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Monday, September 13, 2021

Fatal insomnia

From Wikipedia, the free encyclopedia
 
Fatal insomnia
Cranial imaging of a FFI patient.jpg
Cranial imaging of an FFI patient. In the MRI, there are abnormal signals in the bilateral frontoparietal subcortical area. MRA showed smaller distal branches of cerebral arteries.

SpecialtyPsychiatry, Sleep medicine, Neuropathology
SymptomsProgressive insomnia leading to dementia and death.
ComplicationsPermanent state of hypnagogia later in the illness
Usual onsetMiddle age
TypesFatal familial insomnia, sporadic fatal insomnia
CausesGenetic mutation, sporadic form very rare
Risk factorsFamily history
Diagnostic methodSuspected based on symptoms, Supported by Sleep study, PET scan and genetic testing (If Familial form is suspected)
Differential diagnosisAlzheimer’s disease, frontotemporal dementia, other transmissible spongiform encephalopathies
PreventionNone
TreatmentSupportive care
MedicationNone
PrognosisAlways fatal
FrequencyFewer than 40 families worldwide are known to carry the gene associated with the disease, 24 sporadic cases diagnosed (as of 2016) 

Fatal insomnia is an extremely rare genetic disorder that results in trouble sleeping as its hallmark symptom. The problems with sleeping typically start out gradually and worsen over time. Other symptoms may include speech problems, coordination problems, and dementia. It results in death within a few months to a few years.

It is a prion disease of the brain. It is usually caused by a mutation to the gene encoding protein PrPC. It has two forms: fatal familial insomnia (FFI), which is autosomal dominant and sporadic fatal insomnia (sFI) which is due to a noninherited mutation. Diagnosis is suspected based on symptoms and can be supported by a sleep study, a PET scan, and genetic testing if the patient's family has a history of the disease. Similar to other prion diseases, the diagnosis can only be confirmed by a brain autopsy at post-mortem.

Fatal insomnia has no known cure and involves progressively worsening insomnia, which leads to hallucinations, delirium, confusional states like that of dementia, and eventually death. The average survival time from onset of symptoms is 18 months. The first recorded case was an Italian man, who died in Venice in 1765.

Signs and symptoms

The disease has four stages:

  1. Characterized by worsening insomnia, resulting in panic attacks, paranoia, and phobias. This stage lasts for about four months.
  2. Hallucinations and panic attacks become noticeable, continuing for about five months.
  3. Complete inability to sleep is followed by rapid loss of weight. This lasts for about three months.
  4. Dementia, during which the person becomes unresponsive or mute over the course of six months, is the final stage of the disease, after which death follows.

Other symptoms include: profuse sweating, miosis (pinpoint pupils), sudden entrance into menopause for women, or impotence for men, neck stiffness, and elevation of blood pressure and heart rate. The sporadic form of the disease often presents with double vision. Constipation is common as well. As the disease progresses, the person becomes stuck in a state of pre-sleep limbo, or hypnagogia, which is the state just before sleep in healthy individuals. During these stages, people commonly and repeatedly move their limbs as if dreaming.

The age of onset is variable, ranging from 18 to 60 years, with an average of 50. The disease can be detected prior to onset by genetic testing. Death usually occurs between 6–36 months from onset. The presentation of the disease varies considerably from person to person, even among people within the same family, in the sporadic form for example, sleep problems are not commonly reported and early symptoms are ataxia, cognitive impairment, and double vision.

Cause

Idiogram of chromosome 20 showing gene PRP location

The gene PRNP that provides instructions for making the prion protein PrPC is located on the short (p) arm of chromosome 20 at position p13. Both people with FFI and those with familial Creutzfeldt–Jakob disease (fCJD) carry a mutation at codon 178 of the prion protein gene. FFI is also invariably linked to the presence of the methionine codon at position 129 of the mutant allele, whereas fCJD is linked to the presence of the valine codon at that position. "The disease is where there is a change of amino acid at position 178 when an asparagine (N) is found instead of the normal aspartic acid (D). This has to be accompanied with a methionine at position 129."

Pathophysiology

In itself, the presence of prions causes reduced glucose use by the thalamus and a mild hypo-metabolism of the cingulate cortex. The extent of this symptom varies between two variations of the disease, these being those presenting methionine homozygotes at codon 129 and methionine/valine heterozygotes being the most severe in the later one. Given the relationship between the involvement of the thalamus in regulating sleep and alertness, a causal relationship can be drawn, and is often mentioned as the cause.

Diagnosis

Diagnosis is suspected based on symptoms. Further work up often include a sleep study and PET scan. Confirmation of the familial form is by genetic testing.

Differential diagnosis

Other diseases involving the mammalian prion protein are known. Some are transmissible (TSEs, including FFI) such as kuru, bovine spongiform encephalopathy (BSE, also known as "mad cow disease") in cattle, and chronic wasting disease in American deer and American elk in some areas of the United States and Canada, as well as Creutzfeldt–Jakob disease (CJD). Until recently, prion diseases were only thought to be transmissible by direct contact with infected tissue, such as from eating infected tissue, transfusion, or transplantation; research suggests that prions can be transmitted by aerosols, but that the general public is not at risk of airborne infection.

Treatments

Treatment involves palliative care. Sleeping pills, including barbiturates, have not been found to be helpful; contrarily, they have been suggested to worsen the symptoms.

Prognosis

Similar to other prion diseases, the disease is invariably fatal. Life expectancy ranges from seven months to six years, with an average of 18 months.

Epidemiology

Hypnogram comparing the sleep pattern of a healthy control with five FFI patients, who display decreased sleep efficiency and disrupted sleep cycles. [W: wake; R: REM; N1-3: NREM sleep stages].

In 1998, 40 families were known to carry the gene for FFI globally: eight German, five Italian, four American, two French, two Australian, two British, one Japanese, and one Austrian. In the Basque Country, Spain, 16 family cases of the 178N mutation were seen between 1993 and 2005 related to two families with a common ancestor in the 18th century. In 2011, another family was added to the list when researchers found the first man in the Netherlands with FFI. While he had lived in the Netherlands for 19 years, he was of Egyptian descent. Other prion diseases are similar to FFI and could be related, but are missing the D178N gene mutation.

As of 2016, 24 cases of sporadic fatal insomnia have been diagnosed. Unlike in FFI, sFI sufferers do not have the D178N mutation in the PRNP-prion gene; they all have a different mutation in the same gene causing methionine homozygosity at codon 129. Nonetheless the methionine presence in lieu of the valine (Val129) is what causes the sporadic form of disease. The targeting of this mutation is another strategy that has been suggested as possible for treatment, or hopefully as cure for the disease.

Silvano, 1983, Bologna, Italy

In late 1983, Italian neurologist/sleep expert Dr. Ignazio Roiter received a patient at the University of Bologna hospital's sleep institute. The man, known only as Silvano, decided in a rare moment of consciousness to be recorded for future studies and to donate his brain for research in hopes of finding a cure for future victims.

Unnamed patient of Schenkein and Montagna, 2001

One person was able to exceed the average survival time by nearly one year with various strategies, including vitamin therapy and meditation, using different stimulants and hypnotics, and even complete sensory deprivation in an attempt to induce sleep at night and increase alertness during the day. He managed to write a book and drive hundreds of miles in this time, but nonetheless, over the course of his trials, the person succumbed to the classic four-stage progression of the illness.

Egyptian man, 2011, Netherlands

Timeline of an FFI patient (same as the one above this one)

In 2011, the first reported case in the Netherlands was of a 57-year-old man of Egyptian descent. The man came in with symptoms of double vision and progressive memory loss, and his family also noted he had recently become disoriented, paranoid, and confused. While he tended to fall asleep during random daily activities, he experienced vivid dreams and random muscular jerks during normal slow-wave sleep. After four months of these symptoms, he began to have convulsions in his hands, trunk, and lower limbs while awake. The person died at age 58, seven months after the onset of symptoms. An autopsy revealed mild atrophy of the frontal cortex and moderate atrophy of the thalamus. The latter is one of the most common signs of FFI.

Research

Still with unclear benefit in humans, a number of treatments have had tentative success in slowing disease progression in animal models, including pentosan polysulfate, mepacrine, and amphotericin B. As of 2016, a study investigating doxycycline is being carried out.

In 2009, a mouse model was made for FFI. These mice expressed a humanized version of the PrP protein that also contains the D178N FFI mutation. These mice appear to have progressively fewer and shorter periods of uninterrupted sleep, damage in the thalamus, and early deaths, similar to humans with FFI.

The Prion Alliance was established by husband and wife duo Eric Minikel and Sonia Vallabh after Vallabh's mother was diagnosed with the fatal disease. They conduct research at the Broad Institute to develop therapeutics for human prion diseases. Other research interests involve identifying biomarkers to track the progression of prion disease in living people.

Popular culture

  • In the 2018 novel and online short story series "Tales from the Gas Station" the main character, Jack, believes that he suffers from fatal familial insomnia.
  • Charlie Huston's 2010 novel Sleepless concerns an epidemic of a fatal insomnia that is frequently compared to FFI by characters in the story.
  • In Something's Killing Me with BD Wong, November 2017 (season one, episode five), "Family Curse", FFI is the topic.
  • Nancy Kress's novelette Pathways concerns research into FFI.
  • The 2019 movie, A Score to Settle, starring Nicolas Cage, uses FFI as a plot element.
  • The 2019 movie, Awoken, uses FFI as a major plot element.
  • FFI is a major plot element and is described in detail in the Lewis episode "Falling Darkness".
  • In the first episode of the 2020 TV series Next, one of the main characters confesses to have the disease and says "It's a real thing, look it up." It also features this Wikipedia article about the disease depicted in a book encyclopedia (Episode 6, 9:4
  • In the novel Siphonophore by Jaimie Batchan (2021), the fictional author of the book is diagnosed with the disease midway through writing the novel, under the name of Prionic Fatal Insomnia.
  • In Destiny 2: Beyond Light, the Bray family all suffer from fatal familial insomnia due to their patriarch's experiments with genetic engineering.
  • Law and Order: Special Victims Unit, season 12, episode 19 – Dr. Huang diagnoses a witness who suffers from fatal familial insomnia. The witness is disoriented; unable to sleep; sweats severely and presents altered pupils. Dr. Huang explains to Detectives Olivia and Elliot that the referred disease mainly affects people from a small town in Italy, where the witness came from.

Sleep disorder

From Wikipedia, the free encyclopedia
 
Sleep disorder
Pediatric polysomnogram.jpg
Pediatric polysomnography


A sleep disorder, or somnipathy, is a medical disorder of the sleep patterns of a person. Some sleep disorders are serious enough to interfere with normal physical, mental, social and emotional functioning. Polysomnography and actigraphy are tests commonly ordered for some sleep disorders.

Disruptions in sleep can be caused by a variety of issues, including teeth grinding (bruxism) and night terrors. When a person suffers from difficulty falling asleep and/or staying asleep with no obvious cause, it is referred to as insomnia.

Sleep disorders are broadly classified into dyssomnias, parasomnias, circadian rhythm sleep disorders involving the timing of sleep, and other disorders including ones caused by medical or psychological conditions.

The most common sleep disorder is insomnia. Others are sleep apnea, narcolepsy and hypersomnia (excessive sleepiness at inappropriate times), sleeping sickness (disruption of sleep cycle due to infection), sleepwalking, and night terrors. Management of sleep disturbances that are secondary to mental, medical, or substance abuse disorders should focus on the underlying conditions.

Primary sleep disorders are common in both children and adults. However, there is a significant lack of awareness in children with sleep disorders, due to most cases being unidentified. Several common factors involved in the onset of a sleep disorder include increased medication use, age-related changes in circadian rhythms, environmental and lifestyle changes and pre diagnosed physiological problems and stress. The risk of developing sleep disorders in the elderly is especially increased for sleep disordered breathing, periodic limb movements, restless legs syndrome, REM sleep behavior disorders, insomnia and circadian rhythm disturbances.

List of conditions

There are a number of sleep disorders, the following list includes some of them:

  • Bruxism, involuntarily grinding or clenching of the teeth while sleeping.
  • Catathrenia, nocturnal groaning during prolonged exhalation.
  • Delayed sleep phase disorder (DSPD), inability to awaken and fall asleep at socially acceptable times but no problem with sleep maintenance, a disorder of circadian rhythms. Other such disorders are advanced sleep phase disorder (ASPD), non-24-hour sleep–wake disorder (non-24) in the sighted or in the blind, and irregular sleep wake rhythm, all much less common than DSPD, as well as the situational shift work sleep disorder.
  • Fatal familial insomnia, an extremely rare genetic disorder that causes a complete cessation of sleep, leading quickly to death by sleep deprivation.
  • Hypopnea syndrome, abnormally shallow breathing or slow respiratory rate while sleeping.
  • Idiopathic hypersomnia, a primary, neurologic cause of long-sleeping, sharing many similarities with narcolepsy.
  • Insomnia disorder (primary insomnia), chronic difficulty in falling asleep and/or maintaining sleep when no other cause is found for these symptoms. Insomnia can also be comorbid with or secondary to other disorders.
  • Kleine–Levin syndrome, a rare disorder characterized by persistent episodic hypersomnia and cognitive or mood changes.
  • Narcolepsy, including excessive daytime sleepiness (EDS), often culminating in falling asleep spontaneously but unwillingly at inappropriate times. About 70% of those who have narcolepsy also have cataplexy, a sudden weakness in the motor muscles that can result in collapse to the floor while retaining full conscious awareness.
  • Night terror, Pavor nocturnus, sleep terror disorder, an abrupt awakening from sleep with behavior consistent with terror.
  • Nocturia, a frequent need to get up and urinate at night. It differs from enuresis, or bed-wetting, in which the person does not arouse from sleep, but the bladder nevertheless empties.
  • Parasomnias, disruptive sleep-related events involving inappropriate actions during sleep, for example sleep walking, night-terrors and catathrenia.
  • Periodic limb movement disorder (PLMD), sudden involuntary movement of arms and/or legs during sleep, for example kicking the legs. Also known as nocturnal myoclonus. See also Hypnic jerk, which is not a disorder.
  • Rapid eye movement sleep behavior disorder (RBD), acting out violent or dramatic dreams while in REM sleep, sometimes injuring bed partner or self (REM sleep disorder or RSD).
  • Restless legs syndrome (RLS), an irresistible urge to move legs. RLS sufferers often also have PLMD.
  • Shift work sleep disorder (SWSD), a situational circadian rhythm sleep disorder. (Jet lag was previously included as a situational circadian rhythm sleep disorder, but it doesn't appear in DSM-5 (see Diagnostic and Statistical Manual of Mental Disorders)).
  • Sleep apnea, obstructive sleep apnea, obstruction of the airway during sleep, causing lack of sufficient deep sleep, often accompanied by snoring. Other forms of sleep apnea are less common. Obstructive sleep apnea (OSA) is a medical disorder that is caused by repetitive collapse of the upper airway (back of the throat) during sleep. For the purposes of sleep studies, episodes of full upper airway collapse for at least ten seconds are called apneas
  • Sleep paralysis, characterized by temporary paralysis of the body shortly before or after sleep. Sleep paralysis may be accompanied by visual, auditory or tactile hallucinations. Not a disorder unless severe. Often seen as part of narcolepsy.
  • Sleepwalking or somnambulism, engaging in activities normally associated with wakefulness (such as eating or dressing), which may include walking, without the conscious knowledge of the subject.
  • Somniphobia, one cause of sleep deprivation, a dread/ fear of falling asleep or going to bed. Signs of the illness include anxiety and panic attacks before and during attempts to sleep.

Types

Causes

A systematic review found that traumatic childhood experiences (such as family conflict or sexual trauma) significantly increases the risk for a number of sleep disorders in adulthood, including sleep apnea, narcolepsy, and insomnia. It is currently unclear whether or not moderate alcohol consumption increases the risk of obstructive sleep apnea.

In addition, an evidence-based synopses suggests that the sleep disorder, idiopathic REM sleep behavior disorder (iRBD), may have a hereditary component to it. A total of 632 participants, half with iRBD and half without, completed self-report questionnaires. The results of the study suggest that people with iRBD are more likely to report having a first-degree relative with the same sleep disorder than people of the same age and sex that do not have the disorder. More research needs to be conducted to gain further information about the hereditary nature of sleep disorders.

A population susceptible to the development of sleep disorders is people who have experienced a traumatic brain injury (TBI). Because many researchers have focused on this issue, a systematic review was conducted to synthesize their findings. According to their results, TBI individuals are most disproportionately at risk for developing narcolepsy, obstructive sleep apnea, excessive daytime sleepiness, and insomnia.

Sleep disorders and neurodegenerative diseases

Neurodegenerative diseases have been often associated with sleep disorders, mainly when they are characterized by abnormal accumulation of alpha-synuclein, such as multiple system atrophy (MSA), Parkinson's disease (PD) and Lewy body disease (LBD). For instance, people diagnosed with PD have often presented different kinds of sleep concerns, commonly regard to insomnia (around 70% of the PD population), hypersomnia (more than 50% of the PD population), and REM sleep behavior disorder (RBD) - that may affect around 40% of the PD population and it is associated with increased motor symptoms. Furthermore, RBD has been also highlighted as a strong precursor of future development of those neurodegenerative diseases over several years in prior, which seems to be a great opportunity for improving the treatments of the disease.

Sleep disturbances have been also observed in Alzheimer's disease (AD), affecting about 45% of its population. Moreover, when it is based on caregiver reports this percentage is even higher, about 70%. As well as in PD population, insomnia and hypersomnia are frequently recognized in AD patients, which have been associated with accumulation of Beta-amyloid, circadian rhythm sleep disorders (CRSD) and melatonin alteration. Additionally, changes in sleep architecture are observed in AD too. Even though with ageing the sleep architecture seems to change naturally, in AD patients it is aggravated. SWS is potentially decreased (sometimes totally absent), spindles and the time spent in REM sleep are also reduced, while its latency is increased. The poorly sleep onset in AD has been also associated with dream-related hallucination, increased restlessness, wandering and agitation, that seem to be related with sundowning - a typical chronobiological phenomenon presented in the disease.

The neurodegenerative conditions are commonly related to brain structures impairment, which might disrupt the states of sleep and wakefulness, circadian rhythm, motor or non motor functioning. On the other hand, sleep disturbances are also frequently related to worsening patient's cognitive functioning, emotional state and quality of life. Furthermore, these abnormal behavioural symptoms negatively contribute to overwhelming their relatives and caregivers. Therefore, a deeper understanding of the relationship between sleep disorders and neurodegenerative diseases seems to be extremely important, mainly considering the limited research related to it and the increasing expectancy of life.

Sleep disturbances and Alzheimer’s Disease

More than 70% of people with dementia are affected by Alzheimer's disease (AD). Despite this high number, our understanding of the mechanisms underlying the progression of this disease remains very limited. However, recent studies have highlighted a link between sleep disturbances and Alzheimer's disease.

Sleep changes with normal aging. Indeed, with age, we find a decrease in time sleeping and also a decrease in the quantity of NREM sleep, more precisely in NREM SWS (less than 10% of the SWS is maintained). Older people also are more prone to insomnia or sleep apnea.

In Alzheimer's disease, in addition to cognitive decline and memory impairment, there is also significant sleep disturbances with a modified sleep architecture. The latter may consist in sleep fragmentation, a reduction in sleep duration, insomnia, an increase in daytime napping, a decreased quantity of some sleep stages, and a resemblance between some sleep stages (N1 and N2). More than 65% of people with Alzheimer's disease suffer from this type of sleep disturbance.

One factors that could explain this change in sleep architecture is a change in circadian rhythm, which regulates sleep. A disruption of the circadian rhythm would therefore generate sleep disturbances. Some studies show that people with AD have a delayed circadian rhythm, whereas in normal aging we will find an advanced circadian rhythm.

In addition to these psychological symptoms, at a neurological level there are two main symptoms of Alzheimer's disease. The first is an accumulation of beta-amyloid waste forming aggregate “plaques”. The second is an accumulation of tau protein.

It has been shown that the sleep-wake cycle acts on the beta-amyloid burden which is a central component found in AD. Indeed, during waking, the production of beta-amyloid protein will be more consistent than during sleep. This is explained by two phenomena. The first is that the metabolic activity will be higher during waking and thus will secrete more beta-amyloid protein. The second is that oxidative stress will also be higher and lead to increased AB production.

On the other hand, it is during sleep that beta-amyloid residues are degraded to prevent plaque formation. It is the glymphatic system that is responsible for this and this phenomenon is called glymphatic clearance. Thus, during wakefulness, the AB burden is greater because the metabolic activity and oxidative stress are higher and there is no degradation of the protein by the glymphatic clearance whereas during sleep, the burden will be smaller as there will be less metabolic activity and oxidative stress in addition to the glymphatic clearance that occurs at this time.

The glymphatic clearance occurs during the NREM sleep, and more specifically the NREM SWS sleep. As seen previously, it is a sleep stage that decreases in normal aging. So there is less glymphatic clearance and an increase in AB burden that will form the AB plaques. Therefore, in AD sleep disturbances will amplify this phenomenon.

The decrease in the quantity and quality of the NREM SWS as well as the disturbances of sleep will therefore increase the AB plaques. This will first take place at the hippocampus level, from which memory is dependent. This will result in cell death at this level and will contribute to diminished memory performances and cognitive decline found in AD disease.

Although we do not know the causal relationship, we know that the more the AD progresses, the more we find sleep disorders. In the same way, the more sleep disorders there are, the more the disease progresses, forming a vicious circle. Taken this into account, sleep disturbances are no longer a symptom of AD and relationship between sleep disturbances and AD is bidirectional.

At the same time, it has been shown that memory consolidation in long-term memory (which depends on the hippocampus) occurs during NREM sleep. This indicates that a decrease in the NREM sleep will result in less consolidation and therefore poorer memory performances in hippocampal-dependent long-term memory. This drop in performance is one of the central symptoms of AD.

Recent studies have also linked sleep disturbances, neurogenesis and AD. Indeed, it is now known that neurogenesis exists and that the subgranular zone and the subventricular zone keep on creating new neurons even in an adult brain. These new cells are then incorporated into neuronal circuits and the supragranular zone is found in the hippocampus. These new cells will contribute to learning and memory and will play a role in the hippocampal-dependent memory.

Recent studies, however, have shown that several factors can interrupt this neurogenesis. These include stress and prolonged sleep deprivation (more than one day). The sleep disturbances encountered in AD could therefore suppress neurogenesis and thus impairing hippocampal functions. This would therefore contribute to diminished memory performances and the progression of AD. And progression of AD would aggravate sleep disturbances. It is a second vicious circle.

The changes in sleep architecture found in patients with AD occur during the preclinical phase of AD. These changes could be used to detect those most at risk of developing AD. However, this is still only theoretical.

Although the exact mechanisms and the causal relationship between sleep disturbances and AD are not yet clear, these findings already provide a better understanding. In addition, they open up ideas for the implementation of treatments to curb the cognitive decline of patients suffering from this disease. In the same way, it also makes it possible to better target at risk population.

Sleep disorder symptoms in psychiatric illnesses

Schizophrenia

In individuals with psychiatric illnesses, sleep disorders may include a variety of clinical symptoms such as excessive daytime sleepiness, difficulty falling asleep, difficulty staying asleep, nightmares, sleep talking, sleep walking, and poor quality sleep, among various others. Sleep disturbances - insomnia, hypersomnia and delayed sleep-phase disorder - are quite prevalent in severe mental illnesses such as psychotic disorders. In those with schizophrenia sleep disorders contribute to cognitive deficits in learning and memory. Sleep disturbances often occur before the onset of psychosis. Sleep deprivation can also produce hallucinations, delusions and depression. A 2019 study investigated the three above-mentioned sleep disturbances in schizophrenia-spectrum (SCZ) and bipolar (BP) disorders in 617 SCZ individuals, 440 BP individuals, and 173 healthy controls (HC), sleep disturbances being identified using the Inventory for Depressive Symptoms - clinician rated scale (IDS-C). Results suggested that at least one type of sleep disturbance was reported in 78% of the SCZ population, in 69% individuals with BD, and only in 39% of the healthy controls. The SCZ group reported the most number of sleep disturbances, compared to the BD and HC group, specifically hypersomnia was more frequent among individuals with SCZ and delayed sleep phase disorder was 3 times more common in the SCZ group compared to the BD group. Finally, insomnias were the most frequently reported sleep disturbance across all three groups.

Bipolar disorder

One of the main behavioral symptoms of bipolar disorder is abnormal sleep, and studies have suggested that 23-78% of individuals with bipolar disorders consistently report symptoms of excessive time spent sleeping, or hypersomnia. The pathogenesis of bipolar disorder, including the higher risk of suicidal ideation, could possibly be linked to circadian rhythm variability, and sleep disturbances are a good predictor of mood swings. The most common sleep-related symptom of bipolar disorder is insomnia, in addition to hypersomnia, nightmares, poor sleep quality, OSA, extreme daytime sleepiness, etc. Moreover, animal models have shown that sleep debt can induce episodes of bipolar mania in laboratory mice, but these rodent models are still restricted in their potential to explain bipolar disease in humans with all its multifaceted symptoms, including those related to sleep disturbances.

Major depressive disorder (MDD)

Sleep disturbances (insomnia or hypersomnia) are not a necessary diagnostic criterion but one of the most frequent symptoms of individuals with major depressive disorder (MDD). Insomnia and hypersomnia have prevalence rates of 88% and 27%, respectively, among individuals with MDD whereas individuals with insomnia have a threefold increased risk of developing MDD. Depressed mood and sleep efficiency strongly co-vary, and while sleep regulation problems may precede depressive episodes, such depressive episodes may also precipitate sleep deprivation. Fatigue as well as sleep disturbances such as irregular and excessive sleepiness are linked to symptoms of depression.

Treatment

Sign with text: Sömnförsök pågår (Sleep study in progress), room for sleep studies in NÄL hospital, Sweden.

Treatments for sleep disorders generally can be grouped into four categories:

None of these general approaches is sufficient for all patients with sleep disorders. Rather, the choice of a specific treatment depends on the patient's diagnosis, medical and psychiatric history, and preferences, as well as the expertise of the treating clinician. Often, behavioral/psychotherapeutic and pharmacological approaches are not incompatible and can effectively be combined to maximize therapeutic benefits. Management of sleep disturbances that are secondary to mental, medical, or substance abuse disorders should focus on the underlying conditions.

Medications and somatic treatments may provide the most rapid symptomatic relief from some sleep disturbances. Certain disorders like narcolepsy, are best treated with prescription drugs such as modafinil. Others, such as chronic and primary insomnia, may be more amenable to behavioral interventions, with more durable results.

Chronic sleep disorders in childhood, which affect some 70% of children with developmental or psychological disorders, are under-reported and under-treated. Sleep-phase disruption is also common among adolescents, whose school schedules are often incompatible with their natural circadian rhythm. Effective treatment begins with careful diagnosis using sleep diaries and perhaps sleep studies. Modifications in sleep hygiene may resolve the problem, but medical treatment is often warranted.

Special equipment may be required for treatment of several disorders such as obstructive apnea, the circadian rhythm disorders and bruxism. In these cases, when severe, an acceptance of living with the disorder, however well managed, is often necessary.

Some sleep disorders have been found to compromise glucose metabolism.

Allergy treatment

Histamine plays a role in wakefulness in the brain. An allergic reaction over produces histamine causing wakefulness and inhibiting sleep Sleep problems are common in people with allergic rhinitis. A study from the N.I.H. found that sleep is dramatically impaired by allergic symptoms and that the degree of impairment is related to the severity of those symptoms Treatment of allergies has also been shown to help sleep apnea.

Acupuncture

A review of the evidence in 2012 concluded that current research is not rigorous enough to make recommendations around the use of acupuncture for insomnia. The pooled results of two trials on acupuncture showed a moderate likelihood that there may be some improvement to sleep quality for individuals with a diagnosis insomnia. This form of treatment for sleep disorders is generally studied in adults, rather than children. Further research would be needed to study the effects of acupuncture on sleep disorders in children.

Hypnosis

Research suggests that hypnosis may be helpful in alleviating some types and manifestations of sleep disorders in some patients. "Acute and chronic insomnia often respond to relaxation and hypnotherapy approaches, along with sleep hygiene instructions." Hypnotherapy has also helped with nightmares and sleep terrors. There are several reports of successful use of hypnotherapy for parasomnias specifically for head and body rocking, bedwetting and sleepwalking.

Hypnotherapy has been studied in the treatment of sleep disorders in both adults and children.

Music therapy

Although more research should be done to increase the reliability of this method of treatment, research suggests that music therapy can improve sleep quality in acute and chronic sleep disorders. In one particular study, participants (18 years or older) who had experienced acute or chronic sleep disorders were put in a randomly controlled trial and their sleep efficiency (overall time asleep) was observed. In order to assess sleep quality, researchers used subjective measures (i.e. questionnaires) and objective measures (i.e. polysomnography). The results of the study suggest that music therapy did improve sleep quality in subjects with acute or chronic sleep disorders, however only when tested subjectively. Although these results are not fully conclusive and more research should be conducted, it still provides evidence that music therapy can be an effective treatment for sleep disorders.

In another study, specifically looking to help people with insomnia, similar results were seen. The participants that listened to music experienced better sleep quality than those who did not listen to music. Listening to slower pace music before bed can help decrease the heart rate, making it easier to transition into sleep. Studies have indicated that music helps induce a state of relaxation that shifts an individual's internal clock towards the sleep cycle. This is said to have an effect on children and adults with various cases of sleep disorders. Music is most effective before bed once the brain has been conditioned to it, helping to achieve sleep much faster.

Melatonin

Research suggests that melatonin is useful in helping people fall asleep faster (decreased sleep latency), to stay asleep longer, and to experience improved sleep quality. In order to test this, a study was conducted that compared subjects who had taken melatonin to subjects with primary sleep disorders who had taken a placebo. Researchers assessed sleep onset latency, total minutes slept, and overall sleep quality in the melatonin and placebo groups to note the differences. In the end, researchers found that melatonin decreased sleep onset latency and increased total sleep time  but had an insignificant and inconclusive impact on the quality of sleep compared to a placebo group.

Sleep medicine

Due to rapidly increasing knowledge about sleep in the 20th century, including the discovery of REM sleep in the 1950s and circadian rhythm disorders in the 70s and 80s, the medical importance of sleep was recognized. The medical community began paying more attention than previously to primary sleep disorders, such as sleep apnea, as well as the role and quality of sleep in other conditions. By the 1970s in the US, clinics and laboratories devoted to the study of sleep and sleep disorders had been founded, and a need for standards arose.

Specialists in Sleep Medicine were originally certified by the American Board of Sleep Medicine, which still recognizes specialists. Those passing the Sleep Medicine Specialty Exam received the designation "diplomate of the ABSM." Sleep Medicine is now a recognized subspecialty within internal medicine, family medicine, pediatrics, otolaryngology, psychiatry and neurology in the United States. Certification in Sleep Medicine shows that the specialist:

"has demonstrated expertise in the diagnosis and management of clinical conditions that occur during sleep, that disturb sleep, or that are affected by disturbances in the wake-sleep cycle. This specialist is skilled in the analysis and interpretation of comprehensive polysomnography, and well-versed in emerging research and management of a sleep laboratory."

Competence in sleep medicine requires an understanding of a myriad of very diverse disorders, many of which present with similar symptoms such as excessive daytime sleepiness, which, in the absence of volitional sleep deprivation, "is almost inevitably caused by an identifiable and treatable sleep disorder", such as sleep apnea, narcolepsy, idiopathic hypersomnia, Kleine–Levin syndrome, menstrual-related hypersomnia, idiopathic recurrent stupor, or circadian rhythm disturbances. Another common complaint is insomnia, a set of symptoms which can have a great many different causes, physical and mental. Management in the varying situations differs greatly and cannot be undertaken without a correct diagnosis.

Sleep dentistry (bruxism, snoring and sleep apnea), while not recognized as one of the nine dental specialties, qualifies for board-certification by the American Board of Dental Sleep Medicine (ABDSM). The resulting Diplomate status is recognized by the American Academy of Sleep Medicine (AASM), and these dentists are organized in the Academy of Dental Sleep Medicine (USA). The qualified dentists collaborate with sleep physicians at accredited sleep centers and can provide oral appliance therapy and upper airway surgery to treat or manage sleep-related breathing disorders.

Occupational Therapy is an area of medicine that can also address a diagnosis of sleep disorder, as Rest and Sleep is listed in the Occupational Therapy Practice Framework (OTPF) as its own occupation of daily living. Rest and Sleep is described as restorative in order to support engagement in other Occupational Therapy occupations.  In the OTPF, the occupation of Rest and Sleep is broken down into Rest, Sleep Preparation and Sleep Participation.  Occupational Therapists have been shown to help improve restorative sleep through the use of assistive devices/equipment, Cognitive Behavioral Therapy for Insomnia, therapeutic activities, and/or lifestyle interventions.

In the UK, knowledge of sleep medicine and possibilities for diagnosis and treatment seem to lag. Guardian.co.uk quotes the director of the Imperial College Healthcare Sleep Centre: "One problem is that there has been relatively little training in sleep medicine in this country – certainly there is no structured training for sleep physicians." The Imperial College Healthcare site shows attention to obstructive sleep apnea syndrome (OSA) and very few other sleep disorders. Some NHS trusts have specialist clinics for respiratory and/or neurological sleep medicine.

Epidemiology

Children and young adults

According to one meta-analysis, the two most prevalent sleep disorders among children are confusional arousals and sleep walking. An estimated 17.3% of kids between 3 and 13 years old experience confusional arousals. About 17% of children sleep walk, with the disorder being more common among boys than girls. The peak ages of sleep walking are from 8 to 12 years old. A different systematic review offers a high range of prevalence rates of sleep bruxism for children. Between 15.29 and 38.6% of preschoolers grind their teeth at least one night a week. All but one of the included studies reports decreasing bruxist prevalence as age increased as well as a higher prevalence among boys than girls.

Another systematic review noted 7-16% of young adults suffer from delayed sleep phase disorder. This disorder reaches peak prevalence when people are in their 20s. Between 20 and 26% of adolescents report a sleep onset latency of greater than 30 minutes. Also, 7-36% have difficulty initiating sleep. Asian teens tend to have a higher prevalence of all of these adverse sleep outcomes than their North American and European counterparts.

Insomnia

Combining results from 17 studies on insomnia in China, a pooled prevalence of 15.0% is reported for the country. This is considerably lower than a series of Western countries (50.5% in Poland, 37.2% in France and Italy, 27.1% in USA). However, the result is consistent among other East Asian countries. Men and women residing in China experience insomnia at similar rates. A separate meta-analysis focusing on this sleeping disorder in the elderly mentions that those with more than one physical or psychiatric malady experience it at a 60% higher rate than those with one condition or less. It also notes a higher prevalence of insomnia in women over the age of 50 than their male counterparts.

A study that was resulted from a collaboration between Massachusetts General Hospital and Merck describes the development of an algorithm to identify patients will sleep disorders using electronic medical records. The algorithm that incorporated a combination of structured and unstructured variables identified more than 36,000 individuals with physician-documented insomnia.

Obstructive sleep apnea

Obstructive sleep apnea (OSA) affects around 4% of men and 2% of women in the United States. In general, this disorder is more prevalent among men. However, this difference tends to diminish with age. Women experience the highest risk for OSA during pregnancy. Also, they tend to report experiencing depression and insomnia in conjunction with obstructive sleep apnea. In a meta-analysis of the various Asian countries, India and China present the highest prevalence of the disorder. Specifically, about 13.7% of the Indian population and 7% of Hong Kong's population is estimated to have OSA. The two groups experience daytime OSA symptoms such as difficulties concentrating, mood swings, or high blood pressure, at similar rates (prevalence of 3.5% and 3.57%, respectively).

Sleep paralysis

A systematic review states 7.6% of the general population experiences sleep paralysis at least once in their lifetime. Its prevalence among men is 15.9% while 18.9% of women experience it. When considering specific populations, 28.3% of students and 31.9% of psychiatric patients have experienced this phenomenon at least once in their lifetime. Of those psychiatric patients, 34.6% have panic disorder. Sleep paralysis in students is slightly more prevalent for those of Asian descent (39.9%) than other ethnicities (Hispanic: 34.5%, African descent: 31.4%, Caucasian 30.8%).

Restless leg syndrome

According to one meta-analysis, the mean prevalence rate for North America and Western Europe is estimated to be 14.5±8.0%. Specifically in the United States, the prevalence of restless leg syndrome is estimated to be between 5 and 15.7% when using strict diagnostic criteria. RLS is over 35% more prevalent in American women than their male counterparts.

See also

 

Sleep apnea

From Wikipedia, the free encyclopedia
 
Sleep apnea
Other namesSleep apnoea, sleep apnea syndrome
Obstruction ventilation apnée sommeil.svg
Obstructive sleep apnea
Pronunciation
SpecialtyOtorhinolaryngology, sleep medicine
SymptomsPauses breathing or periods of shallow breathing during sleep, snoring, tired during the day
ComplicationsHeart attack, stroke, diabetes, heart failure, irregular heartbeat, obesity, motor vehicle collisions, Alzheimer's disease, and premature death
Usual onsetVaries; 50% of women age 20-70
TypesObstructive sleep apnea (OSA), central sleep apnea (CSA), mixed sleep apnea
Risk factorsOverweight, family history, allergies, enlarged tonsils
Diagnostic methodOvernight sleep study
TreatmentLifestyle changes, mouthpieces, breathing devices, surgery
Frequency~ 1 in every 10 people, 2:1 ratio of men to women, aging and obesity higher risk 

Sleep apnea, also spelled sleep apnoea, is a sleep disorder in which pauses in breathing or periods of shallow breathing during sleep occur more often than normal. Each pause can last for a few seconds to a few minutes and they happen many times a night. In the most common form, this follows loud snoring. There may be a choking or snorting sound as breathing resumes. Because the disorder disrupts normal sleep, those affected may experience sleepiness or feel tired during the day. In children, it may cause hyperactivity or problems in school.

Sleep apnea may be either obstructive sleep apnea (OSA), in which breathing is interrupted by a blockage of air flow, central sleep apnea (CSA), in which regular unconscious breath simply stops, or a combination of the two. OSA is the most common form. OSA has four key contributors; these include “anatomical compromises" like a narrow, crowded, or collapsible upper airway. Or “non-anatomical” ones like an ineffective pharyngeal dilator muscle function during sleep, airway narrowing during sleep, or unstable control of breathing (high loop gain). Other risk factors include being overweight, a family history of the condition, allergies, and enlarged tonsils. Some people with sleep apnea are unaware they have the condition. In many cases it is first observed by a family member. Sleep apnea is often diagnosed with an overnight sleep study. For a diagnosis of sleep apnea, more than five episodes per hour must occur.

In central sleep apnea (CSA), 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. 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. However, 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.

Treatment may include lifestyle changes, mouthpieces, breathing devices, and surgery. Lifestyle changes may include avoiding alcohol, losing weight, stopping smoking, and sleeping on one's side. Breathing devices include the use of a CPAP machine. With proper use, CPAP improves outcomes. Evidence suggests that CPAP may improve sensitivity to insulin, blood pressure, and sleepiness. Long term compliance, however, is an issue with more than half of people not appropriately using the device. In 2017, only 15% of potential patients in developed countries used CPAP machines, while in developing countries well under 1% of potential patients used CPAP. Without treatment, sleep apnea may increase the risk of heart attack, stroke, diabetes, heart failure, irregular heartbeat, obesity, and motor vehicle collisions.

Alzheimer's Disease and severe obstructive sleep apnea are connected because there is an increase in the protein beta-amyloid as well as white-matter damage. These are the main indicators of Alzheimer's, which in this case comes from the lack of proper rest or poorer sleep efficiency resulting in neurodegeneration. Having sleep apnea in mid-life brings a higher likelihood of developing Alzheimer's in older age, and if one has Alzheimer's then one is also more likely to have sleep apnea. This is demonstrated by cases of sleep apnea even being misdiagnosed as dementia. With the use of treatment through CPAP, there is a reversible risk factor in terms of the amyloid proteins. This usually restores brain structure and cognitive impairment.

OSA is a common sleep disorder affecting 936 million—1 billion people globally, or roughly every 1 in 7 people, and up to 30% of the elderly. Sleep apnea is somewhat more common in men than women, roughly a 2:1 ratio of men to women, and in general more people are likely to have it with older age and obesity.

Signs and symptoms

People with sleep apnea have problems with excessive daytime sleepiness (EDS) and impaired alertness. OSA may increase risk for driving accidents and work-related accidents. If OSA is not treated, people are at increased risk of other health problems, such as diabetes.

Due to the disruption in daytime cognitive state, behavioral effects may be present. These can include moodiness, belligerence, as well as a decrease in attentiveness and energy. These effects may become intractable, leading to depression.

There is evidence that the risk of diabetes among those with moderate or severe sleep apnea is higher. Finally, because there are many factors that could lead to some of the effects previously listed, some people are not aware that they have sleep apnea and are either misdiagnosed or ignore the symptoms altogether.

Risk factors

Sleep apnea can affect people regardless of sex, race, or age. However, risk factors include:

  • being male
  • obesity
  • age over 40
  • large neck circumference (greater than 16–17 inches)
  • enlarged tonsils or tongue
  • narrow upper jaw
  • nasal congestion
  • allergies
  • receding chin
  • gastroesophageal reflux
  • a family history of sleep apnea

Alcohol, sedatives and tranquilizers may also promote sleep apnea by relaxing throat muscles. People who smoke tobacco have sleep apnea at three times the rate of people who have never done so.

Central sleep apnea is more often associated with any of the following risk factors:

High blood pressure is very common in people with sleep apnea.

Mechanism

When breathing is paused, carbon dioxide builds up in the bloodstream. Chemoreceptors in the bloodstream note the high carbon dioxide levels. The brain is signaled to awaken the person, which clears the airway and allows breathing to resume. Breathing normally will restore oxygen levels and the person will fall asleep again. This carbon dioxide build-up may be due to the decrease of output of the brainstem regulating the chest wall or pharyngeal muscles, which causes the pharynx to collapse. People with sleep apnea experience reduced or no slow-wave sleep and spend less time in REM sleep.

Diagnosis

Despite this medical consensus, the variety of apneic events (e.g., hypopnea vs apnea, central vs obstructive), the variability of patients' physiologies, and the inherent shortcomings and variability of equipment and methods, this field is subject to debate. Within this context, the definition of an event depends on several factors (e.g., patient's age) and account for this variability through a multi-criteria decision rule described in several, sometimes conflicting, guidelines.

Oximetry

Oximetry, which may be performed over one or several nights in a person's home, is a simpler, but less reliable alternative to a polysomnography. The test is recommended only when requested by a physician and should not be used to test those without symptoms. Home oximetry may be effective in guiding prescription for automatically self-adjusting continuous positive airway pressure.

Classification

There are three types of sleep apnea. OSA accounts for 84%, CSA for 0.9%, and 15% of cases are mixed.

Obstructive sleep apnea

Screenshot of a PSG system showing an obstructive apnea.
 
No airway obstruction during sleep.
 
Airway obstruction during sleep.

Obstructive sleep apnea (OSA) is the most common category of sleep-disordered breathing. The muscle tone of the body ordinarily relaxes during sleep, and at the level of the throat, the human airway is composed of collapsible walls of soft tissue that can obstruct breathing. Mild occasional sleep apnea, such as many people experience during an upper respiratory infection, may not be significant, but chronic severe obstructive sleep apnea requires treatment to prevent low blood oxygen (hypoxemia), sleep deprivation, and other complications.

Individuals with low muscle-tone and soft tissue around the airway (e.g., because of obesity) and structural features that give rise to a narrowed airway are at high risk for obstructive sleep apnea. The elderly are more likely to have OSA than young people. Men are more likely to suffer sleep apnea than women and children are, though it is not uncommon in the last two population groups.

The risk of OSA rises with increasing body weight, active smoking and age. In addition, patients with diabetes or "borderline" diabetes have up to three times the risk of having OSA.

Common symptoms include loud snoring, restless sleep, and sleepiness during the daytime. Diagnostic tests include home oximetry or polysomnography in a sleep clinic.

Some treatments involve lifestyle changes, such as avoiding alcohol or muscle relaxants, losing weight, and quitting smoking. Many people benefit from sleeping at a 30-degree elevation of the upper body or higher, as if in a recliner. Doing so helps prevent the gravitational collapse of the airway. Lateral positions (sleeping on a side), as opposed to supine positions (sleeping on the back), are also recommended as a treatment for sleep apnea, largely because the gravitational component is smaller in the lateral position. Some people benefit from various kinds of oral appliances such as the Mandibular advancement splint to keep the airway open during sleep. Continuous positive airway pressure (CPAP) is the most effective treatment for severe obstructive sleep apnea, but oral appliances are considered a first-line approach equal to CPAP for mild to moderate sleep apnea, according to the AASM parameters of care. There are also surgical procedures to remove and tighten tissue and widen the airway.

Snoring is a common finding in people with this syndrome. Snoring is the turbulent sound of air moving through the back of the mouth, nose, and throat. Although not everyone who snores is experiencing difficulty breathing, snoring in combination with other risk factors has been found to be highly predictive of OSA. The loudness of the snoring is not indicative of the severity of obstruction, however. If the upper airways are tremendously obstructed, there may not be enough air movement to make much sound. Even the loudest snoring does not mean that an individual has sleep apnea syndrome. The sign that is most suggestive of sleep apneas occurs when snoring stops.

Up to 78% of genes associated with habitual snoring also increase the risk for OSA.

Other indicators include (but are not limited to): hypersomnolence, obesity (BMI ≥ 30), large neck circumference—16 in (410 mm) in women, 17 in (430 mm) in men — enlarged tonsils and large tongue volume, micrognathia, morning headaches, irritability/mood-swings/depression, learning and/or memory difficulties, and sexual dysfunction.

The term "sleep-disordered breathing" is commonly used in the U.S. to describe the full range of breathing problems during sleep in which not enough air reaches the lungs (hypopnea and apnea). Sleep-disordered breathing is associated with an increased risk of cardiovascular disease, stroke, high blood pressure, arrhythmias, diabetes, and sleep deprived driving accidents. When high blood pressure is caused by OSA, it is distinctive in that, unlike most cases of high blood pressure (so-called essential hypertension), the readings do not drop significantly when the individual is sleeping. Stroke is associated with obstructive sleep apnea.

Obstructive sleep apnea is associated with problems in daytime functioning, such as daytime sleepiness, motor vehicle crashes, psychological problems, decreased cognitive functioning, and reduced quality of life. Other associated problems include cerebrovascular diseases (hypertension, coronary artery disease, and stroke) and diabetes. These problems could be, at least in part, caused by risk factors of OSA.

Central sleep apnea

Screenshot of a PSG system showing a central apnea.

In pure central sleep apnea or Cheyne–Stokes respiration, 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 and then starts again. 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.

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. Any sudden drop in oxygen or excess of carbon dioxide (even if tiny) strongly stimulates the brain's respiratory centers to breathe.

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.

  • 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.
  • 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.

Mixed apnea

Some people with sleep apnea have a combination of both types; its prevalence ranges from 0.56% to 18%. The condition is generally detected when obstructive sleep apnea is treated with CPAP and central sleep apnea emerges. The exact mechanism of the loss of central respiratory drive during sleep in OSA is unknown but is most likely related to incorrect settings of the CPAP treatment and other medical conditions the person has.

Management

The treatment of obstructive sleep apnea is different than that of central sleep apnea. Treatment often starts with behavioral therapy. Many people are told to avoid alcohol, sleeping pills, and other sedatives, which can relax throat muscles, contributing to the collapse of the airway at night.

Continuous positive airway pressure

Person using a CPAP mask, covering only the nose
 
CPAP machine with two models of masks
 

For moderate to severe sleep apnea, the most common treatment is the use of a continuous positive airway pressure (CPAP) or automatic positive airway pressure (APAP) device. These splint the person's airway open during sleep by means of pressurized air. The person typically wears a plastic facial mask, which is connected by a flexible tube to a small bedside CPAP machine.

Although CPAP therapy is effective in reducing apneas and less expensive than other treatments, some people find it uncomfortable. Some complain of feeling trapped, having chest discomfort, and skin or nose irritation. Other side effects may include dry mouth, dry nose, nosebleeds, sore lips and gums.

Whether or not it decreases the risk of death or heart disease is controversial with some reviews finding benefit and others not. This variation across studies might be driven by low rates of compliance—analyses of those who use CPAP for at least four hours a night suggests a decrease in cardiovascular events.

Weight loss

Excess body weight is thought to be an important cause of sleep apnea. People who are overweight have more tissues in the back of their throat which can restrict the airway, especially when sleeping. In weight loss studies of overweight individuals, those who lose weight show reduced apnea frequencies and improved Apnoea–Hypopnoea Index (AHI). Weight loss effective enough to relieve obesity hypoventilation syndrome (OHS) must be 25–30% of body weight. It is difficult to achieve and maintain this result without bariatric surgery.

Rapid Palatal Expansion

In children, orthodontic treatment to expand the volume of the nasal airway, such as nonsurgical Rapid Palatal expansion is common. The procedure has been found to significantly decrease the AHI and lead to long-term resolution of clinical symptoms.

Since the palatal suture is fused in adults, regular RPE using tooth-borne expanders cannot be performed. Mini-implant assisted rapid palatal expansion (MARPE) has been recently developed as a non-surgical option for the transverse expansion of the maxilla in adults. This method increases the volume of the nasal cavity and nasopharynx, leading to increased airflow and reduced respiratory arousals during sleep. Changes are permanent with minimal complications.

Palatal expansion is a unique treatment in that it is minimally invasive, has lasting changes and requires minimal patient compliance for treatment success.

Surgery

Illustration of surgery on the mouth and throat.

Several surgical procedures (sleep surgery) are used to treat sleep apnea, although they are normally a third line of treatment for those who reject or are not helped by CPAP treatment or dental appliances. Surgical treatment for obstructive sleep apnea needs to be individualized to address all anatomical areas of obstruction.

Nasal obstruction

Often, correction of the nasal passages needs to be performed in addition to correction of the oropharynx passage. Septoplasty and turbinate surgery may improve the nasal airway, but has been found to be ineffective at reducing respiratory arousals during sleep.

Pharyngeal obstruction

Tonsillectomy and uvulopalatopharyngoplasty (UPPP or UP3) are available to address pharyngeal obstruction.

Uvulopalatopharyngoplasty. A) pre-operative, B) original UPPP, C) modified UPPP, and D) minimal UPPP.

The "Pillar" device is a treatment for snoring and obstructive sleep apnea; it is thin, narrow strips of polyester. Three strips are inserted into the roof of the mouth (the soft palate) using a modified syringe and local anesthetic, in order to stiffen the soft palate. This procedure addresses one of the most common causes of snoring and sleep apnea — vibration or collapse of the soft palate. It was approved by the FDA for snoring in 2002 and for obstructive sleep apnea in 2004. A 2013 meta-analysis found that "the Pillar implant has a moderate effect on snoring and mild-to-moderate obstructive sleep apnea" and that more studies with high level of evidence were needed to arrive at a definite conclusion; it also found that the polyester strips work their way out of the soft palate in about 10% of the people in whom they are implanted.

Hypopharyngeal or base of tongue obstruction

Base-of-tongue advancement by means of advancing the genial tubercle of the mandible, tongue suspension, or hyoid suspension (aka hyoid myotomy and suspension or hyoid advancement) may help with the lower pharynx.

Other surgery options may attempt to shrink or stiffen excess tissue in the mouth or throat, procedures done at either a doctor's office or a hospital. Small shots or other treatments, sometimes in a series, are used for shrinkage, while the insertion of a small piece of stiff plastic is used in the case of surgery whose goal is to stiffen tissues.

Multi-level surgery

Maxillomandibular advancement (MMA) is considered the most effective surgery for people with sleep apnea, because it increases the posterior airway space (PAS). However, health professionals are often unsure as to who should be referred for surgery and when to do so: some factors in referral may include failed use of CPAP or device use; anatomy which favors rather than impedes surgery; or significant craniofacial abnormalities which hinder device use.

Potential complications

Several inpatient and outpatient procedures use sedation. Many drugs and agents used during surgery to relieve pain and to depress consciousness remain in the body at low amounts for hours or even days afterwards. In an individual with either central, obstructive or mixed sleep apnea, these low doses may be enough to cause life-threatening irregularities in breathing or collapses in a patient's airways. Use of analgesics and sedatives in these patients postoperatively should therefore be minimized or avoided.

Surgery on the mouth and throat, as well as dental surgery and procedures, can result in postoperative swelling of the lining of the mouth and other areas that affect the airway. Even when the surgical procedure is designed to improve the airway, such as tonsillectomy and adenoidectomy or tongue reduction, swelling may negate some of the effects in the immediate postoperative period. Once the swelling resolves and the palate becomes tightened by postoperative scarring, however, the full benefit of the surgery may be noticed.

A person with sleep apnea undergoing any medical treatment must make sure their doctor and anesthetist are informed about the sleep apnea. Alternative and emergency procedures may be necessary to maintain the airway of sleep apnea patients.

Other

Neurostimulation

Diaphragm pacing, which involves the rhythmic application of electrical impulses to the diaphragm, has been used to treat central sleep apnea.

In April 2014, the U.S. Food and Drug Administration granted pre-market approval for use of an upper airway stimulation system in people who cannot use a continuous positive airway pressure device. The Inspire Upper Airway Stimulation system senses respiration and applies mild electrical stimulation during inspiration, which pushes the tongue slightly forward to open the airway.

Medications

There is currently insufficient evidence to recommend any medication for OSA. There is limited evidence for medication, but acetazolamide "may be considered" for the treatment of central sleep apnea; it also found that zolpidem and triazolam may be considered for the treatment of central sleep apnea, but "only if the patient does not have underlying risk factors for respiratory depression". Low doses of oxygen are also used as a treatment for hypoxia but are discouraged due to side effects.

Oral appliances

An oral appliance, often referred to as a mandibular advancement splint, is a custom-made mouthpiece that shifts the lower jaw forward and opens the bite slightly, opening up the airway. These devices can be fabricated by a general dentist. Oral appliance therapy (OAT) is usually successful in patients with mild to moderate obstructive sleep apnea. While CPAP is more effective for sleep apnea than oral appliances, oral appliances do improve sleepiness and quality of life and are often better tolerated than CPAP.

Nasal EPAP

Nasal EPAP is a bandage-like device placed over the nostrils that uses a person's own breathing to create positive airway pressure to prevent obstructed breathing.

Oral pressure therapy

Oral pressure therapy uses a device that creates a vacuum in the mouth, pulling the soft palate tissue forward. It has been found useful in about 25 to 37% of people.

Prognosis

Death could occur from untreated OSA due to lack of oxygen to the body.

There is increasing evidence that sleep apnea may lead to liver function impairment, particularly fatty liver diseases (see steatosis).

It has been revealed that people with OSA show tissue loss in brain regions that help store memory, thus linking OSA with memory loss. Using magnetic resonance imaging (MRI), the scientists discovered that people with sleep apnea have mammillary bodies that are about 20% smaller, particularly on the left side. One of the key investigators hypothesized that repeated drops in oxygen lead to the brain injury.

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.

Epidemiology

The Wisconsin Sleep Cohort Study estimated in 1993 that roughly one in every 15 Americans was affected by at least moderate sleep apnea. It also estimated that in middle-age as many as 9% of women and 24% of men were affected, undiagnosed and untreated.

The costs of untreated sleep apnea reach further than just health issues. It is estimated that in the U.S., the average untreated sleep apnea patient's annual health care costs $1,336 more than an individual without sleep apnea. This may cause $3.4 billion/year in additional medical costs. Whether medical cost savings occur with treatment of sleep apnea remains to be determined.

History

A type of CSA was described in the German myth of Ondine's curse where the person when asleep would forget to breathe. The clinical picture of this condition has long been recognized as a character trait, without an understanding of the disease process. The term "Pickwickian syndrome" that is sometimes used for the syndrome was coined by the famous early 20th-century physician William Osler, who must have been a reader of Charles Dickens. The description of Joe, "the fat boy" in Dickens's novel The Pickwick Papers, is an accurate clinical picture of an adult with obstructive sleep apnea syndrome.

The early reports of obstructive sleep apnea in the medical literature described individuals who were very severely affected, often presenting with severe hypoxemia, hypercapnia and congestive heart failure.

Treatment

The management of obstructive sleep apnea was improved with the introduction of continuous positive airway pressure (CPAP), first described in 1981 by Colin Sullivan and associates in Sydney, Australia. The first models were bulky and noisy, but the design was rapidly improved and by the late 1980s, CPAP was widely adopted. The availability of an effective treatment stimulated an aggressive search for affected individuals and led to the establishment of hundreds of specialized clinics dedicated to the diagnosis and treatment of sleep disorders. Though many types of sleep problems are recognized, the vast majority of patients attending these centers have sleep-disordered breathing. Sleep apnea awareness day is April 18 in recognition of Colin Sullivan.

See also

 

Natural science

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