Timothy F. Hoban

A randomized trial of adenotonsillectomy for childhood sleep apnea.

BACKGROUND Adenotonsillectomy is commonly performed in children with the obstructive sleep apnea syndrome, yet its usefulness in reducing symptoms and improving cognition, behavior, quality of life, and polysomnographic findings has not been rigorously evaluated. We hypothesized that, in children with the obstructive sleep apnea syndrome without prolonged oxyhemoglobin desaturation, early adenotonsillectomy, as compared with watchful waiting with supportive care, would result in improved outcomes. METHODS We randomly assigned 464 children, 5 to 9 years of age, with the obstructive sleep apnea syndrome to early adenotonsillectomy or a strategy of watchful waiting. Polysomnographic, cognitive, behavioral, and health outcomes were assessed at baseline and at 7 months. RESULTS The average baseline value for the primary outcome, the attention and executive-function score on the Developmental Neuropsychological Assessment (with scores ranging from 50 to 150 and higher scores indicating better functioning), was close to the population mean of 100, and the change from baseline to follow-up did not differ significantly according to study group (mean [±SD] improvement, 7.1±13.9 in the early-adenotonsillectomy group and 5.1±13.4 in the watchful-waiting group; P=0.16). In contrast, there were significantly greater improvements in behavioral, quality-of-life, and polysomnographic findings and significantly greater reduction in symptoms in the early-adenotonsillectomy group than in the watchful-waiting group. Normalization of polysomnographic findings was observed in a larger proportion of children in the early-adenotonsillectomy group than in the watchful-waiting group (79% vs. 46%). CONCLUSIONS As compared with a strategy of watchful waiting, surgical treatment for the obstructive sleep apnea syndrome in school-age children did not significantly improve attention or executive function as measured by neuropsychological testing but did reduce symptoms and improve secondary outcomes of behavior, quality of life, and polysomnographic findings, thus providing evidence of beneficial effects of early adenotonsillectomy. (Funded by the National Institutes of Health; CHAT ClinicalTrials.gov number, NCT00560859.).

Transient central nervous system white matter abnormality in X-linked Charcot-Marie-Tooth disease

X‐linked Charcot‐Marie‐Tooth disease (CMTX) is a hereditary demyelinating neuropathy caused by mutations in the connexin 32 (Cx32) gene. Cx32 is widely expressed in brain and peripheral nerve, yet clinical manifestations of CMTX mainly arise from peripheral neuropathy. We have evaluated two male patients with CMTX who on separate occasions developed transient ataxia, dysarthria, and weakness within 3 days of returning from ski trips at altitudes above 8,000 feet. Magnetic resonance imaging studies in both patients showed nonenhancing, confluent, and symmetrical white matter abnormalities that were more pronounced posteriorly and that resolved over several months. Magnetic transfer images in one patient demonstrated increased magnetization transfer ratios distinct from that seen in demyelination or edema. Both patients returned to their normal baseline within 2 to 3 weeks. These cases suggest that CMTX patients are at risk for developing an acute, transient, neurological syndrome when they travel to places at high altitudes and return to sea level. Cx32 mutations may cause central nervous system dysfunction by reducing the number of functioning gap junctions between oligodendrocytes and astrocytes, making both cells more susceptible to abnormalities of intercellular exchange of ions and small molecules in situations of metabolic stress.

Aggressive Behavior, Bullying, Snoring, and Sleepiness in Schoolchildren

BACKGROUND To assess whether urban schoolchildren with aggressive behavior are more likely than peers to have symptoms suggestive of sleep-disordered breathing. METHODS Cross-sectional survey of sleep and behavior in schoolchildren. Validated screening assessments for conduct problems (Connors rating scale), bullying behavior, and sleep-disordered breathing (pediatric sleep questionnaire) were completed by parents. Teachers completed Connors teacher rating scale. RESULTS Among 341 subjects (51% female), 110 (32%) were rated by a parent or teacher as having a conduct problem (T-score ⩾65) and 78 (23%) had symptoms suggestive of sleep-disordered breathing. Children with conduct problems, bullying, or discipline referrals, in comparison to non-aggressive peers, more often had symptoms suggestive of sleep-disordered breathing (each p<0.05). Children with vs. without conduct problems were more likely to snore habitually (p<0.5). However, a sleepiness subscale alone, and not a snoring subscale, predicted conduct problems after accounting for age, gender, a measure of socioeconomic status, and stimulant use. CONCLUSIONS Urban schoolchildren with aggressive behaviors may have symptoms of sleep-disordered breathing with disproportionate frequency. Sleepiness may impair emotional regulation necessary to control aggression.

Sleep disorders in children

Although sleep disorders such as insomnia and obstructive sleep apnea are common in both children and adults, the clinical features and treatments for these conditions differ considerably between these two populations. Whereas an adult with obstructive sleep apnea typically presents with a history of obesity, snoring, and prominent daytime somnolence, a child with the condition is more likely to present with normal body weight, tonsillar hypertrophy, and inattentiveness during school classes. The adult with suspected sleep apnea almost always undergoes a baseline polysomnogram and proceeds to treatment only if this test confirms the diagnosis, while many children with suspected sleep apnea are treated empirically with adenotonsillectomy without ever receiving a sleep study to verify the diagnosis. This article reviews sleep disorders in children, with a particular focus on age‐related changes in sleep, conditions that primarily affect children, and disorders for which clinical manifestations and treatment differ substantially from the adult population.

Esophageal Pressures, Polysomnography, and Neurobehavioral Outcomes of Adenotonsillectomy in Children

BACKGROUND Esophageal pressure monitoring during polysomnography in children offers a gold-standard, “preferred” assessment for work of breathing, but is not commonly used in part because prospective data on incremental clinical utility are scarce. We compared a standard pediatric apnea/hypopnea index to quantitative esophageal pressures as predictors of apnea-related neurobehavioral morbidity and treatment response. METHODS Eighty-one children aged 7.8 ± 2.8 (SD) years, including 44 boys, had traditional laboratory-based pediatric polysomnography, esophageal pressure monitoring, multiple sleep latency tests, psychiatric evaluations, parental behavior rating scales, and cognitive testing, all just before clinically indicated adenotonsillectomy, and again 7.2 ± 0.8 months later. Esophageal pressures were used, along with nasal pressure monitoring and oronasal thermocouples, not only to identify respiratory events but also more quantitatively to determine the most negative esophageal pressure recorded and the percentage of sleep time spent with pressures lower than -10 cm H(2)O. RESULTS Both sleep-disordered breathing and neurobehavioral measures improved after surgery. At baseline, one or both quantitative esophageal pressure measures predicted a disruptive behavior disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-defined attention-deficit/hyperactivity disorder, conduct disorder, or oppositional defiant disorder) and more sleepiness and their future improvement after adenotonsillectomy (each P < .05). The pediatric apnea/hypopnea index did not predict these morbidities or treatment outcomes (each P > .10). The addition of respiratory effort-related arousals to the apnea/hypopnea index did not improve its predictive value. Neither the preoperative apnea/hypopnea index nor esophageal pressures predicted baseline hyperactive behavior, cognitive performance, or their improvement after surgery. CONCLUSIONS Quantitative esophageal pressure monitoring may add predictive value for some, if not all, neurobehavioral outcomes of sleep-disordered breathing.

Non-respiratory indications for polysomnography and related procedures in children: An evidence-based review

OBJECTIVE This evidence-based review provides a systematic and comprehensive review of the literature regarding the utility of polysomnography for the evaluation of non-respiratory sleep disorders in children including hypersomnias, parasomnias, sleep-related movement disorders, and sleep in other special populations. METHODS A task force of pediatric sleep medicine experts performed a systematic review of the literature regarding the use of polysomnography for non-respiratory sleep disorders in children. They identified and graded 76 papers as evidence. RESULTS The main results include (1) polysomnography combined with the multiple sleep latency test is useful for evaluating disorders of excessive somnolence to objectively quantify sleepiness. The results have to be interpreted with consideration of the pubertal stage and regularity of the sleep patterns of the child; (2) polysomnography is indicated in children with parasomnias or sleep related movement disorders who have a high likelihood of having obstructive sleep apnea (OSA); (3) polysomnography is not routinely indicated in children with enuresis unless there is a high likelihood of OSA; (4) polysomnography can be helpful in evaluating children with restless legs syndrome (RLS) and when periodic limb movement disorder (PLMD) is suspected. CONCLUSIONS These findings suggest that, in children with non-respiratory sleep disorders, polysomnography should be a part of a comprehensive sleep evaluation in selected circumstances to determine the nature of the events in more detail or when the suspicion of OSA is relatively high.

Pediatric sleep-related breathing disorders and restless legs syndrome: How children are different

Sleep-related breathing disorders and restless legs syndrome have traditionally been felt to affect primarily adults. Recent research suggests that these conditions are surprisingly common in children as well, and that clinical manifestations may differ considerably from those seen in adults. This review summarizes the clinical characteristics, epidemiology, pathophysiology, and treatment of sleep-related breathing disorders and restless legs syndrome in children. Particular emphasis is placed on recent research and on how the presentation and treatment of these conditions are different in children compared with adults.

Sleeplessness in Children with Neurodevelopmental Disorders Epidemiology and Management

Sleeplessness, excessive waking and other disruptions of sleep are frequently evident in children with neurodevelopment disorders such as attention deficit hyperactivity disorder, specific genetic syndromes associated with mental retardation, autistic disorders and Tourette syndrome. The severity of sleep disruption may or may not parallel the severity of associated illness. Sleeplessness in this population is often additionally affected by concurrent medication use (such as central stimulants) and significant behavioural and environmental influences.When attempting to treat sleeplessness in children with neurodevelopmental disorders, the first step is to obtain an accurate sleep history documenting the child’s typical sleep schedule. The child should be screened for the presence of other extrinsic causes of sleep problems such as obstructive sleep apnoea and periodic limb movement, and use of medications known to disrupt sleep. These issues should be addressed if present. Nonpharmacological approaches to treatment include implementation of good sleep hygiene and the use of behavioural programmes. Pharmacotherapy has not been extensively studied in children with neurodevelopmental disorders, although limited data suggest that melatonin, clonidine, guanfacine and hypnosedatives can be moderately effective.

Longer Weekly Sleep Duration Predicts Greater 3-Month BMI Reduction among Obese Adolescents Attending a Clinical Multidisciplinary Weight Management Program

Aims: To determine whether baseline levels of self-reported sleep and sleep problems among obese adolescents referred to an outpatient multidisciplinary family-based weight management program predict reduction in BMI 3 months later. Methods: A retrospective medical chart review was conducted for 83 obese adolescents. The following baseline variables were extracted: self-reported sleep duration (weekdays and weekends), and presence of snoring, daytime fatigue, suspected sleep apnea, and physician-diagnosed sleep apnea. Anthropometric data at baseline and 3 months were also collected. Results: On average, adolescents reported significantly less sleeping on weeknights (7.7 ± 1.3 h) compared to weekend nights (10.0 ± 1.8 h), t(82) = 10.5, p = 0.0001. Reduction in BMI after 3 months of treatment was predicted by more weekly sleep at baseline (R2 = 0.113, F(1, 80) = 10.2, p = 0.002). Adolescents who reduced their BMI by ≥1 kg/m2 reported greater weekly sleep at baseline compared to adolescents who experienced <1 kg/m2 reduction (60.7 ± 7.5 h vs. 56.4 ± 8.6 h; F(1, 80) = 5.7, p = 0.02). Conclusion: Findings from this study, though correlational, raise the possibility that increased duration of sleep may be associated with weight loss among obese adolescents enrolled in a weight management program. Evidence-based behavioral techniques to improve sleep hygiene and increase sleep duration should be explored in pediatric weight management settings.

Do Respiratory Cycle-Related EEG Changes or Arousals from Sleep Predict Neurobehavioral Deficits and Response to Adenotonsillectomy in Children?

STUDY OBJECTIVES Pediatric obstructive sleep apnea (OSA) is associated with hyperactive behavior, cognitive deficits, psychiatric morbidity, and sleepiness, but objective polysomnographic measures of OSA presence or severity among children scheduled for adenotonsillectomy have not explained why. To assess whether sleep fragmentation might explain neurobehavioral outcomes, we prospectively assessed the predictive value of standard arousals and also respiratory cycle-related EEG changes (RCREC), thought to reflect inspiratory microarousals. METHODS Washtenaw County Adenotonsillectomy Cohort II participants included children (ages 3-12 years) scheduled for adenotonsillectomy, for any clinical indication. At enrollment and again 7.2 ± 0.9 (SD) months later, children had polysomnography, a multiple sleep latency test, parent-completed behavioral rating scales, cognitive testing, and psychiatric evaluation. The RCREC were computed as previously described for delta, theta, alpha, sigma, and beta EEG frequency bands. RESULTS Participants included 133 children, 109 with OSA (apnea-hypopnea index [AHI] ≥ 1.5, mean 8.3 ± 10.6) and 24 without OSA (AHI 0.9 ± 0.3). At baseline, the arousal index and RCREC showed no consistent, significant associations with neurobehavioral morbidities, among all subjects or the 109 with OSA. At follow-up, the arousal index, RCREC, and neurobehavioral measures all tended to improve, but neither baseline measure of sleep fragmentation effectively predicted outcomes (all p > 0.05, with only scattered exceptions, among all subjects or those with OSA). CONCLUSION Sleep fragmentation, as reflected by standard arousals or by RCREC, appears unlikely to explain neurobehavioral morbidity among children who undergo adenotonsillectomy. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, ID: NCT00233194.