sure and oxygen desaturation, and elevated sy mpathetic nervous system activity that can
promote progression of heart failure. The clinic al significance of Cheyne-Stokes breathing
in the setting of stroke is no t known, but Cheyne-Stokes breathing may be a transient find-
ing that resolves with time after acute stro ke. Central sleep apnea comorbid with opioid
use has been documented with chro nic use (i.e., several months).
Risk and Prognostic Factors
Genetic and physiological. Cheyne-Stokes breathing is freq uently present in individu-
als with heart failure. The coexistence of atrial fibrillation further increases risk, as do older
age and male gender. Cheyne-Stokes breathing is also seen in association with acute stroke
and possibly renal failure. The underlying ventila tory instability in the setting of heart fail-
ure has been attributed to increased ventilatory chemos ensitivity and hyperventilation
due to pulmonary vascular congestion and ci rculatory delay. Central sleep apnea is seen
in individuals taking long-acting opioids.
Diagnostic Markers
Physical findings seen in individuals with a Cheyne-Stokes breathing pattern relate to its
risk factors. Findings consiste nt with heart failure, such as jugular venous distension, S3
heart sound, lung crackles, and lower extremity edema, may be present. Polysomnogra-
phy is used to characterize the breathing characteristics of  each breathing-related sleep
disorder subtype. Central sl eep apneas are recorded when periods of breathing cessation
for longer than 10 seconds occur. Cheyne-Sto kes breathing is characterized by a pattern of
periodic crescendo-decrescend o variation in tidal volume that results in central apneas
and hypopneas occurring at a frequency of at least five events per hour that are accompa-


nied by frequent arousals. The cycle length of Cheyne-Stokes breathing (or time from end
of one central apnea to the end of the next apnea) is about 60 seconds.


386 Sleep-Wake Disorders
Functional Consequences of Central Sleep Apnea
Idiopathic central sleep apnea has been report ed to cause symptoms of disrupted sleep, in-
cluding insomnia and sleepines s. Cheyne-Stokes breathing with comorbid heart failure
has been associated with excessive sleepine ss, fatigue, and insomnia, although many in-
dividuals may be asymptomatic. Coexistence of heart failure and Cheyne-Stokes breath-
ing may be associated with increased card iac arrhythmias and increased mortality or
cardiac transplantation. Individuals with central sleep apnea comorbid with opioid use
may present with symptoms of sleepiness or insomnia.
Differential Diagnosis
Idiopathic central sleep apnea must be distinguished from other breathing-related sleep
disorders, other sleep disorders, and medical conditions and mental disorders that cause
sleep fragmentation, sleepiness, and fatigue.  This is achieved using polysomnography.
Other breathing-related sleep disorders and sleep disorders. Central sleep apnea can
be distinguished from obstructive sleep apne a hypopnea by the presen ce of at least five
central apneas per hour of sleep. These condit ions may co-occur, but central sleep apnea is
considered to predominate when the ratio of central to obstructive respiratory events ex-
ceeds 50%.
Cheyne-Stokes breathing can be distinguishe d from other mental disorders, including
other sleep disorders, and othe r medical conditions that caus e sleep fragmentation, sleep-
iness, and fatigue based on the presence of a predisposing condition (e.g., heart failure or
stroke) and signs and polysomnographic evidence  of the characteristic breathing pattern.
Polysomnographic respiratory findings can help distinguish Cheyne-Stokes breathing
from insomnia due to other medical conditio ns. High-altitude periodic breathing has a


from insomnia due to other medical conditio ns. High-altitude periodic breathing has a
pattern that resembles Cheyne-Stokes breathin g but has a shorter cycle time, occurs only
at high altitude, and is not associated with heart failure.
Central sleep apnea comorbid with opioid us e can be differentiated from other types of
breathing-related sleep disorders based on the use of long-acting opioid medications in
conjunction with polysomnographic evidence of central apneas and periodic or ataxic
breathing. It can be distinguished from inso mnia due to drug or substance use based on
polysomnographic evidence of central sleep apnea.
Comorbidity
Central sleep apnea disorders are frequently pr esent in users of long-acting opioids, such
as methadone. Individuals taking these medi cations have a sleep-related breathing disor-
der that could contribute to sleep disturbances and symptoms  such as sleepiness, confu-
sion, and depression. While the individual is  asleep, breathing patterns such as central
apneas, periodic apneas, and ataxic breathing may be observed. Obstructive sleep apnea
hypopnea may coexist with central sleep apnea,  and features consiste nt with this condi-
tion can also be present (see “Obstructive Sleep Apnea Hypopnea” earlier in this chapter).
Cheyne-Stokes breathing is more commonly obse rved in association with conditions that
include heart failure, stroke, and renal failure and is seen more frequently in individuals
with atrial fibrillation. Individuals with Ch eyne-Stokes breathing are more likely to be
older, to be male, and to have  lower weight than individual s with obstructive sleep apnea
hypopnea.


Sleep-Related Hypoventilation 387
Sleep-Related Hypoventilation
Diagnostic Criteria
A. Polysomnograpy demonstrates episodes of decreased respiration associated with el-
evated CO2 levels. ( Note:  In the absence of objective measurement of CO2, persistent
low levels of hemoglobin oxygen saturation unassociated with apneic/hypopneic
events may indicate hypoventilation.)
B. The disturbance is not better explained by another current sleep disorder.
Specify whether:
327.24 (G47.34) Idiopathic hypoventilation:  This subtype is not attributable to any
readily identified condition.
327.25 (G47.35) Congenital centr al alveolar hypoventilation:  This subtype is a rare
congenital disorder in which the individual typically presents in the perinatal period with
shallow breathing, or cyanosis and apnea during sleep.
327.26 (G47.36) Comorbid sleep -related hypoventilation: This subtype occurs as a
consequence of a medical condition, such as a pulmonary disorder (e.g., interstitial
lung disease, chronic obstructive pulmonary disease) or a neuromuscular or chest wall
disorder (e.g., muscular dystrophies, postpolio syndrome, cervical spinal cord injury,
kyphoscoliosis), or medications (e.g., benzodiazepines, opiates). It also occurs with
obesity (obesity hypoventilation disorder), where it reflects a combination of increased
work of breathing due to reduced chest wall compliance and ventilation-perfusion mis-
match and variably reduced ventilatory drive. Such individuals usually are character-
ized by body mass index of greater than 30 and hypercapnia during wakefulness (with
a pCO2 of greater than 45), without other evidence of hypoventilation.


Specify current severity:
Severity is graded according to the degree of hypoxemia and hypercarbia present dur-
ing sleep and evidence of end organ impairment due to these abnormalities (e.g., right-
sided heart failure). The presence of blood gas  abnormalities during wakefulness is an
indicator of greater severity.
Subtypes
Regarding obesity hypoventilati on disorder, the prevalence of obesity hypoventilation in
the general population is not known but is thought to be increasing in association with the
increased prevalence of obesity and extreme obesity.
Diagnostic Features
Sleep-related hypoventilation can occur in dependently or, more frequently, comorbid
with medical or neurological disorders, medi cation use, or substa nce use disorder. Al-
though symptoms are not mandatory to make this diagnosis, individuals often report
excessive daytime sleepiness, frequent arou sals and awakenings during sleep, morning
headaches, and insomnia complaints.
Associated Features Supporting Diagnosis
Individuals with sleep-related hypoventilation  can present with sl eep-related complaints
of insomnia or sleepiness. Episodes of orth opnea can occur in individuals with diaphragm
weakness. Headaches upon awakening may be pr esent. During sleep, episodes of shallow
breathing may be observed, an d obstructive sleep apnea hypo pnea or central sleep apnea
may coexist. Consequences of ventilatory in sufficiency, includin g pulmonary hyperten-
sion, cor pulmonale (right heart failure), polycythemia, and neurocognitive dysfunction,


388 Sleep-Wake Disorders
can be present. With progression of ventilato ry insufficiency, bloo d gas abnormalities ex-
tend into wakefulness. Features of the me dical condition causing sleep-related hypoven-
tilation can also be present. Episodes of hy poventilation may be as sociated with frequent
arousals or bradytachycardia. Individuals ma y complain of excessive sleepiness and in-
somnia or morning headaches or may present wi th findings of neuroc ognitive dysfunction
or depression. Hypoventilation may not be present during wakefulness.
Prevalence
Idiopathic sleep-related hypoventilation in adults is very uncommon. The prevalence of
congenital central alveolar hy poventilation is unknown, but the disorder is rare. Comor-
bid sleep-related hypoventilation (i.e., hypo ventilation comorbid with other conditions,
such as chronic obstructive pulmonary diseas e [COPD], neuromuscular disorders, or obe-
sity) is more common.
Development and Course
Idiopathic sleep-related hypove ntilation is thought to be a slowly progressive disorder of
respiratory impairment. When th is disorder occurs comorbidly  with other disorders (e.g.,
COPD, neuromuscular disorders, obesity), diseas e severity reflects the severity of the un-
derlying condition, and the disorder progre sses as the condition worsens. Complications
such as pulmonary hypertension, cor pulmon ale, cardiac dysrhythmias, polycythemia,
neurocognitive dysfunction, and worsening re spiratory failure can develop with increas-
ing severity of blood gas abnormalities.
Congenital central alveolar hypoventilation  usually manifests at birth with shallow,


Congenital central alveolar hypoventilation  usually manifests at birth with shallow,
erratic, or absent breathing. This disorder can also manifest during infancy, childhood,
and adulthood because of va riable penetrance of the PHOX2B  mutation. Children with
congenital central alveolar hypo ventilation are more likely to have disorders of the auto-
nomic nervous system, Hirschsprung’s disease, neural crest tumors, and characteristic box-
shaped face (i.e., the face is short relative to its width).
Risk and Prognostic Factors
Environmental. Ventilatory drive can be reduced in  individuals using central nervous
system depressants, including benzod iazepines, opiates, and alcohol.
Genetic and physiological. Idiopathic sleep-related hypoventilation is associated with
reduced ventilatory drive due to a blunted chemoresponsiveness to CO2 (reduced respi-
ratory drive; i.e., “won’t brea the”), reflecting underlying neurological deficits in centers
governing the control of ventilation. More co mmonly, sleep-related hypoventilation is co-
morbid with another medical condition, su ch as a pulmonary diso rder, a neuromuscular
or chest wall disorder, or hypothyroidism, or with use of medications (e.g., benzodiaze-
pines, opiates). In these conditions, the hy poventilation may be a consequence of in-
creased work of breathing and/or impairment of respiratory muscle function (i.e., “can’t
breathe”) or reduced respiratory drive (i.e., “won’t breathe”).
Neuromuscular disorders influence breathin g through impairment of respiratory mo-
tor innervation or respiratory muscle function. They include conditions such as amyo-


tor innervation or respiratory muscle function. They include conditions such as amyo-
trophic lateral sclerosis, spinal cord injury , diaphragmatic paralysis, myasthenia gravis,
Lambert-Eaton syndrome, toxic or metabolic myopathies, postpolio syndrome, and Char-
cot-Marie-Tooth syndrome.
Congenital central alveolar hypoventilation is a genetic disorder at tributable to muta-
tions of PHOX2B,  a gene that is crucial for the de velopment of the embryonic autonomic
nervous system and neural crest derivatives. Children with congenital central alveolar hy-
poventilation show blunted vent ilatory responses to hypercapnia, especially in non–rapid
eye movement sleep.


Sleep-Related Hypoventilation 389
Gender-Related Diagnostic Issues
Gender distributions for sleep-related hypove ntilation occurring in association with co-
morbid conditions reflect the gender distributions of the co morbid conditions. For exam-
ple, COPD is more frequently present in males and with increasing age.
Diagnostic Markers
Sleep-related hypoventilation is diagnosed using polysomnography showing sleep-related
hypoxemia and hypercapnia that is not better explained by another breathing-related sleep
disorder. The documentation of increased arterial pCO2 levels to greater than 55 mmHg
during sleep or a 10 mmHg or greater increase in pCO2 levels (to a level that also exceeds
50 mmHg) during sleep in comparison to awake supine values, for 10 minutes or longer, is
the gold standard for diagnosis. However, obtaining arterial blood gas determinations dur-
ing sleep is impractical, and non-invasive measures of pCO2 have not been adequately val-
idated during sleep and are not widely used during polysomnography in adults. Prolonged
and sustained decreases in oxyg en saturation (oxygen saturation of less than 90% for more
than 5 minutes with a nadir of at least 85%, or oxygen saturation of less than 90% for at least
30% of sleep time) in the absence of evidence of upper airway obstruction are often used as
an indication of sleep- related hypoventilation; however, this  finding is not sp ecific, as there
are other potential causes of hypoxemia,  such as that due to lung disease.
Functional Consequences of
Sleep-Related Hypoventilation
The consequences of sleep-related hypoventilati on are related to the effects of chronic ex-


The consequences of sleep-related hypoventilati on are related to the effects of chronic ex-
posure to hypercapnia and hypoxemia. Th ese blood gas derangements cause vasocon-
striction of the pulmonary va sculature leading to pulmon ary hypertension, which, if
severe, can result in right-sided heart failure  (cor pulmonale). Hypo xemia can lead to dys-
function of organs such as the brain, blood,  and heart, leading to outcomes such as cog-
nitive dysfunction, polycythemia, and cardiac arrhythmias. Hypercapnia can depress
ventilatory drive, leading to pr ogressive respiratory failure.
Differential Diagnosis
Other medical conditions affecting ventilation. In adults, the idiopathic variety of sleep-
related hypoventilation is very uncommon and is determined by excluding the presence of
lung diseases, skeletal malformations, neuromuscular disorders, and other medical and
neurological disorders or medications that affect ventilation. Sleep-related hypoventila-
tion must be distinguished from other causes of sleep-related hypoxemia, such as that due
to lung disease.
Other breathing-related sleep disorders. Sleep-related hypoventilation can be distin-
guished from obstructive sleep  apnea hypopnea and central sleep apnea based on clinical
features and findings on polysomnography. Sl eep-related hypoventilation typically shows
more sustained periods of oxygen desaturation rather that  the periodic episodes seen in
obstructive sleep apnea hypopnea and central sleep apnea. Obstructive sleep apnea hy-
popnea and central sleep apnea also show a pa ttern of discrete epis odes of re peated air-
flow decreases that can be absent in sleep-related hypoventilation.
Comorbidity


flow decreases that can be absent in sleep-related hypoventilation.
Comorbidity
Sleep-related hypoventilation often occurs in a ssociation with a pulmonary disorder (e.g., in-
terstitial lung disease, COPD), with a neurom uscular or chest wall disorder (e.g., muscular
dystrophies, post-polio syndrome, cervical spinal cord in jury, obesity, kyphoscoliosis), or,


390 Sleep-Wake Disorders
most relevant to the mental he alth provider, with medication use (e.g., benzodiazepines, opi-
ates). Congenital central alveol ar hypoventilation often occurs in association with autonomic
dysfunction and may occur in association with Hirschsprung’s disease. COPD, a disorder of
lower airway obstruction usually associated with cigarette sm oking, can result in sleep-
related hypoventilation and hypoxemia. The pres ence of coexisting obstructive sleep apnea
hypopnea is thought to exacerbate hypoxemia and hypercapnia during sleep and wakeful-
ness. The relationship between congenital central alveolar hypoventilation and idiopathic
sleep-related hypoventilation is unclear; in some individuals, idiopathic sleep-related hy-
poventilation may represent cases of late-onset  congenital central alveolar hypoventilation.
Relationship to Internat ional Classification of
Sleep Disorders
The International Classificat ion of Sleep Disorders,  2nd Edition (ICSD-2), combines sleep-
related hypoventilation and sleep-related hypo xemia under the category of sleep-related
hypoventilation/hypoxemic syndromes. This ap proach to classificati on reflects the fre-
quent co-occurrence of disorder s that lead to hypoventilation  and hypoxemia. In contrast,
the classification used in DS M-5 reflects evidence that th ere are distinct sleep-related
pathogenetic processes le ading to hypoventilation.
Circadian Rhythm Sleep-Wake Disorders
Diagnostic Criteria
A. A persistent or recurrent pattern of sleep disruption that is primarily due to an alteration
of the circadian system or to a misalignment between the endogenous circadian
rhythm and the sleep–wake schedule required by an individual’s physical environment


rhythm and the sleep–wake schedule required by an individual’s physical environment
or social or professional schedule.
B. The sleep disruption leads to excessive sleepiness or insomnia, or both.
C. The sleep disturbance causes clinically significant distress or impairment in social, oc-
cupational, and other important areas of functioning.
Coding note:  For ICD-9-CM, code 307.45 for all subtypes. For ICD-10-CM, code is based
on subtype.
Specify whether:
307.45 (G47.21) Delayed sleep phase type:  A pattern of delayed sleep onset and
awakening times, with an inability to fall asleep and awaken at a desired or convention-
ally acceptable earlier time.
Specify if:
Familial:  A family history of delayed sleep phase is present.
Specify if:
Overlapping with non-24-hour sleep-wake type:  Delayed sleep phase type
may overlap with another circadian rhythm sleep-wake disorder, non-24-hour
sleep-wake type.
307.45 (G47.22) Advanced sleep phase type:  A pattern of advanced sleep onset and
awakening times, with an inability to remain awake or asleep until the desired or con-
ventionally acceptable later sleep or wake times.
Specify if:
Familial:  A family history of advanced sleep phase is present.
307.45 (G47.23) Irregular sleep-wake type:  A temporally disorganized sleep-wake
pattern, such that the timing of sleep and wake periods is variable throughout the 24-
hour period.


Circadian Rhythm Sleep-Wake Disorders 391
307.45 (G47.24) Non-24-hour sleep-wake type:  A pattern of sleep-wake cycles that
is not synchronized to the 24-hour environment, with a consistent daily drift (usually to
later and later times) of sleep onset and wake times.
307.45 (G47.26) Shift work type:  Insomnia during the major sleep period and/or ex-
cessive sleepiness (including inadvertent sleep) during the major awake period asso-
ciated with a shift work schedule (i.e., requiring unconventional work hours).
307.45 (G47.20) Unspecified type
Specify if:
Episodic:  Symptoms last at least 1 month but less than 3 months.
Persistent:  Symptoms last 3 months or longer.
Recurrent: Two or more episodes occur within the space of 1 year.
Delayed Sleep Phase Type
Diagnostic Features
The delayed sleep phase type is based primarily on a history of a delay in the timing of the
major sleep period (usually more than 2 hours)  in relation to the desired sleep and wake-
up time, resulting in symptoms of insomnia and excessive sleepiness. When allowed to set
their own schedule, individuals with delayed sleep phase type exhibit normal sleep qual-
ity and duration for age. Symptoms of slee p-onset insomnia, diffic ulty waking in the
morning, and excessive early day sleepiness are prominent.
Associated Features Supporting Diagnosis
Common associated features of delayed sleep phase type include a hi story of mental dis-
orders or a concurrent mental disorder. Ex treme and prolonged difficulty awakening with
morning confusion is also common. Psychophy siological insomnia may develop as a re-
sult of maladaptive behaviors that impair sleep and increase arousal because of repeated


sult of maladaptive behaviors that impair sleep and increase arousal because of repeated
attempts to fall asleep at an earlier time.
Prevalence
Prevalence of delayed sleep phase type in the general population is approximately 0.17%
but appears to be greater than 7% in adolescents. Although the prevalence of familial de-
layed sleep phase type has not been established , a family history of delayed sleep phase is
present in individuals with delayed sleep phase type.
Development and Course
Course is persistent, lasting longer than 3 mo nths, with intermittent  exacerbations through-
out adulthood. Although age at onset is variable, symptoms begin typically in adolescence
and early adulthood and persist for several mo nths to years before diagnosis is estab-
lished. Severity may decrease with ag e. Relapse of symptoms is common.
Clinical expression may vary across the lif espan depending on social, school, and work
obligations. Exacerbation is usua lly triggered by a change in work or school schedule that
requires an early rise time. Individuals wh o can alter their work schedules to accommo-
date the delayed circadian sleep and wake timing can experience remission of symptoms.
Increased prevalence in adolescence may be a consequence of both physiological and be-
havioral factors. Hormonal changes may be involved specifically, as delayed sleep phase is as-
sociated with the onset of puberty. Thus, de layed sleep phase type in adolescents should be
differentiated from the common delay in the timi ng of circadian rhythms in this age group. In
the familial form, the course is persistent and may not improve significantly with age.


392 Sleep-Wake Disorders
Risk and Prognostic Factors
Genetic and physiological. Predisposing factors may include a longer than average cir-
cadian period, changes in light sensitivity, an d impaired homeostatic sleep drive. Some in-
dividuals with delayed sleep phase type may be hypersensi tive to evening light, which
can serve as a delay signal to the circadian cloc k, or they may be hy posensitive to morning
light such that its phase-advancing effects ar e reduced. Genetic factors may play a role in
the pathogenesis of familial and sporadic forms of delayed sleep phase type, including
mutations in circadian genes (e.g., PER3 , CKIe ).
Diagnostic Markers
Confirmation of the diagnosis includes a complete history and use of a sleep diary or actigra-
phy (i.e., a wrist-worn motion detector that mo nitors motor activity for prolonged periods and
can be used as a proxy for sleep-wake patterns for at least 7 days). Th e period covered should
include weekends, when social an d occupational obligations are le ss strict, to ensure that the
individual exhibits a consistently delayed slee p-wake pattern. Biomarkers such as salivary
dim light melatonin onset should be obtain ed only when the diagnosis is unclear.
Functional Consequences of  Delayed Sleep Phase Type
Excessive early day sleepiness is prominent. Ex treme and prolonged difficulty awakening
with morning confusion (i.e., sleep inertia) is also common. The severity of insomnia and
excessive sleepiness symptoms varies substa ntially among individuals and largely de-
pends on the occupational and social demands on the individual.
Differential Diagnosis
Normative variations in sleep. Delayed sleep phase type must be distinguished from
“normal” sleep patterns in which an individual has a late schedule that does not cause


“normal” sleep patterns in which an individual has a late schedule that does not cause
personal, social, or occupational distress (m ost commonly seen in adolescents and young
adults).
Other sleep disorders. Insomnia disorder and other circadian rhythm sleep-wake dis-
orders should be included in the differenti al. Excessive sleepiness may also be caused by
other sleep disturbances, such as breathing- related sleep disorders, insomnias, sleep-
related movement disorders, and medical, ne urological, and mental disorders. Overnight
polysomnography may help in evaluating for other comorbid sleep disorders, such as
sleep apnea. The circadian nature of delaye d sleep phase type, howe ver, should differen-
tiate it from other disorders with similar complaints.
Comorbidity
Delayed sleep phase type is strongly associated  with depression, personality disorder, and
somatic symptom disorder or illness anxiety d isorder. In addition, comorbid sleep disor-
ders, such as insomnia disorder, restless legs syndrome, and sleep apnea, as well as depres-
sive and bipolar disorders and anxiety disord ers, can exacerbate symptoms of insomnia
and excessive sleepiness. Delayed sleep phase  type may overlap with another circadian
rhythm sleep-wake diso rder, non-24-ho ur sleep-wake type. Sighted individuals with non-
24-hour sleep-wake type disorder commonly also have a history of delayed circadian sleep
phase.


Circadian Rhythm Sleep-Wake Disorders 393
Advanced Sleep Phase Type
Specifiers
Advanced sleep phase type may be document ed with the specified “familial.” Although
the prevalence of familial adva nced sleep phase type has no t been established, a family
history of advanced sleep phase is present in individuals with advanced sleep phase type.
In this type, specific mutations demonstrate an autosomal dominant mode of inheritance.
In the familial form, onset of symptoms ma y occur earlier (during childhood and early
adulthood), the course is persistent, and the se verity of symptoms may increase with age.
Diagnostic Features
Advanced sleep phase type is characterized by sleep-wake times that are several hours
earlier than desired or conventional times. Di agnosis is based primarily on a history of an
advance in the timing of the major sleep period  (usually more than 2 hours) in relation to
the desired sleep and wake-up time, with sy mptoms of early morning insomnia and ex-
cessive daytime sleepiness. When allowed to  set their schedule, individuals with ad-
vanced sleep phase type will exhibit norm al sleep quality and duration for age.
Associated Features Supporting Diagnosis
Individuals with advanced sleep phase type are “morning types,” having earlier sleep-
wake times, with the timing of circadian biom arkers such as melatonin and core body tem-
perature rhythms occurring 2–4 hours earlier th an normal. When required to keep a con-
ventional schedule requiring a delay of bedtim e, these individuals will continue to have an
early rise time, leading to persistent sleep de privation and daytime sleepiness. Use of hyp-
notics or alcohol to combat sleep-maintenance insomnia and stimulants to reduce daytime
sleepiness may lead to substance abuse in these individuals.
Prevalence


sleepiness may lead to substance abuse in these individuals.
Prevalence
The estimated prevalence of advanced sleep phase type is approximately 1% in middle-
age adults. Sleep-wake times and circadian pha se advance in older individuals, probably
accounting for increased prevalence in this population.
Development and Course
Onset is usually in late adulthood. In the familial  form, onset can be earlier. The course is typ-
ically persistent, lasting more than 3 months, but the severity may increase depending on work
and social schedules. The advanced sleep pha se type is more common in older adults.
Clinical expression may vary across the lif espan depending on social, school, and work
obligations. Individuals who can alter their work schedules to ac commodate the advanced
circadian sleep and wake timing can experience remission of symptoms. Increasing age
tends to advance the sleep phase, however, it is unclear whether the common age-associ-
ated advanced sleep phase type is due solely to a change in circadian timing (as seen in the
familial form) or also to age-related changes in the homeostatic regulation of sleep, result-
ing in earlier awakening. Severi ty, remission, and relapse of symptoms suggest lack of ad-
herence to behavioral and environmental trea tments designed to control sleep and wake
structure and lig ht exposure.


394 Sleep-Wake Disorders
Risk and Prognostic Factors
Environmental. Decreased late afternoon/early evening exposure to light and/or expo-
sure to early morning light du e to early morning awakening can increase the risk of ad-
vanced sleep phase type by advancing circadian rhythms. By going to bed early, these
individuals are not exposed to light in the phase delay region of the curve, resulting in per-
petuation of advanced phase. In familial adva nced sleep phase type, a shortening of the
endogenous circadian period can result in an advanced sleep phase, although circadian pe-
riod does not appear to system atically decrease with age.
Genetic and physiological. Advanced sleep phase type ha s demonstrated an autoso-
mal dominant mode of inheritance, including a PER2  gene mutation causing hypophos-
phorylation of the PER2 protein and a missense mutation in CKI.
Culture-Related Diagnostic Issues
African Americans may have a shorter circad ian period and larger magnitude phase ad-
vances to light than do Caucasians, possibly increasing the risk for development of ad-
vanced sleep phase type in this population.
Diagnostic Markers
A sleep diary and actigraphy may be used as diagnostic markers, as described earlier for
delayed sleep phase type.
Functional Consequences of  Advanced Sleep Phase Type
Excessive sleepiness associated with advanced  sleep phase can have a negative effect on
cognitive performance, social interaction, and safety. Use of wake-promoting agents to
combat sleepiness or sedatives for early mo rning awakening may increase potential for
substance abuse.
Differential Diagnosis
Other sleep disorders. Behavioral factors such as irre gular sleep schedules, voluntary
early awakening, and exposure to light in th e early morning should be considered, partic-


early awakening, and exposure to light in th e early morning should be considered, partic-
ularly in older adults . Careful attention should be paid to rule out other sleep-wake dis-
orders, such as insomnia disorder, and other mental disorders and medical conditions that
can cause early morning awakening.
Depressive and bipolar disorders. Because early morning awaken ing, fatigue, and sleep-
iness are prominent features of major depres sive disorder, depressive and bipolar disor-
ders must also be considered.
Comorbidity
Medical conditions and mental disorders wi th the symptom of early morning awakening,
such as insomnia, can co-occur with the advance sleep phase type.
Irregular Sleep-Wake Type
Diagnostic Features
The diagnosis of irregular sleep-wake type is based primarily on a history of symptoms of
insomnia at night (during the usual sleep pe riod) and excessive sleepiness (napping) dur-
ing the day. Irregular sleep-wake type is char acterized by a lack of discernable sleep-wake


Circadian Rhythm Sleep-Wake Disorders 395
circadian rhythm. There is no major sleep period, and sleep is fragmented into at least
three periods during the 24-hour day.
Associated Features Supporting Diagnosis
Individuals with irregular slee p-wake type typically present with insomnia or excessive
sleepiness, depending on the time of day. Sleep and wake periods across 24 hours are frag-
mented, although the longest sleep period tends to occur between 2:00 A.M. and 6:00 A.M.
and is usually less than 4 hours. A history of isolation or reclusion may occur in association
with the disorder and contribute to the symptoms  via a lack of external stimuli to help en-
train a normal pattern. Individuals or their ca regivers report frequent  naps throughout the
day. Irregular sleep-wake type is most comm only associated with neurodegenerative dis-
orders, such as major neurocognitive disorder, and many neurodevelopmental disorders
in children.
Prevalence
Prevalence of irregular sleep-wake type in the general population is unknown.
Development and Course
The course of irregular sleep-wak e type is persistent. Age at onset is variable, but the dis-
order is more common in older adults.
Risk and Prognostic Factors
Temperamental. Neurodegenerative disorders, such as  Alzheimer’s disease, Parkinson’s
disease, and Huntington’s disease, and neur odevelopmental disorders in children in-
crease the risk for irregular sleep-wake type.
Environmental. Decreased exposure to environmenta l light and structured daytime ac-
tivity can be associated with a low-amplitud e circadian rhythm. Hospitalized individuals
are especially prone to such weak external en training stimuli, and even outside the hospi-


are especially prone to such weak external en training stimuli, and even outside the hospi-
tal setting, individuals with major neurocogni tive disorder (i.e., dementia) are exposed to
significantly less bright light.
Diagnostic Markers
A detailed sleep history and a sleep diary (by a caregiver) or actigraphy help confirm the
irregular sleep-wake pattern.
Functional Consequences of
Irregular Sleep-Wake Type
Lack of a clearly discernible major sleep and wake period in irregular sleep-wake type re-
sults in insomnia or excessive sleepiness, depending on the time of day. Disruption of the
caregiver’s sleep also often occurs and is an important consideration.
Differential Diagnosis
Normative variations in sleep. Irregular sleep-wake type sh ould be distinguished from
a voluntary irregular sleep-wake schedule and po or sleep hygiene, which can result in in-
somnia and excessive sleepiness.
Other medical conditions and mental disorders. Other causes of insomnia and daytime
sleepiness, including comorbid medical condit ions and mental disorders or medication,
should be considered.


396 Sleep-Wake Disorders
Comorbidity
Irregular sleep-wake type is often comorbid  with neurodegenerat ive and neurodevelop-
mental disorders, such as major neurocognitive disorder, inte llectual disability (intellec-
tual developmental disorder), and traumatic br ain injury. It is also  comorbid with other
medical conditions and mental disorders in wh ich there is social isolation and/or lack of
light and structured activities.
Non-24-Hour Sleep-Wake Type
Diagnostic Features
The diagnosis of non-24-hour sleep-wake type  is based primarily on a history of symp-
toms of insomnia or excessive sleepiness related to abnormal synchronization between the
24-hour light-dark cycle and the endogenous circadian rhythm. Individuals typically pre-
sent with periods of insomnia, excessive sleepiness, or both, which alternate with short
asymptomatic periods. Starting with the asymptomatic period, when the individual’s
sleep phase is aligned to the external envi ronment, sleep latency will gradually increase
and the individual will complain of sleep-onset insomnia. As the sleep phase continues to
drift so that sleep time is no w in the daytime, the individu al will have trouble staying
awake during the day and will complain of sleepiness. Because the circadian period is not
aligned to the external 24-hour environment,  symptoms will depend on when an individ-
ual tries to sleep in relation to the circadian rhythm of sleep propensity.
Associated Features Supporting Diagnosis
Non-24-hour sleep-wake type is most common among blind or visually impaired individ-
uals who have decreased light perception. In si ghted individuals, there is often a history of
delayed sleep phase and of decreased exposure to light and structured social and physical
activity. Sighted individuals with non-24-h our sleep-wake type also demonstrate in-


activity. Sighted individuals with non-24-h our sleep-wake type also demonstrate in-
creased sleep duration.
Prevalence
Prevalence of non-24-hour sleep-wake type in the general population is unclear, but the
disorder appears rare in sighte d individuals. The prevalence in blind individuals is esti-
mated to be 50%.
Development and Course
Course of non-24-hour sleep-wake type is per sistent, with intermittent remission and ex-
acerbations due to changes in work and social schedules throughout the lifespan. Age at
onset is variable, depending on the onset of visual impairment. In sighted individuals, be-
cause of the overlap with delayed sleep phase  type, non-24-hour sleep-wake type may de-
velop in adolescence or early adulthood. Remi ssion and relapse of symptoms in blind and
sighted individuals largely depend on adhere nce to treatments designed to control sleep
and wake structure and light exposure.
Clinical expression may vary across the lif espan depending on social, school, and work
obligations. In adolescents and adults, irre gular sleep-wake schedules and exposure to
light or lack of light at critical times of the day can exacerbate the effects of sleep loss and
disrupt circadian entrainment. Consequently , symptoms of insomnia, daytime sleepiness,
and school, professional, and interpersonal functioning may worsen.
Risk and Prognostic Factors
Environmental. In sighted individuals, decreased expo sure or sensitivit y to light and so-
cial and physical activity cues may contribute to a free-running circadian rhythm. With the


Circadian Rhythm Sleep-Wake Disorders 397
high frequency of mental disorders involving social isol ation and cases of non-24-hour
sleep-wake type developing after a change in sl eep habits (e.g., night shift work, job loss),
behavioral factors in combination with physi ological tendency may precipitate and per-
petuate this disorder in sighte d individuals. Hospitalized indi viduals with neurological and
psychiatric disorders can become insensitive to  social cues, predisposing them to the de-
velopment of non-24-hour sleep-wake type.
Genetic and physiological. Blindness is a risk factor for non-24-hour sleep-wake type.
Non-24-hour sleep-wake type has been as sociated with traumatic brain injury.
Diagnostic Markers
Diagnosis is confirmed by history and sleep di ary or actigraphy for an extended period.
Sequential measurement of phase markers (e.g ., melatonin) can help determine circadian
phase in both sighted and blind individuals.
Functional Consequences of
Non-24-Hour Sleep-Wake Type
Complaints of insomnia (sleep onset and sleep  maintenance), excessive sleepiness, or both
are prominent. The unpredictability of sleep an d wake times (typically a daily delay drift)
results in an inability to attend  school or maintain a steady job and may increase potential
for social isolation.
Differential Diagnosis
Circadian rhythm sleep-wake disorders. In sighted individuals, non-24-hour sleep-wake
type should be differentiated from delayed sl eep phase type, as individuals with delayed
sleep phase type may display a similar progressive delay in sleep period for several days.
Depressive disorders. Depressive symptoms and depressive disorders may result in
similar circadian dysregulation and symptoms.
Comorbidity


similar circadian dysregulation and symptoms.
Comorbidity
Blindness is often comorbid with non-24-hour sleep-wake type, as are depressive and bi-
polar disorders with social isolation.
Shift Work Type
Diagnostic Features
Diagnosis is primarily based on a history of th e individual working outside of the normal
8:00 A.M. to 6:00 P.M. daytime window (particularly at ni ght) on a regularly scheduled (i.e.,
non-overtime) basis. Symptoms of excessive sleepiness at work, and impaired sleep at
home, on a persistent basis are prominent. Pres ence of both sets of symptoms are usually
required for a diagnosis of shift work type. Ty pically, when the individual reverts to a day-
work routine, symptoms resolve. Although the etiology is slightly different, individuals
who travel across many time zones on a very frequent basis may experience effects similar
to those experienced by individuals with shift work type who work rotating shifts.
Prevalence
The prevalence of shift work ty pe is unclear, but the disorder is estimated to affect 5%–10%
of the night worker population  (16%–20% of the workforce). Prevalence rises with advance-
ment into middle-age and beyond (Drake et al. 2004).


398 Sleep-Wake Disorders
Development and Course
Shift work type can appear in individuals of any age but is more prevalent in individuals
older than 50 years and typically worsens with the passage of time if the disruptive work
hours persist. Although older adults may sh ow similar rates of circadian phase adjust-
ment to a change in routine as  do younger adults, they appear to experience significantly
more sleep disruption as a consequence of the circadian phase shift.
Risk and Prognostic Factors
Temperamental. Predisposing factors include a morn ing-type disposition, a need for
long (i.e., more than 8 hours) sleep duration s in order to feel well rested, and strong com-
peting social and domestic needs (e.g., parents of young children). Individuals who are able
to commit to a nocturnal lifestyle, with fe w competing day-oriented demands, appear at
lower risk for shift work type.
Genetic and physiological. Because shift workers are more likely than day workers to
be obese, obstructive sleep apnea may be present and may exacerbate the symptoms.
Diagnostic Markers
A history and sleep diary or actigraphy may be  useful in diagnosis, as discussed earlier for
delayed sleep phase type.
Functional Consequences  of Shift Work Type
Individuals with shift work type not only ma y perform poorly at work but also appear to
be at risk for accidents both at work and on the drive home. They may also be at risk for
poor mental health (e.g., alcohol use diso rder, substance use diso rder, depression) and
physical health (e.g., gastrointestinal disorder s, cardiovascular dise ase, diabetes, cancer).
Individuals with a history of bipolar disorder  are particularly vulnerable to shift work
type–related episodes of mania resulting from missed nights of sleep. Shift work type of-


type–related episodes of mania resulting from missed nights of sleep. Shift work type of-
ten results in interpersonal problems.
Differential Diagnosis
Normative variations in sleep with shift work. The diagnosis of shift work type, as op-
posed to the “normal” difficulties of shift wo rk, must depend to some  extent on the sever-
ity of symptoms and/or level of distress experienced by the individual. Presence of shift
work type symptoms even when the individual is able to live on a da y-oriented routine for
several weeks at a time may suggest the presence  of other sleep disord ers, such as sleep ap-
nea, insomnia, and narcolepsy, which should be ruled out.
Comorbidity
Shift work type has been associated with in creased alcohol use disorder, other substance
use disorders, and depression. A variety of physical health disorders (e.g., gastrointestinal
disorders, cardiovascular disease, diabetes, ca ncer) have been found to be associated with
prolonged exposure to shift work.
Relationship to Internat ional Classification of
Sleep Disorders
The International Classification of Sleep Disorders,  2nd Edition (ICSD-2), differentiates nine
circadian rhythm sleep disord ers, including jet lag type.


Non–Rapid Eye Movement Sleep Arousal Disorders 399
Parasomnias
Parasomnias are disorders characterized by abnormal behavioral, experiential, or physio-
logical events occurring in association with sleep, specific sleep stages, or sleep-wake tran-
sitions. The most common parasomnia s—non–rapid eye movement (NREM) sleep
arousal disorders and rapid eye movement (REM) sleep behavi or disorder—represent ad-
mixtures of wakefulness and NREM sleep an d wakefulness and REM sleep, respectively.
These conditions serve as a reminder that sleep and wakefulness are not mutually exclu-
sive and that sleep is not necessarily  a global, whole-brain phenomenon.
Non–Rapid Eye Movement
Sleep Arousal Disorders
Diagnostic Criteria
A. Recurrent episodes of incomplete awakeni ng from sleep, usually occurring during the
first third of the major sleep episode, accompanied by either one of the following:
1.Sleepwalking:  Repeated episodes of rising from bed during sleep and walking
about. While sleepwalking, the individual has a blank, staring face; is relatively un-
responsive to the efforts of others to communicate with him or her; and can be
awakened only with great difficulty.
2.Sleep terrors:  Recurrent episodes of abrupt terror arousals from sleep, usually be-
ginning with a panicky scream. There is intense fear and signs of autonomic
arousal, such as mydriasis, tachycardia, rapid breathing, and sweating, during
each episode. There is relative unresponsiveness to efforts of others to comfort the
individual during the episodes.
B. No or little (e.g., only a single visual scene) dream imagery is recalled.
C. Amnesia for the episodes is present.


C. Amnesia for the episodes is present.
D. The episodes cause clinically significant di stress or impairment in social, occupational,
or other important areas of functioning.
E. The disturbance is not attributable to the physiological effects of a substance (e.g., a
drug of abuse, a medication).
F. Coexisting mental and medical disorders do not explain the episodes of sleepwalking
or sleep terrors.
Coding note:  For ICD-9-CM, code 307.46 for all subtypes. For ICD-10-CM, code is based
on subtype.
Specify whether:
307.46 (F51.3)  Sleepwalking type
Specify if:
With sleep-related eating
With sleep-related sexual behavior (sexsomnia)
307.46 (F51.4) Sleep terror type


400 Sleep-Wake Disorders
Diagnostic Features
The essential feature of non– rapid eye movement (NREM) sleep arousal disorders is the
repeated occurrence of incomple te arousals, usually beginning during the first third of the
major sleep episode (Criterion A), that typica lly are brief, lasting 1–10 minutes, but may be
protracted, lasting up to 1 hour. The maximum duration of an event is unknown. The eyes
are typically open during these events. Many individuals exhibit both subtypes of arousals
on different occasions, which underscores the unitary underlying pathophysiology. The
subtypes reflect varying degrees of simult aneous occurrence of wakefulness and NREM
sleep, resulting in complex behaviors arising from sleep with varying degrees of conscious
awareness, motor activity, and autonomic activation.
The essential feature of sleepwalking is repeated episodes of complex motor behavior
initiated during sleep, including rising from bed and walking about (Criterion A1). Sleep-
walking episodes begin during any stage of NREM sleep, most commonly during slow-
wave sleep and therefore most often occurring during the firs t third of the night. During
episodes, the individual has reduced alertness and responsiveness, a blank stare, and rel-
ative unresponsiveness to communication with others or effo rts by others to awaken the
individual. If awakened during the episode (or on awakening the following morning), the
individual has limited recall for the episode. Af ter the episode, there may initially be a brief
period of confusion or difficult y orienting, followed by full recovery of cognitive function
and appropriate behavior.
The essential feature of sleep terrors  is the repeated occurrenc e of precipitous awaken-
ings from sleep, usually beginning with a pani cky scream or cry (Criterion A2). Sleep ter-


rors usually begin during the first third of the major sleep episode and last 1–10 minutes,
but they may last considerably longer, partic ularly in children. The episodes are accom-
panied by impressive autonomic arousal and behavioral manifestations of intense fear.
During an episode, the individual is difficult to  awaken or comfort. If the individual awak-
ens after the sleep terror, little or none of th e dream, or only fragmentary, single images,
are recalled. During a typical episode of sleep terrors, the individual abruptly sits up in
bed screaming or crying, with a frightened ex pression and autonomic signs of intense anx-
iety (e.g., tachycardia,  rapid breathing, sweating, dilati on of the pupils). The individual
may be inconsolable and is usually unresponsive to the efforts of others to awaken or com-
fort him or her. Slee p terrors are also called “night terrors” or “pavor nocturnus.”
Associated Features Supporting Diagnosis
Sleepwalking episodes can include a wide va riety of behaviors. Episodes may begin with
confusion: the individual may simply sit up in  bed, look about, or pick at the blanket or
sheet. This behavior then becomes progress ively complex. The in dividual may actually
leave the bed and walk into closets, out of th e room, and even out of buildings. Individuals
may use the bathroom, eat, talk, or engage in  more complex behaviors. Running and fran-
tic attempts to escape some apparent threat can also occur. Most behaviors during sleep-
walking episodes are routine and of low complexity. However, cases of unlocking doors
and even operating machinery (driving an au tomobile) have been reported. Sleepwalking
can also include inappropriate behavior (e.g.,  commonly, urinating in a closet or waste-


basket). Most episodes l ast for several minutes to a half hour but may be more protracted.
Inasmuch as sleep is a state of relative analgesia, painful injuries sustained during sleep-
walking may not be appreciated until awakening after the fact.
There are two “specialized” fo rms of sleepwalking: sleep-related eating behavior and


walking may not be appreciated until awakening after the fact.
There are two “specialized” fo rms of sleepwalking: sleep-related eating behavior and
sleep-related sexual behavior (sexsomn ia or sleep sex). Individuals with sleep-related eating
experience unwanted recurrent episodes of eating with varying degrees of amnesia, rang-
ing from no awareness to full awareness with out the ability to not eat. During these epi-
sodes, inappropriate foods may be ingested. In dividuals with sleep-re lated eating disorder
may find evidence of their eating only the next morning. In sexsomnia,  varying degrees of


Non–Rapid Eye Movement Sleep Arousal Disorders 401
sexual activity (e.g., masturbation, fondling,  groping, sexual intercourse) occur as complex
behaviors arising from sleep wi thout conscious awareness. Th is condition is more common
in males and may result in serious interper sonal relationship problems or medicolegal
consequences.
During a typical episode of sleep terrors, th ere is often a sense of overwhelming dread,
with a compulsion to escape. Although fragmentary vivid dream images may occur, a story-
like dream sequence (as in nightmares) is not reported. Most commonly,  the individual does
not awaken fully, but returns to sleep and has amnesia for the episode on awakening the next
morning. Usually only one episode will occur on any one night. Occasionally several episodes
may occur at intervals throughout the night. Th ese events rarely arise during daytime naps.
Prevalence
Isolated or infrequent NREM sleep arousal disorders are ve ry common in the general pop-
ulation. From 10% to 30% of children have had at least one episode of sleepwalking, and
2%–3% sleepwalk often. The prevalence of slee pwalking disorder, marked by repeated ep-
isodes and impairment or dist ress, is much lower, probably  in the range of 1%–5%. The
prevalence of sleepwalking episodes (not sleepwalking disorder) is 1.0%–7.0% among
adults, with weekly to monthly episodes o ccurring in 0.5%–0.7%. The lifetime prevalence
of sleepwalking in adults is 29.2%, with a p ast-year prevalence of sleepwalking of 3.6%.
The prevalence of sleep terrors in the general population is unknown. The prevalence


The prevalence of sleep terrors in the general population is unknown. The prevalence
of sleep terror episodes (as op posed to sleep terror disorder, in which there is recurrence
and distress or impairment) is approximately 36.9 % at 18 months of age, 19.7% at 30 months
of age, and 2.2% in adults.
Development and Course
NREM sleep arousal disorders occur most co mmonly in childhood and diminish in fre-
quency with increasing age. The onset of sl eepwalking in adults with no prior history of
sleepwalking as children should prompt a search for specific etiologies, such as obstruc-
tive sleep apnea, nocturnal seiz ures, or effect of medication.
Risk and Prognostic Factors
Environmental. Sedative use, sleep deprivation, sl eep-wake schedule disruptions, fa-
tigue, and physical or emotional stress increa se the likelihood of ep isodes. Fever and sleep
deprivation can produce an increased freq uency of NREM sleep arousal disorders.
Genetic and physiological. A family history for sleepwalking or sleep terrors may oc-
cur in up to 80% of individuals who sleepwal k. The risk for sleepwalking is further in-
creased (to as much as 60% of offspring) when both parents have a history of the disorder.
Individuals with sleep terrors frequently ha ve a positive family history of either sleep
terrors or sleepwalking, with as high as a 10-fo ld increase in the prevalence of the disorder
among first-degree biological relatives. Slee p terrors are much more common in monozy-
gotic twins as compared with dizygotic twins.  The exact mode of inheritance is unknown.
Gender-Related Diagnostic Issues


Gender-Related Diagnostic Issues
Violent or sexual activity during sleepwalking episodes is more likely to occur in adults.
Eating during sleepwalking epis odes is more commonly seen in females. Sleepwalking oc-
curs more often in females during childhood but more often in males during adulthood.
Older children and adults provide a more de tailed recollection of fearful images asso-
ciated with sleep terrors than do younger ch ildren, who are more likely to have complete
amnesia or report only a vague sense of fear. Among children, sleep terrors are more com-
mon in males than in females. Among adults, the sex ratio is even.


402 Sleep-Wake Disorders
Diagnostic Markers
NREM sleep arousal disorders arise from an y stage of NREM sleep but most commonly
from deep NREM sleep (slow-wave sleep). They are most likely to appear in the first third
of the night and do not commonly occur duri ng daytime naps. During the episode, the
polysomnogram may be obscured with movement artifact. In the absence of such artifact,
the electroencephalogram typically shows theta or alpha frequency activity during the ep-
isode, indicating partial or incomplete arousal.
Polysomnography in conjunctio n with audiovisual monitoring  can be used to document
episodes of sleepwalking. In the absence of ac tually capturing an event during a polysomno-
graphic recording, there are no polysomnogra phic features that can serve as a marker for
sleepwalking. Sleep deprivation may increase the likelihood of capturing an event. As a group,
individuals who sleepwalk show instability of de ep NREM sleep, but th e overlap in findings
with individuals who do not sleepwalk is great en ough to preclude use of this indicator in es-
tablishing a diagnosis. Unlike arousals from RE M sleep associated with nightmares, in which
there is an increase in heart rate and respiratio n prior to the arousal, the NREM sleep arousals
of sleep terrors begin precipitou sly from sleep, without anticipatory autonomic changes. The
arousals are associated with impressive autono mic activity, with doubling or tripling of
the heart rate. The pathophysiology is poorly unde rstood, but there appears to be instability in
the deeper stages of NREM sleep. Absent capturing an event during a formal sleep study,
there are no reliable polysomnographic indicators  of the tendency to experience sleep terrors.
Functional Consequences of


Functional Consequences of
Non-REM Sleep Arousal Disorders
For the diagnosis of a NREM sl eep arousal disorder to be ma de, the individual or house-
hold members must experience clinically signi ficant distress or impairment, although pa-
rasomnia symptoms may occur occasionally in nonclinical populations and would be
subthreshold for the diagnosis. Embarrassment concerning the episodes can impair social
relationships. Social isolation or occupational difficulties ca n result. The determination of a
“disorder” depends on a number  of factors, which may vary on an individual basis and
will depend on the frequency of  events, potential for violence  or injurious behaviors, em-
barrassment, or disruption/distr ess of other household member s. Severity determination
is best made based on the nature or consequenc e of the behaviors rather  than simply on fre-
quency. Uncommonly, NREM sleep arousal disorders may result in serious injury to the
individual or to someone trying  to console the individual. Inju ries to others are confined to
those in close proximity; individuals are not “sought out.” Typically, sleepwalking in both
children and adults is not associated with si gnificant mental disorders. For individuals
with sleep-related eating behaviors, unknowingly preparing or eati ng food during the
sleep period may create problems  such as poor diabetes control, weight gain, injury (cuts
and burns), or consequences of  eating dangerous or toxic in edibles. NREM sleep arousal
disorders may rarely result in violent or injurious behaviors with forensic implications.
Differential Diagnosis
Nightmare disorder. In contrast to individuals with NREM sleep arousal disorders, in-
dividuals with nightmar e disorder typically awaken eas ily and completely, report vivid
storylike dreams accompanying the episodes, and tend to have episodes later in the night.


storylike dreams accompanying the episodes, and tend to have episodes later in the night.
NREM sleep arousal disorders occur during NREM sleep, whereas nightmares usually oc-
cur during REM sleep. Parents of children with NREM sleep arousal disorders may mis-
interpret reports of fragme ntary imagery as nightmares.
Breathing-related sleep disorders. Breathing disorders during  sleep can also produce


interpret reports of fragme ntary imagery as nightmares.
Breathing-related sleep disorders. Breathing disorders during  sleep can also produce
confusional arousals with subsequent amnesi a. However, breathin g-related sleep disor-
ders are also characterized by characteristic  symptoms of snoring,  breathing pauses, and


Non–Rapid Eye Movement Sleep Arousal Disorders 403
daytime sleepiness. In some individuals, a breathing-related sleep disorder may precipi-
tate episodes of sleepwalking.
REM sleep behavior disorder. REM sleep behavior disorder may be difficult to distin-
guish from NREM sleep arousal disorders. REM sleep behavior  disorder is characterized
by episodes of prominent, co mplex movements, often involving personal injury arising
from sleep. In contrast to NR EM sleep arousal disorders, REM  sleep behavior disorder oc-
curs during REM sleep. Individuals with REM sleep behavior disorder awaken easily and
report more detailed and vivid dream content than do individuals wi th NREM sleep arousal
disorders. They often report that they “act out dreams.”
Parasomnia overlap syndrome. Parasomnia overlap syndrome consists of clinical and
polysomnographic features of both sleepwa lking and REM sleep behavior disorder.
Sleep-related seizures. Some types of seizures can prod uce episodes of very unusual
behaviors that occur predominantly or exclu sively during sleep. Nocturnal seizures may
closely mimic NREM sleep arousal  disorders but tend to be more stereotypic in nature, oc-
cur multiple times nightly, and be more likel y to occur from daytime naps. The presence of
sleep-related seizures does not preclude the presence of NREM sleep arousal disorders.
Sleep-related seizures should be classified as a form of epilepsy.
Alcohol-induced blackouts. Alcohol-induced blackouts may be associated with extremely
complex behaviors in the absence of other suggestions of intoxication. They do not involve
the loss of consciousness but rather reflect an isolated di sruption of memory for events
during a drinking episode. By history, these behaviors may be  indistinguishable from those
seen in NREM sleep arousal disorders.


seen in NREM sleep arousal disorders.
Dissociative amnesia, with dissociative fugue. Dissociative fugue may be extremely
difficult to distinguish from sleepwalking. Unlike all other parasomnias, nocturnal disso-
ciative fugue arises from a period of wakefu lness during sleep, rather than precipitously
from sleep without intervening wakefulness. A history of recurrent childhood physical or
sexual abuse is usually present (b ut may be difficult to obtain).
Malingering or other voluntary behavior occurring during wakefulness. As with disso-
ciative fugue, malingering or  other voluntary behavior o ccurring during wakefulness
arises from wakefulness.
Panic disorder. Panic attacks may also cause abrupt awakenings from deep NREM sleep
accompanied by fearfulness, but these episode s produce rapid and complete awakening with-
out the confusion, amnesia, or motor activity typical of NREM sleep arousal disorders.
Medication-induced complex behaviors. Behaviors similar to those in NREM sleep
arousal disorders can be induced by use of, or withdrawal from, substances or medica-
tions (e.g., benzodiazepines, nonbenzodiazepine  sedative-hypnotics, opiates, cocaine, nic-
otine, antipsychotics, tricyclic antidepressant s, chloral hydrate). Such behaviors may arise
from the sleep period and may be extremel y complex. The underlying pathophysiology
appears to be a relatively isolated amnesia. In such cases, substance/medication-induced
sleep disorder, parasomnia type, should be diagnosed (see “Substance/Medication-
Induced Sleep Disorder” la ter in this chapter).
Night eating syndrome. The sleep-related eating disorder form of sleepwalking is to be


Night eating syndrome. The sleep-related eating disorder form of sleepwalking is to be
differentiated from night eating syndrome, in which there is a delay in the circadian rhythm
of food ingestion and an association  with insomnia and/or depression.
Comorbidity
In adults, there is an association between sleepwalking and major depressive episodes and
obsessive-compulsive disorder. Children or ad ults with sleep terro rs may have elevated
scores for depression and anxiet y on personality inventories.


404 Sleep-Wake Disorders
Relationship to Internat ional Classification of
Sleep Disorders
The International Classificat ion of Sleep Disorders,  2nd Edition, includes “confusional
arousal” as a NREM sleep arousal disorder.
Nightmare Disorder
Diagnostic Criteria 307.47 (F51.5)
A. Repeated occurrences of extended, extremely dysphoric, and well-remembered
dreams that usually involve efforts to avoid threats to survival, security, or physical in-
tegrity and that generally occur during the second half of the major sleep episode.
B. On awakening from the dysphoric dreams, the individual rapidly becomes oriented and
alert.
C. The sleep disturbance causes clinically significant distress or impairment in social, oc-
cupational, or other important areas of functioning.
D. The nightmare symptoms are not attributable to the physiological effects of a sub-
stance (e.g., a drug of abuse, a medication).
E. Coexisting mental and medical disorders do not adequately explain the predominant
complaint of dysphoric dreams.
Specify if:
During sleep onset
Specify if:
With associated non–sleep disorder, including substance use disorders
With associated othe r medical condition
With associated ot her sleep disorder
Coding note:  The code 307.47 (F51.5) applies to all three specifiers. Code also the
relevant associated mental disorder, medical condition, or other sleep disorder imme-
diately after the code for nightmare disorder in order to indicate the association.
Specify if:
Acute:  Duration of period of nightmares is 1 month or less.
Subacute:  Duration of period of nightmares is greater than 1 month but less than
6 months.
Persistent:  Duration of period of nightmares is 6 months or greater.
Specify current severity:


Specify current severity:
Severity can be rated by the frequency with which the nightmares occur:
Mild:  Less than one episode per week on average.
Moderate: One or more episodes per week but less than nightly.
Severe:  Episodes nightly.
Diagnostic Features
Nightmares  are typically lengthy, elaborate, st orylike sequences of dream imagery that
seem real and that incite anxiety, fear, or  other dysphoric emotio ns. Nightmare content
typically focuses on attempts to avoid or cope with immi nent danger but may involve
themes that evoke other negative emotions. Nightmares occurring after traumatic experi-
ences may replicate the threatening situation (“replicative nightmares”), but most do not.
On awakening, nightmares are well remembered and can be described in detail. They arise


Nightmare Disorder 405
almost exclusively during rapid eye moveme nt (REM) sleep and can thus occur through-
out sleep but are more likely in the second half of the major sleep episode when dreaming
is longer and more intense. Factors that incr ease early-night REM intensity, such as sleep
fragmentation or deprivation, jet lag, and REM-sensitive medications, might facilitate
nightmares earlier in the night, including at sleep onset.
Nightmares usually terminate with awakening and rapid return of full alertness. How-
ever, the dysphoric emotions may persist into wakefulness and contribute to difficulty re-
turning to sleep and lasting daytime distress . Some nightmares, known as “bad dreams,”
may not induce awakening and are recalled only later. If nightmare s occur during sleep-
onset REM periods ( hypnagogic ), the dysphoric emotion is frequently accompanied by a
sense of being both awake and unable to move voluntarily ( isolated sleep paralysis ).
Associated Features Supporting Diagnosis
Mild autonomic arousal, including sweating, tachycardia, and tachypnea, may character-
ize nightmares. Body movements and vocalizations are not characteristic because of REM
sleep–related loss of skeletal  muscle tone, but such behavi ors may occur under situations
of emotional stress or sleep fragmentation and in posttraumatic stress disorder (PTSD).
When talking or emoting occurs, it is typica lly a brief event terminating the nightmare.
Individuals with frequent nightmares are at substantially greater r isk for suicidal ide-
ation and suicide attempts, even when gender  and mental illness are taken into account.
Prevalence
Prevalence of nightmares in creases through childhood into adolescence. From 1.3% to
3.9% of parents report that their preschool children have nightmares “often” or “always”.


Prevalence increases from ages 10 to 13 for both males and females but continues to in-
crease to ages 20–29 for females (while decreasing for males), when it can be twice as high
for females as for males. Prevalen ce decreases steadily with age for both sexes, but the gen-
der difference remains. Among adults, prevalen ce of nightmares at least monthly is 6%,
whereas prevalence for frequent nightmare s is 1%–2%. Estimates often combine idio-
pathic and posttraumatic nightmares indiscriminately.
Development and Course
Nightmares often begin between ages 3 and 6 years but reach a peak prevalence and se-
verity in late adolescence or  early adulthood. Nigh tmares most likely appear in children
exposed to acute or chronic psychosocial stressors and thus may not resolve spontane-
ously. In a minority, frequent nightmares pers ist into adulthood, becoming virtually a life-
long disturbance. Although specific nightm are content may reflect the individual’s age,
the essential features of the diso rder are the same across age groups.
Risk and Prognostic Factors
Temperamental. Individuals who experience nightmares  report more frequent past ad-
verse events, but not necessarily trauma, an d often display personality disturbances or
psychiatric diagnosis.
Environmental. Sleep deprivation or fragmentation, and irregular sleep-wake schedules
that alter the timing, intensity,  or quantity of REM sleep, can put individuals at risk for
nightmares.
Genetic and physiological. Twin studies have identified genetic effects on the disposi-
tion to nightmares and their co-occurrence with other parasomnias (e.g., sleeptalking).
Course modifiers. Adaptive parental bedside behaviors, such as soothing the child fol-
lowing nightmares, may protect agai nst developing chronic nightmares.


406 Sleep-Wake Disorders
Culture-Related Diagnostic Issues
The significance attributed to nightmares may va ry by culture, and sensitivity to such be-
liefs may facilitate disclosure.
Gender-Related Diagnostic Issues
Adult females report having ni ghtmares more frequently th an do adult males. Nightmare
content differs by sex, with adult females tend ing to report themes of sexual harassment or
of loved ones disappearing/dying, and adult males tending to report themes of physical
aggression or war/terror.
Diagnostic Markers
Polysomnographic studies demonstrate abrupt awakenings from REM sleep, usually during
the second half of the night, prior to report of a nightmare. Heart, respiratory, and eye move-
ment rates may quicken or increase in variab ility before awakening.  Nightmares following
traumatic events may also arise during non-REM (NREM), particularly stage 2, sleep. The typ-
ical sleep of individuals with nightmares is mild ly impaired (e.g., redu ced efficiency, less slow-
wave sleep, more awakenings), with more frequent periodic leg movements in sleep and rel-
ative sympathetic nervous system activation after REM sleep deprivation.
Functional Consequences  of Nightmare Disorder
Nightmares cause more significant subjective distress than demonstrable social or occu-
pational impairment. However, if awakenings are frequent or result in sleep avoidance,
individuals may experience excessive daytime sleepiness, poor concentration, depression,
anxiety, or irritability. Freque nt childhood nightmares (e.g.,  several per week), may cause
significant distress to parents and child.
Differential Diagnosis
Sleep terror disorder. Both nightmare disorder and sleep  terror disorder include awak-
enings or partial awakenings with fearfuln ess and autonomic activation, but the two dis-
orders are differentiable. Nightmares typically occur later in the night, during REM sleep,


orders are differentiable. Nightmares typically occur later in the night, during REM sleep,
and produce vivid, storylike, and clearly re called dreams; mild autonomic arousal; and
complete awakenings. Sleep terrors typically arise in the first third of the night during
stage 3 or 4 NREM sleep and produce either no dream recall or images without an elabo-
rate storylike quality. The terr ors lead to partial awakenings that leave the individual con-
fused, disoriented, and only partially resp onsive and with substantial autonomic arousal.
There is usually amnesia for the event in the morning.
REM sleep behavior disorder. The presence of complex motor activity during fright-
ening dreams should prompt further evaluation for REM sleep behavior disorder, which
occurs more typically among late middle-age  males and, unlike nightmare disorder, is as-
sociated with often violent dream enactment s and a history of nocturnal injuries. The
dream disturbance of REM sleep behavior diso rder is described by patients as nightmares
but is controlled by appropriate medication.
Bereavement. Dysphoric dreams may occur during bereavement but typically involve
loss and sadness and are followed by self-refle ction and insight, rather than distress, on
awakening.
Narcolepsy. Nightmares are a frequent complaint in  narcolepsy, but the presence of ex-
cessive sleepiness and cataplexy differentiates  this condition from  nightmare disorder.
Nocturnal seizures. Seizures may rarely manifest as nightmares and should be evalu-
ated with polysomnography and continuous video electroencephalography. Nocturnal
seizures usually involve stereotypical motor activity. Associated nightmares, if recalled,


Rapid Eye Movement Sleep Behavior Disorder 407
are often repetitive in nature or reflect epilept ogenic features such as the content of diurnal
auras (e.g., unmotivated dread), phosphenes, or  ictal imagery. Disord ers of arousal, espe-
cially confusional arousals, may also be present.
Breathing-related sleep disorders. Breathing-related sleep disorders can lead to awaken-
ings with autonomic arousal, but these are not usually accompanied by recall of nightmares.
Panic disorder. Attacks arising during sleep can produce abrupt awakenings with au-
tonomic arousal and fearfulness, but nightmares are typically not reported and symptoms
are similar to panic attacks arising during wakefulness.
Sleep-related dissociative disorders. Individuals may recall actual physical or emo-
tional trauma as a “dream” during elec troencephalography-documented awakenings.
Medication or substance use. Numerous substances/medicat ions can precipitate night-
mares, including dopaminergics; beta-adrener gic antagonists and other antihypertensives;
amphetamine, cocaine, and other stimulants; antidepressants; smoking cessation aids;
and melatonin. Withdrawal of REM sleep–su ppressant medications (e.g., antidepressants)
and alcohol can produce REM sleep rebound accompanied by nightmares. If nightmares
are sufficiently severe to warrant independent clinical attention, a diagnosis of substance/
medication-induced sleep disorder should be considered.
Comorbidity
Nightmares may be comorbid with several medical conditions, including coronary heart
disease, cancer, parkinsonism, and pain, and ca n accompany medical treatments, such as he-
modialysis, or withdrawal from medications or  substances of abuse. Nightmares frequently


modialysis, or withdrawal from medications or  substances of abuse. Nightmares frequently
are comorbid with other mental disorders, in cluding PTSD; insomnia disorder; schizophrenia;
psychosis; mood, anxiety, adjustment, and personality disorders; and grief during be-
reavement. A concurrent nightmare disorder diagnosis should only be considered when in-
dependent clinical attention is warranted (i.e., Criteria A–C are met). Otherwise, no separate
diagnosis is necessary. These conditions should be listed under the appropriate comorbid
category specifier. However, nightmare disorder  may be diagnosed as a separate disorder in
individuals with PTSD if the nightmares are temporally unrelated to PTSD (i.e., preceding
other PTSD symptoms or persisting after other PTSD symptoms have resolved).
Nightmares are normally characteristic of REM sleep behavior disorder, PTSD, and acute
stress disorder, but nightmare di sorder may be independently coded if nightmares preceded
the condition and their frequency or severity necessitates independent clinical attention. The
latter may be determined by asking whether ni ghtmares were a proble m before onset of the
other disorder and whether they continued after other symptoms had remitted.
Relationship to Internat ional Classification of
Sleep Disorders
The International Classification of Sleep Disorders,  2nd Edition (ICSD-2), presents similar di-
agnostic criteria fo r nightmare disorder.
Rapid Eye Movement Sleep Behavior Disorder
Diagnostic Criteria 327.42 (G47.52)
A. Repeated episodes of arousal during sleep associated with vocalization and/or com-
plex motor behaviors.
B. These behaviors arise during rapid eye movement (REM) sleep and therefore usually
occur more than 90 minutes after sleep onset, are more frequent during the later por-
tions of the sleep period, and uncommonly occur during daytime naps.


408 Sleep-Wake Disorders
C. Upon awakening from these episodes, the individual is completely awake, alert, and
not confused or disoriented.
D. Either of the following:
1. REM sleep without atonia on polysomnographic recording.
2. A history suggestive of REM sleep behavior disorder and an established synuclein-
opathy diagnosis (e.g., Parkinson’s disease, multiple system atrophy).
E. The behaviors cause clinically significant distress or impairment in social, occupa-
tional, or other important areas of functioning (which may include injury to self or the
bed partner).
F. The disturbance is not attributable to the physiological effects of a substance (e.g., a
drug of abuse, a medication) or another medical condition.
G. Coexisting mental and medical disorders do not explain the episodes.
Diagnostic Features
The essential feature of rapid eye movement (REM) sleep behavior disorder is repeated
episodes of arousal, often associated with vo calizations and/or complex motor behaviors
arising from REM sleep (Criterion A). These be haviors often reflect motor responses to the
content of action-filled or violent dreams of being attacked or trying to escape from a
threatening situation, which may be termed dream enacting behaviors. The vocalizations are
often loud, emotion-fill ed, and profane. These behaviors may be very bothersome to the
individual and the bed partner and may result in significant injury (e.g., falling, jumping,
or flying out of bed; running, punching, thru sting, hitting, or kicking). Upon awakening,
the individual is immediately awake, alert, and oriented (Criterion C) and is often able to
recall dream mentation, which closely correlates with the observed behavior. The eyes
typically remain closed during these events. The diagnosis of REM sleep behavior disor-
der requires clinically significant distress or  impairment (Criterion  E); this determination


der requires clinically significant distress or  impairment (Criterion  E); this determination
will depend on a number of factors, including the frequency of events, the potential for vi-
olence or injurious behaviors, embarrassment , and distress in othe r household members.
Associated Features Supporting Diagnosis
Severity determination is best made based on  the nature or conseq uence of the behavior
rather than simply on frequency. Although the behaviors are typically prominent and vi-
olent, lesser behaviors may also occur.
Prevalence
The prevalence of REM sleep behavior disord er is approximately 0.38%–0.5% in the gen-
eral population. Prevalence in patients with psychiatric disorders may be greater, possibly
related to medications prescribed for the psychiatric disorder.
Development and Course
The onset of REM sleep behavior disorder may be gradual or rapid, and the course is usu-
ally progressive. REM sleep behavior disorder associated with neurodegenerative disor-
ders may improve as the unde rlying neurodegenerative disorder progresses. Because of
the very high association with the later appe arance of an underlyi ng neurodegenerative
disorder, most notably one of the synucleino pathies (Parkinson’s disease, multiple system
atrophy, or major or mild neurocognitive di sorder with Lewy bodies), the neurological
status of individuals with REM sleep behavior disorder should be closely monitored.
REM sleep behavior disorder overwhelmingly affects males older than 50 years, but in-
creasingly this disorder is being identified in females and in younger individuals. Symp-


Rapid Eye Movement Sleep Behavior Disorder 409
toms in young individuals, particularly young females, should raise the possibility of
narcolepsy or medication-induced REM sleep behavior disorder.
Risk and Prognostic Factors
Genetic and physiological. Many widely prescribed medications, including tricyclic
antidepressants, selective serotonin reuptake inhibitors, serotonin-norepinephrine reup-
take inhibitors, and beta-blockers, may resu lt in polysomnographic evidence of REM sleep
without atonia and in frank REM sleep behavior disorder. It is not known whether the
medications per se result in REM sleep behavi or disorder or they unmask an underlying
predisposition.
Diagnostic Markers
Associated laboratory findin gs from polysomnography indicate increased tonic and/or
phasic electromyographic activi ty during REM sleep that is normally associated with mus-
cle atonia. The increased muscle activity variably affects different muscle groups, mandating
more extensive electromyographi c monitoring than is employed in conventional sleep stud-
ies. For this reason, it is su ggested that electrom yographic monitoring include the submen-
talis, bilateral extensor digito rum, and bilateral anterior tibi alis muscle groups. Continuous
video monitoring is mandator y. Other polysomnographic findings may include very fre-
quent periodic and aperiodic extremity el ectromyography acti vity during non-REM
(NREM) sleep. This polysomnography observation, termed REM sleep without atonia,  is pres-
ent in virtually all cases of REM sleep behavi or disorder but may also be an asymptomatic
polysomnographic finding. Clinical dream-enacting behaviors coupled with the polysom-
nographic finding of REM without atonia is necessary for the diagnosis of REM sleep behav-


nographic finding of REM without atonia is necessary for the diagnosis of REM sleep behav-
ior disorder. REM sleep without atonia with out a clinical history of dream-enacting
behaviors is simply an asymptomatic polyso mnographic observation. It is not known
whether isolated REM sleep without atonia is a precursor to REM sleep behavior disorder.
Functional Consequences of
Rapid Eye Movement Sl eep Behavior Disorder
REM sleep behavior disorder may occur in isol ated occasions in otherwise unaffected in-
dividuals. Embarrassment concer ning the episodes can impair social relationships. Indi-
viduals may avoid situations in which others might become aware of the disturbance,
visiting friends overnight, or sleeping with be d partners. Social isolation or occupational
difficulties can result. Uncommonly, REM sleep  behavior disorder may result in serious
injury to the victim or to the bed partner.
Differential Diagnosis
Other parasomnias. Confusional arousals, sleepwalking, and sleep terrors can easily be
confused with REM sleep behavior disorder. In  general, these disorders occur in younger
individuals. Unlike REM sleep behavior disorder, they arise from deep NREM sleep and
therefore tend to occur in the early portion of the sleep period. Awakening from a confu-
sional arousal is associated with confusion, disorientation, and incomplete recall of dream
mentation accompanying the behavior. Polysomnographic monitoring in the disorders of
arousal reveals normal REM atonia.
Nocturnal seizures. Nocturnal seizures may perfectly mimic REM sleep behavior disor-
der, but the behaviors are generally more st ereotyped. Polysomnographic monitoring em-
ploying a full electroencephalographic seiz ure montage may differentiate the two. REM
sleep without atonia is not present on polysomnographic monitoring.


410 Sleep-Wake Disorders
Obstructive sleep apnea. Obstructive sleep apnea may result in behaviors indistin-
guishable from REM sleep behavior disorder . Polysomnographic monitoring is necessary
to differentiate between the two. In this ca se, the symptoms resolv e following effective
treatment of the obstructive sleep apnea, and REM sleep without atonia is not present on
polysomnography monitoring.
Other specified dissociative disorder (sleep-related psychogenic dissociative disorder).
Unlike virtually all other parasomnias, which arise precipitously from NREM or REM
sleep, psychogenic dissociative behaviors aris e from a period of well-defined wakefulness
during the sleep period. Unlike REM sleep behavi or disorder, this condition is more prev-
alent in young females.
Malingering. Many cases of malingering in which the individual reports problematic
sleep movements perfectly mimic the clinical features of REM sleep behavior disorder,
and polysomnographic documentation is mandatory.
Comorbidity
REM sleep behavior diso rder is present concurrently in  approximately 30% of patients
with narcolepsy. When it occurs in narcolep sy, the demographics reflect the younger age
range of narcolepsy, with equal frequency in  males and females. Based on findings from
individuals presenting to sleep clinics, most individuals (>50%) with initially “idiopathic”
REM sleep behavior disorder will eventually develop a neurodegenerative disease—most
notably, one of the synucleinopathies (Parkins on’s disease, multiple system atrophy, or
major or mild neurocognitive disorder with Lewy bodies).  REM sleep behavior disorder
often predates any other sign of these disorder s by many years (often more than a decade).
Relationship to Internat ional Classification of
Sleep Disorders


Relationship to Internat ional Classification of
Sleep Disorders
REM sleep behavior disorder is virtually identical to REM sleep beha vior disorder in the
International Classification of Sleep Disorders,  2nd Edition (ICSD-2).
Restless Legs Syndrome
Diagnostic Criteria 333.94 (G25.81)
A. An urge to move the legs, usually accompanied by or in response to uncomfortable and
unpleasant sensations in the legs, characterized by all of the following:
1. The urge to move the legs begins or wors ens during periods of rest or inactivity.
2. The urge to move the legs is partial ly or totally relieved by movement.
3. The urge to move the legs is worse in the evening or at night than during the day,
or occurs only in the evening or at night.
B. The symptoms in Criterion A occur at least three times per week and have persisted
for at least 3 months.
C. The symptoms in Criterion A are accompanied by significant distress or impairment in
social, occupational, educational, academic, behavioral, or other important areas of
functioning.
D. The symptoms in Criterion A are not attributable to another mental disorder or medical
condition (e.g., arthritis, l eg edema, peripheral ischemia, leg cramps) and are not better
explained by a behavioral condition (e.g., positional discomfort, h abitual foot tapping).
E. The symptoms are not attributable to the physiological effects of a drug of abuse or
medication (e.g., akathisia).


Restless Legs Syndrome 411
Diagnostic Features
Restless legs syndrome (RLS) is  a sensorimotor, neurological sleep disorder characterized
by a desire to move the legs or arms, usua lly associated with uncomfortable sensations
typically described as creeping, crawling, tingling, burning, or itch ing (Criterion A). The
diagnosis of RLS is based primarily on patient self-report and history. Symptoms are
worse when the individual is at rest, and freq uent movements of the legs occur in an effort
to relieve the uncomfortable sensations. Sympto ms are worse in the evening or night, and
in some individuals they occur only in the ev ening or night. Evening worsening occurs in-
dependently of any differences in activity. It is important to differentiate RLS from other
conditions such as positional discom fort and leg cramps (Criterion D).
The symptoms of RLS can delay sleep onset and awaken the individual from sleep and
are associated with significant sleep fragmentation. The relief obtained from moving the
legs may no longer be apparent in severe ca ses. RLS is associated with daytime sleepiness
and is frequently accompanied by significant clinical distress or functional impairment.
Associated Features Supporting Diagnosis
Periodic leg movements in sleep (PLMS) can serve as corroborating ev idence for RLS, with
up to 90% of individuals di agnosed with RLS demonstratin g PLMS when recordings are
taken over multiple nights. Periodic leg mo vements during wakefulness are supportive of
an RLS diagnosis. Reports of difficulty initiating and maintaining sleep and of excessive
daytime sleepiness may also support the diagnosis of RLS. Additional supportive features
include a family history of RLS among first- degree relatives and a reduction in symptoms,
at least initially, with dopaminergic treatment.
Prevalence


at least initially, with dopaminergic treatment.
Prevalence
Prevalence rates of RLS vary widely when br oad criteria are utilized but range from 2% to
7.2% when more defined criteria are employed . When frequency of symptoms is at least
three times per week with moderate or severe distress, the prevalence rate is 1.6%; when
frequency of symptoms is a minimum of one ti me per week, the prevalence rate is 4.5%.
Females are 1.5–2 times more likely than males to have RLS. RLS also increases with age.
The prevalence of RLS may be lower in Asian populations.
Development and Course
The onset of RLS typically occurs in the seco nd or third decade. Approximately 40% of in-
dividuals diagnosed with RLS during adul thood report having experienced symptoms
before age 20 years, and 20% report having experienced symptoms before age 10 years.
Prevalence rates of RLS increase steadily with age until about age 60 years, with symptoms
remaining stable or decreasing slightly in older age groups. Compared with nonfamilial
cases, familial RLS usually has a younger age at  onset and a slower pr ogressive course. The
clinical course of RLS differs by age at onset.  When onset occurs before age 45, there is of-
ten a slow progression of symptoms. In late-onset RLS, rapid progression is typical, and
aggravating factors are common. Symptoms of RLS appear similar acro ss the lifespan, re-
maining stable or decreasing slightly in older age groups.
Diagnosis of RLS in children can be diff icult because of the self-report component.
While Criterion A for adults assumes that the description of “urge to move” is by the pa-


tient, pediatric diagnosis requir es a description in the child’s own words rather than by a
parent or caretaker. Typically children age 6 years or older are able to provide detailed, ad-
equate descriptors of RLS. However, children rarely use or understand the word “urge,”
reporting instead that their legs “have to” or  “got to” move. Also, potentially related to
prolonged periods of sitting during class, tw o-thirds of children and adolescents report
daytime leg sensations. Thus, fo r diagnostic Criterion A3, it is important to compare equal


412 Sleep-Wake Disorders
duration of sitting or lying down in the day to sitting or lying down in the evening or night.
Nocturnal worsening tends to persist even in the context of pediatric RLS. As with RLS in
adults, there is a significant negative impact on sleep, mood, cognition, and function. Im-
pairment in children and adolescents is mani fested more often in behavioral and educa-
tional domains.
Risk and Prognostic Factors
Genetic and physiological. Predisposing factors includ e female gender, advancing
age, genetic risk variants, an d family history of RLS. Precipitating factors are often time-
limited, such as iron defici ency, with most individuals resuming normal sleep patterns
after the initial triggering even t has disappeared. Genetic risk variants also play a role in
RLS secondary to such disorder s as uremia, suggesting that individuals with a genetic sus-
ceptibility develop RLS in the presence of further risk factors. RLS has a strong familial
component.
There are defined pathophysi ological pathways subserving RLS. Genome-wide asso-
ciation studies have found that RLS is significantly associated with common genetic vari-
ants in intronic or intergenic regions in MEIS1 , BTBD9 , and MAP2K5  on chromosomes 2p,
6p, and 15q, respectively. The ass ociation of these three varian ts with RLS has been inde-
pendently replicated. BTBD9  confers a very large (80%) exce ssive risk when even a single
allele is present. Because of the high frequenc y of this variant in individuals of European
descent, the population attributable risk (P AR) approximates 50%. At-risk alleles associ-


ated with MEIS1  and BTBD9  are less common in individuals of African or Asian descent,
perhaps suggesting lower risk fo r RLS in these populations.
Pathophysiological mechanisms in RLS also in clude disturbances in the central dopa-
minergic system and disturbances in iron  metabolism. The endo genous opiate system
may also be involved. Treatment effect s of dopaminergic drugs (primarily D2 and D3 non-
ergot agonists) provide further support that  RLS is grounded in dysfunctional central
dopaminergic pathways. While the effective treatment of RLS has also been shown to sig-
nificantly reduce depressive symptoms, seroto nergic antidepressants can induce or aggra-
vate RLS in some individuals.
Gender-Related Diagnostic Issues
Although RLS is more prevalent in females than  in males, there are no diagnostic differ-
ences according to gender. However, the prev alence of RLS during pregnancy is two to
three times greater than in the general population. RLS associated with pregnancy peaks
during the third trimester and improves or reso lves in most cases soon after delivery. The
gender difference in prevalence of RLS is explai ned at least in part by parity, with nullipa-
rous females being at the same r isk of RLS as age-matched males.
Diagnostic Markers
Polysomnography demonstrates  significant abnormalities in RLS, commonly increased
latency to sleep, and higher arousal index.  Polysomnography with a preceding immobili-
zation test may provide an indicator of the motor sign of RLS, periodic limb movements,
under standard conditions of sleep and during quiet resting, both of which can provoke RLS
symptoms.
Functional Consequences of Restless Legs Syndrome


symptoms.
Functional Consequences of Restless Legs Syndrome
Forms of RLS severe enough to si gnificantly impair functioning or  associated with mental dis-
orders, including depression an d anxiety, occur in approximately 2%–3% of the population.
Although the impact of milder  symptoms is less well ch aracterized, in dividuals with
RLS complain of disruption in at  least one activity of daily li ving, with up to 50% reporting


Substance/Medication-Induced Sleep Disorder 413
a negative impact on mood, and 47.6% reporting a lack of energy. The most common conse-
quences of RLS are sleep disturbance, includ ing reduced sleep time , sleep fragmentation,
and overall disturbance; depression, generalize d anxiety disorder, panic disorder, and post-
traumatic stress disorder; and quality-of-life impairments. RLS can result in daytime sleep-
iness or fatigue and is frequently accompanied by significant distress or impairment in
affective, social, occupational, educational, academic, behavioral, or cognitive functioning.
Differential Diagnosis
The most important conditions in the differential diagnosis of RLS are leg cramps, posi-
tional discomfort, arthralgias/arthritis, myalgias, positional ischemia (numbness), leg
edema, peripheral neuropathy, radiculopathy,  and habitual foot tapping. “Knotting” of
the muscle (cramps), relief with a single postural shift, limitation to joints, soreness to pal-
pation (myalgias), and other abnormalities on physical exam ination are not characteristic
of RLS. Unlike RLS, nocturnal leg cramps do not typically present with the desire to move
the limbs nor are there frequent limb movements.  Less common conditions to be differen-
tiated from RLS include neuroleptic-induced akathisia, myelopathy, symptomatic venous
insufficiency, peripheral artery disease, ec zema, other orthopedic problems, and anxiety-
induced restlessness. Worsening at night an d periodic limb movements are more common
in RLS than in medication-induced akathisia or peripheral neuropathy.
While is it important that RLS symptoms not be solely accounted for by another medical


While is it important that RLS symptoms not be solely accounted for by another medical
or behavioral condition, it should also be appreciated that any of thes e similar conditions can
occur in an individual with RLS. This necessi tates a separate focus on each possible condi-
tion in the diagnostic process and when assessing impact. For cases in which the diagnosis of
RLS is not certain, evaluation for the supportive features of RLS, particularly PLMS or a fam-
ily history of RLS, may be helpful. Clinical features, such as response to a dopaminergic
agent and positive family history for RLS,  can help with the differential diagnosis.
Comorbidity
Depressive disorders, anxiety disorders, an d attentional disorder s are commonly comor-
bid with RLS and are discussed in the sectio n “Functional Consequences of Restless Legs
Syndrome.” The main medical disorder comorbid with RLS is cardiovascular disease.
There may be an association with numerous other medical disorders,  including hyperten-
sion, narcolepsy, migraine, Parkinson’s disease, multiple sclerosis, peripheral neuropathy,
obstructive sleep apnea, diabetes mellitus, fibromyalgia, osteoporosis, obesity, thyroid
disease, and cancer. Iron defi ciency, pregnancy, and chronic renal failure are also comor-
bid with RLS.
Relationship to Internat ional Classification of
Sleep Disorders
The International Classifica tion of Sleep Disorders, 2nd Edition (ICSD-2), presents similar diag-
nostic criteria for RLS but does not contain a criterion specifying fr equency or duration of
symptoms.
Substance/Medication-Induced Sleep Disorder
Diagnostic Criteria
A. A prominent and severe disturbance in sleep.
B. There is evidence from the history, physical examination, or laboratory findings of both


B. There is evidence from the history, physical examination, or laboratory findings of both
(1) and (2):


414 Sleep-Wake Disorders
1. The symptoms in Criterion A developed during or soon after substance intoxication
or after withdrawal from or exposure to a medication.
2. The involved substance/medication is capable of producing the symptoms in Crite-
rion A.
C. The disturbance is not better explained by a sleep disorder that is not substance/
medication-induced. Such evidence of an independent sleep disorder could include
the following:
The symptoms precede the onset of the substance/medication use; the symptoms
persist for a substantial period of time (e.g., about 1 month) after the cessation of
acute withdrawal or severe intoxication; or there is other evidence suggesting the
existence of an independent non-substance/medication-induced sleep disorder
(e.g., a history of recurrent non-substance/medication-related episodes).
D. The disturbance does not occur exclusively during the course of a delirium.
E. The disturbance causes clinically significant distress or impairment in social, occupa-
tional, or other important areas of functioning.
Note: This diagnosis should be made instead of a diagnosis of substance intoxication or
substance withdrawal only when the symptoms in Criterion A predominate in the clinical
picture and when they are sufficiently severe to warrant clinical attention.
Coding note: The ICD-9-CM and ICD-10-CM codes for the [specific substance/medica-
tion]-induced sleep disorders are indicated in the table below. Note that the ICD-10-CM
code depends on whether or not there is a comorbid substance use disorder present for
the same class of substance. If a mild substance use disorder is comorbid with the sub-
stance-induced sleep disorder, the 4th position character is “1,” and the clinician should