Etiology of Central Sleep Apnea
Patients with central sleep apnea fall into 2 groups based on their carbon dioxide level and ventilatory drive.
Hypercapnia with decreased ventilatory drive
Eucapnia or hypocapnia with increased ventilatory drive but with episodes of apnea, periodic breathing, or both
Causes of hypercapnia with decreased ventilatory drive include hypothyroidism Hypothyroidism Hypothyroidism is thyroid hormone deficiency. It is diagnosed by clinical features such as a typical facial appearance, hoarse slow speech, and dry skin and by low levels of thyroid hormones... read more 
and central lesions (eg, brain stem infarctions, encephalitis Encephalitis Encephalitis is inflammation of the parenchyma of the brain, resulting from direct viral invasion. Acute disseminated encephalomyelitis is brain and spinal cord inflammation caused by a hypersensitivity... read more , Chiari II type malformation).
Cheyne-Stokes breathing, a discrete pattern of the second form of central sleep apnea, is thought to be caused by intrinsic properties of the respiratory control center in the response to hypoxia and acidosis with hyperpnea, causing reoxygenation and alkalosis, leading to hypoventilation by hypopnea and apnea.
Central sleep apnea occurs at high altitude in healthy people as a consequence of hypobaric hypoxia.
Congenital central hypoventilation (a form of Ondine curse) is a rare form of idiopathic CSA in neonates and may be associated with Hirschsprung disease Hirschsprung Disease Hirschsprung disease is a congenital anomaly of innervation of the lower intestine, usually limited to the colon, resulting in partial or total functional obstruction. Symptoms are obstipation... read more 
. A mutation in the PHOX2 gene is responsible for 80 to 90% of cases. This mutation produces variable phenotypes, and clinically evident cases are inherited in a dominant pattern.
Symptoms and Signs of Central Sleep Apnea
Central sleep apnea is usually asymptomatic and is detected by caretakers or bed partners who notice long respiratory pauses, shallow breaths, or restless sleep. Patients with hypercapnic forms may experience daytime somnolence (sometimes called wake-time sleepiness), lethargy, and morning headache.
Diagnosis of Central Sleep Apnea
Clinical evaluation
Often polysomnography
Diagnosis of central sleep apnea is suspected on the basis of history and is confirmed by polysomnography Testing Almost half of all people in the US report sleep-related problems. Disordered sleep can cause emotional disturbance, memory difficulty, poor motor skills, decreased work efficiency, and increased... read more . However, testing may not be necessary if there are no symptoms; instead, aggressive management of medical disorders that can cause sleep apnea (eg, heart failure Heart Failure (HF) Heart failure (HF) is a syndrome of ventricular dysfunction. Left ventricular failure causes shortness of breath and fatigue, and right ventricular failure causes peripheral and abdominal fluid... read more 
) is tried first.
To diagnose central nervous system causes of central sleep apnea, brain or brain stem imaging may be indicated.
Treatment of Central Sleep Apnea
Supportive care
Primary treatment of central sleep apnea is optimal management of underlying disorders and avoidance of opioids, alcohol, and other sedatives. Secondary treatment of symptomatic patients can be a trial of supplemental oxygen or, in patients with hypercapnic CSA who have symptoms despite other treatments, noninvasive continuous or bilevel positive airway pressure.
For patients who have CSA and Cheyne-Stokes breathing, continuous positive airway pressure Continuous positive airway pressure (CPAP) Obstructive sleep apnea (OSA) consists of episodes of partial or complete closure of the upper airway that occur during sleep and lead to breathing cessation (defined as a period of apnea or... read more or supplemental oxygen may decrease apneic and hypopneic episodes, but effects on clinical outcomes are not clear. Acetazolamide is effective in central sleep apnea caused by high altitude.
Electrode pacing of the phrenic nerve and/or diaphragm is an option, such as for children > 2 years with congenital central hypoventilation syndrome.
Recently, a transvenous phrenic nerve stimulation system has become available. The system is programmed to produce a rhythmic breathing pattern that stabilizes tidal volume, airflow, and oxygenation, entraining breathing during sleep and potentially altering disease progression (1 Treatment reference Central sleep apnea (CSA) is a heterogeneous group of conditions characterized by changes in ventilatory drive without airway obstruction. Most of these conditions cause asymptomatic changes... read more ).
Treatment reference
1. Schwartz AR, Sgambati FP, James KJ, et al: Novel phrenic nerve stimulator treats Cheyne-Stokes respiration: Polysomnographic Insights. J Clin Sleep Med 16(5):817–820, 2020. doi: 10.5664/jcsm.8328
More Information
The following is an English-language resource that may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
American Sleep Apnea Association: Provides consumer information, education, and support for patients with sleep apnea
