Handbook of Sleep Disorders in Medical Conditions

States

Preface

Sleep research is a very active field. As a consequence, the physiology of sleep and the nature, etiology, and multiple consequences of sleep disorders are increasingly understood. Much less research however has focused on how sleep interacts with the presence of medical conditions, particularly chronic illnesses. With the aging of the population, the prevalence of the latter is dramatically rising. In 2012, it was estimated that about half of US American adults (i.e., 117 million people) had at least one chronic disease and that one in four had two or more.¹ The Center for Disease Control and Prevention (United States) estimated that 7 of the 10 leading causes of death in 2014 were chronic diseases, with 2 explaining nearly 46% of all deaths, that is heart disease and cancer.² Sleep disorders are highly prevalent in chronic illnesses including cancer, diabetes, cardiovascular disease, and neurological conditions. Some sleep disorders contribute directly to the incidence of the medical disease, such as obstructive sleep apnea increasing the risk of cardiovascular disease, or insomnia increasing the risk for rheumatoid arthritis or cardiometabolic disease. In many cases, however, sleep disorders appear during the trajectory of an illness and can take various forms. For example, patients can suffer from insomnia, sleep apnea, restless legs syndrome, and hypersomnolence.

Sleep disorders may affect the course of the illness, its treatment, as well as patients’ adherence to medical recommendations. For instance, insomnia increases the risk of developing infectious disease during cancer care trajectory. Furthermore, the decrease in quality of life already associated with conditions such as chronic pain or chronic fatigue can be worsened by the presence of sleep problems which add onto the burden of diseases by exacerbating the main symptoms or by increasing the risk of anxiety or depression. In patients with neurological conditions such as stroke or traumatic brain injury, sleep disorders have been shown to decrease the patient’s participation in rehabilitation. In the field of HIV, patients with sleep disorders seem to be less adherent to antiretroviral therapy. Sleep disturbances of patients may also affect the sleep of their caregivers, for example, parents of children with a chronic disease.

In turn, treating sleep disorders may be beneficial in the management of the medical condition. For example, treating insomnia in persons with cardiovascular disease has been shown to reduce rates of rehospitalization and have a positive impact on biomarkers of cardiovascular risk. In multiple sclerosis (MS), treating sleep disorders can have a positive impact on MS-related fatigue. In the context of dementia, treating sleep apnea is associated with improvement in general cognition, and providing education on sleep hygiene can lead to improved sleep in both patients and their caregivers, thus optimizing the care of these patients in the long run.

Although screening, assessment, and treatment of sleep disorders in various medical populations is increasingly recognized as critical, these services are unfortunately not consistently provided to patients. The diagnosis and differential diagnosis of sleep disorders can be more complex in the presence of medical comorbidity. For example, measurement of sleep quality can be arduous during hospitalization or in patients with severe cognitive problems. Furthermore, symptoms of the illness often overlap or are confounded with those of the sleep disturbance. In terms of treatment, although the general principles of sleep medicine may often apply, an adapted approach is warranted in many instances. For example, some pharmacological agents are known to exacerbate symptoms of the medical condition, including memory issues in persons with neurological conditions, gastrointestinal symptoms in those with gastrointestinal disorders, or worsening of sleep-disordered breathing in patients with lung disease. Similarly, nonpharmacological interventions such as cognitive-behavioral therapy for insomnia or exercise often need adaptations to ensure their maximal efficacy in patients with specific medical conditions.

The association of sleep disorders with chronic medical conditions is increasingly recognized and investigated. However, the magnitude of the body of evidence and the level of knowledge on how the presence of medical disorders affects sleep is variable across conditions. As an example, the impact of obstructive sleep apnea on the incidence of cardiovascular disease has received a great deal of attention, while research on sleep disorders in other medical conditions is more in its early stages. Furthermore, the literature on sleep difficulties comorbid with a medical illness has evolved quite independently from one health condition to the other.

In this handbook, we aim to bring together and review the current state of knowledge about the nature and manifestations of sleep disorders associated with a variety of common medical conditions. Furthermore, the handbook provides insights regarding special considerations for assessment or treatment, both pharmacological and nonpharmacological, in specific medical conditions. The book is divided into two sections.

Section I provides general information on the diagnostic criteria and assessment of the sleep disorders that are most likely to be encountered in medical settings including insomnia, sleep apnea, restless legs syndrome, and hypersomnolence (Chapter 1). Subsequently, pharmacological, medical, and psychological interventions for sleep disorders in general are presented, as well as the level of evidence supporting their efficacy. More specifically, Chapter 2 covers the treatment of insomnia, Chapter 3 describes interventions for breathing-related disorders, and Chapter 4 reviews treatment options for the other common sleep disorders, that is restless legs syndrome, periodic limb movement disorder, hypersomnolence disorders, circadian rhythm sleep disorders, and parasomnias.

In Section II, readers will find more specific information for particular chronic medical conditions, for example, cardiovascular disease, lung disease, obesity, diabetes, cancer, chronic pain, traumatic brain injury, dementia, stroke, HIV, inflammatory arthropathies, chronic fatigue syndrome, MS, and gastrointestinal disorders. Two additional chapters cover sleep disorders in pediatric patients with psychiatric and medical conditions and sleep in hospitalized patients. Each chapter reviews information on epidemiological aspects, risk factors and correlates, influence of sleep issues on the course of illness and treatment, consequences for patients, and special considerations regarding evaluation and treatment.

Taking into consideration sleep in the global management of patients with medical conditions is essential. This handbook provides guidance to diagnose and treat sleep disorders in a manner that is appropriately adapted to the comorbid medical condition. By identifying the significant knowledge gaps, it is also hoped that this handbook will urge more research in these various fields.

References

1. Ward BW, Schiller JS, Goodman RA. Multiple chronic conditions among US adults: a 2012 update. Prev Chronic Dis. 2014;11:E62.

2. Centers for Disease Control and Prevention. Leading causes of death and numbers of deaths, by sex, race, and Hispanic origin: United States, 1980 and 2014 (Table 19). Health. <https://www.cdc.gov/nchs/data/hus/hus15.pdf#019>; 2015 [PDF – 13.4 MB] Accessed 04.07.17.

Section I

General Issues

Outline

Chapter 1 Diagnostic Criteria and Assessment of Sleep Disorders

Chapter 2 Treatment of Insomnia

Chapter 3 Treatment of Breathing-Related Disorders

Chapter 4 Treatment of Sleep-Related Movement and Circadian Rhythm Disorders, Hypersomnolence, and Parasomnias

Chapter 1

Diagnostic Criteria and Assessment of Sleep Disorders

Christina Jayne Bathgate and Jack D. Edinger,    Department of Medicine, National Jewish Health, Denver, CO, United States

Abstract

Sleep is essential for survival and plays a key role in maintaining our physical and mental health. Over the past 40 years, the field of sleep medicine has increasingly focused on the role sleep disturbances have in the etiology of medical and psychological disorders and has proposed various methods of classifying sleep disorders as distinct clinical entities or as conditions occurring comorbid to various disorders. This chapter will provide a brief overview of sleep and sleep staging, the current classification systems used for sleep/wake disorders, a description of common sleep disorders and their relationship to various medical and mental health disorders, and frequently used assessment tools used to aid in diagnosis of sleep/wake disorders. The concluding section considers limitations to the classification systems and provides suggestions for future research.

Keywords

Sleep disorder diagnosis; assessment; classification; DSM-5; ICSD-3; ICD-10

Outline

Introduction 3

Current Diagnostic Classification Systems 5

Clinical Features and Diagnostic Considerations for Sleep/Wake Disorders 10

Insomnia 10

Hypersomnolence 11

Narcolepsy 12

Breathing-Related Sleep Disorders 13

Circadian Rhythm Sleep–Wake Disorders 14

Parasomnias 14

Movement-Related Sleep Disorders 16

Psychological, Behavioral, and Laboratory Assessments to Aid Diagnosis 16

Clinical History 16

Daily Self-Monitoring 17

Self-Report Questionnaires 17

Actigraphy 17

Polysomnography 19

Multiple Sleep Latency Test 20

Maintenance of Wakefulness Test 20

Areas for Future Research 20

Conclusion 21

References 23

Introduction

Sleep is essential for survival and plays a key role in maintaining our physical and mental health. Normal human sleep can be categorized into two states, as defined by a cortical electroencephalogram (EEG) readings, typically collected during a polysomnography (PSG) sleep test: nonrapid eye movement (NREM, pronounced non-REM) sleep and rapid eye movement (REM) sleep. NREM sleep produces a variably synchronous EEG that is associated with low muscle tone and minimal psychological activity¹ and is subdivided into three progressively deeper sleep stages: N1 (or Stage 1 sleep), N2 (or Stage 2 sleep), and N3 (or Stage 3 sleep, commonly referred to as slow wave sleep). On the other hand, REM sleep produces a desynchronized EEG with muscular atonia and episodic bursts of REM and is not typically subdivided, except possibly for research purposes (e.g., tonic vs phasic REM).¹ Table 1.1 provides a brief outline of the four sleep stages and general characteristics often associated with each stage. Sleep begins in NREM before the first REM period occurs, typically 80–120 minutes after sleep onset. Throughout the sleep period, we continue to cycle through the NREM to REM sleep stages approximately every 90 minutes, with NREM sleep decreasing and REM sleep increasing over time. This suggests that the beginning of our total sleep period tends to contain longer periods of deeper, more restorative slow wave sleep, and as our sleep period progresses, more time will be spent in REM sleep, where dreams typically occur.

Table 1.1

Current Diagnostic Classification Systems

There are currently three main diagnostic classification systems used widely by clinicians to classify sleep disorders. The International Classification of Sleep Disorders, Third Edition (ICSD-3),³ the Sleep Disorders section of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5),⁴ and the International Classification of Diseases, Tenth Edition (ICD-10).⁵ A schematic crosswalk comparing the specific diagnostic labels used across these three classification systems is presented in Table 1.2.

Table 1.2

Note: The International Classification of Diseases, Tenth Edition, Clinical Modification G codes refer organic sleep disorders, F codes refer to nonorganic sleep disorders, R codes refer to symptoms, signs, and abnormal clinical and laboratory findings, not elsewhere classified, and Z codes refer to factors influencing health status and contact with health services.

The ICSD-3 is currently the most advanced classification of sleep disorders and is intended to be used by sleep experts. This American Academy of Sleep Medicine publication describes nearly 70 highly specific diagnoses classified into six main clinical categories: insomnia, sleep-related breathing disorders, central disorders of hypersomnolence, circadian rhythm sleep–wake disorders, parasomnias, and sleep-related movement disorders. It also contains a supplemental Other category to assist with assigning codes to conditions that do not otherwise fit into any of the above categories, and two appendices (sleep-related medical and neurological disorders, and ICD-10 coding for substance-induced sleep disorders). Pediatric conditions are fully merged within each of the clinical categories, except for the obstructive sleep apnea (OSA) section, which provides a specific delineation between adult and pediatric OSA. The ICSD-3 provides general diagnostic criteria for each condition, and if indicated, will outline variations for pediatric diagnosis and developmental issues pertaining to older adults.

The DSM-5 is a classification system intended for use by mental health and general medical clinicians who are not experts in sleep medicine; however, this most recent revision reflects an overall greater concordance with the ICSD-3 compared to previous editions. This American Psychiatric Association publication features an entire Sleep–Wake Disorders section, outlining 10 disorders or disorder groups: insomnia disorder, hypersomnolence disorder, narcolepsy, breathing-related sleep disorders, circadian rhythm sleep–wake disorders, NREM sleep arousal disorders, nightmare disorder, REM sleep behavior disorder, restless legs syndrome (RLS), and substance/medication-induced sleep disorder. It also contains the additional diagnostic categories, other specified or unspecified which can be applied to insomnia disorder, hypersomnolence disorder, and a more general sleep–wake disorder to assist with assigning codes to conditions that do not otherwise fit into any of the above categories. Similar to the ICSD-3, the DSM-5 does not separate pediatric and adult diagnoses; rather, it provides general diagnostic criteria for each condition and outlines specific developmental features that may be present.

The ICD-10 is another classification system commonly used to classify sleep conditions. This World Health Organization publication is far less complex than the ICSD-3 schema and groups sleep disorders into global categories of organic and nonorganic origin. Organic sleep disorders, which are classified using G codes, focus on medically/neurologically based sleep disorders and diseases of the nervous system, such as sleep apnea or narcolepsy. Nonorganic sleep disorders, which are classified using F codes, focus on mental and behavioral disorders, and are organized into three types of conditions: dyssomnias, parasomnias, and sleep disorders secondary to medical and psychiatric disorders. Dyssomnias refer to a predominant disturbance in the amount, quality, or timing of sleep due to emotional causes, such as nonorganic insomnia, nonorganic hypersomnia, or nonorganic disorder of sleep–wake schedule. Parasomnias refer to abnormal episodic events occurring during sleep, such as sleepwalking, sleep terrors, teeth grinding, bed wetting, or nightmares. There are also sleep-related conditions classified using R and Z codes. R codes focus on symptoms, signs, and abnormal clinical and laboratory findings not elsewhere classified, such as Cheyne–Stokes breathing pattern or snoring. Z codes focus on factors influencing health status and contact with health services, such as sleep deprivation or inadequate sleep hygiene. Similar to the ICSD-3 and DSM-5, the ICD-10 does not separate pediatric and adult sleep diagnoses, with the exception of OSA and the behavioral insomnia of childhood diagnoses.

Clinical Features and Diagnostic Considerations for Sleep/Wake Disorders

Despite the existence of several classification methods used to diagnosis sleep disorders, our goal herein is to provide a brief description of each sleep disorder using the DSM-5 criteria as an overarching framework, since this classification system is intended for general medical clinicians and mental health professionals that may not necessarily be experts in sleep medicine. Diagnostic categories covered in this chapter will include insomnia, hypersomnolence, narcolepsy, breathing-related sleep disorders, circadian rhythm sleep disorders, parasomnias, and movement-related sleep disorders.

Insomnia

Insomnia disorder is characterized by difficulties falling or staying asleep and/or waking up earlier than desired with an inability to fall back asleep. The sleeping disturbance must occur at least 3 nights per week, for at least 3 months, and persist despite having an adequate opportunity for sleep. It must also cause the individual significant daytime impairment in social, occupational, educational, behavioral, or other important areas of function and cannot be better explained by another sleep–wake disorder (e.g., a breathing-related sleep disorder), the physiological effects of a substance, or a coexisting medical or mental health condition. Insomnia is considered episodic if the symptoms last for at least 1 month but less than 3 months, persistent if the symptoms last 3 months of longer, and/or recurrent if two (or more) episodes occur within the space of 1 year.

Insomnia that occurs in the context of another psychological or medical disorder is considered comorbid. Common comorbid conditions include cardiovascular diseases, metabolic disorders, autoimmune conditions, chronic pain, anxiety, and depression.⁴,⁶,⁷ Among a large sample of patients with at least one physician identified chronic condition (hypertension, diabetes, congestive heart failure, myocardial infarction, or depression), 34% reported mild insomnia and 16% reported severe insomnia.⁸ Insomnia was not only comorbid with these conditions at baseline but persisted despite receiving treatment for these concerns, such that at a 2-year follow-up, 59% of patients with mild insomnia at baseline and 83% with severe insomnia at baseline continued to report sleep problems.⁸ This suggests that insomnia should be considered an important treatment target among clinicians, as insomnia symptoms do not always remit during treatment of a comorbid condition.

Of the various aforementioned sleep difficulties, trouble maintaining sleep is the most common, followed by trouble falling asleep; however, patients will often present with a combination of these symptoms.⁴ Insomnia tends to affect women more than men⁹,¹⁰ and is more common in older adults.¹⁰ Research has shown that an average sleep-onset latency or middle-of-the-night wake time of 20 minutes maximizes the sensitivity and specificity for insomnia classification among individuals with insomnia compared to normal sleepers.¹¹

Hypersomnolence

Hypersomnolence disorder (sometimes referred to as hypersomnia) is characterized by self-reported excessive sleepiness despite a main sleep period lasting at least 7 hours. Individuals may exhibit an excessive quantity of sleep or have an increased propensity to sleep during wakefulness (e.g., recurrent periods of sleep or lapses into sleep within the same day). Individuals often have trouble being fully awake after an abrupt awakening, which is also referred to as sleep inertia or sleep drunkenness. This sleeping disturbance must occur at least three times per week, for at least 3 months, and cause the individual significant distress or impairment in cognitive, social, occupational, or other important areas of function. Furthermore, the hypersomnolence cannot be better explained by or attributable to another sleep–wake disorder (e.g., narcolepsy), the physiological effects of a substance, or a coexisting medical or mental health condition. The DSM-5 also provides guidance on specifying whether the hypersomnolence occurs with a mental disorder, with a medical condition, and/or with another sleep disorder, the acuity and persistence of the concern, and the severity of the current concern.

Of the various aforementioned sleep–wake difficulties, approximately 80% of individuals with hypersomnolence report nonrestorative sleep or difficulties waking up in the morning, and 36%–50% report having sleep inertia.⁴ Hypersomnolence tends to affect men and women equally¹² and is comorbid with a number of medical and mental health conditions, including Parkinson’s disease,¹³,¹⁴ Alzheimer’s disease,¹³ multiple system atrophy,¹³ and depressive disorders.¹⁵ Hypersomnolence has a progressive onset; symptoms tend to emerge between the ages of 15 and 25.⁴ Nocturnal PSG shows that individuals with hypersomnolence have a short sleep latency, normal to prolonged sleep duration, and they tend to have a sleep efficiency (total sleep time/time in bed) >90%. When using a multiple sleep latency test (MSLT), the average sleep latency is typically less than 10 minutes, and the transition to REM sleep within 20 minutes of sleep may be present but occurs less than twice during the typical four or five MSLT napping periods.⁴

Narcolepsy

Narcolepsy is characterized by a recurrent, irrepressible need for sleep in the form of daytime naps or lapses into sleep, occurring at least 3 times per week, for at least 3 months. Distinct from hypersomnolence disorder, individuals with narcolepsy must also exhibit at least one of the following: cataplexy episodes (i.e., a sudden loss of muscle tone usually in response to strong emotion) occurring at least a few times a month, a hypocretin deficiency [measured using cerebrospinal fluid (CSF) hypocretin-1 level <1/3 of normal or ≤110 pg/mL if a Stanford reference sample is used for radioimmunoassay], and/or a short-onset REM period (SOREMP) ≤15 minutes using nocturnal PSG or a MSLT showing a mean sleep latency ≤8 minutes and two or more SOREMPs. With regard to SOREMPs, a cutoff of 15 minutes indicates that the individual is going into a REM sleep period faster than what is typical in individuals without sleep complaints.

The DSM-5 also provides guidance on specifying among five different types of narcolepsy. Narcolepsy without cataplexy but with hypocretin deficiency is characterized by meeting all the narcolepsy diagnostic criteria except cataplexy. Narcolepsy with cataplexy but without hypocretin deficiency is characterized by meeting all the narcolepsy diagnostic criteria except the individual has normal hypocretin levels. Autosomal dominant cerebellar ataxia, deafness, and narcolepsy is caused by mutations on exon 21 DNA cytosine-5-methyltranferase-1; onset for this subtype typically occurs between ages of 30 and 40 years and is characterized by low-to-intermediate CSF hypocretin-1 levels, deafness, cerebellar ataxia, and eventually dementia. Autosomal dominant narcolepsy, obesity, and type 2 diabetes are associated with a mutation in the myelin oligodendrocyte glycoprotein gene and is characterized by having low CSF hypocretin-1 levels with narcolepsy, obesity, and type 2 diabetes. Narcolepsy secondary to another medical condition is characterized as narcolepsy that is secondary to a traumatic or infectious medical condition (e.g., Whipple’s disease, sarcoidosis) or a tumoral destruction of hypocretin neurons. The DSM-5 also provides guidance on specifying the severity of the current concern.

One commonality among the different narcolepsy subtypes is that the affected individual will experience excessive sleepiness that results in recurrent daytime naps or lapses into sleep. When cataplexy is present, it will often appear as a sudden, bilateral loss of muscle tone precipitated by emotions, such as laughter or joking, and can last as little as a few seconds or extend to minute-long episodes. During cataplexy, individuals are both awake and aware. Narcolepsy tends to affect men and women equally and is highly heritable; when an individual’s first degree biological relative has narcolepsy, there is a 10- to 40-fold increased risk that the individual will also have narcolepsy.¹⁶ Compared to individuals without narcolepsy, those who have narcolepsy (with or without cataplexy) are 3.8 times more likely to have a mental disorder, 3.7 times more likely to have nervous system complications, 3.5 times more likely to have a musculoskeletal problem, 2.7 times more likely to have a digestive illness, and 2.2 times more likely to have a genitourinary illness.¹⁷ Cell loss of hypothalamic hypocretin (orexin)-producing cells, which causes hypocretin deficiency, tends to be autoimmune related, and approximately 90%–99% of people (99% of Caucasians) carry HLA-DQB1*06:02 allele.⁴ Thus, checking for DQB1*06:02 prior to a lumbar puncture to determine CSF hypocretin-1 immunoreactivity may be useful when making a diagnosis.⁴

Breathing-Related Sleep Disorders

Commonly diagnosed breathing disorders include OSA, central sleep apnea (CSA), and sleep-related hypoventilation. These disorders are categorized by apneas (the total absence of airflow) and hypopneas (a marked reduction in airflow). To diagnose any of these disorders, a nocturnal PSG is required.

OSA is categorized by nocturnal breathing disturbances (e.g., snoring, snorting, gasping for air, or pauses in breathing), daytime sleepiness, fatigue, and experiencing poor, unrefreshing sleep despite getting an adequate sleep opportunity. Evidence from nocturnal PSG is required for diagnosis, such that an individual’s apnea-hypopnea index (AHI; the number of apneas plus hypopneas per hour of sleep) is at least 5 with reported nighttime breathing disturbances and daytime disruption (e.g., sleepiness, fatigue), or the individual has an AHI ≥15, regardless of accompanying symptoms. OSA should not be better explained by or attributable to a coexisting medical or mental health condition. Clinicians should specify the severity of the OSA; mild is an AHI 5–14, moderate is an AHI 15–30, and severe is an AHI greater than 30. Prevalence of OSA tends to be higher among males and older adults,¹⁸ and has been associated with a number of medical and mental health conditions, including obesity, systematic hypertension, coronary artery disease, heart failure, stroke, diabetes, increased mortality, and depression.⁴

CSA is characterized by repeated episodes of apneas and hypopneas during sleep, totaling at least 5 or more per hour, caused by variability in respiratory effort. Within the DSM-5, CSA can be classified as either idiopathic CSA, which refers to apneas and hypopneas caused by variability in respiratory effort without evidence of airway obstruction, Cheyne–Stokes breathing, which presents as a crescendo–decrescendo variation in tidal volume that results in central apneas and hypopneas that are frequently accompanied by an arousal, or CSA comorbid with opioid use, which is attributed to the effects of opioids on the respiratory rhythm generators in the medulla and the hypoxic and hypercapnic effects they may have on respiratory drive. Idiopathic CSA is relatively uncommon, constituting approximately 5% of patients referred to a sleep clinic,¹⁹ but its presence may be much higher in other clinical populations, such as those with heart failure and left ventricular ejection fraction of 45%,²⁰ as well as among those living at higher altitudes.²¹ Most studies also suggest that idiopathic CSA is most common in middle-aged to elderly adults and more frequent in men (although not all studies have found this sex difference).³ CSA with Cheyne–Stokes breathing is generally seen in patients 60 years or older and has been reported to occur in 26%–50% of patients during the acute period following a stroke.³ In addition, when looking at a sample of 450 men and women with congestive heart failure, risk factors for Cheyne–Stokes breathing included being 60 years or older, the presence of atrial fibrillation, male sex, and daytime hypocapnia.²² CSA comorbid with opioid use occurs in approximately 30% of individuals receiving methadone maintenance therapy and those taking chronic opioids for nonmalignant pain.⁴

Sleep-related hypoventilation is characterized by episodes of decreased respiration associated with elevated CO2 levels, as measured by PSG or oximetry, and is not better explained by another sleep disorder. It can be classified as idiopathic hypoventilation, which is not attributable to any readily identified condition, congenital central alveolar hypoventilation, which is a rare disorder typically presenting in the perinatal period with shallow breathing or cyanosis and apnea during sleep, or comorbid sleep-related hypoventilation, which typically occurs as a consequence of another medical condition such as COPD, interstitial lung disease, muscular dystrophies, obesity, or medications (e.g., benzodiazepines, opiates).⁴

Circadian Rhythm Sleep–Wake Disorders

Circadian rhythm disorders are characterized by a misalignment or alteration between an individual’s endogenous circadian rhythm and their required physically, socially, or professionally determined sleep–wake schedule. This disruption leads to insomnia and/or sleepiness and causes significant daytime impairment in social, occupational, educational, behavioral, or other important areas of function. A circadian rhythm sleep–wake disorder is considered episodic if the symptoms last for at least 1 month but less than 3 months, persistent if the symptoms last 3 months of longer, and/or recurrent if two (or more) episodes occur within the space of 1 year.

Delayed sleep phase type occurs when an individual’s sleep is delayed beyond the socially acceptable or conventional bedtime (the so-called night owls), causing difficulty waking up at their desired, or perhaps required, time. Prevalence in the general population is approximately 0.17%⁴ and among adolescents is approximately 3.3%.²³ Advanced sleep phase type occurs when an individual is unable to stay awake in the early evening, goes to bed very early (e.g., between 6:00 and 8:00 p.m.) and then wakes up early in the morning (e.g., between 2:00 and 4:00 a.m.; the so-called morning lark or early birds). Prevalence is estimated to be 1% in middle-aged adults.⁴ While the timing of advanced sleep phase time may be early, the sleep itself tends to be normal. Irregular sleep–wake type refers to a temporally disorganized rhythm, wherein the individual may take numerous naps throughout the day, have no main nighttime sleep episode, and have irregularities in sleep from day-to-day; the prevalence in the general population is unknown.⁴ Non-24-hour sleep–wake type is a pattern of sleep–wake cycling that is not synchronized with a 24-hour environment with gradual drifts (usually in a clockwise direction) of sleep onset and wake times. While prevalence in the general population is unclear, it appears to be rare in sighted individuals and more common (approximately 50%) among blind individuals.⁴ Shift work type occurs when an individual reports insomnia during the major sleep period and/or excessive sleepiness during the major awake period that is typically associated with a schedule of unconventional work hours. Prevalence of shift work type increases with advancement into middle-age and beyond, and is estimated to affect 5%–10% of the night worker population,²⁴ which is 16%–20% of the workforce.⁴

Parasomnias

Parasomnias are characterized by abnormal behavior occurring in association with sleep or sleep–wake transitions, such as sleepwalking, sleep terrors, nightmare disorder, and REM sleep behavior disorder. Other parasomnias which will not be detailed in this chapter include confusional arousals, sleep paralysis, exploding head syndrome, sleep-related hallucinations, and sleep enuresis (see cited articles for more information).²⁵–²⁸ All parasomnias must cause the individual significant daytime impairment in social, occupational, educational, behavioral, or other important areas of function, and cannot be better explained by another sleep–wake disorder, the physiological effects of a substance, or a coexisting medical or mental health condition.

Both sleepwalking and sleep terrors are considered NREM sleep arousal disorders, as they frequently occur during deep, slow wave sleep seen in the first third of the night. NREM sleep arousal disorders occur most often in childhood and decrease as individuals get older. Sleepwalking involves rising from the bed during sleep and walking about, with the individual being relatively unresponsive to people communicating with him or her, having a blank, staring face, and being awakened only with great difficulty. Sleepwalking may also present with eating or sexual behavior. Among adults, the prevalence of sleepwalking episodes is 1%–7% and is more common in males.⁴ Among the children, the prevalence of at least one sleepwalking episode is 10%–30% (with 2%–3% sleepwalking often) and is more common in females.⁴ Eighty percent of individuals who sleepwalk have a family history of sleepwalking or sleep terrors, and the risk for sleepwalking increases if both parents have a history of the disorder.⁴ In a genetics study examining DNA of 22 family members across four generations, researchers found that sleepwalking has a genetic component with an autosomal reduced penetrance pattern, exhibited on a region of chromosome 20.²⁹ Autosomal means that the gene is carried on the nonsex chromosomes, and reduced penetrance means that sleepwalking appears to skip generations because not everyone who inherits the faulty genes has symptoms.

Sleep terrors present as abrupt arousals, usually beginning with a scream and accompanied by intense fear and autonomic arousal (e.g., rapid breathing, sweating, tachycardia, pupil dilation). Among adults, the prevalence of sleep terror episodes is 2.2%, and there are no sex-related differences.⁴,³⁰ Among children, the prevalence of sleep terrors episodes is much higher—36.9% at 18 months of age and 19.7% at 30 months of age—and tends to be more common in males than females.⁴

Nightmare disorder and REM sleep behavior disorder tend to occur during the second half of the night, when REM sleep is more prominent. In both disorders, an individual is both alert and oriented when they are awakened. Nightmare disorder involves dream imagery that seems real and elicits dysphoric emotions, such as anxiety or fear. Nightmares are more prevalent during childhood through young adulthood and tend to decline with age; they are also associated with female sex, increased stress, psychopathology, and dispositional traits, such as the tendency to experience events with distressing, highly reactive emotions.³¹ REM sleep behavior disorder involves repeated episodes of arousal that tend to be accompanied by complex motor behaviors (e.g., kicking, punching) and vocalizations (e.g., loud, emotion-filled profanity). Diagnosis can be made when a PSG indicates REM sleep without atonia or if the patient has a history suggestive of REM sleep behavior disorder and an established synucleinopathy diagnosis, which refers to degenerative diseases of the central nervous system that exhibit excessive accumulation of alpha-synuclein (a brain protein) in the neurons (e.g., multiple system atrophy, Parkinson’s disease, dementia with Lewy bodies). Prevalence among the general population is between 0.38% and 0.5%.⁴ Tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and beta-blockers may result in PSG evidence characteristic of REM sleep behavior disorder; however, it is not known whether the medications result in REM sleep behavior disorder or if they are unmasking an underlying predisposition.⁴

Movement-Related Sleep Disorders

Two frequently diagnosed movement disorders are RLS and periodic limb movement disorder (PLMD). While both conditions involve an inability to keep still, the disorders are distinctly different. With RLS, an individual will report an irresistible urge to move their legs that tends to worsen in the evening/night, during periods of rest or inactivity, and is either partially or totally relieved by movement. These symptoms occur at least 3 times per week and have persisted for at least 3 months. Predisposing factors to RLS include female sex, older age, family history of RLS, and genetic risk variants (e.g., intronic or intergenic regions of MEIS1, BTBD9, and MAP2K5 on chromosomes 2p, 6p, and 15q).⁴,³² RLS is associated with pregnancy, peaking during the third trimester and often resolving itself following delivery.⁴,³³ RLS symptoms occur both when the individual is awake and asleep, and he or she can voluntarily respond to the uncomfortable sensations. On the other hand, PLMD is a sleep disorder in which an individual involuntarily moves his or her limbs during sleep; individuals are often unaware that these movements are occurring. PLMD movements typically occur during NREM sleep and individuals often report excessive daytime sleepiness. PLMD is diagnosed using PSG, which may reveal that these frequent, involuntary leg moves are often, but not always, accompanied by brief arousals or awakenings. Approximately 4% of adults have been diagnosed with PLMD,³² with increasing rates among elderly females (11%).³⁴ Previous studies have found that approximately 80% of individuals with RLS also experience periodic leg movements in sleep (index >5 movements/hour sleep); ³⁵ however, the reverse is not always the case. That is, those with periodic leg movements during sleep do not necessarily experience RLS.

Both RLS and PLMD must cause the individual significant daytime impairment in social, occupational, educational, behavioral, or other important areas of function, and cannot be better explained by another sleep–wake disorder, the physiological effects of a substance, or a coexisting medical or mental health condition.

Psychological, Behavioral, and Laboratory Assessments to Aid Diagnosis

There are a number of useful clinical tools to aid in the diagnosis and assessment of sleep–wake disorders. The most commonly used tools include gathering a thorough clinical history, daily self-monitoring of sleep–wake patterns, self-report questionnaires, actigraphy, PSG, the MSLT, and the maintenance of wakefulness test (MWT).

Clinical History

Collecting information using a structured or semistructured interview can help clinicians gather important details concerning a patient’s sleep complaint, such as acuity or chronicity, course, factors alleviating or exacerbating the condition, and any previous treatment utilization. To help establish the etiology of their sleep concern(s), it is important to inquire about particular medical or mental health conditions, life events, and substance use present at the onset of the sleep problem. Clinicians might consider using the Duke Structured Interview for Sleep Disorders,³⁶ which was developed to assess sleep disorder symptoms according to criteria found in the ICSD and DSM. This semistructured interview is divided into four modules: insomnia disorders, sleep disorders associated with excessive daytime sleepiness and hypersomnia, circadian rhythm disorders, and parasomnias. Bed partners (or parents) are also an important source of clinical information, as they can often fill in gaps that the patient is unaware of, such as sleep apnea symptoms (breathing pauses, snoring), parasomnias (instances of sleepwalking or sleep terrors), or PLMD.

Daily Self-Monitoring

Filling out a prospective sleep diary on a daily basis can help create a more thorough clinical picture to aid in sleep disorder diagnosis and highlight a patient’s sleep habits. It is recommended that clinicians gather 1–2 weeks of data since night-to-night variability of sleeping patterns is common (e.g., differences between sleep during weekdays vs weekends).³⁷,³⁸ A typical sleep diary includes what time the patient got into bed, when they attempted to start sleeping, how long it took them to fall asleep, number and duration of awakenings, time of their final awakening, what time they actually got out of bed, napping behavior, use of sleep aids, and a measure of their perceived sleep quality.³⁹ Once the diaries are collected, a clinician can determine average sleep onset latency, wake after sleep onset (i.e., nocturnal awakenings), early morning awakenings, total wake time, total sleep time, total time in bed, and sleep efficiency [(total sleep time/total time in bed) × 100], which can help with treatment planning and decision-making to help a patient get their sleep back on track.

Self-Report Questionnaires

There are numerous questionnaires that can aid clinicians in the assessment of sleep disorder symptoms, with some being useful tools to employ during treatment to monitor change across time. Table 1.3 provides a brief outline of several commonly used self-report questionnaires.

Table 1.3

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Actigraphy

Actigraphs are small, wristwatch-like units that continuously measure movement and activity using an accelerometer. Some actigraphy recorders also have capability to measure light exposure. This noninvasive device is particularly helpful in determining sleep patterns and circadian rhythms in those with insomnia, hypersomnia, advanced sleep phase syndrome, delayed sleep phase syndrome, shift work disorder, jet lag disorder, and non-24-hours sleep/wake syndrome.⁴⁷ This useful tool can provide clinicians with several days (and sometimes weeks) of data and provides an acceptably accurate estimate of sleep patterns in normal, healthy adult populations and inpatients suspected of having certain sleep disorders.⁴⁷ An actigraphy recorder is typically worn on a patient’s nondominant hand. The manufacturer of the actigraphy devices typically provides a corresponding program that reads the data through a sleep scoring algorithm to compute parameters such as time in bed, sleep onset latency, total wake time, total sleep time, and sleep efficiency. Since actigraphy is based on movement, there may be difficulties distinguishing wake from sleep in patients that are lying awake in bed but not moving (e.g., insomnia); however, previous research has shown that estimates of sleep and wake time in insomnia patients correlate moderately well with analogous measures derived from PSG (r=0.52–0.71) and are sufficiently sensitive to detect sleep improvements resulting from behavioral insomnia therapy.⁴⁸ Increasingly clinicians are seeing more patients come in with data from wearable fitness trackers (e.g., Fitbit, Jawbone, Garmin) that claim reliable measurement of sleep/wake patterns; however, a recent systematic review found that fitness trackers overestimated total sleep time and sleep efficiency, and underestimated wake after sleep onset when comparing it to PSG metrics.⁴⁹ Therefore, clinicians should be cautious in using fitness tracker data to reliably ascertain sleep-related parameters.

Polysomnography

PSG is the gold standard for measuring sleep to confirm several sleep disorder diagnoses, such as sleep apnea, PLMD, narcolepsy (in conjunction with a MSLT), and some parasomnias, such as REM behavior disorder.⁵⁰ PSG can be used to measure a number of parameters during sleep, including heart rate, breathing rate, airflow, oxygen saturation, eye movements, snoring volume, muscle activity, body motion, positions during sleep, and brain activity. A typical PSG study occurs in a sleep center where a patient will spend the night and be continuously monitored; however, an increasing number of insurance companies allow patients to be sent home with an at-home sleep test that can generate either an AHI (the number of apneas or hypopneas recorded during the study per hour of sleep) or a respiratory disturbance index (the number of apneas, hypopneas, and other, more subtle, breathing irregularities occurring per hour of sleep), which may prompt a more detailed overnight PSG sleep study at a sleep center. PSG is also used for continuous positive airway pressure titration in patients with sleep-related breathing disorders and may be indicated for patients with sleep-related symptoms with concurrent neuromuscular or seizure-related disorders.⁵⁰ PSG is not routinely indicated for diagnosing insomnia; however, recent research has suggested that objectively defined total sleep time less than 6 hours (on average) may represent a more severe phenotype of insomnia⁵¹,⁵² that responds to first-line treatments differently.⁵³ Therefore, if a PSG test is available for an individual with insomnia, it may provide useful information to help guide treatment, since it is the only measure that can truly distinguish between wake and sleep stages, as well as the percentage of time a person spends in different sleep stages [e.g., N1 or N2 (lighter sleep) vs N3([slow wave, deeper sleep) vs REM