RESUMO
OBJECTIVE: Ictal central apnea (ICA) is a semiological sign of focal epilepsy, associated with temporal and frontal lobe seizures. In this study, using qualitative and quantitative approaches, we aimed to assess the localizational value of ICA. We also aimed to compare ICA clinical utility in relation to other seizure semiological features of focal epilepsy. METHODS: We analyzed seizures in patients with medically refractory focal epilepsy undergoing intracranial stereotactic electroencephalographic (SEEG) evaluations with simultaneous multimodal cardiorespiratory monitoring. A total of 179 seizures in 72 patients with reliable artifact-free respiratory signal were analyzed. RESULTS: ICA was seen in 55 of 179 (30.7%) seizures. Presence of ICA predicted a mesial temporal seizure onset compared to those without ICA (odds ratio = 3.8, 95% confidence interval = 1.3-11.6, p = 0.01). ICA specificity was 0.82. ICA onset was correlated with increased high-frequency broadband gamma (60-150Hz) activity in specific mesial or basal temporal regions, including amygdala, hippocampus, and fusiform and lingual gyri. Based on our results, ICA has an almost 4-fold greater association with mesial temporal seizure onset zones compared to those without ICA and is highly specific for mesial temporal seizure onset zones. As evidence of symptomatogenic areas, onset-synchronous increase in high gamma activity in mesial or basal temporal structures was seen in early onset ICA, likely representing anatomical substrates for ICA generation. INTERPRETATION: ICA recognition may help anatomoelectroclinical localization of clinical seizure onset to specific mesial and basal temporal brain regions, and the inclusion of these regions in SEEG evaluations may help accurately pinpoint seizure onset zones for resection. ANN NEUROL 2024;95:998-1008.
Assuntos
Epilepsia do Lobo Temporal , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Epilepsia do Lobo Temporal/fisiopatologia , Epilepsia do Lobo Temporal/diagnóstico , Apneia do Sono Tipo Central/fisiopatologia , Apneia do Sono Tipo Central/diagnóstico , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/diagnóstico , Convulsões/fisiopatologia , Convulsões/diagnóstico , Adulto Jovem , Eletrocorticografia/métodos , Eletroencefalografia/métodos , Adolescente , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/diagnósticoRESUMO
BACKGROUND: Congenital Central Hypoventilation Syndrome (CCHS) has devastating consequences if not diagnosed promptly. Despite identification of the disease-defining gene PHOX2B and a facial phenotype, CCHS remains underdiagnosed. This study aimed to incorporate automated techniques on facial photos to screen for CCHS in a diverse pediatric cohort to improve early case identification and assess a facial phenotype-PHOX2B genotype relationship. METHODS: Facial photos of children and young adults with CCHS were control-matched by age, sex, race/ethnicity. After validating landmarks, principal component analysis (PCA) was applied with logistic regression (LR) for feature attribution and machine learning models for subject classification and assessment by PHOX2B pathovariant. RESULTS: Gradient-based feature attribution confirmed a subtle facial phenotype and models were successful in classifying CCHS: neural network performed best (median sensitivity 90% (IQR 84%, 95%)) on 179 clinical photos (versus LR and XGBoost, both 85% (IQR 75-76%, 90%)). Outcomes were comparable stratified by PHOX2B genotype and with the addition of publicly available CCHS photos (n = 104) using PCA and LR (sensitivity 83-89% (IQR 67-76%, 92-100%). CONCLUSIONS: Utilizing facial features, findings suggest an automated, accessible classifier may be used to screen for CCHS in children with the phenotype and support providers to seek PHOX2B testing to improve the diagnostics. IMPACT: Facial landmarking and principal component analysis on a diverse pediatric and young adult cohort with PHOX2B pathovariants delineated a distinct, subtle CCHS facial phenotype. Automated, low-cost machine learning models can detect a CCHS facial phenotype with a high sensitivity in screening to ultimately refer for disease-defining PHOX2B testing, potentially addressing gaps in disease underdiagnosis and allow for critical, timely intervention.
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Face , Proteínas de Homeodomínio , Hipoventilação , Fenótipo , Apneia do Sono Tipo Central , Fatores de Transcrição , Humanos , Proteínas de Homeodomínio/genética , Feminino , Masculino , Fatores de Transcrição/genética , Hipoventilação/congênito , Hipoventilação/diagnóstico , Hipoventilação/genética , Criança , Face/anormalidades , Apneia do Sono Tipo Central/diagnóstico , Apneia do Sono Tipo Central/genética , Pré-Escolar , Diagnóstico por Computador/métodos , Análise de Componente Principal , Adolescente , Aprendizado de Máquina , Adulto Jovem , Lactente , Genótipo , Fotografação , Estudos de Casos e Controles , Modelos LogísticosRESUMO
ABSTRACT: Central sleep apnea (CSA) is common in patients with heart failure. Recent studies link ticagrelor use with CSA. We aimed to evaluate CSA prevalence in patients with coronary heart disease (CHD) and whether ticagrelor use is associated with CSA. We reviewed consecutive patients with CHD who underwent a polysomnography (PSG) test over a 5-year period from 3 sleep centers. We sampled patients who were on ticagrelor or clopidogrel during a PSG test at a 1:4 ticagrelor:clopidogrel ratio. Patients with an active opioid prescription during PSG test were excluded. Age, left ventricle (LV) dysfunction, and P2Y12 inhibitor use were included in a multivariate logistic regression. A total of 135 patients were included with 26 on ticagrelor and 109 on clopidogrel (age 64.1 ± 11.4, 32% male). High CSA burden (12%) and strict CSA (4.4%) were more common in patients on ticagrelor than in those on clopidogrel (27% vs. 8.3% and 10.0% vs. 1.8%). Ticagrelor use (vs. clopidogrel) was associated with high CSA burden (OR 3.53, 95% CI 1.04-12.9, P = 0.039) and trended toward significance for strict CSA (OR 6.32, 95% CI 1.03-51.4, P = 0.052) when adjusting for age and LV dysfunction. In an additional analysis also adjusting for history of atrial fibrillation, ticagrelor use and strict CSA became significantly associated (OR 10.0, 95% CI 1.32-117, P = 0.035). CSA was uncommon in patients with CHD undergoing sleep studies. Ticagrelor use (vs. clopidogrel) was associated with high CSA burden and trended toward significance for strict CSA.
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Doença das Coronárias , Apneia do Sono Tipo Central , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Apneia do Sono Tipo Central/induzido quimicamente , Apneia do Sono Tipo Central/diagnóstico , Apneia do Sono Tipo Central/epidemiologia , Clopidogrel , Ticagrelor/efeitos adversos , Analgésicos Opioides , Doença das Coronárias/diagnóstico , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/epidemiologiaRESUMO
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.
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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
PURPOSE: To investigate the prevalence of treatment-emergent central sleep apnea (TECSA) in individuals with obstructive sleep apnea syndrome (OSAS) during continuous positive airway pressure (CPAP) titration and assess their polysomnographic characteristics. METHODS: A total of 116 patients with OSAS who underwent full-night CPAP titration at the Sleep Laboratory of Adana City Research and Education Hospital from September 2017 to January 2018 were recruited for the study. The patients' polysomnographic data related to respiratory events and sleep stages were reviewed in a retrospective manner. RESULTS: While on CPAP titration, 20 of the 116 patients developed central sleep apnea (CSA). The prevalence of TECSA in the patients with OSAS was 17.2%, being separately determined as 16.3% and 2.2% for the male and female patients, respectively. In the baseline PSG, the groups did not statistically significantly differ in relation to the apnea hypopnea index (AHI), central apnea index (CAI), arousal index (AI), or oxygen desaturation index (ODI). However, the TECSA group had a significantly higher mean oxygen saturation value compared to the non-TECSA group (p = 0.01). The total AHI, CAI, and AI values of the TECSA group were significantly higher during the whole CPAP titration compared to the non-TECSA group. No significant difference was observed in the comparison of the two groups in relation to the titration pressure and ODI. CONCLUSION: TECSA is a phenomenon that can occur with obstructive sleep apnea treatment and mostly regress spontaneously following appropriate CPAP treatment. TECSA is observed at different rates of prevalence. In this study, the prevalence of TECSA was higher than previously reported.
Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Polissonografia , Apneia do Sono Tipo Central , Apneia Obstrutiva do Sono , Humanos , Masculino , Feminino , Apneia Obstrutiva do Sono/terapia , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/diagnóstico , Pessoa de Meia-Idade , Apneia do Sono Tipo Central/epidemiologia , Apneia do Sono Tipo Central/terapia , Apneia do Sono Tipo Central/diagnóstico , Adulto , Estudos Retrospectivos , Prevalência , IdosoRESUMO
OBJECTIVE: To study the trinucleotide repeats of GCN (GCA, GCT, GCC, GCG) encoding Alanine in exon 3 of the PHOX2B gene among healthy individuals from southwest China and two patients with Congenital central hypoventilation syndrome (CCHS). METHODS: The number and sequence of the GCN repeats of the PHOX2B gene were analyzed by capillary electrophoresis, Sanger sequencing and cloning sequencing of 518 healthy individuals and two newborns with CCHS, respectively. RESULTS: Among the 1036 alleles of the 518 healthy individuals, five alleles were identified, including (GCN)7, (GCN)13, (GCN)14, (GCN)15 and (GCN)20. The frequency of the (GCN)20 allele was the highest (94.79%). And five genotypes were identified, which included (GCN)7/(GCN)20, (GCN)13/(GCN)20, (GCN)14/(GCN)20, (GCN)15/(GCN)20, (GCN)20/(GCN)20. The homozygous genotypes were all (GCN)20/(GCN)20, and the carrier rate was 89.58%. Four GCN sequences of the (GCN)20 homozygous genotypes were identified among the 464 healthy individuals. The GCN repeat numbers in the exon 3 of the PHOX2B gene showed no significant difference between the expected and observed values, and had fulfilled the,Hardy-Weinberg equilibrium. The genotypes of the two CCHS patients were (GCN)20/(GCN)25 and (GCN)20/(GCN)30, respectively. CONCLUSION: It is important to determine the GCN repeats and genotypic data of the exon 3 of the PHOX2B gene among the healthy individuals. The number of GCN repeats in 518 healthy individuals was all below 20. The selection of appropriate methods can accurately detect the polyalanine repeat mutations (PARMs) of the PHOX2B gene, which is conducive to the early diagnosis, intervention and treatment of CCHS.
Assuntos
Apneia do Sono Tipo Central , Fatores de Transcrição , Humanos , Recém-Nascido , Proteínas de Homeodomínio/genética , Hipoventilação/diagnóstico , Hipoventilação/genética , Hipoventilação/congênito , Mutação , Apneia do Sono Tipo Central/diagnóstico , Apneia do Sono Tipo Central/genética , Fatores de Transcrição/genéticaRESUMO
Objective. Monitoring of apnea of prematurity, performed in neonatal intensive care units by detecting central apneas (CAs) in the respiratory traces, is characterized by a high number of false alarms. A two-step approach consisting of a threshold-based apneic event detection algorithm followed by a machine learning model was recently presented in literature aiming to improve CA detection. However, since this is characterized by high complexity and low precision, we developed a new direct approach that only consists of a detection model based on machine learning directly working with multichannel signals.Approach. The dataset used in this study consisted of 48 h of ECG, chest impedance and peripheral oxygen saturation extracted from 10 premature infants. CAs were labeled by two clinical experts. 47 features were extracted from time series using 30 s moving windows with an overlap of 5 s and evaluated in sets of 4 consecutive moving windows, in a similar way to what was indicated for the two-step approach. An undersampling method was used to reduce imbalance in the training set while aiming at increasing precision. A detection model using logistic regression with elastic net penalty and leave-one-patient-out cross-validation was then tested on the full dataset.Main results. This detection model returned a mean area under the receiver operating characteristic curve value equal to 0.86 and, after the selection of a FPR equal to 0.1 and the use of smoothing, an increased precision (0.50 versus 0.42) at the expense of a decrease in recall (0.70 versus 0.78) compared to the two-step approach around suspected apneic events.Significance. The new direct approach guaranteed correct detections for more than 81% of CAs with lengthL≥ 20 s, which are considered among the most threatening apneic events for premature infants. These results require additional verifications using more extensive datasets but could lead to promising applications in clinical practice.
Assuntos
Apneia do Sono Tipo Central , Recém-Nascido , Lactente , Humanos , Apneia do Sono Tipo Central/diagnóstico , Recém-Nascido Prematuro , Apneia/diagnóstico , AlgoritmosRESUMO
INTRODUCTION: Periodic breathing (PB) is considered physiological in the neonatal period and usually disappears in the first months of life. There are few data available on persistent PB after the neonatal period. The objective of this study was to characterize infants born at term with persistent PB after the age of 1 month through polysomnography (PSG) performed during symptoms. METHODS: This retrospective case series included infants born at term between 2012 and 2021, without an underlying disease, who presented with symptoms of persistent PB during a PSG. Persistent PB was defined as more than 1 % of total sleep time (TST) of PB after 1 month of life, and PB was defined as a succession of at least three episodes of central apnea lasting more than 3 s and separated by less than 20 s of normal breathing. RESULTS: A total of 10 infants born at term were included. They underwent PSG for brief resolved unexplained events, desaturation, pauses in breathing, cyanosis, and/or signs of respiratory distress. The percentage of TST spent with PB was 18.1 % before 3 months of age (n = 7), and 4.7 % between 3 and 6 months of age (n = 10). During the first PSG, ≥3 % of desaturation events were observed in 77-100 % of the PB episodes. At the first PSG, nine of the 10 infants had an obstructive apnea-hypopnea index of >10/h and five of 10 infants had a central apnea index of >5/h. Gastroesophageal reflux (GER) was suspected in eight infants. All infants showed improvement in the initial symptoms during the first year of life. CONCLUSION: This study presents cases of persistent and symptomatic PB after 1 month of life in infants born at term. The interesting finding was the presence of obstructive sleep apnea syndrome and/or central apnea syndrome in the majority of children, along with GER.
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Polissonografia , Humanos , Estudos Retrospectivos , Masculino , Feminino , Lactente , Recém-Nascido , Síndromes da Apneia do Sono/diagnóstico , Apneia do Sono Tipo Central/diagnóstico , Apneia do Sono Tipo Central/terapiaRESUMO
Recent scientific findings in the field of sleep disordered breathing have characterised a variety of phenotypes in obstructive sleep apnoea. These findings have prompted investigations aiming to achieve a more precise differentiation and description of the entities of central sleep apnoea (CSA). There is increasing evidence for the heterogeneity of CSA in terms of underlying aetiology, pathophysiological concepts, treatment response and outcome. Assigning patients to these phenotypes allows for the selection of individualised therapies. Major pathophysiological characteristics include loop gain, apnoeic threshold, breathing regulation and neuromuscular mechanics. Chronic heart failure is the most important underlying disease, leading to nonhypercapnic CSA based on increased loop and controller gain. Although many questions remain, this review tries to describe the current knowledge on the pathophysiology of the clinical entities. The description of prognostic aspects may guide treatment indication and the selection of pharmacotherapy and invasive options. In addition, the paper provides an update on the current understanding of adaptive servo-ventilation and its role in the treatment of CSA.
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Insuficiência Cardíaca , Síndromes da Apneia do Sono , Apneia do Sono Tipo Central , Apneia Obstrutiva do Sono , Humanos , Apneia do Sono Tipo Central/diagnóstico , Apneia do Sono Tipo Central/genética , Apneia do Sono Tipo Central/terapia , Síndromes da Apneia do Sono/terapia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/terapia , Respiração , Pressão Positiva Contínua nas Vias Aéreas/efeitos adversosRESUMO
Congenital central hypoventilation syndrome (CCHS) is an autosomal dominant disease that is caused by heterozygous mutations in the paired-like homeobox 2B gene (PHOX2B). Madani et al. described an abnormally high degree of not only central apnea but also obstructive and mixed apnea in Phox2b27Ala/+newborn mice. Newborns with CCHS must undergo polysomnography for obstructive respiratory events in order to guide the optimal ventilation strategy if oxygen desaturation, bradycardia, and malaise persist under noninvasive ventilation. Newborns and infants with CCHS must be systematically tested for obstructive apnea, especially in cases of inefficient noninvasive ventilation.
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Obstrução das Vias Respiratórias , Hipoventilação , Apneia do Sono Tipo Central , Apneia Obstrutiva do Sono , Animais , Criança , Humanos , Lactente , Recém-Nascido , Camundongos , Obstrução das Vias Respiratórias/etiologia , Proteínas de Homeodomínio/genética , Hipoventilação/congênito , Mutação , Apneia do Sono Tipo Central/diagnóstico , Apneia do Sono Tipo Central/genética , Apneia do Sono Tipo Central/terapia , Fatores de Transcrição/genéticaRESUMO
INTRODUCTION: Central sleep apnea (CSA) is a sleep-related breathing disorder in which the effort to breathe is intermittently diminished or absent. CSA is a common disorder among patients with different cardiovascular disorders, including heart failure. In addition, a growing number of medications have been shown to induce CSA and CSA can emerge after initiation of treatment for obstructive sleep apnea. Accumulating evidence shows that CSA is a heterogeneous disorder with individual differences in clinical and biological characteristics and/or underlying pathophysiological mechanisms. AREAS COVERED: This narrative review offers an overview of the diagnostic aspects and classification of CSA, with an emphasis on heart failure patients, patients with CSA due to a medication and treatment-emergent CSA. The importance of evaluation of prognostic biomarkers in patients with different types of CSA is discussed. This narrative review synthesizes literature on CSA sourced from the PubMed database up to February 2024. EXPERT OPINION: CSA presents a remarkably diverse disorder, with treatment modalities exhibiting potentially varied efficacy across its various phenotypes. This highlights the imperative for tailored management strategies that are rooted in phenotype classification.
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Insuficiência Cardíaca , Apneia do Sono Tipo Central , Humanos , Apneia do Sono Tipo Central/fisiopatologia , Apneia do Sono Tipo Central/diagnóstico , Apneia do Sono Tipo Central/terapia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/diagnóstico , Biomarcadores/metabolismo , Prognóstico , Fenótipo , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/terapiaRESUMO
BACKGROUND: Sleep-disordered breathing (SDB) is common in patients with neuromuscular diseases (NMD). Focusing on hypercapnia may lead to the neglect of other SDB such as obstructive and/or central sleep apnea syndrome (SAS). Our objectives were to assess the risk of inappropriate SDB management according to different screening strategies and to evaluate the prevalence and determinants of isolated and overlapping sleep apnea in patients with slowly progressive NMD. METHODS: This monocentric, cross-sectional, retrospective study analyzed medical records of adult NMD patients referred to a sleep department. Diagnostic strategies, including respiratory polygraphy (RP), nocturnal transcutaneous capnography (tcCO2), and blood gases (BG), were assessed for their performance in diagnosing SDB. Demographics and pulmonary function test results were compared between patients with or without SDB to identify predictors. RESULTS: Among the 149 patients who underwent a full diagnostic panel (RP + tcCO2 + BG), 109 were diagnosed with SDB. Of these, 33% had isolated SAS, and central apneas were predominant. Using single diagnostic strategies would lead to inappropriate SDB management in two thirds of patients. A combination of 2 diagnostic tools resulted respectively in 21.1, 22.9 and 42.2 % of inappropriate SDB management for RP + tcCO2, RP + BG and tcCO2 + BG. CONCLUSION: The significant prevalence of sleep apnea syndrome in patients with slowly progressive NMD highlights the need for increased awareness among clinicians. Improved diagnostics involve a systematic approach addressing both sleep apnea and diurnal and nocturnal alveolar hypoventilation to avoid inappropriate management and limit the consequences of SDB.
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Doenças Neuromusculares , Síndromes da Apneia do Sono , Apneia do Sono Tipo Central , Adulto , Humanos , Estudos Retrospectivos , Estudos Transversais , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/epidemiologia , Doenças Neuromusculares/complicações , Doenças Neuromusculares/epidemiologia , Apneia do Sono Tipo Central/diagnóstico , Apneia do Sono Tipo Central/epidemiologia , Monitorização Transcutânea dos Gases SanguíneosRESUMO
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.
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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
BACKGROUND: This study investigated the association of sex with cardiovascular outcomes in a prospective cohort of patients with heart failure (HF) with obstructive sleep apnea or central sleep apnea. METHODS AND RESULTS: Patients were screened for sleep apnea on admission using multichannel cardiopulmonary monitoring from May 2015 to July 2018. The primary outcome was a composite of cardiovascular death or unplanned hospitalization for worsening HF. Ultimately, 453 patients with HF with obstructive sleep apnea or central sleep apnea were included; 71 (15.7%) and 382 (84.3%) were women and men, respectively. During a median follow-up of 2.33 years, 248 (54.7%) patients experienced the primary outcome. In the overall population, after adjusting for potential confounders, women had an increased risk of the primary outcome (66.2% versus 52.6%; hazard ratio [HR], 1.47 [95% CI, 1.05-2.04]; P=0.024) and HF rehospitalization (62.0% versus 46.6%; HR, 1.55 [95% CI, 1.10-2.19]; P=0.013) compared with men but a comparable risk of cardiovascular death (21.1% versus 23.3%; HR, 0.78 [95% CI, 0.44-1.37]; P=0.383). Likewise, in patients with HF with obstructive sleep apnea, women had a higher risk of the primary outcome (81.8% versus 46.3%, HR, 2.37 [95% CI, 1.28-4.38]; P=0.006) and HF rehospitalization (81.8% versus 44.7%, HR, 2.46 [95% CI, 1.32-4.56], P=0.004). However, in patients with HF with central sleep apnea, there was no statistically significant difference between women and men. CONCLUSIONS: In hospitalized patients with HF, female sex was associated with an increased risk of the primary outcome and HF rehospitalization, especially in those with obstructive sleep apnea. Screening for sleep apnea should be emphasized to improve the prognosis. REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02664818.
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Insuficiência Cardíaca , Síndromes da Apneia do Sono , Apneia do Sono Tipo Central , Apneia Obstrutiva do Sono , Feminino , Humanos , Masculino , Insuficiência Cardíaca/diagnóstico , Estudos Prospectivos , Síndromes da Apneia do Sono/complicações , Apneia do Sono Tipo Central/diagnóstico , Apneia do Sono Tipo Central/epidemiologia , Apneia do Sono Tipo Central/terapia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologiaRESUMO
INTRODUCTION: Congenital Central Hypoventilation Syndrome (CCHS) is a rare disease due to a severely impaired central control of breathing and dysfunction of the autonomic nervous system. Ophthalmologic abnormalities are common in patients with CCHS and include horizontal strabismus, pupil and iris abnormalities and ptosis. We report a unique case of CCHS in association with monocular elevation deficit (MED) in a boy diagnosed with CCHS at birth. CASE DESCRIPTION: We report a case of a boy with a confirmed diagnosis of CCHS (complete sequencing of the paired-like homeobox 2b (PHOX2B) gene) after presenting little respiratory effort and cyanosis at birth. The ophthalmological examination shows an impaired elevation of the left eye, both in adduction and abduction, associated with mild and variable left ptosis. His mother has observed that the left eyelid elevates when the child feeds. A deviation in the primary gaze position or a chin-up position are not present. The funduscopic examination is normal. Given that deviation is limited to upgaze, the ptosis is mild and the patient's age, observation is decided. CONCLUSIONS: Ophthalmologic abnormalities are common in patients with CCHS and include horizontal strabismus, pupil and iris abnormalities and ptosis. To the best of our knowledge, this is the first report of MED in association with CCHS. Further studies are needed to determine if an association between MED and CCHS exists or is just a casual finding in this case.
Assuntos
Blefaroptose , Hipoventilação , Hipoventilação/congênito , Apneia do Sono Tipo Central , Humanos , Masculino , Hipoventilação/diagnóstico , Hipoventilação/genética , Hipoventilação/fisiopatologia , Blefaroptose/diagnóstico , Blefaroptose/congênito , Blefaroptose/fisiopatologia , Apneia do Sono Tipo Central/diagnóstico , Apneia do Sono Tipo Central/fisiopatologia , Apneia do Sono Tipo Central/genética , Proteínas de Homeodomínio/genética , Recém-Nascido , Fatores de Transcrição/genética , Estrabismo/diagnóstico , Estrabismo/fisiopatologiaRESUMO
Paired-like homeobox 2B (PHOX2B) is a gene essential in the development of the autonomic nervous system. PHOX2B mutations are associated with neurocristopathies-Hirschsprung disease (HSCR) and congenital central hypoventilation syndrome (CCHS)-and peripheral neuroblastic tumours. PHOXB2 plays an important role in the diagnostics of these conditions.Genotyping of a PHOX2B pathogenic variant is required to establish a diagnosis of CCHS. In HSCR patients, PHOX2B immunohistochemical staining has proven to be a valuable tool in identifying this disease. Furthermore, PHOXB2 is a predisposition gene for neuroblastoma, in which PHOX2B immunohistochemical staining can be used as a highly sensitive and specific diagnostic marker. The utility of PHOX2B immunohistochemistry in pheochromocytoma and paraganglioma has also been studied but yields conflicting results.In this review, an overview is given of PHOX2B, its associated diseases and the usefulness of PHOX2B immunohistochemistry as a diagnostic tool.
Assuntos
Proteínas de Homeodomínio , Hipoventilação , Imuno-Histoquímica , Neuroblastoma , Fatores de Transcrição , Humanos , Proteínas de Homeodomínio/genética , Fatores de Transcrição/genética , Hipoventilação/congênito , Hipoventilação/diagnóstico , Hipoventilação/genética , Neuroblastoma/diagnóstico , Neuroblastoma/genética , Neuroblastoma/patologia , Apneia do Sono Tipo Central/diagnóstico , Apneia do Sono Tipo Central/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Doença de Hirschsprung/diagnóstico , Doença de Hirschsprung/genética , Doença de Hirschsprung/patologia , Mutação , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/patologia , Predisposição Genética para DoençaRESUMO
BACKGROUND: The presence of sleep-disordered breathing (SDB) in congestive heart failure (CHF) is associated with poor prognosis and is underdiagnosed despite advances in CHF management. The prevalence of SDB in CHF remains understudied in South East Asia. METHODS: A prospective, observational single-centre study was conducted where 116 consecutive patients in a specialised heart failure clinic underwent level 1, attended polysomnography (PSG). RESULTS: The prevalence of SDB was 78% using the apnoea-hypopnea index (AHI), AHI ⩾ 5/h threshold, and 59% with the AHI ⩾ 15/h threshold. Obstructive sleep apnoea (OSA) was the predominant type of SDB and was associated with increased body mass index and neck circumference. STOP-BANG was predictive of SDB, especially in men. Central sleep apnoea (CSA) patients had worse sleep indexes and lower awake arterial carbon dioxide. SDB was also homogenously present in preserved ejection fraction (EF) CHF. CONCLUSION: Most of the CHF patients were found to have SDB with the utility of PSG. Local CHF guidelines should include sleep testing for all patients with CHF.The study is registered on ClinicalTrials.gov (NCT05332223) as 'The Epidemiological Characteristics of SDB in Patients with Reduced or Preserved EF CHF'.
Assuntos
Insuficiência Cardíaca , Síndromes da Apneia do Sono , Apneia do Sono Tipo Central , Humanos , Masculino , Sudeste Asiático/epidemiologia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/epidemiologia , Estudos Prospectivos , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/epidemiologia , Síndromes da Apneia do Sono/complicações , Apneia do Sono Tipo Central/epidemiologia , Apneia do Sono Tipo Central/complicações , Apneia do Sono Tipo Central/diagnóstico , FemininoRESUMO
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
BACKGROUND: Sacubitril/valsartan has been demonstrated to significantly improve left ventricular performance and remodelling in patients with heart failure. However, its effects on the right ventricle in patients with chronic heart failure and sleep-disordered breathing (SDB) have not been studied. AIM: To investigate the impact of sacubitril/valsartan treatment on right ventricular function in patients with SDB. METHODS: This was a subanalysis of an observational prospective multicentre study involving 101 patients. At inclusion, patients were evaluated by echocardiography and nocturnal ventilatory polygraphy, which allowed patients to be divided into three groups: "central-SDB"; "obstructive-SDB"; and "no-SDB". RESULTS: After 3 months of sacubitril/valsartan therapy, a positive impact on right ventricular function was observed. In the general population, tricuspid annular plane systolic excursion increased by +1.32±4.74mm (P=0.024) and systolic pulmonary artery pressure decreased by -3.1±10.91mmHg (P=0.048). The central-SDB group experienced the greatest echocardiographic improvement, with a significant increase in tricuspid annular plane systolic excursion of +2.1±4.9mm (P=0.045) and a significant reduction in systolic pulmonary artery pressure of -8.4±9.7mmHg (P=0.001). CONCLUSIONS: Sacubitril/valsartan improved right ventricular function in patients with heart failure and SDB after only 3 months of treatment. The greatest improvement in right ventricular function was observed in the central-SDB group.