31: Sleep Disorders

Thirty-five percent of adults experience sleep-related symptoms over the course of a year, making them among the most common symptoms seen in medical practice. Ten to fifteen percent of adults suffer chronic insomnia and account for the largest proportion of patients seeing health care providers for sleep-related problems. Insomnia increases risk for other chronic diseases, including hypertension, diabetes, depression, and dementia. Daytime sleepiness impairs work performance and increases the risk of industrial and motor vehicle accidents. Sleep loss due to sleep-related breathing problems leads to profound sleepiness and life-threatening cardiovascular and pulmonary diseases. Sleep deprivation is known to increase risk for depression and dementia. Sleep medications themselves carry morbidity such as falls, daytime anxiety, and worsened sleep apnea. In this chapter, we review normal sleep, disorders of both sleep and wakefulness, and a logical clinical approach to these disorders.

Sleep has a structure, or architecture, that consists of nonrapid eye movement (non-REM) and REM sleep cycles. The wake electroencephalogram (EEG) contains low-voltage, high-frequency waveforms that become dominated by alpha waveforms (8–12 cps) as a person becomes drowsy. There are four stages of non-REM sleep. Stage 1 is defined by the disappearance of the alpha pattern, the appearance of slower theta waveforms (2–7 cps) along with slow, rolling eye movements. Stage 2 is defined by the appearance of low-frequency, high-amplitude discharges (K complexes) and brief high frequency (12–14 cps), variable-amplitude discharges (sleep spindles) on a background of theta waveforms similar to stage 1. The majority of sleep time is spent in stage 2 non-REM. The emergence of slow waves (high-amplitude, low-frequency [0.5–2 cps] delta waveforms) heralds stage 3 sleep, when they make up at least 20% of sleep time, and stage 4 sleep when they comprise more than 50% of sleep time. These two stages are known as the “deep stages” of sleep, because they are associated with high-arousal thresholds. REM sleep is a distinct state of sleep characterized by wake pattern EEG, skeletal muscle paralysis, and rapid, conjugate eye movements. The central nervous system (CNS) is predominantly active during REM sleep, and this is when a majority of dreams occur.

With the initiation of sleep, the healthy adult will descend through the non-REM stages within 45–60 minutes before beginning the first REM cycle, which tends to be brief. As the night progresses, less time is spent in slow-wave sleep, and REM cycle duration increases, eventually comprising 20–25% of total sleep time. The non-REM/REM cycle typically lasts 90–110 minutes, with about four complete cycles per night.

The timing and duration of sleep are controlled by many factors. Although most adults have some control over when they go to bed and when they get up, they have less control over how much sleep they need, and the quality of the sleep they get. Although stimulants such as caffeine and habituation to a state of chronic fatigue can help people cope with inadequate sleep, they must ultimately pay the price of diminished energy and mental efficiency. Individual sleep requirements vary; although most people need 6–9 hours of sleep per night, the human range is thought to be from 3 to 12 hours. Children generally need more sleep than adults, but after adolescence, daily sleep requirement remains fairly stable until late life. In old age, sleep need may increase or decrease, but the most dramatic changes are in sleep quality and duration. There is a gradual reduction in the amount of time spent in deep sleep as we age, plus a tendency to have more awakenings at night and more naps during the day.

The body clock (hypothalamic suprachiasmatic nucleus or SCN), functions as the circadian pacemaker. It superimposes a rhythm of sleepiness and alertness to days and nights and determines whether a person is a night owl, morning lark, or somewhere in between. The light–dark cycle and nightly rhythm of melatonin secretion by the pineal gland act synergistically to keep the body clock synchronized with the day–night cycle, allowing alertness during the day and sleepiness at night for people who are entrained to a conventional diurnal schedule. The interaction of the SCN, melatonin cycle, and exposure to dawn and dusk time cues determines how well a person adapts to changes in sleep schedule in order to accommodate travel across time zones, seasonal changes in photoperiod, or work and social schedules that keep people active during the night. Blindness imposes special challenges in adaptation of sleep to the light–dark cycle. Consequently, sleep complaints are common among visually impaired people.

Yawning is a phenomenon that has intrigued humans for decades. Yawning is thought to be an arousal mechanism that provides signals to the diencephalon to remain awake. It may also serve a social function. “Contagious” yawning is seen in most mammalian species and most commonly occurs between individuals that are closely related to each other or engaged in collaborative activity.

Childhood

Newborns typically spend about 70% of each day asleep, with more time in REM than older children and adults. A circadian pattern of wake and sleep does not usually develop until 1–2 months of age, and rhythmic melatonin secretion is identified at 12 weeks. Sleeping through the night is one of the first maturational milestones, and this development is of great interest to parents. Children’s sleep is initially polyphasic, with day as well as night sleep. There are decreasing amounts of daytime napping until the child is 4 or 5 years. From the age of 5 to 10 years, children are usually consummate nocturnal sleepers with few arousals. Total sleep time gradually decreases throughout childhood, but for hormonal and psychosocial reasons the amount and quality of sleep drops sharply with puberty.

Daytime restlessness, including the full spectrum of attention deficit hyperactivity disorder (AD/HD), should prompt consideration of obstructive sleep apnea (OSA) syndrome, often due to enlarged tonsils and adenoids in children (see Chapter 27). There is ongoing debate over household arrangements for children’s sleep. Some anthropologists point out that isolating a newborn in a separate bedroom is unique to western cultures and that co-sleeping with infants is more natural and may be beneficial. Recent studies have linked bed sharing with Sudden Infant Death Syndrome (SIDS), however, and the current recommendation of the American Academy of Pediatrics is to place infants in a separate sleeping area in the same room with the parent.

Adolescence and Young Adulthood

Adolescents are generally able to maintain the high sleep efficiency of childhood, with few nighttime arousals and little daytime sleepiness. In practice, adolescents frequently become more night-oriented, staying up late to do homework, work part-time jobs, chat with friends via text or phone, using Internet social media sites or socializing away from home. Many adolescents and young adults develop strong tendencies to being “night owls” (see Delayed Sleep Phase Disorder in the “Chronobiological” section of this chapter). Getting up for school may become an extreme challenge for some, and overall sleep deprivation with daytime sleepiness (especially in the morning) is endemic in high schools. Also, high prevalence rates of mood and anxiety disorders and the normal emotional highs and lows of this period of life make transient insomnia more common, with difficulty falling asleep, staying asleep or both. Early experiences with various substances affecting sleep, such as caffeine, nicotine, alcohol, marijuana, hallucinogens, and stimulants also can be strong factors. Serious mental illness such as schizophrenia or bipolar spectrum mood disorders start to express themselves with significant prevalence in adolescence and young adulthood, sometimes expressed with sleep or wake disorders. Physical illnesses producing inflammation, pain, endocrine, and metabolic imbalances can all impact sleep and need to be considered in clinical assessment. Excessive daytime sleepiness at this age is usually due to sleep deprivation, but substance abuse and narcolepsy need to be considered. People may suffer for many years with narcolepsy before the diagnosis is made. It should be considered in anyone with spells of sleepiness off and on during the day, especially if a very brief nap is very helpful for an hour or two.

Middle Adulthood and Old Age

Sleep tends to be lighter as people age, with more frequent awakenings and the near disappearance of deep or slow-wave sleep. Sleep timing may “phase advance” with earlier bedtimes and early morning awakenings. Whereas younger insomniacs typically struggle with sleep onset, older people with insomnia may just as likely complain of sleep maintenance problems due to this tendency toward phase-advanced sleep–wake cycle. More frequent daytime napping, either through boredom or need, is very common in older adults. This, along with decreased daytime physical activity, further erodes nighttime sleep efficiency. Frequent nocturia and esophageal reflux can make a bad situation worse with regard to sleep. Clinical sleep disorders also increase with age. Obstructive sleep apnea, periodic leg movements, restless legs syndrome (RLS), depression, anxiety, alcohol, and pain all affect the restorative qualities of sleep. Little wonder, then, that insomnia becomes more prevalent in midlife, especially in women and people with multiple chronic diseases.

Sleep disorders are generally grouped into three categories: disorders of initiating and maintaining sleep (insomnia); disorders of excessive daytime sleepiness (hypersomnia); and abnormal sleep behaviors (parasomnia) (Table 31-1).

Every review of systems should include screening patients for daytime sleepiness and nighttime sleep problems. Four basic questions give clinicians a head start in diagnosing sleep disorders and determining whether they warrant treatment:

• How are you sleeping?

• How much sleep do you get in a typical night?

• How much sleep do you typically need to feel your best?

• Do you feel alert during the day?

Follow-up questions should sharpen the differential diagnosis of specific disorders of either sleep or wakefulness. In both pediatrics and geriatrics, it is often the parent, spouse, or caregiver who notices a problem. With children, ascertain whether the parent or caregiver is knowledgeable about normal sleep patterns for children. If the behavior is outside of the norm, then further questioning is necessary for diagnosis.

The sleep–wake cycle is a complex electrophysiologic process consisting of alternating periods of wakefulness, REM sleep, and non-REM sleep. Each of these periods has a characteristic EEG, peripheral muscle, and autonomic nervous system pattern that can be documented by polysomnographic (PSG) recording in hospital and clinic-based sleep laboratories or in the home, using technologies that allow for unattended in-home recordings. PSG allows clinicians to make specific diagnoses based on electrophysiologic monitoring of EEG, electrooculogram, electromyogram, nasal airflow, ear oximetry, and electrocardiogram.

Insomnia: Insufficient and Nonrestorative Sleep

Transient and Chronic Insomnia

Insomnia is one of the most common complaints in primary care practice. It is diagnosed when there is either insufficient or nonrestorative sleep. It is essentially a subjective diagnosis although more objective means of assessment will be discussed later in the chapter. Certainly one of the first tasks is to confirm deficient sleep quantity or quality relative to normal sleep requirement for that person. Sleep requirement is best defined by how much sleep a person needs to be alert through the day, with perhaps a brief dip in alertness midday. Sleep requirement is genetically determined and also influenced by age, activity, and health. Eight hours is the adult mean sleep requirement with a range of 6–9 hours for most people. There can also be seasonal variation at high latitudes. Nonrestorative sleep diagnoses (e.g., sleep apnea, periodic leg movements, pain, depression, nightmares, etc.) should be pursued when there is adequate sleep time but poor daytime function.

It is best to think of insomnia as a symptom rather than a diagnosis. Many factors combine to produce insomnia, which often occurs when a delicate balance is tipped; for example, a constitutionally light sleeper may be fine until he or she enters a period of stress or uses a medication that has alerting effects. It may be necessary to deal with several causative factors concurrently to restore a natural sleep cycle.

Insomnia is often described as initial insomnia (trouble falling asleep), and middle or terminal insomnia (trouble staying asleep or early awakening). Insomnia may be transient (self-limited) or chronic (persistent or relapsing). Transient insomnia can evolve into chronic insomnia through a number of factors.

Transient insomnia caused by stress, environment (cold, noise, new baby), acute illness, or pain is easy to identify and usually needs no special intervention other than addressing the underlying problem. A brief course of sedative–hypnotic medication is occasionally warranted and may reduce the risk of developing long-term insomnia. Travel across time zones can cause a mismatch between the body clock and the day–night cycle, resulting in transient insomnia known as “jet lag.” Combined with fatigue from travel, jet lag can ruin the first few days of a trip. Shift workers may experience the same phenomenon and can suffer severe health and social consequences because of it.

Persistent or chronic insomnia accounts for 40–88% of patients who present with a primary complaint of insomnia. Chronic insomnia is a diagnosis of exclusion, and must be differentiated from the many other causes of long-term sleep disruption. Chronic insomnia may be due to persistence of the stress that initially caused transient insomnia. Occasionally, the insomnia continues even when the precipitating factors have resolved, presumably through a process of operant conditioning to an arousal state incompatible with sustained, restful sleep. “Conditioned” or learned insomnia may persist secondary to poor sleep hygiene, such as erratic sleep schedules, alcohol, caffeine, nicotine, work on finances, nighttime television or Internet and other habits that can prevent achieving the peaceful state of mind that is important to overcome sleep resistance. Growing frustration with failed attempts to sleep increases the psychophysiologic arousal that is the underlying cause of sleeplessness. In fact, this type of insomnia, developing over time in association with stress, worry, and frustration over sleep, is often called “psychophysiologic” insomnia. People with this type of insomnia show high levels of physiologic stress markers (hormonal, autonomic, and cognitive). Despite severe sleep deprivation and pent up sleep drive, the arousal mechanisms of the stress response create too much sleep resistance to be overcome. Occasionally, this psychophysiologic arousal may be seen early in life in a form of “primary insomnia” due to intrinsic biological variation in either sleep drive (reduced) or stress response (increased). In contrast to people with transient insomnia and sleep deprivation, patients with the psychophysiologic and primary forms of chronic insomnia report inability to nap.

As a model psychosomatic illness, chronic insomnia requires a holistic approach that can include use of medication as well as cognitive strategies to reduce anxiety and changes to improve sleep hygiene (Table 31-2). Short-term use of sedative–hypnotic medications is appropriate to break the cycle of anxiety, arousal, and insomnia (see “Medical Treatment,” below). In some patients, the symptoms suggest another disorder that can be targeted separately (depression, RLS, pain, etc.).

Chronobiological Disorders

Many cases of both transient and chronic insomnia are due to underlying chronobiological or circadian rhythm disturbances. If there is a mismatch between a person’s attempts to sleep and their endogenous circadian rhythm for sleep, insomnia may result. The circadian rhythm of the sleep–wake cycle is driven by the hypothalamic circadian pacemaker or “body clock.” Disturbances in the circadian timing of sleep may be transient, as in jet lag and shift work syndromes, or chronic, as in delayed sleep phase syndrome (DSPS), advanced sleep phase syndrome, and free-running sleep syndrome. The last is most common in blind persons, who lack the critical input of the light–dark cycle in regulating circadian rhythms. Diagnosis of chronobiological disorders is based on the understanding that except for its timing, sleep is normal in these conditions.

In DSPS, patients are “obligate” night owls, staying up late into the night through varying proportions of choice and biological drive. Patients with this condition struggle to awaken in the morning for school or work. They tend to have more energy as the day progresses and may “come alive” in the evening. Attempts to fall asleep before midnight can result in hours of tossing and turning. Sleep efficiency is usually normal when they are free to choose their own bedtimes. The condition is common in young people but can persist into middle adulthood and even old age, although it does tend to moderate with time. Adults with DSPS typically migrate to jobs in which they can work swing or night shifts, or keep totally flexible hours. They may have particular difficulty flying east across time zones, as they are relatively resistant to circadian “phase advance.” Most “night owls” have flexibility in their circadian pacemaker and can adapt to earlier sleep hours with effort. Those with true DSPS cannot adjust to conventional hours at all, or only with great effort and treatment.

Children and adolescents with DSPS may be thought of as “lazy” because of how difficult it is for them to get out of bed in the morning and their tendency to “sleep in” on weekends. When school is in session, Sunday night bedtime and Monday morning awakenings are particularly challenging. With a late sleep-onset, the child has trouble waking up Monday mornings and this starts the week off “on the wrong side of the bed.” This may lead to disruptive behavior, hyperactivity, distractibility, failure to attend, and learning problems in school. Parents and teachers must recognize that DSPS is not a behavioral problem but a circadian rhythm disorder that can improve with proper treatment. A phase shift approach by the whole family of consistent bed times 7 days a week is very helpful. Practicing good sleep hygiene, bright light therapy and melatonin have been shown to be effective (see “Treatment for Insomnia”).

Other forms of chronobiological sleep disorders are seen in practice. Shift workers often try to live on a conventional schedule to spend days off with friends or family. This can result in failure to adapt to either day or night and leads to poor sleep, poor energy, and chronically elevated risk for chronic illness and premature death. Scheduled exposure to bright light and melatonin can accelerate adaptation to shift work schedules.

Many blind individuals also have problems maintaining synchronicity between sleep and the day–night cycle. Lacking photic input to the circadian pacemaker via the retinohypothalamic tract, blind individuals can have an internal sleep propensity rhythm that is chronically out of phase with the day–night cycle, leading to frequent bouts of insomnia. Chronobiological insomnia from “free-running” circadian rhythms in blind patients is treatable with properly timed melatonin administration, but this and other chronobiological disorders should be treated in consultation with a sleep disorder specialist.

Neuropsychiatric Disorders

Sleep disturbances are among the most common symptoms of mental illnesses, particularly mood and anxiety disorders. Depression should always be considered in patients complaining of frequent nighttime awakenings and early morning arousal, particularly when those arousals are accompanied by anxiety and worry. On the other hand, many depressed patients complain of hypersomnia with fatigue and difficulty getting going in the morning. This symptom is especially characteristic of seasonal affective disorder (SAD) and so-called atypical depression. Both are common in young and middle-aged adults. Depressed patients find the sleep changes of their mood disorder very distressing, in contrast to manic patients. Bipolar patients in manic or less severe hypomanic states, typically experience less sleep drive and will enjoy their round-the-clock energy even as it impairs their judgment and physical health (see Chapter 25).

Sedating antidepressant medications (e.g., mirtazapine) may help with the insomnia secondary to depression, but can also lead to daytime sedation. Trazodone and the more sedating tricyclic antidepressants (TCAs)—e.g., doxepin, amitriptyline, and nortriptyline—may be considered. The TCAs combine moderate-to-severe sedation with effective antidepressant activity but must be used with caution due to overdose toxicity and anticholinergic effects. Serotonin reuptake inhibitors (either SSRIs or SNRIs) generally will not improve sleep immediately, and can even increase leg movements and arousals. A brief course of a sedative–hypnotic agent for help with sleep is a comforting strategy for some patients. The sleep medication can be tapered and discontinued as the depression and secondary insomnia improve.

Anxiety disorders can also present with initial and middle insomnia (see Chapter 26). Nightmares, particularly in posttraumatic stress disorder (PTSD), frequently complicate the picture. Antidepressant medications, prazosin, and clonidine have been reported to be helpful with the sleep-related symptoms. Bereavement is usually accompanied by anxiety and insomnia. Short-term use of sedative–hypnotic medications may help patients who struggle to get through long nights.

Attention deficit disorder (ADD) and AD/HD may be associated with disturbances in REM sleep as well as frequent myoclonic or periodic movements throughout the night. Insomnia is common; many patients with the condition report difficulty controlling racing thoughts and restlessness day or night. Snoring and obstructive apneas are frequently present in children who have mild symptoms of ADD–AD/HD. In these cases, the cognitive and behavioral syndrome of ADD–AD/HD can improve with treatment of the sleep-related breathing disorder by tonsillectomy or dental appliances.

Traumatic brain injuries and stroke impair alertness more often than sleep, but disruption of circadian rhythms with daytime sleep and nighttime awakenings are common. Neurodegenerative diseases such as Alzheimer disease (AD) and Parkinson disease (PD) disrupt sleep. Alzheimer disease can erode normal diurnal sleep–wake patterns, resulting in long nighttime awakenings and increased daytime sleep. This can be stressful for caregivers, who must be vigilant during these nocturnal wanderings. Sleep disruption is among the most stressful aspects of caring for a person with dementia at home. Severe insomnia can develop in some patients with AD, with little sleep day or night. Others may sleep all the time, creating a form of chronic delirium as the disease progresses into late stages. Structured daytime activity can help reduce daytime sleepiness, especially if boredom appears to be one of the contributing factors. Antihistamines and benzodiazepines should be avoided given the risk for confusion and paradoxical excitement. Cautious use of melatonin, trazodone, or quetiapine may be helpful, although the data are limited. However, given how stressful sleep disruption is for families and patients, trials of sleep-promoting medications at low doses can be justified.

Parkinson Disease patients can also have severe sleep problems. Akinesia causes physical discomfort over pressure points that normally would be relieved by tossing and turning in sleep. Medications used to treat PD can also impair sleep. Furthermore, the neurodegenerative and neurotransmitter changes caused by the disease adversely affect sleep quality. Dementia with Lewy Bodies, a disease related to PD, is associated both with impaired nighttime sleep, poor daytime alertness, and increased motor activity during REM sleep (see “REM Behavior Disorder,” below).

Alcohol and Drugs

Alcohol has variable influence on sleep patterns, but it generally impairs both alertness and sleep. Like other sedatives, alcohol suppresses slow-wave sleep, making sleep lighter. With its short half-life, alcohol also tends to produce a rebound arousal in the second half of the night and can reduce total sleep time.

Other drugs can affect sleep. Amphetamines and cocaine cause marked reduction in sleep during acute intoxication and profound hypersomnia during the withdrawal phase. Opiates have acute tranquilizing effects and improve sleep when nighttime pain contributes to insomnia. Caffeine causes longer sleep latency (time needed to fall asleep) and increased wakefulness during the night. Some people do not perceive the effects of caffeine on sleep even when they are documented on sleep EEG; others are very aware of these effects. Caffeine can even affect sleep when ingested several hours before bedtime.

Both prescription and over-the-counter (OTC) sedative–hypnotic medications can contribute to rebound insomnia when doses are missed. Medication with short half-lives can lead to rebound insomnia in the second half of the night, whereas drugs with long half-lives can cause daytime sedation. Although they are common geriatric problems, memory impairment and unexplained falls should cue the physician to consider alcohol or sedative–hypnotic abuse in elderly patients. For example, the antihistamine diphenhydramine, a component of many OTC sleep-promoting products, has potent anticholinergic effects and can cause mild cognitive impairment and, rarely, frank delirium in older people.

Education about the effects of these substances on sleep may motivate patients to reduce their intake. Patients with more severe dependency and abuse problems need referral to specific treatment programs for chemical dependency (see Chapter 24).

Medical Disorders

Cardiac and pulmonary diseases, dyspepsia, inflammatory bowel diseases, and nocturia may all contribute to insomnia. Gastroesosphageal reflux disease (GERD) is an extremely common cause of nighttime awakening. Limiting nighttime meals and eating no later than 2 hours before bedtime can be helpful. Acquired immunodeficiency syndrome (AIDS) has been associated with daytime sleepiness, decreased total slow-wave sleep with alpha wave intrusions, increasing arousals, and frequent nightmares. The high comorbidity of major depression in patients with many chronic diseases should lead the clinician to consider using sedating antidepressants to improve sleep in this population.

Acute illness may cause diffuse cerebral dysfunction in the frail elderly. The resulting delirium is almost always accompanied by disruption of sleep and alertness. Medications can also cause insomnia and daytime drowsiness. Bronchodilators, activating antidepressants, and steroids, for example, often interfere with sleep, whereas many psychotropic medications, opioid analgesics, and clonidine can cause daytime drowsiness.

Pain and rheumatological disorders deserve special mention. Pain perception tends to be greater at night, and more time in bed may increase certain types of musculoskeletal pain. One of the classic medical syndromes affecting sleep is fibromyalgia syndrome (FMS), a condition characterized by nonrestorative sleep; patients complain of feeling tired despite sleep duration in the normal range. In overnight PSG recordings, the EEG of fibromyalgia patients reveals alpha wave intrusions into stages 2, 3, and 4 of non-REM sleep. This alpha–delta sleep may signify cortical arousals that impair sleep continuity. Sleep may be additionally fragmented in FMS patients by RLS (20% of patients) and OSA (5% of patients). Fibromyalgia syndrome patients have decreased slow wave and REM sleep duration. In addition to nonrestorative sleep, FMS is characterized by widespread muscle pain, focal tender points, and chronic fatigue. The common complaint of patients with fibromyalgia is the restless sleep pattern that blunts their daytime energy and vigor. In studies with normal human adult subjects, it has been shown that sleep deprivation lowers the pain threshold. Investigators have documented increases in generalized body pain, back pain, abdominal pain, and a heightened hyperalgesic state the following day after a night of disrupted sleep. Improved sleep can produce significant remission in pain.

Restless Legs Syndrome

Restless legs syndrome (RLS) comes on with rest and produces an irresistible need to move, stretch, or rub the lower extremities. Severe dysesthesia may occur, which can variably be described as “creepy-crawling sensations,” aching, tension, tingling, or prickling. The restless need to move makes it difficult to fall asleep, so the most common symptom of RLS is insomnia, particularly at sleep onset. The vast majority (80–90%) of people with RLS also have periodic limb movements during sleep, potentially causing further sleep disruption. Beyond sleep initiation, RLS can also interfere with any sedentary activity, such as plane travel, driving, theaters and concerts, deskwork, video media, and reading.

Restless legs syndrome is common, affecting 3–10% of the population (prevalence varies with ethnicity), and may be even more common as an intermittent cause of symptoms. In women it sometimes first appears during pregnancy, but in both genders it can run in families and worsen with age. It is especially common in patients with renal failure and PD. Many physicians do not think to ask about this symptom and hence fail to recognize it as a cause of discomfort and insomnia.

Diagnosis of RLS is based on four essential criteria: (1) an urge to move; (2) onset or exacerbation with rest; (3) relief with movement; and (4) nighttime onset or worsening of symptoms. The differential diagnosis includes neuropathy, nocturnal leg cramps, and akathisia induced by dopamine antagonists. Restless legs syndrome can be exacerbated by drugs and medications, especially caffeine, alcohol, and antidepressants. Iron appears to play an important role in RLS. Reduced iron levels, particularly in the substantia nigra, can contribute to worsening symptoms. This mechanism may contribute to the higher prevalence of RLS in women, since menstrual blood loss and pregnancy can worsen iron deficiency. It is recommended that ferritin and transferrin saturation be measured in all RLS patients. If the ferritin is less than 50 mcg/L, iron supplementation for 3 months is recommended with a goal of raising ferritin above 100 mcg/L.

The first-line treatment of RLS involves the use of the newer nonergotamine dopamine agonists (e.g., pramipexole and ropinirole). Dopamine precursor treatment levadopa/carbidopa is effective as well, but more frequently causes “rebound” or “augmentation” effects, with a tendency for the symptoms to develop earlier in the day. Benzodiazepines (clonazepam) and anticonvulsants (gabapentin) are second-line agents. Combination therapy can be effective for more severe symptoms, and opiates can also be considered in refractory cases. The syndrome is so distressful for some of its sufferers that there is a national support group and newsletter (see website www.rls.org).

Periodic Limb Movements of Sleep

Periodic limb movements of sleep (PLMS) are repetitive myoclonic movements of the extremities, most commonly in the legs, that occur every 5–90 seconds over many hours; they are more common in, but not limited to, the first half of the night. The movements can be associated with brief EEG arousals and potentially cause nonrestorative sleep and daytime somnolence (although larger studies have failed to show a consistent association with excessive daytime sleepiness). Prevalence estimates range from 5% in people aged 30–50 years, to 29% in those aged 50–65 years, and 44% in those over the age of 65 years. PLMS are often seen in metabolic and neurodegenerative diseases. Periodic limb movements of sleep should be distinguished from nocturnal leg cramps, which are painful, prolonged involuntary contractions of the muscles of the lower legs. Antidepressants, lithium carbonate, and withdrawal from benzodiazepines and alcohol can induce or worsen PLMS. It is often asymptomatic, but in severe cases patients may have sleep-onset insomnia, nonrestorative sleep, or frequent arousals during the night from more robust myoclonic movements. Not infrequently, the bed partner is the one complaining about the jerking leg movements at night.

Whereas RLS is primarily a clinical diagnosis based on patient-reported symptoms, PLMS are best documented by PSG in the home or sleep laboratory. PLMS are treated similarly to RLS. Dopaminergic agents are the treatment of choice, since they reduce the frequency of leg kicking, but rebound of symptoms in the second half of the night or during the following day can complicate treatment. Sedative–hypnotics can improve sleep continuity in PLMS patients, but do not reduce the number of leg movements. Opiates, such as a bedtime dose of codeine, work well in PLMS (as in RLS), but should be reserved for patients with severe symptoms.

Reframing the Psychosocial Context of Sleep Disturbance

Sleep problems in children and adolescents usually affect the rest of the family, causing sleep loss in parents and siblings who may in some respects suffer as much as the patient. Because misinformation and inappropriate blaming may confound the problem, the disturbed sleep of such patients needs to be addressed as a problem for the whole family.

Modifying family routines may be helpful. Good sleep hygiene, including well-maintained bedtime rituals such as bathing, storytelling, and rocking a small child can facilitate the winding-down process that is an important prelude to sleep. Occasionally, a child becomes overly dependent on a particular routine (e.g., repeated drinks of water every time he or she wakes up) and the parents must set limits. After an expected period of protest, most children relinquish the need for unnecessary attention. These benign disruptions must be differentiated from the more serious panic that some children experience with separation. For this latter kind of anxiety, parental access through the night may be necessary, at least for some time.

In adolescence, sleep is often shortened at both ends by social demands. In the evening, there is homework, socializing, school athletic events, and family life. In the morning, high school schedules often begin quite early, sometimes preceded by an even earlier bus ride. For many teenagers, the morning includes a formidable grooming ritual. Add to this the increasing tendency for teenagers to take part-time jobs after school, and the result is an epidemic of chronic sleep deprivation that is of increasing societal concern. Weekend sleeping-in may recover some of the lost sleep, but it tends to produce a phase delay that reinforces the tendency to stay up late during the week. In one experiment, high school students increased their IQ scores by 20 points after a week in which they systematically extended their sleep time.

In counseling teenagers, some flexibility and compromise are usually most effective. Adding naps during the day may improve alertness. A warning about the dangers of driving while sleepy, intoxicated, or both is important. Chronobiological interventions, such as light therapy, may be needed to counteract extremely delayed sleep. Outside the office, informed physicians may be able to influence public policy to help alleviate the problem, such as adopting sensible work rules for teens and scheduling school activities at reasonable hours.

Adults are not immune to the effects of social and occupational demands on sleep. Many working adults become progressively more sleep deprived as the workweek progresses. Educating patients about appropriate sleep hygiene and cognitive measures helps them regain some sense of control over their symptoms of fatigue (see Table 31-2). New knowledge of the health consequences of sleep deprivation can help motivate people to prioritize sleep as an important health behavior.

Persons with more persistent insomnia or those who appear to have severe emotional distress (as a result or cause of the sleep disturbance) may warrant evaluation by a mental health specialist.

As they do in children, sleep disorders in adults can affect family members. Partners and caregivers of patients with severe sleep disorders may need both emotional support and education about the nature of the sleep disturbance. Understanding the problem can help them to support the patient in following treatment recommendations.

Cognitive Behavioral Therapy

There is now ample evidence that cognitive behavioral therapy (CBT) for primary insomnia, especially over the long term, is at least as effective as sleep medication. The basic approach is to counsel patients to change critical beliefs that induce anxiety around falling asleep and to motivate them to change bedtime behaviors that may be perpetuating insomnia. The basic approach is to motivate patients to practice cognitive skills that will help minimize the worry and frustration that induces the physiologic stress response and impedes sleep. With time, patients can learn to suppress intrusive, unwanted thoughts and activate calming ones. Certain audio books or meditation CDs can help this practice. The “behavioral” component of CBT is the application of sleep hygiene measures. The National Sleep Foundation web site (www.sleepfoundation.org) has many helpful suggestions for people interested in improving sleep hygiene.

Medical Treatment

Insomnia has a good prognosis acutely, but can become chronic and recurrent. Acute insomnia can be treated with sedative–hypnotic drugs in conjunction with a sleep-hygiene program to maximize efficacy and reduce the dosage and duration of treatment (Table 31-3). These medications should not be used in pregnancy. People with secondary insomnia from depression, pain, substance abuse, medications, or circadian rhythm disorders are at risk for chronic insomnia if the acute symptoms do not resolve, and may need specific sleep therapies in addition to treating the underlying cause of sleeplessness.

Benzodiazepines

All benzodiazepines have sleep-promoting effects, although only five are currently marketed as sedative–hypnotics. These drugs work well for short-term treatment of insomnia; tolerance and dependence can develop quickly in some patients. However, some patients, especially those with an anxiety component to their insomnia, may benefit from long-term use. Benzodiazepines alter sleep structure, reducing both REM and slow-wave sleep, but the clinical significance of this is unknown. They are generally safe for younger adults, even in overdose, although combining them with alcohol and other depressants can produce potentially catastrophic synergistic effects. In older individuals, the safety profile is less benign; amnesia, ataxia, confusion, and worsening sleep apnea may develop.

Choosing one benzodiazepine over another for a specific patient is partly based on drug half-life, and this will require prioritizing goals. Short-acting drugs such as triazolam are useful for the treatment of sleep-onset insomnia, but many individuals will have rebound insomnia in the second half of the night or anxiety the following day. Longer-acting drugs may work better for middle-of-the-night insomnia, but some persons will have morning “hangover” effects. Longer-acting drugs can be particularly troublesome in the elderly, as drug accumulation will lead to ataxia, confusion, and daytime sedation. Temazepam and estazolam are intermediate in half-life and represent reasonable compromises for patients with sleep maintenance insomnia who get hangover effects from the longer-acting drugs.

These drugs should not be prescribed for patients with sleep apnea, severe respiratory disease, gait and balance problems, or alcohol abuse. Doses should be kept low in elderly patients and those with hepatic insufficiency. Rebound insomnia can complicate withdrawal from these drugs, causing patients to return to their use.

Benzodiazepine Receptor Agonists

These drugs are structurally unrelated to benzodiazepines, but share some characteristics with them due to the fact that they have agonist activity at more sleep-specific benzodiazepine receptors (GABAα). They have varying half-lives (eszopiclone and zolpidem, 1.4–3.8 hours; zaleplon, 1.0 hours), so they are most suitable for patients with sleep-onset or initial sleep maintenance problems. These medications preserve natural sleep architecture, which provides at least a theoretical advantage over benzodiazepines. Precautions similar to benzodiazepines apply to these medications in terms of dependency, abuse, and adverse effects. Eszopiclone (Lunesta) and zolpidem in continuous-release formulation (Ambien CR) have been shown to retain efficacy over 6 months, and are the only benzodiazepine or benzodiazepine receptor agonists that are FDA-approved for chronic insomnia (see Table 31-3).

Melatonin Agonist

Ramelteon (rozerem) is a potent melatonin agonist that is the first nonscheduled, prescription sedative–hypnotic. It has the capacity to shorten sleep latency in people with sleep-onset insomnia, but does not help people stay asleep. It has no potential for abuse, tolerance, or physical dependency, and does not cause ataxia, confusion, or worsen sleep-related breathing disorders. In the clinical trials, the drug was associated with an increase in prolactin in a few subjects. Ramelteon is prescribed at 8 mg before bedtime. Higher doses have not been shown to improve response, but there is some evidence that the response improves over several weeks. Combining ramelteon with CBT or sleep hygiene measures seems a benign and potentially effective long-term strategy for many insomnia patients.

Sedating Antidepressants

Many clinicians use sedating antidepressants such as trazodone, mirtazapine, doxepin, and amitriptyline for long-term treatment of insomnia, especially when chronic pain, depression, or anxiety are comorbid conditions. Theoretical advantages over benzodiazepines include less cognitive impairment, more slow-wave sleep and treatment of underlying depression if present. Tolerance to the sedating effects of these drugs develops in some patients. Side effects are numerous, and special care must be taken in elderly patients, especially with amitriptyline, because of its potent anticholinergic effects. There are data indicating efficacy of doxepin and mirtazepine at very low doses (under 10 mg) that may enhance sleep while minimizing side effects.

Antihistamines

Diphenhydramine is sedating and is found in many OTC preparations. It is generally safe and effective for short-term use, although tolerance develops very quickly after nightly ingestion. Diphenhydramine has some anticholinergic properties and can cause confusion and urinary retention in elderly persons.

Complementary and Alternative Medicines

The pineal hormone melatonin, sold in this country as a food supplement, has sleep-promoting effects in some people. Melatonin is the best studied of the food supplements and OTC remedies for insomnia and is commonly available at health food stores and pharmacies. Patients should be cautioned that melatonin remains an experimental drug and a naturally occurring hormone with potential neuroendocrine, immunologic, and reproductive effects, although it appears to be quite safe with short-term administration. Results from placebo-controlled trials of melatonin for insomnia in various populations suggest it has only modest efficacy, though some individuals respond quite well. Moreover, when taken at the correct point in the circadian cycle, melatonin can be an effective remedy for jet lag and can help people adapt to shift work. Commercial preparations may contain 0.5–5 mg of melatonin per capsule (sometimes in combination with vitamins). The most effective dose is unknown, and may vary from person to person.

Chronobiological Therapies

Sleep–wake cycle disorders can be treated with scheduled exposure to bright natural or artificial light. Patients with advanced sleep phase syndrome need to have a corrective phase delay with exposure to bright light in the evening. Bright light exposure must be carefully timed so that the circadian pacemaker is phase shifted to move sleep propensity to later hours, allowing these patients to be more alert in the evening. For the more common DSPS, patients need to force themselves awake by receiving appropriately timed light exposure, which should begin around the time they want to wake up. The first few days are very difficult, but after several mornings of 30-minute light exposure, patients can begin falling asleep before midnight and wake up for morning classes or work. For safety and efficacy, patients should use special fixtures marketed to treat SAD (“SAD lights”). Light fixtures are available from numerous commercial vendors.

Melatonin may achieve this same goal with greater convenience, although probably with less robustness and with opposite timing. For example, people with DSPS who want to advance the timing of their sleep might take synthetic melatonin (0.5–1 mg) in the evening at 9:00 or 10:00 p.m.—hours before their own phase-delayed melatonin secretion begins and more synchronous with the timing of melatonin onset in people with earlier sleep—to reset their body clock to the desired phase position. Ramelteon can be effective when used in this same way. These treatments may also be of value in helping shift workers, time zone travelers and persons with visual impairments adapt to a new sleep–wake schedule. Shift workers should be counseled to try to maintain their workweek sleep schedule on their days off work, although this can be difficult because of family and social demands. Some cases may require referral to a sleep specialist.

The Sleepy Patient: Disorders of Excessive Somnolence

Patients are more likely to complain about insomnia than about excessive daytime sleepiness. They may complain of fatigue or feeling tired, but sleepiness per se may not be acknowledged without specific inquiry by the clinician. Two questions that should be included in every sleep-related “review of systems” are:

• Do you struggle to stay awake while driving, reading, watching television and movies, or listening to lectures during daytime hours?

• Do you feel tired, fatigued, and lacking in energy during the day, especially in the morning?

If the answer is “yes” to either question, follow-up questions should determine if the problem is inadequate nighttime sleep, drowsiness from medications, narcolepsy, or sleep-related breathing problems. The Epworth Sleepiness Scale (see Table 31-4) is a validated instrument used to assess pathological sleepiness in patients. It is a questionnaire that scores a patient’s tendency to fall asleep in eight hypothetical situations on a 0–3 scale, with zero scored for “not at all likely to doze” and three for “extremely likely to doze” in each situation. A cumulative score above 10 suggests the need for referral to a sleep disorders specialist. A discussion of driving or operating machinery while sleepy should also be initiated. Excessive daytime sleepiness requires a thoughtful diagnostic approach.

Sleep-Related Breathing Problems

Obstructive Sleep Apnea Syndrome and Snoring

Obstructive sleep apnea (OSA) is increasingly recognized as a common, important, and treatable disease. Originally thought of as a relatively rare disturbance in severely obese patients with the classic “Pickwickian Syndrome” of somnolence, hypoventilation, and polycythemia, OSA is now known to represent a range of upper airway narrowing in sleep. Epidemiologic studies in middle-aged adults show a prevalence of 2% of women and 4% of men, but these estimates are likely very low, especially given recent trends in increased body weight.

Obstructive sleep apnea is a significant cause of fatigue, daytime somnolence, and cardiovascular morbidity in adults. Nighttime symptoms of OSA include loud snoring (often beginning early in adulthood and worsening with age and increased weight), apnea witnessed by the sleeping partner, snorting or gagging sounds, restlessness, night sweats, and abrupt awakenings with a feeling of choking. Electroencephalogram arousals triggered by the apneic episodes cause interrupted sleep quality, excessive daytime sleepiness, and subjective fatigue. There is also mounting evidence of objective deficits in cognitive processing, attention, and executive functions. Although less common, insomnia may be the presenting complaint. Patients are often unaware of the severity of the sleep disruption and may attribute their sleepiness to some other cause, such as working too hard. The degree of sleepiness is variable, but is a key symptom. Questions about dozing while reading or watching television, nodding off at the wheel, or poor concentration need to be posed directly to patients. Assessment with a standardized scale measuring daytime sleepiness such as the Epworth Sleepiness Scale may be helpful (Table 31-4).

Cardiovascular morbidity and mortality has now been strongly associated with severe OSA (Apnea Hypopnea Index [AHI] > 30). Cardiovascular manifestations of OSA include hypertension, heart failure, stroke, and possibly myocardial infarction. Although not a randomized trial, in the long-term observational study from Spain, continuous positive airway pressure (CPAP) treatment reduced the incidence of cardiovascular events, thus strengthening the rationale for CPAP treatment, particularly in severe OSA.

Diagnosis of OSA begins with a clinical assessment, but a sleep study is necessary to confirm the diagnosis and severity of OSA. A formal PSG in a sleep laboratory remains the gold standard for diagnosis, but less-detailed home testing using portable technology that does not require a sleep technician to be in attendance can provide diagnostic information in some cases. When PSG in the sleep laboratory confirms the diagnosis of OSA, there is an opportunity for the patient to try CPAP treatment with a supervised mask fitting by an experienced sleep technologist. If the diagnosis is made with a home-based study, it is still best if they come to the sleep laboratory for PSG-monitored CPAP mask fitting and pressure titration.

Treatment options should be individualized depending on the severity of OSA, and also patient symptoms and comorbidities. Initial treatments to reduce OSA include weight loss, avoidance of sedating medications or alcohol near bedtime, and appliances to prevent back sleeping (tennis balls sewn in the back of nightshirt are an inexpensive option). Continuous positive airway pressure (with either mask or nasal pillows) remains the most common and effective treatment for improving sleep quality, reducing daytime symptoms, and reducing cardiovascular risk. In patients who cannot tolerate CPAP, other treatment options are typically ENT surgery or oral (dental) devices. A variety of surgical techniques are available, but the low success rates make surgery a less appealing initial treatment in most cases. Some adults will have significant tonsillar hypertrophy and be better surgical candidates. Tracheotomy has a very high success rate, but is a morbid procedure that has been much less frequently performed since CPAP has a high success rate. Oral appliances fitted and adjusted by an experienced dentist can maintain the tongue in a more forward position to improve airway patency in mild-to-moderate cases of OSA or for those who cannot tolerate CPAP (see Figure 31-1). Patients who have surgical or dental treatments should have a follow-up sleep study to document the efficacy of those treatments. The correct diagnosis and effective treatment of OSA can help improve quality of life, prevent serious accidents, and reduce cardiovascular risk.

Snoring is a common sleep symptom. Apart from being a nuisance to bed partners, snoring may herald the development of serious respiratory obstruction during sleep along a continuum of partial to complete airway closure. Men snore more than women, but the prevalence increases in women after menopause. Aside from male gender, other factors associated with snoring include anatomic narrowing of the airway, body habitus (obesity) and sleep position (supine), the use of alcohol and sedative–hypnotics, endocrinopathy (hypothyroidism, acromegaly), smoking, and, possibly, genetic factors. Since snoring is a common presenting symptom of OSA, it is important to ask questions regarding apnea and OSA symptoms in any patient who complains of snoring. Similarly to OSA, initial treatments to reduce snoring include weight loss, the avoidance of sedating medications and alcohol, and appliances to prevent back sleeping. If a sleep study confirms the absence of apnea, but snoring remains disruptive, then potential interventions include oral (dental) appliances, surgery, and nasal valve resistors. Oral appliances thrust the tongue or mandible forward during sleep, and are best fitted by an experienced dental provider. Ear, nose, and throat surgical techniques to reduce the uvula and soft palate are available, but the long-term effects are unknown. Because surgery can eliminate the noise of snoring without relieving airway obstruction, sleep study evaluation should be performed to rule out OSA prior to surgery.

Obstructive sleep apnea also occurs in 1–3% of younger children. Tonsil and adenoid hypertrophy are thought to contribute, since resection of these results in relief from OSA in the majority of children. However, the size of these tissues does not correlate with the presence or degree of OSA. Obstructive sleep apnea should also be considered in children with craniofacial abnormalities, macroglossia, neuromuscular disease, and obesity. As in adults, loud snoring, restless sleep, and witnessed pauses in breathing are symptomatic. Children with OSA may not complain of sleepiness; instead they may manifest daytime irritability, hyperactivity, decreased attention, or declining school performance. Secondary nocturnal enuresis is another important symptom of OSA. Parents should be asked about snoring and breath-holding during sleep. Consultation with an ENT specialist is advised whenever OSA is suspected. Tonsillectomy is curative in up to 90% of cases and should be the first step in treatment. Other causes of OSA can be treated with CPAP, though careful monitoring for midface hypoplasia should be undertaken in children aged less than 12 years. Surgical approaches such as tracheostomy or craniofacial reconstruction may be necessary in rare cases.

Central Sleep Apnea

Central sleep apnea (CSA) is defined as the cessation of airflow for at least 10 seconds with no ventilatory effort. In adults, central apnea accounts for approximately 5% of apnea cases, so CSA is much less common than OSA. Patients with predominantly central apnea tend to complain more of insomnia than of hypersomnolence, which may be a helpful distinguishing feature from OSA. The differential diagnosis of CSA includes congestive heart failure (CHF), hypoventilation (from chest wall, neuromuscular, or CNS disease), stroke, nasal obstruction, GERD, postnasal drip, and opiates. Congestive heart failure patients with reduced left ventricular function who show waxing and waning respiration during sleep are a particular type of CSA called Cheyne–Stokes respiration, which has been associated with reduced survival. Optimal treatment is unclear, but options include servo-ventilation (a form of bilevel), CPAP, and nocturnal oxygen. In patients with hypoventilation due to neuromuscular disease, chest wall disease or neurodegenerative diseases that affect the CNS respiratory control, bilevel treatment can address both the central apnea and hypoventilation. Gastroesophageal reflux disease and postnasal drip are infrequent causes of CSA, but should be addressed if no other causes are present. Opiates can cause CSA in a minority of patients, and the risk appears to be dose related; these cases may be more frequently seen because more patients are being treated for chronic pain issues. Lastly, the term “complex” sleep apnea has been used to describe OSA patients who develop central apnea when they are treated with CPAP. Complex sleep apnea has been estimated to occur in 6% of OSA patients treated with CPAP, but usually resolves over time with continued CPAP treatment. If necessary, both opiate CSA and complex apnea can be treated with a bilevel machine that delivers a back-up rate. Complex sleep apnea remains difficult and challenging, but is much less common than OSA.

Central sleep apnea can also be seen in prematurity, neonates, and children, but the differential diagnosis is broad and complex. A detailed discussion is beyond the scope of this review. The differential diagnosis ranges from apnea of premature infants, to GERD, to neurologic syndromes, and to hypoventilation syndromes such as congenital central hypoventilation syndrome (CCHS is caused by a PHOX2b mutation). Pediatric CSA may contribute to sudden infant death syndrome (SIDS). The cause of SIDS remains a mystery, but a wide variety of intrinsic and extrinsic factors are thought to play a role. A public information campaign to encourage mothers to avoid placing infants prone face down (“Back to Sleep”) has been ongoing since 1995, and subsequent epidemiologic assessments have shown a dramatic decrease in the number of SIDS cases.

Narcolepsy

Narcolepsy is a disorder in which elements of sleep intrude into wakefulness and wakefulness intrudes into sleep. It consists of four primary symptoms: excessive daytime sleepiness, cataplexy, and less frequently, sleep paralysis and hypnagogic hallucinations. It occurs in approximately 1 in 2000 people. Narcolepsy usually begins in the teens or early twenties, but onset as old as the eighth decade has been reported. Prevalence is roughly equal in men and women, and a formal diagnosis is frequently not made until 5 or 10 years after the onset of symptoms.

The cardinal symptom is sleepiness that comes on suddenly and irresistibly in what are called “sleep attacks.” Low-grade, persistent sleepiness affecting concentration, thinking, and memory may also occur. Sleep episodes may be brief (several minutes to an hour), but the person usually awakens feeling more alert, and the next sleep episode usually does not come on for at least an hour. Narcolepsy can impair nighttime sleep with frequent awakenings, vivid nightmares, and intense, realistic hallucinations prior to sleep onset (hypnagogic). The hallucinations are usually visual, but may involve any sensory modality. Cataplexy, the brief, sudden loss of muscle tone leading to neck muscle weakness, buckling of the knees, or rarely, complete collapse, is triggered by strong emotional reactions such as laughter or anger. Sleep paralysis is transient immobility on awakening, often accompanied by the vivid hallucinations of REM dreaming, all while the patient is lying in bed perfectly alert. The spells are brief, lasting several minutes at most. If the syndrome is not diagnosed and treated, people with the disorder may be perceived as lazy and unmotivated due to persistence of significant symptoms. Additional sequelae of a missed diagnosis include poor school and work performance, social stigma, and accidents.

Hypocretin-1 (Orexin), an alerting neuropeptide secreted by the hypothalamus, has been shown to play an important role in this disorder; a low CSF hypocretin-1 concentration below 110 pg/mL can be used as a diagnostic criteria. A combination of infectious, immune, and genetic factors appear to play a role in narcolepsy, and a human leucocyte antigen (HLA) linkage to DQB1∗0602 has been demonstrated. Confirmation of the diagnosis should be undertaken with overnight PSG followed by a multiple sleep latency test (MSLT). The finding of mean sleep latency less than 5 minutes and REM periods during at least two naps confirms the diagnosis. Since diagnosis can be challenging in atypical cases, the testing should be supervised by a sleep disorders specialist who can integrate both clinical history and sleep testing data. Without the symptoms of cataplexy, the diagnosis is more difficult. An accurate diagnosis is advisable, since narcolepsy is a life-long condition that often requires a commitment to long-term treatment.

Excessive daytime somnolence (EDS) of narcolepsy may be treated with modafinil (200–400 mg) or armodafinil (150–250 mg) each morning, which can significantly improve daytime function. Sodium oxybate (Xyrem), a relative of gamma-hydroxybutyrate (GHB), is FDA-approved to treat cataplexy, and is used by some clinicians to treat EDS. The older CNS stimulants, dextroamphetamine (5–60 mg/day), methamphetamine (20–25 mg/day), and methylphenidate (10–60 mg/day), are commonly used as well. Scheduling brief naps into one’s daily routine can be very helpful in improving function and reducing sleep attacks. Cataplexy and sleep paralysis can also be treated with REM-suppressant drugs such as TCAs and selective serotonin reuptake inhibitors (SSRIs). Joining a narcolepsy support group will help patients cope with the psychological sequelae, which result from the social and occupational stigma of having little control over sleep onset.

Kleine–Levin Syndrome

Kleine–Levin Syndrome is a condition characterized by periods of excessive hypersomnia and increased sleep time with frequent recurrences of the symptoms. The peculiar disorder is usually seen in people in their late adolescent years. These episodes can last from less than a week to 30 days. While the disease is active, some people experience other symptoms of excessive eating and hypersexuality. Social aspects of the patient’s life will suffer during the active periods, such as not attending school or work. In between the flare-ups, the patient functions normally in all respects, but recurring symptomatic periods will begin to show sporadically. In most cases, the frequency and intensity of the spells decreases as the adolescent matures and eventually will resolve itself. It is thought to be caused by a virus or local encephalitis in the diencephalon region. Amphetamines, methlyphenidates, and modafinil have been used as treatment, but usually they are only effective for a few hours.

Patients With Abnormal Nighttime Behavior: The Parasomnias

An accurate diagnosis of the underlying cause of bizarre nighttime behavior can be challenging. Diagnostic considerations include seizure disorders, psychosis, delirium, and intoxication. Parasomnias, the least common class of sleep disorders, but perhaps the most dramatic in their presentation, need to be included in the differential.

Pavor Nocturnus

Sleep terrors (pavor nocturnus) are very disconcerting to parents but are usually quite benign. The child (usually aged 3–6 years) awakens with a scream and appears terrified, with signs of autonomic arousal: eyes bulging, heart racing, and sweating. Most episodes last only a few minutes. Attempts at comfort are to no avail and may exacerbate or prolong the episode. In the morning, the child is amnestic for the episode or may have a fragmentary memory of a bad dream. Sleep terrors involve partial arousals from stage 4 (deep) sleep. Reassurance of the parents is the usual treatment; in persistent night terrors, however, benzodiazepines may be justified.

Nightmares

True nightmares occur in REM sleep and occasionally occur in stage 1 or 2 sleep. The nightmares involve a narrative story people can often relate once awake. This story is not necessarily a recall of the day’s actual events but a stressful episodic account that can be linked to the day’s events. Nightmares are usually a transient problem, presumably triggered by a stressful personal incident. Persistent nightmares are a serious concern, however, and may require referral to a mental health specialist.

Post traumatic stress disorder has many accompanying symptoms, and one indication the patient is suffering from the disorder is persistent recurring nightmares (see Chapter 26). The nightmares of PTSD patients are distinguished from other nightmares because they are narratives of the actual traumatic event, usually set in a previous time, and mimic the memory of the experience. For example, many wartime veterans have persistent nightmares that they are on the battlefield, and they feel all the fear and terror they felt when they were actually taking part in the war. When a person is stressed from normal life expectancies, dreaming can be cathartic and help to sort out feelings. For people with PTSD, dreaming about what had caused them so much stress is detrimental and just reinforces the traumatic events they experienced. The other dreams they have that do not relate directly to the trauma also have negative emotional contents of threat, aggression, and are extremely vivid compared with control populations. There is no specific treatment for the nightmares that patients with PTSD experience, but by treating the disorder with medications and cognitive behavior therapy, the nightmare frequency will reduce. Controlled trial data and clinical experience supports the use of alpha-1 adrenergic receptor antagonists (e.g., prazocin) in reducing the intensity and frequency of nightmare in PTSD. Alpha-2 receptor agonists (e.g., clonidine and guanfacine) may help sleep and other autonomic arousal symptoms in PTSD. Antidepressant and mood-stabilizing atypical antipsychotic medications are generally used to help with daytime symptoms but can sometimes help sleep as well.

Somnambulism

Like sleep terrors, sleepwalking is a partial arousal from stage 4 sleep. Occasional sleepwalking is very common in childhood and may follow a period of stress or sleep deprivation. The main concern is accidental injury, and protective measures, such as placing gates in front of a stairwell, may be needed.

Rem Behavior Disorder

In this syndrome, loss of normal REM sleep muscle atonia leads to dream-enactment behavior. The diagnosis is made in patients with sudden bursts of excited, intense, sometimes violent activity during sleep. The syndrome may be subtle, in the form of leg movements and talking, or dramatic, with punching, kicking, grabbing, strangling, running, and moving about the bedroom. Dreams of an intense, violent nature are typical. REM behavior disorder is seen frequently in toxic or metabolic delirium, but the most persistent forms of the syndrome occur in old age, and are presumed to be idiopathic, ischemic, or neurodegenerative in etiology. The syndrome is especially common in patients with PD and dementia with Lewy Bodies and can start to develop even before other signs of the diseases. Once documented by PSG, the condition can be effectively treated with clonazepam, although there are reports of other agents, such as cholinesterase inhibitors, working as well.

Movement Disorders in Children

Other movement disorders such as rhythmic sleep disorders (head banging, body rocking, and head rolling) interestingly do not cause insomnia, but are usually brought to the examiner’s attention by the caregiver for hazardous concerns. Rhythmic movements are observed in normal children at 9 months of age, and the occurrence decreases by 50% by the age of 18 months. By 4 years of age, the prevalence is only 8%. These movement disorders are usually seen on PSGs just before sleep onset and can persist into stage 1 non-REM sleep or after spontaneous arousal. Because these various movements can disrupt sleep, the child experiences excessive daytime sleepiness. Fortunately, between the ages of 2 and 4 years, the intensity decreases, and usually resolves spontaneously. Rarely is this disorder observed in healthy adolescents or adults.

Epilepsy

Epileptic discharges often occur during sleep and may be misinterpreted as other sleep arousal phenomena, such as somnambulism or pavor nocturnus. Onset of a seizure disorder can be at any age, but most commonly will begin in adolescence. Epileptic events generally occur in the non-REM stages of sleep and rarely in the REM stages. Nocturnal seizures may produce arousals that may or may not be remembered by the patient, and depending on the frequency and duration of arousals, can cause daytime sleepiness. Postictal sleepiness can also persist into daytime. In fact, daytime sleepiness in patients with epilepsy is not always attributable to antiepileptic medications.

There are particular types of seizures more prone to occur during sleep. Benign childhood epilepsy with centrotemporal spikes (BECT), or benign Rolandic epilepsy, is triggered by sleep and is recognized by unilateral facial paresthesias with tonic or tonic–clonic movement. If the pharyngeal muscles are involved, these symptoms will be coupled with drooling.

Seizures that involve the frontal lobe present themselves as peculiar behavior involving motor activity and unusual vocalizations. Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) involves thrashing activity with spastic posture and speaking vociferously. These patients may also sleep walk and become violent. Nocturnal paroxysmal dystonia involves tonic spasms of the limbs and laughter as the vocalization. Pure tonic seizures also involve the frontal lobes and appear as insomnia or hypersomnia because of periodic arousals.

Diagnosis of seizure disorder involves routine EEGs or prolonged video EEGs combined with clinical symptoms to classify the seizure type. Anticonvulsant medications are given to those diagnosed to prevent further electrical discharges.

DIAGNOSTIC EVALUATION & REFERRAL

Most types of insomnia are diagnosed on the basis of history, and PSG evaluation of insomnia is rarely necessary or reimbursed. Clinicians should be able to accurately diagnose and treat transient insomnia without referral or consultation. Referral to a sleep specialist should be considered for patients with persistent symptoms who do not respond to initial treatment. Patients with severe RLS and chronobiological sleep disorders should usually be referred. Sleep-related breathing problems, periodic leg movements, narcolepsy, and the adult parasomnias all require PSG validation and expert management and will require a sleep specialist to validate the diagnosis and initial treatment plans.

The National Sleep Foundation. www.sleepfoundation.org. Accessed February 2014.

The Society of Behavioral Sleep Medicine. www.behavioralsleep.org. Accessed February 2014.

American Academy of Sleep Medicine. www.aasmnet.org. Accessed February 2014.

Willis-Ekbom Disease Foundation. www.rls.org. Accessed February 2014