Central sleep apnea

Central sleep apnea (CSA) or central sleep apnea syndrome (CSAS) is a sleep-related disorder in which the effort to breathe is diminished or absent, typically for 10 to 30 seconds, either intermittently or in cycles and is usually associated with a reduction in blood oxygen saturation.^[1][2] It is a collective term referring to two breathing disorders: Cheyne-Stokes respiration and periodic breathing.^[3] CSA is usually due to an instability in the body's feedback mechanisms that control respiration.^[4] Central sleep apnea can also be an indicator of Arnold–Chiari malformation.^[5]

Definition

In pure central sleep apnea, the brain's respiratory control centers are imbalanced during sleep. Blood levels of carbon dioxide, and the neurological feedback mechanism that monitors them, do not react quickly enough to maintain an even respiratory rate, with the entire system cycling between apnea and hyperpnea, even during wakefulness. The sleeper stops breathing for up to two minutes and then starts again.^[6] There is no effort made to breathe during the pause in breathing: there are no chest movements and no struggling. After the episode of apnea, breathing may be faster (hyperpnea) for a period of time, a compensatory mechanism to blow off retained waste gases and absorb more oxygen. There are symptoms that one can find for the two different types of sleep apnea (central versus obstructive) as follows.

Symptoms of central sleep apnea

• observed breathing pauses during sleep lack of abdominal and thoracic movement for 10 seconds or longer

Symptoms of obstructive sleep apnea^[7]

• snoring
• sleepiness and oftentimes even excessive daytime sleepines
• fatigue or tiredness
• gasping or choking awakenings
• dry mouth or throat
• large circumference neck (>16" for females, > 17" for males)
• observed breathing pauses during sleep, i.e. a lack of air flow in spite of efforts to breathe, i.e. ineffective respiratory movements
• obesity

While sleeping, a normal individual is "at rest" as far as cardiovascular workload is concerned. Breathing is regular in a healthy person during sleep, and oxygen levels and carbon dioxide levels in the bloodstream stay fairly constant.^[8] The respiratory drive is so strong that even conscious efforts to hold one's breath do not overcome it. Any sudden drop in oxygen or excess of carbon dioxide, even if tiny, strongly stimulates the brain's respiratory centers to breathe.

In central sleep apnea, the basic neurological controls for breathing rate malfunction and fail to give the signal to inhale, causing the individual to miss one or more cycles of breathing. A part of the human brain known as the preBotzinger complex regulates one's breathing habits.^[9] If the pause in breathing is long enough, the percentage of oxygen in the circulation will drop to a lower than normal level (hypoxaemia) and the concentration of carbon dioxide will build to a higher than normal level (hypercapnia). In turn, these conditions of hypoxia and hypercapnia will trigger additional effects on the body. Brain cells need constant oxygen to live, and if the level of blood oxygen goes low enough for long enough, the consequences of brain damage and even death will occur. Fortunately, central sleep apnea is more often a chronic condition that causes much milder effects than sudden death. The exact effects of the condition will depend on how severe the apnea is and on the individual characteristics of the person having the apnea. Several examples are discussed below, and more about the nature of the condition is presented in the section on Clinical Details.

In any person, hypoxia and hypercapnia have certain common effects on the body. The heart rate will increase, unless there are such severe co-existing problems with the heart muscle itself or the autonomic nervous system that makes this compensatory increase impossible. The more translucent areas of the body will show a bluish or dusky cast from cyanosis, which is the change in hue that occurs owing to lack of oxygen in the blood ("turning blue"). Overdoses of drugs that are respiratory depressants (such as heroin, and other opiates) kill by damping the activity of the brain's respiratory control centers. In central sleep apnea, the effects of sleep alone can remove the brain's mandate for the body to breathe. Even in severe cases of central sleep apnea, the effects almost always result in pauses that make breathing irregular, rather than cause the total cessation of breathing.

• Normal respiratory drive: after exhalation, the blood level of oxygen decreases and that of carbon dioxide increases. Exchange of gases with a lungful of fresh air is necessary to replenish oxygen and rid the bloodstream of built-up carbon dioxide. Oxygen and carbon dioxide receptors in the blood stream (called chemoreceptors) send nerve impulses to the brain, which then signals reflex opening of the larynx (so that the opening between the vocal cords enlarges) and movements of the rib cage muscles and diaphragm. These muscles expand the thorax (chest cavity) so that a partial vacuum is made within the lungs and air rushes in to fill it.^[10]

• Physiologic effects of central apnea: During central apneas, the central respiratory drive is absent, and the brain does not respond to changing blood levels of the respiratory gases. No breath is taken despite the normal signals to inhale. The immediate effects of central sleep apnea on the body depend on how long the failure to breathe endures. At worst, central sleep apnea may cause sudden death. Short of death, drops in blood oxygen may trigger seizures, even in the absence of epilepsy. In people with epilepsy, the hypoxia caused by apnea may trigger seizures that had previously been well controlled by medications. In other words, a seizure disorder may become unstable in the presence of sleep apnea. In adults with coronary artery disease, a severe drop in blood oxygen level can cause angina, arrhythmias, or heart attacks (myocardial infarction). Longstanding recurrent episodes of apnea, over months and years, may cause an increase in carbon dioxide levels that can change the pH of the blood enough to cause a respiratory acidosis.

Diagnosis

AHI	Rating
5 to <15 apneas or hypopneas per hour of sleep	Mild sleep apnea/hypopnea
15 to <30 apneas or hypopneas per hour of sleep	Moderate sleep apnea/hypopnea

If the majority of the events are central apneas or hypopneas it is classified as central sleep apnea/hypopnea.

If the majority of the events are obstructive apneas or hypopneas it is classified as obstructive sleep apnea/hypopnea.

Polysomnography of sleep apnea shows interruption in breathing, that are followed by drops/reduction in blood oxygen and hike/increase in blood carbon dioxide level. In adults, a pause must last 10 seconds to be scored as an apnea. However in young children, who normally breathe at a much faster rate than adults, the pause may be shorter and still be considered apnea. The cessation of airflow in central sleep apnea has an association with no physical attempts to breathe. On polysomnograms, there is an absence of rib cage and abdominal movements while airflow ceases at the nose and lips. Obstructive sleep apnea shows pauses in breathing for at least 10 seconds causing a decrease in blood oxygen and associates with physical attempts to breathe.

Hypopneas in adults are defined as a 30% reduction in air flow for more than ten seconds, followed by either an oxygen desaturation of a 3% drop or more and/or EEG arousal. The Apnea-Hypopnea Index (AHI) is expressed as the number of apneas or hypopneas per hour of sleep.^[11]

Any individual, no matter how healthy, who is given enough of a central respiratory depressant drug will develop apnea on a central basis. Generally, drugs that are central respiratory depressants also have sedative effects, and so the individual taking a toxic dose of such a drug is likely to be asleep, or at least in an altered state of consciousness, when breathing becomes irregular. Alcohol is such a central respiratory depressant in large doses; so are opiates, barbiturates, benzodiazepines, and many other tranquilizers. Some individuals have abnormalities that predispose them to central sleep apnea. The treatment for the condition depends on its specific cause.

Similarly, in any person who has some form of sleep apnea (including obstructive sleep apnea), breathing irregularities during sleep can be dangerously aggravated by taking one of these drugs. Quantities that are normally considered safe may cause the person with chronic sleep apnea to stop breathing altogether. Should these individuals have general anesthesia, for example, they require prolonged monitoring after initial recovery, as compared to a person with no history of sleep apnea, because apnea is likely to occur with even low levels of the drugs in their system.

Premature infants with immature brains and reflex systems are at high risk for central sleep apnea syndrome, even if these babies are otherwise healthy. Fortunately, those premature babies who have the syndrome will generally outgrow it as they mature, providing they receive careful enough monitoring and supportive care during infancy to survive. Because of the propensity toward apnea, medications that can cause respiratory drive depression are either not given to premature infants, or given under careful monitoring, with equipment for resuscitation immediately available. Such precautions are routinely taken for premature infants after general anesthesia. Caffeine has been found to help reduce apnea in preterm infants and to aid in care after general anesthesia.^[12]

Sudden infant death syndrome is sometimes theorized to be attributable to sleep apnea.

Congenital Central Hypoventilation Syndrome (CCHS): This very severe condition of abnormally low breathing during sleep is rare and is an inborn condition that involves a specific gene, PHOX2B. This homeobox gene guides maturation of the autonomic nervous system, and loss-of-function mutations lead to the failure of the brain to effectively control breathing during sleep in patients with the syndrome. There may be a recognizable pattern of facial features among individuals affected with this syndrome.^[13]

Once almost uniformly fatal, CCHS is now treatable. The children who have it must have tracheotomies and access to mechanical ventilation on respirators while sleeping, but most do not need to use a respirator while awake. The use of a diaphragmatic pacemaker may offer an alternative for some patients. When pacemakers have enabled some children to sleep without the use of a mechanical respirator, reported cases still required the tracheotomy to remain in place because the vocal cords did not move apart with inhalation. This form of central sleep apnea has been called Ondine's curse. People with the syndrome who survive to adulthood need to avoid certain risk factors, such as alcohol use, which can easily prove lethal.^[14]

Association with heart disease

Adults suffering from congestive heart failure are at risk for a form of central sleep apnea called Cheyne-Stokes respiration. This is periodic breathing with recurrent episodes of apnea alternating with episodes of rapid breathing. In those who have it, Cheyne-Stokes respirations occur while both awake and asleep. There is good evidence that replacement of the failed heart (heart transplant) cures central apnea in these patients. The use of some medications that are respiratory stimulants decrease the severity of apnea in some patients.

There is an association between atrial fibrillation (AF) and central sleep apnea. A study found that the prevalence of atrial fibrillation among patients with idiopathic central sleep apnea was significantly higher than the prevalence among patients with obstructive sleep apnea or no sleep apnea (27%, 1.7%, and 3.3%, respectively). The study was based on 180 subjects with 60 people in each of the 3 groups. Possible explanations for the association between CSA and AF are a causal relationship between the two conditions, or an abnormality of central cardiorespiratory regulation.^[15]

Treatment

A diagnosis of sleep apnea requires examination by a physician. The examination will require a study of an individual in a sleep lab. There, the patient will be monitored at rest to measure the periods when breathing ceases.^[16] After a patient receives a diagnosis, the physician can provide different options of treatment. One of the more common treatments is CPAP (continuous positive airway pressure). During CPAP a mask that fits over the nose, or nose and mouth, is used and is connected to a device that compresses normal room air, and blows it into the airway at a constant pressure. This pressure must be optimal to prevent the airway from collapsing in patients suffering from Obstructive Sleep Apnea. Treatment for central sleep apnea differs slightly in that the device is not set at one optimal constant pressure as with CPAP, but at two different settings for inhalation (IPAP) and for exhalation (EPAP), therefore aiding respiration. Other specifications, for instance the breathing rate and the duration of a single breath, can also be programmed. This device is called BiPAP (bi-level positive airway pressure, meaning it is set at two different pressures). Both CPAP and BiPAP devices can be connected to a humidifier to humidify and heat the inhaled air, thus reducing unpleasant symptoms such as a sore throat or blocked nose that can result from inhaling cold, dry air. An experimental pacemaker for the diaphragm has recently shown promising results in overcoming CAS.^[17]

See also

• Sleep apnea
• Obstructive sleep apnea

References

Additional references

• Macey PM, Macey KE, Woo MA, Keens TG, Harper RM (April 2005). "Aberrant neural responses to cold pressor challenges in congenital central hypoventilation syndrome". Pediatric Research 57 (4): 500–9. doi:10.1203/01.PDR.0000155757.98389.53. PMID 15718375. 
• Bradley TD, Floras JS (April 2003). "Sleep apnea and heart failure: Part II: central sleep apnea". Circulation 107 (13): 1822–6. doi:10.1161/01.CIR.0000061758.05044.64. PMID 12682029. 
• Mansfield DR, Solin P, Roebuck T, Bergin P, Kaye DM, Naughton MT (November 2003). "The effect of successful heart transplant treatment of heart failure on central sleep apnea". Chest 124 (5): 1675–81. doi:10.1378/chest.124.5.1675. PMID 14605034. 
• Javaheri S (January 2006). "Acetazolamide improves central sleep apnea in heart failure: a double-blind, prospective study". American Journal of Respiratory and Critical Care Medicine 173 (2): 234–7. doi:10.1164/rccm.200507-1035OC. PMID 16239622. 

Pathology of the nervous system, primarily CNS (G04–G47, 323–349) Inflammation Brain Encephalitis Viral encephalitis Herpesviral encephalitis Limbic encephalitis Encephalitis lethargica Cavernous sinus thrombosis Brain abscess Amoebic Spinal cord Myelitis: Poliomyelitis Demyelinating disease Transverse myelitis Tropical spastic paraparesis Epidural abscess Both/either Encephalomyelitis Acute disseminated Meningoencephalitis Brain/ encephalopathy Degenerative Extrapyramidal and movement disorders Basal ganglia disease Parkinsonism PD Postencephalitic NMS PKAN Tauopathy PSP Striatonigral degeneration Hemiballismus HD OA Dyskinesia Dystonia Status dystonicus Spasmodic torticollis Meige's Blepharospasm Athetosis Chorea Choreoathetosis Myoclonus Myoclonic epilepsy Akathisia Tremor Essential tremor Intention tremor Restless legs Stiff person Dementia Tauopathy Alzheimer's Early-onset Primary progressive aphasia Frontotemporal dementia/Frontotemporal lobar degeneration Pick's Dementia with Lewy bodies Posterior cortical atrophy Vascular dementia Mitochondrial disease Leigh's disease Demyelinating autoimmune Multiple sclerosis Neuromyelitis optica Schilder's disease hereditary Adrenoleukodystrophy Alexander Canavan Krabbe ML PMD VWM MFC CAMFAK syndrome Central pontine myelinolysis Marchiafava-Bignami disease Alpers' disease Episodic/ paroxysmal Seizure/epilepsy Focal Generalised Status epilepticus Myoclonic epilepsy Headache Migraine Familial hemiplegic Cluster Tension Cerebrovascular TIA Amaurosis fugax Transient global amnesia Acute aphasia Stroke MCA ACA PCA Foville's Millard-Gubler Lateral medullary Weber's Lacunar stroke Sleep disorders Insomnia Hypersomnia Sleep apnea Obstructive Ondine's curse Narcolepsy Cataplexy Kleine-Levin Circadian rhythm sleep disorder Advanced sleep phase disorder Delayed sleep phase disorder Non-24-hour sleep–wake disorder Jet lag CSF Intracranial hypertension Hydrocephalus/NPH Choroid plexus papilloma Idiopathic intracranial hypertension Cerebral edema Intracranial hypotension Other Brain herniation Reye's Hepatic encephalopathy Toxic encephalopathy Hashimoto's encephalopathy Spinal cord/ myelopathy Syringomyelia Syringobulbia Morvan's syndrome Vascular myelopathy Foix-Alajouanine syndrome Spinal cord compression Both/either Degenerative SA Friedreich's ataxia Ataxia telangiectasia MND UMN only: Primary lateral sclerosis Pseudobulbar palsy Hereditary spastic paraplegia LMN only: Distal hereditary motor neuropathies Spinal muscular atrophies SMA SMAX1 SMAX2 DSMA1 Congenital DSMA SMA-PCH SMA-LED SMA-PME Progressive muscular atrophy Progressive bulbar palsy Fazio–Londe Infantile progressive bulbar palsy both: Amyotrophic lateral sclerosis Index of the central nervous system Description Anatomy meninges cortex association fibers commissural fibers lateral ventricles basal ganglia diencephalon mesencephalon pons cerebellum medulla spinal cord tracts Physiology neutrotransmission enzymes intermediates Development Disease Cerebral palsy Meningitis Demyelinating diseases Seizures and epilepsy Headache Stroke Sleep Congenital Injury Neoplasms and cancer Other paralytic syndromes ALS Symptoms and signs head and neck eponymous lesions Tests CSF Treatment Procedures Drugs general anesthetics analgesics addiction epilepsy cholinergics migraine Parkinson's vertigo other