Brain Changes in Pediatric OSA

Obstructive sleep apnea (OSA) is highly prevalent in children and is often caused by overgrowth of the child's adenoids and/or tonsils. Consequently, adenotonsillectomy (removal of the tonsils and adenoids) is the most common treatment of OSA in children, although just the tonsils or adenoids may be removed depending on the case. As well, OSA in children is often associated with cognitive dysfunction and mood issues, suggesting brain changes due to the condition. However, the link between brain changes, cognitive and moods issues, and OSA in children has not been thoroughly explored. Therefore, this study aims to examine brain changes, cognition and mood in pediatric OSA subjects compared to controls as well as before and after removal of the adenoids and/or tonsils. This study hopes to enroll 70 subjects, ages 7-12 years, 35 healthy controls and 35 subjects diagnosed with OSA and scheduled for an adenoidectomy and/or tonsillectomy. Control subjects will schedule one visit to UCLA and OSA subjects will schedule two. Upon the first visit, all subjects will undergo cognitive, mood and sleep questionnaires and MRI scanning. That will be the duration of the controls' participation in the study; however, OSA subjects will return 6 months later (after their adenoidectomy and/ or tonsillectomy) to repeat the same procedures. Sleep quality, mood, cognition and brain images will be compared between OSA and controls and between OSA subjects before surgery and after surgery.

Pediatric obstructive sleep apnea (OSA) is a common and progressive syndrome accompanied by severe cognition, mood, and daytime behavioral issues, as well as poor school performance, presumably stemming from compromised neural tissue, induced by intermittent hypoxia and perfusion changes. However, it is unclear whether the brain tissue injury is in acute or chronic condition, and whether myelin is preferentially affected than axons, an essential step to understand, since interventions for neural repair/recovery differ for acute vs chronic and myelin vs axonal injury. Also, it is unclear whether accompanying brain changes in pediatric OSA have functional consequences, resulting to cognitive or mood deficits. In addition, intermittent hypoxia triggers a cascade of injurious processes affecting endothelial cells, but unclear whether regional cerebral blood flow (CBF) is reduced in pediatric OSA. Treatment methods for pediatric OSA include tonsillectomy and/or adenoidectomy, and it is unclear whether brain tissue changes, regional CBF, and neural responses to cognitive challenge improve post-treatment. Using diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI)-based procedures, acute and chronic tissue changes and axonal status and myelin integrity can be assessed. Regional brain CBF can be assessed by validated arterial spin labeling (ASL) imaging, and regional neural activity to cognitive challenge can be examined with blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (MRI). Thus, using 35 treatment-naïve, pediatric OSA and 35 control children, the specific aims are to; determine the nature and types of brain tissue injury, using DTI and DKI measures, in untreated pediatric OSA over healthy controls; identify regional brain CBF, using ASL imaging, and neural responses to cognitive challenge, using BOLD functional MRI in pediatric OSA over healthy children; assess cognitive (by the differential ability scale II and NEPSY II) and emotion functions (by the child behavior checklist) in pediatric OSA compared to control children, and examine relationships between brain injury and cognitive and emotion dysfunctions in pediatric OSA; and examine whether brain tissue changes, reduced CBF, and altered neural responses to cognitive challenge reverse, and cognition and mood signs improve after adenotonsillectomy at 6 months in pediatric OSA. In summary, the nature and types of brain injury, regional CBF changes, and neural responses to cognitive challenge, and whether brain tissue changes, altered CBF, and diminished neural responses, as well as mood and cognitive functions recover after adenotonsillectomy in pediatric OSA will be examined. Evaluation of pathological characteristics is essential to assess the mechanisms of damage, and to suggest intervention strategies before and after surgery. The findings will also help guide potential treatments to rescue/restore brain tissue (e.g., nonsteroidal anti-inflammatory drugs) and improve CBF that could be implemented to benefit cognitive and mood health, and improve academic performance in pediatric OSA.

The investigators will also determine whether brain tissue changes, reduced CBF, and altered neural responses to cognitive challenge reverse, and cognition and mood signs improve after standard surgical procedure "adenotonsillectomy" for breathing condition at 6 months in pediatric OSA.

Adenotonsillectomy is a standard surgical procedure for pediatric OSA treatment, which involves removal of hypertrophied tonsils and adenoids.

The investigators will examine whether brain tissue changes reverse after adenotonsillectomy in pediatric obstructive sleep apnea subjects. The investigators will use diffusion tensor imaging based mean diffusivity and diffusion kurtosis imaging based mean kurtosis measures to examine brain tissue changes; both procedures examine brain tissue integrity with mean diffusivity showing reduced and mean kurtosis indicating increased values in acute tissue changes, and with mean diffusivity showing increased and mean kurtosis showing reduced values in chronic tissue changes.

Using arterial spin labeling magnetic resonance imaging, the investigators will assess if regional cerebral blood flow improves after standard obstructive sleep apnea surgery in pediatric subjects. The cerebral blood flow values reduce with hypo-perfusion and increase with hyper-perfusion.

Using functional magnetic resonance imaging, the investigators will examine whether neural responses in brain cognitive control sites to arithmetic cognitive challenge will improve after adenotonsillectomy compared to baseline in pediatric obstructive sleep apnea subjects.

The investigators will examine cognitive symptom changes after adenotonsillectomy in pediatric obstructive sleep apnea subjects. The investigators will use the Differential Ability Scale II for cognition evaluation. The Differential Ability Scale II scores range from 30-170, with reduced values indicating impaired cognition (General Conceptual Ability score <90, abnormal; General Conceptual Ability score > 90-170, normal).

The investigators will assess cognition changes after adenotonsillectomy in pediatric obstructive sleep apnea subjects. The investigators will use the NEuroPSYchological Assessment II for cognition examination. The NEuroPSYchological Assessment II scores will be lower with impaired cognition (Scaled score <8, abnormal; Scaled score 8-19, normal).

The investigators will examine mood changes after adenotonsillectomy in pediatric obstructive sleep apnea subjects using the Child Behavior Checklist. The Child Behavior Checklist scores will be higher with mood symptoms in pediatric obstructive sleep apnea compared to control children (t-scores, 65-69 borderline; >70 clinical).

Inclusion Criteria: OSA Pediatric OSA subjects will be in the age range 7-12 years (upper and lower age limit will be chosen to avoid developmental-related brain changes and potential requirement of anesthesia for brain MRI) Have a diagnosis of at least moderate OSA (AHI>5 events/hour) via overnight polysomnography at a sleep laboratory Without obesity (≥95th percentile BMI for age and sex) to avoid perioperative issues No treatment for the breathing condition Undergoing for adenotonsillectomy. Control subjects Healthy children Age-range from 7-12 years (within ±3 months) Sex- and BMI-matched (±2 kg/m2) to pediatric OSA No medications for brain disorders Without any diagnosed neurological condition Exclusion Criteria: Previous history of diagnosed psychiatric diseases (depression and other brain disorders that may introduce brain injury) Cystic fibrosis, concussion, and presence of space-occupying brain lesions Metallic or electronic implants and other MRI-specific exclusion criteria

Once the findings have been published, the MRI data (devoid of individual identifiers) will be placed on a read-only anonymous file transfer protocol (ftp) server, with access in the conventional fashion by email ID. Investigators, who request access to the data, will e-mail us with an academic e-mail address and provide a description of their proposed project/purpose. Access to the data will be given to requesting investigator, as long as project does not require personal identifiable information. Such storage represents a substantial commitment of capacity, since the data are expected to require several terabytes. The MRI data (both pre- and post-surgery at 6 months), cognition and mood scores, and OSA disease severity from the same population will be especially valuable to the field, as it is rare to have from patients with pediatric OSA.

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