The Effects of Obstructive Sleep Apnea Syndrome on the Dentate Gyrus and Learning and Memory in Children.

Obstructive sleep apnea syndrome (OSAS) is associated with intermittent hypoxia and sleep loss. In children, impairments of cognitive function are important manifestations, but the underlying pathology is unknown. We hypothesized that OSAS would affect the dentate gyrus, a hippocampal subdivision essential to neurogenesis and cognition, and that this impact would further affect cognitive function in children. In children with OSAS (n = 11) and control subjects (n = 12; age and sex matched), we performed diffusion tensor imaging and structural MRI, polysomnography, and neuropsychological assessments. We found that OSAS was associated with decreased mean diffusivity of the left dentate gyrus (p = 0.002; false discovery rate corrected; adjusting for sex, age, and body mass index), showing a large effect size (partial η2 = 0.491), but not with any other structural measures across the brain. Decreased dentate gyrus mean diffusivity correlated with a higher apnea hypopnea index (Spearman's r = -0.50, p = 0.008) and a greater arousal index (r = -0.44, p = 0.017). OSAS did not significantly affect neuropsychological measures (p values >0.5); however, a lower verbal learning score correlated with lower dentate gyrus mean diffusivity (r = 0.54, p = 0.004). Path analysis demonstrated that dentate gyrus mean diffusivity mediates the impact of OSAS on verbal learning capacity. Finally, the diagnostic accuracy of a regression model based on dentate gyrus mean diffusivity reached 85.8% (cross validated). This study demonstrates a likely pathway of effects of OSAS on neurocognitive function in children, as well as potential utility of the dentate gyrus mean diffusivity as an early marker of brain pathology in children with OSAS.SIGNIFICANCE STATEMENT In this study we investigate the relationships between dentate gyrus structure, hippocampus-dependent cognition, and obstructive sleep apnea syndrome (OSAS). We demonstrate lower mean diffusivity of the dentate gyrus in children with OSAS, which correlates with a lower verbal learning and memory score. This study provides new evidence of disrupted microstructure of the dentate gyrus in children with OSAS that may help explain some of the neurocognitive deficits described in these children.

Aerodigestive evaluation of pediatric patients with chronic aspiration.

OBJECTIVE: To evaluate the effectiveness of coordinated endoscopy with otolaryngology, pulmonology, and gastroenterology in diagnosing and managing chronic aspiration in pediatric patients. METHODS: We reviewed our REDCap Pediatric Aerodigestive Database for patients with chronic aspiration who underwent coordinated endoscopy between January 2013 and July 2023. Patient demographics, comorbidities, operative findings, interventions, and outcomes were reviewed. RESULTS: Forty-nine patients were identified with a diagnosis of aspiration. Their mean (SD) age was 28 (36) months (range 1.2-163 months) with more than half of the patients younger than 24 months. The most common findings noted on combined endoscopies were laryngeal cleft (n = 30), positive bacterial culture (n = 18), positive viral PCR (n = 17), and active reflux-induced esophagitis/gastritis (n = 9). Patients with a positive bacterial culture were associated with a history of recurrent pneumonia (p = 0.009). There were no other significant associations between endoscopy findings and patient demographics, co-morbidities, or symptoms. Twenty-five (51 %) had multiple abnormalities identified by at least 2 different specialists at the time of endoscopy and 6 patients (12 %) had abnormalities across all three specialists. CONCLUSION: Coordinated endoscopy should be considered in pediatric patients presenting with aspiration on MBS or non-specific symptoms suggestive for chronic aspiration for comprehensive diagnosis and management.

Complicated and dislodged airway foreign body in an intubated child: case report.

OBJECTIVE: We report a case of missed foreign body aspiration in a child presenting with status epilepticus. On admission, the patient was found to have pneumonia, which progressed to respiratory failure and acute respiratory distress syndrome. While the patient was intubated and mechanically ventilated, the patient experienced acute respiratory deterioration. Subsequently, it was determined that a previously undetected foreign body had dislodged from the right main to the left main bronchus and was the underlying cause for the child's illness. CONCLUSIONS: A combination of sudden change of physical and radiographic findings with unilateral lung hyperinflation is highly suspicious for an obstructing airway foreign body. This case demonstrates that foreign body aspiration can lead to significant morbidity. It should be in the differential diagnosis for any acute pulmonary process in an otherwise well child because there is no specific clinical or radiographic finding to rule it out.

Increased incidence of pediatric narcolepsy following the 2009 H1N1 pandemic: a report from the pediatric working group of the sleep research network.

This study was aimed to evaluate the yearly incidence of pediatric narcolepsy prior to and following the 2009 H1N1 pandemic and to evaluate seasonal patterns of narcolepsy onset and associations with H1N1 influenza infection in the United States. This was a multicenter retrospective study with prospective follow-up. Participants were recruited from members of the Pediatric Working Group of the Sleep Research Network including 22 sites across the United States. The main outcomes were monthly and yearly incident cases of childhood narcolepsy in the United States, and its relationship to historical H1N1 influenza data. A total of 950 participants were included in the analysis; 487 participants were male (51.3%). The mean age at onset of excessive daytime sleepiness (EDS) was 9.6  ±â€… 3.9 years. Significant trend changes in pediatric narcolepsy incidence based on EDS onset (p  <  .0001) occurred over the 1998-2016 period, peaking in 2010, reflecting a 1.6-fold increase in narcolepsy incidence. In addition, there was significant seasonal variation in narcolepsy incident cases, with increased cases in spring (p  <  .05). Cross-correlation analysis demonstrated a significant correlation between monthly H1N1 infection and monthly narcolepsy incident cases (p  =  .397, p  <  .0001) with a lag time of 8 months. We conclude that there is a significant increase in pediatric narcolepsy incidence after the 2009 H1N1 pandemic in the United States. However, the magnitude of increase is lower than reported in European countries and in China. The temporal correlation between monthly H1N1 infection and monthly narcolepsy incidence, suggests that H1N1 infection may be a contributing factor to the increased pediatric narcolepsy incidence after the 2009 H1N1 pandemics.

Venous thrombosis and pulmonary embolism in a child with pneumonia due to Mycoplasma pneumoniae.

A 13-year-old boy with Mycoplasma pneumoniae pulmonary infection developed deep vein thrombosis and pulmonary embolism. He was found to have protein S deficiency and transient antiphospholipid antibodies. Though uncommon, it is important to consider venous thromboembolic disease in children whose clinical course is atypically severe.

Association Between Periodic Limb Movements in Sleep and Cerebrovascular Changes in Children With Sickle Cell Disease.

STUDY OBJECTIVES: Periodic limb movements (PLMs) have been associated with increased risk of stroke, but there is currently scarce research exploring this relationship in the setting of sickle cell disease (SCD). The aim of this study was to explore whether increased PLMs in children with SCD are associated with increased risk of cerebrovascular disease and to determine if there are any clinical or laboratory differences between children with SCD with elevated periodic limb movement index (PLMI) versus those with normal PLMI. METHODS: This study is a comprehensive review of medical records of 129 children with SCD (aged ≤ 18 years) who had undergone polysomnography for evaluation of sleep-disordered breathing. RESULTS: Elevated PLMI (PLMI > 5 events/h) was present in 42% (54/129) of children with SCD. Children with elevated PLMI were found to have higher percentage of hemoglobin S, lower total iron, higher arousal index and tendency toward elevated transcranial Doppler velocity (P = .063, odds ratio = 3.9, 95% CI 0.93-16.22). While association between elevated PLMI and isolated cerebrovascular stenosis (P = .050, odds ratio 5.6, 95% CI 1.0-31.10) trended toward significance, there was significantly greater proportion of children with elevated PLMI who had cerebrovascular stenosis with Moyamoya disease (P = .046) as demonstrated by magnetic resonance imaging (MRI). CONCLUSIONS: The prevalence of elevated PLMI in children with SCD was higher than in previously published data. Elevated PLMI was significantly associated with greater rates of cerebrovascular disease as detected by MRI.

Adenotonsillectomy for sleep-disordered breathing in a predominantly obese pediatric population.

OBJECTIVES: To determine the efficacy of adenotonsillectomy (T&A) in the treatment of pediatric sleep-disordered breathing, and to determine the natural history in untreated children. METHODS: The charts of children aged 1-12 who underwent polysomnography (PSG) between 1/2006 and 6/2009 were reviewed to identify children with positive studies. Children not treated by T&A were recruited and matched by age, time since initial PSG, and apnea-hypopnea index (AHI) to children who underwent T&A. All participants were evaluated by a clinical assessment score (CAS-15), follow-up PSG, and the Child Behavior Checklist (CBCL). RESULTS: Sixteen matched pairs completed the study. Ten (63%) T&A patients were overweight or obese compared with 14 (88%) untreated patients. There was a greater median improvement in AHI in the surgical group compared to the nonsurgical group (10.3 vs. 6.5, p=0.044). Although the T&A children were more likely to have a follow-up AHI<5 (81% vs. 69%) and <1 (44% vs. 25%), these results were not significant. The T&A group had significantly lower mean (SD) scores on the CAS-15 [8.9(6.1) vs. 29.4(16.2), p<0.001] and the CBCL total problem score [43.9(8.7) vs. 58.9(13.0), p<0.001]. Younger age at presentation (rho=-0.76, p<0.001), initial AHI (0.87, p<0.001), and initial AI (0.63, p=0.05) were correlated with change in AHI among T&A subjects. CONCLUSIONS: T&A was more effective in reducing AHI than no surgery. Median AHI improved in the nonsurgical group, and 4/16 (25%) untreated patients were cured (AHI<1).

Validation of a clinical assessment score for pediatric sleep-disordered breathing.

OBJECTIVES/HYPOTHESIS: To validate a clinical assessment score for pediatric sleep-disordered breathing. STUDY DESIGN: Prospective instrument validation. METHODS: One hundred children scheduled for overnight polysomnography were evaluated by a standardized history and physical examination and assigned a clinical assessment score. Parents completed the Obstructive Sleep Apnea (OSA)-18, the Pediatric Quality of Life Inventory (PedsQL) 4.0, and the Child Behavior Checklist questionnaires. Children with positive polysomnography underwent adenotonsillectomy or adenoidectomy. The identical assessments were performed at a mean follow-up of 8 months. RESULTS: Item reduction yielded a score of 15 items (Clinical Assessment Score-15 [CAS-15]) that demonstrated the best internal consistency and predictive utility (Cronbach α = .80). Intraclass correlation (ICC) demonstrated good intrarater (ICC, 0.78; 95% confidence interval [CI], 0.58 to 0.89) and inter-rater agreement (ICC, 0.65; 95% CI, 0.26 to 0.84). All change scores were significantly improved after surgery. Effect sizes were large for the CAS-15 (2.6), OSA-18 (2.4), and apnea-hypopnea index (1.4), and moderate for the Child Behavior Checklist (0.7) and PedsQL 4.0 (-0.5). Moderate to strong correlation was found between the initial CAS-15 scores and the external measures (|r| between 0.32 and 0.65). Receiver operating characteristic curves were constructed to determine the optimal initial CAS-15 score for predicting positive polysomnography. The area under the curve was 0.77 (95% CI, 0.67 to 0.87); and a score ≥32 yielded a sensitivity of 77.3% (95% CI, 65.3 to 86.7) and a specificity of 60.7% (95% CI, 40.6 to 78.5). CONCLUSIONS: The CAS-15 proved useful in an office setting and correctly diagnosed 72% of referred children when compared to polysomnography. It correlated well with external measures and demonstrated a good response to clinical change.

Polysomnography outcomes for partial intracapsular versus total tonsillectomy.

OBJECTIVE: To demonstrate similar improvement in pediatric sleep-disordered breathing (SDB) as determined by polysomnography (PSG) with microdebrider-assisted partial intracapsular tonsillectomy and adenoidectomy (PITA) versus Bovie electrocautery complete tonsillectomy and adenoidectomy (T&A). METHODS: In this retrospective cohort study, 30 children found to have SDB by PSG who have undergone either PITA (15 participants) or T&A (15 participants) as treatment were evaluated with standardized history and physical examination and unattended home overnight PSG. RESULTS: Median change in apnea-hypopnea index (AHI) was 1.7 (-4.9 to 29.8) for the PITA group and 2.3 (-10.9 to 64.1) for the T&A group, although there was substantially more variability in the T&A group. A mixed linear model evaluating the relation of surgical group with change in AHI demonstrated no significant differences in group means (F[1,13]=0.31, P=.590) but the variances differed significantly (residual likelihood ratio chi-square=5.24, df=1, P=.022). Five of 15 (33%) PITA patients and 4 of 15 (27%) T&A patients had postoperative AHI scores of ≤5; this difference was not statistically significant (Fisher exact test P=1.000). There was no significant interaction or substantial confounding effect of age, sex, race, preoperative tonsil size, preoperative AHI, or body mass index in the model relating surgery type to reduction of postoperative AHI to ≤5. CONCLUSIONS: Our study demonstrates no clinically or statistically significant differences in PSG and clinical outcomes between PITA and T&A for treatment of pediatric SDB in otherwise healthy children.