This chapter primarily focuses on sleep and sleep disorders in adults. While many basic and clinical aspects are similar in children, developmental issues and some disorders not present in adults, for example, sudden infant death syndrome, are beyond the scope of this chapter. For further information the reader is referred to Principles and Practice of Sleep Medicine in the Child (Ferber and Kryger, 1995).
General Approach to the Patient
Clinicians should ask routinely about sleep and wakefulness. A thorough sleep history lays the foundation for accurate diagnosis and effective treatment of sleep disorders (Table 27–1). Patients’ sleep complaints will usually fall into four general categories: Complaints of difficulty initiating sleep or staying asleep (insomnia), difficulty staying awake during the day (hypersomnia); abnormal movements or behavior during sleep (parasomnia), timing of the sleep–wake cycle at undesired or inappropriate times over a 24-hour day (circadian rhythm disorder), or a combination of the above (see Figure 27–1).
Table 27–1. Office Evaluation of Chronic Sleep Complaints |Favorite Table|Download (.pdf)
Table 27–1. Office Evaluation of Chronic Sleep Complaints
Detailed history and review of the sleep complaint, as well as predisposing, precipitating, and perpetuating factors
Review of the difficulties falling asleep, maintaining sleep, and awakening early
Timing of sleep and wakefulness over the 24-h day
Evidence of EDS and fatigue
Bedtime routines, sleep setting, preoccupations, anxiety, beliefs about sleep and sleep loss, fears about consequences of sleep loss, nightmares, enuresis, and sleepwalking
Medical and neurologic history and examination and routine laboratory examinations
Review of use of prescription and nonprescription medications, hypnotics, alcohol, and stimulants
Evidence of sleep-related breathing disorders: Snoring; orthopnea, dyspnea; headaches; falling out of bed; nocturia; obesity; short, fat neck; enlarged tonsils; narrow upper oral airway; and foreshortened jaw (retrognathia)
Abnormal movements during sleep; “jerky legs,” leg movements, myoclonus, “restless legs,” leg cramps, and cold feet
Psychiatric history and examination
Social and occupational history, marital status, living conditions, financial and security concerns, and physical activity
Sleep environment—ambient noise, light, and temperature
Sleep–wake diary for 2 weeks
Typical exposure to light (sunlight and artificial) and darkness across a 24-h day
Interview with bed partners or persons who observe the patient during sleep
Tape recording of respiratory sounds during sleep to screen for sleep apnea
Steps for a sleep disturbance algorithm. (Adapted from Gillin JC, Ancoli-Israel S, Erman M: Sleep and sleep–wake disorders. In: Tasman A, Kay J, Lieberman JA (eds). Psychiatry. 2nd edn. Philadelphia: Saunders, 1996, pp. 1217–1248.)
During the evaluation, the patient's bed partner or other informants should be included whenever possible. Since the patient may be unaware of sleep and wakefulness difficulties, bed partners often initiate the sleep evaluation for sleep apnea, periodic limb movements (PLMs) during sleep, or excessive daytime sleepiness (EDS). Sleep disorders can be disruptive to a household, not just the patient (e.g., sleepwalking, loud snoring).
The clinician should take a thorough history of all pertinent medical and psychiatric problems and family history, review medications, personal relationships, environmental stressors, and review of systems and complete a physical examination including a thorough neurologic examination.
Sleep Laboratory Evaluation
Most sleep complaints can be managed by the nonspecialist, with the motivation and cooperation of the patient, through behavioral modification, treatment of underlying and comorbid diagnoses, and appropriate use of medication for symptomatic relief of sleep-related symptoms. For sleep apnea, PLMs during sleep, narcolepsy, parasomnias with potential for serious injury, or intractable insomnia, referral to a sleep disorder center should be considered.
Nocturnal polysomnography (PSG) records the patient's sleep overnight in a sleep laboratory. Polygraphic sleep recordings are obtained in a quiet, dark, comfortable laboratory environment. Surface electrodes are affixed to the skin to monitor the electroencephalogram (EEG), bilateral eye movement activity or electrooculogram (EOG), and chin muscle tonus or electromyogram (EMG). Sleep staging is determined by a scanning of these tracings visually. The anterior tibial EMG reflects PLMS when present. Additional physiologic monitoring includes respiratory effort monitoring of the chest and abdomen, airflow such as end tidal CO2 or nasal-oral thermistor, blood O2 saturation, and electrocardiogram.
Changes in EEG frequencies discriminate waking and nonrapid eye movement (non-REM) sleep stages; the concurrent presence of eye movements in the EOG. A dramatic decrease in muscle tone in the EMG and a desynchronized EEG distinguish rapid eye movement (REM) sleep. Table 27–2 defines terms commonly used in sleep studies.
Table 27–2. Glossary of Terms Used in Sleep Studies |Favorite Table|Download (.pdf)
Table 27–2. Glossary of Terms Used in Sleep Studies
|Polysomnography (PSG)||Multi channel physiologic recording of sleep|
|REM sleep||Rapid eye movement sleep, characterized by bursts of rapid eye movements, low-voltage fast EEG, and atonia; associated with dreaming|
|NREM sleep||Non-Rapid eye movement sleep; consists of four stages|
|Stage 1||A transitional state of lighter sleep between wakefulness and full sleep; characterized by low voltage, mixed frequency EEG and slow rolling eye movements|
|Stage 2||Sleep characterized by EEG waveforms called K-complexes and spindles, usually around 50–75% of TST|
|Stage 3||Sleep characterized by 20–50% high amplitude slow EEG waves (25–50%)|
|Stage 4||Sleep characterized by > 50% high amplitude slow EEG waves|
|Total sleep time (TST)||Total minutes of NREM sleep + total minutes REM sleep|
|Sleep latency||Elapsed time from “lights out” to onset of sleep|
|REM latency||Elapsed time from sleep onset to REM onset; normally varies from 70–100 min (in young adults) to 55–70 min (in elderly); may be abnormally short in narcolepsy, depression and other conditions|
|Sleep efficiency (SE)||Time asleep divided by total time in bed; usually expressed as a percentage, normally ≥ 90% in young adults; decreases somewhat with age|
|Wakefulness after sleep onset (WASO)||Time spent awake after sleep onset|
|Respiratory disturbance index (RDI)||Respiratory events (apneas + hypopneas) per hour of sleep; sometimes referred to as apnea-hypopnea index (AHI)|
|Apnea||A cessation of airflow of 10 s or longer|
|Hypopnea||A reduction by 50% in airflow of 10 s or longer|
|Multiple Sleep Latency Test (MSLT)||An objective measure of EDS in which sleep latency and REM latency are measured during four to five 20-min nap opportunities spaced 2 h apart across the day|
|Periodic Limb Movements (PLMs)||Intermittent (every 20 –40 s) leg jerks or leg kicks during sleep|
Sleep Stages & Architecture
Normal sleep involves two states: REM sleep and non-REM sleep. REM sleep is often associated with dreaming. Non-REM sleep is a period of decreased physiologic and psychological activity and is further divided into stages 1, 2, 3, and 4 on the basis of visually scored EEG patterns.
Sleep normally begins with non-REM stage 1, before progressing successively into non-REM stages 2 through 4, during which the EEG generally declines in frequency and increases in amplitude. Stages 3 and 4 sleep, also called slow-wave sleep (SWS), are typically most intense early in the sleep period. The amount of SWS declines across the night. REM sleep is characterized by high-frequency; low-amplitude EEG, loss of muscle tone in the major antigravity muscles, and REMs (see Figure 27–2).
Hypnogram of sleep stages in young versus old. (Adapted from Gillin JC, Ancoli-Israel S: The impact of age on sleep and sleep disorders. In: Salzman C (ed). Clinical Geriatric Psychopharmacology, 4th edn. Baltimore: Lippincott Williams & Wilkins, 2005.)
The Neurobiology of Sleep
The neurophysiologic underpinnings of sleep and wakefulness are incompletely understood. Aspects of REM sleep such as periodic REMs and atonia are generated within the brain stem. Non-REM sleep is partially controlled by rostral brain regions such as the hypothalamus, basal forebrain, and thalamus.
A variety of neurotransmitter systems and brain regions appear to regulate sleep and wakefulness. The arousal network involves the activity of neurons containing acetylcholine, norepinephrine, serotonin, orexin (hypocretin), and dopamine (DA), whereas Gamma aminobutyric acid (GABA)-ergic mechanisms figure prominently in initiating non-REM sleep (Table 27–3).
Table 27–3. Neurotransmitters and Neuromodulators that may Regulate Sleep–wake States |Favorite Table|Download (.pdf)
Table 27–3. Neurotransmitters and Neuromodulators that may Regulate Sleep–wake States
|Substance||Involved in Control of Wakefulness|
|Acetylcholine||Cholinergic neurons of the dorsal midbrain and pons densely innervate the thalamus and thus regulate alertness and cortical activation.|
|Serotonin||Dorsal raphe neurons (DRN) are active during waking, less active during NREM sleep, and virtually inactive during REM sleep.|
|Norepinephrine||Noradrenergic neurons in locus coeruleus (LC) are very active during waking, and are thought to promote wakefulness. These neurons cease firing in REM sleep.|
|Dopamine||Extracellular levels of DA are elevated during waking. D1 and D2 antagonists (typical antipsychotics) tend to promote sleep.|
|Histamine||Histaminergic neuronal activity is high during wakefulness, and H1 antagonists produce drowsiness and sleep.|
|Hypocretin/orexin||Orexin neurons are most active during waking and locomotor activity. Deficiencies in this system are presumed to cause narcolepsy.|
|Involved in control of NREM or REM sleep.|
|GABAergic||Preoptic anterior hypothalamic neurons appear to promote sleep by inhibiting wakefulness via GABAergic projections. Hypnotic effects of BZDs may be mediated by enhancement of GABA.|
|Melatonin||Melatonin is secreted by the pineal gland and is best established as a marker of circadian rhythm. MEL may hasten sleep or ease jet lag.|
|Interleukins and other immune modulators||Interleukins promote SWS in animals, and immune modulators may be increased in plasma at sleep onset in normal control subjects. NREM sleep measures may correlate with natural killer cell activity in humans.|
|Adenosine||Adenosine appears to promote sleep. Alerting effects of caffeine may be mediated by blockade of adenosine receptors.|
|Serotonin||l-tryptophan has hypnotic effects, increases delta sleep. Serotonergic neurons in DRN cease firing in REM sleep and may inhibit cholinergic neurons in laterodorsal tegmentum-pedunculopontine tegmentum (LDT-PPT), ponto-geniculo-occipital (PGO) waves, and REM sleep.|
|Prostaglandins||Prostaglandins D2 and E2 increase sleep and wakefulness, respectively, in animals.|
|Endogenous sleep factors||Putative hypnotoxins include delta sleep inducing peptide (DSIP), uridine, arginine vasotocin, and muramyl peptides.|
Sleep & Circadian Rhythms
The rhythm of sleep and wakefulness is governed by one or more internal biological “clocks,” by environmental stimuli, and by a host of processes that promote or inhibit arousal (see Table 27–4.) In the absence of zeitgebers (time cues such as social activities, meals, and bright lights), humans tend to self-select a sleep–wake cycle of about 25 hours from wake time to wake time. In other words, if a person lives in an experimental environment free of time cues and is allowed to go to bed and arise at will, that person will tend to go to sleep about an hour later each “night” and wake up about an hour later each “morning.” For this reason, shifts in the sleep–wake cycle activity are usually easier when the cycle is lengthened rather than shortened—in traveling west rather than east, for example—or when rotating from an afternoon to an evening work shift, rather than from an afternoon to a morning work shift.
Table 27–4. Glossary: Terms Commonly used in the Study of Circadian Rhythms |Favorite Table|Download (.pdf)
Table 27–4. Glossary: Terms Commonly used in the Study of Circadian Rhythms
|Chronobiology||The Study of Circadian Rhythms|
|Circadian rhythms||Refers to biological rhythms having a cycle length of about 24 h. Derived from Latin: circa dies, “about 1 day.” Examples include the sleep–wake cycle in humans and temperature, cortisol, and psychological variation over the 24-h day. Characterized by exact cycle length, amplitude, and phase position.|
|Phase position||Temporal relationship between rhythms or between one rhythm and the environment. For example, the maximum daily temperature peak usually occurs in the late afternoon.|
|Phase-advanced rhythm||Patient retires and arises early.|
|Phase-delayed rhythm||Patient retires and arises late.|
|Zeitgebers||Time cues such as social activities, meals, and bright lights.|
Normally, the circadian oscillator is entrained to the 24-hour environment by zeitgebers such as social activities and meals, and especially by environmental light. Information about light reaching the retina is conveyed to the suprachiasmatic nuclei (SCN) in the anterior hypothalamus. The SCN are important oscillators that maintain the circadian rhythm of sleep–wakefulness.
In addition to synchronizing the circadian oscillator with the environment, the timing of light exposure can also shift the phase position of the oscillator (i.e., the temporal relationship between rhythms or between one rhythm and the environment). Bright light (1500 lux) in the evening hours (6–9 pm) coupled with darkness from 9 pm to 9 am tends to cause a phase delay in sleep–wake and other biological oscillators (i.e., one would go to bed later and wake up later). In contrast, exposure to bright light in the early morning hours (5–7 am) coupled with darkness in the evening tends to advance the phase position of the oscillator (i.e., one would go to bed earlier and wake up earlier). Furthermore, bright light during daylight hours can enhance the amplitude of the circadian rhythm, thereby demarcating the periods of both nocturnal sleep and daytime wakefulness. Bright light has been reported to have antidepressant effects in seasonal depressions occurring in the winter and in some patients with major depressive disorder or premenstrual depression.
Sleep Changes with Development & Aging
Sleep–wake states change dramatically across the life span, not only with regard to the amount of sleep, but also to circadian timing. With advancing age, REM latency tends to decrease and the length of the first REM period tends to increase.
The amount of time spent each night in SWS is high in childhood, peaks in early adolescence, and gradually declines with age until it nearly disappears around the sixth decade of life. Young adults typically spend about 15–20% of total sleep time (TST) in SWS. Sleep tends to be shallower, more fragmented, and shorter in duration in middle-aged and elderly adults compared to young adults. In addition, daytime sleepiness increases. The relative amount of “shallower” stages 1 and 2 sleep tends to increase as the “deeper” stages 3 and 4 sleep tend to decrease. Men tend to lose SWS at an earlier age than women do.
After the age of 65, about one in three women and one in five men report that they take over 30 minutes to fall asleep. Wakefulness after sleep onset (WASO) and number of arousals increase with age, an increase that may be due at least in part to the greater incidence of sleep-related breathing disorders, PLMS, and other physical conditions in these age groups. WASO may also increase with age because older people are more easily roused by internal and external stimuli.
Changes in the circadian rhythm may lead to daytime fatigue, napping, and poor nocturnal sleep. Related to a phase-advanced temperature rhythm, elders tend to retire and arise earlier than younger adults. Psychosocial alterations can disrupt zeitgebers and light exposure. Napping also increases with age, but the TST per 24 hours does not change with age.
This section follows the system in the International Classification of Sleep Disorders, Revised (ICSD-2). which groups sleep complaints by primary symptomatology: Insomnia, or disorders of initiating and maintaining sleep; hypersomnia, or disorders of EDS; parasomnias; and circadian rhythm disorders. The section also comprises of a brief discussion of sleep alterations associated with psychiatric disorders, substance use, medical conditions, and the reproductive cycle.