Pediatric Sleep Apnea: The Overnight Electroencephalogram as a Phenotypic Biomarker

Abstract

Pediatric obstructive sleep apnea (OSA) is a prevalent disorder that disrupts sleep and is associated with neurocognitive and behavioral negative consequences, potentially hampering the development of children for years. However, its relationships with sleep electroencephalogram (EEG) have been scarcely investigated. Here, our main objective was to characterize the overnight EEG of OSA-affected children and its putative relationships with polysomnographic measures and cognitive functions. A two-step analysis involving 294 children (176 controls, 57% males, age range: 5–9 years) was conducted for this purpose. First, the activity and irregularity of overnight EEG spectrum were characterized in the typical frequency bands by means of relative spectral power and spectral entropy, respectively: δ1 (0.1–2 Hz), δ2 (2–4 Hz), θ (4–8 Hz), α (8–13 Hz), σ (10–16 Hz), β1 (13–19 Hz), β2 (19–30 Hz), and γ (30–70 Hz). Then, a correlation network analysis was conducted to evaluate relationships between them, six polysomnography variables (apnea–hypopnea index, respiratory arousal index, spontaneous arousal index, overnight minimum blood oxygen saturation, wake time after sleep onset, and sleep efficiency), and six cognitive scores (differential ability scales, Peabody picture vocabulary test, expressive vocabulary test, design copying, phonological processing, and tower test). We found that as the severity of the disease increases, OSA broadly affects sleep EEG to the point that the information from the different frequency bands becomes more similar, regardless of activity or irregularity. EEG activity and irregularity information from the most severely affected children were significantly associated with polysomnographic variables, which were coherent with both micro and macro sleep disruptions. We hypothesize that the EEG changes caused by OSA could be related to the occurrence of respiratory-related arousals, as well as thalamic inhibition in the slow oscillation generation due to increases in arousal levels aimed at recovery from respiratory events. Furthermore, relationships between sleep EEG and cognitive scores emerged regarding language, visual–spatial processing, and executive function with pronounced associations found with EEG irregularity in δ1 (Peabody picture vocabulary test and expressive vocabulary test maximum absolute correlations 0.61 and 0.54) and β2 (phonological processing, 0.74; design copying, 0.65; and Tow 0.52). Our results show that overnight EEG informs both sleep alterations and cognitive effects of pediatric OSA. Moreover, EEG irregularity provides new information that complements and expands the classic EEG activity analysis. These findings lay the foundation for the use of sleep EEG to assess cognitive changes in pediatric OSA.

Sensorimotor Cortical Activity during Respiratory Arousals in Obstructive Sleep Apnea

“…However, it should be noted that Ohisa et al did not further classify the different OSA severities and focused on sleep efficiency rather than disease severity. On the other hand, similar to our findings, Gutierrez-Tobal et al showed in their study that patients with obstructive apnea showed a higher EEG frequency and SpEn measures [41]. Even though they attribute this to thalamic inhibition in obstructive sleep apnea, the reason why the thalamus function is inhibited remains unclear.…”

Gain-of-function mutations in KCNK3 cause a developmental disorder with sleep apnea

“…Despite the many phenotypic features shared by the probands, the two with variants in the M4 helix were much less severely affected than those with variants in M2, showing only mild developmental delay and no structural abnormalities combined with only mild or borderline moderate sleep apnea according to their AHI classification, which differs in children compared to adults 55,56 . Interestingly, these M4 variants (L239P and L241F) produced the smallest overall increase in whole-cell currents.…”

Changes in Functional Connectivity of Hippocampal Subregions in Patients with Obstructive Sleep Apnea after Six Months of Continuous Positive Airway Pressure Treatment

“…The study by Lee et al showed that the nodal betweenness centrality of the left FFG in children with OSA was significantly reduced (a higher nodal betweenness centrality indicates a high degree of interaction between brain regions), and hypoxia may be a key factor leading to the decrease in structural interaction between brain regions [78]. In addition, multiple OSArelated studies have found abnormalities in visual network function [79][80][81]. Maresky et al reported that CPAP treatment can improve the functional anisotropy and mean diffusivity of white matter fibrous nodules in visual network-related areas of patients with OSA, and that the changes in white matter fibers were related to rCBF and cerebral blood volume increase [82].…”