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      Childhood Obstructive Sleep Apnea Associates with Neuropsychological Deficits and Neuronal Brain Injury

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          Abstract

          Background

          Childhood obstructive sleep apnea (OSA) is associated with neuropsychological deficits of memory, learning, and executive function. There is no evidence of neuronal brain injury in children with OSA. We hypothesized that childhood OSA is associated with neuropsychological performance dysfunction, and with neuronal metabolite alterations in the brain, indicative of neuronal injury in areas corresponding to neuropsychological function.

          Methods and Findings

          We conducted a cross-sectional study of 31 children (19 with OSA and 12 healthy controls, aged 6–16 y) group-matched by age, ethnicity, gender, and socioeconomic status. Participants underwent polysomnography and neuropsychological assessments. Proton magnetic resonance spectroscopic imaging was performed on a subset of children with OSA and on matched controls. Neuropsychological test scores and mean neuronal metabolite ratios of target brain areas were compared.

          Relative to controls, children with severe OSA had significant deficits in IQ and executive functions (verbal working memory and verbal fluency). Children with OSA demonstrated decreases of the mean neuronal metabolite ratio N-acetyl aspartate/choline in the left hippocampus (controls: 1.29, standard deviation [SD] 0.21; OSA: 0.91, SD 0.05; p = 0.001) and right frontal cortex (controls: 2.2, SD 0.4; OSA: 1.6, SD 0.4; p = 0.03).

          Conclusions

          Childhood OSA is associated with deficits of IQ and executive function and also with possible neuronal injury in the hippocampus and frontal cortex. We speculate that untreated childhood OSA could permanently alter a developing child's cognitive potential.

          Abstract

          Childhood obstructive sleep apnea is associated with deficits of IQ and executive function and also with possible neuronal injury in the hippocampus and frontal cortex.

          Editors' Summary

          Background.

          Sleep is essential for health, and in children it is crucial to normal development. Symptomatic childhood sleep-disordered breathing (SDB) is the name for a range of conditions in which children have difficulties with breathing when they are asleep. The conditions range from simple snoring to the most severe condition, known as obstructive sleep apnea (OSA). Apnea means a temporary absence of breathing, and in OSA this is caused by a temporary but repeated blockage of the flow of air to the lungs. In children, OSA occurs for a number of reasons including enlarged tonsils, long-term allergy, and obesity. About two in every hundred children have OSA. The symptoms of OSA are loud snoring at night, disrupted, restless sleep, undue tiredness, and difficulties in concentration. The main test for it is a sleep study (polysomnography). If untreated, researchers believe that it may lead to a number of long-term problems with health and learning; children with disorders of sleep have been shown to have memory problems, lower general intelligence, and worse executive function (the ability to adapt to new situations), and may have behavioral problems similar to those of attention deficit hyperactivity disorder (ADHD).

          Why Was This Study Done?

          Adults with sleep apnea have been shown to have abnormalities of parts of their brain, specifically the frontal cortex, cerebellum, and hippocampus, but so far there are no data on whether there are similar changes in children. Children with sleep apnea may have cognitive deficits, but the research on this topic is limited.

          What Did the Researchers Do and Find?

          The researchers wanted to investigate the brains of children with OSA to see if there was any evidence of changes in the brain and if these changes were associated with any learning problems. They studied 31 children (19 with OSA and 12 healthy controls, aged 6–16 y). Participants underwent polysomnography and neuropsychological assessments, such as IQ tests and tests of their ability to perform tasks involving decision making. Some of the children also had specialized scans of their brains (known as proton magnetic resonance spectroscopic imaging) that can measure the levels of certain metabolites—substances that are produced as a result of brain activity. The researchers then compared the neuropsychological test scores with the levels of the metabolites. They found that relative to controls, children with severe OSA had lower IQ and ability to perform tasks involving decision making. Children with OSA also had changes in metabolites in the brain similar to those seen in diseases in which there is damage to brain cells.

          What Do These Findings Mean?

          It seems clear that OSA in children is associated with learning problems, and that these learning problems may in turn be associated with changes in brain metabolites. The changes in metabolites are not necessarily permanent—in other diseases where changes have been found they can be reversed with treatment. If these results are confirmed in other children with OSA, it will highlight the importance of treating children for OSA as soon as possible. In addition, the measurement of metabolites may be a way of measuring how well children are responding to treatment.

          Additional Information.

          Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030301.

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          Most cited references 85

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          Generalized eta and omega squared statistics: measures of effect size for some common research designs.

          The editorial policies of several prominent educational and psychological journals require that researchers report some measure of effect size along with tests for statistical significance. In analysis of variance contexts, this requirement might be met by using eta squared or omega squared statistics. Current procedures for computing these measures of effect often do not consider the effect that design features of the study have on the size of these statistics. Because research-design features can have a large effect on the estimated proportion of explained variance, the use of partial eta or omega squared can be misleading. The present article provides formulas for computing generalized eta and omega squared statistics, which provide estimates of effect size that are comparable across a variety of research designs.
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            EEG arousals: scoring rules and examples: a preliminary report from the Sleep Disorders Atlas Task Force of the American Sleep Disorders Association.

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              Sleep-disordered breathing and school performance in children.

               D Gozal (1998)
              To assess the impact of sleep-associated gas exchange abnormalities (SAGEA) on school academic performance in children. Prospective study. Urban public elementary schools. Two hundred ninety-seven first-grade children whose school performance was in the lowest 10th percentile of their class ranking. Children were screened for obstructive sleep apnea syndrome at home using a detailed parental questionnaire and a single night recording of pulse oximetry and transcutaneous partial pressure of carbon dioxide. If SAGEA was diagnosed, parents were encouraged to seek medical intervention for SAGEA. School grades of all participating children for the school year preceding and after the overnight study were obtained. SAGEA was identified in 54 children (18.1%). Of these, 24 underwent surgical tonsillectomy and adenoidectomy (TR), whereas in the remaining 30 children, parents elected not to seek any therapeutic intervention (NT). Overall mean grades during the second grade increased from 2.43 +/- 0.17 (SEM) to 2.87 +/- 0.19 in TR, although no significant changes occurred in NT (2.44 +/- 0.13 to 2.46 +/- 0.15). Similarly, no academic improvements occurred in children without SAGEA. SAGEA is frequently present in poorly performing first-grade students in whom it adversely affects learning performance. The data suggest that a subset of children with behavioral and learning disabilities could have SAGEA and may benefit from prospective medical evaluation and treatment.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS Med
                pmed
                PLoS Medicine
                Public Library of Science (San Francisco, USA )
                1549-1277
                1549-1676
                August 2006
                22 August 2006
                : 3
                : 8
                Affiliations
                [1 ]Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
                [2 ]Department of Radiology, Johns Hopkins University School of Medicine, and FM Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United States of America
                [3 ]Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
                [4 ]Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
                [5 ]Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
                [6 ]Department of Neuropsychology, Kennedy Krieger Institute, Baltimore, Maryland, United States of America
                [7 ]Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
                Sleep Medicine Research Center, United States of America
                Author notes
                * To whom correspondence should be addressed. E-mail: ahalbowe@ 123456jhmi.edu
                Article
                06-PLME-RA-0016R2 plme-03-08-33
                10.1371/journal.pmed.0030301
                1551912
                16933960
                e48e519f-dc2a-4d82-9f80-4ca6e1633011
                Copyright: © 2006 Halbower et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                Page count
                Pages: 12
                Categories
                Research Article
                Neuroscience
                Psychology
                Medical Imaging
                Mental Health
                Pediatrics
                Respiratory Medicine
                Pediatrics
                Children
                Sleep Disorders
                Custom metadata
                Halbower AC, Degaonkar M, Barker PB, Earley CJ, Marcus CL, et al. (2006) Childhood obstructive sleep apnea associates with neuropsychological deficits and neuronal brain injury. PLoS Med 3(8): e301. DOI: 10.1371/journal.pmed.0030301

                Medicine

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