ABSTRACT
OBJECTIVE: This study aimed to investigate how central sleep apnea (CSA) impacts sleep patterns in children with obstructive sleep apnea (OSA). METHODS: Children undergoing polysomnography (PSG) were enrolled and sorted into two groups: those with OSA alone (Group A) and those with both OSA and CSA (CAI <1 nd: children with 10 % CSA or more and less than 50 %, Group B). Statistical analysis was conducted to compare sleep structure and clinical features between Group A and Group B. RESULTS: Group B exhibited significantly higher respiratory events, apnea hypoventilation index, apnea index and oxygen desaturation index (ODI) compared to Group A (p < 0.05). Group B also showed higher total sleep time and arousal index than Group A (P < 0.05). The proportion of time spent in stage N3 was lower in Group B than in Group A (P < 0.05). Moreover, mean heart rate and minimum heart rate were higher in Group B compared to Group A (P < 0.05).Minimum oxygenation levels (including non-rapid eye movement (NREM) stages) were lowe in Group B than in Group A (P < 0.05). Additionally, the prevalence of positional obstructive sleep apnea (P-OSA) was greater in Group B than in Group A (P < 0.05). CONCLUSION: In comparison to those with OSA alone, children with OSA and concurrent CSA exhibited distinct sleep patterns, including reduced N3uration, higher arousal index, longer respiratory events, higher ODI, and lower oxygen saturation, higher heart rate.
Subject(s)
Polysomnography , Sleep Apnea, Central , Sleep Apnea, Obstructive , Humans , Male , Sleep Apnea, Central/complications , Sleep Apnea, Central/physiopathology , Sleep Apnea, Central/epidemiology , Female , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/physiopathology , Child , Child, Preschool , Sleep Stages/physiologyABSTRACT
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.
Subject(s)
Autism Spectrum Disorder , Autonomic Nervous System , Hypoventilation , Sleep Apnea, Central , Humans , Autism Spectrum Disorder/physiopathology , Female , Male , Hypoventilation/congenital , Hypoventilation/physiopathology , Retrospective Studies , Sleep Apnea, Central/physiopathology , Sleep Apnea, Central/epidemiology , Adolescent , Child , Autonomic Nervous System/physiopathology , Young Adult , Autonomic Nervous System Diseases/physiopathology , Child, Preschool , Risk FactorsABSTRACT
Congenital disorders of ventilatory control typically manifest as central apneas, periodic breathing, and hypoventilation in the neonatal period, but some may present at a later age. Obstructive apneas may be the initial presentation, and some may have associated autonomic nervous system dysfunction. Individuals with these disorders can have absent or impaired ventilatory and arousal responses to hypoxemia and hypercapnia. This article discusses the presentation, pathophysiology, evaluation, and management of congenital central hypoventilation syndrome, rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome, Prader-Willi syndrome, and myelomeningocele.
Subject(s)
Hypoventilation , Sleep Apnea, Central , Humans , Sleep Apnea, Central/therapy , Sleep Apnea, Central/physiopathology , Sleep Apnea, Central/diagnosis , Hypoventilation/congenital , Hypoventilation/therapy , Hypoventilation/physiopathology , Hypoventilation/diagnosis , Prader-Willi Syndrome/physiopathology , Prader-Willi Syndrome/therapy , Prader-Willi Syndrome/complications , Prader-Willi Syndrome/diagnosis , Infant, NewbornABSTRACT
INTRODUCTION: Central sleep apnea (CSA) is a sleep-related breathing disorder in which the effort to breathe is intermittently diminished or absent. CSA is a common disorder among patients with different cardiovascular disorders, including heart failure. In addition, a growing number of medications have been shown to induce CSA and CSA can emerge after initiation of treatment for obstructive sleep apnea. Accumulating evidence shows that CSA is a heterogeneous disorder with individual differences in clinical and biological characteristics and/or underlying pathophysiological mechanisms. AREAS COVERED: This narrative review offers an overview of the diagnostic aspects and classification of CSA, with an emphasis on heart failure patients, patients with CSA due to a medication and treatment-emergent CSA. The importance of evaluation of prognostic biomarkers in patients with different types of CSA is discussed. This narrative review synthesizes literature on CSA sourced from the PubMed database up to February 2024. EXPERT OPINION: CSA presents a remarkably diverse disorder, with treatment modalities exhibiting potentially varied efficacy across its various phenotypes. This highlights the imperative for tailored management strategies that are rooted in phenotype classification.
Subject(s)
Heart Failure , Sleep Apnea, Central , Humans , Sleep Apnea, Central/physiopathology , Sleep Apnea, Central/diagnosis , Sleep Apnea, Central/therapy , Heart Failure/physiopathology , Heart Failure/diagnosis , Biomarkers/metabolism , Prognosis , Phenotype , Sleep Apnea, Obstructive/physiopathology , Sleep Apnea, Obstructive/diagnosis , Sleep Apnea, Obstructive/therapyABSTRACT
BACKGROUND: Sacubitril/valsartan has been demonstrated to significantly improve left ventricular performance and remodelling in patients with heart failure. However, its effects on the right ventricle in patients with chronic heart failure and sleep-disordered breathing (SDB) have not been studied. AIM: To investigate the impact of sacubitril/valsartan treatment on right ventricular function in patients with SDB. METHODS: This was a subanalysis of an observational prospective multicentre study involving 101 patients. At inclusion, patients were evaluated by echocardiography and nocturnal ventilatory polygraphy, which allowed patients to be divided into three groups: "central-SDB"; "obstructive-SDB"; and "no-SDB". RESULTS: After 3 months of sacubitril/valsartan therapy, a positive impact on right ventricular function was observed. In the general population, tricuspid annular plane systolic excursion increased by +1.32±4.74mm (P=0.024) and systolic pulmonary artery pressure decreased by -3.1±10.91mmHg (P=0.048). The central-SDB group experienced the greatest echocardiographic improvement, with a significant increase in tricuspid annular plane systolic excursion of +2.1±4.9mm (P=0.045) and a significant reduction in systolic pulmonary artery pressure of -8.4±9.7mmHg (P=0.001). CONCLUSIONS: Sacubitril/valsartan improved right ventricular function in patients with heart failure and SDB after only 3 months of treatment. The greatest improvement in right ventricular function was observed in the central-SDB group.
Subject(s)
Aminobutyrates , Biphenyl Compounds , Drug Combinations , Heart Failure , Recovery of Function , Valsartan , Ventricular Function, Right , Humans , Valsartan/therapeutic use , Male , Female , Aminobutyrates/therapeutic use , Aminobutyrates/adverse effects , Ventricular Function, Right/drug effects , Prospective Studies , Middle Aged , Treatment Outcome , Aged , Heart Failure/physiopathology , Heart Failure/drug therapy , Heart Failure/diagnosis , Time Factors , Sleep Apnea, Central/physiopathology , Sleep Apnea, Central/diagnosis , Sleep Apnea, Central/drug therapy , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Angiotensin II Type 1 Receptor Blockers/adverse effects , Tetrazoles/therapeutic use , Tetrazoles/adverse effects , Protease Inhibitors/therapeutic use , Protease Inhibitors/adverse effects , Polysomnography , Neprilysin/antagonists & inhibitors , Chronic DiseaseABSTRACT
Catathrenia is a loud expiratory moan during sleep that is a social embarrassment and is sometimes confused with central apnea on polysomnography. It affects about 4% of adults, but cases are rarely referred to sleep centers. Catathrenia affects males and females, children and adults, who are usually young and thin. A "typical" catathrenia begins with a deep inhalation, followed by a long, noisy exhalation, then a short, more pronounced exhalation, followed by another deep inhalation, often accompanied by arousal. The many harmonics of the sound indicate that it is produced by the vocal cords. It is often repeated in clusters, especially during REM sleep and at the end of the night. It does not disturb the sleepers, but their neighbors, and is associated with excessive daytime sleepiness in one-third of cases. The pathophysiology and treatment of typical catathrenia are still unknown. Later, a more atypical catathrenia was described, consisting of episodes of short (2 s), regular, semi-continuous expiratory moans during NREM sleep (mainly in stages N1 and N2) and REM sleep, often in people with mild upper airway obstruction. This atypical catathrenia is more commonly reduced by positive airway pressure and mandibular advancement devices that promote vertical opening.
Subject(s)
Polysomnography , Adult , Child , Female , Humans , Male , Parasomnias/physiopathology , Respiratory Sounds , Sleep Apnea, Central/physiopathology , Sleep Apnea, Central/therapy , Sleep Stages/physiology , Sleep, REM/physiologyABSTRACT
In contrast to obstructive sleep apnoea, the peak of sympathetic tone in central sleep apnoea occurs during the hyperventilation phase. To explore the temporal association of premature ventricular complex (PVC) burden in the context of the apnoea/hypopnoea-hyperpnoea cycle, the duration of apnoea/hypopnoea was defined as 100 %. We assessed the PVC burden throughout the apnoea/hypopnoea-hyperpnoea cycle during the periods of ±150 % in 50 % increments before and after the apnoea/hypopnoea phase. In this subanalysis of 54 SERVE-HF patients, PVC burden was 32 % higher in the late hyperventilation period (50-100 % after apnoea/hypopnoea) compared to the apnoea/hypopnoea phase.
Subject(s)
Heart Failure , Sleep Apnea, Central , Ventricular Premature Complexes , Humans , Sleep Apnea, Central/physiopathology , Sleep Apnea, Central/complications , Heart Failure/complications , Heart Failure/physiopathology , Male , Female , Ventricular Premature Complexes/physiopathology , Ventricular Premature Complexes/complications , Middle Aged , Aged , Polysomnography , Hyperventilation/physiopathology , Hyperventilation/complicationsABSTRACT
Wolfram syndrome is a rare autosomal recessive disorder affecting approximately 1 in 500,000 individuals. The disorder is most commonly caused by mutations in the WFS1 gene, which encodes an endoplasmic reticulum protein, wolframin, which is thought to protect against endoplasmic reticulum stress-related apoptosis. The major clinical findings of Wolfram syndrome are diabetes mellitus and optic atrophy, both of which usually appear before 16 years of age. Common additional findings include sensorineural hearing impairment, central diabetes insipidus, nonautoimmune hypothyroidism, delayed puberty, neurogenic bladder, cerebellar ataxia, and psychiatric disorders. Central sleep apnea is an uncommon but serious feature of Wolfram syndrome. However, the clinical details of this manifestation have not been documented. Herein, we report an adolescent with recently diagnosed Wolfram syndrome who demonstrated severe central sleep apnea on polysomnography testing. CITATION: Harris JC, Kenkare JD, Schramm CM. An adolescent with Wolfram syndrome and central sleep apnea. J Clin Sleep Med. 2024;20(7):1205-1208.
Subject(s)
Polysomnography , Sleep Apnea, Central , Wolfram Syndrome , Humans , Wolfram Syndrome/genetics , Wolfram Syndrome/complications , Wolfram Syndrome/physiopathology , Wolfram Syndrome/diagnosis , Adolescent , Sleep Apnea, Central/genetics , Sleep Apnea, Central/physiopathology , Sleep Apnea, Central/complications , MaleABSTRACT
OBJECTIVE: Ictal central apnea (ICA) is a semiological sign of focal epilepsy, associated with temporal and frontal lobe seizures. In this study, using qualitative and quantitative approaches, we aimed to assess the localizational value of ICA. We also aimed to compare ICA clinical utility in relation to other seizure semiological features of focal epilepsy. METHODS: We analyzed seizures in patients with medically refractory focal epilepsy undergoing intracranial stereotactic electroencephalographic (SEEG) evaluations with simultaneous multimodal cardiorespiratory monitoring. A total of 179 seizures in 72 patients with reliable artifact-free respiratory signal were analyzed. RESULTS: ICA was seen in 55 of 179 (30.7%) seizures. Presence of ICA predicted a mesial temporal seizure onset compared to those without ICA (odds ratio = 3.8, 95% confidence interval = 1.3-11.6, p = 0.01). ICA specificity was 0.82. ICA onset was correlated with increased high-frequency broadband gamma (60-150Hz) activity in specific mesial or basal temporal regions, including amygdala, hippocampus, and fusiform and lingual gyri. Based on our results, ICA has an almost 4-fold greater association with mesial temporal seizure onset zones compared to those without ICA and is highly specific for mesial temporal seizure onset zones. As evidence of symptomatogenic areas, onset-synchronous increase in high gamma activity in mesial or basal temporal structures was seen in early onset ICA, likely representing anatomical substrates for ICA generation. INTERPRETATION: ICA recognition may help anatomoelectroclinical localization of clinical seizure onset to specific mesial and basal temporal brain regions, and the inclusion of these regions in SEEG evaluations may help accurately pinpoint seizure onset zones for resection. ANN NEUROL 2024;95:998-1008.
Subject(s)
Epilepsy, Temporal Lobe , Humans , Male , Female , Adult , Middle Aged , Epilepsy, Temporal Lobe/physiopathology , Epilepsy, Temporal Lobe/diagnosis , Sleep Apnea, Central/physiopathology , Sleep Apnea, Central/diagnosis , Drug Resistant Epilepsy/physiopathology , Drug Resistant Epilepsy/diagnostic imaging , Drug Resistant Epilepsy/diagnosis , Seizures/physiopathology , Seizures/diagnosis , Young Adult , Electrocorticography/methods , Electroencephalography/methods , Adolescent , Epilepsies, Partial/physiopathology , Epilepsies, Partial/diagnosisABSTRACT
Medication-induced central sleep apnea (CSA) is one of the eight categories of causes of CSA but in the absence of awareness and careful history may be misclassified as primary CSA. While opioids are a well-known cause of respiratory depression and CSA, non-opioid medications including sodium oxybate, baclofen, valproic acid, gabapentin, and ticagrelor are less well-recognized. Opioids-induced respiratory depression and CSA are mediated primarily by µ-opioid receptors, which are abundant in the pontomedullary centers involved in breathing. The non-opioid medications, sodium oxybate, baclofen, valproic acid, and gabapentin, act upon brainstem gamma-aminobutyric acid (GABA) receptors, which co-colonize with µ-opioid receptors and mediate CSA. The pattern of ataxic breathing associated with these medications is like that induced by opioids on polysomnogram. Finally, ticagrelor also causes periodic breathing and CSA by increasing central chemosensitivity and ventilatory response to carbon dioxide. Given the potential consequences of CSA and the association between some of these medications with mortality, it is critical to recognize these adverse drug reactions, particularly because discontinuation of the offending agents has been shown to eliminate CSA.
Subject(s)
Sleep Apnea, Central , Humans , Sleep Apnea, Central/chemically induced , Sleep Apnea, Central/physiopathology , Analgesics, Opioid/adverse effects , Ticagrelor/adverse effects , Sodium Oxybate/adverse effects , Baclofen/adverse effects , Valproic Acid/adverse effects , Valproic Acid/therapeutic use , Adenosine/adverse effects , Gabapentin/adverse effects , Polysomnography/drug effectsABSTRACT
INTRODUCTION: Congenital Central Hypoventilation Syndrome (CCHS) is a rare disease due to a severely impaired central control of breathing and dysfunction of the autonomic nervous system. Ophthalmologic abnormalities are common in patients with CCHS and include horizontal strabismus, pupil and iris abnormalities and ptosis. We report a unique case of CCHS in association with monocular elevation deficit (MED) in a boy diagnosed with CCHS at birth. CASE DESCRIPTION: We report a case of a boy with a confirmed diagnosis of CCHS (complete sequencing of the paired-like homeobox 2b (PHOX2B) gene) after presenting little respiratory effort and cyanosis at birth. The ophthalmological examination shows an impaired elevation of the left eye, both in adduction and abduction, associated with mild and variable left ptosis. His mother has observed that the left eyelid elevates when the child feeds. A deviation in the primary gaze position or a chin-up position are not present. The funduscopic examination is normal. Given that deviation is limited to upgaze, the ptosis is mild and the patient's age, observation is decided. CONCLUSIONS: Ophthalmologic abnormalities are common in patients with CCHS and include horizontal strabismus, pupil and iris abnormalities and ptosis. To the best of our knowledge, this is the first report of MED in association with CCHS. Further studies are needed to determine if an association between MED and CCHS exists or is just a casual finding in this case.
Subject(s)
Blepharoptosis , Hypoventilation , Hypoventilation/congenital , Sleep Apnea, Central , Humans , Male , Hypoventilation/diagnosis , Hypoventilation/genetics , Hypoventilation/physiopathology , Blepharoptosis/diagnosis , Blepharoptosis/congenital , Blepharoptosis/physiopathology , Sleep Apnea, Central/diagnosis , Sleep Apnea, Central/physiopathology , Sleep Apnea, Central/genetics , Homeodomain Proteins/genetics , Infant, Newborn , Transcription Factors/genetics , Strabismus/diagnosis , Strabismus/physiopathologyABSTRACT
PURPOSE: Lateral sleep position has a significant beneficial effect on the severity of Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) in patients with heart failure (HF). We hypothesized that a reduction in rostral fluid shift from the legs in this position compared with the supine position may contribute to this effect. METHODS: In patients with CSR-CSA and an apnea-hypopnea index (AHI) ≥ 15/h (by standard polysomnography), uncalibrated leg fluid volume was measured in the supine, left lateral decubitus, and right lateral decubitus positions (in-laboratory assessment). The correlation between postural changes in fluid volume and corresponding changes in AHI was evaluated. Since there was no difference in both leg fluid volume and AHI between the right and left positions, measurements in these two conditions were combined into a single lateral position. RESULTS: In 18 patients with CSR-CSA, leg fluid volume increased by 2.7 ± 3.1% (p = 0.002) in the lateral position compared to the supine position, while AHI decreased by 46 ± 20% (p < 0.0001) with the same postural change. The correlation between postural changes in AHI and leg fluid volume was 0.22 (p = 0.42). Changes in leg fluid volume were a slow phenomenon, whereas changes in CSR-CSA severity were almost synchronous with changes in posture. CONCLUSION: Lateral position causes a reduction in rostral fluid shift compared to the supine position, but this change does not correlate with the corresponding change in CSR-CSA severity. The two changes occur on different time scales. These findings question the role of postural changes in rostral fluid shift as a determinant of corresponding changes in CSR-CSA severity.
Subject(s)
Cheyne-Stokes Respiration , Fluid Shifts , Heart Failure , Polysomnography , Posture , Humans , Cheyne-Stokes Respiration/physiopathology , Heart Failure/physiopathology , Male , Female , Middle Aged , Aged , Fluid Shifts/physiology , Posture/physiology , Sleep Apnea, Central/physiopathology , Supine Position/physiology , Severity of Illness Index , Leg/physiopathologyABSTRACT
Rationale: Congenital central hypoventilation syndrome (CCHS) is a rare autonomic disorder with altered regulation of breathing, heart rate (HR), and blood pressure (BP). Aberrant cerebral oxygenation in response to hypercapnia/hypoxia in CCHS raises the concern that altered cerebral autoregulation may contribute to CCHS-related, variably impaired neurodevelopment. Objectives: To evaluate cerebral autoregulation in response to orthostatic challenge in CCHS cases versus controls. Methods: CCHS and age- and sex-matched control subjects were studied with head-up tilt (HUT) testing to induce orthostatic stress. Fifty CCHS and 100 control HUT recordings were included. HR, BP, and cerebral oxygen saturation (regional oxygen saturation) were continuously monitored. The cerebral oximetry index (COx), a real-time measure of cerebral autoregulation based on these measures, was calculated. Measurements and Main Results: HUT resulted in a greater mean BP decrease from baseline in CCHS versus controls (11% vs. 6%; P < 0.05) and a diminished increase in HR in CCHS versus controls (11% vs. 18%; P < 0.01) in the 5 minutes after tilt-up. Despite a similar COx at baseline, orthostatic provocation within 5 minutes of tilt-up caused a 50% greater increase in COx (P < 0.01) and a 29% increase in minutes of impaired autoregulation (P < 0.02) in CCHS versus controls (4.0 vs. 3.1 min). Conclusions: Cerebral autoregulatory mechanisms appear to be intact in CCHS, but the greater hypotension observed in CCHS consequent to orthostatic provocation is associated with greater values of COx/impaired autoregulation when BP is below the lower limits of autoregulation. Effects of repeated orthostatic challenges in everyday living in CCHS necessitate further study to determine their influence on neurodevelopmental disease burden.
Subject(s)
Brain/physiopathology , Homeostasis/physiology , Hypotension, Orthostatic/etiology , Hypoventilation/congenital , Oxygen/metabolism , Posture/physiology , Sleep Apnea, Central/physiopathology , Adolescent , Biomarkers/metabolism , Brain/metabolism , Case-Control Studies , Child , Female , Humans , Hypotension, Orthostatic/physiopathology , Hypoventilation/metabolism , Hypoventilation/physiopathology , Male , Oximetry , Sleep Apnea, Central/metabolism , Tilt-Table Test , Young AdultSubject(s)
Hypertension, Pulmonary/epidemiology , Hypertension, Pulmonary/physiopathology , Iron Deficiencies/epidemiology , Lung Diseases/physiopathology , Aged , Chronic Disease , Female , Humans , Hypertension, Pulmonary/etiology , Iron Deficiencies/metabolism , Lung Diseases/complications , Lung Diseases, Interstitial/complications , Lung Diseases, Interstitial/physiopathology , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Emphysema/complications , Pulmonary Emphysema/physiopathology , Pulmonary Fibrosis/complications , Pulmonary Fibrosis/physiopathology , Pulmonary Wedge Pressure/physiology , Receptors, Transferrin/metabolism , Severity of Illness Index , Sleep Apnea, Central/complications , Sleep Apnea, Central/physiopathology , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/physiopathology , Vascular Resistance/physiology , Vascular Stiffness/physiologyABSTRACT
CASE PRESENTATION: An 8-month-old previously healthy, full-term girl presented with altered mental status after falling approximately 3 feet from a bed, landing on her head. In the ED, she had a CT scan of her head (Fig 1) and was intubated for airway protection. While in the PICU, initial chest radiography showed bilateral infiltrates that were consistent with ARDS, which subsequently resolved. Her respiratory status continued to improve, which allowed a trial on CPAP with invasive neurally adjusted ventilatory assist (NAVA) support, which she was unable to tolerate because of the need for increased support during sleep. On hospital day 8, she was extubated to noninvasive NAVA and was noted to have poor truncal tone and inability to lift or rotate her head. Repeat head CT scans were unchanged. Despite nasal CPAP and NAVA support, she experienced hypercapnia to 83 mm Hg that required reintubation. Brain MRI was completed on hospital day 10 (Fig 1). Lumbar puncture results were obtained, which were unremarkable. Extubation was attempted again on hospital days 15 and 22 with subsequent hypercapnia that required reintubation. She was able to gradually lengthen her CPAP trials but continued to have periods of hypercapnia and bradypnea.
Subject(s)
Accidental Falls , Magnetic Resonance Imaging/methods , Medulla Oblongata , Sleep Apnea, Central , Tomography, X-Ray Computed/methods , Diagnosis, Differential , Female , Humans , Infant , Interactive Ventilatory Support/methods , Long-Term Care/methods , Medulla Oblongata/diagnostic imaging , Medulla Oblongata/pathology , Patient Care Management/methods , Polysomnography/methods , Sleep Apnea, Central/diagnosis , Sleep Apnea, Central/etiology , Sleep Apnea, Central/physiopathology , Sleep Apnea, Central/therapy , Tracheostomy/methods , Ventilator Weaning/methodsABSTRACT
Rationale: Congenital central hypoventilation syndrome (CCHS) is characterized by life-threatening sleep hypoventilation and is caused by PHOX2B gene mutations, most frequently the PHOX2B27Ala/+ mutation, with patients requiring lifelong ventilatory support. It is unclear whether obstructive apneas are part of the syndrome. Objectives: To determine if Phox2b27Ala/+ mice, which present the main symptoms of CCHS and die within hours after birth, also express obstructive apneas, and to investigate potential underlying mechanisms. Methods: Apneas were classified as central, obstructive, or mixed by using a novel system combining pneumotachography and laser detection of abdominal movement immediately after birth. Several respiratory nuclei involved in airway patency were examined by immunohistochemistry and electrophysiology in brainstem-spinal cord preparations. Measurements and Main Results: The median (interquartile range) of obstructive apnea frequency was 2.3 (1.5-3.3)/min in Phox2b27Ala/+ pups versus 0.6 (0.4-1.0)/min in wild types (P < 0.0001). Obstructive apnea duration was 2.7 seconds (2.3-3.9) in Phox2b27Ala/+ pups versus 1.7 seconds (1.1-1.9) in wild types (P < 0.0001). Central and mixed apneas presented similar significant differences. In Phox2b27Ala/+ preparations, the hypoglossal nucleus had fewer (P < 0.05) and smaller (P < 0.01) neurons, compared with wild-type preparations. Importantly, coordination of phrenic and hypoglossal motor activities was disrupted, as evidenced by the longer and variable delay of hypoglossal activity with respect to phrenic activity onset (P < 0.001). Conclusions: The Phox2b27Ala/+ mutation predisposed pups not only to hypoventilation and central apneas, but also to obstructive and mixed apneas, likely because of hypoglossal dysgenesis. These results thus demand attention toward obstructive events in infants with CCHS.
Subject(s)
Hypoventilation/congenital , Hypoventilation/diagnosis , Hypoventilation/genetics , Hypoventilation/physiopathology , Sleep Apnea, Central/congenital , Sleep Apnea, Central/diagnosis , Sleep Apnea, Central/genetics , Sleep Apnea, Central/physiopathology , Animals , Animals, Newborn , Disease Models, Animal , Homeodomain Proteins/genetics , Humans , Mice , Mutation , Transcription Factors/geneticsABSTRACT
STUDY OBJECTIVES: The use of mouse models in sleep apnea study is limited by the belief that central (CSA) but not obstructive sleep apneas (OSA) occur in rodents. We aimed to develop a protocol to investigate the presence of OSAs in wild-type mice and, then, to apply it to a validated model of Down syndrome (Ts65Dn), a human pathology characterized by a high incidence of OSAs. METHODS: In a pilot study, nine C57BL/6J wild-type mice were implanted with electrodes for electroencephalography (EEG), neck electromyography (nEMG), and diaphragmatic activity (DIA), and then placed in a whole-body-plethysmographic (WBP) chamber for 8 h during the rest (light) phase to simultaneously record sleep and breathing activity. CSA and OSA were discriminated on the basis of WBP and DIA signals recorded simultaneously. The same protocol was then applied to 12 Ts65Dn mice and 14 euploid controls. RESULTS: OSAs represented about half of the apneic events recorded during rapid-eye-movement-sleep (REMS) in each experimental group, while the majority of CSAs were found during non-rapid eye movement sleep. Compared with euploid controls, Ts65Dn mice had a similar total occurrence rate of apneic events during sleep, but a significantly higher occurrence rate of OSAs during REMS, and a significantly lower occurrence rate of CSAs during NREMS. CONCLUSIONS: Mice physiologically exhibit both CSAs and OSAs. The latter appear almost exclusively during REMS, and are highly prevalent in Ts65Dn. Mice may, thus, represent a useful model to accelerate the understanding of the pathophysiology and genetics of sleep-disordered breathing and to help the development of new therapies.
Subject(s)
Down Syndrome/physiopathology , Sleep Apnea, Central/physiopathology , Sleep Apnea, Obstructive/physiopathology , Sleep, REM/physiology , Animals , Disease Models, Animal , Electroencephalography , Electromyography , Mice , Pilot Projects , Plethysmography, Whole BodyABSTRACT
Rationale: Determining whether an individual has obstructive or central sleep apnea is fundamental to selecting the appropriate treatment. Objectives: Here we derive an automated breath-by-breath probability of obstruction, as a surrogate of gold-standard upper airway resistance, using hallmarks of upper airway obstruction visible on clinical sleep studies. Methods: From five nocturnal polysomnography signals (airflow, thoracic and abdominal effort, oxygen saturation, and snore), nine features were extracted and weighted to derive the breath-by-breath probability of obstruction (Pobs). A development and initial test set of 29 subjects (development = 6, test = 23) (New York, NY) and a second test set of 39 subjects (Solingen, Germany), both with esophageal manometry, were used to develop Pobs and validate it against gold-standard upper airway resistance. A separate dataset of 114 subjects with 2 consecutive nocturnal polysomnographies (New York, NY) without esophageal manometry was used to assess the night-to-night variability of Pobs. Measurements and Main Results: A total of 1,962,229 breaths were analyzed. On a breath-by-breath level, Pobs was strongly correlated with normalized upper airway resistance in both test sets (set 1: cubic adjusted [adj.] R2 = 0.87, P < 0.001, area under the receiver operating characteristic curve = 0.74; set 2: cubic adj. R2 = 0.83, P < 0.001, area under the receiver operating characteristic curve = 0.7). On a subject level, median Pobs was associated with the median normalized upper airway resistance (set 1: linear adj. R2 = 0.59, P < 0.001; set 2: linear adj. R2 = 0.45, P < 0.001). Median Pobs exhibited low night-to-night variability [intraclass correlation(2, 1) = 0.93]. Conclusions: Using nearly 2 million breaths from 182 subjects, we show that breath-by-breath probability of obstruction can reliably predict the overall burden of obstructed breaths in individual subjects and can aid in determining the type of sleep apnea.
Subject(s)
Clinical Decision Rules , Polysomnography , Sleep Apnea, Central/diagnosis , Sleep Apnea, Obstructive/diagnosis , Adult , Aged , Airway Resistance , Diagnosis, Differential , Female , Humans , Logistic Models , Male , Middle Aged , ROC Curve , Reproducibility of Results , Sleep Apnea, Central/physiopathology , Sleep Apnea, Obstructive/physiopathologyABSTRACT
This document summarizes suggestions of the central sleep apnea (CSA) Technical Expert Panel working group. This paper shares our vision for bringing the right device to the right patient at the right time. For patients with CSA, current coverage criteria do not align with guideline treatment recommendations. For example, CPAP and oxygen therapy are recommended but not covered for CSA. On the other hand, bilevel positive airway pressure (BPAP) without a backup rate may be a covered therapy for OSA, but it may worsen CSA. Narrow coverage criteria that require near elimination of obstructive breathing events on CPAP or BPAP in the spontaneous mode, even if at poorly tolerated pressure levels, may preclude therapy with BPAP with backup rate or adaptive servoventilation, even when those devices provide demonstrably better therapy. CSA is a dynamic disorder that may require different treatments over time, sometimes switching from one device to another; an example is switching from BPAP with backup rate to an adaptive servoventilation with automatic end-expiratory pressure adjustments, which may not be covered. To address these challenges, we suggest several changes to the coverage determinations, including: (1) a single simplified initial and continuing coverage definition of CSA that aligns with OSA; (2) removal of hypoventilation terminology from coverage criteria for CSA; (3) all effective therapies for CSA should be covered, including oxygen and all PAP devices with or without backup rates or servo-mechanisms; and (4) patients shown to have a suboptimal response to one PAP device should be allowed to add oxygen or change to another PAP device with different capabilities if shown to be effective with testing.