RESUMO
Congenital Central Hypoventilation Syndrome (CCHS) is a rare genetic condition affecting the autonomic nervous system and respiratory center due to mutations in the PHOX2B gene, and it is associated with alveolar hypoventilation during sleep and sudden death. It requires early invasive mechanical ventilation (IMV). OBJECTIVE: To report a neonatal case successfully treated with non-invasive ventilatory support (NVS), avoiding tracheostomy. CLINICAL CASE: Full-term newborn, whose mother uses nocturnal NVS due to CCHS. During the transition period, she presented desaturations associated with hypercapnia and respiratory acidosis, without pulmonary involvement. She developed severe hypoventilation during sleep, with no respiratory effort, peripheral oxygen saturation (SpO2) < 80%, plus respiratory acidosis. While awake, she had good respiratory effort and normal SpO2 without assistance. Noninvasive continuous positive airway pressure and oxygen therapy worsened her condition while sleeping. Complete NVS with nasal interface and bi-level airway positive pressure, inspiratory/expiratory pressure 14-16/4 cm H2O, normalized SpO2 during sleep, and arterial blood gases while awake. Sequencing of the PHOX2B gene confirmed the presence of a heterozygous pathogenic variant with the 20/26 genotype. At 2 months of age, she was discharged maintaining NVS with nasal interface and 0 PEEP, achieving adequate neurodevelopment. CONCLUSION: We highlight the importance of genetic diagnosis of CCHS in neonates with clinical presentation of early alveolar hypoventilation, especially if there is a family history. We are not aware of other reports of neonatal onset in which NVS prevents IMV, in this potentially lethal pathology.
Assuntos
Proteínas de Homeodomínio , Hipoventilação , Apneia do Sono Tipo Central , Fatores de Transcrição , Humanos , Apneia do Sono Tipo Central/diagnóstico , Apneia do Sono Tipo Central/terapia , Apneia do Sono Tipo Central/genética , Recém-Nascido , Hipoventilação/congênito , Hipoventilação/terapia , Hipoventilação/diagnóstico , Hipoventilação/genética , Feminino , Proteínas de Homeodomínio/genética , Fatores de Transcrição/genética , Ventilação não Invasiva , Pressão Positiva Contínua nas Vias Aéreas , Acidose Respiratória/diagnóstico , Acidose Respiratória/terapia , Acidose Respiratória/etiologia , Mutação , OxigenoterapiaRESUMO
Chronic hypercapnic respiratory failure occurs in several conditions associated with hypoventilation. The mechanisms underlying the development of chronic hypercapnia include a combination of processes that increase metabolic CO2 production, reduce minute ventilation (V'e), or increase dead space fraction (Vd/Vt). Fundamental to the pathophysiology is a mismatch between increased load and a reduction in the capacity of the respiratory pump to compensate. Though neural respiratory drive may be decreased in a subset of central hypoventilation disorders, it is more commonly increased in attempting to maintain the load-capacity homeostatic balance.
Assuntos
Hipercapnia , Insuficiência Respiratória , Humanos , Hipercapnia/fisiopatologia , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/terapia , Doença Crônica , Hipoventilação/fisiopatologia , Hipoventilação/terapiaRESUMO
PURPOSE: Glial fibrillary acidic protein astrocytopathy (GFAP-A) pathogenesis remains uncertain, with potential viral involvement. More clinical cases are needed to deepen our understanding of this disease, along with the exploration of more effective treatment options to provide clinicians with additional choices. METHODS: We report a severe case of GFAP-A secondary to EBV infection, characterized predominantly by central respiratory failure. Additionally, we conducted a literature review summarizing the characteristics of GFAP-IgG-positive patients associated with EBV infection. RESULTS: Among the 13 patients identified, fever (92.3%) and headache (84.6%) were the most common initial symptoms, while urinary dysfunction was universally present in all patients. Over half of the patients with altered consciousness required endotracheal intubation (7/11, 63.6%), with only one individual experiencing complete resolution without any residual sequela. Only two patients (16.7%) displayed the classic feature of periventricular enhancement on neuroimaging, whereas T2-FLAIR hyperintensities were more prevalent. All patients tested positive for GFAP-IgG in CSF, and 91.7% (11/12) had detectable serum GFAP-IgG antibodies. Three patients (23.1%) achieved full recovery solely through antiviral therapy. In patients receiving various immunotherapies, 60% (6/10) still had residual sequelae. CONCLUSION: EBV infection may contribute to the pathogenesis of GFAP-A. GFAP antibody testing is recommended for diagnostic evaluation in cases of central nervous system viral infections presenting with respiratory insufficiency. For severe GFAP-A patients, Protein A immunoadsorption (Protein A IA).
Assuntos
Infecções por Vírus Epstein-Barr , Proteína Glial Fibrilar Ácida , Imunoglobulinas Intravenosas , Humanos , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/terapia , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Hipoventilação/terapia , Feminino , Herpesvirus Humano 4 , AdultoRESUMO
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.
Assuntos
Hipoventilação , Apneia do Sono Tipo Central , Humanos , Apneia do Sono Tipo Central/terapia , Apneia do Sono Tipo Central/fisiopatologia , Apneia do Sono Tipo Central/diagnóstico , Hipoventilação/congênito , Hipoventilação/terapia , Hipoventilação/fisiopatologia , Hipoventilação/diagnóstico , Síndrome de Prader-Willi/fisiopatologia , Síndrome de Prader-Willi/terapia , Síndrome de Prader-Willi/complicações , Síndrome de Prader-Willi/diagnóstico , Recém-NascidoRESUMO
OBJECTIVE: To investigate the factors influencing carbon dioxide transfer in a system that integrates an oxygenation membrane in series with high-bicarbonate continuous veno-venous hemodialysis in hypercapnic animals. METHODS: In an experimental setting, we induced severe acute kidney injury and hypercapnia in five female Landrace pigs. Subsequently, we initiated high (40mEq/L) bicarbonate continuous veno-venous hemodialysis with an oxygenation membrane in series to maintain a pH above 7.25. At intervals of 1 hour, 6 hours, and 12 hours following the initiation of continuous veno-venous hemodialysis, we performed standardized sweep gas flow titration to quantify carbon dioxide transfer. We evaluated factors associated with carbon dioxide transfer through the membrane lung with a mixed linear model. RESULTS: A total of 20 sweep gas flow titration procedures were conducted, yielding 84 measurements of carbon dioxide transfer. Multivariate analysis revealed associations among the following (coefficients ± standard errors): core temperature (+7.8 ± 1.6 °C, p < 0.001), premembrane partial pressure of carbon dioxide (+0.2 ± 0.1/mmHg, p < 0.001), hemoglobin level (+3.5 ± 0.6/g/dL, p < 0.001), sweep gas flow (+6.2 ± 0.2/L/minute, p < 0.001), and arterial oxygen saturation (-0.5 ± 0.2%, p = 0.019). Among these variables, and within the physiological ranges evaluated, sweep gas flow was the primary modifiable factor influencing the efficacy of low-blood-flow carbon dioxide removal. CONCLUSION: Sweep gas flow is the main carbon dioxide removal-related variable during continuous veno-venous hemodialysis with a high bicarbonate level coupled with an oxygenator. Other carbon dioxide transfer modulating variables included the hemoglobin level, arterial oxygen saturation, partial pressure of carbon dioxide and core temperature. These results should be interpreted as exploratory to inform other well-designed experimental or clinical studies.
Assuntos
Injúria Renal Aguda , Bicarbonatos , Dióxido de Carbono , Terapia de Substituição Renal Contínua , Modelos Animais de Doenças , Hipercapnia , Animais , Dióxido de Carbono/sangue , Feminino , Injúria Renal Aguda/terapia , Injúria Renal Aguda/metabolismo , Suínos , Bicarbonatos/sangue , Terapia de Substituição Renal Contínua/métodos , Hipercapnia/terapia , Hipercapnia/sangue , Hipercapnia/metabolismo , Hipoventilação/terapia , Hipoventilação/etiologia , Hipoventilação/sangue , Oxigenação por Membrana Extracorpórea/métodos , Oxigenação por Membrana Extracorpórea/efeitos adversosRESUMO
BACKGROUND: Rett syndrome is a progressive neurological disorder associated to several comorbidities that contribute significantly to impair lung function. Respiratory morbidity represents a major cause of death in this population. Little is known about the benefit of noninvasive ventilation. METHODS: We retrospectively enrolled patients with Rett syndrome who underwent a pneumological evaluation combined with a cardiorespiratory polygraphy and/or a pulse oximetry and capnography from 2012 to 2022. RESULTS: Medical records of 11 patients with Rett syndrome, mean age 13 ± 6 years, were evaluated. Most patients presented with both epilepsy and scoliosis. Five patients showed a pathologic sleep study and/or impaired night gas exchange: mean obstructive apnea-hypopnea index was 4 ± 3 events/hour; mean and minimal SpO2 were, respectively, 93% ± 2% and 83% ± 6%, while mean and maximal transcutaneous carbon dioxide monitoring (PtcCO2) were, respectively, 51 ± 5 mm Hg and 55 ± 8 mm Hg; and mean oxygen desaturation index was 13 ± 11 events/hour. These patients started noninvasive ventilation with clinical benefit and improved gas exchange mostly in terms of PtcCO2 (mean PtcCO2 51 ± 5 mm Hg before and 46 ± 6 mm Hg after noninvasive ventilation). CONCLUSIONS: Noninvasive ventilation is a suitable option for patients with Rett syndrome.
Assuntos
Hipoventilação , Ventilação não Invasiva , Síndrome de Rett , Humanos , Síndrome de Rett/complicações , Síndrome de Rett/terapia , Síndrome de Rett/fisiopatologia , Feminino , Hipoventilação/terapia , Hipoventilação/etiologia , Estudos Retrospectivos , Adolescente , Criança , Adulto Jovem , Oximetria , Pré-Escolar , Polissonografia , Resultado do TratamentoRESUMO
Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder characterized by hypoventilation due to impaired breathing control by the central nervous system and other symptoms of autonomic dysfunction. Mutations in paired-like homeobox 2 B (PHOX2B) are responsible for most cases of CCHS. Patients with CCHS have various phenotypes and severities, making the diagnosis difficult. This study aimed to present a comprehensive single-center experience of patients with CCHS, including key clinical features, treatment strategies, and outcomes. A retrospective chart review was performed for patients diagnosed with CCHS between January 2001 and July 2023 at Seoul National University Children's Hospital. Finally, we selected 24 patients and collected their demographic data, genotypes, ventilation methods, and clinical features related to autonomic dysfunction. The relationship between the clinical manifestations and genotypes was also examined. All patients used home ventilators, and tracheostomy was performed in 87.5% of patients. Fifteen (62.5%) patients had constipation and nine (37.5%) were diagnosed with Hirschsprung disease. Arrhythmia, endocrine dysfunction, and subclinical hypothyroidism were present in nine (37.5%), six patients (25.0%), and two patients (16.7%), respectively. A significant number of patients exhibited neurodevelopmental delays (19 patients, 79.2%). There was a correlation between the phenotype and genotype of PHOX2B in patients with CCHS. (r = 0.71, p < 0.001). Conclusion: There was a positive correlation between paired-like homeobox 2 B mutations (especially the number of GCN repeats in the polyalanine repeat mutations sequence) and clinical manifestations. This study also demonstrated how initial treatment for hypoventilation affects neurodevelopmental outcomes in patients with CCHS. What is Known: ⢠Congenital central hypoventilation syndrome is a rare genetic disorder characterized by hypoventilation and dysfunction of autonomic nervous system. ⢠The disease-defining gene of CCHS is PHOX2B gene - most of the cases have heterozygous PARMs and the number of GCN triplets varies among the patients(20/24 - 20/33). What is New: ⢠We have noted in the Korean patients with CCHS that there is a correlation between genotype (number of GCN repeats) and severity of phenotype. ⢠National support for rare diseases allowed for a prompter diagnosis of patients with CCHS in Korean population.
Assuntos
Proteínas de Homeodomínio , Hipoventilação , Apneia do Sono Tipo Central , Humanos , Feminino , Masculino , Apneia do Sono Tipo Central/genética , Apneia do Sono Tipo Central/terapia , Apneia do Sono Tipo Central/diagnóstico , Estudos Retrospectivos , Hipoventilação/congênito , Hipoventilação/terapia , Hipoventilação/genética , Hipoventilação/diagnóstico , Lactente , República da Coreia/epidemiologia , Pré-Escolar , Proteínas de Homeodomínio/genética , Fatores de Transcrição/genética , Respiração Artificial/estatística & dados numéricos , Recém-Nascido , Criança , Fenótipo , Genótipo , Mutação , TraqueostomiaRESUMO
OBJECTIVE: Seizures can be difficult to control in infants and toddlers. Seizures with periods of apnea and hypoventilation are common following severe traumatic brain injury (TBI). We previously observed that brief apnea with hypoventilation (A&H) in our severe TBI model acutely interrupted seizures. The current study is designed to determine the effect of A&H on subsequent seizures and whether A&H has potential therapeutic implications. METHODS: Piglets (1 week or 1 month old) received multifactorial injuries: cortical impact, mass effect, subdural hematoma, subarachnoid hemorrhage, and seizures induced with kainic acid. A&H (1 min apnea, 10 min hypoventilation) was induced either before or after seizure induction, or control piglets received subdural/subarachnoid hematoma and seizure without A&H. In an intensive care unit, piglets were sedated, intubated, and mechanically ventilated, and epidural electroencephalogram was recorded for an average of 18 h after seizure induction. RESULTS: In our severe TBI model, A&H after seizure reduced ipsilateral seizure burden by 80% compared to the same injuries without A&H. In the A&H before seizure induction group, more piglets had exclusively contralateral seizures, although most piglets in all groups had seizures that shifted location throughout the several hours of seizure. After 8-10 h, seizures transitioned to interictal epileptiform discharges regardless of A&H or timing of A&H. SIGNIFICANCE: Even brief A&H may alter traumatic seizures. In our preclinical model, we will address the possibility of hypercapnia with normoxia, with controlled intracranial pressure, as a therapeutic option for children with status epilepticus after hemorrhagic TBI.
Assuntos
Apneia , Lesões Encefálicas Traumáticas , Modelos Animais de Doenças , Hipoventilação , Convulsões , Animais , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/fisiopatologia , Suínos , Convulsões/etiologia , Convulsões/fisiopatologia , Hipoventilação/terapia , Hipoventilação/fisiopatologia , Hipoventilação/etiologia , Apneia/fisiopatologia , Eletroencefalografia , Fatores de Tempo , Ácido Caínico , MasculinoRESUMO
BACKGROUND: Duchenne muscular dystrophy (DMD) is a neuromuscular disorder with progressive decline of pulmonary function increasing the risk of early mortality. The aim of this study was to explore the respiratory-related comorbidities, and the effect of these comorbidities and treatments on life expectancy and causes of death. METHODS: All male patients living in Sweden with DMD, born and deceased 1970-2019, were included. Data regarding causes of death were collected from the Cause of Death Registry and cross-checked with the medical records along with diagnostics and relevant clinical features. RESULTS: Hundred and twenty nine patients were included with a median lifespan of 24.3 years. Acute respiratory failure accounted for 63.3% of respiratory-related causes of death. 70.1% suffered at least one pneumonia, with first episode at a median age of 17.8 years. Hypoventilation was found in 73.0% with onset at 18.1 years. 60.5% had their first pneumonia before established hypoventilation. Age at onset of hypoventilation showed a strong correlation with age at first pneumonia. First pneumonia and scoliosis non-treated with scoliosis surgery increased the risk of dying of respiratory-related causes. In 10% of the patients, first pneumonia resulted in acute tracheostomy or early death. Patients treated with assisted ventilation had higher life expectancy compared to untreated patients. CONCLUSIONS: Our results highlight the importance of identifying subclinical hypoventilation in a timely manner and the importance of an active treatment regime upon clinical signs of pneumonia.
Assuntos
Causas de Morte , Comorbidade , Expectativa de Vida , Distrofia Muscular de Duchenne , Insuficiência Respiratória , Humanos , Distrofia Muscular de Duchenne/mortalidade , Distrofia Muscular de Duchenne/terapia , Distrofia Muscular de Duchenne/epidemiologia , Distrofia Muscular de Duchenne/complicações , Masculino , Adolescente , Adulto , Adulto Jovem , Suécia/epidemiologia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/mortalidade , Insuficiência Respiratória/terapia , Insuficiência Respiratória/epidemiologia , Criança , Pneumonia/epidemiologia , Pneumonia/mortalidade , Sistema de Registros , Hipoventilação/terapia , Hipoventilação/epidemiologia , Hipoventilação/etiologia , Hipoventilação/mortalidade , Pré-EscolarRESUMO
STUDY OBJECTIVES: Congenital central hypoventilation syndrome (CCHS) is a rare disease predisposing children to respiratory failure due to abnormal ventilatory drive. Variability in hypoventilation and respiratory support need have been reported. We aim to identify clinical variables associated with incident tracheostomy and common etiologies of hospitalization among children with CCHS. METHODS: Hospital discharge records were obtained for children (<21 years) with CCHS hospitalized between 2006 and 2019 from the Kid's Inpatient Database. Primary diagnostic categories for hospitalizations with CCHS were summarized. Multivariable logistic regression models were used to explore risk factors associated with incident tracheostomy. RESULTS: Among 2404 hospitalizations with CCHS, 133 (5.5%) had incident tracheostomy, 1230 (51.2%) had established tracheostomy, and 1041 (43.3%) had no tracheostomy. Compared with children without tracheostomy, those with incident tracheostomy were younger, had a history of prematurity, congenital heart disease, laryngeal, glottic, and subglottic stenosis (LGSS), congenital airway anomalies, neuromuscular weakness, gastroesophageal reflux disease. Children without tracheostomy had higher mortality than those with tracheostomy status (2.19% vs. 0.66%). Multivariable-adjusted analyses showed that incident tracheostomy was associated with infancy (0-1 years), neuromuscular weakness, and congenital heart disease. Most common diagnostic categories include (1) diseases of the respiratory system (30.23%), (2) injury and poisoning (9.35%), and (3) diseases of the nervous system and sense organs (6.71%). CONCLUSIONS: Children with CCHS who received incident tracheostomy are more likely to be younger and with LGSS, neuromuscular weakness and congenital heart disease. Clinicians should be aware of these risk factors representing more severe CCHS with earlier manifestation needing tracheostomy. Higher mortality among nontracheostomy group highlights the need for considering tracheostomy in caring for children with CCHS.
Assuntos
Bases de Dados Factuais , Hipoventilação , Apneia do Sono Tipo Central , Traqueostomia , Humanos , Traqueostomia/estatística & dados numéricos , Apneia do Sono Tipo Central/epidemiologia , Apneia do Sono Tipo Central/terapia , Apneia do Sono Tipo Central/complicações , Feminino , Masculino , Lactente , Criança , Pré-Escolar , Hipoventilação/congênito , Hipoventilação/epidemiologia , Hipoventilação/terapia , Adolescente , Fatores de Risco , Recém-Nascido , Hospitalização/estatística & dados numéricos , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
Acute hypoxemic respiratory failure is defined by Pao2 less than 60 mm Hg or SaO2 less than 88% and may result from V/Q mismatch, shunt, hypoventilation, diffusion limitation, or low inspired oxygen tension. Acute hypercapnic respiratory failure is defined by Paco2 ≥ 45 mm Hg and pH less than 7.35 and may result from alveolar hypoventilation, increased fraction of dead space, or increased production of carbon dioxide. Early diagnostic maneuvers, such as measurement of SpO2 and arterial blood gas, can differentiate the type of respiratory failure and guide next steps in evaluation and management.
Assuntos
Hipoventilação , Síndrome do Desconforto Respiratório , Humanos , Hipoventilação/diagnóstico , Hipoventilação/terapiaRESUMO
Congenital central hypoventilation syndrome (CCHS), a rare disease caused by paired-like homeobox 2B variants, affects control of breathing. We report on a 21-month-old boy with CCHS caused by a novel nonpolyalanine repeat mutation, neuroblastoma, severe obstructive and central sleep apnea, and sleep-related hypoxemia without hypoventilation. At 10 months, due to persistent central sleep apnea during serial polysomnography, bilevel positive airway pressure therapy was initiated despite the absence of hypoventilation. Nonpolyalanine repeat mutations are associated with severe phenotypes requiring continuous assisted ventilation, Hirschsprung's disease, and neural crest tumors; however, our patient had a relatively milder respiratory phenotype requiring sleep-only assisted ventilation without tracheostomy. Although alveolar hypoventilation is the hallmark of CCHS, our patient lacked hypoventilation. Bilevel positive airway pressure could be considered in some infants with CCHS requiring sleep-only assisted ventilation for tracheostomy avoidance. Our case demonstrates the expanding phenotypic spectrum in CCHS and the importance of formulating an individualized care plan. CITATION: Fain ME, Raghunandan S, Pencheva B, Leu RM, Kasi AS. Images: atypical presentation of congenital central hypoventilation syndrome in an infant with central and obstructive sleep apnea. J Clin Sleep Med. 2024;20(3):478-481.
Assuntos
Hipoventilação/congênito , Apneia do Sono Tipo Central , Apneia Obstrutiva do Sono , Masculino , Lactente , Humanos , Hipoventilação/complicações , Hipoventilação/genética , Hipoventilação/terapia , Apneia do Sono Tipo Central/complicações , Apneia do Sono Tipo Central/genética , Apneia do Sono Tipo Central/terapia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/terapia , SonoRESUMO
Congenital central hypoventilation syndrome (CCHS) is a rare condition characterized by central hypoventilation, leading to the majority of patients being dependent on ventilatory support during sleep. This condition is often accompanied by various associated symptoms, due to a PHOX2B gene variant involved in neuronal crest cell migration. This study is the first to review the characteristics and outcomes in children with CCHS on long-term mechanical ventilation in the Netherlands. We performed a retrospective study of all CCHS patients treated in the 4 Centers of Home Mechanical Ventilation of the University Medical Centers in the Netherlands from 2000 till 2022 by collecting information from the electronic medical records, documented during follow-up. We included 31 patients, out of which 27 exhibited a known genetic profile associated with CCHS, while no PHOX2B variant was identified in the remaining patients. Among the 27 patients with known genetic profiles, 10 patients had a non-polyalanine repeat expansion mutation (NPARM), followed by 20/27, 20/25, and 20/26 polyalanine repeat expansion mutations (PARMs) in descending order. The most common presentation involved respiratory failure or apneas during the neonatal period with an inability to wean off ventilation. The majority of patients required ventilatory support during sleep, with four patients experiencing life-threatening events related to this dependency. Daily use of ventilatory support varied among different genetic profiles. All genotypes reported comorbidities, with Hirschsprung's disease and cardiac arrhythmias being the most reported comorbidities. Notably, Hirschprung's disease was exclusively observed in patients with a 20/27 PHOX2B variant. CONCLUSION: 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. WHAT IS KNOWN: ⢠The majority of CCHS patients are dependent on ventilatory support. ⢠Variants in the PHOX2B gene are responsible for the characteristics of CCHS. WHAT IS NEW: ⢠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.
Assuntos
Hipoventilação , Hipoventilação/congênito , Apneia do Sono Tipo Central , Criança , Recém-Nascido , Humanos , Hipoventilação/genética , Hipoventilação/terapia , Proteínas de Homeodomínio/genética , Respiração Artificial , Estudos Retrospectivos , Países Baixos , Fatores de Transcrição/genética , Mutação , Apneia do Sono Tipo Central/genética , Apneia do Sono Tipo Central/terapiaRESUMO
INTRODUCTION: Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder with a mutation in the PHOX2B gene. Patients need ventilatory support by noninvasive ventilation or tracheostomy to treat alveolar hypoventilation. Patients with CCHS have a defect in chemosensitivity signal integration. Recently, due to the COVID-19 pandemic, the entire world has had to get used to wearing medical masks (MM). OBJECTIVES: The aim of the study was to evaluate the effect of an MM on gas exchange and to determine the role of central and peripheral chemoresponsiveness on the partial pressure of transcutaneous carbon dioxide (PtcCO2) in patients with CCHS wearing an MM. METHODS: This study was based on the analysis of recordings obtained without and with an MM during hospitalization and was conducted to assess the impact of MM on PtcCO2 and SpO2 recordings with the SenTec Digital Monitor and their relationships with peripheral CO2 chemosensitivity obtained during tidal breathing measurement and with the hypercapnic hyperoxic ventilatory response. RESULTS: Sixteen patients were included (13 boys) and were 10.2 (7.5; 18.5) years old. The use of an MM had a negative impact on gas exchange in patients with CCHS. The median PtcCO2 increased significantly. Peripheral chemosensitivity correlated with MM-induced PtcCO2 changes (R = -0.72, p = 0.005), but central chemosensitivity (the hypercapnic ventilator response slope) did not (R = -0.22, p = 0.510). CONCLUSION: The use of an MM had a negative impact on gas exchange in patients with CCHS.
Assuntos
Hipoventilação , Apneia do Sono Tipo Central , Masculino , Humanos , Adolescente , Hipoventilação/terapia , Hipoventilação/congênito , Máscaras , Pandemias , Apneia do Sono Tipo Central/terapia , Hipercapnia/terapia , Proteínas de Homeodomínio/genéticaRESUMO
Sleep disordered breathing (SDB) is prevalent among children with neuromuscular disorders (NMD). The combination of respiratory muscle weakness, altered drive, and chest wall distortion due to scoliosis make sleep a stressful state in this population. Symptomatology can range from absent to snoring, nocturnal awakenings, morning headaches, and excessive daytime sleepiness. Sequelae of untreated SDB includes cardiovascular effects, metabolic derangements, and neurocognitive concerns which can be compounded by those innate to the NMD. The clinician should have a low threshold for obtaining polysomnography and recognize the nuances of individual disorders due to disproportionately impacted muscle groups such as hypoventilation in ambulating patients from diaphragm weakness. Non-invasive or invasive ventilation are the mainstay of treatment. In this review we explore the diagnosis and treatment of SDB in children with various NMD.
Assuntos
Doenças Neuromusculares , Síndromes da Apneia do Sono , Humanos , Criança , Sono , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/terapia , Doenças Neuromusculares/complicações , Doenças Neuromusculares/diagnóstico , Doenças Neuromusculares/terapia , Hipoventilação/complicações , Hipoventilação/terapia , PolissonografiaRESUMO
INTRODUCTION: Home noninvasive ventilation (HNIV) has expanded globally, with a greater evidence base for its use. HNIV improves multiple patient related outcomes in patients with chronic hypercapnic respiratory failure. Obesity hypoventilation syndrome (OHS) is rapidly taking over as the primary indication for HNIV and COPD patients who overlap with obstructive sleep apnea hypoventilation syndromes (OSAHS) and are increasingly recognized but add to the complexity of HNIV prescribing. Optimal settings vary for differing diseases, with higher inspiratory pressures often required in those with OHS and COPD, yet which settings translate into greatest patient benefit remains unknown. AREAS COVERED: We cover the evidence base underpinning the common indications for HNIV in COPD, OHS, neuromuscular disease (NMD), and chest wall disease (CWD) and highlight common HNIV modes used. EXPERT OPINION: Active screening for nocturnal hypoventilation in OHS and COPD may be important to guide earlier ventilation. Further research on which HNIV modalities best improve patient related outcomes and the right time for initiation in different patient phenotypes is rapidly needed. Worldwide, clinical research trials should aim to bridge the gap by reporting on patient-related outcomes and cost effectiveness in real-world populations to best understand the true benefit of HNIV amongst heterogenous patient populations.
Assuntos
Ventilação não Invasiva , Síndrome de Hipoventilação por Obesidade , Doença Pulmonar Obstrutiva Crônica , Humanos , Ventilação não Invasiva/efeitos adversos , Hipoventilação/diagnóstico , Hipoventilação/terapia , Respiração Artificial , Síndrome de Hipoventilação por Obesidade/terapia , Doença Pulmonar Obstrutiva Crônica/terapia , HipercapniaRESUMO
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.
Assuntos
Apneia do Sono Tipo Central , Humanos , Criança , Masculino , Feminino , Lactente , Apneia do Sono Tipo Central/terapia , Respiração Artificial , Hipoventilação/terapia , Hipoventilação/congênito , OxigênioRESUMO
PURPOSE: To provide an overview of the discovery, presentation, and management of Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD). To discuss a search for causative etiology spanning multiple disciplines and continents. METHODS: The literature (1965-2022) on the diagnosis, management, pathophysiology, and potential etiology of ROHHAD was methodically reviewed. The experience of several academic centers with expertise in ROHHAD is presented, along with a detailed discussion of scientific discovery in the search for a cause. RESULTS: ROHHAD is an ultra-rare syndrome with fewer than 200 known cases. Although variations occur, the acronym ROHHAD is intended to alert physicians to the usual sequence or unfolding of the phenotypic presentation, including the full phenotype. Nearly 60 years after its first description, more is known about the pathophysiology of ROHHAD, but the etiology remains enigmatic. The search for a genetic mutation common to patients with ROHHAD has not, to date, demonstrated a disease-defining gene. Similarly, a search for the autoimmune basis of ROHHAD has not resulted in a definitive answer. This review summarizes current knowledge and potential future directions. CONCLUSION: ROHHAD is a poorly understood, complex, and potentially devastating disorder. The search for its cause intertwines with the search for causes of obesity and autonomic dysregulation. The care for the patient with ROHHAD necessitates collaborative international efforts to advance our knowledge and, thereby, treatment, to decrease the disease burden and eventually to stop, and/or reverse the unfolding of the phenotype.