Congenital central hypoventilation syndrome (CCHS) is a rare condition characterized by dysfunction of automatic control of breathing, most dramatically during sleep, and was first described by Mellins et al in 1970. The term Ondine’s curse was originally used to describe this syndrome, based on a literary reference to the unfaithful husband of the daughter of Poseidon, but is now largely out of favor. At present there are a few hundred known cases worldwide. The estimated incidence varies widely in different reports, from 1 in 10,000 to 1 in 200,000 live births. The clinical manifestations of CCHS appear to be related to a spectrum of neural crest disorders. Between 15% and 20% of patients have aganglionic megacolon (Hirschsprung disease [HD]), and 2 to 5% acquire neural crest tumors such as neuroblastoma, [...]
Any respiratory system disorder that produces hypoxemia may potentially worsen during sleep. Compensatory hyperventilation may not be sustainable as a result of the state-dependent and postural changes in control of breathing and respiratory mechanics previously discussed, and any increase in PaC02 with sleep onset, even if still within the normal range, must result in a corresponding fall in oxyhemoglobin saturation. Diseases known to cause nocturnal hypoxemia and/or hypoventilation include cystic fibrosis (CF), interstitial pneumonitides, hypersensitivity pneumonitis, pulmonary hypertension (primary, or due to other causes such as recurrent pulmonary emboli), and hemoglobinopathies such as sickle-cell anemia. Of all of these disorders, CF and sickle-cell anemia have been studied most extensively with respect to gas exchange during sleep.
The phenomenon of nocturnal hypoxemia complicating COPD has been recognized for at least 50 years. It has also long been recognized that, in comparison to their nonhypoxemic brethren, hypoxemic COPD patients have greater degrees of pulmonary hypertension and cor pulmonale, require more frequent hospitalizations, and sustain higher mortality rates. Not surprisingly, sleep-related hypoxemia in the COPD patient is most frequently associated with awake oxyhemoglobin desaturation and diurnal hypercapnia, both of which may be quite modest in degree; and individuals who are already significantly hypoxemic while awake are more likely to exhibit profound desaturation during sleep. In one study, all patients with diurnal oxyhemoglobin saturations 95% were hypoxemic at night; another study found a high correlation between diurnal PaC02 > 50 mm Hg and nocturnal hypoxemia.
Patients with a variety of neurologic conditions, such as Arnold-Chiari malformation, brainstem tumors, space occupying lesions, vascular malformations, CNS infection, stroke, or neurosurgical procedures, may demonstrate central hypoventilation. However, a small number of patients demonstrate hypoventilation even after all of these conditions have been excluded. The condition of decreased alveolar ventilation resulting in sleep-related hypoxemia in patients with normal mechanical properties of the lung and chest wall (no apparent primary lung disease, skeletal malformations, or neuromuscular disorder) is, by definition, idiopathic. This entity is uncommon and not well characterized. It seems probable that many of these patients have subtle or incipient manifestations of known causes of hypoventilation.
The availability of new technology, applied in original ways, has often been responsible for rapid advances in a variety of medical disciplines. This been particularly apparent in sleep medicine, in which the introduction of equipment capable of continuously monitoring oxyhemoglobin saturation and PaC02 has permitted detailed study of gas exchange during sleep in both health and disease. Indeed, the linkage of technologies for continuous measurement of gas exchange with the technology of EEG essentially created the contemporary field of sleep medicine. This review will set forth the mechanisms thought to be responsible for sleep-induced hypoventilation and hypoxemia, and then discuss recent developments related to sleep-induced hypoventilation and hypoxemic syndromes reflecting a portion of the recently published second edition of The International Classification of Sleep Disorders: Diagnostic and Coding Manual [...]