Transitional care and clinical management of adolescents, young adults, and suspected new adult patients with congenital central hypoventilation syndrome.

PURPOSE: With contemporaneous advances in congenital central hypoventilation syndrome (CCHS), recognition, confirmatory diagnostics with PHOX2B genetic testing, and conservative management to reduce the risk of early morbidity and mortality, the prevalence of identified adolescents and young adults with CCHS and later-onset (LO-) CCHS has increased. Accordingly, there is heightened awareness and need for transitional care of these patients from pediatric medicine into a multidisciplinary adult medical team. Hence, this review summarizes key clinical and management considerations for patients with CCHS and LO-CCHS and emphasizes topics of particular importance for this demographic. METHODS: We performed a systematic review of literature on diagnostics, pathophysiology, and clinical management in CCHS and LO-CCHS, and supplemented the review with anecdotal but extensive experiences from large academic pediatric centers with expertise in CCHS. RESULTS: We summarized our findings topically for an overview of the medical care in CCHS and LO-CCHS specifically applicable to adolescents and adults. Care topics include genetic and embryologic basis of the disease, clinical presentation, management, variability in autonomic nervous system dysfunction, and clarity regarding transitional care with unique considerations such as living independently, family planning, exposure to anesthesia, and alcohol and drug use. CONCLUSIONS: While a lack of experience and evidence exists in the care of adults with CCHS and LO-CCHS, a review of the relevant literature and expert consensus provides guidance for transitional care areas.

Persistent obstructive sleep apnoea in children: treatment options and management considerations.

Unresolved obstructive sleep apnoea (OSA) after an adenotonsillectomy, henceforth referred to as persistent OSA, is increasingly recognised in children (2-18 years). Although associated with obesity, underlying medical complexity, and craniofacial disorders, persistent OSA also occurs in otherwise healthy children. Inadequate treatment of persistent OSA can lead to long-term adverse health outcomes beyond childhood. Positive airway pressure, used as a one-size-fits-all primary management strategy for persistent childhood OSA, is highly efficacious but has unacceptably low adherence rates. A pressing need exists for a broader, more effective management approach for persistent OSA in children. In this Personal View, we discuss the use and the need for evaluation of current and novel therapeutics, the role of shared decision-making models that consider patient preferences, and the importance of considering the social determinants of health in research and clinical practice. A multipronged, comprehensive approach to persistent OSA might achieve better clinical outcomes in childhood and promote health equity for all children.

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.

Clinical efficacy and safety of intravenous ferric carboxymaltose treatment of pediatric restless legs syndrome and periodic limb movement disorder.

BACKGROUND: Iron supplementation is the most commonly considered treatment option for children with restless legs syndrome (RLS) or periodic limb movement disorder (PLMD); however, there is a scarcity of evidence on the effectiveness of intravenous preparations. In this study, we evaluated the effectiveness and tolerability of intravenous ferric carboxymaltose (IV FCM) on clinical symptoms and iron indices in children with RLS or PLMD. METHODS: This was a single-center retrospective data analysis. Children with a diagnosis of RLS or PLMD, who underwent a single infusion of IV FCM, were included. Clinical Global Impression (CGI) Scale scores, serum ferritin, and serum iron profile at baseline and after eight weeks post infusion were obtained. Adverse effects were assessed. RESULTS: Thirty-nine children received IV FCM, 29 with RLS and 10 with PLMD. Pre-infusion CGI-Severity revealed moderate illness, with post-infusion CGI-Improvement between "very much improved" and "much improved". Ferritin increased from 14.6 µg/L±7.01 to 112.4 µg/L±65.86 (p < 0.00001), together with improvements in iron, total iron binding capacity, and transferrin levels from baseline to post-treatment. When compared to children with RLS, those with PLMD had a similar improvement in clinical symptoms and laboratory parameters. Seven subjects (14.3%) experienced one or two adverse events; all were mild. CONCLUSIONS: Children with RLS and PLMD responded to IV iron supplementation with improvement in both clinical severity and laboratory parameters. Treatment was well tolerated. Although larger, randomized-controlled trials are needed, IV FCM appears to be a promising alternative to oral iron supplementation for the treatment of pediatric RLS or PLMD.

Cleft palate morphology, genetic etiology, and risk of mortality in infants with Robin sequence.

Robin sequence (RS) has many genetic and nongenetic causes, including isolated Robin sequence (iRS), Stickler syndrome (SS), and other syndromes (SyndRS). The purpose of this study was to determine if the presence and type of cleft palate varies between etiologic groups. A secondary endpoint was to determine the relationship of etiologic group, cleft type, and mortality. Retrospective chart review of patients with RS at two high-volume craniofacial centers. 295 patients with RS identified. CP was identified in 97% with iRS, 95% with SS, and 70% of those with SyndRS (p < .0001). U-shaped CP was seen in 86% of iRS, 82% with SS, but only 27% with SyndRS (p < .0001). At one institution, 12 children (6%) with RS died, all from the SyndRS group (p < .0001). All died due to medical comorbidities related to their syndrome. Only 25% of children who died had a U-shaped CP. The most common palatal morphology among those who died was an intact palate. U-shaped CP was most strongly associated with iRS and SS, and with a lower risk of mortality. RS with submucous CP, cleft lip and palate or intact palate was strongly suggestive of an underlying genetic syndrome and higher risk of mortality.

Lifetime Care of Duchenne Muscular Dystrophy.

Individuals with Duchenne muscular dystrophy (DMD) have evolving sleep and respiratory pathophysiology over their lifetimes. Across the lifespan of DMD, various sleep-related breathing disorders (SRBD) have been described, including obstructive sleep apnea, central sleep apnea, and nocturnal hypoventilation. In addition to SRBD, individuals with DMD can be affected by insomnia, chronic pain and other factors interfering with sleep quality, and daytime somnolence. The natural progression of DMD pathophysiology has changed with the introduction of therapies for downstream pathologic pathways and will continue to evolve with the development of therapies that target function and expression of dystrophin.

Sleep intervention for children with asthma and their parents (SKIP Study): a novel web-based shared management pilot study.

STUDY OBJECTIVES: The objective of this study was to describe the feasibility, acceptability, and preliminary efficacy of a novel Sleep Intervention for Kids and Parents (SKIP). Parent and child primary sleep outcomes were total sleep time, wake after sleep onset (WASO), sleep efficiency (SE), and bedtime range. METHODS: Children 6-11 years of age with asthma and 1 parent, both with behavioral sleep disturbance, enrolled in this single-group pilot. The 8-week shared management intervention included weekly online educational modules, goal setting, and progress reporting. Feasibility was measured by the number of dyads who were eligible, enrolled, and retained. Acceptability was measured by survey and semistructured interview. Total sleep time, WASO, SE, and bedtime range were measured by actigraphy at baseline, after the intervention, and 12-week follow-up. Mixed-effects regression models were used to determine change in sleep outcomes from baseline. RESULTS: Thirty-three of 39 eligible dyads enrolled; of 29 dyads that started the intervention, 25 (86%) completed all study visits. SKIP was acceptable for 61% of children and 92% of parents. Compared with baseline, at follow-up, children had significantly improved WASO (-37 minutes; 95% confidence interval [CI], -44.5 to -29.7; P < .001), SE (5.4%; 95% CI, 4.2-6.5; P < .001), and bedtime range (-35.2 minutes; 95% CI, -42.9 to -27.5; P < .001). Parents also had significantly improved WASO (-13.9 minutes; 95% CI, -19.5 to -8.2; P < .001), SE (2.7%; 95% CI, 1.7-.7; P < .001), and bedtime range (-35.3 minutes; 95% CI, -51.0 to -19.7; P < .001). CONCLUSIONS: SKIP was feasible, acceptable, and we observed improved child and parent sleep outcomes except total sleep time. Following refinements, further testing of SKIP in a controlled clinical trial is warranted. Clinical Trial Registration: Registry: ClinicalTrials.gov; Name: Sleep Intervention for Kids and Parents: A Self-Management Pilot Study; URL: https://www.clinicaltrials.gov/ct2/show/study/NCT03144531; Identifier: NCT03144531.

Polysomnography outcomes of sleep endoscopy-directed intervention in surgically naïve children at risk for persistent obstructive sleep apnea.

PURPOSE: Drug-induced sleep endoscopy (DISE) is useful in children with obstructive sleep apnea (OSA) that persists after adenotonsillectomy (AT), but its utility in surgically naïve children is unclear. We report polysomnography outcomes of surgically naïve children who underwent DISE-directed intervention because they were considered high risk for persistent OSA after adenotonsillectomy. METHODS: This study is a case series of 62 surgically naïve children with OSA who were considered high risk for persistence after AT and underwent DISE-directed intervention with pre- and postoperative polysomnography between 2012 and 2016. Analysis was performed with the paired t test. RESULTS: Children were on average 5.9 (± 5.5, 0.2-18.6) years old at the time of surgery, 68% male, 18% obese, and 60% white. Thirty-eight percent had a syndromic diagnosis: 19% trisomy 21, 11% hypotonic neuromuscular disorder, and 8% craniofacial condition. The remaining 62% were non-syndromic but underwent DISE because they had at least one risk factor for OSA persistence after AT (age > 7 years, black race, 1+ tonsils, obesity, and/or severe OSA). Forty-two percent underwent AT, while 58% underwent treatment other than AT, including 18% who had multilevel surgery. Children improved significantly in 4 out of 5 polysomnography parameters tested, including obstructive apnea-hypopnea index (oAHI; 22.2 to 7.2, p < 0.01) and oxygen nadir (82 to 87, p < 0.01). Thirty-eight (61%) had a postoperative oAHI < 5; 16 (21%) had a postoperative oAHI < 2. CONCLUSION: DISE resulted in intervention other than AT in 58% of surgically naïve children at high risk for persistent OSA after AT. DISE-directed intervention resulted in significant mean improvement in postoperative OSA.

Healthcare recommendations for Joubert syndrome.

Joubert syndrome (JS) is a recessive neurodevelopmental disorder defined by a characteristic cerebellar and brainstem malformation recognizable on axial brain magnetic resonance imaging as the "Molar Tooth Sign". Although defined by the neurological features, JS is associated with clinical features affecting many other organ systems, particularly progressive involvement of the retina, kidney, and liver. JS is a rare condition; therefore, many affected individuals may not have easy access to subspecialty providers familiar with JS (e.g., geneticists, neurologists, developmental pediatricians, ophthalmologists, nephrologists, hepatologists, psychiatrists, therapists, and educators). Expert recommendations can enable practitioners of all types to provide quality care to individuals with JS and know when to refer for subspecialty care. This need will only increase as precision treatments targeting specific genetic causes of JS emerge. The goal of these recommendations is to provide a resource for general practitioners, subspecialists, and families to maximize the health of individuals with JS throughout the lifespan.

Polysomnography outcomes in children with small tonsils undergoing drug-induced sleep endoscopy-directed surgery.

OBJECTIVES/HYPOTHESIS: The optimal surgical treatment to improve sleep apnea in children with small tonsils is not known. Drug-induced sleep endoscopy (DISE) may be useful in selecting effective surgical procedures for this patient population. This study compared polysomnography (PSG) measures before and after DISE-directed surgery in children with small tonsils. We hypothesize that DISE-directed surgery improves PSG measures in children with small tonsils. We also aimed to identify the most common surgery performed in this population. STUDY DESIGN: Retrospective chart review. METHODS: A retrospective review was performed of subjects who underwent DISE at a single pediatric tertiary care center over a 6-year period. Inclusion criteria were 1+ tonsils and PSG performed before and after DISE-directed surgery. Exclusion criteria were previous tonsillectomy and tonsils score 2+ or greater. Pre- and postoperative PSG parameters were compared using paired t tests. RESULTS: Average age was 7 ± 4 years old at the time of surgery. The most common DISE-directed intervention was supraglottoplasty (n = 23). DISE-directed surgery significantly improved mean apnea-hypopnea index (AHI) from 14.4 to 8.0 (P = .02). Although improvements were seen in mean obstructive AHI (12.5 to 5.5), O2 nadir (87.0 to 88.3), and ODI (10.6 to 5.8), these measures did not reach statistical significance. CONCLUSIONS: DISE-directed surgery significantly improves AHI in children with small tonsils. The most common intervention performed on these children was supraglottoplasty. Interestingly, adenotonsillectomy was rarely performed in this cohort. Additionally, supraglottic collapse, prompting supraglottoplasty, is difficult to accurately assess in an awake child, supporting use of a DISE-directed approach in this patient population. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:2771-2774, 2019.

Does drug induced sleep endoscopy-directed surgery improve polysomnography measures in children with Down Syndrome and obstructive sleep apnea?

BACKGROUND: Children with Down Syndrome (DS) and obstructive sleep apnea (OSA) are difficult to treat, as first line therapies may not lead to significant improvement. Drug-induced sleep endoscopy (DISE) directed surgery may be particularly beneficial for these patients. OBJECTIVE: To assess change in polysomnography (PSG) measures of patients with DS who underwent DISE-directed surgery. METHODS: Retrospective chart review was performed on patients with DS who underwent DISE-directed surgery and had pre- and post-surgery PSG. Patients were analyzed in groups defined by previous adenotonsillectomy. Two-sided t-tests with equal variances were used to assess statistical significance. RESULTS: Of 24 patients reviewed, 14 were surgically naïve and 10 had undergone prior adenotonsillectomy. The primary outcome was change in PSG parameters including apnea hypopnea index, obstructive apnea hypopnea index, oxygen nadir, oxygen desaturation index, and mean carbon dioxide level. While improvement was seen in all PSG parameters, only improvement in oxygen nadir in children who had undergone prior adenotonsillectomy was statistically significant (88.5% to 90.9%, p = .04). CONCLUSIONS AND SIGNIFICANCE: DISE-directed surgery may be beneficial for children with DS and OSA, with improvement in the means of main PSG measures observed. A larger, prospective study is warranted to further explore DISE utility.

Clinically small tonsils are typically not obstructive in children during drug-induced sleep endoscopy.

OBJECTIVE: To determine whether the degree of lateral pharyngeal wall (LPW) obstruction on pediatric drug-induced sleep endoscopy (DISE) correlates with preprocedure tonsillar hypertrophy score on physical examination, and to determine if clinically small tonsils are obstructive. METHODS: Retrospective review of 154 patients who underwent DISE at a single pediatric tertiary care center over a 4-year period. Inclusion criteria were documentation of Brodsky tonsil score on preoperative physical examination. Exclusion criteria were previous tonsillectomy, adenoidectomy, or adenotonsillectomy. Lateral pharyngeal wall obstruction was graded for each patient from 0 (no obstruction) to 3 (severe obstruction) using a validated pediatric DISE scoring system known as the Chan-Parikh scoring system (C-P). Data were analyzed using multivariate linear regression controlling for age at time of DISE and presence of comorbid conditions. RESULTS: One hundred fifteen patients met criteria for analysis. Median age at DISE was 5.1 years. A moderate positive correlation was calculated between Brodsky score and DISE score, Spearman correlation coefficient 0.55, P = < 0.001. Linear regression modeling determined that for every 1-point increase in tonsil score, there was a 0.7-point increase in C-P LPW score (95% confidence interval [0.45, 0.92]). Sensitivity analysis did not detect a difference in correlation between children with comorbid conditions and children who were otherwise in good health. Of the 65 children with a pre-DISE Brodsky tonsil score of 1, 39 (60%) had a LPW score of 0 (no obstruction); nine (14%) had a score of 1 (< 50% obstruction); 11 (17%) had a score of 2 (> 50% obstruction); and six (9%) had a score of 3 (100% obstruction). CONCLUSION: There is a positive correlation between Brodsky Score and DISE LPW score. The majority of children with sleep-disordered breathing with a Brodsky score of 1 did not demonstrate LPW obstruction. These children may benefit from DISE for identification of alternative sites of upper airway obstruction. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:1943-1949, 2017.

Airway Obstruction during Drug-Induced Sleep Endoscopy Correlates with Apnea-Hypopnea Index and Oxygen Nadir in Children.

OBJECTIVE: To determine if standardized intraoperative scoring of anatomic obstruction in children with obstructive sleep apnea correlates with the apnea-hypopnea index (AHI) and lowest oxygen saturation on preprocedural polysomnogram (PSG). A secondary objective was to determine if age, presence of a syndrome, or previous adenotonsillectomy affect this correlation. STUDY DESIGN: Case series with chart review. SETTING: Two tertiary care children's hospitals. SUBJECTS: Patients with a preprocedural PSG who underwent drug-induced sleep endoscopy (DISE) over a 4-year period. METHODS: All DISEs were graded in a systematic manner with the Chan-Parikh (C-P) scoring system. AHI and nadir oxygen saturations were extracted from preprocedural PSG. Data were analyzed with a multivariate linear regression model that controlled for age at time of sleep endoscopy, syndrome diagnosis, and previous adenotonsillectomy. RESULTS: A total of 127 children underwent PSG prior to DISE: 56 were syndromic, and 21 had a previous adenotonsillectomy. Mean AHI was 13.6 ± 19.6 (± SD), and mean oxygen nadir was 85.4% ± 9.4%. Mean C-P score was 5.9 ± 2.7. DISE score positively correlated with preoperative AHI (r = 0.36, P < .0001) and negatively correlated with oxygen nadir (r = -0.26, P = .004). The multivariate linear regression models estimated that for every 1-point increase in C-P score, there is a 2.6-point increase in AHI (95% confidence interval: 1.4-3.8, P < .001) and a 1.1% decrease in the lowest oxygen saturation (95% confidence interval: -1.7 to -0.6, P < .001). CONCLUSION: The C-P scoring system for pediatric DISE correlates with both AHI and lowest oxygen saturation on preprocedural PSG.

Midfacial and Dental Changes Associated with Nasal Positive Airway Pressure in Children with Obstructive Sleep Apnea and Craniofacial Conditions.

STUDY OBJECTIVES: Nasal positive airway pressure (nPAP) for treatment of pediatric obstructive sleep apnea (OSA) is a widespread therapy that currently lacks longitudinal data describing how mask pressure impacts the developing facial skeleton. This retrospective cohort study compared midfacial growth in pediatric patients with underlying craniofacial conditions diagnosed with OSA who were compliant vs. noncompliant with nPAP therapy, and explored correlations between demographic, medical, and sleep variables with annual rate of facial change. METHODS: Records from Seattle Children's Hospital's Craniofacial Center and Sleep Disorders Center were reviewed to identify patients prescribed nPAP for OSA with serial cephalographic images obtained during routine clinical care for concomitant craniofacial diagnosis. Lateral cephalometric analysis was used to determine mean annual change in midfacial structures from T1 (pre-nPAP) to T2 (post-nPAP) in compliant vs. noncompliant subjects. Compliance was indicated by nPAP usage of > 20 h/week for > 6 months. RESULTS: 50 subjects were compliant with nPAP therapy (mean age 10.42 years) for an average of 2.57 years, and 50 subjects were noncompliant (mean age 8.53 years). Compliant subjects experienced negative mean annual change (retrusion) of the midface compared to forward growth seen in noncompliant subjects (SNA: -0.57° vs. 0.56°), counterclockwise rotation of palatal plane (SN-PP: -1.15° vs. 0.09°), and upper incisor flaring (U1-SN: 2.41° vs. -0.51°). CONCLUSIONS: Pressure to the midface from compliant nPAP use may alter normal facial growth. Cephalometric findings indicate a greater need for collaboration between sleep medicine physicians and orthodontists to monitor midfacial growth during nPAP treatment.

Obesity management in Prader-Willi syndrome.

Prader-Willi Syndrome (PWS) is one of the most common genetic causes of obesity. The phenotype of obesity in PWS is unique and characterized by hyperphagia, earlier meal initiation, delayed meal termination, reduced energy expenditure, abnormal gut hormone profiles, as well as irregular responses to food in areas of the brain associated with satiety and reward. Management of obesity is necessary to avoid major morbidity. The relentless food-seeking behavior associated with PWS such as stealing, hoarding food, eating inedibles, and lying about eating, can cause turmoil both inside and outside of the home. Management is challenging for both patients and caretakers, but at this time there are limited medical therapies available besides dietary restriction and behavior management. However, current research shows promise for discovery of additional treatment options for hyperphagia and obesity management in PWS.

Supraglottoplasty for sleep endoscopy diagnosed sleep dependent laryngomalacia.

OBJECTIVES: To evaluate the polysomnographic outcomes of supraglottoplasty (SGP) performed for sleep endoscopy diagnosed sleep dependent laryngomalacia as treatment for obstructive sleep apnea syndrome (OSAS). METHODS: Nine subjects aged 6-55 months underwent supraglottoplasty for sleep dependent laryngomalacia. All subjects underwent both pre- and post-procedural polysomnograms. RESULTS: Supraglottoplasty for sleep dependent laryngomalacia resulted in improvement of OSAS as measured by collective improvements in 8 different primary polysomnogram parameters: apnea-hypopnea index (AHI), minimum (nadir) and mean oxygen saturation, mean and maximum carbon dioxide, total sleep time, sleep efficiency, arousal index, as well as improvement in weight for length percentiles. Subjects had a significant 80% decrease in percentage change in AHI (p<0.005), with decrease in mean AHI from 23.4 to 4.8 following supraglottoplasty. Seven of 9 subjects demonstrated improvement in nadir saturations, 6 of 9 subjects had improvement in sleep efficiency, and 7 of 8 subjects under 4 years of age had improvement in weight for length percentile. CONCLUSIONS: Supraglottoplasty for sleep dependent laryngomalacia is an effective treatment of OSAS, and can be readily diagnosed using sleep endoscopy. Further investigation is warranted to increase awareness and outcomes related to sleep dependent laryngomalacia.

Sleep-disordered breathing in children with thoracic insufficiency syndrome.

Thoracic insufficiency syndrome (TIS) is a collection of chest and spine malformations that results in progressively restrictive pulmonary mechanics and an inability of the thorax to adequately support lung growth. Many children with TIS are too young to perform standard pulmonary function tests, yet need functional assessments of their restrictive thoracic disease. We report on the sleep architecture and frequency of sleep-related breathing abnormalities in 11 children with TIS who underwent overnight polysomnography from retrospective chart review. Ten of 11 (92%) had sleep disordered breathing as defined by currently accepted criteria of apnea-hypopnea index (AHI) >2 events/hr. The median AHI was 4.3 events/hr, with obstructive hypopneas (median 3.7 events/hr) accounting for 75% of abnormalities. Respiratory events occurred most frequently during REM sleep (median REM-AHI 17.3 events/hr), and were associated with oxyhemoglobin desaturation, and rarely carbon dioxide retention. Sleep disordered breathing with hypoxemia appears to be a common but under recognized problem among children with TIS. Polysomnogram may have a role as a non-invasive screening tool used in conjunction with other functional respiratory assessments in children with TIS, and warrants further study in a prospective manner.