Brief report: effect of intravenous methotrexate dose and infusion rate on neuropsychological function one year after diagnosis of acute lymphoblastic leukemia.

OBJECTIVE: To compare the effects of two intravenous (IV) methotrexate (MTX) infusion protocols on cognitive function in children newly diagnosed with acute lymphoblastic leukemia (ALL). METHODS: We compared 19 children treated with 1 g/m(2) of IV MTX over 24 hr (Group 1) to 13 children treated with 2 g/m(2) of IV MTX over 4 hr (Group 2) on measures of working memory, nonverbal, and verbal skills shortly after diagnosis (Time 1) and 1 year later (Time 2). RESULTS: A significant GroupxTime interaction was found for a composite measure of working memory with Group 2 declining from Time 1 to Time 2. Group 2 performed significantly worse than Group 1 on a composite measure of nonverbal skills at both time points. CONCLUSIONS: Findings suggest that difficulties in working memory and nonverbal skills may be evident during the first year of treatment for ALL and that severity may be dependent on IV MTX dose and/or infusion rate.

Clinical screening of school children for polysomnography to detect sleep-disordered breathing--the Tucson Children's Assessment of Sleep Apnea study (TuCASA).

STUDY OBJECTIVES: This report describes the associations, specificities, sensitivities, and positive likelihood ratios of clinical symptoms to a finding of sleep-disordered breathing (SDB) on polysomnography in children. METHODS: Four hundred eighty unattended home polysomnograms were completed in a community-based cohort of children 6 to 11 years of age (50% boys, 42.3% Hispanic, and 52.9% between the ages of 6 and 8 years). SDB was present if the child had a respiratory disturbance index of > or = 1 event per hour. MEASUREMENTS AND RESULTS: Boys were twice as likely as girls to have SDB (p < .01); however, witnessed apnea, ethnicity, age, obesity, and airway size (based on clinical evaluation) were not significantly different between those with SDB and without SDB. The sensitivity of any individual or combined clinical symptoms was poor, with male sex (60%) and snoring (29.5%) having the greatest proportion of SDB children. However, high specificities for snoring (89.5%), excessive daytime sleepiness (86.3%), and learning problems (95.9%) were noted. Combinations of symptoms such as snoring+male sex (95.1%), snoring+excessive daytime sleepiness (97.0%), and snoring+learning problems (98.9%) had specificities approaching 1. Positive likelihood ratios for snoring (2.8), learning (2.8), and symptoms combined with snoring such as snoring+male sex (3.9), snoring+learning problems (4.0), and snoring+excessive daytime sleepiness (2.9) were observed. CONCLUSIONS: Snoring, excessive daytime sleepiness, and learning problems are each highly specific, but not sensitive, for SDB in 6- to 11-year old children. However, specificities and positive likelihood ratios for the combination of some of these symptoms is sufficiently high to suggest that some children may not require a polysomnogram for the diagnosis of SDB.

Bilateral hippocampal volume predicts verbal memory function in temporal lobe epilepsy.

The present study used quantitative volume estimates of the hippocampus based on structural magnetic resonance imaging (MRI) to predict memory performance of individuals with epilepsy of temporal lobe origin (TLE). Twenty individuals with TLE completed standardized neuropsychological tests and a quality of life inventory, and participated in a brain MRI protocol designed to obtain high-resolution images of the hippocampus. The combined volume of the left and right hippocampi was found to be the best predictor of objective verbal memory performance. This finding is consistent with the functional adequacy model of hippocampal function. In contrast, the asymmetry between right and left hippocampal volume was the best predictor of subjective ratings of cognitive functioning, which is consistent with the functional reserve model. The collective and complementary functions of the left and right hippocampi merit further exploration in prospective studies of memory function and TLE.

Ventilatory drive and the apnea-hypopnea index in six-to-twelve year old children.

BACKGROUND: We tested the hypothesis that ventilatory drive in hypoxia and hypercapnia is inversely correlated with the number of hypopneas and obstructive apneas per hour of sleep (obstructive apnea hypopnea index, OAHI) in children. METHODS: Fifty children, 6 to 12 years of age were studied. Participants had an in-home unattended polysomnogram to compute the OAHI. We subsequently estimated ventilatory drive in normoxia, at two levels of isocapnic hypoxia, and at three levels of hyperoxic hypercapnia in each subject. Experiments were done during wakefulness, and the mouth occlusion pressure measured 0.1 seconds after inspiratory onset (P0.1) was measured in all conditions. The slope of the relation between P0.1 and the partial pressure of end-tidal O2 or CO2 (PETO2 and PETCO2) served as the index of hypoxic or hypercapnic ventilatory drive. RESULTS: Hypoxic ventilatory drive correlated inversely with OAHI (r = -0.31, P = 0.041), but the hypercapnic ventilatory drive did not (r = -0.19, P = 0.27). We also found that the resting PETCO2 was significantly and positively correlated with the OAHI, suggesting that high OAHI values were associated with resting CO2 retention. CONCLUSIONS: In awake children the OAHI correlates inversely with the hypoxic ventilatory drive and positively with the resting PETCO2. Whether or not diminished hypoxic drive or resting CO2 retention while awake can explain the severity of sleep-disordered breathing in this population is uncertain, but a reduced hypoxic ventilatory drive and resting CO2 retention are associated with sleep-disordered breathing in 6-12 year old children.

Parasomnias and sleep disordered breathing in Caucasian and Hispanic children - the Tucson children's assessment of sleep apnea study.

BACKGROUND: Recent studies in children have demonstrated that frequent occurrence of parasomnias is related to increased sleep disruption, mental disorders, physical harm, sleep disordered breathing, and parental duress. Although there have been several cross-sectional and clinical studies of parasomnias in children, there have been no large, population-based studies using full polysomnography to examine the association between parasomnias and sleep disordered breathing. The Tucson Children's Assessment of Sleep Apnea study is a community-based cohort study designed to investigate the prevalence and correlates of objectively measured sleep disordered breathing (SDB) in pre-adolescent children six to 11 years of age. This paper characterizes the relationships between parasomnias and SDB with its associated symptoms in these children. METHODS: Parents completed questionnaires pertaining to their child's sleep habits. Children had various physiological measurements completed and then were connected to the Compumedics PS-2 sleep recording system for full, unattended polysomnography in the home. A total of 480 unattended home polysomnograms were completed on a sample that was 50% female, 42.3% Hispanic, and 52.9% between the ages of six and eight years. RESULTS: Children with a Respiratory Disturbance Index of one or greater were more likely to have sleep walking (7.0% versus 2.5%, p < 0.02), sleep talking (18.3% versus 9.0%, p < 0.006), and enuresis (11.3% versus 6.3%, p < 0.08) than children with an Respiratory Disturbance Index of less than one. A higher prevalence of other sleep disturbances as well as learning problems was observed in children with parasomnia. Those with parasomnias associated with arousal were observed to have increased number of stage shifts. Small alterations in sleep architecture were found in those with enuresis. CONCLUSIONS: In this population-based cohort study, pre-adolescent school-aged children with SDB experienced more parasomnias than those without SDB. Parasomnias were associated with a higher prevalence of other sleep disturbances and learning problems. Clinical evaluation of children with parasomnias should include consideration of SDB.

Math weaknesses in survivors of acute lymphoblastic leukemia compared to healthy children.

Difficulties in math are the most frequently reported area of academic deficit in survivors of acute lymphoblastic leukemia (ALL) and the most frequent academic complaint among parents of ALL survivors. However, previous studies that included measures of math skills have been limited by the use of only a single measure of math skills, most often a measure of written calculations, without any assessment of math reasoning or math application skills. Further, the nature of these math difficulties has not been adequately investigated. The purpose of this study was to examine the performance of ALL survivors using multiple measures of math skills. Performance was compared to a group of healthy controls matched for age and sex as well as to normative levels. Other measures of neuropsychological function were also administered, and the relationships between these measures and the math measures were explored. Converging evidence for math difficulties in ALL survivors compared to healthy controls and normative levels was found. While ALL survivors generally performed within the average range on measures of math skills, math performance was mostly related to memory function and dominant-hand psychomotor speed. By contrast, math performance of healthy children was mostly related to basic reading skills and visual-motor integration. These findings shed light on the nature of math difficulties in ALL survivors and have implications for intervention.

Learning following prenatal alcohol exposure: performance on verbal and visual multitrial tasks.

Verbal Learning deficits have been reported following prenatal alcohol exposure (PAE). This study examined verbal and visual multitrial learning in children with fetal alcohol syndrome (FAS) or fetal alcohol effects (FAE) and controls matched on age and gender from the same community. In this study, the FAS/FAE group's immediate memory on the Verbal Learning and Visual Learning tasks from the Wide Range Assessment of Memory and Learning (WRAML) was significantly weaker than that of the control group. Although the FAS/FAE group also recalled significantly less information after a delay, they did retain an equivalent proportion of the visual and verbal information as compared to the control group. Thus, the overall pattern of performance on both verbal and visual measures was consistent with that observed in previous studies of Verbal Learning: despite weaker learning, the FAS/FAE group's relative retention of information was no different than that of controls.

Sleep architecture in normal Caucasian and Hispanic children aged 6-11 years recorded during unattended home polysomnography: experience from the Tucson Children's Assessment of Sleep Apnea Study (TuCASA).

OBJECTIVE: To obtain normative sleep architecture data from unattended home polysomnography in Caucasian and Hispanic children aged 6-11 years. DESIGN AND SUBJECTS: Unattended home polysomnography was performed on a single night in Caucasian and Hispanic children aged 6-11 years as part of the Tucson Children's Assessment of Sleep Apnea Study (TuCASA), a cohort study designed to examine the prevalence and correlates of sleep disordered breathing. A subset of 42 children enrolled in TuCASA who had no symptoms of any sleep disorder and had polysomnograms without technical recording problems. RESULTS: Sleep architecture in preadolescent Caucasian and Hispanic children was not different between boys and girls. However, total sleep time (TST), sleep efficiency (SLE) and time spent in REM sleep declined with increasing age. In addition, the number of sleep to wake stage shifts was slightly higher in younger children. Hispanic children had less Stage 3/4 sleep (18+/-1 vs. 22+/-1%, P

Clinical outcomes associated with sleep-disordered breathing in Caucasian and Hispanic children--the Tucson Children's Assessment of Sleep Apnea study (TuCASA).

STUDY OBJECTIVES: This report describes clinical outcomes and threshold levels of respiratory disturbance index (RDI) associated with sleep-disordered breathing in children participating in the Tucson Children's Assessment of Sleep Apnea study. DESIGN: A community-based, prospective cohort study designed to assess the severity of sleep-related symptoms associated with sleep-disordered breathing in children aged 6 to 11 years. SETTING: Students attending elementary school in the Tucson Unified School District. PARTICIPANTS: Unattended home polysomnograms were completed on 239 children-55.2% boys, 51% Hispanic, and 55% between the ages of 6 and 8 years. MEASUREMENTS AND RESULTS: Based on full home polysomnography, levels of RDI that correspond to a higher prevalence of clinical symptoms of sleep-disordered breathing in children aged 6 to 11 were observed. An RDI of at least 5 was associated with frequent snoring (20.3% vs 9.1%, P<.01), excessive daytime sleepiness (22.9% vs 10.7%, P<.01), and learning problems (8.5% vs 2.5%, P<.04) when no oxygen desaturation accompanied the respiratory event. An RDI of at least 1 was associated with these symptoms when a 3% oxygen desaturation was required, snoring (24.0% vs 10.4%, P<.006), excessive daytime sleepiness (24.0% vs 13.4%, P<.04), and learning problems (10.7% vs 3.0%, P<.02). Hispanic or Caucasian ethnicity, sex, age category, obesity, insomnia, and witnessed apnea were not associated with RDI regardless of event definition. CONCLUSIONS: The Tucson Children's Assessment of Sleep Apnea study has shown that there are values of RDI based on polysomnography that correspond to an increased rate of clinical symptoms in children ages 6 to 11 years.

Symptoms related to sleep-disordered breathing in white and Hispanic children: the Tucson Children's Assessment of Sleep Apnea Study.

STUDY OBJECTIVES: The Tucson Children's Assessment of Sleep Apnea (TuCASA) study is designed to investigate the prevalence and correlates of objectively measured sleep-disordered breathing (SDB) in preadolescent children. This article describes the parental report of sleep symptoms associated with SDB in Hispanic and white children. DESIGN: A 13-question sleep habits screening questionnaire designed to assess the severity of sleep-related symptoms associated with SDB in children 4 to 11 years of age. SETTING: Questionnaires were completed by the parents of children attending elementary school in the Tucson Unified School District, Tucson, AZ. PARTICIPANTS: There were 1,494 questionnaires returned, which comprised a sample of whites (38%), Hispanics (45%), and other races (17%). Of these questionnaires, 1,214 were returned for the children of white (45.8%; 556 children) or Hispanic (54.2%; 658 children) ethnicity only. The primary analysis was completed on these 613 boys (50.5%) and 601 girls (49.5%). RESULTS: In the total sample of 1,494 children, parents were more likely to report excessive daytime sleepiness (EDS) in female children than in male children (p <.01), however, this association did not achieve significance in the sample of only white and Hispanic children (p <.07). Composite variables for EDS and witnessed apnea (WITAP) show that parents of Hispanic children were more likely to report EDS (p <.01) and WITAP (p <.007). Hispanic children were also more likely to have learning problems (LPs) [p <.03] and to snore frequently (SN) [p <.02] than were white children. There were no significant differences between boys and girls for SN or WITAP. Hispanic boys were more likely to have reports of EDS (p <.02) and LPs (p <.04) than white boys, however, there were no other significant differences in gender or ethnicity in reports of EDS or LPs for white or Hispanic boys and girls. Those children with frequent LPs were significantly more likely to have SN (p <.001), EDS (p <.001), and WITAP (p <.001). A logistic regression model predicting LP resulted in significant adjusted odds ratios (ORs) of 2.4 for SN, 2.5 for EDS, and 2.1 for children aged 8 to 11 years. A similar model for EDS resulted in significant adjusted ORs of 3.2 for SN, 5.7 for WITAP, and 1.6 for female gender. Ethnicity was not significant in either model. CONCLUSIONS: Hispanic children in the population-based TuCASA study experienced more frequent symptoms associated with SDB, such as SN, EDS, WITAP, and LPs, than did white children. Children with LPs are 2.4 times more likely to have SN, 2.5 times more likely to have EDS, and were 2.1 times more likely to be between the ages of 8 and 11 years. Children with EDS were 3.2 times more likely to have SN, 5.7 times more likely to have WITAP, and were 1.6 times more likely to be a girl.

Learning in children and sleep disordered breathing: findings of the Tucson Children's Assessment of Sleep Apnea (tuCASA) prospective cohort study.

We examined the relationship between nocturnal respiratory disturbance and learning and compared learning in children with and without nocturnal respiratory disturbance. Subjects were 149 participants in a prospective cohort study examining sleep in children ages 6-12: The Tucson Children's Assessment of Sleep Apnea study (TuCASA). Sleep was assessed via home polysomnography. Intelligence, learning and memory, and academic achievement were assessed. Parents rated attention. Group comparisons were used to test the hypothesis that the group with an apnea/hypopnea index (AHI) of 5 or more (n = 77) would have weaker performance than the group with AHI less than 5 (n = 72). The group with AHI of 5 or more had weaker learning and memory though differences between groups decreased when arousals were taken into account. There was a greater percentage of Stage 1 sleep in the AHI 5 or more group, and Stage 1 percentage was negatively related to learning and memory in the sample (n = 149). There were negative relationships between AHI and immediate recall, Full Scale IQ, Performance IQ, and math achievement. Hypoxemia was associated with lower Performance IQ. Thus, findings suggest that nocturnal respiratory disturbance is associated with decreased learning in otherwise healthy children, that sleep fragmentation adversely impacts learning and memory, and that hypoxemia adversely influences nonverbal skills.