in a group of long-term survivors of acute lymphoblastic leukemia (ALL) compared with a group of healthy controls. Differences in regional white matter volume were expected, given previous reports of white matter changes during treatment for ALL and reduced brain white matter volumes in long-term survivors. Follow-up analyses examined the relationship of regional brain volumes to cognitive function. MATERIALS AND METHODS: We compared 9 long-term survivors of ALL with 14 healthy controls. Survivors of ALL were treated with systemic and intrathecal chemotherapy only. T1-weighted axial 3D spoiled gradient high-resolution images collected on a 1.5T MR imaging scanner were used for the VBM analysis. Neuropsychological evaluations were conducted within 2 months of the MR imaging to assess cognitive function. RESULTS: VBM analysis revealed 2 specific regions of reduced white matter in the right frontal lobes of survivors of ALL compared with healthy controls. Survivors of ALL had lower performances on tests of attention, visual-constructional skills, mental flexibility, and math achievement compared with healthy individuals. Decreased performance on neuropsychological measures was associated with decreased regional white matter volumes. No differences were found between the groups with respect to gray matter regions. CONCLUSION: These findings are consistent with previous literature describing the long-term cognitive, academic, and imaging findings of survivors of ALL and suggest that right frontal white matter is particularly vulnerable to disruption following intensive chemotherapy for ALL. Future studies should focus on further clarifying the white matter changes observed.

Cognitive appraisal accuracy moderates the relationship between injury severity and psychosocial outcomes in traumatic brain injury.

OBJECTIVE: Traumatic brain injury (TBI) frequently results in significant changes in physical, cognitive and emotional status. Outcomes after TBI may be related to accurate appraisal of these changes. This study examined the relationship between cognitive appraisal accuracy and psychosocial outcomes in TBI survivors. METHODS: Participants were male and female TBI survivors (n=103) who were at least 6 months post-injury and a family member of each survivor. Appraisal accuracy was assessed using self- and observer-report measures of perceived cognitive difficulties. Family members also completed a measure of psychosocial function. Hierarchical regression techniques were used to determine whether cognitive appraisal accuracy accounted for a significant proportion of variance in psychosocial outcomes. RESULTS: Study findings indicated cognitive appraisal accuracy moderated the relationship between injury severity and aspects of psychosocial function. CONCLUSIONS: The results suggest that brain injury outcomes may be improved when an individual is able to accurately assess limitations.

Sleep-disordered breathing, pharyngeal size and soft tissue anatomy in children.

We tested the hypothesis that pharyngeal geometry and soft tissue dimensions correlate with the severity of sleep-disordered breathing. Magnetic resonance images of the pharynx were obtained in 18 awake children, 7-12 yr of age, with obstructive apnea-hypopnea index (OAHI) values ranging from 1.81 to 24.2 events/h. Subjects were divided into low-OAHI (n = 9) and high-OAHI (n = 9) groups [2.8 +/- 0.7 and 13.5 +/- 4.9 (SD) P < 0.001]. The OAHI correlated positively with the size of the tonsils (r2 = 0.42, P = 0.024) and soft palate (r2 = 0.33, P = 0.049) and inversely with the volume of the oropharyx (r2 = 0.42, P = 0.038). The narrowest point in the pharyngeal airway was smaller in the high-compared with the low-OAHI group (4.4 +/- 1.2 vs. 6.0 +/- 1.3 mm; P = 0.024), and this point was in the retropalatal airway in all but two subjects. The airway cross-sectional area (CSA)-airway length relation showed that the high-OAHI group had a narrower retropapatal airway than the low-OAHI group, particularly in the retropalatal region where the soft palate, adenoids, and tonsils overlap (P = 0.001). The "retropalatal air space," which we defined as the ratio of the retropalatal airway CSA to the CSA of the soft palate, correlated inversely with the OAHI (r2 = 0.49, P = 0.001). We conclude that 7- to 12-yr-old children with a narrow retropalatal air space have significantly more apneas and hypopneas during sleep compared with children with relatively unobstructed retropalatal airways.

Feasibility of using unattended polysomnography in children for research--report of the Tucson Children's Assessment of Sleep Apnea study (TuCASA).

STUDY OBJECTIVES: The Tucson Children's Assessment of Sleep Apnea study (TuCASA) is designed to investigate the prevalence and correlates of objectively measured sleep-disordered breathing in pre-adolescent children. This paper documents the methods and feasibility of attaining quality unattended polysomnograms in the first 162 TuCASA children recruited. DESIGN: A prospective cohort study projected to enroll 500 children between 5 and 12 years of age who will undergo unattended polysomnography, neurocognitive evaluation, and physiological and anatomical measurements thought to be associated with sleep-disordered breathing. SETTING: Children are recruited through the Tucson Unified School District. Polysomnograms and anthropometric measurements are completed in the child's home. PARTICIPANTS: Of the 157 children enrolled in TuCASA, there were 100 children (64%) between 5-8 years old and 57 children (36%) between the ages of 9 to 12. There were 74 (47%) Hispanic children, and 68 (43%) female participants. INTERVENTIONS: N/A. MEASUREMENTS & RESULTS: Technically acceptable studies were obtained in 157 children (97%). The initial pass rate was 91%, which improved to 97% when 9 children who failed on the first night of recording completed a second study which was acceptable. In 152 studies (97%), greater than 5 hours of interpretable respiratory, electroencephalographic, and oximetry signals were obtained. The poorest signal quality was obtained from the chin electromyogram and from the combination thermister/nasal cannula. Parents reported that 54% of children slept as well as, or better than usual, while 40% reported that their child slept somewhat worse than usual. Only 6% were observed to sleep much worse than usual. Night-to-night variability in key polysomnographic parameters (n=10) showed a high degree of reproducibility on 2 different nights of study using identical protocols in the same child. In 5 children, polysomnograms done in the home were comparable to those recorded in a sleep laboratory. CONCLUSIONS: The high quality of data collected in TuCASA demonstrates that multi-channel polysomnography data can be successfully obtained in children aged 5-12 years in an unattended setting under a research protocol.

Spatial memory following prenatal alcohol exposure: more than a material specific memory deficit.

Spatial memory deficits have been reported following prenatal alcohol exposure and animal studies have demonstrated hippocampal vulnerability to alcohol. This study examined spatial memory in children diagnosed with fetal alcohol syndrome (FAS) or fetal alcohol effects (FAE) and matched controls. Spatial memory was examined with location recall measures. Since visual perceptual skills and nonspecific memory impairment could impact spatial memory, tasks assessing perception and verbal memory were administered. Analyses revealed group differences on perceptual and verbal and spatial memory tasks. There was no significant difference in spatial memory once perceptual and verbal memory task performance was taken into account, suggesting that differences in spatial memory were not solely attributable to a material specific memory deficit.