Long-Term Survival of a Patient with Congenital Central Hypoventilation Syndrome despite the Lack of Continuous Ventilatory Support

Respiration ◽  
2004 ◽  
Vol 71 (2) ◽  
pp. 195-198 ◽  
Author(s):  
Wolfram Windisch ◽  
Ellen Hennings ◽  
Jan Hendrik Storre ◽  
Heinrich Matthys ◽  
Stephan Sorichter
Keyword(s):  
Ventilatory Support ◽  
Congenital Central Hypoventilation Syndrome ◽  
Term Survival ◽  
Long Term Survival ◽  
Central Hypoventilation ◽  
Hypoventilation Syndrome

scholarly journals Congenital Central Hypoventilation Syndrome: A Comprehensive Review and Future Challenges

2014 ◽  
Vol 2014 ◽  
pp. 1-8
Author(s):  
Karin Ljubič ◽  
Iztok Fister ◽  
Iztok Fister
Keyword(s):  
Ventilatory Support ◽  
Congenital Central Hypoventilation Syndrome ◽  
Phox2b Gene ◽  
Central Controller ◽  
Future Challenges ◽  
The Central Nervous System ◽  
Central Hypoventilation ◽  
Hypoventilation Syndrome ◽  
Cardiovascular Functions

Congenital central hypoventilation syndrome is a disorder predisposed by a paired-like homebox PHOX2B gene. A mutation in the PHOX2B gene is a requisite when diagnosing congenital central hypoventilation syndrome. This mutation is identified in 93–100% of diagnosed patients. The mutation regarding this disorder affects the sensors, the central controller, and the integration of the signals within the central nervous system. This, inter alia, leads to insufficient ventilation and a decrease in PaO2, as well as an increase in PaCO2. Affected children are at risk during and after the neonatal period. They suffer from hypoventilation periods which may be present whilst sleeping only or in more severe cases when both asleep and awake. It is important for clinicians to perform an early diagnosis of congenital central hypoventilation in order to prevent the deleterious effects of hypoxaemia, hypercapnia, and acidosis on the neurocognitive and cardiovascular functions. Patients need long-term management and appropriate ventilatory support for improving the qualities of their lives. This paper provides a detailed review of congenital central hypoventilation syndrome, a congenital disorder that is genetic in origin. We describe the genetic basis, the wider clinical picture, and those challenges during the diagnosis and management of patients with this condition.

Long-Term Follow-up of Children With Congenital Central Hypoventilation Syndrome

PEDIATRICS ◽  
1987 ◽  
Vol 80 (3) ◽  
pp. 375-380
Author(s):  
Joseph Oren ◽  
Dorothy H. Kelly ◽  
Daniel C. Shannon
Keyword(s):  
Mechanical Ventilation ◽  
Initial Period ◽  
Ventilatory Support ◽  
Congenital Central Hypoventilation Syndrome ◽  
Speech Acquisition ◽  
Ventilatory Responses ◽  
Long Term Follow Up ◽  
Central Hypoventilation ◽  
Hypoventilation Syndrome

The long-term clinical course of six patients with congenital central hypoventilation syndrome is described. During the neonatal period, the patients had prolonged apneas and hypoventilation, in the absence of cardiac, pulmonary, or neuromuscular disease. After an initial period of respirator dependency, they became able to sustain normal gas exchange while awake. During sleep, however, profound hypoventilation developed, and tracheostomy and mechanical ventilation were required. Ventilatory responses to hypercapnia and hypoxia were depressed or absent and did not improve with time. One patient was able, at 2 years of age, to breathe spontaneously during sleep with only moderate hypoventilation. The others, now 4 to 14 years of age, still need ventilatory support during sleep. Complications, such as cardiac failure and hypoxic seizures, mostly occurred early in the course and resolved with correction of insufficient mechanical ventilation. Speech acquisition was possible with the use of a special stoma plug. All patients were managed at home, and with appropriate support, the parents were able to provide safe ventilatory care with low morbidity and no mortality.

scholarly journals 0874 Patients with Congenital Central Hypoventilation Syndrome Do Not Wake Up to Ventilator Alarms

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A333-A333
Author(s):  
S K Mathur ◽  
S Kun ◽  
T G Keens ◽  
I A Perez
Keyword(s):  
Pulse Oximetry ◽  
Sleep Disturbances ◽  
Ventilatory Support ◽  
Tube Feeding ◽  
Low Frequency ◽  
Congenital Central Hypoventilation Syndrome ◽  
Diaphragm Pacing ◽  
Central Hypoventilation ◽  
Hypoventilation Syndrome ◽  
Night Waking

Abstract Introduction Congenital Central Hypoventilation Syndrome (CCHS) requires lifelong ventilatory support during sleep. CCHS patients are vulnerable to sleep disturbances associated with treatments, monitoring alarms, and care they receive. We hypothesized that sleep would be disrupted in CCHS patient’s due to ventilatory support and other treatments at night. Methods An anonymous survey of CCHS patients aged 0-17 years was conducted through REDCAP. Patients were recruited in person, by flyer, email, and social media. Data collected included demographics, PHOX2B genotype, ventilatory support, treatments, nursing, and sleep parameters. Results We received 22 responses (27% Female, 8.1 years ± 5.7). PHOX2B genotypes were 20/27 PARM (8), 20/26 PARM (2), 20/24 PARM (2), 20/25 PARM (4), ≥ 20/28 PARM (2), and 2 NPARM (2). Two respondents did not indicate the PHOX2B genotype. 13/22 were ventilated by PPV via tracheostomy, 7/22 by BPAP, and 2/22 by diaphragm pacing. Additional treatments received at night included suctioning (8), aerosol (1), G-tube feeding (2), and none (11). Only 9 received nursing at night. 13 used pulse oximetry for monitoring, and 9 used both pulse oximetry and end tidal CO2 monitor. 16/22 rarely woke up due to ventilator or monitor alarms. 15/22 slept within 20 minutes after going to bed. Sleep latency was not affected by mode of ventilation. 11/22 reported night waking ≥ 2 nights/week and 10/22 returned to sleep without help after night waking. 6/7 BPAP dependent patients reported low frequency of night waking (0-1 time/week). Of the PPV + trach group, 7/13 reported high frequency of night wakings, mostly 5-7 times/week. Conclusion Most CCHS patients do not awaken in response to ventilator alarms. Sleep is rarely disrupted by nursing or feeding intervention. We speculate that CCHS patients contemplating to live independently should be tested to see if they awaken in response to ventilator alarms. Support None

scholarly journals Congenital central hypoventilation syndrome: Diagnosis, management, and long-term outcome in thirty-two children

1992 ◽  
Vol 120 (3) ◽  
pp. 381-387 ◽  
Author(s):  
Debra E. Weese-Mayer ◽  
Jean M. Silvestri ◽  
Lisa J. Menzies ◽  
Anna S. Morrow-Kenny ◽  
Carl E. Hunt ◽  
...  
Keyword(s):  
Congenital Central Hypoventilation Syndrome ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Syndrome Diagnosis ◽  
Central Hypoventilation ◽  
Hypoventilation Syndrome

scholarly journals OBSTRUCTIVE APNEAS IN A MOUSE MODEL OF CONGENITAL CENTRAL HYPOVENTILATION SYNDROME

2021 ◽  
Author(s):  
Amélia Madani ◽  
Gabriel Pitollat ◽  
Eléonore Sizun ◽  
Laura Cardoit ◽  
Maud Ringot ◽  
...  
Keyword(s):  
Ventilatory Support ◽  
Gene Mutations ◽  
Original System ◽  
Hypoglossal Nucleus ◽  
Congenital Central Hypoventilation Syndrome ◽  
Airway Patency ◽  
Obstructive Apnea ◽  
Central Hypoventilation ◽  
Underlying Mechanisms ◽  
Hypoventilation Syndrome

AbstractRationaleCongenital Central Hypoventilation Syndrome is characterized by life-threatening sleep hypoventilation, and is caused by PHOX2B gene mutations, most frequently the PHOX2B27Ala/+ mutation. Patients require lifelong ventilatory support. It is unclear whether obstructive apneas are part of the syndrome.ObjectivesTo determine whether Phox2b27Ala/+ mice, which presented main symptoms of Congenital Central Hypoventilation Syndrome and died within hours after birth, also presented obstructive apneas and investigate potential underlying mechanisms.MethodsApneas were classified as central, obstructive or mixed by using an original system combining pneumotachography and laser detection of abdominal movement immediately after birth. Some respiratory nuclei involved in airway patency were analyzed by immunohistochemistry and electrophysiology in brainstem-spinal cord preparation.Measurements and Main ResultsThe median (interquartile range) of obstructive apnea frequency was 2.3/min (1.5-3.3) in Phox2b27Ala/+ pups versus 0.6/min (0.4-1.0) in wildtypes (P < 0.0001). Obstructive apnea duration was 2.7s (2.3-3.9) in Phox2b27Ala/+ pups versus 1.7s (1.1- 1.9) in wildtypes (P < 0.0001). Central and mixed apneas presented similar, significant differences. In Phox2b27Ala/+ preparations, hypoglossal nucleus had fewer neurons (P < 0.05) and smaller size (P < 0.01), compared to wildtypes. Importantly, coordination of phrenic and hypoglossal activities was disrupted, as shown by the longer and variable delay of hypoglossal with respect to phrenic onset, compared to wildtypes (P < 0.001).ConclusionsThe Phox2b27Ala/+ mutation predisposed pups not only to hypoventilation and central apneas, but also obstructive and mixed apneas likely due to hypoglossal dysgenesis. These results call for attention toward obstructive events in infants with Congenital Central Hypoventilation Syndrome.Subject category15.1 Animal Models of Sleep Apnea

848 Refractory Hypoventilation in Congenital Central Hypoventilation Syndrome: A Case for Average Volume-Assured Pressure Support

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A330-A330
Author(s):  
Megan Gubichuk ◽  
Erin McHugh ◽  
Sonal Malhotra ◽  
Marianna Sockrider ◽  
Binal Kancherla
Keyword(s):  
Quality Of Life ◽  
Phrenic Nerve ◽  
Pressure Support ◽  
Ventilatory Support ◽  
Congenital Central Hypoventilation Syndrome ◽  
Average Volume ◽  
Non Invasive ◽  
Central Hypoventilation ◽  
Hypoventilation Syndrome

Abstract Introduction Congenital Central Hypoventilation Syndrome (CCHS) is a rare cause of alveolar hypoventilation in children resulting in lifelong ventilatory support. In older children requiring nocturnal support alone, the use of diaphragmatic pacing in conjunction with or independent of non-invasive ventilatory (NIV) support has been demonstrated to improve quality of life. We present a case of refractory hypoventilation despite escalation of NIV. Report of case(s) 20-year-old female with Hirschsprung’s disease and CCHS (20/26 polyalanine repeats) with history of invasive ventilation via tracheostomy who underwent bilateral diaphragmatic phrenic nerve stimulator placement at 13 years-of-age with subsequent tracheostomy decannulation. Diaphragmatic pacing was discontinued three years later in the setting of pneumonia and patient discomfort because of receiver positioning. At that time, she had improved subjective sleep quality and adequate ventilatory support on bi-level positive airway pressure (PAP) despite discontinuation of diaphragmatic pacing. Titration of bi-level PAP was done via polysomnogram four years later demonstrating nocturnal hypoventilation with transcutaneous CO2 values greater than 50 mmHg for 80% of the study and an oxygen nadir of 87% despite titration of inspiratory pressure and respiratory rate to maximize ventilatory assistance. The patient was subsequently admitted to the intensive care unit for transition to non-invasive average volume-assured pressure support (AVAPS) mode. Ventilation improved with nocturnal pCO2 values via capillary blood gas of 31 mmHg and 45 mmHg at 2 am and 6 am respectively. The patient was discharged on AVAPS therapy while undergoing evaluation to resume diaphragmatic pacing via cervical phrenic nerve stimulators for improved comfort. Conclusion Several ventilatory strategies may be employed in the care of patients with CCHS, with individualization of support based on phenotype, comorbidities, and patient and family preference. This case highlights the unique challenges of adequately ventilating patients as they age. The use of NIV via an AVAPS mode in patients with CCHS has been infrequently reported in the literature, though is promising in reported efficacy with regards to ensured ventilation. This, in conjunction with diaphragmatic pacing, may allow patients to achieve appropriate ventilation while maintaining quality of life, and could be considered in patients with refractory hypoventilation despite other modes of NIV. Support (if any):

scholarly journals Guidelines for diagnosis and management of congenital central hypoventilation syndrome

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Ha Trang ◽  
Martin Samuels ◽  
Isabella Ceccherini ◽  
Matthias Frerick ◽  
Maria Angeles Garcia-Teresa ◽  
...  
Keyword(s):  
Ventilatory Support ◽  
Rare Condition ◽  
Future Research ◽  
Congenital Central Hypoventilation Syndrome ◽  
Diagnosis And Management ◽  
Health Community ◽  
Life Threatening ◽  
Alveolar Hypoventilation ◽  
Central Hypoventilation ◽  
Hypoventilation Syndrome

Abstract Background Congenital Central Hypoventilation Syndrome (CCHS) is a rare condition characterized by an alveolar hypoventilation due to a deficient autonomic central control of ventilation and a global autonomic dysfunction. Paired-like homeobox 2B (PHOX2B) mutations are found in most of the patients with CCHS. In recent years, the condition has evolved from a life-threatening neonatal onset disorder to include broader and milder clinical presentations, affecting children, adults and families. Genes other than PHOX2B have been found responsible for CCHS in rare cases and there are as yet other unknown genes that may account for the disease. At present, management relies on lifelong ventilatory support and close follow up of dysautonomic progression. Body This paper provides a state-of-the-art comprehensive description of CCHS and of the components of diagnostic evaluation and multi-disciplinary management, as well as considerations for future research. Conclusion Awareness and knowledge of the diagnosis and management of this rare disease should be brought to a large health community including adult physicians and health carers.

scholarly journals 862 Volume-Assured Pressure Support improves outcomes in a patient with Congenital Central Hypoventilation Syndrome

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A335-A335
Author(s):  
Vlad Ianus ◽  
Madeleine Grigg-Damberger ◽  
Shanna Diaz ◽  
Nicholas Cutrufello
Keyword(s):  
Pressure Support ◽  
Minute Ventilation ◽  
Ventilatory Support ◽  
Patient Comfort ◽  
Congenital Central Hypoventilation Syndrome ◽  
Autonomic Nervous System Dysfunction ◽  
Patient Reported ◽  
Central Hypoventilation ◽  
Hypoventilation Syndrome ◽  
Pressure Controlled

Abstract Introduction Congenital Central Hypoventilation Syndrome (CCHS) is a condition caused by a mutation of the PHOX2B gene and an incidence of 1 in 50,000 live births. Clinically the condition is characterized by autonomic nervous system dysfunction, the most prominent feature of which is the failure of respiratory homeostasis during sleep. In patients severely affected, life-long ventilatory support is required. This might start as early as the newborn period. Subsequent adjustments are required due to their growth and development. The role of Volume-Assured Pressure Support (VAPS) ventilation in treatment of CCHS was only described in a couple reports before. Report of case(s) A 17-year-old female patient born at term and diagnosed with CCHS at birth at our center with a PHOX2B mutation confirmed. Her daytime ventilatory support was weaned at age 18 months and the tracheostomy was removed at age 10 years old. She relocated to another state, was lost to follow-up, and returned this year for adjustments of her ventilator whose settings had not been adjusted for several years. She was on a Trilogy 100 ventilator, in pressure-controlled mode with settings of EPAP 5, IPAP 20, and a rate of 22/min without supplemental oxygen. Her measured weight is 69kg, body mass index (BMI) 27. The patient complained of difficulty breathing while on those settings and reported decreased desire to use the machine. The patient was empirically switched to VAPS due to titration availability limitations during the COVID-19 pandemic. Initial AVAPS settings were: EPAP 4–7, PS 3–12, breath rate 16/min, TV 350mL. Upon implementing the changes, the patient reported improved comfort and increased usage. Average minute ventilation decreased from 10.5 to 5.8 L/min, patient triggered breaths increased from 1.1% to 12.3%, average breaths per minute decreased from 22.0/min to 16.2/min, the average peak flow 31.8 to 26.2L/min, tidal volume decreased from 463 to 355mL. Conclusion AVAPS ventilation can be successfully used in managing patients with CCHS, and it might be superior to pressure-controlled mode in certain cases, improving patient comfort and compliance. Support (if any) Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM.

Neonatal Congenital Central Hypoventilation Syndrome: Why We Should not Sleep on it. Literature Review of Forty-two Neonatal Onset Cases

2019 ◽  
Vol 15 (3) ◽  
pp. 139-153 ◽  
Author(s):  
Flaminia Bardanzellu ◽  
Maria Cristina Pintus ◽  
Vassilios Fanos ◽  
Maria Antonietta Marcialis
Keyword(s):  
Early Recognition ◽  
Correct Diagnosis ◽  
Delayed Diagnosis ◽  
Clinical Manifestations ◽  
Congenital Central Hypoventilation Syndrome ◽  
Phox2b Gene ◽  
Central Hypoventilation ◽  
Hypoventilation Syndrome ◽  
System Disorder

: Congenital Central Hypoventilation Syndrome (CCHS), also referred with the expression “Ondine’s Curse”, is a rare genetic life-long disease resulting from the mutation of PHOX2B gene on chromosome 4p12.3. CCHS represents an autonomic nervous system disorder; its more fearsome manifestation is central hypoventilation, due to a deficient response of chemoreceptors to hypercapnia and hypoxia. Several associated symptoms can occur, such as pupillary anomalies, arrhythmias, reduced heart rate variability, esophageal dysmotility, and structural comorbidities (Hirschsprung’s Disease or neural crest tumours). : CCHS typical onset is during the neonatal period, but cases of delayed diagnosis have been reported; moreover, both sporadic or familial cases can occur. : In preterm newborns, asphyxia and typical prematurity-related findings may overlap CCHS clinical manifestations and make it harder to formulate a correct diagnosis. : The early recognition of CCHS allows appropriate management, useful to reduce immediate and long- term consequences.

Human thymic epithelial cells maintain long-term survival of clonogenic myeloid and erythroid progenitor cells in vitro

2000 ◽  
Vol 111 (1) ◽  
pp. 363-370 ◽  
Author(s):  
Katsuto Takenaka ◽  
Mine Harada ◽  
Tomoaki Fujisaki ◽  
Koji Nagafuji ◽  
Shinichi Mizuno ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Progenitor Cells ◽  
Thymic Epithelial Cells ◽  
Erythroid Progenitor ◽  
Term Survival ◽  
Long Term Survival ◽  
Erythroid Progenitor Cells
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