Autism spectrum disorder in young patients with congenital central hypoventilation syndrome: role of the autonomic nervous system dysfunction.

BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare condition characterized by alveolar hypoventilation and autonomic nervous system (ANS) dysfunction requiring long-term ventilation. CCHS could constitute a risk factor of autism spectrum disorder (ASD) due to birth injury related to respiratory failure, which remains to be determined. ANS dysfunction has also been described in ASD and there are indications for altered contribution of ANS-central nervous system interaction in processing of social information; thus, CCHS could be a risk factor for ASD based on pathophysiological background also. Our study aimed to determine the prevalence of ASD among CCHS patients, identify risk factors, and explore the relationship between the ANS, evaluated by heart rate variability indices, and adaptative functioning. RESULTS: Our retrospective study, based on the analysis of records of a French national center of patients with CCHS under 20 years of age, determined that the prevalence of ASD (diagnosed by a psychiatrist, following the criteria of DSM-4 or DSM-5) was 6/69 patients, 8.7% (95% confidence interval: 3.3-18.0%). In a case (CCHS with ASD, n = 6) - control (CCHS without ASD, n = 12) study with matching on sex, longer neonatal hospitalization stay and glycemic dysfunction were associated with ASD. Adaptative functioning was assessed using Vineland Adaptative behavioral scales (VABS) and heart rate variability indices (including daytime RMSSD as an index of parasympathetic modulation) were obtained from ECG Holter performed the same day. In 19 young subjects with CCHS who had both ECG Holter and VABS, significant positive correlations were observed between RMSSD and three of four sub-domains of the VABS (communication: R = 0.50, p = 0.028; daily living skills: R = 0.60, p = 0.006; socialization: R = 0.52, p = 0.021). CONCLUSION: Our study suggests a high prevalence of ASD in patients with CCHS. Glycemic dysfunction and longer initial hospitalization stays were associated with ASD development. A defect in parasympathetic modulation was associated with worse adaptative functioning.

Tracheostomy and inpatient outcomes among children with congenital central hypoventilation syndrome: A kids' inpatient database study.

STUDY OBJECTIVES: Congenital central hypoventilation syndrome (CCHS) is a rare disease predisposing children to respiratory failure due to abnormal ventilatory drive. Variability in hypoventilation and respiratory support need have been reported. We aim to identify clinical variables associated with incident tracheostomy and common etiologies of hospitalization among children with CCHS. METHODS: Hospital discharge records were obtained for children (<21 years) with CCHS hospitalized between 2006 and 2019 from the Kid's Inpatient Database. Primary diagnostic categories for hospitalizations with CCHS were summarized. Multivariable logistic regression models were used to explore risk factors associated with incident tracheostomy. RESULTS: Among 2404 hospitalizations with CCHS, 133 (5.5%) had incident tracheostomy, 1230 (51.2%) had established tracheostomy, and 1041 (43.3%) had no tracheostomy. Compared with children without tracheostomy, those with incident tracheostomy were younger, had a history of prematurity, congenital heart disease, laryngeal, glottic, and subglottic stenosis (LGSS), congenital airway anomalies, neuromuscular weakness, gastroesophageal reflux disease. Children without tracheostomy had higher mortality than those with tracheostomy status (2.19% vs. 0.66%). Multivariable-adjusted analyses showed that incident tracheostomy was associated with infancy (0-1 years), neuromuscular weakness, and congenital heart disease. Most common diagnostic categories include (1) diseases of the respiratory system (30.23%), (2) injury and poisoning (9.35%), and (3) diseases of the nervous system and sense organs (6.71%). CONCLUSIONS: Children with CCHS who received incident tracheostomy are more likely to be younger and with LGSS, neuromuscular weakness and congenital heart disease. Clinicians should be aware of these risk factors representing more severe CCHS with earlier manifestation needing tracheostomy. Higher mortality among nontracheostomy group highlights the need for considering tracheostomy in caring for children with CCHS.

The epidemiological characteristics of sleep disordered breathing in congestive heart failure: A prospective, single centre study in Southeast Asia.

BACKGROUND: The presence of sleep-disordered breathing (SDB) in congestive heart failure (CHF) is associated with poor prognosis and is underdiagnosed despite advances in CHF management. The prevalence of SDB in CHF remains understudied in South East Asia. METHODS: A prospective, observational single-centre study was conducted where 116 consecutive patients in a specialised heart failure clinic underwent level 1, attended polysomnography (PSG). RESULTS: The prevalence of SDB was 78% using the apnoea-hypopnea index (AHI), AHI ⩾ 5/h threshold, and 59% with the AHI ⩾ 15/h threshold. Obstructive sleep apnoea (OSA) was the predominant type of SDB and was associated with increased body mass index and neck circumference. STOP-BANG was predictive of SDB, especially in men. Central sleep apnoea (CSA) patients had worse sleep indexes and lower awake arterial carbon dioxide. SDB was also homogenously present in preserved ejection fraction (EF) CHF. CONCLUSION: Most of the CHF patients were found to have SDB with the utility of PSG. Local CHF guidelines should include sleep testing for all patients with CHF.The study is registered on ClinicalTrials.gov (NCT05332223) as 'The Epidemiological Characteristics of SDB in Patients with Reduced or Preserved EF CHF'.

The prevalence and polysomnographic characteristics of treatment-emergent central sleep apnea with obstructive sleep apnea.

PURPOSE: To investigate the prevalence of treatment-emergent central sleep apnea (TECSA) in individuals with obstructive sleep apnea syndrome (OSAS) during continuous positive airway pressure (CPAP) titration and assess their polysomnographic characteristics. METHODS: A total of 116 patients with OSAS who underwent full-night CPAP titration at the Sleep Laboratory of Adana City Research and Education Hospital from September 2017 to January 2018 were recruited for the study. The patients' polysomnographic data related to respiratory events and sleep stages were reviewed in a retrospective manner. RESULTS: While on CPAP titration, 20 of the 116 patients developed central sleep apnea (CSA). The prevalence of TECSA in the patients with OSAS was 17.2%, being separately determined as 16.3% and 2.2% for the male and female patients, respectively. In the baseline PSG, the groups did not statistically significantly differ in relation to the apnea hypopnea index (AHI), central apnea index (CAI), arousal index (AI), or oxygen desaturation index (ODI). However, the TECSA group had a significantly higher mean oxygen saturation value compared to the non-TECSA group (p = 0.01). The total AHI, CAI, and AI values of the TECSA group were significantly higher during the whole CPAP titration compared to the non-TECSA group. No significant difference was observed in the comparison of the two groups in relation to the titration pressure and ODI. CONCLUSION: TECSA is a phenomenon that can occur with obstructive sleep apnea treatment and mostly regress spontaneously following appropriate CPAP treatment. TECSA is observed at different rates of prevalence. In this study, the prevalence of TECSA was higher than previously reported.

Association of Sex With Cardiovascular Outcomes in Heart Failure Patients With Obstructive or Central Sleep Apnea.

BACKGROUND: This study investigated the association of sex with cardiovascular outcomes in a prospective cohort of patients with heart failure (HF) with obstructive sleep apnea or central sleep apnea. METHODS AND RESULTS: Patients were screened for sleep apnea on admission using multichannel cardiopulmonary monitoring from May 2015 to July 2018. The primary outcome was a composite of cardiovascular death or unplanned hospitalization for worsening HF. Ultimately, 453 patients with HF with obstructive sleep apnea or central sleep apnea were included; 71 (15.7%) and 382 (84.3%) were women and men, respectively. During a median follow-up of 2.33 years, 248 (54.7%) patients experienced the primary outcome. In the overall population, after adjusting for potential confounders, women had an increased risk of the primary outcome (66.2% versus 52.6%; hazard ratio [HR], 1.47 [95% CI, 1.05-2.04]; P=0.024) and HF rehospitalization (62.0% versus 46.6%; HR, 1.55 [95% CI, 1.10-2.19]; P=0.013) compared with men but a comparable risk of cardiovascular death (21.1% versus 23.3%; HR, 0.78 [95% CI, 0.44-1.37]; P=0.383). Likewise, in patients with HF with obstructive sleep apnea, women had a higher risk of the primary outcome (81.8% versus 46.3%, HR, 2.37 [95% CI, 1.28-4.38]; P=0.006) and HF rehospitalization (81.8% versus 44.7%, HR, 2.46 [95% CI, 1.32-4.56], P=0.004). However, in patients with HF with central sleep apnea, there was no statistically significant difference between women and men. CONCLUSIONS: In hospitalized patients with HF, female sex was associated with an increased risk of the primary outcome and HF rehospitalization, especially in those with obstructive sleep apnea. Screening for sleep apnea should be emphasized to improve the prognosis. REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02664818.

Central Sleep Apnea in Patients With Coronary Heart Disease Taking P2Y12 Inhibitors.

ABSTRACT: Central sleep apnea (CSA) is common in patients with heart failure. Recent studies link ticagrelor use with CSA. We aimed to evaluate CSA prevalence in patients with coronary heart disease (CHD) and whether ticagrelor use is associated with CSA. We reviewed consecutive patients with CHD who underwent a polysomnography (PSG) test over a 5-year period from 3 sleep centers. We sampled patients who were on ticagrelor or clopidogrel during a PSG test at a 1:4 ticagrelor:clopidogrel ratio. Patients with an active opioid prescription during PSG test were excluded. Age, left ventricle (LV) dysfunction, and P2Y12 inhibitor use were included in a multivariate logistic regression. A total of 135 patients were included with 26 on ticagrelor and 109 on clopidogrel (age 64.1 ± 11.4, 32% male). High CSA burden (12%) and strict CSA (4.4%) were more common in patients on ticagrelor than in those on clopidogrel (27% vs. 8.3% and 10.0% vs. 1.8%). Ticagrelor use (vs. clopidogrel) was associated with high CSA burden (OR 3.53, 95% CI 1.04-12.9, P = 0.039) and trended toward significance for strict CSA (OR 6.32, 95% CI 1.03-51.4, P = 0.052) when adjusting for age and LV dysfunction. In an additional analysis also adjusting for history of atrial fibrillation, ticagrelor use and strict CSA became significantly associated (OR 10.0, 95% CI 1.32-117, P = 0.035). CSA was uncommon in patients with CHD undergoing sleep studies. Ticagrelor use (vs. clopidogrel) was associated with high CSA burden and trended toward significance for strict CSA.

Sleep disordered breathing assessment in patient with slowly progressive neuromuscular disease.

BACKGROUND: Sleep-disordered breathing (SDB) is common in patients with neuromuscular diseases (NMD). Focusing on hypercapnia may lead to the neglect of other SDB such as obstructive and/or central sleep apnea syndrome (SAS). Our objectives were to assess the risk of inappropriate SDB management according to different screening strategies and to evaluate the prevalence and determinants of isolated and overlapping sleep apnea in patients with slowly progressive NMD. METHODS: This monocentric, cross-sectional, retrospective study analyzed medical records of adult NMD patients referred to a sleep department. Diagnostic strategies, including respiratory polygraphy (RP), nocturnal transcutaneous capnography (tcCO2), and blood gases (BG), were assessed for their performance in diagnosing SDB. Demographics and pulmonary function test results were compared between patients with or without SDB to identify predictors. RESULTS: Among the 149 patients who underwent a full diagnostic panel (RP + tcCO2 + BG), 109 were diagnosed with SDB. Of these, 33% had isolated SAS, and central apneas were predominant. Using single diagnostic strategies would lead to inappropriate SDB management in two thirds of patients. A combination of 2 diagnostic tools resulted respectively in 21.1, 22.9 and 42.2 % of inappropriate SDB management for RP + tcCO2, RP + BG and tcCO2 + BG. CONCLUSION: The significant prevalence of sleep apnea syndrome in patients with slowly progressive NMD highlights the need for increased awareness among clinicians. Improved diagnostics involve a systematic approach addressing both sleep apnea and diurnal and nocturnal alveolar hypoventilation to avoid inappropriate management and limit the consequences of SDB.

Prevalence of central sleep apnea in people with tetraplegic spinal cord injury: a retrospective analysis of research and clinical data.

STUDY OBJECTIVES: Over 80% of people with tetraplegia have sleep-disordered breathing (SDB), but whether this is predominantly obstructive or central is unclear. This study aimed to estimate the prevalence of central sleep apnea (CSA) in tetraplegia and the contributions of central, obstructive, and hypopnea respiratory events to SDB summary indices in tetraplegia. METHODS: Research and clinical data from 606 individuals with tetraplegia and full overnight polysomnography were collated. The proportions of different respiratory event types were calculated; overall and for mild, moderate, and severe disease. The prevalence of Predominant CSA (Central Apnea Index [CAI] ≥ 5 and more central than obstructive apneas) and Any CSA (CAI ≥ 5) was estimated. Prevalence of sleep-related hypoventilation (SRH) was estimated in a clinical sub-cohort. RESULTS: Respiratory events were primarily hypopneas (71%), followed by obstructive (23%), central (4%), and mixed apneas (2%). As severity increased, the relative contribution of hypopneas and central apneas decreased, while that of obstructive apneas increased. The prevalence of Predominant CSA and Any CSA were 4.3% (26/606) and 8.4% (51/606) respectively. Being male, on opiates and having a high tetraplegic spinal cord injury were associated with CSA. SRH was identified in 26% (26/113) of the clinical sub-cohort. CONCLUSIONS: This is the largest study to characterize SDB in tetraplegia. It provides strong evidence that obstructive sleep apnea is the predominant SDB type; 9-18 times more prevalent than CSA. The prevalence of CSA was estimated to be 4%-8%, significantly lower than previously reported.

The prevalence of treatment-emergent central sleep apnea with mandibular advancement device therapy.

STUDY OBJECTIVES: Treatment-emergent central sleep apnea (TECSA) describes the appearance or persistence of central sleep apnea while undergoing treatment for obstructive sleep apnea. TECSA is well studied in continuous positive airway pressure therapy with an estimated prevalence of 8%. Based on a few case reports, mandibular advancement devices (MAD) may also provoke TECSA. This study aims to gain insight into the prevalence of TECSA with MAD therapy. METHODS: This retrospective study includes a total of 129 patients with moderate to severe obstructive sleep apnea who were treated with a custom-made titratable MAD. Baseline and follow-up sleep studies were compared to identify patients with TECSA. Since different diagnostic criteria to define TECSA are used in literature, prevalence was calculated according to three definitions (TECSA-1, -2, and -3). Demographics, MAD treatment variables, and findings of the diagnostic polysomnography were compared between TECSA and non-TECSA patients to identify possible predictors. RESULTS: Depending on the definition used, TECSA was found in 3.1%-7.8% of patients undergoing MAD therapy. TECSA patients had a higher apnea index (9.2 vs 2.0 events/h, P = .042), central apnea-hypopnea index (4.1 vs 0.2 events/h, P = .045) and oxygen desaturation index (23.9 vs 16.3 events/h, P = .018) at baseline compared to non-TECSA patients. No differences were found in demographics and treatment variables. CONCLUSIONS: These findings demonstrate that TECSA also occurs in patients starting MAD treatment. Patients with TECSA had a higher apnea index, central apnea-hypopnea index, and oxygen desaturation index at baseline compared to non-TECSA patients. CITATION: Hellemans S, Van de Perck E, Braem MJ, Verbraecken J, Dieltjens M, Vanderveken OM. The prevalence of treatment-emergent central sleep apnea with mandibular advancement device therapy. J Clin Sleep Med. 2023;19(12):2035-2041.

Contribution of central sleep apnea to severe sleep apnea hypopnea syndrome.

PURPOSE: Central sleep apnea (CSA) is usually distinguished from obstructive sleep apnea (OSA). In fact, CSA is often a component of severe sleep apnea hypopnea syndrome (SAHS), rather than occurring alone. We investigated the clinical characteristics and polysomnography (PSG) parameters of CSA components in patients with severe SAHS. METHODS: The clinical characteristics and PSG parameters were retrospectively analyzed. RESULTS: Pure or dominant CSA was rare (5% of all patients). Of all patients with CSA, 72% also exhibited other apnea subtypes that contributed to severe SAHS. Among patients with severe SAHS, those with CSA were more likely than others to be older; thinner; exhibit higher prevalences of comorbid coronary heart disease, arrhythmia, and heart failure; a higher apnea/hypopnea index (AHI); mixed apnea index (MAI); an elevated oxygen desaturation index (ODI); and more nighttime oxygen saturation levels < 90%. Multivariate logistic regression analysis revealed that older age, comorbid arrhythmia or heart failure, and an elevated ODI were independently associated with CSA. CONCLUSION: Patients who complain of snoring or apnea may be better evaluated by comprehensive PSG prior to treatment if they are old, show greater hypoxia, or suffer from arrhythmia and/or heart failure, because such patients are more likely than others to exhibit CSA.

The burden of sleep disordered breathing in infants with Down syndrome referred to tertiary sleep center.

INTRODUCTION: Children with Down Syndrome (DS) are at high risk of sleep disordered breathing (SDB). We aimed to examine the burden of SDB in infants with DS referred to tertiary sleep center. METHODS: Infants (≤12 months old) with DS who underwent consecutive polysomnography (PSG) at a single academic sleep center over a 6-year period were included. obstructive sleep apnea (OSA) (obstructive apnea hypopnea index [oAHI]>1/hr), central sleep apnea (central apnea index > 5/h) and the presence of hypoventilation (% time spent with CO2 > 50 mmHg either by end-tidal or transcutaneous> 25% of total sleep time) and hypoxemia (time spent with O2 saturation <88% >5 min) were ascertained. RESULTS: A total of 40 infants were included (Mean age 6.6 months, male 66%). PSGs consisted of diagnostic (n = 13) and split night (n = 27, 68%) studies. All met criteria for OSA with mean oAHI 34.6/h (32.3). Central sleep apnea was present in 11 (27.5%) of infants. A total of 11 (27.5%) had hypoxemia. Hypoventilation was present in 10 (25%) infants. CONCLUSION: This study highlights the high prevalence of SDB in infants with DS referred to a sleep center, and supports early PSG assessment in this patient population.

Prevalence and clinical characteristics of sleep-disordered breathing in patients with heart failure of different left ventricular ejection fractions.

PURPOSES: The prevalence of sleep-disordered breathing (SDB) is high in patients with heart failure (HF), while the prevalence of SDB in HF with different left ventricular ejection fractions (LVEF) has rarely been reported. We aimed to explore the prevalence and clinical characteristics of SDB in patients with HF having different LVEF. METHODS: Patients with stable HF were consecutively enrolled. All patients underwent portable overnight cardiorespiratory polygraphy and echocardiography. According to their LVEF, the patients were divided into the HFrEF (HF with reduced EF, EF < 40%), HFmrEF (HF with mid-range EF, 40 ≤ EF < 50), and HFpEF groups (HF with preserved EF, EF ≥ 50%). The prevalence and clinical data of SDB among the 3 groups were then compared. RESULTS: A total of 252 patients, including 134 men, were enrolled in the study. The prevalence of SDB in patients with HF was 70%. Obstructive sleep apnea (OSA) was diagnosed in 48% and central sleep apnea (CSA) in 22%. The prevalence of SDB in the HFrEE, HFmrEF, and HFpEF groups was 86%, 86%, and 62%, respectively (P = 0.001). The prevalence of OSA among the 3 groups was 42%, 47%, and 49%, respectively (P = 0.708), while the prevalence of CSA among the 3 groups was 44%, 40%, and 13% (P < 0.001). Logistic regression analysis revealed that age and BMI were independent risk factors for OSA in patients with HF, while LVEF and smoking were independent risk factors for CSA in patients with HF. Correlational analyses revealed that LVEF was negatively correlated with apnea-hypopnea index (AHI) (r = -0.309, P < 0.001) and central apnea index (CAI) ( r = -0.558, P < 0.001), while there was no significant correlation with obstructive apnea index (OAI). The ROC curve revealed that LVEF could predict the occurrence of CSA and SDB, with AUC = 0.683 (95%CI 0.600-0.767, P < 0.001) and AUC = 0.630 (95%CI 0.559-0.702, P = 0.001), but not of OSA. CONCLUSIONS: SDB was highly common in HF, and the prevalence of SDB was different in HF with different LVEF, mainly due to the difference in cardiac functions. The prevalence and severity of SDB in HFrEF and HFmrEF were significantly higher than those in HFpEF, which was mainly related to the increase in CSA. When HFmrEF was similar to HFrEF in cardiac functions, the prevalence, type, and severity of SDB were similar between the two groups. Changes in LVEF had a significant impact on CAI, but not on OAI. LVEF can predict the occurrence of CSA and SDB to a certain extent.

Heart rate variability in congenital central hypoventilation syndrome: relationships with hypertension and sinus pauses.

BACKGROUND: Autonomic nervous system (ANS) dysregulation has been described in congenital central hypoventilation syndrome (CCHS). The objectives were to describe heart rate variability (HRV) analyses in children suffering from CCHS both while awake and asleep and their relationships with both ambulatory blood pressure (BP) and ECG monitoring results. METHODS: This retrospective study enrolled children with CCHS (n = 33, median age 8.4 years, 18 girls) who had BP and ECG monitored during the same 24 h. From the latter, HRV analyses were obtained during daytime and nighttime. RESULTS: The prevalences of hypertension and sinus pauses were 33% (95% confidence interval [CI]: 18-52) and 18% (95% CI: 7-35), respectively. The decrease in systolic BP at night negatively correlated with an increase in very low frequency (VLF) and LF powers at night, and the longest RR interval positively correlated with daytime VLF and LF powers. Among the three groups of children (polyalanine repeat expansion mutation [PARM], moderate [20/25 and 20/26], severe [20/27 and 20/33], and non-PARMs), the prevalence of elevated BP or hypertension was different: in PARM subjects: 6/18 moderate, 7/9 severe versus 0/6 in non-PARM (p = 0.002). CONCLUSION: Modifications of cardiac ANS are associated with systemic hypertension and the occurrence of sinus pauses in CCHS. IMPACT: Children with congenital central hypoventilation syndrome (CCHS) exhibit an increased prevalence of hypertension and sinus pauses that are linked to cardiac autonomic nervous system dysfunction. Sinus pauses are the main manifestation of sinus nodal dysfunction in children with CCHS. The increased prevalence of hypertension, especially at nighttime, is a new finding in CCHS. Sinus nodal dysfunction can be due to the sole impairment of the cardiac autonomic nervous system. Ambulatory blood pressure and ECG monitoring are mandatory in patients with CCHS.

Evaluation and Treatment of Central Sleep Apnea in Patients with Heart Failure.

Sleep-disordered breathing (SDB) is a common comorbidity in patients with heart failure (HF). Prevalence of the most common subtypes of SDB, central sleep apnea (CSA) and obstructive sleep apnea (OSA), is increasing, which is concerning due to the association of SDB with increased mortality in patients with HF. Despite an increasing burden of CSA in HF, it is difficult to detect using current diagnostic tools and the treatment modalities are limited by variable efficacy and patient adherence. Though positive airway pressure therapies remain the cornerstone of OSA treatment, the management of CSA in the setting of HF continues to evolve. The association of the presence of CSA with worse prognosis in HF patients warrants the need for routine screening for signs and symptoms of CSA in this population. In this review, we examine the connection between CSA and HF, and highlight advancements in timely diagnostics, treatment modalities, and strategies to promote facilitation of compliance in this high-risk cohort.

Impact of sleep-disordered breathing on the management of children with Chiari malformation type I.

OBJECTIVES: Children with Chiari malformation type I (CM-I) have an increased risk of sleep apnea. The aim of the study was to describe the management of CM-I patients in relation to symptoms, magnetic resonance imaging (MRI) findings and sleep apnea syndrome (SAS). METHODS: We performed a retrospective analysis of clinical charts of all 57 CM-I patients seen between September 2013 and April 2017. RESULTS: A total of 45 patients had isolated CM-I or associated co-morbidity (CM-Iia), 5 had craniosynostosis (CM-Ics), and 7 a polymalformative syndrome (CM-Ipm). The prevalence of SAS, defined as an apnea-hypopnea index >1 event/h, was high in CM-I ranging from 50% to 80% according to the CM-I group. The prevalence of central sleep apnea (CSA) was low, with 5 (9%) patients having CSA and only 3 patients with CM-Iia having isolated CSA. A total of 17 patients (30%) had foramen magnum decompression (FMD). Neither positive symptoms of CM-I nor MRI findings alone, nor both combined were good indicators for FMD. No correlation was observed between the cerebellar tonsil descent and SAS in CM-I. But all 5 patients with CSA had a FMD. The combination of MRI findings and/or symptoms of CM-I together with moderate-to-severe SAS best discriminated patients who needed a FMD. CONCLUSION: Our findings highlight the importance of a combined evaluation of symptoms, MRI and polygraphy results in the management of CM-I patients.

Sleep-disordered breathing in pediatric neurofibromatosis type 1.

The relationship between neurofibromatosis type 1 (NF1) and sleep-disordered breathing (SDB) has not been widely studied. The aim of the study was to analyze SDB in children with NF1 of the respiratory system. All children with NF1 followed between September 2008 and July 2020 who had a respiratory polygraphy (RP) were included. The clinical charts, cerebral and cervical magnetic resonance imaging (MRI), and RP were analyzed. Twenty-two patients (11 girls, median age at RP 8.3 [0.2-18.2] years) were included in the study. Nine patients (41%) had a NF1 involvement of the upper airways, 13 (59%) patients of the central nervous system (CNS), the cranial nerves (CN) and/or medulla, and 17 (77%) patients had a hypertrophy of the adenoids and/or tonsils. Five patients were treated with Continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV) before their first evaluation because of severe obstructive sleep apnea (OSA). Accordingly, 10 (45%) patients had no OSA, one (5%) mild OSA, 2 (9%) moderate OSA, and nine (41%) severe OSA. None of the patients had central sleep apnea. Despite upper airway surgery, three patients required CPAP, two could be weaned and one died after a switch to tracheostomy. None of the patients treated with CPAP/NIV could be weaned, one patient required tracheostomy. Neither the clinical nor the MRI findings were able to predict OSA on a RP. The prevalence of OSA in NF1 is high, regardless of the nature of airway obstruction and the clinical and MRI findings, underlining the value of a systematic RP. CPAP may reduce the need of tracheostomy.

Management of Sleep Apnea in Children with Chiari I Malformation: A Retrospective Study.

INTRODUCTION: The literature indicates that decompression of Chiari I malformations (CM-1) may resolve symptoms of sleep apnea. This study aims to identify the incidence of obstructive sleep apnea (OSA), central sleep apnea (CSA), and mixed sleep apnea in a cohort of pediatric CM-1 patients treated at our institution. We also assessed apnea-hypopnea index and symptomatology before and after surgery to investigate if Chiari decompression is a viable treatment for sleep apnea in CM-1 patients. Improvement relative to ENT surgical intervention was also considered. METHODS: We identified 75 patients who underwent polysomnography (PSG) from our database of 465 CM-1 patients. Sleep apnea diagnosis was based on the sleep physician's overall interpretation of the PSG. Symptomatology pre- and post-surgery was analyzed. RESULTS: Of the 75 CM-1 patients that underwent PSG, 23 were diagnosed with sleep apnea. Sixteen had OSA, 6 had CSA, and 1 had mixed apnea. Twelve OSA patients received ENT intervention. Eight improved and 2 further improved after Chiari decompression. Of the 4 patients that did not improve, one of those later improved following Chiari decompression. Of the 6 CSA patients, 2 underwent Chiari decompression, but only one improved. The mixed apnea patient underwent several ENT interventions that did not relieve symptoms but improved following Chiari decompression. DISCUSSION/CONCLUSIONS: Based on our results, sleep apnea in CM-1 patients may be obstructive, central, or mixed and is likely multifactorial. A multidisciplinary approach to the management of these patients is important, including neurosurgery, otolaryngology, and sleep medicine. Future prospective studies will lend further insight into this condition and its management.

Central Apneas Are More Detrimental in Female Than in Male Patients With Heart Failure.

Background Central apneas (CA) are a frequent comorbidity in patients with heart failure (HF) and are associated with worse prognosis. The clinical and prognostic relevance of CA in each sex is unknown. Methods and Results Consecutive outpatients with HF with either reduced or mildly reduced left ventricular ejection fraction (n=550, age 65±12 years, left ventricular ejection fraction 32%±9%, 21% women) underwent a 24-hour ambulatory polygraphy to evaluate CA burden and were followed up for the composite end point of cardiac death, appropriate implantable cardioverter-defibrillator shock, or first HF hospitalization. Compared with men, women were younger, had higher left ventricular ejection fraction, had lower prevalence of ischemic etiology and of atrial fibrillation, and showed lower apnea-hypopnea index (expressed as median [interquartile range]) at daytime (3 [0-9] versus 10 [3-20] events/hour) and nighttime (10 [3-21] versus 23 [11-36] events/hour) (all P<0.001), despite similar neurohormonal activation and HF therapy. Increased chemoreflex sensitivity to either hypoxia or hypercapnia (evaluated in 356 patients, 65%, by a rebreathing test) was less frequent in women (P<0.001), but chemoreflex sensitivity to hypercapnia was a predictor of apnea-hypopnea index in both sexes. At adjusted survival analysis, daytime apnea-hypopnea index ≥15 events/hour (hazard ratio [HR], 2.70; 95% CI, 1.06-7.34; P=0.037), nighttime apnea-hypopnea index ≥15 events/hour (HR, 2.84; 95% CI, 1.28-6.32; P=0.010), and nighttime CA index ≥10 events/hour (HR, 5.01; 95% CI, 1.88-13.4; P=0.001) were independent predictors of the primary end point in women but not in men (all P>0.05), also after matching women and men for possible confounders. Conclusions In chronic HF, CA are associated with a greater risk of adverse events in women than in men.

Sleep-disordered breathing in school-aged children with Prader-Willi syndrome.

STUDY OBJECTIVES: Studies of sleep-disordered breathing (SDB) in children with Prader-Willi syndrome (PWS) have focused on early childhood and growth hormone (GH)-naïve children, but little is known about older children, including those on long-term GH therapy. This study aimed to describe the nature and prevalence of SDB in school-aged children with PWS in the growth hormone era. METHODS: This retrospective single-center chart review included children aged 6-18 years with PWS who had overnight polysomnography not involving respiratory support over 5 years (2012-2017). The main outcome measures were the presence of obstructive sleep apnea, central sleep apnea, or hypoventilation defined by an elevated transcutaneous partial pressure of carbon dioxide (TcPCO2) as per standard pediatric criteria. RESULTS: Seventeen children (8 males; median age 11.6 years, range 6.6-16.1 years) were included. Fifteen demonstrated SDB of different types: central sleep apnea (18%), obstructive sleep apnea (24%), both obstructive and central sleep apnea (29%), or hypoventilation without obstructive or central sleep apnea (18%). Twelve (71%) children had evidence of hypoventilation. Those with hypoventilation had a higher central apnea-hypopnea index but no difference in the obstructive apnea-hypopnea index, age, sex, growth parameters, or the presence of scoliosis or sleep-related symptoms compared with those without hypoventilation. CONCLUSIONS: Sleep-related hypoventilation is common in school-aged children with PWS. The presence of central sleep apnea, including the quantification of central hypopneas, but not obstructive sleep apnea or clinical factors, predicted the presence of hypoventilation. Long-term polysomnography surveillance in children with PWS should include identification of central hypopneas and measurement of continuous pCO2. CITATION: Schaefer J, Davey MJ, Nixon GM. Sleep-disordered breathing in school-aged children with Prader-Willi syndrome. J Clin Sleep Med. 2022;18(4):1055-1061.

Central Sleep Apnea.

Central sleep apnea (CSA) is characterized by intermittent repetitive cessation and/or decreased breathing without effort caused by an abnormal ventilatory drive. Although less prevalent than obstructive sleep apnea, it is frequently encountered. CSA can be primary (idiopathic) or secondary in association with Cheyne-Stokes respiration, drug-induced, medical conditions such as chronic renal failure, or high-altitude periodic breathing. Risk factors have been proposed, including gender, age, heart failure, opioid use, stroke, and other chronic medical conditions. This article discusses the prevalence of CSA in the general population and within each of these at-risk populations, and clinical presentation, diagnostic methods, and treatment.