Central Hypoventilation Research Articles

Profile of Sleep-related Breathing Disorders in Chronic Obstructive Pulmonary Disease-obstructive Sleep Apnea Overlap Syndrome

Introduction: Overlap syndrome (OS) is defined by the combined occurrence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD). Sleep-related breathing disorders (SRBDs) in OS can also manifest with central sleep apnea (CSA) and hypoventilation; besides OSA. Methods: This study was carried out to evaluate various SRBD in OS and its therapeutic implications patients having postbronchodilator obstruction in spirometry with respiratory symptoms were classified as COPD. Those found to have an apnea–hypopnea Index (AHI) >5/h in polysomnography (PSG) were diagnosed as OS. All 37 patients diagnosed as OS underwent a subsequent positive airway pressure (PAP) titration. Results: On the evaluation of the SRBD, over half (51%) of the patients had OSA with no hypoventilation. More than one-third of the patients (35%) had associated hypoventilation with OSA, three patients had hypercapnic CSA, and two patients had hypocapnic CSA with Cheyne–Stokes breathing (CSA-CSB). The OSA group was easily titrated and corrected by CPAP therapy. OSA with hypoventilation group had underlying COPD with severe obstruction requiring bilevel PAP titration. Patients with CSA-CSB were elderly hypertensive patients with congestive heart failure who were corrected by PAP and optimization of cardiac medications. Patients with hypoventilation and hypercapnic CSA were most difficult to titrate and needed a backup rate along with PAP therapy for correction. On classifying patients on the basis of severity of OSA and COPD, there was no correlation found between AHI and forced expiratory volume 1 (FEV1). Patients with mild COPD with severe OSA were easily titrated with CPAP with a mean pressure of 8 cm H2 0. The most challenging cases were with severe COPD with severe OSA who required high pressures in both exhalation PAP and inspiratory PAP titration; two of such patients required backup rate by spontaneous/timed mode of PAP therapy. Conclusions: There are many profiles of SRBD in OS, and a detailed in-hospital PSG with a PAP titration can help in effectively managing the patients.

Acquired Central Alveolar Hypoventilation as a Sequelae of Brainstem Tuberculoma

Acquired Central Alveolar Hypoventilation as a Sequelae of Brainstem Tuberculoma

A rare case of congenital central hypoventilation syndrome in a premature neonate with multiple coexisting morbidities: A comprehensive clinical analysis

A rare case of congenital central hypoventilation syndrome in a premature neonate with multiple coexisting morbidities: A comprehensive clinical analysis

Structural characterization of PHOX2B and its DNA interaction shed light on the molecular basis of the +7Ala variant pathogenicity in CCHS.

An expansion of poly-alanine up to +13 residues in the C-terminus of the transcription factor PHOX2B underlies the onset of congenital central hypoventilation syndrome (CCHS). Recent studies demonstrated that the alanine tract expansion influences PHOX2B folding and activity. Therefore, structural information on PHOX2B is an important target for obtaining clues to elucidate the insurgence of the alanine expansion-related syndrome and also for defining a viable therapy. Here we report by NMR spectroscopy the structural characterization of the homeodomain (HD) of PHOX2B and HD + C-terminus PHOX2B protein, free and in the presence of the target DNA. The obtained structural data are then exploited to obtain a structural model of the PHOX2B-DNA interaction. In addition, the variant +7Ala, responsible for one of the most frequent forms of the syndrome, was analysed, showing different conformational proprieties in solution and a strong propensity to aggregation. Our data suggest that the elongated poly-alanine tract would be related to disease onset through a loss-of-function mechanism. Overall, this study paves the way for the future rational design of therapeutic drugs, suggesting as a possible therapeutic route the use of specific anti-aggregating molecules capable of preventing variant aggregation and possibly restoring the DNA-binding activity of PHOX2B.

The straight line from retro-olivary sulcus to median sulcus is a useful limit line associated with risk of intubation due to central hypoventilation in lateral medullary syndrome

The straight line from retro-olivary sulcus to median sulcus is a useful limit line associated with risk of intubation due to central hypoventilation in lateral medullary syndrome

Elevated transaminases in congenital central hypoventilation syndrome.

Patients with CCHS who also have Hirschsprung disease, elevated or low BMI, or pulmonary hypertension may be predisposed to elevated transaminases and may need periodic follow-up of their hepatic function https://bit.ly/3uW7AUG.

Pediatric long-term noninvasive respiratory support in children with central nervous system disorders.

The use of long-term noninvasive respiratory support is increasing in children along with an extension of indications, in particular in children with central nervous system (CNS) disorders. The aim of this study was to describe the characteristics of children with CNS disorders treated with long-term noninvasive respiratory support in France. Data were collected from 27 French pediatric university centers through an anonymous questionnaire filled for every child treated with noninvasive ventilatory support ≥3 months on 1st June 2019. The data of 182 patients (55% boys, median age: 10.2 [5.4;14.8] years old [range: 0.3-25]) were collected: 35 (19%) patients had nontumoral spinal cord injury, 22 (12%) CNS tumors, 63 (35%) multiple disabilities, 26 (14%) central alveolar hypoventilation and 36 (20%) other CNS disorders. Seventy five percent of the patients were treated with noninvasive ventilation (NIV) and 25% with continuous positive airway pressure (CPAP). The main investigations performed before CPAP/NIV initiation were nocturnal gas exchange recordings, alone or coupled with poly(somno)graphy (in 29% and 34% of the patients, respectively). CPAP/NIV was started in an acute setting in 10% of the patients. Median adherence was 8 [6;10] hours/night, with 12% of patients using treatment <4 h/day. Nasal mask was the most common interface (70%). Airway clearance techniques were used by 31% of patients. CPAP/NIV may be a therapeutic option in children with CNS disorders. Future studies should assess treatment efficacy and patient reported outcome measures.

Characteristics and outcomes in children with congenital central hypoventilation syndrome on long-term mechanical ventilation in the Netherlands.

Our study results suggest that in our cohort, the genotype is not easily associated to the phenotype in CCHS. Consistent with these findings and international literature, we recommend a thorough annual evaluation for all patients with CCHS to ensure optimal management and follow-up. • The majority of CCHS patients are dependent on ventilatory support. • Variants in the PHOX2B gene are responsible for the characteristics of CCHS. • This study provides insight into the clinical course and long-term outcomes of CCHS patients in the Netherlands. • In CCHS, the genotype is not easily associated with the phenotype, requiring a thorough life-long follow-up for all patients.

ROHHAD syndrome spectrum in an adult: a possible new variant.

This case report describes for the first time the evolution of a mature patient with all the diagnostic criteria for ROHHAD syndrome. It shows a rare case of central alveolar hypoventilation with hypothalamic impairment, dysautonomia and rapid weight gain. https://bit.ly/49AN3Vv.

Systematic review: clinical characteristics of anti-N-methyl-D-aspartate receptor encephalitis.

The number of reported cases of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis has gradually increased since its discovery in 2007, while there are no uniform treatment guidelines. To summarize the clinical characteristics of patients with anti-NMDAR encephalitis and to analyze the factors affecting the disease prognosis. A systematic analysis of medical records was conducted, and PubMed, Embase, and Cochrane Library were searched from January 1, 2011, to December 31, 2021. Data were extracted, analyzed, and recorded in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. This study included 472 case reports. Most patients had prodromal symptoms of about 2 weeks, including psychiatric symptoms (53.2%), flu-like symptoms (51.5%), and seizures (23.9%), among others. Poor prognoses were associated with patients who had autonomic instability (p = 0.010), central hypoventilation (p = 0.014), and ICU support (p = 0.002). Patients with a higher age of onset were more likely to develop central hypoventilation (OR 1.024, CI 1.006-1.042, p = 0.009), cognitive impairment (OR 1.023, CI 1.009-1.037, p = 0.001), and memory impairment (OR 1.034, CI 1.017-1.050, p < 0.001), whereas patients with a lower age were more likely to have seizures (OR 0.979, CI 0.965-0.993, p = 0.003). In this study, 97.0% of patients received immunotherapy, with the most commonly used treatment regimen being intravenous methylprednisolone (IVGC) and intravenous immunoglobulin (IVIG). When compared with other treatment regimens, the IVGC+IVIG regimen (p < 0.001) resulted in better prognoses. When encountering patients with fever, headache, and initial psychiatric symptoms of unknown etiology, clinicians should test their CSF for antibodies to distinguish autoimmune encephalitis. Patients with autonomic instability, central hypoventilation, and ICU support had poorer prognoses. Clinicians should be aware that older patients are more likely to develop central hypoventilation, cognitive impairment, and memory impairment, while younger patients are more likely to develop seizures. The IVGC+IVIG treatment regimen has better prognoses than others. This study includes case reports, which have obvious selection bias, and there are no unified standards to measure the severity of the disease. Therefore, in the future, larger samples and randomized controlled trials are needed to evaluate the efficacy of different treatment regimens.

KONJENİTAL SANTRAL HİPOVENTİLASYON SENDROMU VE SEREBRAL PALSİLİ OLGUDA FİZYOTERAPİ VE REHABİLİTASYON PROGRAMININ ETKİSİNİN İNCELENMESİ: BİR OLGU SUNUMU

Congenital Central Hypoventilation Syndrome is a rare genetic disorder that presents from birth and prevents automatic control of respiration. Our aim in this study was to examine the effectiveness of a 6-month physical therapy program applied to a patient with Congenital Central Hypoventilation Syndrome and cerebral palsy. A 6-month-old patient who was diagnosed with Congenital Central Hypoventilation Syndrome and subsequently developed Cerebral Palsy due to asphyxia was included in the study. The case was enrolled in a physical therapy program for 2 days a week for 6 months in the home environment where they lived. The case was evaluated before and after treatment. In our case, the Modified Ashworth Scale, the Alberta Infant Motor Scale, the Hammersmith Infant Neurological Examination, Test of Sensory Functions in Infants, and the Face, Legs, Activity, Cry, Consol ability scale were used. In our case, pre-treatment and post-treatment scores were as follows, respectively: Alberta Infant Motor Scale score 3-8, Hammersmith Infant Neurological Examination score 6-17, Test of Sensory Functions in Infants score 2-9, and Face, Legs, Activity, Cry, Consol ability scale score 8-3. In our case, there was a significant improvement in Modified Ashworth Scale scores before and after treatment. Additionally, at the conclusion of the study, it was noted that the heightened pain and sensitivity resulting from the patient's extended stay in the intensive care unit reduced with the treatment. We believe that the administered physiotherapy and rehabilitation program offered support to the patient in achieving neuro-motor and sensory integration, underscoring the essential role of physiotherapy in rare diseases.

'It gives me more freedom': Family perspectives on travelling with children on nocturnal ventilation.

Children with neuromuscular weakness or central hypoventilation often require nocturnal ventilation. Children with these conditions are living longer and the numbers of children affected are increasing. The challenges associated with managing ventilation at home have been documented; however, there has been limited investigation into accessing wider experiences such as travel. Air travel, in particular, may be considered challenging for children with these conditions because oxygen levels are lower in airplane cabins than at sea levels. We sought to understand experiences of and attitudes towards travel amongst families of children using nocturnal ventilation for neuromuscular weakness or central hypoventilation. Two semi-structured interviews were conducted amongst participants enrolled in a trial of a new pre-flight assessment of their tolerance of reduced oxygen levels during flight (known as a hypoxic challenge test). Children participating in the trial were aged 19 months to 18 years. Parents were interviewed and provided proxy views for younger children, and older children were encouraged to present their own views during these interviews. One interview was conducted immediately after the assessment, and a second 3 months later. Data were analysed utilising the framework approach to thematic analysis. Seventeen families participated in the first interview with 14 of these families completing the follow-up interview. Three further families participated in the follow-up interview only. Here, we report three themes relating to participant experience of travel and how this is impacted by their condition. The three themes and their sub-themes were (1) insight into children's lives: hospital attendances, gaining knowledge and confidence, and child as a person; (2) travelling with your child: planes, trains and automobiles, rules of air travel, and uncertainty; and (3) the meaning of travel: normalisation, connection to extended family, expanded experiences, and freedom and equality. This population of children and their families aspire to travel but face challenges from clinical and social barriers. It is essential that we further our understanding of the physiological, social and cultural aspects of their experience to facilitate their access to broadened life experiences.

P010 Delivery of volume assured pressure support (VAPS) through tracheostomy in paediatric patients

Abstract INTRODUCTION Volume assured pressure support (VAPS) allows the ventilator to deliver a constant pre-set tidal volume or alveolar ventilation by automatically adjusting the inspiratory pressures within a set range, providing targeted pressure support. Data on its use in children are limited. We describe a series of four children effectively and safely ventilated using VAPS mode through tracheostomy. METHODS Retrospective review of patient notes. PROGRESS TO DATE Four paediatric patients were identified in our cohort who were successfully and safely ventilated using the VAPS mode through tracheostomy. The patients were between 6-14 years of age inclusive, with four differing underlying disease processes – Prader-Willi syndrome, congenital central hypoventilation syndrome, Guillain-Barré syndrome and Moebius-type syndrome. INTENDED OUTCOME AND IMPACT Whilst there have been previous paediatric case reports and case series which have demonstrated efficacy of VAPS mode used non-invasively, the use of VAPS mode to provide effective and safe ventilation through tracheostomy in children has been described in only one recent case series. The advantages of its use over conventional bilevel positive airway pressure support include its ability to compensate for changes in tidal volume, which can occur with changes in lung compliance and during different stages of sleep. This case series highlights safe and effective use of VAPS mode in children with tracheostomy.

Hirschsprung disease.

Hirschsprung disease (HSCR) is a rare congenital intestinal disease that occurs in 1 in 5,000 live births. HSCR is characterized by the absence of ganglion cells in the myenteric and submucosal plexuses of the intestine. Most patients present during the neonatal period with the first meconium passage delayed beyond 24 h, abdominal distension and vomiting. Syndromes associated with HSCR include trisomy 21, Mowat-Wilson syndrome, congenital central hypoventilation syndrome, Shah-Waardenburg syndrome and cartilage-hair hypoplasia. Multiple putative genes are involved in familial and isolated HSCR, of which the most common are the RET proto-oncogene and EDNRB. Diagnosis consists of visualization of a transition zone on contrast enema and confirmation via rectal biopsy. HSCR is typically managed by surgical removal of the aganglionic bowel and reconstruction of the intestinal tract by connecting the normally innervated bowel down to the anus while preserving normal sphincter function. Several procedures, namely Swenson, Soave and Duhamel procedures, can be undertaken and may include a laparoscopically assisted approach. Short-term and long-term comorbidities include persistent obstructive symptoms, enterocolitis and soiling. Continued research and innovation to better understand disease mechanisms holds promise for developing novel techniques for diagnosis and therapy, and improving outcomes inpatients.

Volume assured pressure support mode use for non-invasive ventilation in pediatrics.

There has been increasing interest in utilizing volume assured pressure support (VAPS) modes of ventilation for children, which historically had only been favored in adult populations. In addition to patients with obesity hypoventilation syndrome, newer pediatric populations for which it has recently been prescribed include congenital central hypoventilation syndrome and children with neuromuscular disease such as Duchenne muscular dystrophy and spinal muscular atrophy. Given its expanding use in pediatrics, greater familiarity with VAPS is essential for pediatric pulmonologists and sleep physicians. This review article will highlight methods of initiation for this mode, specific ventilator settings, discussion of suitable pediatric patient populations, ventilator titrations via formal polysomnograms and detailed ventilator data downloads specific interpretation. Finally, common challenges to be aware of and how to troubleshoot relevant machine alarms will be reviewed.

Congenital central hypoventilation syndrome in Chinese population: Analysis of three new cases and review of the literature.

Congenital central hypoventilation syndrome (CCHS) is a rare autosomal dominant disease that is mainly caused by PHOX2B mutations. The purpose of this study is to analyze and summarize the clinical and genetic characteristics of CCHS patients in the Chinese population from our study and previous literature. The potential pathogenic gene mutations of CCHS were identified and verified by next generation sequencing combined with Sanger sequencing, fluorescent probe PCR and capillary electrophoresis. The clinical characteristics and gene mutations of CCHS cases in Chinese population were summarized from our study and previous literature to explore the genotype-phenotype correlations. We identified 48 CCHS cases including three new cases from our report in China. Overall, 77.1% of the patients had PHOX2B polyalanine repeat expansion mutations (PARMs), and the remaining 22.9% had 10 distinct PHOX2B non-polyalanine repeat expansion mutations (NPARMs). Compared to those with PARMs, patients with NPARMs were more likely to have premature birth (54.5% vs. 2.8%, p < 0.001) and lower birth weight (33.3% vs. 3.2%, p = 0.030), with statistical significance. The patients with PARMs were more likely to have cardiovascular defects (64.9% vs. 27.3%, p = 0.063), cerebral hemorrhage (29.7% vs. 9.1%, p = 0.322) and seizures (37.8% vs. 9.1%, p = 0.151) than those with NPARMs, with no statistical significance. CCHS patients with PHOX2B NPARMs were more likely to have premature birth and low birth weight, while PHOX2B PARMs tended to be positively associated with the risk of cardiovascular defects, cerebral hemorrhage and seizures in Chinese population.

Congenital Central Hypoventilation Syndrome (Ondine’s Curse): Clinical Case

Background. Congenital central hypoventilation syndrome (CCHS), or Ondine’s Curse, is rare, incurable and life-threatening disease characterized by autonomic nervous system disorders, it manifests with disability to maintain ventilation function during sleep. Sensitivity to hypoxia and hypercapnia is reduced in case of CCHS, thus, it leads to recurrent episodes of deep apnea. The world literature describes just over 1000 cases of this disease. Clinical case description. An infant born at 37th week of gestation, weight of 3330 g, had episodes of apnea and hypercapnia from the first day of life. CCHS was suspected by the 28th day of life after excluding other causes of respiratory disorders, and it was genetically confirmed by the 43rd day of life — pathogenic variant of PHOX2B gene was revealed. Mechanical ventilation has been initiated by the age of 1 month after disease worsening. Analysis of CCHS cases published in Russian-language medical literature was performed. Typical symptoms and timing of their manifestation, as well as the time before correct diagnosis were mentioned. Conclusion. Symptoms that can be suggestive of CCHS presence early after birth and can urge to perform all the necessary genetic testing that are crucial for timely treatment onset and for minimizing the negative effect of hypoxemia and hypercapnia on the child are described.

Congenital central hypoventilation syndrome in children: a Hong Kong perspective.

Congenital central hypoventilation syndrome in children: a Hong Kong perspective.

Blood Lymphocyte Subsets and Proinflammatory Cytokine Profile in ROHHAD(NET) and non-ROHHAD(NET) Obese Individuals.

Rapid-onset obesity with central hypoventilation, hypothalamic dysfunction, and autonomic dysregulation with neural crest tumors (ROHHAD-NET) syndrome pathophysiology remains elusive. Acquired neuroimmunological dysfunction has been proposed as a possible pathogenetic pathway. The aim of our study was to characterize lymphocyte subpopulations subsets in peripheral blood (PB) and to evaluate a panel of proinflammatory cytokines/chemokines in ROHHAD(NET) patients vs controls. We included 11 ROHHAD(NET) patients, 7 ROHHAD and 4 ROHHAD-NET, selected by clinical criteria. Controls were 11 simple obese children, matched for age and sex. Flow cytometric analysis and enzyme-linked immunosorbent assay were performed on PB and serum samples of the 2 groups. Analysis revealed that T lymphocytes are significantly increased in ROHHAD(NET) patients (P = .04) with a prevalence of CD4-T cells (P = .03) and a lower number of activated CD8-T cells (P = .02). With regard to regulatory subset, patients displayed increased regulatory B cells (P = .05) and type-1 regulatory T cells (P = .03). With regard to CD8-T cells, a lower number of T effector memory was observed (P = .02). In contrast, among CD4-T cells, we found a higher number of T naive (P = .04) and T effector (P = .0008). Interleukin-8 (IL-8) levels and monocyte chemotactic protein-1 were increased in patients vs controls (P = .008 and P = .01, respectively). Furthermore, IL-8 levels were higher in the subgroup with neural tumor (P = .0058) (ROHHAD-NET) than in patients without neural tumor (ROHHAD). Soluble HLA-G was significantly lower in patients vs controls (P = .03). Our findings contribute to support the hypothesis of immune dysregulation, which may underlie this complex, often fatal disease. Because ROHHAD(NET) syndrome is an ultra-rare disease, multicentric studies are needed to improve the effect of our data in the management of this condition.

Two children with late-onset congenital central hypoventilation syndrome

Two children with late-onset congenital central hypoventilation syndrome were reported, one of whom was male and had no abnormal manifestations after birth, respiratory failure occurs at the age of 1 year and 6 months. After being hospitalized, he was treated with oxygen inhalation and non-invasive ventilation, but carbon dioxide retention could not be corrected. After one month of tracheal intubation, he was failure to wean from ventilator, so tracheostomy was performed. He needs a ventilator to help breath while sleeping, and can breath autonomously during the day without ventilator. The other case was a female, with no abnormalities after birth. At the age of 11 months, she developed respiratory failure. During sleep, the child needs non-invasive assisted ventilation through a nasal mask, and during the day, she breathed autonomously.Two patients were followed up forever 2 years and their growth and development were normal.