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.
Fewer
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.
Hallucinations and panic attacks become noticeable, continuing for about five months.
Complete inability to sleep is followed by rapid loss of weight. This lasts for about three months.
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 methioninehomozygosity 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.
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.
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.
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.
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.
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 tactilehallucinations. 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
Dyssomnias – A broad category of sleep disorders characterized by either hypersomnia or insomnia.
The three major subcategories include intrinsic (i.e., arising from
within the body), extrinsic (secondary to environmental conditions or
various pathologic conditions), and disturbances of circadian rhythm.
Insomnia:
Insomnia may be primary or it may be comorbid with or secondary to
another disorder such as a mood disorder (i.e., emotional stress,
anxiety, depression) or underlying health condition (i.e., asthma, diabetes, heart disease, pregnancy or neurological conditions).
Primary hypersomnia. Hypersomnia of central or brain origin.
Narcolepsy: A chronic neurological disorder (or dyssomnia), which is caused by the brain's inability to control sleep and wakefulness.
Idiopathic hypersomnia:
a chronic neurological disease similar to narcolepsy in which there is
an increased amount of fatigue and sleep during the day. Patients who
suffer from idiopathic hypersomnia cannot obtain a healthy amount of
sleep for a regular day of activities. This hinders the patients'
ability to perform well, and patients have to deal with this for the
rest of their lives.
Parasomnias
– A category of sleep disorders that involve abnormal and unnatural
movements, behaviors, emotions, perceptions, and dreams in connection
with sleep.
Sleep terror
(or Pavor nocturnus)- Characterized by a sudden arousal from deep
sleep with a scream or cry, accompanied by some behavioral
manifestations of intense fear.
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.
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.
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.
"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.
Lifestyle 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:
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.
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.
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.
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.
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.
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.
