Treatment of Childhood OSA Reverses Brain Abnormalities

Oral presentation: Sunday, May 20, 10:15AMMini-symposium: 8:15-10:45 a.m.Location: Room 2020-2022 (West Building, Level 2), Moscone Center

PRESS CONFERENCE: Sunday, May 20, 4:45 p.m.

Treatment of Childhood OSA Reverses Brain Abnormalities

Newswise — ATS 2012, SAN FRANCISCO - Treatment of obstructive sleep apnea (OSA) in children normalizes disturbances in the neuronal network responsible for attention and executive function, according to a new study.

"OSA is known to be associated with deficits in attention, cognition, and executive function," said lead author Ann Halbower, MD, Associate Professor at the Children's Hospital Sleep Center and University of Colorado Denver. "Our study is the first to show that treatment of OSA in children can reverse neuronal brain injury, correlated with improvements in attention and verbal memory in these patients."

The results will be presented at the ATS 2012 International Conference in San Francisco.

In the study, children (ages 8-11) with moderate-severe OSA were compared to healthy controls. Brain imaging with magnetic resonance spectroscopy imaging was performed at baseline in 15 OSA patients and seven controls, along with neuropsychological testing. OSA treatment consisted of adenotonsillectomy followed by monitored continuous positive airway pressure (CPAP) or nasal treatments. Brain imaging and neuropsychological testing was performed again in 11 OSA patients and the seven controls six months after treatment.

Compared with controls at baseline, children with OSA exhibited significantly decreased N-acetyl aspartate to choline ratios (NAA/Cho) in the left hippocampus and left frontal cortex, along with significant decreases in the executive functions of verbal memory, and attention. Following treatment, both left and right frontal cortex neuronal metabolites normalized, and hippocampal metabolites improved with a medium effect size (0.5).

More complete reversal of hippocampal abnormalities was seen in children with milder OSA when apnea-hypopnea index (AHI) improved (although this is very preliminary data). Verbal memory and attention improved with medium to large effect sizes. Improvements in attention and verbal memory were correlated with normalization of NAA/Cho in the right and left frontal cortex (p=0.5).

"We have demonstrated for the first time that treatment of OSA in children normalizes brain metabolites in portions of the neuronal network responsible for attention and executive function," concluded Dr. Halbower. “We speculate that if OSA is treated earlier, there may be a more brisk improvement in the hippocampus, a relay station for executive function, learning, and memory.”

“Our results point to the importance of early diagnosis and treatment of OSA in children, as it could potentially have profound effects on their development."

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“Brain Injury And Cognitive Deficits Reverse With Treatment Of Childhood Obstructive Sleep Apnea” (Session A19, Sunday, May 20, 10:15 a.m., Room 2020-2022, Moscone Center; Abstract 33865)

* Please note that numbers in this release may differ slightly from those in the abstract. Many of these investigations are ongoing; the release represents the most up-to-date data available at press time.

Abstract 33865Brain Injury And Cognitive Deficits Reverse With Treatment Of Childhood Obstructive Sleep ApneaType: Late Breaking AbstractCategory: 14.04 - Pediatric Sleep and Control of Breathing (PEDS/SRN)Authors: A.C. Halbower1, J. Janusz1, M. Brown2, J. Strain1, N. Friedman2, F. Accurso1, P.L. Smith3; 1Children's Hospital Colorado and University of Colorado Denver - Aurora, CO/US, 2University of Colorado Denver - Aurora/US, 3Johns Hopkins University - Baltimore/US

Abstract BodyIntroduction : To determine the reversibility of brain neuronal abnormalities with treatment of Pediatric Obstructive Sleep Apnea (OSA), OSA patients were compared to healthy controls (HC) matched by age, gender, race, and SES. We hypothesized that neuronal alterations of the hippocampus and frontal cortex associated with childhood sleep-disordered breathing would reverse with treatment.

Methods : OSA patients (N=17) and healthy controls (N=11) age 8-11 years, Tanner stage I-II, underwent neuropsychological tests spanning 7 domains. Magnetic resonance spectroscopy imaging of the brain was performed in 15 OSA and 7 HC. OSA patients underwent Adenotonsillectomy followed by monitored CPAP if AHI>3, or nasal treatments if AHI 2-3. Six months after treatment, 11 OSA patients returned for brain imaging and neuropsychological tests compared to HC.

Results : Results: Children were mean age 10 yr, 55% male, 50% Hispanic, 20% AA. Mean OAHI for OSA patients = 13.6, for HC =0.3. Confirming our previous findings, N-acetyl aspartate to choline ratios (NAA/Cho) in the left hippocampus and left frontal cortex were significantly decreased in OSA patients compared to HC (p=0.03 and 0.04 respectively). OSA patients had a significant decrease in the executive function of working memory (p= 0.00), attention (p=0.00) and verbal memory (p=0.02). After treatment, both left and right frontal cortex neuronal metabolites normalized (p= 0.03) while the hippocampal metabolites did not. Verbal memory improved (p=0.04) and improvements in attention were correlated with the normalization of NAA/Cho in the frontal lobes (r=0.67, p=0.05).

Conclusion: Conclusion: This is the first study demonstrating that brain metabolites of the neuronal network responsible for attention and executive function, the frontal cortex, normalize with treatment of pediatric OSA. Improvements in attention were correlated with the normalization of metabolites in the frontal lobes. We speculate that earlier diagnosis and treatment of childhood OSA may improve the trajectory of development, thus implying the need to identify these patients and expedite management.

Funded by: National Institutes of Health, National Center for Research Resources