case 3

notes.docx

Glen P. Greenough, Brooke G. Judd

Sleep disorders are associated with major functional impairments, including loss of productivity, work-related and vehicular accidents, social impairment, and cognitive and mood disturbances, as well as morbidity and mortality as a result of cardiovascular, endocrine, and immune disturbances. Given the significance of these disorders, it is incumbent on primary care providers to recognize the symptoms of sleep disorders, to make accurate diagnoses, to initiate sound referrals, and to develop successful treatment plans in collaboration with sleep medicine specialists.

In this chapter, an overview of normal sleep is presented along with a description of the most common disorders of sleep. The most recent edition of the International Classification of Sleep Disorders 1 (ICSD) organizes the conditions into seven major categories: insomnias, sleep-related breathing disorders, central disorders of hypersomnolence (excessive sleepiness not related to other sleep disorders), circadian rhythm sleep-wake disorders, sleep-related movement disorders, parasomnias (abnormal behaviors or events arising from sleep), and other sleep disorders. These categories, which are largely symptom based (e.g., insomnia or hypersomnias), serve as a guide to obtaining a detailed history and initiating essential diagnostic procedures.

From a practical standpoint, fundamental assessment of sleep, which should be part of any complete patient history, can begin with three basic questions: How are you sleeping at night? Are you excessively sleepy during the daytime? Are there any unusual events or problems with your sleep, especially heavy snoring? More detailed aspects of assessment are included in individual sections within this chapter.

Normal Sleep

Definition and Physiology

Sleep is an active, dynamic physiologic process. Normal human sleep consists of two major states of consciousness: non–rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. NREM sleep is further divided into three stages from lightest (N1) to deepest (N3, also referred to as slow-wave or delta sleep). These stages unfold in a predictable, repeated cycle. In young adults, NREM sleep occupies about 75% of the night and REM the remaining 25%. Delta sleep is most prominent in young children and gradually diminishes through the life cycle. REM sleep (or its ontogenetic precursor) is seen in very high percentages in neonates and infants but diminishes rapidly in the first years of life and remains fixed at about 25% thereafter. Normal total sleep time varies considerably with age. 2 Although young children require longer sleep times, total sleep time begins to decline by the second decade, remains relatively stable from the third decade through the fifth decade, and falls off more dramatically after the age of 70 years. It remains unclear to what extent the decline in nocturnal sleep in older individuals is a function of diminished sleep need as opposed to decreased 1210ability to sleep. Time to fall asleep (sleep latency) and wake time after sleep onset are increased in older adults, as is daytime napping, although much of this may be related to factors that often accompany aging as opposed to the aging process itself.

NREM sleep is associated with a decline in respirations, heart rate, and blood pressure; muscle relaxation; and diminished cognitive activity. Sleep starts (sudden muscle contractions involving part or all of the body) may occur during wake-sleep transitions. REM sleep is marked by pronounced changes in physiology, including skeletal muscle atonia; increased variability in heart rate, blood pressure, respiration, and autonomic function; REM; and heightened cognitive activity associated with dreaming. Ventilatory drive to hypoxia and hypercapnia is decreased during NREM sleep and reaches its lowest point in REM sleep.

Current theories of sleep regulation focus on the two-process model. 3 This model suggests that sleep is regulated by two factors: homeostatic sleep drive, which increases progressively during wake time; and circadian wake drive, which is based on the oscillating 24-hour rhythm of the major circadian clock, located in the suprachiasmatic nucleus of the hypothalamus. Thus, the timing and amount of sleep are influenced by complex interactions between the biologic rhythms and the length of time since the last sleep period. Average human circadian cycles naturally run slightly longer than 24 hours (about 24.2 hours) but are reset daily (entrained) to a 24-hour rhythm by a variety of environmental cues, the most important of which is exposure to light. Sleep-wake rhythms are normally synchronized with myriad other clock-regulated physiologic functions, including endocrine-metabolic, immune, and cardiovascular.

Insomnia and Nonrestorative Sleep

Definition and Epidemiology

Current epidemiologic data indicate that about 30% to 35% of individuals in Western society report at least occasional insomnia. 4 Multiple studies place the prevalence of chronic insomnia at about 10%. 4 Insomnia is a complex condition that may represent a final common pathway with numerous contributing factors. Acute or transient insomnia (days to a few weeks) is an almost universal problem that is typically related to an acute stress or time zone shift (i.e., jet lag) and is usually self-resolving. Good sleep hygiene and, for some patients, short-term sleep medications are usually adequate. A potential complication of short-term insomnia is that some patients will begin to exhibit cognitions and behaviors that establish a foundation for development of a chronic insomnia problem.

Pathophysiology

A widely accepted model of chronic insomnia suggests that it is a function of predisposing, precipitating, and perpetuating factors. Little is known about predisposing biologic or psychological factors, although it does seem clear that certain persons are at greater risk than others for the development of a chronic insomnia problem. Precipitating factors (which are sometimes referred to as causes of chronic insomnia) are identified in Box 227-1 and are discussed in greater detail later.

Box 227-1

Some Key Precipitants of Chronic Insomnia

Psychiatric Disorders

Adjustment disorders

Mood disorders

• Major depressive disorder

• Bipolar disorder

• Dysthymic disorder

Anxiety disorders

• Generalized anxiety disorder

• Post-traumatic stress disorder

• Panic disorder

Psychotic disorders

Personality disorders

Substances and Medications

Alcohol

Stimulants

• Amphetamines, methylphenidate, modafinil, cocaine, ecstasy (MDMA, or 3,4-methylenedioxymethamphetamine), or caffeine

• Steroids

• Bronchodilators

• Some antihypertensives

Some antidepressants

Cholesterol-lowering agents

Medical and Neurologic Disorders

Degenerative neurologic diseases

Stroke

Recurrent nocturnal headache

Traumatic brain injury

Chronic obstructive pulmonary disease, nocturnal dyspnea, cough

Nocturnal angina

Gastroesophageal reflux disease, other nocturnal gastrointestinal disturbance

Pain from any source

Nocturia

Endocrine disorders

Other Sleep Disorders

Obstructive or central sleep apnea

Restless legs syndrome, periodic limb movements

Nightmare disorder

Circadian rhythm disorders

A unifying concept in the pathophysiology of chronic insomnia is that of hyperarousal. 5 Data indicate that patients with this condition exhibit evidence of both physiologic and cognitive hyperarousal, in the form of increased 24-hour metabolic rate, increased temperature, muscle tension, sleep electroencephalogram frequency, overactivity of the hypothalamic-pituitary-adrenal axis, and cognitive activity. It remains unclear how this hyperarousal develops, although preliminary data suggest that it is, at least in part, acquired and is amenable to change with therapeutic interventions such as cognitive behavioral treatment.

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Clinical Presentation

Psychiatric disorders, especially major depression, are the most common precipitating factors. Generalized anxiety, panic, and post-traumatic stress disorders are also associated with elevated rates of insomnia. Substance abuse or dependence, including alcohol, sedative-hypnotics, stimulants, and opiates, frequently manifests with insomnia, which may persist even after discontinuation of the substance. Excessive use of caffeine or even moderate use later in the day may also be problematic.

Circadian disorders, especially shift work and delayed sleep-wake phase disorder, are commonly associated with sleep complaints. Significant percentages of night shift workers experience abnormal sleep, with reduced total sleep times and poor quality of sleep. This pattern does not tend to improve during long periods of night work for most shift workers. As a result of circadian misalignment and sleep disturbances, shift workers are at increased risk for a number of medical disorders (ulcer disease, breast cancer among female shift workers, and cardiovascular disease) as well as accidents. Delayed sleep-wake phase disorder occurs most commonly in adolescents and younger adults and is characterized by an inability to sleep at normal clock times, with normal sleep onset occurring late (e.g., 4 AM), and subsequent inability to arise at conventional times (e.g., noon awakening). Sleep is otherwise restorative and normal, but the schedule is clearly inconsistent with meeting of normal school or work times. Advanced sleep-wake phase disorder is a less common circadian rhythm disorder, with normal sleep quantity and quality occurring early in the 24-hour day (e.g., 7 PM to 3 AM). It appears to be most common in older adults.

Medical conditions and medications may contribute to sleep disturbance. Among the most common are those associated with nocturnal pain, chronic lung disease, end-stage organ failure, endocrine disorders and other metabolic conditions, and especially neurodegenerative diseases. Likewise, many medications may aggravate sleep, most notably steroids, methylxanthines, some antihypertensives, stimulants, and certain antidepressant medications.

Other physiologic sleep disorders may result in an insomnia problem. The patient with restless legs syndrome (RLS) reports distressing, “creepy-crawly” sensations in the legs or, less commonly, arms. The sensation is associated with an irresistible urge to move the extremities. The sensations may interfere with sleep onset. RLS is often associated with periodic limb movements (PLMs), which are characterized by repetitive, periodic (every 20 to 40 seconds) limb movements, often resulting in arousals that the sleeper is unaware of (much as in obstructive sleep apnea [OSA]). RLS is discussed in greater detail in the section on movement disorders.

Although OSA is most often associated with complaints of daytime sleepiness rather than with insomnia, these patients may have clinically significant complaints of insomnia. This association may be more prevalent among women with OSA. Therefore OSA must also be considered in the differential diagnosis, particularly in obese patients and those with heavy snoring.

The essential features of chronic insomnia according to the ICSD-3 are frequent and persistent difficulty initiating or maintaining sleep with a daytime consequence. An important subtype of chronic insomnia is psychophysiologic insomnia (PPI), a conditioned arousal in response to efforts to sleep and negative expectations regarding the ability to sleep. Individuals with PPI may be able to sleep better when they are not trying to fall asleep or in settings other than their own bedroom. Symptoms may include difficulty getting to sleep as well as trouble returning to sleep after awakening. This type of insomnia exists commonly as a disorder in its own right. However, the hyperarousal and negative conditioning that occur in this disorder are frequent complicating factors in insomnia that is associated with the numerous precipitating factors described earlier. Often, when an initial precipitating factor (e.g., a major depression, acute stress, or medical illness) resolves, it is these conditioned psychophysiologic elements that serve as the perpetuating factors noted earlier in this chapter.

Diagnostics

The essential element in the evaluation of an insomnia complaint is the history. The nature of the onset, course, complications, and treatments of the condition must be elicited in detail. Sleep-wake schedule, including napping, is critical to assessment. Sleep logs, usually conducted for 1 or 2 weeks, can be a helpful adjunct to history. The log should contain the following information for each night: time of getting into bed, time lights are actually turned out (e.g., after television, reading), estimate of sleep latency (time to fall asleep after lights out), estimate of the number of awakenings and total awake time across the night, time of final awakening, and time of actual arising. Evidence of other sleep-related symptoms (e.g., snoring and observed pauses in breathing, limb movement or restless legs, nightmares, behavioral disturbances, headaches, pain, gastroesophageal reflux) must be sought from the patient and, whenever possible, the bed partner. Daytime consequences, particularly evidence of significant sleepiness, should be assessed. Medical, neurologic, and psychiatric evaluations as well as pertinent physical examination and appropriate laboratory procedures are essential.

Polysomnography (PSG), overnight sleep recording, contributes little to the diagnosis of most insomnia presentations and is usually reserved for those cases in which demonstrable physiologic disturbances are suspected, typically breathing disorders, hypersomnias, and some parasomnias. PSG may also be appropriate for patients with treatment-refractory insomnia.

Differential Diagnosis

Insomnia

• Chronic insomnia disorder

• Excessive time in bed

• Circadian rhythm disorders (shift work, delayed or advanced sleep phase)

• Short sleeper

• Other primary sleep disorder (RLS, periodic limb movement disorder, sleep-related breathing disorder)

• Short-term insomnia disorder

Management

The management of insomnia begins with careful identification of the contributing factors. Treatment is tailored based on those 1212factors. When clear precipitating causes are present (e.g., major depression or RLS), specific therapies appropriate to those factors must be instituted (e.g., antidepressant medication or dopamine agonists for RLS). Attention must also be directed to substances or medications that may be disturbing sleep. Sleep hygiene education is an essential component for management of any insomnia problem but is typically not sufficient treatment in its own right.

Treatment of circadian rhythm sleep disorders is often complex and in many cases is best administered by sleep medicine specialists. Bright light therapy and melatonin have demonstrated therapeutic benefit in certain patients with sleep-wake schedule disorders. Chronotherapy (planned behavioral adjustments of schedule) involving progressive phase delay has also been used for patients with delayed sleep phase disorder.

1. Once precipitating factors have been evaluated and treated, additional therapeutic approaches lie largely in the pharmacologic and behavioral realm.

2. The most commonly employed hypnotic medications are benzodiazepine receptor agonists, so called because they act selectively at the benzodiazepine receptor. This category includes standard benzodiazepines and newer agents such as zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta), which bind at the benzodiazepine receptor. In addition to the benzodiazepine receptor agonists, the very-short-acting melatonin agonist ramelteon (Rozerem) is approved for treatment of sleep initiation problems.

3. The benzodiazepine receptor agonists and ramelteon have comparable efficacy and, like the benzodiazepines themselves, differ primarily with respect to the clinical duration of action. Although hypnotic medications have been indicated only for short-term use until recently, emerging data have demonstrated safe and effective long-term use of some benzodiazepine receptor agonists, without dosage escalation or evidence of dependency in controlled settings. 6 However, a clear algorithm for long-term use of pharmacologic therapies and the interaction of these therapies with nonpharmacologic approaches has yet to be elucidated.

4. Cognitive behavioral therapy for chronic insomnia (CBT-I), particularly PPI, is brief and produces sustained benefit. 7 Compared with short-term courses of medication, CBT-I produces durable improvement, whereas improvements seen with time-limited courses of hypnotics tend to dissipate rapidly after drug discontinuation. Behavioral therapies include sleep restriction therapy, stimulus control, and relaxation training (Table 227-1). These therapies are often combined on a case-by-case basis. The common component of the most successful therapeutic approaches is marked reduction of the time spent in bed awake. In addition to the behavioral components, successful CBT regimens also include cognitive restructuring to identify and to alter the distorted cognitions that are often so much a part of the fabric of insomnia.

TABLE 227-1

Common Behavioral Therapies for Chronic Insomnia

Sleep restriction	Maintain a sleep log and determine the mean TST for the baseline period (e.g., 1-2 wk). Set bedtime and wake-up times to approximate the mean TST to achieve >85% sleep efficiency (TST/TIB × 100%) during 7 days. The goal is for the total TIB (not <5 hours) to approximate the TST. Make weekly adjustments:
	1. For sleep efficiency (TST/TIB × 100%) >85%-90%, TIB can be increased by 15-20 min.
	2. For sleep efficiency <80%, TIB can be further decreased by 15-20 min.
	Repeat TIB adjustment every 7 days.
Stimulus control	Go to bed only when sleepy; maintain a regular schedule; avoid naps; use the bed only for sleep. If unable to fall asleep (or back to sleep) within 20 minutes, remove yourself from bed—engage in relaxing activity until drowsy, then return to bed; repeat this as necessary.
Relaxation therapy	Progressive muscle relaxation training involves methodical tensing and relaxing of different muscle groups throughout the body. Specific techniques are widely available in written and audio form.

TIB, time in bed; TST, total sleep time.

5. Access to CBT-I by skilled and experienced clinicians can be problematic, particularly in primary care settings outside of larger centers. Training in behavioral therapy for insomnia is available to primary care providers in brief continuing education courses, and a referral to a psychologist familiar with the use of these therapies should be readily available in most urban communities. Internet-based CBT-I programs are currently evolving and offer promise of delivery of this much-needed therapy to larger populations of patients.

Life Span Considerations

Advanced sleep phase syndrome, which may lead to sleep maintenance issues, is most common in older adult populations.

Complications

Insomnia is associated with mood disorder.

Indications for Referral and Hospitalization

Patients with insomnia that is persistent and causing impairment in daytime activities should be referred to a sleep specialist.

Patient and Family Education

Tips for good sleep hygiene from the National Sleep Foundation (http://sleepfoundation.org/ask-the-expert/sleep-hygiene) are as follows:

• Avoid napping during the day. It can disturb the normal pattern of sleep and wakefulness.

• Avoid stimulants such as caffeine, nicotine, and alcohol too close to bedtime. Although alcohol is well known to speed the onset of sleep, it disrupts sleep in the second half as the body begins to metabolize the alcohol, causing arousal.

• Exercise can promote good sleep. Vigorous exercise should be taken in the morning or late afternoon. A relaxing exercise, such as yoga, can be done before bed to help initiate a restful night's sleep.

• Food can be disruptive right before sleep. Stay away from large meals close to bedtime. Also, dietary changes can cause sleep problems; if someone is struggling with a sleep problem, it is not a good time to start experimenting with spicy dishes. And, remember, chocolate contains caffeine.

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• Ensure adequate exposure to natural light. This is particularly important for older people, who may not venture outside as frequently as children and adults. Light exposure helps maintain a healthy sleep-wake cycle.

• Establish a regular relaxing bedtime routine. Try to avoid emotionally upsetting conversations and activities before trying to go to sleep. Do not dwell on your problems or bring them to bed.

• Associate your bed with sleep. It is not a good idea to use your bed to watch TV, listen to the radio, or read.

Sleep-Related Breathing Disorders

Definition and Epidemiology

The sleep-related breathing disorders encompass a number of disorders, including the OSA disorders, central sleep apnea (CSA) syndromes, and the sleep-related hypoventilation disorders.

OSA is the most common sleep-related breathing disorder. Clinically significant OSA occurs in at least 2% to 4% of women and 4% to 10% of men in North America. 8 The predominant physiologic derangement in OSA is repetitive upper airway narrowing or closure, which occurs during sleep. The closures (or near-closures) can occur many times a night, leading to significant sleep fragmentation and poor-quality sleep.

CSA is less common than OSA, although increasingly recognized. The CSA syndromes are characterized by reduced or absent airflow because of decreased or absent respiratory effort. As with OSA, CSA events often recur many times a night and can be associated with sleep fragmentation and poor-quality sleep. Many patients have a combination of OSA and CSA.

Pathophysiology

OSA is characterized by repetitive episodes of complete upper airway occlusions (known as apneas) or partial upper airway occlusions (known as hypopneas) during sleep. These partial or complete airway closures lead to increased efforts to breathe, finally terminating in a brief central nervous system (CNS) arousal from sleep to reestablish patency of the upper airway. These events are often, although not always, associated with transient reductions in blood oxygen saturation. The cause of the upper airway narrowing may be related to craniofacial structure predisposing to a narrowed airway, as well excessive soft tissue bulk impinging on upper airway (excessive fat deposition in the tongue, soft palate, and lateral pharyngeal walls). The airway is kept patent by the pharyngeal dilating muscles. The activity of these muscles decreases with sleep onset, although it is normally adequate to maintain patency of the airway. In patients with OSA, however, the activity of the pharyngeal dilator muscles during sleep is not adequate to maintain full patency, and partial or complete obstruction ensues. With each brief arousal, the muscle activity returns to wakefulness levels and patency is reestablished.

In CSA, the primary derangement is altered CNS respiratory drive, such that the patient does not receive the usual metabolic feedback to the CNS during sleep to drive the breathing in its normal pattern. This leads to repetitive cycles characterized by cessation of airflow because of lack of respiratory effort, which terminates once the metabolic trigger to breathe (usually blood carbon dioxide levels) increases sufficiently to drive respiratory output from the CNS. As with OSA, there are often brief CNS arousals associated with these events, leading to fragmented sleep.

CSA has a variety of causes, the hallmark of all of them related to processes that affect chemoresponsiveness and respiratory pattern stability. The more common causes of CSA include underlying significant cardiac or neurologic disease, such as atrial fibrillation or flutter, congestive heart failure, stroke, or brainstem disorders. These illnesses are often associated with a type of CSA known as Cheyne-Stokes breathing. This pattern is characterized by recurrent central apneas alternating with a waxing and waning pattern of airflow. Another, more common cause of CSA is the use of opioid medications, particularly the long-acting opioids, which affect respiratory drive.

Clinical Presentation

A history of OSA is most often suggested by loud, disruptive snoring, with or without witnessed apneas, nocturnal gasping, or choking. Patients may report frank excessive daytime sleepiness (EDS), daytime fatigue and tiredness without unintentional sleep, or even vague depressive symptoms. They are often not aware of fragmented sleep because the respiratory-related arousals are often too brief to be consciously registered during the night. In fact, patients not uncommonly report that they sleep well through the night and are puzzled by their daytime sleepiness. Nocturia is a frequent complication of the disorder.

The most common risk factor for OSA is obesity, and patients may be able to relate the onset of their symptoms to weight gain. The disorder is more common in men, although the prevalence rate in postmenopausal women approaches the same level as in men. A substance history is helpful in that particular substances may alter airway muscle tone and further increase risk for obstructive respiratory events. This includes the use of alcohol, opiates, or muscle relaxant medication such as the benzodiazepines in the evening. It is also helpful to elicit other medical history, such as heart disease, hypertension, or stroke, because these disorders may be seen with OSA. On physical examination, the presence of obesity and a crowded oropharynx may be suggestive of OSA in a patient with symptoms associated with the disease.

In addition to leading to EDS and impairment of daytime functioning, untreated OSA has been found to have associations with a variety of longer term health consequences. There is substantial convincing evidence that untreated OSA is an independent cause of systemic hypertension, other cardiovascular disease, and stroke. 9 , 10 In addition, there is mounting evidence of an association with metabolic syndrome and type 2 diabetes mellitus. 11 Individuals with CSA may be noted by their bed partner to have pauses in their breathing, which may or may not be followed by a period of more rapid breathing. They typically will not, however, have a history of snoring. These patients may also have complaints of EDS or daytime fatigue because the central apneic events disrupt sleep in a way similar to OSA events. Risk factors for CSA include decompensated congestive heart failure and the use of opioid medications, particularly the long-acting opioid medications such as methadone.

Diagnostics

Overnight Sleep Testing

• Full overnight PSG is the gold standard for the diagnosis of sleep-related breathing disorders. 12

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• Unattended out-of-center sleep testing (OCST) is increasingly being used for the diagnosis of OSA. OCST is typically performed at home and assesses fewer biometric measures than full PSG. OCST is more accessible and cost-effective than full PSG, although it is crucial to understand the limitations of the usefulness of OCST and potential pitfalls. 12 OCST is indicated for patients with moderate to high pretest probability of OSA and no significant comorbidities or use of medications that increase risk for other breathing disorders, such as CSA or hypoventilation. It is also important to understand that OCST generally underestimates the number of obstructive respiratory events, and full PSG should be considered if the OCST result is negative in a patient with significant OSA risk factors or reported symptoms.

• Overnight pulse oximetry is not sufficiently sensitive to be used as a reliable screening test for sleep apnea.

Differential Diagnosis

Sleep-related breathing disorders often overlap and cannot be distinguished by clinical history alone. Nocturnal breathing disorders may also occur as a symptom of other underlying cardiopulmonary disorders. It is important to identify whether the nocturnal disorder is related to other concurrent disease (such as chronic obstructive pulmonary disease [COPD] or congestive heart failure).

Other causes of sleep fragmentation and/or EDS should also be considered (see separate sections on insomnia and hypersomnia for list).

Management

Obstructive Sleep Apnea

• Continuous positive airway pressure (CPAP).

• This is the most common and effective treatment, with efficacy rates of 95%. It is also essentially free of dangerous side effects.

• The major impediments to successful CPAP therapy are comfort and acceptance. Careful counseling and initial attention to equipment fit can go a long way toward ensuring patient adherence with the device.

• Weight loss may also be helpful in the overall management strategy, although this should not be used as the sole treatment modality in patients with anything more than mild OSA.

• Custom-fit oral appliances.

• Designed to increase posterior airway dimensions.

• May be effective for milder OSA; not as effective as CPAP.

• Upper airway surgical procedures.

• Standard procedures are designed to remove excessive upper airway tissue. These modalities, however, are less effective than CPAP, and success cannot be predicted before treatment. Less commonly, appropriate treatment choices may include tracheotomy or, in patients who have undergone a careful preoperative evaluation and failed to respond to less-invasive therapies, more extensive maxillofacial surgery.

Central Sleep Apnea

• If possible, tapering or discontinuation of medication that may be causing CSA.

• If CSA is related to decompensated or unstable cardiovascular process, the CSA may improve with improvement in the cardiovascular process.

• Positive airway pressure (PAP).

• CSA may improve with CPAP, although there are newer PAP devices that are able to vary ventilatory support and rapidly adapt to changes in respiratory drive to alleviate the CSA events in patients in whom CPAP therapy fails.

Life Span Considerations

OSA may occur at any age, although it is most common between young adulthood and middle age. OSA does occur in older adults, although development of OSA does not necessarily increase with age.

Complications

As discussed earlier, substantial evidence implicates untreated OSA as a risk factor for multiple cardiovascular diseases, including systemic hypertension, coronary artery disease, congestive heart failure, and stroke. There is also accumulating evidence linking OSA to various arrhythmias, as well as increased risk for development of type 2 diabetes mellitus. OSA may also increase the severity of depression. Risk of motor vehicle accidents is significantly increased among those with OSA.

As opposed to OSA, CSA has not been identified as an independent risk factor for increased morbidity or mortality, although it can cause sleep fragmentation with associated hypersomnia, insomnia, or both.

Indications for Referral or Hospitalization

In general, sleep-related breathing disorders are managed in an outpatient setting by sleep medicine specialists.

Patient and Family Education

Patients should be educated about the impact of obesity on OSA, and weight loss should be encouraged. They should also be educated about the risks of untreated OSA and the importance of adhering to PAP treatment. They should understand that they should speak with the sleep provider if they are having problems tolerating PAP, because adjustments can be made to increase tolerance and acceptance.

Central Nervous System Hypersomnias

Definition and Epidemiology

The primary disorders of hypersomnolence are characterized by an intrinsic CNS deficit resulting in a sleep-wake system that is inadequate for maintaining wakefulness or overactive in promoting sleep. The predominant clinical characteristic of these syndromes is EDS not caused by disturbed nocturnal sleep or misaligned circadian rhythms.

The primary hypersomnias include narcolepsy, idiopathic hypersomnia, and post-traumatic hypersomnia. Narcolepsy, the best defined of the primary hypersomnias, is characterized by EDS and inappropriate manifestations of REM sleep. These include such phenomena as cataplexy (sudden onset of REM-related muscle atonia precipitated by emotion during wakefulness) and hallucinations and paralysis occurring at sleep onset (hypnagogic) or offset (hypnopompic) related to inappropriately timed REM. The EDS and the REM-related symptoms can 1215be extremely disabling and potentially dangerous, depending on when they occur.

Idiopathic CNS hypersomnia also involves CNS sleep system dysfunction, which results in profound EDS. However, with idiopathic CNS hypersomnia, there is no known disease of the REM system, and other symptoms present in narcolepsy are absent. Post-traumatic hypersomnia is not readily distinguishable from idiopathic hypersomnia, other than that the symptoms follow head injury or another CNS insult such as an infection.

Clinical Presentation

Assessment of the patient with EDS usually begins with either the patient or a family member complaining of sleepiness or unintentional sleep in undesired situations. This may include falling asleep unintentionally while watching television or reading, in noisy gatherings, at work, in conversation, or even while driving. Information obtained from a family member can be essential to accurate diagnosis because patients with EDS may not recognize or may minimize the severity of their symptoms. It is important to obtain a full sleep history, including 24-hour sleep-wake schedules, time and duration of naps, and associated symptoms that may point to the underlying cause of the EDS symptoms.

The key clinical feature of narcolepsy is EDS. Cataplexy, hypnagogic or hypnopompic hallucinations, sleep paralysis, and fragmented, disturbed nocturnal sleep may be present, but not all are required for the diagnosis. Cataplexy is seen almost exclusively in narcolepsy and is characterized by sudden episodes of muscle atonia during wakefulness. Cataplexy is often brought on when the patient is experiencing a strong emotion, particularly laughter. Such episodes may pose potential danger, depending on when and where they occur. They are often only seconds in duration but can last for minutes or longer in some cases. The sleep paralysis involves REM-related atonia (excluding the ocular muscles and diaphragm) and is often described as terrifying by patients. The hypnagogic or hypnopompic hallucinations are dreamlike and often frightening fragments that occur near sleep onset or offset and typically involve the patient's confusion about whether he or she is awake or asleep. The typical onset of narcolepsy symptoms is in the second or third decade, although it can occur earlier or later in life. There is no gender predominance. There are no features on physical examination that are particularly helpful in identifying narcolepsy.

The diagnosis of idiopathic CNS hypersomnia is most often a diagnosis of exclusion. Patients typically have complaints of EDS despite adequate or prolonged total sleep time, and they do not have the symptoms that otherwise characterize narcolepsy. A careful history should be obtained regarding possible CNS insult from infection or trauma.

In addition to using the history to identify these disorders, the health care provider should also question the patient for symptoms suggestive of RLS or periodic limb movement disorder (PLMD; discussed in further detail later in this chapter). The patient's sleep-wake schedule should also be evaluated to make certain that insufficient sleep is not playing a role, and a complete medication and substance history should be obtained because many medications and drugs may cause sleepiness as a side effect.

Diagnostics

Overnight PSG is generally employed in assessing the primary hypersomnias. The purpose is to exclude other underlying causes of the patient's sleepiness symptoms, such as an occult sleep-related breathing disorder. If no cause of EDS is identified on overnight PSG, the next step is to perform a multiple sleep latency test (MSLT). 13 The MSLT is used to determine one's propensity for daytime sleep. The subject is given multiple opportunities to nap under standardized conditions, and a mean sleep-onset latency (i.e., time to fall asleep) is determined and compared with normative values. This is the most objective means of determining EDS, although daytime continuous PSG can confirm findings. The presence of sleep-onset REM episodes on the MSLT is a required diagnostic finding for narcolepsy.

Differential Diagnosis

See differential diagnosis box.

Differential Diagnosis

Excessive Daytime Somnolence

• Insufficient sleep

• Sleep-wake system deficit

• Narcolepsy

• Idiopathic CNS hypersomnia

• Post-traumatic hypersomnia

• Sleep fragmentation

• OSA or CSA

• PLMD

• Circadian rhythm disorder

• Substances, medication, or primary medical or neurologic disorder

Management

EDS as a result of CNS-based disorders has historically been treated with psychostimulants (e.g., dextroamphetamine or methylphenidate). The non–habit-forming stimulant modafinil is increasingly used. Cataplexy is treated by use of REM-suppressing medications. Most commonly, these have included the tricyclic antidepressants and the selective serotonin reuptake inhibitor–type antidepressants. More recently, γ-hydroxybutyrate has become available as a therapy for cataplexy.

Sleep-Related Movement Disorders

Definition and Epidemiology

Sleep-related movement disorders are conditions in which patients have simple stereotyped movements or other sleep-related monophasic movements that disturb sleep. Sleep-related leg cramps, sleep-related rhythmic movement disorder, PLMD, and sleep-related bruxism are disorders that fall into this category. RLS, because of its association with PLMs, is included in this category. Because RLS is so common (5% to 10% in populations derived from Western Europe), 1 this will be the focus of this section.

Restless Legs Syndrome

The prevalence of RLS increases with age, but symptoms may start in childhood. RLS is seen more commonly in women. RLS is an uncomfortable sensation, usually in the legs, associated with a strong desire to move the legs. Because this discomfort occurs primarily in the evening, it may lead to sleep-onset difficulties.

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Pathophysiology

The pathophysiology of RLS is unclear. RLS may occur in association with a wide variety of conditions. Pregnancy, renal failure, and ferritin levels below 50 µg/L have the best-established associations. Peripheral neuropathy and Parkinson disease may also be associated with RLS. A number of widely used medications, including most antidepressants, sedating antihistamines, and dopamine antagonists, may cause or exacerbate RLS. 1 RLS, however, is often idiopathic or familial. Given the efficacy of dopaminergic agents in treating RLS, a CNS dysfunction in a dopaminergic system has been postulated as a cause of this syndrome.