Central sleep apnea leads to a disorganized, interrupted sleep. Patients report a feeling of fatigue during the day, frequent arousals during the night, insomnia and sleepiness during daytime [11]. Even though the patients themselves may be unaware of the apneic event, as it occurs during their sleep, partners often observe the incident. Some patients also experience shortness of breath and choking.

Except for the symptoms related to the apnea itself, individuals who suffer from an underlying medical condition will display the corresponding symptomatology.

Laboratory examinations are of little diagnostic value in cases of people with a suspected sleep disorder. Decreased levels of arterial blood oxygen may be detected in individuals with an underlying heart failure or apnea related to an ascent to a high altitude.

Polysomnography, a type of sleep study, is the most useful diagnostic tool. Findings are categorized depending on the type of apnea:

• Primary central sleep apnea: Features more than 5 central apneic incidences per hour, with a minimum 10-second duration. They are observed during the first and second sleep stage and the patient may be prevented from reaching the stage of delta sleep. The periodic circle of apneic events is lasts no longer than 45 seconds.
• CSB-CSA: PaCO2 values tend to reach levels near the apneic threshold and the cycle of apnea and hyperpnea has a duration greater than 45 seconds.
• High-altitude central sleep apnea: The apneic cycle length lasts for 12-34 seconds. The first and second sleep stages last for a longer period of time than in healthy individuals and delta sleep is of decreased duration.
• Central sleep apnea related to drug abuse: More commonly observed during NREM sleep.The patterns of breathing-apneas may have a periodic nature but this is not always necessary.

If the central sleep apnea incidents lead to no profound symptomatology and do not cause discomfort or decreased functionality during the day, simple monitoring may suffice. Individuals who are suitable candidates for monitoring are those who experience apneic events during sleep-wake transition, those who do not display considerably decreased oxygen levels in their blood or those whose apnea occurs while using a CPAP breathing machine. It should be noted that 1 out of 5 cases of central sleep apnea resolve without any intervention.

As far as therapeutic options are concerned, both medications and breathing enhancement devices are available to treat cases of central sleep apnea

Breathing assistance devices

Patients with CSB-CSA can significantly benefit from the use of continuous positive airway pressure devices (CPAP). Apneic syndromes induced by hypoventilation can be treated with the use of a bilevel positive airway pressure device (BIPAP). Another therapeutic option involves the addition of dead space, by means of attaching a plastic cylinder of 400 to 800 mL to a mask; this can help to increase carbon dioxide reserve over the apneic threshold and reduce the occurrence of sleep apneas. This method has been attempted in cases of primary sleep apnea and CSB-CSA.

Central sleep apnea due to Cheyne-Stokes breathing can also be treated with the use of adapted servo-ventilation (ASV), as well as with the administration of oxygen, if the patient suffers from heart failure as well [12]. Oxygen is also an option for sleep apneas due to high altitude, or apneas accompanied by very low levels of circulating oxygen.

Medications

Patients affected by CSB-CSA or sleep apneas caused by high altitude can benefit from the administration of acetazolamide, a drug that induces bicarbaturia, lowering the apneic threshold. Theophylline can also be employed in patients with heart failure causing central sleep apnea [13]. Lastly, sedatives such as zolpidem and temazepam can be used to relieve apneic events that are not accompanied by high levels of CO2 in the blood. They are believed to lead to a stabilize sleep pattern, with a more progressive and delayed transition from sleep to wakefulness.

Prognosis depends on the underlying condition and is especially positive from patients displaying idiopathic (primary) sleep apnea.

Central sleep apnea due to Cheyne-Stokes breathing pattern (CSB-CSA)

CSB-CSA is frequently associated with an underlying condition such as a cerebrovascular event, heart failure or kidney failure. The sleep pattern is usually disorganized and interrupted. The intermittent breathing occurs every 45 seconds or more and follows a typical crescendo-decrescendo pattern.

Central sleep apnea due to a condition, unrelated to Cheyne-Stokes breathing

This type of apnea is linked to an underlying disorder other than heart or kidney failure. It is not characterized by a crescendo-decrescendo pattern.

Central sleep apnea due to high altitude

Occurs when the patient has recently been in surroundings of high altitude (5000m or more).

Central sleep apnea due to narcotic use

It is primarily caused by the abuse of substances such as opiates or depressants of the central nervous system.

Primary central sleep apnea

This type of central sleep apnea syndrome is not associated with an underlying pathology, does not feature the crescendo-decrescendo pattern of breathing and does not lead to hypoxia. Patients usually experience 5 or more apneic events per hour that lasts for at least 10 seconds.

Complex sleep apnea

It can develop during titration of CPAP or after a tracheostomy, in cases of patients who are affected by obstructive sleep apnea [3].

Despite the fact that the respiratory function is a continual process indispensable for the maintenance of satisfactory oxygen levels in the blood and tissues, there are two distinct circumstances, wherein an apneic event is considered normal and does not constitute a sign of ventilatory dysfunction:

• Transition from sleep to wakefulness. Apneic events during this period of time are possibly related to impaired respiratory control, caused by the resetting of chemoreceptors. It is believed that nearly half of the healthy individuals will, at some point, exhibit such an event.
• Arousal or sigh apnea: after an arousal or a sigh, the resulting hyperventilation may lead to a brief cessation of breathing.

Predominant central apnea is an uncommon medical condition, estimated to affect under 1% of the population worldwide [4]. Central sleep apnea due to Cheyne-Stokes breathing is more commonly diagnosed in male individuals older than 60 years old; women who have not yet reached menopause are unlikely to develop an apnea syndrome [5].

Mortality and morbidity have not been sufficiently studied; they are however greatly influenced by a potential underlying pathology, such as heart or renal failure, a cerebrovascular event etc.

The normal values of arterial carbon dioxide tension (PaCO2) are different during wakefulness and sleep. Depending on the normal range, values below the lowest normal limit lead to a periodic breathing cessation. The threshold for PaCO2 is higher during when an individual is asleep. Apneas are observed during the resetting of this threshold which occurs when the individual is starting to wake up.

Pathophysiologically, apneas develop either due to unstable ventilation or due to depression of the ventilatory center or chemoreceptors in the brainstem.

It is typically seen in patients suffering from CSB-CSA, primary sleep apnea and apnea related to a recent ascent to a high altitude [6]. Individuals affected by heart failure and those who have recently been to a location higher than 5000m display a lower PaCO2 baseline, which renders them susceptible to apneas. Generally a lower PaCO2 leads to an excessive response, should its value be even more diminished; this leads to a state of sleep instability and further exacerbates an existing medical condition.

On the other hand, opiates are known to suppress the ventilatory center in the brainstem, even though many individuals gradually develop tolerance to the narcotic substances [7]. Despite the tolerance effect, many individuals who engage in chronic drug abuse display a high rate of sleep apneas, hypoxia and hypercapnia [8] [9]. Even though the suppression of the respiratory function can be observed at any time during the day, sleep aggravates the phenomenon, due to an absent behavior drive. Conditions of the central nervous system, such as meningitis, cerebral hemorrhage or a tumor may also interfere with breathing, leading to an unstable breathing with a central etiology, known as Biot respiratory pattern.

Even though central sleep apnea is a different medical entity from obstructive sleep apnea, some individuals are affected by a type of mixed apnea, with both obstructive and central characteristics [10].

Central sleep apnea that is idiopathic cannot be prevented. The other types of the disease can only be prevented if the conditions that may induce the apnea are prevented. Having a healthy body weight and avoiding alcohol or drug abuse can be successful steps towards the prevention of heart failure.

The syndromes categorized under the term central sleep apnea (CSAS) include a multitude of disorders which lead to respiratory impairment during sleeping hours. Patients affected by central sleep apnea display a breathing pattern during sleep, which falls under the two following categories [1].:

• Periodic cessation of breathing during sleep
• Decreased breathing capacity during sleep

Central sleep apnea is closely linked to obstructive sleep apnea syndromes; alternative causes include a high altitude, narcotics or an underlying pathology.

The cessation of the respiratory effort, if present, is characterized by a minimum duration of 10 seconds during which no flow of air is detected in the lungs. In general, the two pathophysiological mechanisms that lead to the development of such sleep-related breathing dysfunction. This condition is either associated to hyperventilation or hypoventilation. The latter occurs in cases of people with neurological conditions that affect breathing control and the former is primarily linked to primary CSAS or high altitude.

CSAS features six syndromes, each of which is caused by a distinct etiological factor [2].:

• Primary sleep apnea of infancy
• Primary central sleep apnea
• Central sleep apnea due to Cheyne-Stokes breathing pattern
• Central sleep apnea due to an underlying pathology, unrelated to Cheyne-Stokes breathing pattern
• Central sleep apnea due to high altitude
• Central sleep apnea due to illegal substance use (narcotics)

Central sleep apnea syndromes are a group of diseases which lead to interrupted breathing during a person's sleep. Central sleep apnea does not involve the loss of one's ability to breathe, but rather the absence of the necessary brain stimuli that lead to breathing.There are various types of central sleep apnea, either caused by an underlying condition or primary. Heart failure, kidney failure, having recently ascended to a high altitude, illegal substance abuse, strokes and neurological degenerative diseases may lead to apneic events.

Patients are usually unaware of the fact that they periodically stop breathing during their sleep. However, sleep is usually interrupted, an individual feels weak and sleepy during daytime accompanied by insomnia. Snoring is commonly reported by partners, as well as shortness of breath or frequent choking. Partners are usually the ones to observe that another person stops breathing during their sleep.

Central sleep apnea cannot be diagnosed with laboratory tests; these tests are likely to reveal the underlying pathology that can lead to an apneic syndrome, but not the apnea itself. A sleep study, known as a polysomnogram is conducted to diagnose the sleep disorder. In this test, the patient is monitored during their sleep and sleeping patterns in the brain are recorded together with periods when breathing temporarily stops are also tracked down.

Central sleep apnea can be treated with devices that are used during sleep and help to prevent the cessation of breathing. Nasal continuous positive airway pressure (CPAP), adaptive servo-ventilation (ASV) and bilevel positive airway pressure (BiPAP) are various options that are suggested depending on the type of apnea an individual suffers from. Oxygen may also be an option under some circumstances, alongside medications that can help to reduce the apneic events.

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