Sleep Flashcards
(108 cards)
1
Q
Sleep is a reversible behavioral state of perceptual disengagement from, and unresponsiveness to, the environment
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In addition to the wake state, we divide sleep into stages, including 3 stages of NonREM sleep and REM sleep. The staging of sleep is based on measurements of the electroencephalogram (EEG), electro-oculogram (EOG) and chin electromyogram (EMG)
2
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This picture represents some of the changes in the EEG waves across the different stages of sleep. The deeper stages of NonREM sleep are associated with slowing frequency and increased amplitude of the EEG waves.
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3
Q
What pattern is this?
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This is an example of wakefulness. The length of this epoch is 30 seconds.
On the left are the channel labels: E’s are for the eye movement channels (EOG), the F, C, and O channels are the frontal, central, and occipital EEG channels respectively. The EOG and EEG channels are referenced to the opposite Mastoid process. The even numbers are for the right side, and odd numbers are on the left side of the head. The bottom channel is the chin EMG. The epoch of wake shows an individual with his/her eyes closed. The frequency of the EEG is generally in the alpha range (8-12 Hz), and the chin EMG tone is high.
4
Q
What sleep stage is this?
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In the lightest stage of sleep, N1, there are some subtle slow eye movements. The EEG frequency has slowed and the chin tone remains high
5
Q
In N2 sleep, the chin tone has lessened somewhat. There are larger amplitude slow waves seen as well, called K-complexes.
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In N3 sleep, also known as slow-wave sleep, or “deep sleep” the majority of the 30 second epoch is occupied by the larger amplitude slow waves.
6
Q
Rapid Eye Movement Sleep, also known as REM or stage R, is characterized by low voltage, mixed frequency EEG waves, very low chin muscle tone, and the defining feature of the rapid movements of the eyes. As identified in the picture, the eye movement waves can also be picked up by the EEG leads, especially the frontal leads (F4 and F3)
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This picture summarizes the EEG characteristics across the stages of wake and sleep.
During eyes open wakefulness, there are low voltage, mixed frequencies.
7
Q
With awake eyes closed, the majority of people demonstrate:
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a posterior dominant rhythm in the alpha range of 8 – 12 Hz.
8
Q
What are the main EEG findings of N1-N3?
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In N1 sleep, the EEG slows into the theta range (4-7 Hz).
With N2 come the appearance of sleep spindles (brief bursts of 12-14 Hz) and K complexes.
N3 is characterized by delta frequency, high amplitude slow waves.
9
Q
In R, the EEG returns to a low-voltage mixed frequency, and may include what are known as:
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saw tooth waves.
10
Q
Here we see more examples of the characteristic wave forms, including slow waves, sleep spindles, and K complexes
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11
Q
This table summarizes the stages of sleep, including EEG, EOG, and EMG changes.
As also demonstrated in the next slide, the sleep architecture is made up of sleep cycles – N1 lasting about 5-10 minutes, N2 about 20 minutes, 30-45 minutes of N3, followed by R.
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The entire sleep cycle is about 70-100 minutes. The duration of each stage varies across the different sleep cycles over the course of the sleep period.
12
Q
Overall, sleep is composed of approximately 5% N1, 50% N2 (erroneously switched in the table), 20% N3, and 25% R.
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Our ease of waking up from sleep, or the arousal threshold, varies according to our stage of sleep. It is easiest to wake from “light sleep” or N1, the most difficult to wake from N3, with N2 and R in between.
13
Q
What is a Hypnogram?
A
A graphic representation of a total sleep period, with the X axis representing time, and the Y axis representing the different stages of sleep.
We can see the length of each cycle of sleep is not constant, with variable duration of each episode of the different sleep stages.
14
Q
The bulk of the slow wave sleep (N3 or in this graph stages 3 and 4 using the old nomenclature) occurs in the first third of the night; with the bulk of the R sleep occurring in the final third of the night.
And notice that there are several brief awakenings over the course of the night, which is normal. An excess of wake after sleep onset (WASO), however, is abnormal
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15
Q
In addition to the approximately 90 minute sleep cycle rhythm and 7-9 hour rhythm demonstrated by the hypnogram, humans and all animals also have a circadian rhythm which helps determine WHEN we have our sleep periods.
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16
Q
The circadian rhythm is hypothesized as a two-process model:
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the homeostatic sleep drive (Process S) increases with continued wakefulness, and the circadian alerting signal governed primarily by light signals (Process C) falls overnight with darkness.
17
Q
There are several influences or “zeitgegers” (German for “time giver”) on the circadian rhythm. What are they?
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The most powerful is light.
But physical activity, when we eat, and even our emotions are cues that affect our circadian rhythms. What kind of effect they have on the rhythm is determined by where they act on the phase response curve, as will be shown shortly.
18
Q
The existence of these zeitgebers is necessary because the human circadian rhythm is on average about 24.2 hours (with some having shorter or longer rhythms), so the environmental cues are required to maintain synchronization of the earth’s clock with our bodies’ clocks.
These rhythms not only affect our sleep schedule, but have a variety of effects on our physiology and homeostasis, including the insulin/glucagon balance, thyroid function, the hypothalamic pituitary adrenal (HPA) axis, and many others.
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19
Q
This picture demonstrates the balance between the alerting Process C and the building homeostatic need for sleep (Process S). The tipping point occurs generally after 16 hours of wakefulness and decreasing influence of light, around 10pm for most individuals. The act of sleep reduces the need for sleep (Process S declines) and with increased time in darkness, Process C continues to wane.
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21
Q
How is Light perceived and processed?
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Perceived in the retina by specialized cells called retinal ganglion cells (RGC), and this signal is sent across the retino hypothalamic tract to the suprachiasmic nucleus (SCN).
“Lights on” signals suppress release of melatonin from the pineal gland, and absence of signal from the retinal ganglion cells across the retino-hypothalamic tract to the suprachiasmatic nucleus permits the release of melatonin.
22
Q
The Phase Response Curve, which is unique for each zeitgeber, is a representation of the type of influence each cue will have on the circadian rhythm.
In general, light “pushes” or delays the circadian rhythm, and melatonin “pulls” or advances the circadian rhythm.
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But one can see that melatonin given “too late” in the middle of the sleep period can actually delay the sleep rhythm, and light given “too early” in the very early morning hours can advance the sleep rhythm. So watching television (too much light exposure) in the middle of the night if one cannot sleep, or taking OTC melatonin sleep aid when one wakes in the middle of the night can significantly negatively affect one’s sleep rhythm.
23
Q
These graphs demonstrate two major changes over the course of the day – the core body temperature nadir, and the dim light melatonin onset (DLMO). Our body temperature swings by nearly one degree over the course of the day, with the most rapid drop in body temperature occurring around sleep onset. This correlates with the sharpest rise in melatonin as the lights are turned off, known as the dim light melatonin onset
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24
Q
The next several slides demonstrate some of the changes in human sleep architecture as we age. In general, humans’ need for sleep decreases with age.
The largest decrease comes as a drop in the percentage of slow wave sleep. The largest increase is in the amount of time spent awake after initially falling asleep, known as wake after sleep onset, or WASO
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Infants go through the most rapid changes in sleep, spending only about 1/3 of the day awake, and nearly equal portions of REM and NONREM sleep compared to adults.
Premature babies spend a large percentage of time in R sleep, also known as active sleep. The drop in REM sleep time over the first year of life is largely accounted for by increased time awake, with slight increase in the overall amount of NonREM sleep.
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With prematurity, the EEG waves are predominantly asynchronous, which gradually become more synchronized with age. Furthermore, there are certain EEG patterns, such as delta brushes, that are only seen in prematurity; with the defining EEG patterns of sleep such as K complexes and sleep spindles emerging only after the first few months of life.
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Even a baby’s circadian rhythm is undeveloped at birth.
This actigraphy plot presents the averaged activity level of many infants over the first year-and-a-half of life.
The Y axis represents time, with birth at the top and age 500 days at the bottom. The X axis is a 24 hour day. **The black lines represent activity, with the white gaps indicating sleep and rest periods.** One can see chaos initially, with a primary sleep period only beginning to emerge around 3 months with several short nap periods, later the emergence of 3 and then 2 major activity periods during daytime separated by naps
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The overall sleep duration per 24 hours decreases as we age, with infants requiring 12-16 hours total (overnight sleep plus naps) and school age children requiring about 10-12 hours with no napping.
During adolescence the trend continues, but with the majority of teenagers still requiring 8-10 hours of sleep.
Achieving these sleep needs is often directly challenged by school hours, extracurricular activities, and adolescent dispositions, leading to significant negative impacts of academic performance, driving safety, and behavioral problems
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We will now talk briefly about the anatomy and neurochemistry of sleep and wakefulness. The primary anatomical players are:
the ascending arousal system, also known as the reticular activating system; the hypothalamus, and the pineal gland as previously described in its role of releasing melatonin
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This slide demonstrates the various anatomic locations involved in promoting either wakefulness or sleep. What does the suprachiasmatic nucleus do?
under the influence of light, inhibits the release of melatonin by the pineal gland.
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What does the locus coeruleus and dorsal raphe nuclei (as components of the ascending arousal system) do?
produce wakefulness promoting mono-aminergic neurotransmitters norepinephrine and serotonin, respectively.
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What does the tubomamillary nucleus do?
produces histamine, another wake-promoting neurotransmitter (it’s blockage with “anti-histamine” medications such as diphenhydramine produces drowsiness).
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What is orexin made?
Orexin (also known has hypocretin) is produced in the lateral hypothalamus; orexin acts as a stabilizing force for wakefulness.
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In addition to melatonin release from the pineal gland, the main site of sleep promotion is where?
**the preoptic area of the hypothalamus**.
Here, cells in the ventrolateral preoptic nucleus and medial preoptic nucleus release inhibitory neurotransmitters GABA and Galanin, including to the cerebral cortex.
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Sleep spindles are generated in the thalamus. Inhibition of spinal motor neurons by glycine leads to sleep-related paralysis in REM sleep, so that we don’t “act out” our dreams.
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This table summarizes some of the neurochemistry of sleep and wakefulness, including the actions of and locations of norepinephrine, dopamine, acetyl choline, histamine, glutamate, and orexin/hypocretin.
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This picture summarizes some of the interactions required to generate the different stages of wake and sleep.
Wakefulness results from the action ascending arousal system/reticular activating system with serotonin, norepinephrine, and acetylcholine.
With NonREM sleep, the action of the monoaminergic neurotransmitters significantly diminishes, and the “REM-off” actions of the locus coeruleus and dorsal raphe nuclei act to inhibit the cholinergic action of the pedunculopontine nucleus and lateral dorsal tegmentum.
During REM sleep, the cholinergic “REM-on” cells inhibit the release of serotonin and norepinephrine, in addition to triggering the release of spinal glycine, which leads to the low muscle tone and paralysis during REM sleep.
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This switch between wake and sleep, and the action of the ascending arousal system and monoamines vs the inhibitory signals of GABA is best represented by a see-saw model. The primary regulator of this balance, helping to tip it one direction or another, is orexin (also known as hypocretin).
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These pictures summarize the action of the various systems involved in wake and sleep.
In part A on the left, the locus coeruleus, dorsal raphe nucleus, tubomamillary nucleus, and cholinergic pedunculopontine and lateral dorsal tegmentum send their arousing signals ascending to the cerebral cortex, with inhibition of the pre-optic areas of the hypothalamus.
In part B on the right, we see activation (actually disinhibition) of the pineal gland, and the inhibition of the ascending arousal system by GABA and galanin released from the ventral lateral preoptic and dorsal medial preoptic nuclei of the hypothalamus
40
In addition to a good history and physical, sleep physicians utilize a specialized set of tools to assess patients’ sleep. This includes a number of questionnaires, the sleep log, and a number of objective sleep studies.
The most heavily utilized sleep questionnaire is the Epworth Sleepiness Scale. Patients rate on a scale of 0 – 3 the likelihood of dozing or accidentally falling asleep across 8 different scenarios. Scores higher than 10 (out of a possible 24) indicate pathologic sleepiness.
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The Berlin Questionnaire is a validated screening assessment for obstructive sleep apnea. Question topics include the volume and frequency of snoring, sleepiness upon waking and during the day, and a history of obesity, hypertension, or treatment of hypertension.
The STOP-BANG questionnaire is a frequently used screen for sleep apnea; it was validated as a tool to predict difficult extubations by anesthesiologists following surgery. “Positive” screen increases the likelihood of post-surgery airway complications and correlates well with the presence of obstructive sleep apnea.
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The Morningness-Eveningness Questionnaire assesses a patient’s likelihood of advanced (morningness) or delayed (eveningness) sleep-wake circadian rhythm disorders.
The Insomnia Severity Index is a good way to track subjective response to insomnia treatment
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The Restless Legs Syndrome Severity Scale helps to qualify RLS symptoms as Mild Moderate Severe or Very Severe
A Sleep Log or Sleep Diary is a patient’s recording of their bedtimes, estimated times of falling asleep, wake after sleep time, and wake up time.
Additionally, daytime activities such as caffeine and alcohol consumption, exercise, and medication use are also tracked. The information from a sleep log is often paired with other objective sleep studies.
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What is actigraphy?
Actigraphy is the objective recording of a patient’s activity and rest. Watch-like devices are equipped with multi-plane gyroscopes and light sensors. Using several computer algorithms, actigraphy can accurately measure wake and sleep times, including wake after sleep onset, leg movements of sleep, and other measures such as calories burned and pedometry.
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An actogram plot demonstrates 24 or 48 hours across the X axis, activity level and light level (lux) on the Y axis, with each line representing one day. The dark bars represent activity, and on the second plot, the yellow lines represent light exposure. The first plot is normal, with fairly consistent wake and sleep times. The second plot demonstrates a tendency toward circadian delay over the weekend, followed by sleep restriction
The most widely utilized sleep study is polysomnography (measuring many elements of sleep) also known as PSG. **As discussed earlier, the main channels required to stage sleep are EEG, EOG, and chin EMG**. Polysomnography also records EKG and pulse, oximetry, respiratory airflow using thermal and/or pressure sensors, respiratory effort from thoracic and abdominal belts, lower limb EMG, body position, and snoring by microphone.
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The EEG channels in polysomnography include at least a frontal, central, and occipital lead referenced to the opposite mastoid process. In this example, leads are on the left side of the scalp referenced to right mastoid. Leads are actually placed on both side of scalp, in case back-up in the event of signal failure or artifact.
This page demonstrates a typical split view of a polysomnogram. The top half is used for sleep staging, using a 30 second epoch. The bottom half, with the EKG, oximetry, limb EMG, and respiratory measures is using a broader, 5 minute epoch.
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This page demonstrates an example of an abnormal PSG along with small window of the video feed from the patient’s room. One can appreciate the fluctuations in the oximetry, correlating with variation in airflow and respiratory effort.
This diagram is a hypnogram for a PSG – notice the sleep staging hypnogram at the top which we’ve previously seen examples of. The full PSG hypnogram also includes a whole night view of body position, arousals, oximetry, (end-tidal carbon dioxide levels, which is only occasionally measured), respiratory events and pulse changes.
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Due to cost and availability problems, an increasing number of patients are being evaluated with Home Sleep Testing, also known as Portable Monitoring, or Out of Center Sleep Testing.
There are a variety of devices available. Most measure respiratory flow, effort, and pulse oximetry (without EEG, EOG, or chin EMG for sleep staging). Unique devices measure arterial dilation changes (Watch-PAT), or single channel sensor for monochannel EEG, oximetry, and frontalis muscle EMG along with respiratory airflow without effort.
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Home Sleep Test recording appears very similar to PSG, just with fewer channels
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The two other main sleep studies are variations of polysomnography know as Multiple Sleep Latency Test and the Maintenance of Wakefulness Test.
Rather than recording the major sleep period, they involve repeated brief naps recorded during the day. Using only EEG, EOG, chin EMG and EKG, they are objective measures sleepiness (MSLT) and response of sleepiness to treatment (MWT).
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We will now shift our focus to an overview of the diagnoses made in sleep medicine. We will spend the most time with obstructive sleep apnea, the most common condition treated in sleep disorders centers (although insomnia overall is more prevalent in the general population). We will also discuss briefly the other major categories of sleep disorders.
While there are many classification schemes for sleep disorders, including the World Health Organization’s International Statistical Classification of Diseases and Related Health Problems (ICD, now in the 10th revision) and the Diagnostic and Statistical Manual of Mental Disorders (DSM, now in 5th edition), the American Academy of Sleep Medicine has organized the International Classification of Sleep Disorders (ICSD), now in its third edition. The manual includes diagnostic criteria, associated features, demographic and other risk factor information, complications including developmental issues, and objective sleep study and laboratory findings.
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Insomnia was previously categorized into multiple subtypes, however, there was no significant evidence to support these distinctions, and no difference in response to treatment, so these subtypes were discarded in favor of **Short-Term and Chronic Insomnia**. _The only real difference is in the duration of symptoms._ “Other” Insomnia disorder is used for cases that do not meet all the criteria for either Short-Term or Chronic.
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Chronic insomnia requires a complaint by the patient (or caregiver for pediatric and geriatric patients) of difficulty initiating or maintaining sleep (including the need for frequent intervention), with resulting daytime consequences. These may range from dissatisfaction with sleep, to sleepiness, to problems with attention, memory, mood or behavior.
As in the DSM, the disorder cannot be better accounted for by another condition, including not providing oneself with the opportunity to sleep. The cut-off for chronic insomnia from short-term insomnia is 3 months, and the insomnia symptoms must be present at least 3 nights per week of average for both.
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Chronic insomnia is quite prevalent, with about 10% of the population meeting criteria. Transient insomnia is even more common, affecting about 1/3rd of the population at any given time. Insomnia is more common in older individuals, in women, in those of a lower socioeconomic class, and those with co-morbidities. Insomnia usually has significant variability in its course.
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How is insomnia tx?
The most commonly utilized treatment for insomnia is pharmacotherapy. You will hear more about pharmacology of sleep in another talk.
There are a number of FDA-approved therapies, including the new orexin/hypocretin antagonist suvorexant (marketed as Belsomra), benzodiazepine-like receptor agonists such as zolpidem (marketed as Ambien), and the H1 antagonist effect of the tricyclic antidepressant doxepin (marketed as Silenor).
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Insomnia tx
The most commonly used medications are “off-label,” including trazodone, amitriptyline, and alprazolam. **However, the most effective treatment for insomnia in the short-term (6-12 weeks) and long term (\> 1year) is what’s known as Cognitive Behavioral Therapy for Insomnia, or CBT-i**.
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Describe CBT for insomnia (CBT-i)
It is best performed by a board-certified behavioral sleep psychologist; therefore, availability is quite limited. Alternative models using online courses are increasing in popularity.
The main components of CBT-i are: Stimulus Control, Cognitive Therapy, and Sleep Restriction. Stimulus Control aims to change the unconscious associations of the bedroom – any non-sleep activity is excluded from the bedroom, and if the patient is unable to fall asleep within 15-20 minutes, he/she exits the bedroom and does not return until feeling sleepy. Cognitive Therapy aims to correct false beliefs and destructive narratives about sleep, such as “If I don’t get 8 hours tonight, I’ll never be able to function” or “My sleep is so bad and I’ve tried everything, so it’s always gonna be this way.” Sleep restriction involves increasing the patient’s sleep efficiency – the amount of sleep spent per time spent in the bed. Patients are instructed to stay up well past their desired bedtime, maintaining a consistent wake time. With restricted sleep time and increasing Process S (sleep drive), individuals spend the majority of that restricted time in bed asleep. Then the sleep onset time can be slowly advanced every few days to the desired bedtime while maintaining improved sleep efficiency.
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What is sleep hygiene?
The basis for all healthy sleep, but vitally important in the treatment of insomnia, is what is known as sleep hygiene. These behaviors are helpful in improving sleep in everyone, but are insufficient alone in improving clinical insomnia disorders. They include maintaining good sleep/wake schedule (especially keeping the same wake-up time), maintaining a comfortable sleeping environment (including comfortable temperature and being free from excess noise, pets in the bed, etc), regular exercise and meals, avoiding afternoon or evening caffeine, and avoiding alcohol, nicotine, and sedating antihistamine medications close to desired bedtime.
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There are several sleep-related breathing disorders, including hypoventilation. The most common, however, is obstructive sleep apnea (OSA), which we will spend some time focusing on now.
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OSA is a common disorder. Prevalence rates of 2 to 4% used to be commonly discussed; however approximately 15% of the United States population is actually affected by a sleep breathing disorder. It is now known that the prevalence rate for men with an AHI greater than 5 is 24% compared to 9% for women. For an AHI greater than 15, the prevalence is 9% for men compared to 4% for women.3 If subdivided into common disorders, the prevalence for OSA in (1) systemic hypertension patients is about 30%, (2) heart failure is 38% for men and 31% for women, (3) stroke is variable although some suggested a higher prevalence that likely predated the stroke, and it has been shown that sleep apnea increases the risk of developing diabetes.7
Furthermore in a population based study in Switzerland, up to 84% of men and 61% of women had an AHI of 5 or more using AASM Scoring Criteria from 2012. An AHI of 15 or more per hour was observed in 50% of men and 23% of women. Hypopneas were defined as 30% or greater decrease in airflow accompanied by a 3% or more desaturation or cortical arousal.
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There are 3 characteristic patterns of apnea
An **obstructive apnea** is defined by the absence of airflow despite persistent ventilatory efforts, demonstrated by movement of the chest and abdomen or contraction of respiratory muscles such as the diaphragm.
A **central apnea**, in contrast, is the absence of airflow due to the lack of ventilatory effort. Since no effort is made to breathe, no airflow occurs.
A **mixed apnea** includes both central and obstructive components, usually with an initial central component followed by the obstructive component.
The clinical and pathological consequences of, and treatment for, mixed and obstructive apneas and hypopneas are the same, so we will refer to them together as OSA. Clinically significant central apneas are less common and will not be discussed further in this presentation.
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This slide shows the effect of sleep on the upper airway in an obstructive sleep apnea patient. In the figure on the left, the patient is awake and the airway is narrowed but patent. The upper airway dilator muscles are responsible for maintaining the patency of the airway despite the reduced size of the airway, which may be due to fat deposition from obesity or structural abnormalities such as retrognathia.
Note that collapse, shown on the right, may occur anywhere along the upper airway, from the retropalatal space to the hypopharynx, and often occurs in multiple places.
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This figure depicts the repetitive pathophysiologic events which occur during obstructive sleep apnea. The primary problem in the obstructive sleep apnea patient is the presence of an anatomically small pharyngeal airway. To prevent airway collapse during wakefulness, the action of the airway dilator muscles is augmented – a neuromuscular compensation for the small airway.
With sleep onset, there is a loss of the upper airway reflex which drives this neuromuscular compensation. As a result, dilator muscle activity falls, the pharynx closes and the apnea begins. During the apnea, hypoxia and hypercapnia develop, leading to increasing ventilatory effort. Once this effort reaches a threshold level, the patient arouses. Pharyngeal muscle activity is restored, and the airway opens. The patient then hyperventilates to correct the blood gas derangements, returns to sleep, and the cycle begins again.
As a result, sleep can be severely disrupted by the repetitive arousals needed to end the apneas, and episodes of cyclic hypoxia and hypercapnia occur. These events lead to the observed clinical consequences.
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As we proceed to detail the many clinical consequences of OSA, it will be helpful to recall that all of these adverse effects are the result of the two fundamental abnormalities which characterize OSA.
First, the patient has cyclical apneas and hypopneas which may be associated with arousal many times each night which leads to severe sleep fragmentation.
Second, most apneic episodes are accompanied by hypoxemia and hypercapnia, which repeatedly impacts regulation of the patient’s cardiovascular and metabolic systems.
The many ill-effects which result from these two abnormalities can be broadly grouped into two categories Symptoms and Complications. Symptoms the OSA patients experience include daytime sleepiness, insomnia and poor daytime functioning.
OSA is associated with cardiovascular and metabolic complication including heart attack, stroke and diabetes.
The end result of all of these adverse effects is a substantial increase in morbidity and mortality as well as decreased quality of life among OSA patients.
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This graphic illustrates the mechanism of cardiovascular disease from OSA. The hypoxemia, hypercapnea, arousals and pressure changes lead to oxidative stress, endothelial dysfunction, sympathetic surges and metabolic dysfunction which promote cardiac disease and arrhythmias.
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The second major category of morbidity from OSA is that caused by cardiovascular dysfunction. Systemic hypertension has been reported in up to 50% of patients with OSA. This is in part related to the common risk factor for both disorders of obesity. With apneic events, there are cyclical increases in systemic blood pressure associated with increased sympathetic tone. In some patients, the elevation in sympathetic tone persists into the daytime. Mean morning blood pressure has been shown to increase almost linearly with increasing apneic activity in both obese and non-obese patients. Cardiac arrhythmias have also been associated with OSA.
In the Sleep Heart Health Study, atrial fibrillation, non-sustained ventricular tachycardia and complex ventricular ectopy were all observed at higher rates in the subjects with OSA as compared to those without. In patients with underlying coronary artery disease, myocardial ischemia and perhaps infarction may be triggered by the hypoxemia, the reduction in heart rate, and the rise in blood pressure seen during severe apneic events. There is also evidence for increased prevalence of congestive heart failure in patients with sleep-disordered breathing. Finally, there are two large cohort studies that have found a relationship between sleep-disordered breathing and an increased incidence of stroke.
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Several reports have shown an increased mortality for patients with OSA. This slide demonstrates the worsening survival over ten years in subjects by AHI quartile. In adjusted analysis, the cohort with greater severity of OSA had a higher risk of death.
Several reports have shown an increased mortality for patients with obstructive sleep apnea. This slide shows the mortality related results from two cohorts. For the Wisconsin Cohort Study, a large (n = 1500 subjects) longitudinal cohort study, the plot on the left shows mortality with a follow-up of up to 18 years from initial sleep study. In this study, all-cause mortality, adjusted for gender, BMI and age was significantly increased (hazard ratio = 3.0). This effect was still observed after removing 126 subjects who had been treated with CPAP. In the Busselton cohort from Australia, subjects were followed for a mean of 14 years from initial sleep study. As can be seen in the plot on the right, moderate-severe OSA (AHI greater than 15) was also associated with increased mortality. The adjusted hazard ratio was 6.
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Similarly, worsening severity of sleep apnea is associated with a greater risk of cardiovascular events compared to age, BMI adjusted controls and those with OSA on treatment as demonstrated in this landmark cohort study by Marin, et al.
A recent article, summarized published data on the relationship between sleep apnea and stroke. OSA is extremely common in patients after acute stroke, although other forms of sleep disordered breathing were also seen. A review of CPAP use after stroke indicated that compliance with treatment was variable but poor
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Incident stroke also appears to be more common in subjects with sleep apnea. Sleep apnea likely increases the risk of stroke. Those with an AHI over 20 had a much higher likelihood of stroke in this cohort study by Redline.
Atrial Fibrillation is highly associated with OSA. OSA increases the risk of developing A-fib. This 15 year observational study of obese subjects found that those with OSA had a much greater likelihood of developing A-fib.
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Finally, OSA is thought to be a contributor to sudden cardiac death. Studies show an association of nocturnal cardiac death with worsening sleep apnea. Those with OSA are much more likely to die “in their sleep”. As we can see here, this figure shows the outcome of patients from the Wisconsin sleep cohort and that survival decreases as severity of obstructive sleep apnea increases.
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Other symptoms relate to daytime functioning and sleepiness include fatigue, pain syndromes, headaches, depression, family discord, and overall decreased quality of life.
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The goals of treatment for patients with OSA should be the reduction of morbidity and mortality and improvement of their quality of life. This can be accomplished by preventing the cardiovascular, metabolic and other systemic consequences of OSA and by reducing the complications of daytime sleepiness.
Quality care measures aimed at optimizing care for adult patients with OSA were published in 2015. These specifically include outcomes of improved disease detection and categorization, improved quality of life and reduction of cardiovascular risk.
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As part of the therapeutic approach to OSA, all patients should be counseled regarding their increased risk of motor vehicle crashes, job related injuries and impairment of judgment.
The treatment of OSA and existing or consequent comorbidities can include behavioral, medical or surgical interventions.
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A variety of behavioral interventions are available to modify OSA. Where appropriate, weight loss should be encouraged.
Alcohol and sedatives should be avoided as they induce instability and promote collapsibility of the upper airway during sleep. Sleep deprivation also leads to upper airway instability during sleep, increasing the likelihood of collapse. Avoiding the supine position may correct OSA in patients with position-dependent OSA as documented in a study.
Finally, smoking cessation should be encouraged since data suggests that smoking is an independent risk factor for OSA. Finally, maintaining nasal patency can decrease the risk of OSA or sleep fragmentation due to increased nasal airway resistance.
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Because of the high correlation between OSA and obesity, particularly increased upper body mass, all patients who are obese should be encouraged to lose weight. Exercise and fitness should be recommended to all patients, both to improve the OSA and to reduce cardiovascular disease risk. Weight loss can be very effective and, in some cases, even curative to OSA.
The problem that frequently occurs is that weight loss, while effective, is difficult to achieve and to maintain. There are several FDA approved medications for weight loss. There is increasing evidence that bariatric surgery may be an effective modality for weight loss and reduction in the severity of sleep-disordered breathing.120 In a meta-analysis, bariatric surgery was shown to reduce BMI by 14 and AHI by 29 compared to non surgical weight loss with reduction of BMI by 3 and AHI by 11.
In patients with significant OSA, other forms of treatment should not be delayed until proper weight loss is achieved since they may continue to experience the complications of OSA during the period of attempted weight loss. Once adequate weight loss is achieved, OSA needs to be re-evaluated via a sleep study to verify resolution of apnea before interim therapy can be discontinued.
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A number of medical interventions are available for the treatment of OSA. Positive pressure devices act as pneumatic splints to keep the airway from collapsing. These include continuous positive airway pressure systems and bi-level positive airway pressure systems. A variety of oral appliances have been developed which mechanically hold the airway open, preventing collapse.
In certain circumstances medications and/or oxygen may play a limited role in treatment.
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This slide depicts the therapeutic effect of CPAP. In the panel on the left, you can see upper airway closure in an untreated OSA patient. Note that the airway closure is diffuse, involving both the palate and the base of the tongue. In the second panel, CPAP is applied and the airway is splinted open by the positive pressure.
This slide depicts a patient sleeping while using a positive airway pressure system. These devices are highly portable, fit on a nightstand, and can easily be transported outside of the home.
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CPAP has been objectively shown to improve daytime sleepiness. Lamphere et al. measured the recovery of alertness after treatment with CPAP in OSA patients and showed that treatment with CPAP increased the latency to sleep onset, a measure of sleepiness as determined by the Multiple Sleep Latency Test (MSLT), into the normal range. This corresponds with a decrease in the propensity to fall asleep – the less sleepy one is, the longer it takes to fall asleep. The effect could be seen after one night on CPAP, and continued to improve with continued use, shown by increasing sleep latency after 14 and 42 nights on CPAP.
More recently, a study by Weaver et al, on 149 subjects intended to evaluate the number of hours of CPAP used and its effects on sleepiness (as assessed by Epworth Sleepiness Scale, ESS) and daily functioning (as assessed by Functional Outcomes of Sleep Questionnaire, FOSQ). 41% of subjects normalized sleepiness with CPAP average use of one to two hours per night compared to 92% at greater than 7 hours per night use. As shown in the graph, objective evaluation of sleepiness showed similar results with improvements in sleep latency on MSLT evaluation for those with increased time per night of CPAP therapy. Quality of life also improved.
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A variety of problems may be encountered when patients are treated with positive airway pressure therapy.
The most common complaints are related to discomfort with the mask: the mask is too tight, it hurts the bridge of the nose, it leaves marks, or air leaks.
Nasal problems account for the highest rate of adverse effects: obstruction from nasal congestion, rhinorrhea, or dry nose and throat. Approximately 10% of patients will experience claustrophobia with a nasal mask. Some patients complain of air in the stomach or of chest discomfort. There is also a subset of patients who discontinue therapy because they find the use of a positive pressure system via nasal interface to be inconvenient.
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Subjective patient adherence to nasal CPAP therapy has been quite favorable, with reports of 75% or greater long-term compliance. However, objective measures of compliance have been less encouraging. Studies indicate that many patients do not accept CPAP and initiate therapy. In addition, approximately 25% of patients do not regularly follow with their sleep physician and 75% of these patients are non-adherent.
Only about half the patients are regular CPAP users, defined by use of their CPAP for four or more hours at least five nights a week.Looking at multiple articles regarding CPAP use by this same definition, Weaver and Grunstein reported a range from 29 to 83% to be nonadherent.
Compliance with positive pressure therapy is similar to compliance with other types of chronic medical therapy, such as use of asthma medication, which has found by Dekker et al to be about 30%. In the largest study to date on long-term adherence (Mc Ardle et al, American Journal of Respiratory and Critical Care Medicine, 1999), 68% of 1,103 patients who took CPAP home were still using CPAP at five years.
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A non-PAP option for snoring and OSA are oral appliances (OA). These devices are designed on the general principle that advancing the mandible or tongue during sleep will allow for unobstructed breathing. There are several types of oral appliances available for the treatment of OSA. In this slide a mandibular repositioning device is shown. The OA causes the mandible to move forward and the bite to open slightly. Devices typically advance the mandible 6-10 mm, or from 50 to 75% of the maximum that patients can protrude the mandible on request. There are many styles available but comparisons between devices are limited and thus there is no preferred design or technique. The effect of this mandibular repositioning is to enlarge the airway and/or reduce airway collapsibility, thereby decrease airway resistance.
Less commonly used are tongue retaining devices, appliances that hold the tongue in a forward position via insertion of the tongue into a suction bulb at the front of the device. Tongue retaining devices do not advance the mandible.
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Patients report using an OA a median of 77% of nights at one year. Adherence rates tend to decrease over time due to side effects and lack of efficacy.
The frequency of OA side effects varies. Adverse events can be minor and temporary or moderate to severe and continuous. They include TMJ pain or sounds, myofascial pain, tooth pain, salivation, dry mouth, gum irritation, gagging, and morning-after occlusal changes. Minor tooth movement and small changes in occlusion develop in some patients but the long term dental significance is unclear.
Early and frequent dental follow-up is important to assess for adherence, response, and side effects. Once optimal OA fit is obtained, patients with OSA should have a polysomnogram or attended cardiorespiratory (Type 3) sleep study to assess oral appliance efficacy. Continued follow-up with the dental specialist is advised every six months for the first year, and at least annually thereafter to monitor patient adherence, evaluate for OA deterioration or maladjustment, check oral health and occlusion, and assess for worsening OSA.
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Supplemental oxygen is not a first-line therapy for OSA but may be useful in patients who will not accept more definitive therapy and have severe nocturnal desaturation. Because collapse of the airway continues to occur, use of oxygen alone does not prevent the fragmentation of sleep caused by the recurrent OSA events. As a result, there is no improvement in the symptoms of daytime sleepiness.
Oxygen therapy may prolong apnea duration by increasing oxygen stores prior to the apnea, thus delaying one of the signals of arousal. The depth of oxyhemoglobin desaturation during the apneic events, however, may be decreased. The use of oxygen may reduce the frequency of dysrhythmias in patients who have dysrhythmias that are related to hypoxemia but should be used with caution in patients with obstructive lung disease and CO2 retention. Oxygen may be indicated as additional therapy after optimal CPAP is determined and the patient still has significant oxygen desaturation during sleep.
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Uvulopalatopharyngoplasty (UPPP) has been the most common upper airway surgery performed on patients with OSA. This slide depicts the UPPP surgical technique. The panel on the left depicts the preoperative upper airway, demonstrating a long soft palate and the presence of palatine tonsils. The incision site is marked with the dotted line. The panel on the right depicts the postoperative oropharynx, with amputation of the uvula, bilateral palatine tonsillectomy, and trimming and suturing together of the anterior and posterior tonsillar pillars.
Persistent side-effects after UPPP include difficulty swallowing, globus sensation, voice changes, and taste disturbance. A recent report showed complications in 1.5% of patients
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The AASM convened a task force in 2007 to systematically review the available literature to provide a basis for updated standards of practice recommendations on surgical modifications of the upper airway for treatment of OSA. The task force report and accompanying standards of practice paper were published in 2010.
This slide depicts the task force’s review of the UPPP literature.Fifteen papers describing outcomes following UPPP were included. The group had a mean age of 44 years and was comprised of 91.9% males. The average body mass index, where reported, was 29kg per m2. The apnea-hypopnea index (AHI) at baseline averaged 40.3/hour of sleep. Follow-up sleep studies (some attended, in-lab multi-channel, others portable polygraphy) occurred anywhere from 3 months to one year later.
To describe the effects of surgery on AHI, the AASM task force used a relative measure of effect, the ratio of means (ROM), which describes the extent to which the mean postoperative AHI was changed compared to the mean preoperative AHI. The ROMs from each study were pooled across studies – rendering a pooled ROM and its associated 95% confidence interval (CI) -- using the inverse variance method for random effects meta-analysis. To interpret this measure, one must subtract the ratio of mean from 1 and multiply the result times 100 to obtain the percentage change in AHI with surgery, a procedure akin to the estimation of relative risk reduction from measures of relative risk. In the case of UPPP, there was an overall reduction in AHI of 33% (95 CI 23-42%). Post-operative residual AHI remained elevated, averaging 29.8events per hour. If UPPP is utilized as a treatment option, a follow-up sleep study should be performed to assess the impact on OSA.
The AASM Standards of Practice Committee concluded on UPPP that as a single surgical procedure, with or without tonsillectomy, UPPP does not reliably normalize the AHI when treating moderate to severe OSA, and therefore patients with severe OSA should initially be offered positive airway pressure therapy, while those with moderate OSA should initially be offered either PAP therapy or oral appliances.153
Whether standardized clinical measures or imaging studies will improve patient selection for UPPP is not clear. Also, the extent of the impact of UPPP on the cardiovascular and systemic sequelae of OSA remains under explored.
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This slide demonstrates Idiopathic Central Sleep Apnea. The EEG tracing shows that the patient is actually awake, but the respiratory data on the bottom half shows clear absence of airflow or respiratory effort. This irregularity of respirations can also be seen with narcotic-induced central apnea in chronic opioid users.
This PSG tracing shows central apneas during sleep. There is a repeating pattern of 2-3 breaths, followed by central apnea resulting in desaturation.
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With mixed apnea, there is an absence of airflow (bottom tracing). Initially, there is absence of respiratory effort, but as the apnea continues, effort gradually increases
With Cheyne-Stokes respirations, there is a pattern of waxing and waning effort and airflow. This pattern can be seen in conditions such as congestive heart failure and stroke
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The bottom half of this PSG tracing is a 10-minute epoch, definitively showing the waxing-waning pattern of Cheyne-Stokes Respirations.
Although often seen in the context of obstructive sleep apnea, with hypoventilation, there are no discrete decreases in airflow as seen with apneas. Rather, the amplitude of respirations is slightly low, leading to elevations in carbon dioxide and slow decline in oxygen levels. When the patient takes normal healthy breaths about half-way through the 5 minute epoch, respiration amplitude shortly normalizes, oxygen returns to normal, and CO2 levels decline before the pattern repeats (decreased respiration amplitude and decrease in O2).
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Let’s move on to some of the Hypersomnias of Central Origin. The most common is narcolepsy now categorized as type 1 (with cataplexy or low CSF hypocretin/orexin) or type 2 (without cataplexy or normal CSF hypocretin/orexin). Other hypersomnia disorders including Idiopathic hypersomnia (somewhat similar to narcolepsy type 2), recurrent hypersomnia also known as Klein Levin Syndrome, and secondary causes of hypersomnia, related to acquired damage to the sleep/wake anatomy.
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Narcolepsy is classically defined by a tetrad of symptoms, including excessive daytime sleepiness, hypnagogic or hypnopompic hallucinations, sleep paralysis, and interrupted sleep, with or without cataplexy.
Narcolepsy type 1 is a disorder primarily characterized by excessive daytime sleepiness and signs of REM-sleep dissociation, the most specific of which is cataplexy. It is now firmly established that narcolepsy type 1 is caused by a deficiency of hypothalamic hypocretin (orexin) signaling. Patients with low or undetectable concentrations of hypocretin-1 in the CSF compose a specific disease population with a single etiology and relatively homogeneous clinical and polysomographic features. Patients with sleepiness and low or absent CSF hypocretin-1 levels are classified as having narcolepsy type 1 even if they do not manifest cataplexy.
Excessive daytime sleepiness is the cardinal symptom, and often the most disabling. Patients experience repeated daily episodes of irrepressible need to sleep or lapses into sleep. Most patients awaken refreshed after a sleep episode, but begin to feel sleepy again at variable times. Sleepiness is most likely to occur in monotonous situations that require no active participation, such as watching television or riding in a car. Sleepiness generally has a serious impact on the ability of the patient to function in educational, social, and occupational situations.
Hypnagogic hallucinations are defined as vivid dreamlike experiences occurring at the transition of wake to sleep. They typically have a holistic character combining visual, auditory and tactile phenomena. Hypnopompic hallucinations are similar, but occur at sleep to wake transitions.
Sleep paralysis describes the disturbing temporary inability to move voluntary muscles at sleep-wake transitions. Patients are awake and conscious, but unable to move limbs or open eye lids. It may last several minutes and can be very distressing
Diagnosis of narcolepsy type 1 requires sleepiness plus low CSF hypocretin, or sleepiness plus cataplexy and certain sleep study criteria (namely, average sleep onset latency of under 8 minutes with at least 2 episodes of Sleep Onset Rapid Eye Movement Periods or SOREMPs on a Multiple Sleep Latency Test. Narcolepsy Type 2 requires the sleepiness and MSLT findings, but without a history of cataplexy and normal CSF hypocretin if measured.
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Cataplexy involves the brief loss of muscle tone without any effect on the level of consciousness. This represents the normal REM-sleep related muscle atonia Intruding into wakefulness. It is often triggered by strong emotions, most commonly laughter. If examined during a cataplectic episode, a patient will demonstrate loss of deep tendon reflexes.
Narcolepsy is a relatively rare condition compared to OSA or insomnia. There is a higher prevalence among those with specific HLA subtypes. And while nearly all patients with narcolepsy type 1 are HLA DQB1\*0602 positive, about 38% of Caucasians and 12% of Asians are, so it is not a useful screening test.
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The cardinal symptom of narcolepsy is sleepiness, appearing typically in the 2nd decade. In narcolepsy type 1, cataplexy usually emerges about 1 year after start of excessive sleepiness.
The pathophysiology of narcolepsy type 1 is the selective loss of hypocretin/orexin-producing cells of the hypothalamus. While there is some evidence of an autoimmune mechanism, conclusive evidence is still lacking
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The treatment of narcolepsy is aimed at both consolidating overnight sleep and improving daytime alertness. This is accomplished with a combination of good sleep hygiene habits, strategic daytime napping (usually less than 20 minutes), and alertness promoting medications. First line are modafinil (marketed as Provigil) and its R-enantiomer armodafinil (marketed as Nuvigil) which act on dopamine transporter, but the exact mechanism of action is unclear. Now second line are the traditional stimulants, including amphetamine salts (such as Adderall) and methylphenidate (marketed as Ritalin, Focalin).
Treatment of cataplexy was previously limited to poorly effective off-label use of tricyclic antidepressants and SSRIs. Now available is the only FDA-approved treatment for both cataplexy and the excessive daytime sleepiness – sodium oxybate (marketed as Xyrem). It is the salt of gamma hydroxybutyrate (GHB, a date rape drug) and is one of the most highly controlled medications on the market with a single central pharmacy.
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There are a number of Sleep-related Movement Disorders. The most well-known is Restless Legs Syndrome, also known as Willis-Ekbom Syndrome. RLS is better categorized as a “going to sleep” disorder, as by definition, it occurs during wakefulness at rest and when attempting to go to sleep. Its correlate during sleep is Periodic Limb Movement Disorder. While limb movements during sleep are relatively common, PLMD is rare. Rhythmic Movement Disorder includes head-banging and body rocking behaviors commonly seen in young children. Bruxism is also known as teeth-grinding or jaw clenching during sleep.
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RLS is a sensorimotor disorder characterized by a complaint of a strong, nearly irresistible urge to move the limbs. This urge to move is often but not always accompanied by other uncomfortable sensations felt deep inside the limbs or by a feeling that is simply difficult or impossible to describe. Although the legs are most prominently affected, “restless legs” is a misnomer, in that 21% - 57% of individuals with RLS describe some arm sensations. The most common descriptors used by adult patients are “restless” “uncomfortable” “twitchy” “need to stretch” “urge to move” “legs want to move on their own” “heebee jeebees”
About half express RLS symptoms as painful. “Numb” and “cold” are very uncommon descriptors
RLS is relatively common, affecting 5-10% of Western populations, but only about one-half to 1% in Asian populations. Risk factors include a family history and female sex. Symptoms may be precipitated by a number of factors, including iron deficiency, medications (especially SSRIs, but also antihistamines and several others), pregnancy, and renal failure to name a few.
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Treatment of RLS starts with avoidance of triggers if known (such as medications). If an underlying condition is discovered, such as iron deficiency, treatment should be aimed at correcting that first. Conservative treatment measures include massage therapy and warm baths.
First line medical therapy are now the alpha-2-delta calcium channel antagonists gabapentin, enacarbil, and pregabalin. Previous first line therapies included dopaminergic medications, including carbidopa/levodopa and the dopamine agonists pramipexole and ropinirole. However, these relatively short-acting medications when used most nights of the week can frequently cause augmentation – the worsening of RLS symptoms including increased severity, increased body areas affected by symptoms, and symptoms occurring earlier in the day. There is a single FDA-approved device for the treatment of RLS, which is essentially a leg massager called Relaxis.
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Circadian Rhythm Disorders are symptomatic misalignment between extrinsic or desired sleep/wake rhythm and intrinsic sleep/wake rhythm. These include shifts to earlier or later schedules (Advanced and Delayed Sleep Wake Disorders, respectively), Non-24 hour rhythms, typically seen in individuals who lack zeitgebers (usually blind individuals or severely disabled), irregular rhythm, and other disorders including Shift Work and Jet Lag.
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Advanced Sleep Wake Phase Disorder (ASWPD) is characterized by a stable advance (earlier timing) of the major sleep episode, such that habitual sleep onset and offset occur typically 2 or more hours prior to required or desired times. Affected individuals complain of early morning or maintenance insomnia and excessive evening sleepiness. When affected individuals are allowed to maintain an advanced schedule, sleep quality and quantity are improved.
This slide shows what’s known as a double raster plot of actigraphy data – the X axis is actually 48 hours, with the right-sided day also represented on the left plot immediately below. This patient’s data shows a consistent sleep onset time of about 8pm with a wake time about 4:30am.
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Delayed Sleep-Wake Phase Disorder (DSWPD) is characterized by habitual sleep-wake timing that is delayed, usually more than 2 hour, relative to conventional or socially acceptable timing. Affected individuals complain of difficulty falling asleep at a socially acceptable time, as required to obtain sufficient sleep duration on a school or work night. Once sleep onset occurs, it is reportedly of normal duration. These individuals also experience difficulty arising at a socially acceptable wake time, as required to prepare for school or work. When allowed to follow his or her preferred schedule, the patients timing of sleep is delayed.
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Non 24 Hour Sleep Wake Rhythm Disorder (N24SWD) is characterized by symptoms of insomnia or excessive sleepiness that occur because the intrinsic circadian pacemaker is not entrained to a 24-hour light/dark cycle. The non 24 hour period can be short, or more typically longer than 24 hours. Because the endogenous circadian rhythm is not aligned to the external 24 hour environment, symptoms will depend on when an individual tries to sleep in relation to the circadian rhythm of sleep wake propensity. Individuals typically present with episodes of difficulty falling asleep or staying asleep, excessive sleepiness, or both, alternating with short asymptomatic periods.
The severity of individual sleep-wake symptoms can be variable. Starting with the asymptomatic period when the individuals endogenous rhythm is aligned to the external environment and required sleep wake times, sleep latency will gradually increase and the individual will complain of sleep onset insomnia. As the sleep phase continues to drift so that maximal endogenous sleep propensity is now in the daytime, individuals will have trouble staying awake during the day
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Here again is the diagram we saw earlier demonstrating the pathway of light hitting the retinal ganglion cells, with the signal passing along the retino-hypothalamic tract to the suprachiasmatic nucleus. From there, signals pass to other nuclei in the hypothalamus as well as inhibiting the release of melatonin from the pineal gland. One can see how a patient with anterior (non-cortical) blindness may not be able to suppress melatonin release from the pineal gland if the suprachiasmatic nucleus is not receiving any light data from the retina. Without this important zeitgeber, the body would run only on its intrinsic circadian rhythm, which is on average about 24.2 hours (not 24 hours).
This double-raster plot of actigraphy data demonstrates this slowly advancing rhythm due to a slightly longer intrinsic day. This individual has an intrinsic rhythm closer to 25 hours, causing the rapid cycling. One can see how frustrating the mismatch can be, with alternating hypersomnia and insomnia with only a few days at a time when extrinsic and intrinsic rhythms align appropriately.
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Shift Work Disorder is characterized by complaints of insomnia or excessive sleepiness that occur in association with work hours that occur, at least in part, during the usual sleep episode. There are several types of shift-work schedules, including evening shifts, night shifts, early morning shifts, rotating shifts, split shifts, on-call overnight duty, and long duration work shifts that include work hours at night.
The sleep disturbance is most commonly reported in association with night shifts, early morning shifts and rotating shifts. Total sleep time is typically curtained by one to four hours, and sleep quality is perceived as unsatisfactory. In addition to impairment of performance at work, reduced alertness may also be associated with consequences for safety during the work schedule and on the commute to and from work. The sleep disorder occurs despite attempts to optimize environmental conditions for sleep. The condition usually persists only for the duration of the shift work schedule.
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Irregular Sleep-Wake Rhythm Disorder (ISWRD) is characterized by a lack of a clearly defined circadian rhythm of sleep and wake. The chronic or recurring sleep-wake pattern is temporally disorganized so that sleep and wake episodes are variable throughout the 24 hour cycle. Individuals have symptoms of insomnia and excessive sleepiness, depending on the time of day and their particular sleep-wake pattern. It is most commonly seen in institutionalized individuals, especially those with neurodegenerative disorders such as dementia, and in children with severe developmental disorders.
This double raster plot of actigraphy data shows that there is no consistent major sleep or wake period and no discernible pattern.
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Treatment of Circadian Rhythm Disorders is aimed at re-aligning the patient’s internal clock with the environment. This is accomplished primarily with light and melatonin. Chronotherapy is a method used primarily for Delayed Sleep Wake Phase Disorder in which the major sleep period is progressively delayed by 15-60 minutes every day until the desired sleep-onset time is reached. This causes obvious disruption of school or work schedules, and has not been shown to be as helpful as light therapy and melatonin.
As described earlier, in general melatonin pulls and light pushes the circadian rhythm, though this depends on when treatment is given based on the phase response curve again shown here. For ASWPD, evening light, and/or early morning melatonin help push forward the major sleep period to the desired time. For DSWPD, evening melatonin and midmorning light therapy help pull the circadian rhythm earlier. There are commercially available light boxes and glasses for light therapy. The exact lux and duration of light therapy varies considerably across studies, but in general is at least several thousand lux for about 30 minutes.
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. Parasomnias are undesirable physical events or experiences that occur during entry into sleep, within sleep, or during arousal from sleep. They may occur during REM, NREM, or during transitions to and from sleep. They compass abnormal sleep-related complex movements, behaviors, emotions, perceptions, dreams, and autonomic nervous system activity. Parasomnias are clinical disorders because of the resulting injuries, sleep disruption, adverse health effects and untoward psychosocial effects. The consequences of the parasomnias can affect the patient, bed partner or both. As the sleep-wake cycle oscillates, the normally distinct states of consciousness (wake, NREM, and REM) may be rendered into a state that is not fully declared, resulting in temporary unstable state of dissociation. Parasomnias are the results of such dissociation.
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REM Sleep Behavior Disorder (RBD) is characterized by abnormal behaviors emerging during REM sleep that may cause injury or sleep disruption. RBD is also associated with EMG abnormalities during REM; the EMG demonstrates an excess of muscle tone or phasic activity during REM. Recall that EMG muscle tone is lower in REM sleep than during any other state including NREM or wakefulness.
A complaint of sleep-related injury is common with RBD, which usually manifests as an attempted enactment of unpleasant, action-filled and violent dreams in which the individual is being confronted, attacked, or chased by unfamiliar people or animals. Typically at the end of an episode, the patient awakens quickly, becomes rapidly alert, and reports a dream with a coherent story. The dream action corresponds closely to the observed sleep behaviors. It predominantly affects males over the age of 50. Cases in childhood are usually related to the loss of REM atonia in narcolepsy. Antidepressant use, especially SSRIs increases the EMG muscle tone during REM and has been linked with triggering RBD. The vast majority of patients with RBD initially diagnosed as “idiopathic” that are followed later develop neurogenerative disorders, primarily the synucleinopathies such as Multiple System Atrophy, Dementia with Lewy Bodies, and Parkinson Disease. Treatment generally involves evaluation for and treatment of associated conditions such as narcolepsy or synucleinopathies. RBD-specific treatment first line, is melatonin. Treatment with clonazepam is also effective, but associated with significant daytime dysfunction and not recommended for individuals with dementia.
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. NREM disorders of arousal frequently appear to involve the disinhibition of “basic drive states” such as feeding, sex, and aggression. It has been postulated that central pattern generators elicit primal fixed action patterns that would otherwise have been inhibited by the prefrontal cortex during wake. In this regard, aggression is typically abrupt in onset and characterized by apparent instinctual defensive posturing as opposed to behaviors that are complex and procedural. These can emerge in pathological forms with the parasomnias, as seen with sleep related aggression and locomotion, sleep related eating disorder, and abnormal sleep related sexual behaviors. NREM disorders of arousal, which include confusional arousals, sleep-walking, and sleep terrors, arise as a result of incomplete arousal from deep sleep.
The conditions share similar genetic and familial patterns, similar pathophysiology of partial arousals from deep sleep, and similar priming by sleep deprivation and biopsychosocial stressors. These disorders of arousal are not secondary to psychiatric disease, not generally secondary to neuropathology or head injury, associated with absent or minimal cognitive functioning, associated with amnesia for the prior episode, and may be triggered by sound, touch or other stimuli. Treatment is generally aimed at addressing any potential triggers, most commonly sleep deprivation or other sleep disorders such as OSA or RLS. Environmental safety is also important, including locking doors and windows, and eliminating floor clutter for sleep walkers.
