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Showing papers on "Hypoventilation published in 2020"


Journal Article
TL;DR: Except for mild hypoventilation and hypoxemia, a patient has been followed for 7 years after exposure to silage gas and chest film showed diffuse reticular and fine nodular infiltrates.
Abstract: A patient has been followed for 7 years after exposure to silage gas. His chest film showed diffuse reticular and fine nodular infiltrates. Except for mild hypoventilation and hypoxemia hi...

59 citations


Journal ArticleDOI
TL;DR: The clinical timeline of symptoms of ROHHAD(NET) is described and guidance for systematic follow-up and multidisciplinary management is proposed with the aim of improving prognosis and life expectancy.
Abstract: Context Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, autonomic dysregulation and neural crest tumor (ROHHHAD[NET]) is a rare and potentially fatal disease. No specific diagnostic biomarker is currently available, making prompt diagnosis challenging. Since its first definition in 2007, a complete clinical analysis leading to specific diagnosis and follow-up recommendations is still missing. Objective The purpose of this work is to describe the clinical timeline of symptoms of ROHHAD(NET) and propose recommendations for diagnosis and follow-up. Design We conducted a systematic review of all ROHHAD(NET) case studies and report a new ROHHAD patient with early diagnosis and multidisciplinary care. Methods All the articles that meet the definition of ROHHAD(NET) and provide chronological clinical data were reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis individual patient data guidelines. The data were grouped into 7 categories: hypothalamic dysfunction, autonomic dysregulation, hypoventilation, NET, psychiatric symptoms, other clinical manifestations, and outcome. Results Forty-three individual patient data descriptions were analyzed. The timeline of the disease shows rapid-onset obesity followed shortly by hypothalamic dysfunction. Dysautonomia was reported at a median age of 4.95 years and hypoventilation at 5.33 years, or 2.2 years after the initial obesity. A NET was reported in 56% of the patients, and 70% of these tumors were diagnosed within 2 years after initial weight gain. Conclusion Because early diagnosis improves the clinical management and the prognosis in ROHHAD(NET), this diagnosis should be considered for any child with rapid and early obesity. We propose guidance for systematic follow-up and advise multidisciplinary management with the aim of improving prognosis and life expectancy.

30 citations


Journal ArticleDOI
TL;DR: Obesity hypoventilation syndrome can be treated with either continuous positive airway pressure (CPAP) or non‐invasive ventilation (NIV) therapy; the device choice has important economic and operational implications.
Abstract: Background and objective Obesity hypoventilation syndrome (OHS) can be treated with either continuous positive airway pressure (CPAP) or non-invasive ventilation (NIV) therapy; the device choice has important economic and operational implications. Methods This multicentre interventional trial investigated the safety and short-term efficacy of switching stable OHS patients who were on successful NIV therapy for ≥3 months to CPAP therapy. Patients underwent an autotitrating CPAP night under polysomnography (PSG); if the ensuing parameters were acceptable, they were sent home on a fixed CPAP for a 4-6-week period. It was hypothesized that blood gas analysis, PSG parameters and lung function tests would remain unchanged. Results A total of 42 OHS patients were recruited, of whom 37 patients were switched to CPAP therapy. All patients had a history of severe obstructive sleep apnoea syndrome; chronic obstructive pulmonary disease (COPD) (Global Initiative for Obstructive Lung Disease (GOLD) I/II) was present in 52%. Regarding the primary outcome, 30 of 42 patients (71%, 95% CI: 55-84%) maintained daytime partial pressure of carbon dioxide (PaCO2 ) levels ≤45 mm Hg after the home CPAP period. There was no further impairment in quality of life, sleep parameters or lung function. Interestingly, 24 patients (65%) preferred CPAP as their long-term therapy, despite the high pressure levels used (mean: 13.8 ± 1.8 mbar). After the CPAP period, 7 of 37 patients were categorized as CPAP failure, albeit only due to mild hypercapnia (mean: 47.9 ± 2.7 mm Hg). Conclusion It is feasible to switch most stable OHS patients from NIV to CPAP therapy, a step that could significantly reduce health-related costs. The auto-adjusted CPAP device, used in combination with the analysis of the PSG and capnometry, is a valid titration method in OHS patients.

23 citations


Journal ArticleDOI
TL;DR: The clinical presentations of the acute stage of anti-N-methyl-d-aspartate (NMDA) receptor encephalitis and the neurocritical care strategy in intensive care units are summarized.
Abstract: In this review, we summarize the clinical presentations of the acute stage of anti-N-methyl-d-aspartate (NMDA) receptor encephalitis and the neurocritical care strategy in intensive care units. Anti-NMDA receptor encephalitis has characteristic clinical features and is predominantly seen in young adults and children. Most patients have five stages of clinical presentation, including a prodromal phase, psychotic and/or seizure phase, unresponsive and/or catatonic phase, hyperkinetic phase, and gradual recovery phase. The clinical course usually begins with viral infection-like symptoms that last for up to 2 weeks (prodromal phase), followed by the rapid development of schizophrenia-like psychiatric symptoms and seizures (psychotic and seizure phase). Patients may have a decreased level of consciousness with central hypoventilation, frequently requiring mechanical ventilation. In the subsequent hyperkinetic phase, patients present with orofacial-limb dyskinesia and autonomic instability. Children with significant neurological symptoms of anti-NMDA receptor encephalitis should initially be managed in a pediatric intensive care unit. The acute critical presentations are, refractory seizures, autonomic dysfunction, hypoventilation, cardiac arrhythmia, and hyperkinetic crisis. Symptom-guided therapies and critical care are necessary in the acute stage to improve the prognosis.

19 citations


Journal ArticleDOI
TL;DR: In vitro studies demonstrated that DAMGO reduced the frequency of excitatory post-synaptic currents in hypoglossal motoneurons and that application of leptin restoredexcitatory synaptic neurotransmission, suggesting that intranasal leptin may prevent opioid respiratory depression during sleep in obese patients receiving opioids without reducing analgesia.
Abstract: Respiratory depression is the main cause of morbidity and mortality associated with opioids. Obesity increases opioid-related mortality, which is mostly related to comorbid obstructive sleep apnea. Naloxone, a μ-opioid receptor blocker, is an effective antidote, but it reverses analgesia. Like humans with obesity, mice with diet-induced obesity hypoventilate during sleep and develop obstructive sleep apnea, which can be treated with intranasal leptin. We hypothesized that intranasal leptin reverses opioid-induced sleep-disordered breathing in obese mice without decreasing analgesia. To test this hypothesis, mice with diet-induced obesity were treated with morphine at 10 mg/kg subcutaneously and with leptin or placebo intranasally. Sleep and breathing were recorded by barometric plethysmography, and pain sensitivity was measured by the tail-flick test. Excitatory postsynaptic currents were recorded in vitro from hypoglossal motor neurons after the application of the μ-opioid receptor agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin and leptin. Morphine dramatically increased the frequency of apneas and greatly increased the severity of hypoventilation and obstructive sleep apnea. Leptin decreased the frequency of apneas, improved obstructive sleep apnea, and completely reversed hypoventilation, whereas morphine analgesia was enhanced. Our in vitro studies demonstrated that [D-Ala2, N-MePhe4, Gly-ol]-enkephalin reduced the frequency of excitatory postsynaptic currents in hypoglossal motoneurons and that application of leptin restored excitatory synaptic neurotransmission. Our findings suggest that intranasal leptin may prevent opioid respiratory depression during sleep in patients with obesity receiving opioids without reducing analgesia.

16 citations


Journal ArticleDOI
TL;DR: A greater ventilation, through voluntary hyperventilation, does not influence global or posterior cerebral blood flow during carbon dioxide breathing, and Cerebrovascular reactivity to carbon dioxide is not influenced by an individual's ventilatory sensitivity tocarbon dioxide.
Abstract: New findings What is the central question of this study? Do differing magnitudes of ventilation influence cerebrovascular CO2 reactivity and the cerebral blood flow response to increases in arterial carbon dioxide? What is the main finding and its importance? While a greater ventilation, through voluntary hyperventilation, is associated with a higher anterior cerebral blood flow during carbon dioxide breathing, this elevated cerebral blood flow is due to a higher blood pressure and not ventilation per se. A greater ventilation, through voluntary hyperventilation, does not influence global or posterior cerebral blood flow during carbon dioxide breathing. Cerebrovascular reactivity to carbon dioxide is not influenced by an individual's ventilatory sensitivity to carbon dioxide. Abstract Recent work demonstrated an influence of ventilation on cerebrovascular reactivity to CO2 ; however, the concomitant influence of changes in mean arterial blood pressure (MAP) on ventilation-induced differences in cerebral blood flow (CBF) has yet to be examined in this context. Healthy participants (n = 15; 25 ± 3 years of age; 179 ± 6 cm height; 74 ± 10 kg weight; 3 female) underwent end-tidal forcing to increase their partial pressure of end-tidal CO2 by +3, +6 and +9 mmHg above baseline in 5-min sequential steps while maintaining iso-oxia. This protocol was then repeated twice, with participants hyperventilating and hypoventilating by ∼30% compared to the first trial. Intra-cranial and extra-cranial CBF were measured using ultrasound. The MAP (finger photo-plethysmography) was higher during the hyperventilation and hypoventilation trials compared to normal ventilation (main effects, P 0.05 for all). Retrospective analysis of a larger data set (n = 53) confirmed these observations and demonstrated no relationships between the ventilatory and global CBF response to hypercapnia (r2 = 0.04; P = 0.14). Therefore, when differences in MAP are accounted for, cerebrovascular CO2 reactivity (assessed via end-tidal forcing) is independent of the magnitude of ventilation.

16 citations


Journal ArticleDOI
TL;DR: The findings show that NHF can improve ventilation during sedation, which may reduce the risk of complications related to hypoventilation.

14 citations


Journal ArticleDOI
TL;DR: There is a high prevalence of obstructive sleep apnea (OSA) in children with Down syndrome (DS), sometimes associated with alveolar hypoventilation.
Abstract: Background There is a high prevalence of obstructive sleep apnea (OSA) in children with Down syndrome (DS), sometimes associated with alveolar hypoventilation. Objective To compare transcutaneous partial pressure of carbon dioxide (PtcCO2 ) and pulse oximetry (SpO2 ) in children with DS and in control children with OSA. Patients and methods This retrospective case-control study involved children followed in Trousseau Hospital (Paris) Sleep Center. Polysomnography (PSG) recordings and clinical files of children with DS were reviewed to identify clinical signs of OSA and comorbidities associated with DS. Controls were children who presented with OSA of ENT origin without other comorbidities (exceptions: two overweight, one obese, and three with well-controlled asthma). DS subjects and controls were matched for age and apnea hypopnea index. Results There were 28 children in each group. Mean PtcCO2 during sleep was significantly higher in patients with DS compared to controls (44 mm Hg vs 42 mm Hg, P = .001). Five (21%) patients with DS met the American Academy of Sleep medicine criteria for hypoventilation, compared to one (4%) in the control group. The mean PtcO2 during sleep was significantly lower in patients with DS (77 mm Hg vs 82 mm Hg, P = .003). Conclusions This is the first study to compare nocturnal gas exchange in children with DS to a control group of children with similar OSA. Our data demonstrate that children with DS have increased PtcCO2 regardless of the presence of OSA and its severity. This may be due to respiratory muscle hypotonia and/or ventilatory control alteration in patients with DS.

11 citations


Book ChapterDOI
01 Jan 2020
TL;DR: Different methods of monitoring ventilation in patients with obesity hypoventilation syndrome are considered and discussed in both an inpatient and outpatient clinical settings to ensure patient safety, as well as effectiveness and efficiency of treatment.
Abstract: This chapter aims to consider and discuss different methods of monitoring ventilation in patients with obesity hypoventilation syndrome (OHS) in both an inpatient and outpatient clinical settings. Monitoring ventilation is essential to ensure patient safety, as well as effectiveness and efficiency of treatment. OHS is associated with increased mortality, impaired quality of life, and increased healthcare utilization. Therefore, ensuring the effectiveness of treatment with continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV) is imperative for achieving good patient outcomes while providing high value health care. Ventilation can be monitored by measuring symptoms, carbon dioxide, bicarbonate levels, pulse oximetry, and ventilator data downwards. It is likely that a combination of these methods will aid clinicians in determining optimal care.

10 citations


Journal ArticleDOI
TL;DR: This review summarizes a number of important topics with recent advances put into the context of the existing literature, ranging from anatomic and nonanatomic pathophysiological mechanisms of obstructive sleep apnoea, nocturnal symptoms and hypoxaemia in pulmonary disease and positive airway pressure.
Abstract: Considerable progress has been made in the area of sleep and breathing. We write this review to summarize a number of important topics with recent advances put into the context of the existing literature. While we recognize major progress in many different areas of sleep and ventilation, ranging from anatomic and nonanatomic pathophysiological mechanisms of obstructive sleep apnoea (OSA), nocturnal symptoms and hypoxaemia in pulmonary disease and positive airway pressure (PAP), we have focused on those felt to be most important and likely to affect clinical practice.

10 citations


Journal ArticleDOI
TL;DR: Hypoxia-induced ventilatory depression during fentanyl induced apnea opposes the spontaneous emergence of a respiratory rhythm, which would have rescued the animals otherwise, and prevents the effects of high dose naloxone.
Abstract: Background As severe acute hypoxemia produces a rapid inhibition of the respiratory neuronal activity through a nonopioid mechanism, we have investigated in adult rats the effects of hypoxemia after fentanyl overdose-induced apnea on (1) autoresuscitation and (2) the antidotal effects of naloxone. Methods In nonsedated rats, the breath-by-breath ventilatory and pulmonary gas exchange response to fentanyl overdose (300 µg · kg · min iv in 1 min) was determined in an open flow plethysmograph. The effects of inhaling air (nine rats) or a hypoxic mixture (fractional inspired oxygen tension between 7.3 and 11.3%, eight rats) on the ability to recover a spontaneous breathing rhythm and on the effects of naloxone (2 mg · kg) were investigated. In addition, arterial blood gases, arterial blood pressure, ventilation, and pulmonary gas exchange were determined in spontaneously breathing tracheostomized urethane-anesthetized rats in response to (1) fentanyl-induced hypoventilation (7 rats), (2) fentanyl-induced apnea (10 rats) in air and hyperoxia, and (3) isolated anoxic exposure (4 rats). Data are expressed as median and range. Results In air-breathing nonsedated rats, fentanyl produced an apnea within 14 s (12 to 29 s). A spontaneous rhythmic activity always resumed after 85.4 s (33 to 141 s) consisting of a persistent low tidal volume and slow frequency rhythmic activity that rescued all animals. Naloxone, 10 min later, immediately restored the baseline level of ventilation. At fractional inspired oxygen tension less than 10%, fentanyl-induced apnea was irreversible despite a transient gasping pattern; the administration of naloxone had no effects. In sedated rats, when PaO2 reached 16 mmHg during fentanyl-induced apnea, no spontaneous recovery of breathing occurred and naloxone had no rescuing effect, despite circulation being maintained. Conclusions Hypoxia-induced ventilatory depression during fentanyl induced apnea (1) opposes the spontaneous emergence of a respiratory rhythm, which would have rescued the animals otherwise, and (2) prevents the effects of high dose naloxone.

Journal ArticleDOI
TL;DR: The diagnostic performance of the MND-DS was better than the respiratory domain of the ALSFRS-R for screening reduced respiratory function in patients with MND, and is, therefore, the preferred method for (remotely) monitoring respiratory function.
Abstract: Poor monitoring of respiratory function may lead to late initiation of non-invasive ventilation (NIV) in patients with motor neuron diseases (MND). Monitoring could be improved by remotely assessing hypoventilation symptoms between clinic visits. We aimed to determine which patient-reported hypoventilation symptoms are best for screening reduced respiratory function in patients with MND, and compared them to the respiratory domain of the amyotrophic lateral sclerosis functional rating scale (ALSFRS-R). This prospective multi-center study included 100 patients with MND, who were able to perform a supine vital capacity test. Reduced respiratory function was defined as a predicted supine vital capacity ≤ 80%. We developed a 14-item hypoventilation symptom questionnaire (HYSQ) based on guidelines, expert opinion and think-aloud interviews with patients. Symptoms of the HYSQ were related to dyspnea, sleep quality, sleepiness/fatigue and pneumonia. The diagnostic performances of these symptoms and the ALSFRS-R respiratory domain were determined from the receiver operating characteristic (ROC) curves, area under the curve (AUC), sensitivity, specificity, predictive values and accuracy. Dyspnea-related symptoms (dyspnea while eating/talking, while lying flat and during light activity) were combined into the MND Dyspnea Scale (MND-DS). ROC curves showed that the MND-DS had the best diagnostic performance, with the highest AUC = 0.72, sensitivity = 75% and accuracy = 71%. Sleep-quality symptoms, sleepiness/fatigue-related symptoms and the ALSFRS-R respiratory domain showed weak diagnostic performance. The diagnostic performance of the MND-DS was better than the respiratory domain of the ALSFRS-R for screening reduced respiratory function in patients with MND, and is, therefore, the preferred method for (remotely) monitoring respiratory function.

Journal ArticleDOI
TL;DR: Respiratory complications often result from acute spinal cord injury and hypoventilation and airway secretions must be effectively treated to prevent lung disease and to maintain normal O2 saturation and CO2 levels without supplemental O2.

Journal ArticleDOI
TL;DR: It appears that patients with central-predominant hypoventilation are more sensitive to propofol during the induction of sedation, and RESP values could be used to tailor sedation management specifically to individual patients.
Abstract: Capnography involves the measurement of end-tidal CO2 (EtCO2) values to detect hypoventilation in patients undergoing sedation. In a previous study, we reported that initiating a flexible bronchoscopy (FB) examination only after detecting signs of hypoventilation could reduce the risk of hypoxemia without compromising the tolerance of the patient for this type of intervention. We hypothesize that hypoventilation status could be determined with greater precision by combining thoracic impedance-based respiratory signals, RESP, and EtCO2 signals obtained from a nasal-oral cannula. Retrospective analysis was conducted on RESP and EtCO2 waveforms obtained from patients during the induction of sedation using propofol for bronchoscopic examination in a previous study. EtCO2 waveforms associated with hypoventilation were then compared with RESP patterns, patient variables, and sedation outcomes. Signals suitable for analysis were obtained from 44 subjects, 42 of whom presented indications of hypoventilation, as determined by EtCO2 waveforms. Two subtypes of hypoventilation were identified by RESP: central-predominant (n = 22, flat line RESP pattern) and non-central-predominant (n = 20, RESP pattern indicative of respiratory effort with upper airway collapse). Compared to cases of non-central-predominant hypoventilation, those presenting central-predominant hypoventilation during induction were associated with a lower propofol dose (40.2 ± 18.3 vs. 60.8 ± 26.1 mg, p = 0.009), a lower effect site concentration of propofol (2.02 ± 0.33 vs. 2.38 ± 0.44 µg/ml, p = 0.01), more rapid induction (146.1 ± 105.5 vs. 260.9 ± 156.2 s, p = 0.01), and lower total propofol dosage (96.6 ± 41.7 vs. 130.6 ± 53.4 mg, p = 0.04). Hypoventilation status (as revealed by EtCO2 levels) could be further classified by RESP into central-predominant or non-central-predominant types. It appears that patients with central-predominant hypoventilation are more sensitive to propofol during the induction of sedation. RESP values could be used to tailor sedation management specifically to individual patients.

Journal ArticleDOI
TL;DR: The findings on the main current treatment modalities OHS will be discussed and the importance of early diagnosis and effective treatment for improved patient outcomes is discussed.

Journal ArticleDOI
TL;DR: Invasive ventilation via tracheotomy represents the ultimate alternative for children with severe disease and little or no ventilatory autonomy and in patients with neuromuscular, neurological or lung disorders, non-invasive management in case of NIV failure is more challenging.
Abstract: Non-invasive ventilation (NIV) and continuous positive airway pressure (CPAP) are effective treatments for children with severe sleep disordered breathing (SBD). However, some patients may present too severe SDB that do not respond to NIV/CPAP or insufficient compliance to treatment. A careful revaluation of the interface and of ventilator settings should be performed before considering alternative treatments. In patients with obstructive sleep apnea (OSA), alternatives to CPAP/NIV rely on the underlying disease. Ear-nose-throat (ENT) surgery such as adeno-tonsillectomy (AT), turbinectomy or supraglottoplasty represent an effective treatment in selected patients before starting CPAP/NIV and should be reconsidered in case of CPAP failure. Rapid maxillary expansion (RME) is restricted to children with OSA and a narrow palate who have little adenotonsillar tissue, or for those with residual OSA after AT. Weight loss is the first line therapy for obese children with OSA before starting CPAP and should remain a priority in the long-term. Selected patients may benefit from maxillo-facial surgery such as mandibular distraction osteogenesis (MDO) or from neurosurgery procedures like fronto-facial monobloc advancement. Nasopharyngeal airway (NPA) or high flow nasal cannula (HFNC) may constitute efficient alternatives to CPAP in selected patients. Hypoglossal nerve stimulation has been proposed in children with Down syndrome not tolerant to CPAP. Ultimately, tracheostomy represents the unique alternative in case of failure of all the above-mentioned treatments. All these treatments require a multidisciplinary approach with a personalized treatment tailored on the different diseases and sites of obstruction. In patients with neuromuscular, neurological or lung disorders, non-invasive management in case of NIV failure is more challenging. Diaphragmatic pacing has been proposed for some patients with central congenital hypoventilation syndrome (CCHS) or neurological disorders, however its experience in children is limited. Finally, invasive ventilation via tracheotomy represents again the ultimate alternative for children with severe disease and little or no ventilatory autonomy. However, ethical considerations weighting the efficacy against the burden of this treatment should be discussed before choosing this last option.

Journal ArticleDOI
TL;DR: In view of the consequences associated with sleep apnea and hypoventilation, it is advised to perform a polysomnography in children with MECP2 duplication.
Abstract: There is limited knowledge on the occurrence of respiratory manifestations and sleep-disordered breathing in particular in children with the MECP2 duplication syndrome. Although sleep-disordered breathing and nocturnal hypoventilation are currently not cited as an important symptom in these children, we present three cases who all had an abnormal breathing during sleep. In view of the consequences associated with sleep apnea and hypoventilation, we advise to perform a polysomnography in children with MECP2 duplication. Different treatment modalities (ENT surgery, CPAP, and non-invasive ventilation) can be applied to successfully treat these conditions.

Journal ArticleDOI
TL;DR: A questionnaire is proposed to help physicians identify patients with ROHHAD-syndrome, a rare, potentially fatal, pediatric syndrome with rapid onset of obesity that was underestimated, and the patients were misdiagnosed with other more common obesity syndromes.
Abstract: Objectives Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) is a rare, potentially fatal, pediatric syndrome. Case presentations We describe three cases of ROHHAD-syndrome in Greece. The main and earliest symptom was the excessive and rapid weight gain at 5, 2, and 3 years of age. Years after the onset of obesity, the patients developed hypothalamic dysfunction with various endocrinological abnormalities (at 9, 8, and 6.8 years, respectively), autonomic dysregulation and finally, alveolar hypoventilation (at 14.6, 8, and 7.8 years, respectively), leading to the diagnosis of ROHHAD-syndrome. Conclusions The rarity of the syndrome, the variable symptoms' presentation, and the lack of specific diagnostic tests could explain why no previous cases have been reported from our country. The rapid onset of obesity was underestimated, and the patients were misdiagnosed with other more common obesity syndromes. Therefore, we propose a questionnaire to help physicians identify patients with ROHHAD-syndrome.

Journal ArticleDOI
TL;DR: The original narrative of central alveolar hypoventilation syndrome, its characters, and how it is linked to the most relevant aspects of the disease are reviewed.
Abstract: Central alveolar hypoventilation syndrome has been known for decades as Ondine's curse. It was named as such after a German myth. Although most of the stories resemble one another, word of mouth has led to misinterpretation of this tale among the medical community. The present paper reviews the original narrative, its characters, and how it is linked to the most relevant aspects of the disease.

Journal ArticleDOI
TL;DR: Rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare condition and little is known about sleep/wake and slow-wave activation in these patients.
Abstract: Study Objectives:Rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare condition. Little is known about sleep/wake and slow-wave activ...

Journal ArticleDOI
TL;DR: A retrospective study identifies four patients with recurrent late-onset post-lesional PH episodes of 1–26-day duration that occurred 6–46 years after the brain insult, and identifies patients associated with sleep disorders and hypoventilation, for which investigations and treatment should be considered.
Abstract: Paroxysmal hypothermia (PH) is a rare condition characterized by recurrent episodes of spontaneous hypothermia, bradycardia, disorders of consciousness and, in some cases, hyperhidrosis. When associated with a detectable hypothalamic lesion, PH episodes usually occur shortly after the brain insult. We performed a retrospective study to identify patients who had demonstrated at least one episode of symptomatic spontaneous PH as defined by (i) tympanic temperature < 35 °C; (ii) drowsiness and/or confusion state and/or coma; (iii) duration of the episode ≥ 24 h; (iv) absence of other condition resulting in hypothermia Among 8824 patients, we identified four patients with recurrent late-onset PH episodes of 1–26-day duration that occurred 6–46 years after the brain insult. The lesion always involved the diencephalon. All patients suffered from epilepsy and three of hypopituitarism. PH episode typically included severe hypothermia, bradycardia, drowsiness, thrombocytopenia and in some patients central hypoventilation and narcolepsy-like hypersomnia. In ¼ of episodes, confusion was mistaken as non-convulsive epileptic manifestation resulting in benzodiazepine administration which aggravated symptoms. In the two patients with nocturnal hypoventilation, chronic non-invasive ventilation with bi-level positive airway pressure allowed cessation of symptomatic episodes. Late-onset post-lesional PH is exceptional with only a single case hitherto reported in the literature. Distinguishing hypothermia-related disturbances of consciousness from epileptic seizures or post-ictal phenomena is crucial since treatment with benzodiazepines may worsen hypothermia through their action on GABAa receptors. Lastly, PH may be associated with sleep disorders and hypoventilation, for which investigations and treatment should be considered.

Journal ArticleDOI
TL;DR: In patients with rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) syndrome, sleep-disordered breathing should be determined early and appropriate treatment should be initiated immediately to reduce morbidity and mortality.
Abstract: Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) syndrome; is a rare but crucial disorder. Sleep-disordered breathing can occur at the beginning or after of obesity. A disease-specific test for diagnosis is not yet available. Neural crest tumors (ganglioneuroma, ganglioneuroblastoma) have been reported in 40% of patients. In our study, three patients diagnosed as having ROHHAD syndrome are presented from our hospital. In the evaluation of the hypothalamic functions of the patients, one of them had growth hormone deficiency and hyperprolactinemia; recurrent hypernatremia reflecting irregular water balance was detected in another. One of the patients had abnormal pupil reflex and heart rate irregularity while another had excessive sweating as autonomic dysfunction. One of the patients was diagnosed with paravertebral ganglioma accompanying ROHHAD syndrome. Non-invasive ventilation treatment was started in all patients because there was a sleep-disorder breathing clinic diagnosis. ROHHAD syndrome deserves a multidisciplinary team approach as it can affect more than one organ system. In these patients, should be sleep-disorder breathing determined early and appropriate treatment should be initiated immediately to reduce morbidity and mortality.

Journal ArticleDOI
TL;DR: Current evidence for indications, adverse effects and long term follow up including adherence to NIV in children with chronic lung disease is reviewed, with survival benefit with NIV suggested in addition to being an effective bridge to transplantation.
Abstract: Advances in medical care and supportive care options have contributed to the survival of children with complex disorders, including children with chronic lung disease. By delivering a positive pressure or a volume during the patient's inspiration, NIV is able to reverse nocturnal alveolar hypoventilation in patients who experience hypoventilation during sleep, such as patients with chronic lung disease. Bronchopulmonary dysplasia (BPD) is a common complication of prematurity, and despite significant advances in neonatal care over recent decades its incidence has not diminished. Most affected infants have mild disease and require a short period of oxygen supplementation or respiratory support. However, severely affected infants can become dependent on positive pressure support for a prolonged period. In case of established severe BPD, respiratory support with non-invasive or invasive positive pressure ventilation is required. Patients with cystic fibrosis (CF) and advanced lung disease develop hypoxaemia and hypercapnia during sleep and hypoventilation during sleep usually predates daytime hypercapnia. Hypoxaemia and hypercapnia indicates poor prognosis and prompts referral for lung transplantation. The prevention of respiratory failure during sleep in CF may prolong survival. Long-term oxygen therapy has not been shown to improve survival in people with CF. A Cochrane review on the use NIV in CF concluded that NIV in combination with oxygen therapy improves gas exchange during sleep to a greater extent than oxygen therapy alone in people with moderate to severe CF lung disease. Uncontrolled, non-randomized studies suggest survival benefit with NIV in addition to being an effective bridge to transplantation. Complications of NIV relate mainly to prolonged use of a face or nasal mask which can lead to skin trauma, and neurodevelopmental delay by acting as a physical barrier to social interaction. Another associated risk is pulmonary aspiration caused by vomiting whilst wearing a face mask. Adherence to NIV is one of the major barriers to treatment in children. This article will review the current evidence for indications, adverse effects and long term follow up including adherence to NIV in children with chronic lung disease.

Journal ArticleDOI
16 Jan 2020-Cureus
TL;DR: The case of a full-term male infant diagnosed with C CHS at two months of age with repeated extubation failure secondary to CCHS is reported, and the patient was discharged at five months ofAge with a home ventilator.
Abstract: Congenital central hypoventilation syndrome (CCHS) is a critical and rare autosomal dominant disorder that was first described by Robert Mellins in 1970. CCHS is defined to be an autonomic nervous system (ANS) dysfunction that usually presents in the neonatal period with hypoventilation and dysregulated autonomic homeostasis on a multi-system level. Classically, CCHS presents with normal ventilation while awake, and hypoventilation with normal respiratory rate during sleep. CCHS has been causally linked to the paired-like homeobox 2B (PHOX2B) gene. We report the case of a full-term male infant diagnosed with CCHS at two months of age with repeated extubation failure secondary to CCHS. The patient was discharged at five months of age with a home ventilator.

Journal ArticleDOI
TL;DR: ASV devices improved central hypopnea/hypoventilation events without inducing hyperpnea events and therefore were better adapted than AVAPS and iVAPS devices, with notable differences in their responses to hypoventilated events.
Abstract: BACKGROUND: Adaptive servoventilation (ASV) is a recently developed ventilation mode designed to stabilize ventilation in patients with central sleep apnea and Cheyne-Stokes respiration. Alternatively, modes aiming to maintain average ventilation over several breaths, such as average volume-assured pressure support (AVAPS) and intelligent volume-assured pressure support (iVAPS), could be efficient during ventilation instability by reducing central events. These modes are available on a variety of devices. This bench evaluation studied the response of these different modes and devices to simulated transient hypoventilation events. METHODS: Three home ventilation devices operating in ASV modes (AirCurve 10 CS Pacewave, ResMed; DreamStation autoSV, Philips; Prisma CR, Lowenstein) and 2 ventilators with the AVAPS mode (DreamStation BiPAP, Philips; Lumis 150 iVAPS, ResMed) were evaluated during transient central hypopnea/hypoventilation simulations characterized by a constant breathing frequency of 15 breaths/min and a progressive decrease of tidal volume (VT) from 500 mL to 50 mL, in 18, 12, 9, and 6 breaths, respectively, followed by a progressive return to the baseline at the same rate. RESULTS: The AirCurve 10 CS Pacewave reacted to a VT decrease between 80% and 50% of baseline VT. DreamStation BiPAP and Prisma CR reacted when VT decreased to between 60% and 30% of baseline VT, whereas the AVAPS response to hypopnea occurred during the crescendo phase of hypopnea/hypoventilation VT. The iVAPS response was between that of the AirCurve 10 CS Pacewave and the other ASV devices. Among the ASV devices, the minimum VT was higher with AirCurve 10 CS Pacewave, followed by the Prisma CR and the DreamStation BiPAP. Minimum VT was not influenced by AVAPS and was improved by iVAPS without outperforming the AirCurve 10 CS Pacewave. Maximum VT was increased by iVAPS, whereas ASV devices did not induce a significant VT overshoot. CONCLUSIONS: ASV devices improved central hypopnea/hypoventilation events without inducing hyperpnea events and therefore were better adapted than AVAPS and iVAPS devices, with notable differences in their responses to hypoventilation events.


Journal ArticleDOI
TL;DR: Mutations in the PHOX2B gene cause congenital central hypoventilation syndrome, a rare autonomic nervous system dysfunction disorder characterized by a decreased ventilatory response to hypercapnia, and is associated with disorders characterized by the defective migration/differentiation of neural crest derivatives, including aganglionic megacolon or milder gastrointestinal phenotypes, such as constipation.
Abstract: Background Mutations in the PHOX2B gene cause congenital central hypoventilation syndrome (CCHS), a rare autonomic nervous system dysfunction disorder characterized by a decreased ventilatory response to hypercapnia. Affected subjects develop alveolar hypoventilation requiring ventilatory support particularly during the non-REM phase of sleep. In more severe cases, hypoventilation may extend into wakefulness. CCHS is associated with disorders characterized by the defective migration/differentiation of neural crest derivatives, including aganglionic megacolon or milder gastrointestinal phenotypes, such as constipation. Most cases of CCHS are de novo, caused by heterozygosity for polyalanine repeat expansion mutations (PARMs) in exon 3. About 10% of cases are due to heterozygous non-PARM missense, nonsense or frameshift mutations. Methods We describe a three-generation Maltese-Caucasian family with a variable respiratory/Hirschsprung phenotype, characterized by chronic constipation, three siblings with Hirschsprung disease necessitating surgery, chronic hypoxia, and alveolar hypoventilation requiring non-invasive ventilation. Results The sequencing of PHOX2B revealed a novel heterozygous c.241+2delT splice variant in exon 1 that segregates with the CCHS/Hirschsprung phenotype in the family. The mutation generates a non-functional splice site with a deleterious effect on protein structure and is pathogenic according to ACMG P VS1, PM2, and PP1 criteria. Conclusion This report is significant as no PHOX2B splice-site mutations have been reported. Additionally, it highlights the variability in clinical expression and disease severity of non-PARM mutations.

Journal ArticleDOI
TL;DR: The polysomnographic characteristics of a MECP2‐mutated male are described in detail and the relevance of severe central apneas is shown, which may represent a new clinical clue to suggest the diagnosis of RTT syndrome in males.
Abstract: Rett syndrome (RTT, MIM * 312750) is an X-linked neurodevelopmental disorder caused by pathogenic variants at the Xq28 region involving the gene methyl-CpG-binding protein 2 (MECP2, MIM * 300005). The spectrum of MECP2-related phenotypes is wide and it ranges from asymptomatic female carriers to severe neonatal-onset encephalopathy in males. Abnormal breathing represents one of the leading features, but today little is known about polysomnographic features in RTT females; no data are available about males. We report the case of a male of Moroccan origins with a MECP2 pathogenic variant and a history of encephalopathy and severe breathing disturbances in the absence of dysmorphic features. For the first time we describe in detail the polysomnographic characteristics of a MECP2-mutated male and we show the relevance of severe central apneas, which may represent a new clinical clue to suggest the diagnosis. Moreover, we want to highlight the importance to maintain a high index of suspicion for MECP2-related disorders in the presence of severe hypotonia, apneic crises, and respiratory insufficiency in males to permit an earlier diagnosis and the consequent definition of recurrence risk of the family and to avoid other useless and invasive exams.

Journal ArticleDOI
TL;DR: Long-term nocturnal noninvasive ventilation is the mainstay of treatment but evidence suggests that CPAP may be effective in stable patients and specific perioperative management is required to reduce complications.

Book ChapterDOI
01 Jan 2020
TL;DR: Sleep disordered breathing is a common disorder characterized by complete or partial obstruction of the upper airway during sleep and apnea caused by decreased central drive of breathing, which leads to chronic intermittent hypoxia, carbon dioxide retention, repeated micro-awakening, abnormal sleep structure, daytime sleepiness, memory decline, and group of syndromes causing autonomic nervous dysfunction.
Abstract: Sleep disordered breathing (SDB) is a common disorder characterized by complete or partial obstruction of the upper airway during sleep and apnea caused by decreased central drive of breathing, which leads to chronic intermittent hypoxia, carbon dioxide retention, repeated micro-awakening, abnormal sleep structure, daytime sleepiness, memory decline, and group of syndromes causing autonomic nervous dysfunction [1]. They can be divided into obstructive sleep apnea (OSA), central sleep apnea (CSA), and sleep-related hypoventilation.