Tracheostomy decannulation to noninvasive positive pressure ventilation in congenital central hypoventilation syndrome.

PURPOSE: Noninvasive positive pressure ventilation (NPPV) may permit tracheostomy decannulation (TD) in patients with congenital central hypoventilation syndrome (CCHS) requiring nocturnal positive pressure ventilation via tracheostomy (PPV-T). There is limited evidence on optimal strategies for transitioning patients from PPV-T to NPPV. This study aimed to describe the clinical course and outcome of children with CCHS who underwent TD and transitioned from PPV-T to NPPV. METHODS: Retrospective review was conducted on patients with CCHS using nocturnal PPV-T who underwent TD to NPPV. The results of clinical evaluations, airway endoscopy, polysomnography, and clinical course leading to TD were analyzed. RESULTS: We identified 3 patients with CCHS aged 8-17 years who required PPV-T only during sleep. Patients underwent systematic multidisciplinary evaluations with a pediatric psychologist, pulmonologist, sleep physician, and otolaryngologist utilizing a TD algorithm. These included evaluation in the sleep clinic, NPPV mask fitting and desensitization, endoscopic airway evaluation, daytime tracheostomy capping, acclimatization to low-pressure NPPV, polysomnography with capped tracheostomy and NPPV titration, and if successful, TD. All patients underwent successful TD following optimal titration of NPPV during polysomnography. The duration to TD from decision to pursue NPPV was between 2.4 and 10.6 months, and the duration of hospitalization for TD was between 4 and 5 days. There were no NPPV-related complications; however, all patients required surgical closure of tracheocutaneous fistula. CONCLUSION: NPPV may be an effective and feasible option for patients with CCHS requiring PPV-T during sleep and permits TD. In patients with CCHS, a systematic multidisciplinary algorithm may optimize successful transition to NPPV and TD.

Multisystem approach for management of OSA in Down syndrome: a case report.

Obstructive sleep apnea (OSA) is common in children with Down syndrome, with reported prevalence rates as high as 69-76%. Multiple factors predispose children with Down syndrome for OSA, including craniofacial hypoplasia (maxillary and mandibular), airway abnormalities, macroglossia, generalized hypotonia, airway hypotonia, adenotonsillar hypertrophy, and obesity. Despite the fact that the pathophysiology for OSA in children with Down syndrome is multifactorial in nature, treatment methods have focused on soft tissue in the upper airway using adenotonsillectomy and/or continuous positive airway pressure therapy. Here we present a case of a patient with Down syndrome whose severe OSA was approached in a multisystem manner, including upper airway soft tissue, orthognathic, maxillofacial, and bariatric surgery, resulting in resolution of the OSA without reliance on a continuous positive airway pressure device. CITATION: Finch CE, Raol N, Roser SM, Leu RM. Multisystem approach for management of OSA in Down syndrome: a case report. J Clin Sleep Med. 2024;20(3):471-473.

Images: Atypical presentation of congenital central hypoventilation syndrome in an infant with central and obstructive sleep apnea.

Congenital central hypoventilation syndrome (CCHS), a rare disease caused by paired-like homeobox 2B variants, affects control of breathing. We report on a 21-month-old boy with CCHS caused by a novel nonpolyalanine repeat mutation, neuroblastoma, severe obstructive and central sleep apnea, and sleep-related hypoxemia without hypoventilation. At 10 months, due to persistent central sleep apnea during serial polysomnography, bilevel positive airway pressure therapy was initiated despite the absence of hypoventilation. Nonpolyalanine repeat mutations are associated with severe phenotypes requiring continuous assisted ventilation, Hirschsprung's disease, and neural crest tumors; however, our patient had a relatively milder respiratory phenotype requiring sleep-only assisted ventilation without tracheostomy. Although alveolar hypoventilation is the hallmark of CCHS, our patient lacked hypoventilation. Bilevel positive airway pressure could be considered in some infants with CCHS requiring sleep-only assisted ventilation for tracheostomy avoidance. Our case demonstrates the expanding phenotypic spectrum in CCHS and the importance of formulating an individualized care plan. CITATION: Fain ME, Raghunandan S, Pencheva B, Leu RM, Kasi AS. Images: atypical presentation of congenital central hypoventilation syndrome in an infant with central and obstructive sleep apnea. J Clin Sleep Med. 2024;20(3):478-481.

Increasing access to evidence-based insomnia care in the United States: findings from an American Academy of Sleep Medicine stakeholder summit.

Challenges exist in access to high-quality care for insomnia disorder. After the recent publication of a clinical practice guideline on behavioral and psychological treatments for insomnia in adults, the American Academy of Sleep Medicine (AASM) hosted a 1-day virtual Insomnia Summit in September 2022 to discuss improving care for patients with insomnia disorder. Fifty participants representing a variety of organizations (eg, medical, psychological, and nursing associations; patient advocacy groups; and federal institutions) participated in the event. Videos highlighting patient perspectives on insomnia and an overview of current insomnia disorder treatment guidelines were followed by thematic sessions, each with 3 to 4 brief, topical presentations by content experts. Breakout groups were used to brainstorm and prioritize issues in each thematic area. Top barriers to care for insomnia disorder include limited access, limited awareness of treatment options, low perceived value of insomnia treatment, and an insufficient number of trained clinicians. Top facilitators of high-quality care include education and awareness, novel care models to increase access, expanding the insomnia patient care workforce, incorporating research into practice, and increasing reimbursement for psychotherapies. Priorities for the future include increasing awareness among patients and providers, increasing the number of skilled behavioral sleep medicine providers, increasing advocacy efforts to address insurance issues (eg, billing, reimbursement, and performance measures), and working collaboratively with multidisciplinary organizations to achieve common goals. These priorities highlight that goals set to improve accessible, high-quality care for insomnia disorder will require sustained, coordinated efforts to increase awareness, improve reimbursement, and grow the necessary skilled health care workforce. CITATION: Schotland H, Wickwire E, Aaronson RM, et al. Increasing access to evidence-based insomnia care in the United States: findings from an American Academy of Sleep Medicine stakeholder summit. J Clin Sleep Med. 2024;20(3):455-459.

Restless legs syndrome in children with chronic kidney disease.

BACKGROUND: Restless legs syndrome (RLS) is considerably more common among adults with chronic kidney disease (CKD) than in the general population and is associated with increased morbidity and mortality. There is limited information on RLS in children with CKD. Failure to account for conditions that might mimic RLS can lead to overdiagnosis of this syndrome. METHODS: In a prospective, cross-sectional study, RLS prevalence was compared between pediatric CKD patients and healthy children. RLS was assessed via a questionnaire that included exclusion of mimics. Sleep characteristics and health-related quality of life (HRQoL) were also assessed. RESULTS: Restless legs syndrome was more prevalent in CKD patients (n = 124) than in 85 normal children (15.3 vs. 5.9 %; p = 0.04). There was no significant association between RLS and CKD stage, CKD etiology, CKD duration, and dialysis or transplant status. Children with RLS were more likely to rate their sleep quality as fairly bad or very bad (41.2 vs. 8.8 %; p = 0.003) and report using sleep medications (42.1 vs. 14.7 %; p = 0.01). RLS was associated with lower HRQoL by parent report (p = 0.03). Only five of the 19 patients (26.3 %) with CKD and RLS had discussed RLS symptoms with a healthcare provider, and only one of these patients had been diagnosed with RLS prior to this study. CONCLUSIONS: The prevalence of RLS is increased in children with CKD and appears to be underdiagnosed. Systematic screening for RLS and sleep problems would therefore appear to be warranted in children with CKD.

Sleep disturbances in parental caregivers and patients with congenital central hypoventilation syndrome.

STUDY OBJECTIVES: Congenital central hypoventilation syndrome (CCHS) is a rare disease characterized by impaired control of breathing caused by paired-like homeobox 2B (PHOX2B) gene variants, necessitating lifelong assisted ventilation (AV). This study aimed to assess sleep quality in patients with CCHS and their parents using sleep questionnaires. METHODS: Parents of patients with CCHS completed the Pittsburgh Sleep Quality Index (PSQI) regarding their sleep and the Sleep Disturbance Scale for Children (SDSC) regarding their child's sleep. RESULTS: Twenty participants completed the questionnaires. The median (interquartile range) ages of the parents and patients were 41.5 (38.5-51.5) and 11.5 (7.4-16.7) years, respectively. The median (interquartile range) PSQI and SDSC scores were elevated at 6.5 (4-10) and 41.5 (34-51.5), respectively, suggesting that parents and patients with CCHS can experience sleep disturbances and poor sleep quality. There were no significant differences in SDSC (P = 1.0) and PSQI (P = .76) scores for AV with or without tracheostomy. Similarly, there were no significant differences in SDSC (P = .22) and PSQI (P = .34) scores based on PHOX2B genotypes. There was a moderately strong, significant, and positive correlation between the CCHS SDSC scores and parental PSQI scores (r = .48, P = .03), suggesting that sleep disturbances in patients with CCHS were associated with poor parental sleep quality. There was no difference in the median parental sleep duration between those with and without nighttime home nursing (P = .09). CONCLUSIONS: Patients with CCHS and their parents are at risk for sleep disturbances regardless of their AV modality and PHOX2B genotype. In addition to AV management, patients with CCHS and their parents should be assessed for sleep disturbances. CITATION: Finch CE, Leu RM, Harford K-L, Westbrook AL, Kasi AS. Sleep disturbances in parental caregivers and patients with congenital central hypoventilation syndrome. J Clin Sleep Med. 2023;19(3):549-554.

Images: Caffeine therapy for central sleep apnea, hypoxemia, and hypoventilation in a term neonate.

The evaluation of higher-risk infants with brief resolved unexplained events and term infants with central sleep apnea can be clinically challenging due to the multitude of potential etiologies. We report a 7-day-old term neonate hospitalized for evaluation of brief resolved unexplained events with oxygen desaturations during sleep. Polysomnography showed central sleep apnea, hypoxemia, hypoventilation, periodic breathing, and mild obstructive sleep apnea. Following initial evaluations and while awaiting genetic testing, primary central sleep apnea of infancy was suspected and caffeine was initiated. Three days after initiating caffeine, polysomnography showed resolution of hypoxemia, hypoventilation, obstructive sleep apnea, and periodic breathing and improved central sleep apnea. The central apnea-hypopnea index reduced from 58 to 6.8 events/h. Although caffeine is utilized in apnea of prematurity, there is limited literature regarding caffeine in term infants with apnea. Our case demonstrates that in term infants with primary central sleep apnea of infancy, immature regulation of respiration may persist and a trial of caffeine could be considered. CITATION: Shah AS, Leu RM, Shah SP, Martinez F, Kasi AS. Caffeine therapy for central sleep apnea, hypoxemia, and hypoventilation in a term neonate. J Clin Sleep Med. 2023;19(5):1005-1008.

Congenital Central Hypoventilation Syndrome: Optimizing Care with a Multidisciplinary Approach.

Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder affecting respiratory control and autonomic nervous system function caused by variants in the paired-like homeobox 2B (PHOX2B) gene. Although most patients are diagnosed in the newborn period, an increasing number of patients are presenting later in childhood, adolescence, and adulthood. Despite hypoxemia and hypercapnia, patients do not manifest clinical features of respiratory distress during sleep and wakefulness. CCHS is a lifelong disorder. Patients require assisted ventilation throughout their life delivered by positive pressure ventilation via tracheostomy, noninvasive positive pressure ventilation, and/or diaphragm pacing. At different ages, patients may prefer to change their modality of assisted ventilation. This requires an individualized and coordinated multidisciplinary approach. Additional clinical features of CCHS that may present at different ages and require periodic evaluations or interventions include Hirschsprung's disease, gastrointestinal dysmotility, neural crest tumors, cardiac arrhythmias, and neurodevelopmental delays. Despite an established PHOX2B genotype and phenotype correlation, patients have variable and heterogeneous clinical manifestations requiring the formulation of an individualized plan of care based on collaboration between the pulmonologist, otolaryngologist, cardiologist, anesthesiologist, gastroenterologist, sleep medicine physician, geneticist, surgeon, oncologist, and respiratory therapist. A comprehensive multidisciplinary approach may optimize care and improve patient outcomes. With advances in CCHS management strategies, there is prolongation of survival necessitating high-quality multidisciplinary care for adults with CCHS.

Recurrent apnoea and respiratory failure in an infant: congenital central hypoventilation syndrome with a novel PHOX2B gene variant.

A 20-day-old term infant presented with recurrent apnoea, lethargy and respiratory failure. Examination revealed episodes of apnoea and desaturation to 85% without any signs of respiratory distress requiring initiation of non-invasive positive pressure ventilation (NPPV). Capillary blood gas was indicative of respiratory acidosis and serum bicarbonate was elevated at 35 mmol/L. Chest radiograph, echocardiogram and evaluations for infectious aetiologies resulted normal. Due to inability to wean off NPPV with ensuing apnoea and desaturation, polysomnogram was performed and showed central and obstructive sleep apnoea, hypoxaemia and hypoventilation. Central apnoeas and hypoventilation were worse in non-rapid eye movement sleep. Paired-like homeobox 2B genetic studies showed a novel non-polyalanine repeat mutation (c.429+1G>A) establishing the diagnosis of congenital central hypoventilation syndrome (CCHS). Our case highlights the utility of polysomnography in the evaluation of term infants with apnoea. Although rare, clinicians should consider a diagnosis of CCHS in the evaluation of infants with apnoea and hypoventilation.

Annual Respiratory Evaluations in Congenital Central Hypoventilation Syndrome and Changes in Ventilatory Management.

Background: Annual in-hospital respiratory evaluations (AREs) during wakefulness and sleep are recommended to assess ventilatory requirements in patients with congenital central hypoventilation syndrome (CCHS) aged ≥2-3 years based on expert consensus. This study aimed to determine if AREs in patients with CCHS led to changes in ventilatory management. Methods: Retrospective review of patients with CCHS who underwent AREs with or without polysomnography between 2017 and 2019 was conducted. Clinical symptoms, results of AREs, and subsequent changes in ventilatory management were analyzed. Results: We identified 10 patients with CCHS aged 4-20 years. All patients required assisted ventilation (AV) only during sleep delivered by positive pressure ventilation via tracheostomy (n = 7) or diaphragm pacing (n = 3). In total, 7 (70%) patients had abnormal oxygenation and/or ventilation requiring changes in ventilator settings or duration of AV. Six patients required an increase in settings and/or duration of AV, and only 1 patient required a decrease in ventilator settings. Two patients had awake hypercapnia during a routine outpatient visit that improved following increase in ventilator settings and a period of continuous AV. One patient who was previously ventilator-dependent only during sleep was identified to require 16 h per day of AV. All patients (n = 3) who reported symptoms such as headache or oxygen desaturations during sleep required an increase in ventilator settings. Conclusion: We report a high prevalence of changes in AV management following an ARE. Our results demonstrate the importance of regular AREs in patients with CCHS to assess their ventilatory requirements and optimize AV.

Images: Polysomnographic artifacts in a child with congenital central hypoventilation syndrome.

NONE: Diaphragm pacing (DP), a modality of ventilatory support in children with congenital central hypoventilation syndrome, generates respiration using the patient's own diaphragm as the respiratory pump. We report a 14-year-old boy with congenital central hypoventilation syndrome who uses DP with an uncapped tracheostomy during sleep. Polysomnography to titrate DP settings identified artifacts occurring in regular intervals coinciding with the onset of inspiration during all sleep stages in several channels including legs, snore, and electrocardiogram. Clinicians interpreting polysomnograms performed during DP should become familiar with the multichannel artifacts due to DP impulses. We also identified that our patient was hyperventilated on home DP settings that led to adjustment of DP settings during the polysomnogram to achieve optimal oxygenation and ventilation. Our case also highlights the utility of polysomnography to ensure optimal gas exchange during sleep in children with congenital central hypoventilation syndrome using DP.

Obstructive sleep apnea in pediatric obesity and the effects of sleeve gastrectomy.

The prevalence of severe pediatric obesity is rising and poses many adverse health risks. Children with obesity are at increased risk of several cardiovascular and metabolic diseases. They are also more likely to have obstructive sleep apnea (OSA), which increases the risk of cardiovascular and metabolic problems. In this review, we examine the relationship between OSA and obesity, improvements in OSA after non-surgical and surgical weight loss, and explore potential directions for future research.

Positional impairment of gas exchange during diaphragm pacing alleviated by increasing amplitude settings in congenital central hypoventilation syndrome.

None: Diaphragm pacing (DP) by phrenic nerve stimulation is a modality of chronic ventilatory support in individuals with congenital central hypoventilation syndrome (CCHS). We report a 9-year-old girl with CCHS who uses DP without tracheostomy during sleep. Her parents report hypoxemia and hypercapnia related to positional changes of the body during sleep requiring frequent adjustment of pacer settings. Overnight polysomnography was performed to titrate DP settings that showed adequate gas exchange in the supine position, but intermittent hypoxemia and hypercapnia were noted in the left decubitus position without obstructive sleep apnea occurring. Subsequently, the DP amplitude settings were increased during polysomnography, thereby identifying and treating positional hypoxemia and hypercapnia in various body positions. Our case emphasizes the importance of polysomnography in children with CCHS using DP to monitor for sleep-disordered breathing and titration of DP settings to achieve optimal oxygenation and ventilation with different body positions during sleep.

Restless Legs Syndrome in Chronic Kidney Disease: Is Iron or Inflammatory Status To Blame?

STUDY OBJECTIVES: Restless legs syndrome (RLS) is increased in pediatric chronic kidney disease (CKD). In adults without CKD, central nervous system iron deficiency is involved in RLS pathogenesis and a low serum ferritin levels is consequently an indication for initiation of iron therapy. However, children with CKD are at risk for iron deficiency and inflammation, which raises serum ferritin. We examined the role of iron deficiency and inflammation in RLS in pediatric CKD. METHODS: This cross-sectional study examined RLS prevalence in three groups of pediatric patients with CKD: nontransplant, nondialysis CKD (estimated GFR < 60 mL/min/1.73 m²) (n = 27); renal transplant recipients (n = 65); and dialysis (n = 32). RLS was diagnosed using a validated questionnaire. Serum ferritin < 100 ng/mL or transferrin saturation < 20% defined iron deficiency. Serum high sensitivity C-reactive protein ≥ 1 mg/L defined inflammation. RESULTS: Among 124 patients, RLS prevalence was 15.3%; this did not differ across groups. There was no significant difference in RLS prevalence between those with and without iron deficiency, defined by either reduced ferritin or transferrin. Median ferritin levels in patients with RLS tended to be higher than in those without RLS (51.2 versus 40.1 ng/mL; P = .08). Inflammation (elevated CRP) also did not differ significantly by RLS status (57.9% [with RLS] versus 41.2% [without RLS], P = .18). CONCLUSIONS: Neither ferritin nor inflammation differentiated pediatric patients with CKD with and without RLS. This study suggests that the factors mediating the pathogenesis and, potentially, treatment, of RLS in pediatric CKD may be different from non-CKD populations.

Sensorineural hearing loss in children with sickle cell disease.

INTRODUCTION: Sensorineural hearing loss (SNHL) has been reported to occur at increased frequency in the pediatric sickle cell disease (SCD) population, likely secondary to ototoxic medication regimens and repeat sickling events that lead to end organ damage. Risk and protective factors of SNHL in this population are not fully characterized. The objective of this study was to describe audiology results in children with SCD and the prevalence and sequelae of SNHL. METHODS: A comprehensive clinical database of 2600 pediatric SCD patients treated at 1 institution from 2010-16 was retrospectively reviewed to identify all patients who were referred for audiologic testing. Audiologic test results, patient characteristics, and SCD treatments were reviewed. RESULTS: 181 SCD children (97 male, 153 HbSS) underwent audiologic testing, with 276 total audiology encounters, ranging 1-9 per patient. Mean age at first audiogram was 8.9 ±â€¯5.2 years. 29.8% had prior cerebrovascular infarct and an additional 25.4% had prior abnormal transcranial Doppler screens documented at time of first audiogram. Overall, 13.3% had documented hearing loss, with 6.6% SNHL. Mean pure tone average (PTA) among patients with SNHL ranged from mild to profound hearing loss (Right: 43.3 ±â€¯28.9, Left: 40.8 ±â€¯29.7), sloping to more severe hearing loss at higher frequencies. CONCLUSIONS: Hearing loss was identified in a significant subset of children with SCD and the hearing loss ranged from normal to profound. Though the overall prevalence of SNHL in SCD patients was low, baseline audiology screening should be considered.

Adenotonsillectomy in children with sickle cell disease and obstructive sleep apnea.

INTRODUCTION: Obstructive sleep apnea (OSA) is prevalent and may be more severe in children with Sickle Cell Disease (SCD) compared to the general pediatric population. OBJECTIVES: The objective of this study was to describe the therapeutic effects and complications of tonsillectomy and adenoidectomy (T&A) for treatment of OSA in children with SCD. METHODS: A comprehensive database of pediatric SCD patients was reviewed to identify all patients who underwent T&A between 2010 and 2016. An IRB-approved, retrospective review of laboratory values, perioperative course, pre- and post-T&A hospital utilization, and polysomnography was conducted. RESULTS: There were 132 SCD children (108 HbSS) who underwent T&A. Mean age was 7.6 ±â€¯4.6 years. The mean baseline hemoglobin of these patients was 9.3 ±â€¯1.4 g/dL; 72.7% of patients had pre-operative transfusion, such that the mean Hb at time of T&A was 11.4 ±â€¯1.0 g/dL. The average admission length surrounding T&A was 3.5 ±â€¯1.2 days. Complications were documented in 11.4% of operative cases. Polysomnography was available in 104 pre-T&A and 45 post-T&A. The Apnea-Hypopnea Index decreased on post-T&A polysomnogram (7.6 ±â€¯8.7 vs. 1.3 ±â€¯1.9, p = 0.0001). The O2 nadir improved on post-T&A polysomnogram (81.2 ±â€¯10.8 vs. 89.3 ±â€¯7, p = 0.0003). Emergency room visits (mean events per year) decreased post-operatively (2.6 ±â€¯2.8 vs. 1.8 ±â€¯2.2, p = 0.0002). CONCLUSIONS: T&A can be a safe and effective option to treat OSA in pediatric patients with SCD and was significantly associated with reduced AHI and fewer ER visits post-operatively.

Sleep-Related Breathing Disorders and the Chiari 1 Malformation.

The Chiari 1 malformation is characterized by > 5-mm herniation of the cerebellar tonsils through the foramen magnum. Consequent compression of the brain stem and nearby neuronal structures involved in respiratory control and maintenance of pharyngeal wall muscle tone may result in respiratory changes during sleep. These changes include respiratory failure and arrest, as well as sleep-related breathing disorders (ie, OSA and central sleep apnea). Although data have accrued on the significance of sleep-related breathing disorders in patients with the Chiari 1 malformation, many management questions remain unanswered. This article reviews the available literature on prevalence and management of sleep-related breathing disorders in patients with the Chiari 1 malformation.

Genetic variation in melatonin pathway enzymes in children with autism spectrum disorder and comorbid sleep onset delay.

Sleep disruption is common in individuals with autism spectrum disorder (ASD). Genes whose products regulate endogenous melatonin modify sleep patterns and have been implicated in ASD. Genetic factors likely contribute to comorbid expression of sleep disorders in ASD. We studied a clinically unique ASD subgroup, consisting solely of children with comorbid expression of sleep onset delay. We evaluated variation in two melatonin pathway genes, acetylserotonin O-methyltransferase (ASMT) and cytochrome P450 1A2 (CYP1A2). We observed higher frequencies than currently reported (p < 0.04) for variants evidenced to decrease ASMT expression and related to decreased CYP1A2 enzyme activity (p ≤ 0.0007). We detected a relationship between genotypes in ASMT and CYP1A2 (r(2) = 0.63). Our results indicate that expression of sleep onset delay relates to melatonin pathway genes.

Relation of melatonin to sleep architecture in children with autism.

Children with autism often suffer from sleep disturbances, and compared to age-matched controls, have decreased melatonin levels, as indicated by urine levels of the primary melatonin metabolite, 6-sulfatoxymelatonin (6-SM). We therefore investigated the relationship between 6-SM levels and sleep architecture in children with autism spectrum disorders (ASD). Twenty-three children, aged 4-10 years, completed two nights of polysomnography and one overnight urine collection for measurement of urinary 6-SM excretion rate. Parents completed the Children's Sleep Habits Questionnaire. We found that higher urinary 6-SM excretion rates were associated with increased N3 sleep, decreased N2 sleep, and decreased daytime sleepiness. The results warrant further examination to examine the effects of supplemental melatonin on sleep architecture and daytime sleepiness.