Brain Tissue Integrity and Autonomic Function Alterations in Childhood OSA and ADHD, and After Adenotonsillectomy.

Summary

Obstructive sleep apnea (OSA) and attention-deficit/hyperactivity disorder (ADHD) are two common, severe disorders in children. Unfortunately, pediatric OSA is closely associated with ADHD, and both diseases can cause cognitive impairment, behavior problems, and low academic performance. OSA can damage the brain and induce autonomic dysfunction, and then cause cognitive, behavioral, and quality-of-life problems. The presence of ADHD can further exacerbate these adverse effects of OSA. Therefore, the identification of robust biomarkers of OSA and ADHD is a key imperative to facilitate early identification of the pathological features and mechanisms and to optimize the treatment of OSA and ADHD for the pediatric population. Diffusion MRI of the brain is one of the most widely used technology for assessment of brain tissue integrity and heart rate variability is one of the most widely used measurements of autonomic function. However, the effects of ADHD and adenotonsillectomy on MRI and HRV biomarkers in children with OSA have not been reported. We hypothesize that comorbid ADHD can deteriorate brain damage and autonomic dysfunction, and adenotonsillectomy can reverse these alternations in children with OSA. The aims of this study are (1) to investigate the differences in pediatric brain tissue integrity, autonomic function, attention, behavior, quality-of-life, and sleep factors between the 'OSA with ADHD', 'OSA without ADHD', and 'healthy control' group; (2) to evaluate the efficacy of adenotonsillectomy versus watchful waiting with supportive care, with respect to the same variables of interest; (3) to evaluate whether the relative efficacy of the treatment differs according to baseline ADHD, weight, or OSA severity; and (4) to develop a predictive model for surgical success rate using both conventional well-known factors and MRI/HRV biomarkers. This is a 3-year prospective study that includes two parts. The Part I study is a cross-sectional study recruiting 100 children (5 to 9 years of age) to investigate the differences in brain tissue integrity (voxel-based morphometry and fractional anisotropy; assessed by structure MRI \[T1\] for volumetric alternations of gray and white matter, resting-state functional MRI for functional connectivity, and diffusion MRI for white matter integrity), autonomic function (time-domain and frequency-domain analyses; assessed by a wearable, real-time HRV measurement), severity pf attentive and behavioral problems (assessed by the Swanson, Nolan and Pelham IV-Teacher and Parent Rating Scale), quality-of-life (assessed by OSA-18), and sleep factors (apnea-hypopnea index, obstructive apnea index, arousal index, mean and least oxygen saturation, and sleep stage; assessed by polysomnography) between the OSA with ADHD group (Study Group 1; n = 40), the OSA without ADHD group (Study Group 2; n = 40), and the healthy control group (Control Group; n = 20). The Part II study is a randomized controlled trial includes a total of 64 children with OSA (32 children will be recruited from Study Group 1 and Study Group 2, respectively). We randomly assigned (1:1) these 64 pediatric patients with OSA to adenotonsillectomy or a strategy of watchful waiting with supportive care, matched by ADHD, obesity, and severe OSA. Variables of interest using the same methodology are assessed at baseline and at 7 months.

Conditions

• Attention-deficit/Hyperactivity Disorder
• Autonomic Nervous System Imbalance
• Obstructive Sleep Apnea of Child

Interventions

BEHAVIORAL

Sleep and healthy lifestyle education

Participants in both groups will receive age-appropriate standardized educational material for both Optimal Sleep Hygiene and Healthy Habits. Educational play will also be encouraged by providing take-home materials. Participant and parent/legal guardian (s) will be given verbal and written directions on the use of these materials at the time of the visit. Research Coordinators will encourage and track utilization of the sleep hygiene educational tools during the trial.

OTHER

Other supportive care

Throughout the course of the trial participants identified by the principal investigator as having suboptimal asthma or rhinitis will be referred to their primary care physician for management and further treatment of these problems. All participants will receive a generic brand of an over-the-counter saline nasal spray to use as needed for nasal dryness and crusting. Proper use of the spray will be reviewed and demonstrated by the research coordinator at the baseline visit.

PROCEDURE

Adenotonsillectomy

Surgery will be performed by board-certified otolaryngologists with or without the assistance of resident physicians in accredited otolaryngology training programs. Prior to the surgical procedure, tonsillar size will be graded using a standardized scale of 0-4. Extent of adenoid tissue will also be graded as mild (0-33%), moderate (34-66%) or severely (67-100%) obstructing the posterior choanae. Complete bilateral tonsillectomy and removal of obstructing adenoid tissue will be performed by cold dissection, monopolar electrocautery or plasma knife-assisted surgical technique under general anesthesia. All procedures will be performed using inpatient facility for 3-4 days.

Sponsors & Collaborators

• Ministry of Science and Technology, Taiwan

  collaborator OTHER_GOV

• Chang Gung Memorial Hospital

  lead OTHER

Principal Investigators

• Li-Ang Lee, M.D., M.Sc. · Chang Gung Memorial Hospital, Linkou Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

5 Years

Max Age

10 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-08-01

Primary Completion

2023-07-31

Completion

2023-10-30

Countries

• Taiwan

Study Locations