Other Specified Elimination Disorder 359
Prevalence
It is estimated that approximately 1% of 5-year-olds have encopresis, and the disorder is
more common in males than in females.
Development and Course
Encopresis is not diagnosed until a child has re ached a chronological ag e of at least 4 years
(or for children with developmental delays, a mental age of at least 4 years). Inadequate,
inconsistent toilet training and psychosocial st ress (e.g., entering school, the birth of a sib-
ling) may be predisposing factors. Two types of  course have been described: a “primary”
type, in which the individual has never established fecal continence, and a “secondary”
type, in which the disturbance develops after a period of established fecal continence. En-
copresis can persist, with interm ittent exacerbations, for years.
Risk and Prognostic Factors
Genetic and physiological. Painful defecation can lead to co nstipation and a cycle of with-
holding behaviors that make encopresis more likely. Use of some medications (e.g., anti-
convulsants, cough suppressants) may increase constipation and make encopresis more
likely.
Diagnostic Markers
In addition to physical examination, gastrointestinal imaging (e.g., abdominal radiograph)
may be informative to assess retained stool an d gas in the colon. Additional tests, such as
barium enema and anorectal ma nography, may be used to help exclude other medical
conditions, such as Hirschsprung’s disease.
Differential Diagnosis
A diagnosis of encopresis in the presence of  another medical condition is appropriate only
if the mechanism involves constipation that cannot be explained by other medical condi-


if the mechanism involves constipation that cannot be explained by other medical condi-
tions. Fecal incontinence related to other me dical conditions (e.g., chronic diarrhea, spina
bifida, anal stenosis) would not warrant a DSM-5 diagnosis of encopresis.
Comorbidity
Urinary tract infections can be comorbid with encopresis and are more common in females.
Other Specified Elimination Disorder

This category applies to presentations in which symptoms characteristic of an elimination
disorder that cause clinically significant distress or impairment in social, occupational, or
other important areas of functioning predominate but do not meet the full criteria for any of
the disorders in the elimination disorders di agnostic class. The other specified elimination
disorder category is used in situations in which the clinician chooses to communicate the
specific reason that the presentation does not meet the criteria for any specific elimination
disorder. This is done by recording “other s pecified elimination disorder” followed by the
specific reason (e.g., “low-frequency enuresis”).
Coding note:  Code 788.39 (N39.498)  for other specified elimi nation disorder with urinary
symptoms; 787.60 (R15.9)  for other specified elimination disorder with fecal symptoms.


360 Elimination Disorders
Unspecified Elimination Disorder

This category applies to presentations in which symptoms characteristic of an elimination
disorder that cause clinically significant distress or impairment in social, occupational, or
other important areas of functioning predominate but do not meet the full criteria for any of
the disorders in the elimination disorders di agnostic class. The unspecified elimination dis-
order category is used in situations in which the clinician chooses not  to specify the reason
that the criteria are not met for a specific elimination disorder, and includes presentations
in which there is insufficient information to make a more specific diagnosis (e.g., in emer-
gency room settings).
Coding note: Code 788.30 (R32) for unspecified elimination disorder with urinary symp-
toms; 787.60 (R15.9)  for unspecified elimination disorder with fecal symptoms.


361Sleep-Wake
 Disorders
The DSM-5 classification  of sleep-wake disorders is intended for use by general
mental health and medical clinicians (those caring for adult, geriatric, and pediatric pa-
tients). Sleep-wake disorders encompass 10 d isorders or disorder groups: insomnia disor-
der, hypersomnolence disorder, narcolepsy, br eathing-related sleep disorders, circadian
rhythm sleep-wake disorders,  non–rapid eye movement (NRE M) sleep arousal disorders,
nightmare disorder, rapid eye movement (REM) sleep behavior disorder, restless legs syn-
drome, and substance/medication-induced sleep disorder. Individuals with these disor-
ders typically present with sleep-wake complain ts of dissatisfaction regarding the quality,
timing, and amount of sleep. Resulting dayt ime distress and impairme nt are core features
shared by all of these sleep-wake disorders.
The organization of this chapter is designed to  facilitate differential diagnosis of sleep-
wake complaints and to clarify when referral to a sleep specialist is appropriate for further
assessment and treatment planning. The DSM-5 sleep disorders nosology uses a simple,
clinically useful approach, while also reflecti ng scientific advances  in epidemiology, ge-
netics, pathophysiology, assessment, and in terventions research since DSM-IV. In some
cases (e.g., insomnia disorder ), a “lumping” approach has been adopted, whereas in oth-
ers (e.g., narcolepsy), a “spli tting” approach has been taken, reflecting the availability of
validators derived from epidem iological, neurobiological, and interventions research.
Sleep disorders are often accompanied by de pression, anxiety, an d cognitive changes
that must be addressed in treatment planni ng and management. Fu rthermore, persistent


that must be addressed in treatment planni ng and management. Fu rthermore, persistent
sleep disturbances (both insomn ia and excessive sleepiness) ar e established risk factors for
the subsequent development of mental illne sses and substance use disorders. They may
also represent a prodromal expression of an episode of mental illness, allowing the possi-
bility of early intervention to preemp t or to attenuate a full-blown episode.
The differential diagnosis of sleep-wake co mplaints necessitates a multidimensional
approach, with consideration of  possibly coexisting medical and neurological conditions.
Coexisting clinical conditions are the rule, no t the exception. Sleep disturbances furnish a
clinically useful indicator of medical and ne urological conditions that often coexist with
depression and other common mental disord ers. Prominent among these comorbidities
are breathing-related sleep disorders, disord ers of the heart and lungs (e.g., congestive
heart failure, chronic obstructive pulmonary disease), neurodegenerative disorders (e.g.,
Alzheimer’s disease), and disorders of the musculoskeletal system (e.g., osteoarthritis).
These disorders not only may disturb sleep but also may th emselves be worsened during
sleep (e.g., prolonged apneas or electrocardi ographic arrhythmias during REM sleep; con-
fusional arousals in patients with dementing illness; seizures in persons with complex
partial seizures). REM sleep behavior disorder is often an early indicator of neurodegen-
erative disorders (alpha synucleinopathies) li ke Parkinson’s disease. For all of these rea-
sons—related to differential diagnosis, clinic al comorbidity, and fa cilitation of treatment
planning—sleep disorders are included in DSM-5.


planning—sleep disorders are included in DSM-5.
The approach taken to the clas sification of sleep-wake disorders in DSM-5 can be under-
stood within the context of “lumping versus splitting.” DSM-IV represented an effort to
simplify sleep-wake disorders cl assification and thus aggregated diagnoses under broader,
less differentiated labels. At the other pole, the International Classification of Sleep Disorders,


362 Sleep-Wake Disorders
2nd Edition (ICSD-2) elaborated numerous diagnostic subtypes. DSM-IV was prepared for
use by mental health and general medical clinicians who are not experts in sleep medicine.
ICSD-2 reflected the science and opinions of  the sleep specialist community and was pre-
pared for use by specialists.
The weight of available evidence supports the superior performance characteristics
(interrater reliability, as well as convergent, discriminant, and face validity) of simpler, less-
differentiated approaches to diagnosis of sleep-wake disord ers. The text accompanying
each set of diagnostic criteria provides linka ges to the corresponding disorders included in
ICSD-2. The DSM-5 sleep-wake disorders classif ication also specifies corresponding non-
psychiatric listings (e.g., ne urology codes) from the International Classification of Diseases
(ICD).
The field of sleep disorders medicine has progressed in this direction since the publi-
cation of DSM-IV. The use of biological validators is now embodied in the DSM-5 classi-
fication of sleep-wake disorder s, particularly for disorders of  excessive sleepiness, such as
narcolepsy; for breathing-rela ted sleep disorders, for whic h formal sleep studies (i.e.,
polysomnography) are indicated; and for rest less legs syndrome, which can often coexist
with periodic limb movements during sleep, detectable via polysomnography.
Insomnia Disorder
Diagnostic Criteria 307.42 (F51.01)
A. A predominant complaint of dissatisfaction with sleep quantity or quality, associated
with one (or more) of the following symptoms:
1. Difficulty initiating sleep. (In children, this may manifest as difficulty initiating sleep
without caregiver intervention.)
2. Difficulty maintaining sleep, characterized by frequent awakenings or problems re-


2. Difficulty maintaining sleep, characterized by frequent awakenings or problems re-
turning to sleep after awakenings. (In children, this may manifest as difficulty return-
ing to sleep without caregiver intervention.)
3. Early-morning awakening with inability to return to sleep.
B. The sleep disturbance causes clinically significant distress or impairment in social, oc-
cupational, educational, academic, behavioral, or other important areas of functioning.
C. The sleep difficulty occurs at least 3 nights per week.
D. The sleep difficulty is present for at least 3 months.
E. The sleep difficulty occurs despite adequate opportunity for sleep.
F. The insomnia is not better explained by and does not occur exclusively during the
course of another sleep-wake disorder (e.g., narcolepsy, a breathing-related sleep dis-
order, a circadian rhythm sleep-wake disorder, a parasomnia).
G. The insomnia is not attributable to the physiological effects of a substance (e.g., a drug
of abuse, a medication).
H. Coexisting mental disorders and medical conditions do not adequately explain the pre-
dominant complaint of insomnia.
Specify if:
With non–sleep disorder  mental comorbidity, including substance use disorders
With other medical comorbidity
With other sleep disorder
Coding note: The code 307.42 (F51.01) applies to all three specifiers. Code also the
relevant associated mental disorder, medica l condition, or other sleep disorder imme-
diately after the code for insomnia disorder in order to indicate the association.


Insomnia Disorder 363
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 within the space of 1 year.
Note:  Acute and short-term insomnia (i.e., symptoms lasting less than 3 months but oth-
erwise meeting all criteria with regard to frequency, intensity, distress, and/or impairment)
should be coded as an other specified insomnia disorder.
Note.  The diagnosis of insomnia disorder is given whether it occurs as an independent
condition or is comorbid with another mental disorder (e.g., major depressive disorder),
medical condition (e.g., pain), or another sleep disorder (e.g., a breathing-related sleep dis-
order). For instance, insomnia may develop it s own course with some anxiety and depres-
sive features but in the absenc e of criteria being met for an y one mental disorder. Insomnia
may also manifest as a clinical feature of a more predominant ment al disorder . Persistent
insomnia may even be a risk factor for depression and is a common residual symptom af-
ter treatment for this condition. With comorb id insomnia and a mental disorder, treatment
may also need to target both conditions. Give n these different courses, it is often impossi-
ble to establish the precise nature of the rela tionship between these clinical entities, and
this relationship may change over time. Therefore, in th e presence of insomnia and a co-
morbid disorder, it is not ne cessary to make a causal attribution between the two condi-
tions. Rather, the diagnosis of insomnia disord er is made with concurrent specification of
the clinically comorbid conditions. A concurre nt insomnia diagnosis should only be con-


the clinically comorbid conditions. A concurre nt insomnia diagnosis should only be con-
sidered when the insomnia is sufficiently severe  to warrant independent clinical attention;
otherwise, no separate diagnosis is necessary.
Diagnostic Features
The essential feature of insomnia disorder is dissatisfaction with sleep quantity or quality
with complaints of difficulty initiating or maintaining sleep. The sleep complaints are ac-
companied by clinically significant distress or  impairment in social, occupational, or other
important areas of functioning. The sleep dist urbance may occur during the course of an-
other mental disorder or medical condition, or it  may occur independently.
Different manifestations of insomnia can oc cur at different times of the sleep period. Sleep-
onset insomnia  (or initial insomnia ) involves difficulty initia ting sleep at bedtime. Sleep mainte-
nance insomnia  (or middle insomnia ) involves frequent or prol onged awakenings throughout
the night. Late insomnia involves early-morning awakening with an inability to return to sleep.
Difficulty maintaining sleep is the most co mmon single symptom of insomnia, followed by
difficulty falling asleep, while a combination of  these symptoms is th e most common presen-
tation overall. The specific type of sleep comp laint often varies over time. Individuals who
complain of difficulty falling asleep at one time may later complain of difficulty maintaining
sleep, and vice versa. Symptoms of difficulty falling asleep and difficulty maintaining sleep
can be quantified by the individual’s retrospect ive self-report, sleep di aries, or other methods,
such as actigraphy or polysomnography, but th e diagnosis of insomnia disorder is based on
the individual’s subjecti ve perception of sleep or a caretaker’s report.
Nonrestorative sleep,  a complaint of poor sleep quality that does not leave the individual
rested upon awakening despite adequate du ration, is a common sleep complaint usually


rested upon awakening despite adequate du ration, is a common sleep complaint usually
occurring in association with difficulty initiating or maintaining sleep, or less frequently in
isolation. This complaint can also be reported in association with other sleep disorders
(e.g., breathing-related sleep disorder). When  a complaint of nonres torative sleep occurs
in isolation (i.e., in the absence of difficulty initiating and/or maintaining sleep) but all di-


(e.g., breathing-related sleep disorder). When  a complaint of nonres torative sleep occurs
in isolation (i.e., in the absence of difficulty initiating and/or maintaining sleep) but all di-
agnostic criteria with regard to frequency, duration, and daytime distress and impairments
are otherwise met, a diagnosis of other specif ied insomnia disorder or unspecified insom-
nia disorder is made.


364 Sleep-Wake Disorders
Aside from the frequency and du ration criteria required to make the diagnosis, addi-
tional criteria are useful to quantify insomnia severity. These quantitative criteria, while
arbitrary, are provided for illustrative purpose only. For instance, difficulty initiating sleep
is defined by a subjective sleep latency greater than 20–30 minutes, and difficulty maintain-
ing sleep is defined by a subjective time awake after sleep onset greater than 20–30 min-
utes. Although there is no standard definition  of early-morning awakening, this symptom
involves awakening at least 30 minutes before the scheduled time and before total sleep
time reaches 6½ hours. It is essential to take into account no t only the final awakening time
but also the bedtime on the previ ous evening. Awakening at 4:00 A.M. does not have the
same clinical significance in those who go to bed at 9:00 P.M. as in those who go to bed at
11:00 P.M. Such a symptom may also reflect an age- dependent decrease in the ability to sus-
tain sleep or an age-dependent shift in the timing of the main sleep period.
Insomnia disorder involves daytime impairments as well as nighttime sleep difficulties.
These include fatigue or, less commonly, dayt ime sleepiness; the latter is more common
among older individuals and wh en insomnia is comorbid with another medical condition
(e.g., chronic pain) or sleep disorder (e.g., sl eep apnea). Impairment in  cognitive performance
may include difficulties with attention, concentration and memory, and even with performing
simple manual skills. Associated mood disturba nces are typically described as irritability or
mood lability and less commonly as depressive or anxiety symptoms. Not all individuals with
nighttime sleep disturbances are distressed or have functional impairment. For example, sleep


nighttime sleep disturbances are distressed or have functional impairment. For example, sleep
continuity is often interrupted in healthy olde r adults who nevertheless identify themselves
as good sleepers. A diagnosis of insomnia disorder should be reserved for those individuals
with significant daytime distress or impairment related to their nighttime sleep difficulties.
Associated Features Supporting Diagnosis
Insomnia is often associated  with physiological and cognitive arousal and conditioning
factors that interfere with sleep. A preoccupati on with sleep and distress due to the inabil-
ity to sleep may lead to a vicious cycle: the more the individual strives to sleep, the more
frustration builds and further im pairs sleep. Thus, excessive attention and efforts to sleep,
which override normal sleep-onset mechanisms, may contribute to the development of in-
somnia. Individuals with  persistent insomnia may also acquire maladapt ive sleep habits
(e.g., spending excessive time in bed; following an erratic sleep schedule; napping) and
cognitions (e.g., fear of sleeplessness; apprehensions of daytime impairments; clock mon-
itoring) during the course of the disorder. Engaging in such activities in an environment in
which the individual has frequently spent sleepless nights may further compound the con-
ditioned arousal and perpetuate sleep difficulties. Conversely, the individual may fall asleep
more easily when not trying to do so. Some individuals also report better sleep when away
from their own bedrooms and their usual routines.
Insomnia may be accompanied by a variety of daytime complaints and symptoms, in-
cluding fatigue, decreased en ergy, and mood disturbances. Symptoms of anxiety or de-
pression that do not meet criteria for a specif ic mental disorder may be present, as well as
an excessive focus on the perceived effect s of sleep loss on daytime functioning.
Individuals with inso mnia may have elevated scores on self-report psychological or


Individuals with inso mnia may have elevated scores on self-report psychological or
personality inventories with profiles indicati ng mild depression and anxiety, a worrisome
cognitive style, an emotion-focused and intern alizing style of conflict resolution, and a so-


personality inventories with profiles indicati ng mild depression and anxiety, a worrisome
cognitive style, an emotion-focused and intern alizing style of conflict resolution, and a so-
matic focus. Patterns of neurocognitive impairment among individuals with insomnia dis-
order are inconsistent, although  there may be impairments in performing tasks of higher
complexity and those requiring frequent ch anges in performance strategy. Individuals
with insomnia often require more effo rt to maintain cognitive performance.
Prevalence
Population-based estimates indicate that about one-third of adults report insomnia symp-
toms, 10%–15% experience associated daytime impairments, and 6%–10% have symptoms


Insomnia Disorder 365
that meet criteria for insomnia  disorder. Insomnia disorder is the most prevalent of all
sleep disorders. In primary care settings, approximately 10%–20% of individuals complain
of significant insomnia symp toms. Insomnia is a more prevalent complaint among fe-
males than among males, with a gender ratio of about 1.44:1. Although insomnia can be a
symptom or an independent disorder, it is mo st frequently observed as a comorbid con-
dition with another medical condition or ment al disorder. For instance, 40%–50% of indi-
viduals with insomnia also present with a comorbid mental disorder.
Development and Course
The onset of insomnia symptoms  can occur at any time during life, but the first episode is
more common in young adulthood. Less frequently, insomnia begins in childhood or ad-
olescence. In women, new-onset insomnia may occur during menopause and persist even
after other symptoms (e.g., hot flashes) have resolved. Insomnia may have a late-life onset,
which is often associated with the onse t of other health-related conditions.
Insomnia can be situational, persistent, or recurrent. Situational or  acute insomnia usu-
ally lasts a few days or a few weeks and is often associated with life events or rapid changes
in sleep schedules or environment. It usually resolves once the initial precipitating event
subsides. For some individuals, perhaps those more vulnerable to sl eep disturbances, in-
somnia may persist long after the initial trigge ring event, possibly because of conditioning
factors and heightened arousal. The factors that precipitate insomnia may differ from
those that perpetuate it. For example, an in dividual who is bedridden with a painful injury
and has difficulty sleeping may then develop negative associations for sleep. Conditioned


and has difficulty sleeping may then develop negative associations for sleep. Conditioned
arousal may then persist and lead to persiste nt insomnia. A similar course may develop in
the context of an acute psychological stress or a mental disorder. For instance, insomnia that
occurs during an episode of major depressive disorder can become a focus of attention,
with consequent negative conditioning, and pe rsist even after resolution of the depressive
episode. In some cases, insomnia may also have an insidious onse t without any identifi-
able precipitating factor.
The course of insomnia may also be episodic,  with recurrent episodes of sleep difficul-
ties associated with the occurrence of stress ful events. Chronicity rates range from 45%
to 75% for follow-ups of 1–7 years. Even wh en the course of the insomnia has become
chronic, there is night-to -night variability in sleep patterns, with an occasional restful night’s
sleep interspersed with several nights of poor sleep. The characteristics of insomnia may
also change over time. Many individuals with insomnia have a history of “light” or easily
disturbed sleep prior to onset of more persistent sleep problems.
Insomnia complaints are mo re prevalent among middle-age and older adults. The type
of insomnia symptom changes as a function of age, with difficulties initiating sleep being
more common among young adults and proble ms maintaining sleep occurring more fre-
quently among middle-age and older individuals.
Difficulties initiating and maintaining sleep can also occur in children and adolescents,
but there are more limited data on prevalence, risk factors, and comorbidity during these
developmental phases of the lifespan. Sleep diff iculties in childhood can result from con-
ditioning factors (e.g., a child who does not lear n to fall asleep or return to sleep without


the presence of a parent) or from the absence of consistent sleep schedules and bedtime
routines. Insomnia in adolescenc e is often triggered or exacer bated by irregular sleep sched-
ules (e.g., phase delay). In both children an d adolescents, psycholo gical and medical fac-
tors can contribute to insomnia.
The increased prevalence of insomnia in olde r adults is partly explained by the higher


tors can contribute to insomnia.
The increased prevalence of insomnia in olde r adults is partly explained by the higher
incidence of physical health problems with aging. Changes in sleep patterns associated with
the normal developmental process must be diff erentiated from those exceeding age-related
changes. Although polysomnography is of limit ed value in the routine evaluation of in-
somnia, it may be more useful in the differen tial diagnosis among older adults because the
etiologies of insomnia (e.g., sleep apnea) are more often identifiable in older individuals.


366 Sleep-Wake Disorders
Risk and Prognostic Factors
While the risk and prognostic factors discussed in this section increase vulnerability to in-
somnia, sleep disturbances are more likely to  occur when predisposed individuals are ex-
posed to precipitating events, such as major lif e events (e.g., illness, separation) or less
severe but more chronic daily stress. Most individuals resume normal sleep patterns after
the initial triggering event ha s disappeared, but others—perha ps those more vulnerable to
insomnia—continue experiencing persistent sleep difficulties. Perpetuating factors such as
poor sleep habits, irregular sleep scheduling, an d the fear of not sleeping feed into the in-
somnia problem and may contribute to a vicious  cycle that may induce persistent insomnia.
Temperamental. Anxiety or worry-prone personality or cognitive styles, increased arousal
predisposition, and tendency to repress emot ions can increase vulne rability to insomnia.
Environmental. Noise, light, uncomfortably high or low temperature, and high altitude
may also increase vulnerability to insomnia.
Genetic and physiological. Female gender and advancing age are associated with in-
creased vulnerability to insomn ia. Disrupted sleep and insomnia display a familial dispo-
sition. The prevalence of insomnia is hi gher among monozygoti c twins relative to
dizygotic twins; it is also higher in first-degree family members comp ared with the general
population. The extent to which this link is  inherited through a genetic predisposition,
learned by observations of pare ntal models, or established as  a by-product of another psy-
chopathology remains undetermined.
Course modifiers. Deleterious course modifiers incl ude poor sleep hygiene practices
(e.g., excessive caffeine use,  irregular sleep schedules).
Gender-Related Diagnostic Issues


(e.g., excessive caffeine use,  irregular sleep schedules).
Gender-Related Diagnostic Issues
Insomnia is a more prevalent complaint among females than among males, with first onset
often associated with the birth of a new child or with menopause. Despite higher preva-
lence among older females, polysomnographic studies su ggest better preservation of
sleep continuity and slow-wave sleep in  older females than in older males.
Diagnostic Markers
Polysomnography usually shows impairments of sleep continuity (e.g., increased sleep la-
tency and time awake after sleep onset and de creased sleep efficiency [percentage of time
in bed asleep] and may show increased stage 1 sleep and decreased stages 3 and 4 sleep.
The severity of these sleep im pairments does not always ma tch the individual’s clinical
presentation or subjective complaint of poor sleep, as individuals with insomnia often un-
derestimate sleep duration and overestimate wakefulness relative to polysomnography.
Quantitative electroencephalographic analyses  may indicate that individuals with insom-
nia have greater high-frequency electroencepha lography power relative to good sleepers
both around the sleep onset period and duri ng non–rapid eye movement sleep, a feature
suggestive of increased cortical arousal. Individual s with insomnia disorder may have a
lower sleep propensity and typically do not show increased daytime sleepiness on objec-
tive sleep laboratory measures compared wi th individuals without sleep disorders.
Other laboratory measures show evidence, although not consistently, of increased
arousal and a generalized activation of the hypothalamic-pituitary-adrenal axis (e.g., in-
creased cortisol levels, heart rate  variability, reactivity to stre ss, metabolic rate). In general,
findings are consistent with the hypothesis that increased physiological and cognitive
arousal plays a significant role in insomnia disorder.


arousal plays a significant role in insomnia disorder.
Individuals with insomnia di sorder may appear either fatigued or haggard or, con-
versely, overaroused and “wired.” However, there are no consistent or characteristic
abnormalities on physical examination. Ther e may be an increased incidence of stress-


Insomnia Disorder 367
related psychophysiological symptoms (e.g., tension headache, muscle tension or pain,
gastrointestinal symptoms).
Functional Consequences  of Insomnia Disorder
Interpersonal, social, and occupational problems may develop as a result of insomnia or
excessive concern with sleep, increased daytim e irritability, and poor concentration. De-
creased attention and concentrat ion are common and may be related to higher rates of ac-
cidents observed in insomnia. Persistent in somnia is also associated with long-term
consequences, including increased risks of ma jor depressive disorder, hypertension, and
myocardial infarction; increased absenteeism and reduced productivity at work; reduced
quality of life; and increased economic burden.
Differential Diagnosis
Normal sleep variations. Normal sleep duration varies considerably across individuals.
Some individuals who require little sleep (“short sleepers”) may be concerned about their
sleep duration. Short sl eepers differ from individuals with insomnia disorder by the lack of
difficulty falling or staying asleep and by the absence of characteristic daytime symptoms
(e.g., fatigue, concentration pr oblems, irritability). However,  some short sleepers may desire
or attempt to sleep for a longer period of time and, by prolonging time in bed, may create an
insomnia-like sleep pattern. Clinical insomnia  also should be distinguished from normal,
age-related sleep changes. Insomnia must also be distinguished from sleep deprivation due
to inadequate opportunity or circumstance for sleep resulting, for example, from an emer-
gency or from professional or  family obligations forcing th e individual to stay awake.
Situational/acute insomnia. Situational/acute insomnia  is a condition lasting a few days
to a few weeks, often associated with life events  or with changes in sleep schedules. These
acute or short-term insomnia symptoms may also produce si gnificant distress and inter-


acute or short-term insomnia symptoms may also produce si gnificant distress and inter-
fere with social, personal, and occupational functioning. When such symptoms are fre-
quent enough and meet all other criteria exce pt for the 3-month duration, a diagnosis of
other specified insomnia disorder or unspecified insomnia disorder is made.
Delayed sleep phase and shift work types of circadian rhythm sleep-wake disorder.
Individuals with the delayed sleep phase type of circadian rhythm sl eep-wake disorder re-
port sleep-onset insomnia only when they try to  sleep at socially normal times, but they do
not report difficulty falling asleep or stayin g asleep when their bed and rising times are
delayed and coincide with thei r endogenous circadian rhythm. Shift work type differs from
insomnia disorder by the history of recent shift work.
Restless legs syndrome. Restless legs syndrome often produces difficulties initiating
and maintaining sleep. However, an urge to move the legs and any accompanying unpleas-
ant leg sensations are features that differentiate this disorder fr om insomnia disorder.
Breathing-related sleep disorders. Most individuals with a breathing-related sleep dis-
order have a history of loud snoring, breath ing pauses during sleep, and excessive daytime
sleepiness. Nonetheless, as many as 50% of individuals with sleep apnea may also report
insomnia symptoms, a feature that is more  common among females and older adults.
Narcolepsy. Narcolepsy may cause insomnia complaints but is distinguished from in-
somnia disorder by the predominance of sy mptoms of excessive daytime sleepiness, cat-
aplexy, sleep paralysis, and sleep-related hallucinations.
Parasomnias. Parasomnias are characterized by a comp laint of unusual behavior or events
during sleep that may lead to intermittent  awakenings and difficulty resuming sleep.


during sleep that may lead to intermittent  awakenings and difficulty resuming sleep.
However, it is these behavioral events, rather than the insomnia per se, that dominate the
clinical picture.


368 Sleep-Wake Disorders
Substance/medication-induced sl eep disorder, insomnia type. Substance/medication-
induced sleep disorder, insomnia type, is distinguished from insomnia disorder by the fact
that a substance (i.e., a drug of abuse, a medica tion, or exposure to a toxin) is judged to be
etiologically related to the insomnia (see  “Substance/Medicatio n-Induced Sleep Disor-
der” later in this chapter). Fo r example, insomnia occurring only in the context of heavy
coffee consumption would be diagnosed as caffeine-induced sleep disorder, insomnia
type, with onset during intoxication.
Comorbidity
Insomnia is a common comorbidity of many medical conditions, including diabetes, cor-
onary heart disease, chronic obstructive pulm onary disease, arthritis, fibromyalgia, and
other chronic pain conditions. The risk relati onship appears to be bidirectional: insomnia
increases the risk of medical conditions, and medical problems increase the risk of insom-
nia. The direction of the relationship is not always clear and may change over time; for this
reason, comorbid insomnia is the preferred terminology in th e presence of coexisting in-
somnia with another medical co ndition (or mental disorder).
Individuals with insomnia disorder frequent ly have a comorbid mental disorder, par-
ticularly bipolar, depressive, and anxiety diso rders. Persistent insomnia represents a risk
factor or an early symptom of subsequent bi polar, depressive, anxi ety, and substance use
disorders. Individuals with insomnia may misuse medicati ons or alcohol to help with
nighttime sleep, anxiolytics to combat tension or anxiety, and caffeine or other stimulants
to combat excessive fatigue. In addition to worsening the insomnia, this type of substance


to combat excessive fatigue. In addition to worsening the insomnia, this type of substance
use may in some cases progress to a substance use disorder.
Relationship to Internat ional Classification of
Sleep Disorders
There are several distinct inso mnia phenotypes relating to the perceived source of the in-
somnia that are recognized by the International Classifica tion of Sleep Disorders,  2nd Edition
(ICSD-2). These include psychophysiological insomnia,  idiopathic insomnia,  sleep-state mispercep-
tion, and inadequate sleep hygiene.  Despite their clinical appeal and heuristic value, there is
limited evidence to support these distinct phenotypes.
Hypersomnolence Disorder
Diagnostic Criteria 307.44 (F51.11)
A. Self-reported excessive sleepiness (hypersomnolence) despite a main sleep period
lasting at least 7 hours, with at least one of the following symptoms:
1. Recurrent periods of sleep or lapses into sleep within the same day.
2. A prolonged main sleep episode of more than 9 hours per day that is nonrestorative
(i.e., unrefreshing).
3. Difficulty being fully awake after abrupt awakening.
B. The hypersomnolence occurs at least three times per week, for at least 3 months.
C. The hypersomnolence is accompanied by si gnificant distress or impairment in cogni-
tive, social, occupational, or other important areas of functioning.
D. The hypersomnolence is not better explai ned by and does not occur exclusively during
the course of another sleep disorder (e.g., narcolepsy, breathing-related sleep disor-
der, circadian rhythm sleep-wake disorder, or a parasomnia).
E. The hypersomnolence is not attributable to the physiological effects of a substance


E. The hypersomnolence is not attributable to the physiological effects of a substance
(e.g., a drug of abuse, a medication).


Hypersomnolence Disorder 369
F. Coexisting mental and medical disorders do not adequately explain the predominant
complaint of hypersomnolence.
Specify if:
With mental disorder , including substance use disorders
With medical condition
With another sleep disorder
Coding note: The code 307.44 (F51.11) applies to all three specifiers. Code also the
relevant associated mental disorder, medi cal condition, or other sleep disorder im-
mediately after the code for hypersomnolence disorder in order to indicate the associ-
ation.
Specify if:
Acute:  Duration of less than 1 month.
Subacute:  Duration of 1–3 months.
Persistent:  Duration of more than 3 months.
Specify current severity:
Specify severity based on degree of difficulty maintaining daytime alertness as manifested
by the occurrence of multiple attacks of irresistible sleepiness within any given day occur-
ring, for example, while sedentary, driving, visiting with friends, or working.
Mild:  Difficulty maintaining daytime alertness 1–2 days/week.
Moderate: Difficulty maintaining daytime alertness 3–4 days/week.
Severe:  Difficulty maintaining daytime alertness 5–7 days/week.
Diagnostic Features
Hypersomnolence  is a broad diagnostic term and incl udes symptoms of excessive quantity
of sleep (e.g., extended nocturnal sleep or involuntary daytime sleep),  deteriorated quality
of wakefulness (i.e., sleep propensity duri ng wakefulness as shown by difficulty awaken-
ing or inability to remain awake when required ), and sleep inertia (i.e., a period of im-
paired performance and reduced vigilance following awakening from the regular sleep
episode or from a nap) (Criterion A). Indivi duals with this disorder fall asleep quickly and


have a good sleep efficiency (>90%). They may have difficulty waking up in the morning,
sometimes appearing confused, co mbative, or ataxic. This pr olonged impairment of alert-
ness at the sleep-wake transition  is often referred to as sleep inertia  (i.e., sleep drunkenness).
It can also occur upon awaken ing from a daytime nap. During that period, the individual
appears awake, but there is a decline in moto r dexterity, behavior may be very inappro-
priate, and memory deficits, di sorientation in time and spac e, and feelings of grogginess
may occur. This period may last some minutes to hours.
The persistent need for sleep can lead to auto matic behavior (usually of a very routine,
low-complexity type) that the individual carrie s out with little or no subsequent recall. For
example, individuals may find themselves having driven several miles from where they
thought they were, unaware of the “automatic”  driving they did in the preceding minutes.
For some individuals with hypersomnolence disorder, the major sleep episode (for most
individuals, nocturnal sleep) has a duration of 9 hours or more. However, the sleep is often
nonrestorative and is followed by difficulty awakening in the morning. For other individ-
uals with hypersomnolence disorder, the majo r sleep episode is of normal nocturnal sleep
duration (6–9 hours). In these cases, the excessive sleepiness is characterized by several un-
intentional daytime naps. These daytime naps tend to be relatively long (often lasting 1 hour
or more), are experienced as no nrestorative (i.e., unrefreshing),  and do not lead to improved
alertness. Individuals with hypersomnolence have daytime naps near ly everyday regard-


alertness. Individuals with hypersomnolence have daytime naps near ly everyday regard-
less of the nocturnal sleep duration. Subjective  sleep quality may or may not be reported as
good. Individuals typically feel sleepiness developing over a period of time, rather than


370 Sleep-Wake Disorders
experiencing a sudden sleep “attack.” Unintent ional sleep episodes typically occur in low-
stimulation and low-activity situations (e.g ., while attending lectures, reading, watching
television, or driving long dist ances), but in more severe cases they can manifest in high-
attention situations such as at work, in meetings, or at social gatherings.
Associated Features Supporting Diagnosis
Nonrestorative sleep, automatic behavior, di fficulties awakening in the morning, and
sleep inertia, although common in hypersomnolence disorder, may also be seen in a variety
of conditions, including narcolepsy. Appr oximately 80% of indi viduals with hyper-
somnolence report that their sleep is nonres torative, and as many have difficulties awak-
ening in the morning. Sleep inertia, thou gh less common (i.e., observed in 36%–50% of
individuals with hypersomnolence disorder), is highly specific to hypersomnolence. Short
naps (i.e., duration of less than 30 minutes)  are often unrefreshing. Individuals with hy-
persomnolence often appear sleepy and may even  fall asleep in the clinician’s waiting
area.
A subset of individuals with hypersomnolenc e disorder have a family history of hy-
persomnolence and also have symptoms of autonomic nervous system dysfunction, in-
cluding recurrent vascular-type headaches, reactivity of the peripheral vascular system
(Raynaud’s phenomenon), and fainting.
Prevalence
Approximately 5%–10% of individuals who cons ult in sleep disorders clinics with com-
plaints of daytime sleepiness are diagnosed as having hypersomnolence disorder. It is es-


timated that about 1% of the European and U.S. general population has episodes of sleep
inertia. Hypersomnolence occurs with relati vely equal frequency in males and females.
Development and Course
Hypersomnolence disorder has a persistent course, with a prog ressive evolution in the se-
verity of symptoms. In most extreme cases, sl eep episodes can last up to 20 hours. How-
ever, the average nighttime sleep duration is  around 9½ hours. While many individuals
with hypersomnolence are able to reduce their sleep time during working days, weekend
and holiday sleep is greatly increased (by up to 3 hours). Awakenings are very difficult
and accompanied by sleep inertia episodes in nearly 40% of cases. Hypersomnolence fully
manifests in most cases in late adolescence or early adulthood, with a mean age at onset of
17–24 years. Individuals with hypersomnolence disorder are diagnosed, on average, 10–15
years after the appearance of the firs t symptoms. Pediatric cases are rare.
Hypersomnolence has a progressive onset, wi th symptoms beginning between ages 15
and 25 years, with a gradual progression over weeks to months. For most individuals, the
course is then persistent and stable, unless tr eatment is initiated. The development of other
sleep disorders (e.g., breathing-related sleep disorder) may worsen the degree of sleepi-
ness. Although hyperactivity may be one of th e presenting signs of daytime sleepiness in
children, voluntary napping increases with ag e. This normal phenomenon is distinct from
hypersomnolence.
Risk and Prognostic Factors
Environmental. Hypersomnolence can be increased te mporarily by psychological stress


Environmental. Hypersomnolence can be increased te mporarily by psychological stress
and alcohol use, but they have not been documented as environmental precipitating
factors. Viral infections have been report ed to have preceded or accompanied hyper-
somnolence in about 10% of cases. Viral infections, such as HIV pneumonia, infectious
mononucleosis, and Guillain-Barré syndrome, can also evolve into hypersomnolence within


Hypersomnolence Disorder 371
months after the infection. Hypersomnolenc e can also appear within 6–18 months follow-
ing a head trauma.
Genetic and physiological. Hypersomnolence may be fami lial, with an autosomal-
dominant mode of  inheritance.
Diagnostic Markers
Nocturnal polysomnography demonstrates a no rmal to prolonged sleep duration, short
sleep latency, and normal to increased slee p continuity. The distribution of rapid eye
movement (REM) sleep is also normal. Sleep e fficiency is mostly greater than 90%. Some
individuals with hypersomnolence disorder have increased amounts of slow-wave sleep.
The multiple sleep latency te st documents sleep tendency, typically indicated by mean
sleep latency values of less than 8 minutes.  In hypersomnolence disorder, the mean sleep
latency is typically less than 10 minutes and fr equently 8 minutes or less. Sleep-onset REM
periods (SOREMPs; i.e., the occurrence of REM sleep within 20 minutes of sleep onset)
may be present but occur less than two time s in four to five nap opportunities.
Functional Consequences of Hypersomnolence Disorder
The low level of alertness that occurs while an individual fights the need for sleep can lead
to reduced efficiency, diminished concentration, and poor memory during daytime activ-
ities. Hypersomnolence can lead to significan t distress and dysfunction in work and social
relationships. Prolonged nocturnal sleep and difficulty awakening can result in difficulty
in meeting morning obligations, such as arrivi ng at work on time. Unintentional daytime
sleep episodes can be embarrassing and even dangerous, if, for instance, the individual is
driving or operating machinery when the episode occurs.
Differential Diagnosis


driving or operating machinery when the episode occurs.
Differential Diagnosis
Normative variation in sleep. “Normal” sleep duration varies considerably in the general
population. “Long sleepers” (i.e., individuals who require a greater than average amount
of sleep) do not have excessive sleepiness, sleep  inertia, or automatic behavior when they
obtain their required amount of nocturnal sleep . Sleep is reported to be refreshing. If social
or occupational demands lead to shorter nocturnal sleep, daytime symptoms may appear.
In hypersomnolence disorder, by contrast, symp toms of excessive sleepiness occur regard-
less of nocturnal sleep duration. An inad equate amount of no cturnal sleep, or behaviorally
induced insufficient sleep syndrome,  can produce symptoms of daytime sleepiness very similar
to those of hypersomnolence. An average slee p duration of fewer than 7 hours per night
strongly suggests inadequate nocturnal sleep , and an average of more than 9–10 hours of
sleep per 24-hour period suggests hypersomnole nce. Individuals with inadequate noctur-
nal sleep typically “catch up” with longer sleep durations on days when they are free from
social or occupational demands or on vaca tions. Unlike hypersom nolence, insufficient
nocturnal sleep is unlikely to persist unabat ed for decades. A diagnosis of hypersomno-
lence disorder should not be made if there is  a question regarding the adequacy of noctur-
nal sleep duration. A diagnostic and therapeutic trial of sleep extension for 10–14 days can
often clarify the diagnosis.
Poor sleep quality and fatigue. Hypersomnolence disorder should be distinguished
from excessive sleepiness related to insufficient  sleep quantity or quality and fatigue (i.e.,
tiredness not necessarily relieved by increase d sleep and unrelated to sleep quantity or


tiredness not necessarily relieved by increase d sleep and unrelated to sleep quantity or
quality). Excessive sleepiness and fatigue ar e difficult to differentiate and may overlap
considerably.
Breathing-related sleep disorders. Individuals with hypersomnolence and breathing-
related sleep disorders may have similar patterns of excessive sleepiness. Breathing-


372 Sleep-Wake Disorders
related sleep disorders are suggested by a hist ory of loud snoring, pauses in breathing
during sleep, brain injury, or cardiovascular disease and by the presence of obesity, oro-
pharyngeal anatomical abnormalities, hyperten sion, or heart failure on physical examina-
tion. Polysomnographic studies can confirm the presence of apneic events in breathing-
related sleep disorder (and their ab sence in hypersomnolence disorder).
Circadian rhythm sleep-wake disorders. Circadian rhythm sleep-wake disorders are
often characterized by daytime sleepiness. A  history of an abnormal sleep-wake schedule
(with shifted or irregular hours) is present in individuals with a circadian rhythm sleep-
wake disorder.
Parasomnias. Parasomnias rarely produce the prol onged, undisturbed nocturnal sleep
or daytime sleepiness characterist ic of hypersomnolence disorder.
Other mental disorders. Hypersomnolence disorder must be distinguished from mental
disorders that include hypersomnolence as an essential or associated fe ature. In particular,
complaints of daytime sleepiness may occur in a major depressive  episode, with atypical fea-
tures, and in the depressed phase of bipolar di sorder. Assessment for ot her mental disorders is
essential before a diagnosis of hypersomnolence disorder is co nsidered. A diagnosis of hyper-
somnolence disorder can be made in the presence  of another current or past mental disorder.
Comorbidity
Hypersomnolence can be associated with depressive disorders, bipolar disorders (during a
depressive episode), and major depressive disorder, with seas onal pattern. Many individu-
als with hypersomnolence disorder have symptoms  of depression that may meet criteria for


als with hypersomnolence disorder have symptoms  of depression that may meet criteria for
a depressive disorder. This presentation may be  related to the psycho social consequences of
persistent increased sleep need. Individuals with hypersomnolence disorder are also at
risk for substance-related disord ers, particularly related to self-medication with stimulants.
This general lack of specificity may contribu te to very heterogeneous profiles among indi-
viduals whose symptoms meet the same diagnostic criteria for hypersomnolence disorder.
Neurodegenerative conditions, such as Alzhei mer’s disease, Parkinson’s disease, and mul-
tiple system atrophy, may also be associated with hypersomnolence.
Relationship to Internat ional Classification of
Sleep Disorders
The International Classification of Sleep Disorders,  2nd Edition (ICSD-2), differentiates nine
subtypes of “hypersomnias of central origin ,” including recurrent  hypersomnia (Kleine-
Levin syndrome).
Narcolepsy
Diagnostic Criteria
A. Recurrent periods of an irrepressible need to sleep, lapsing into sleep, or napping oc-
curring within the same day. These must have been occurring at least three times per
week over the past 3 months.
B. The presence of at least one of the following:
1. Episodes of cataplexy, defined as either (a) or (b), occurring at least a few times
per month:
a. In individuals with long-standing disease, brief (seconds to minutes) episodes
of sudden bilateral loss of muscle tone with maintained consciousness that are
precipitated by laughter or joking.


Narcolepsy 373
b. In children or in individuals within 6 months of onset, spontaneous grimaces or
jaw-opening episodes with tongue thrusting or a global hypotonia, without any
obvious emotional triggers.
2. Hypocretin deficiency, as measured usi ng cerebrospinal fluid (CSF) hypocretin-1
immunoreactivity values (less than or equal to one-third of values obtained in
healthy subjects tested using the same assay, or less than or equal to 110 pg/mL).
Low CSF levels of hypocretin-1 must not be observed in the context of acute brain
injury, inflammation, or infection.
3. Nocturnal sleep polysomnography showing rapid eye movement (REM) sleep la-
tency less than or equal to 15 minutes, or a multiple sleep latency test showing a
mean sleep latency less than or equal to 8 minutes and two or more sleep-onset
REM periods.
Specify whether:
347.00 (G47.419) Na rcolepsy without cataplexy but  with hypocretin deficiency:  Cri-
terion B requirements of low CSF hypocretin-1 levels and positive polysomnography/
multiple sleep latency test are met, but no cataplexy is present (Criterion B1 not met).
347.01 (G47.411) Narcolepsy with cataplexy but without hypocretin deficiency:
In this rare subtype (less than 5% of narcolepsy cases), Criterion B requirements of
cataplexy and positive polysomnography/multiple sleep latency test are met, but CSF
hypocretin-1 levels are normal (Criterion B2 not met).
347.00 (G47.419) Autosomal dominant cereb ellar ataxia, deafness, and narco-


lepsy:  This subtype is caused by exon 21 DNA (cytosine-5)-methyltransferase-1 mu-
tations and is characterized by late-onset (age 30–40 years) narcolepsy (with low or
intermediate CSF hypocretin-1 levels), deafness, cerebellar ataxia, and eventually de-
mentia.
347.00 (G47.419) Autosomal dominant narcolepsy, obesity, and type 2 diabetes:
Narcolepsy, obesity, and type 2 diabetes and low CSF hypocretin-1 levels have been
described in rare cases and are associated with a mutation in the myelin oligodendro-
cyte glycoprotein gene.
347.10 (G47.429) Narcolepsy secondary to a nother medical condition:  This sub-
type is for narcolepsy that develops secondary to medical conditions that cause infec-
tious (e.g., Whipple’s disease, sarcoidosis), traumatic, or tumoral destruction of
hypocretin neurons.
Coding note  (for ICD-9-CM code 347.10 only): Code first the underlying medical con-
dition (e.g., 040.2 Whipple’s disease; 347.10 narcolepsy secondary to Whipple’s dis-
ease).
Specify current severity:
Mild:  Infrequent cataplexy (less than once per week), need for naps only once or twice
per day, and less disturbed nocturnal sleep.
Moderate: Cataplexy once daily or every few days, disturbed nocturnal sleep, and
need for multiple naps daily.
Severe:  Drug-resistant cataplexy with multiple attacks daily, nearly constant sleepi-


ness, and disturbed nocturnal sleep (i.e., movements, insomnia, and vivid dreaming).
Subtypes
In narcolepsy without cataplexy but with hypocretin deficiency, unclear “cataplexy-like”
symptoms may be reported (e.g., the symptoms are not triggered by emotions and are un-
usually long lasting). In extremely rare cases,  cerebrospinal fluid (CSF) levels of hypocre-
tin-1 are low, and polysomnographic/multiple sleep latency test (MSLT) results are
negative: repeating the test is advised before  establishing the subtype diagnosis. In narco-


374 Sleep-Wake Disorders
lepsy with cataplexy but withou t hypocretin deficiency, test  results for human leukocyte
antigen (HLA) DQB1*06:02 may be negative. Seiz ures, falls of other origin, and conversion
disorder (functional neurological symptom disorder) should be excluded. In narcolepsy
secondary to infectious (e.g., Whipple’s dise ase, sarcoidosis), traumatic, or tumoral de-
struction of hypocretin neuron s, test results for HLA DQB1* 06:02 may be positive and may
result from the insult triggeri ng the autoimmune process. In other cases, the destruction of
hypocretin neurons may be secondary to trau ma or hypothalamic surgery. Head trauma
or infections of the central nervous system can, however, produce tran sitory decreases in
CSF hypocretin-1 levels without hypocret in cell loss, complicating the diagnosis.
Diagnostic Features
The essential features of sleepiness in narcolep sy are recurrent daytime naps or lapses into
sleep. Sleepiness typica lly occurs daily but must occur at a minimum three times a week
for at least 3 months (Criterion A). Narcolep sy generally produces cataplexy, which most
commonly presents as brief episodes (seconds to minutes) of sudden, bilateral loss of mus-
cle tone precipitated by emotions, typically  laughing and joking. Muscles affected may
include those of the neck, jaw, arms, legs, or  whole body, resulting in head bobbing, jaw
dropping, or complete falls. Individuals are awake and aware during cataplexy. To meet
Criterion B1(a), cataplexy must be triggered by  laughter or joking and must occur at least
a few times per month when the condition is untreated or in the past.


a few times per month when the condition is untreated or in the past.
Cataplexy should not be confused with “wea kness” occurring in the context of athletic
activities (physiological) or ex clusively after unusual emotiona l triggers such as stress or
anxiety (suggesting possible psychopathology). Episodes lasting hours or days, or those not
triggered by emotions, are unlikely to be cata plexy, nor is rolling on the floor while laugh-
ing hysterically.
In children close to onset, genuine cataplexy can be atypical, affecting primarily the
face, causing grimaces or jaw opening with tongue thrusting (“cataplectic faces”). Alter-
natively, cataplexy may present as low-grad e continuous hypotonia, yielding a wobbling
walk. In these cases, Criterion B1(b) can be met in children or in individuals within 6 months
of a rapid onset.
Narcolepsy-cataplexy nearly always results from the loss of hypothalamic hypocretin
(orexin)–producing cells, causin g hypocretin deficiency (less than or equal to one-third of
control values, or 110 pg/mL in most laboratori es). Cell loss is likely autoimmune, and ap-
proximately 99% of affected individuals carry HLA-DQB1*06:02 (vs. 12%–38% of control
subjects). Thus, checking  for the presence of DQB1*06:02 pr ior to a lumbar puncture for eval-
uation of CSF hypocretin-1 immu noreactivity may be useful. Ra rely, low CSF levels of hypo-
cretin-1 occur without cataplexy, notably in youths who may develop cataplexy later. CSF


hypocretin-1 measurement represents the gold standard, excepting associated severe con-
ditions (neurological, inflammatory, infectious , trauma) that can inte rfere with the assay.
A nocturnal polysomnographic sleep study followed by an MSLT can also be used to
confirm the diagnosis (Criterion B3). These tests must be performed after the individual
has stopped all psychotropic medications, fo llowing 2 weeks of adequate sleep time (as
documented with sleep diaries, actigraphy). Short rapid eye movement (REM) latency
(sleep-onset REM period, REM latency less than  or equal to 15 minutes) during polysom-
nography is sufficient to confirm the diagnosi s and meets Criterion B3. Alternatively, the
MSLT result must be positive, showing a mean sleep latency of less than or equal to 8 min-
utes and two or more sleep-onset REM periods in four to five naps.
Associated Features Supporting Diagnosis


MSLT result must be positive, showing a mean sleep latency of less than or equal to 8 min-
utes and two or more sleep-onset REM periods in four to five naps.
Associated Features Supporting Diagnosis
When sleepiness is severe, automatic behavior s may occur, with the individual continuing
his or her activities in a semi-automatic, ha zelike fashion without memory or conscious-
ness. Approximately 20%–60% of individuals experience vivid hypnagogic hallucinations


Narcolepsy 375
before or upon falling asleep or hypnopompic  hallucinations just after awakening. These
hallucinations are distinct from the less vivid, nonhallucinatory dreamlike mentation at
sleep onset that occurs in normal sleepers.  Nightmares and vivid dreaming are also fre-
quent in narcolepsy, as is REM sleep behavior disorder. Approximately 20%–60% of indi-
viduals experience sleep paralysis upon falling asleep or awakening, leaving them awake
but unable to move or speak. However, many  normal sleepers also report sleep paralysis,
especially with stress or slee p deprivation. Nocturnal eating  may occur. Obesity is com-
mon. Nocturnal sleep disruption with freque nt long or short awakenings is common and
can be disabling.
Individuals may appear sleepy or fall asleep in the waiting area or during clinical ex-
amination. During cataplexy, individuals may slump in a chair and have slurred speech or
drooping eyelids. If the clinician has time to  check reflexes during cataplexy (most attacks
are less than 10 seconds), reflexes are abo lished—an important finding distinguishing gen-
uine cataplexy from conversion disorder.
Prevalence
Narcolepsy-cataplexy affects 0.02%–0.04% of the general population in most countries.
Narcolepsy affects both genders, with possibly a slight male preponderance.
Development and Course
Onset is typically in children and adolescents/young adults but rarely in older adults.
Two peaks of onset are suggested, at ages 15–25 years and ages 30–35 years. Onset can be
abrupt or progressive (over years). Severity is highest when onset is abrupt in children,


abrupt or progressive (over years). Severity is highest when onset is abrupt in children,
and then decreases with age or with treatment, so that symptoms such as cataplexy can oc-
casionally disappear. Abrupt onset in young, prepubescent children can be associated
with obesity and premature puberty, a phenotype more frequently observed since 2009. In
adolescents, onset is more difficu lt to pinpoint. Onset in adults is often unclear, with some
individuals reporting having ha d excessive sleepiness since bi rth. Once the disorder has
manifested, the course is persistent and lifelong.
In 90% of cases, the first symptom to manife st is sleepiness or in creased sleep, followed
by cataplexy (within 1 year in 50% of cases, within 3 years in 85%). Sleepiness, hypnagogic
hallucinations, vivid dreaming , and REM sleep behavior disorder (excessive movements
during REM sleep) are early symptoms. Excessiv e sleep rapidly progresses to an inability
to stay awake during the day, and to maintain  good sleep at night, without a clear increase
in total 24-hour sleep needs. In the first months, cataplexy may be atypical, especially in
children. Sleep paralysis usually develops ar ound puberty in child ren with prepubertal
onset. Exacerbations of symptoms suggest la ck of compliance with medications or devel-
opment of a concurrent sleep disorder, notably sleep apnea.
Young children and adolescents with narcolepsy often develop a ggression or behav-
ioral problems secondary to sleepiness and/ or nighttime sleep disruption. Workload and
social pressure increase thro ugh high school and college, reducing available sleep time at
night. Pregnancy does not seem  to modify symptoms consisten tly. After retirement, indi-


viduals typically have more opportunity for napping, reducing the need for stimulants.
Maintaining a regular schedule benefits individuals at all ages.
Risk and Prognostic Factors
Temperamental. Parasomnias, such as sleepwalking, bruxism, REM sleep behavior dis-
order, and enuresis, may be more common in  individuals who deve lop narcolepsy. Indi-
viduals commonly report that they need more sleep than other family members.
Environmental. Group A streptococcal throat infect ion, influenza (notably pandemic
H1N1 2009), or other winter infections are lik ely triggers of the autoimmune process, pro-


376 Sleep-Wake Disorders
ducing narcolepsy a few months later. Head trauma and abrupt changes in sleep-wake
patterns (e.g., job changes, stress) may be additional triggers.
Genetic and physiological. Monozygotic twins are 25%–32% concordant for narcolepsy.
The prevalence of narcolepsy is 1%–2% in firs t-degree relatives (a 10- to 40-fold increase
overall). Narcolepsy is strongly  associated with DQB1*06:02  (99% vs. 12%–38% in control
subjects of various ethnic gr oups; 25% in the general U.S. population). DQB1*03:01 in-
creases, while DQB1*05:01, DQB1*06:01, and DQB1*06:03 reduce risk in the presence of
DQB1*06:02, but the effect is small. Polymorphisms within the T-cell receptor alpha gene
and other immune modulating gene s also modulate risk slightly.
Culture-Related Diagnostic Issues
Narcolepsy has been described in all ethnic groups and in many cultures. Among African
Americans, more cases present without cataplexy or with atypical cataplexy, complicating
diagnosis, especially in the presence of obesity and obstructive sleep apnea.
Diagnostic Markers
Functional imaging suggests impaired hypo thalamic responses to humorous stimuli.
Nocturnal polysomnography followed by an MS LT is used to confirm the diagnosis of
narcolepsy, especially when the disorder is first being diagnosed and before treatment has
begun, and if hypocretin deficiency has not been documented biochemically. The poly-
somnography/MSLT should be performed after the individual is no longer taking any


somnography/MSLT should be performed after the individual is no longer taking any
psychotropic drugs and after re gular sleep-wake patterns, with out shift work or sleep de-
privation, have been documented.
A sleep-onset REM period during the poly somnography (REM sleep latency less than
or equal to 15 minutes) is highly specific (a pproximately 1% positive in control subjects)
but moderately sensitive (approximately 50%). A positive MSLT  result displays an aver-
age sleep latency of less than or equal to 8 minutes, and sleep-onset REM periods in two or
more naps on a four- or five-nap test. The MS LT result is positive in 90%–95% of individ-
uals with narcolepsy versus 2%–4% of control subjects or individuals with other sleep dis-
orders. Additional polysomnographic findings often include frequent  arousals, decreased
sleep efficiency, and increased stage 1 sleep.  Periodic limb moveme nts (found in about
40% of individuals with narcolepsy) and sleep apnea are often noted.
Hypocretin deficiency is demonstrated by  measuring CSF hypocretin-1 immunoreac-
tivity. The test is particular ly useful in individuals with suspected conversion disorder
and those without typical cataplexy, or in treatment-refractory cases. The diagnostic value
of the test is not affected by medications, sleep deprivation, or circadian time, but the find-
ings are uninterpretable when the individual is severely ill with a concurrent infection or
head trauma or is comatose. CSF cytology, protein, and glucose are within normal range
even when sampled within weeks of rapid onse t. CSF hypocretin-1 in these incipient cases


is typically already very diminished or undetectable.
Functional Consequenc es of Narcolepsy
Driving and working are impaired, and indivi duals with narcolepsy should avoid jobs
that place themselves (e.g., working with mach inery) or others (e.g., bus driver, pilot) in
danger. Once the narcolepsy is controlled wi th therapy, patients can usually drive, al-
though rarely long distances alone. Untreated individuals are also at risk for social isola-
tion and accidental injury to themselves or  others. Social relations may suffer as these
individuals strive to avert cataplexy by exerting control over emotions.
Differential Diagnosis
Other hypersomnias. Hypersomnolence and narcolepsy are similar with respect to the
degree of daytime sleepiness, age at onset, an d stable course over time but can be distin-


Narcolepsy 377
guished based on distinctive clinical and labo ratory features. Individuals with hypersom-
nolence typically have longer and less disrupted nocturnal sleep, greater difficulty
awakening, more persistent daytime sleepine ss (as opposed to more discrete “sleep at-
tacks” in narcolepsy), longer and less refreshing daytime sleep episodes, and little or no
dreaming during daytime naps. By contrast, individuals with narcolepsy have cataplexy
and recurrent intrusions of elements of REM sleep into the transition between sleep and
wakefulness (e.g., sleep-related hallucination s and sleep paralysis). The MSLT typically
demonstrates shorter sleep latenc ies (i.e., greater physiological  sleepiness) as well as the
presence of multiple sleep-onset REM periods in individuals with narcolepsy.
Sleep deprivation and insufficient nocturnal sleep. Sleep deprivation and insufficient
nocturnal sleep are common in adolescents and shift workers. In adolescents, difficulties
falling asleep at night are common, causing sleep deprivation. The MSLT result may be
positive if conducted while the individual is  sleep deprived or while his or her sleep is
phase delayed.
Sleep apnea syndromes. Sleep apneas are especially likely in the presence of obesity.
Because obstructive sleep apnea is more freque nt than narcolepsy, ca taplexy may be over-
looked (or absent), and the individual is as sumed to have obstructive sleep apnea unre-
sponsive to usual therapies.
Major depressive disorder. Narcolepsy or hypersomnia may be associated or confused
with depression. Cataplexy is not present in depression. The MSLT re sults are most often
normal, and there is dissociation between subj ective and objective sleepiness, as measured


normal, and there is dissociation between subj ective and objective sleepiness, as measured
by the mean sleep latency during the MSLT.
Conversion disorder (functional neurological symptom disorder). Atypical features,
such as long-lasting cataplexy or unusual tr iggers, may be present in conversion disorder
(functional neurological symptom disorder).  Individuals may report sleeping and dream-
ing, yet the MSLT does not show the characteristic sleep-onset REM period. Full-blown,
long-lasting pseudocataplexy may occur during consultation, allowing the examining
physician enough time to verify reflexes, which remain intact.
Attention-deficit/hyperactivity disord er or other behavioral problems. In children and
adolescents, sleepiness can ca use behavioral problems, including aggressiveness and in-
attention, leading to a misdiagnosis of attention-deficit/hype ractivity disorder.
Seizures. In young children, cataplexy can be misd iagnosed as seizures. Seizures are not
commonly triggered by emotions, and when they are, the trigger is not usually laughing or
joking. During a seizure, individuals are more  likely to hurt themselves when falling. Sei-
zures characterized by isolated atonia are rare ly seen in isolation of other seizures, and
they also have signatures on  the electroencephalogram.
Chorea and movement disorders. In young children, cataplexy can be misdiagnosed as
chorea or pediatric autoimmune neuropsychiatric disorders associated with streptococcal
infections, especially in the co ntext of a strep throat infectio n and high antistreptolysin O
antibody levels. Some children may have an overlapping movement d isorder close to on-
set of the cataplexy.


set of the cataplexy.
Schizophrenia. In the presence of florid and vivid hypnagogic hallucinations, individuals
may think these experiences are real—a feature that suggests schizophrenia. Similarly,
with stimulant treatment, pers ecutory delusions may develop. If cataplexy is present, the
clinician should first assume that these sympto ms are secondary to narcolepsy before con-
sidering a co-occurring diagnosis of schizophrenia.
Comorbidity
Narcolepsy can co-occur with bipolar, depressi ve, and anxiety disorders, and in rare cases
with schizophrenia. Narcolepsy is also associ ated with increased body mass index or obe-


378 Sleep-Wake Disorders
sity, especially when the narcolepsy is untreated. Rapid weight gain is common in young
children with a sudden disease onset. Comorbid sleep apnea sh ould be considered if there
is a sudden aggravation of preexisting narcolepsy.
Relationship to Internat ional Classification of
Sleep Disorders
The International Classificat ion of Sleep Disorders,  2nd Edition (ICSD-2), differentiates five
subtypes of narcolepsy.
Breathing-Related Sleep Disorders
The breathing-related sleep disorders category encompasses three relatively distinct dis-
orders: obstructive sleep apnea hypopnea, ce ntral sleep apnea, an d sleep-related hypo-
ventilation.
Obstructive Sleep Apnea Hypopnea
Diagnostic Criteria 327.23 (G47.33)
A. Either (1) or (2):
1. Evidence by polysomnography of at least five obstructive apneas or hypopneas per
hour of sleep and either of the following sleep symptoms:
a. Nocturnal breathing disturbances: snor ing, snorting/gasping, or breathing
pauses during sleep.
b. Daytime sleepiness, fatigue, or unrefreshing sleep despite sufficient opportuni-
ties to sleep that is not better explained by another mental disorder (including a
sleep disorder) and is not attribut able to another medical condition.
2. Evidence by polysomnography of 15 or more obstructive apneas and/or hypopneas
per hour of sleep regardless of accompanying symptoms.
Specify current severity:
Mild:  Apnea hypopnea index is less than 15.
Moderate: Apnea hypopnea index is 15–30.
Severe:  Apnea hypopnea index is greater than 30.
Specifiers


Severe:  Apnea hypopnea index is greater than 30.
Specifiers
Disease severity is measured by a count of  the number of apneas plus hypopneas per hour
of sleep (apnea hypopnea index) using polysomnography or other ov ernight monitoring.
Overall severity is also informed by levels of nocturnal desaturation and sleep fragmen-
tation (measured by brain cortical arousal frequency and sleep stages) and degree of as-
sociated symptoms and daytime impairment. However, the exact number and thresholds
may vary according to the specific measureme nt techniques used, and these numbers may
change over time. Regardless of the apnea hy popnea index (count) pe r se, the disorder is
considered to be more severe when apneas and hypopneas are accompanied by significant
oxygen hemoglobin desaturation (e.g., when more than 10% of the sleep time is spent at
desaturation levels of less than 90%) or wh en sleep is severely fragmented as shown by an


Obstructive Sleep Apnea Hypopnea 379
elevated arousal index (arousal index greater th an 30) or reduced stages in deep sleep (e.g.,
percentage stage N3 [slow-wave sleep] less than 5%).
Diagnostic Features
Obstructive sleep apnea hypopnea is the most  common breathing-related sleep disorder.
It is characterized by repeated episodes of upper (pharyngeal) airw ay obstruction (apneas
and hypopneas) during sleep. Apnea  refers to the total absence of airflow, and hypopnea  re-
fers to a reduction in airflow. Each apnea or  hypopnea represents a reduction in breathing
of at least 10 seconds in duration in adults or two missed breaths in children and is typi-
cally associated with drops in oxygen saturation  of 3% or greater and/or an electroenceph-
alographic arousal. Both sleep-related (nocturnal) and wake-time symptoms are common.
The cardinal symptoms of obstructive sleep apnea hypopnea are snoring and daytime
sleepiness.
Obstructive sleep apnea hypopnea in adults  is diagnosed on the basis of polysom-
nographic findings and symptoms. The diagnosis is based on symptoms of 1) nocturnal
breathing disturbances (i.e., snoring, snorti ng/gasping, breathing pauses during sleep), or
2) daytime sleepiness, fatigue, or unrefreshi ng sleep despite suffic ient opportunities to
sleep that are not better explained by another mental disorder and not attributable to an-
other medical condition, along with 3) eviden ce by polysomnography of five or more ob-
structive apneas or hypopneas per hour of sleep (Criterion A1). Diagnosis can be made in


the absence of these symptoms if there is evidence by polysomnography of 15 or more ob-
structive apneas and/or hypopneas pe r hour of sleep (Criterion A2).
Specific attention to disturbe d sleep occurring in association with snoring or breathing
pauses and physical findings that increase ri sk of obstructive sleep apnea hypopnea (e.g.,
central obesity, crowded pharyngeal airway, el evated blood pressure) is needed to reduce
the chance of misdiagnosing this treatable condition.
Associated Features Supporting Diagnosis
Because of the frequency of nocturnal awakenin gs that occur with obstructive sleep apnea
hypopnea, individuals may report symptoms  of insomnia. Other common, though non-
specific, symptoms of obstructive sleep apne a hypopnea are heartbur n, nocturia, morning
headaches, dry mouth, erectile  dysfunction, and reduced li bido. Rarely, individuals may
complain of difficulty breathing while lying supine or sleeping. Hypertension may occur
in more than 60% of individuals with obstructive sleep apnea hypopnea.
Prevalence
Obstructive sleep apnea hypopnea is a very common disorder, affecting at least 1%–2% of
children, 2%–15% of middle-age adults, and mo re than 20% of older individuals. In the
general community, prevalence  rates of undiagnosed obst ructive sleep apnea hypopnea
may be very high in elderly individuals. Sinc e the disorder is strongly associated with obe-
sity, increases in obesity rates are likely to be accompanied by an increased prevalence of
this disorder. Prevalen ce may be particularly high amon g males, older adults, and certain


racial/ethnic groups. In adults, the male-to-female ratio of obstructive sleep apnea hypop-
nea ranges from 2:1 to 4:1. Ge nder differences decline in olde r age, possibly because of an
increased prevalence in females after menopause. There is no gender difference among
prepubertal children.
Development and Course
The age distribution of obstructive sleep apnea hypopnea likely follows a J-shaped distri-
bution. There is a peak in children ages 3–8 years when the nasopharynx may be compro-
mised by a relatively large mass of tonsillar tissue compared with the size of the upper


380 Sleep-Wake Disorders
airway. With growth of the airway and regression of lymphoid tissue during later child-
hood, there is reduction in prevalence. Then, as obesity prevalence increases in midlife and
females enter menopause, obstructive sleep apnea hypopnea again increases. The course
in older age is unclear; the disorder may level off after age 65 years, but in other individ-
uals, prevalence may increase with aging. Beca use there is some age dependency of the oc-
currence of apneas and hypopneas, polysomnog raphic results must be interpreted in light
of other clinical data. In particular, signific ant clinical symptoms of insomnia or hyper-
somnia should be investigated re gardless of the individual’s age.
Obstructive sleep apnea hypopnea usually ha s an insidious onset, gradual progression,
and persistent course. Typically the loud snorin g has been present for many years, often since
childhood, but an increase in its severity may lead the individual to seek evaluation. Weight
gain may precipitate an increase in sympto ms. Although obstructive sleep apnea hypopnea
can occur at any age, it most commonly mani fests among individuals ages 40–60 years. Over
4–5 years, the average apnea hypo pnea index increases in adults and older individuals by ap-
proximately two apneas/hypopneas per hour. Th e apnea hypopnea index is increased and in-
cident obstructive sleep apnea hypopnea is greater among indivi duals who are older, who are
male, or who have a higher baseline body mass  index (BMI) or increa se their BMI over time.
Spontaneous resolution of obstructive sleep ap nea hypopnea has been reported with weight


Spontaneous resolution of obstructive sleep ap nea hypopnea has been reported with weight
loss, particularly after bariatric surgery. In children, seasonal va riation in obstructive sleep ap-
nea hypopnea has been observed, as has improvement with overall growth.
In young children, the signs and symptoms of obstructive sleep apnea hypopnea may be
more subtle than in adults, making diagnosis more difficult to establish. Polysomnography is
useful in confirming diagnosis. Evidence of  fragmentation of sleep on the polysomnogram
may not be as apparent as in studies of older individuals, possibly because of the high homeo-
static drive in young individuals. Symptoms su ch as snoring are usually parent-reported and
thus have reduced sensitivity. Agitated arousals and unusual sleep postures, such as sleeping
on the hands and knees, may oc cur. Nocturnal enuresis also may occur and should raise the
suspicion of obstructive sleep apnea hypopnea if it recurs in a child who was previously dry at
night. Children may also manife st excessive daytime sleepiness, although this is not as com-
mon or pronounced as in adults. Daytime mouth breathing, difficulty in swallowing, and poor
speech articulation are also common features in children. Children younger than 5 years more
often present with nighttime symptoms, such as  observed apneas or labored breathing, than
with behavioral symptoms (i.e., the nighttime symptoms are more noticeable and more often
bring the child to clinical attention). In childre n older than 5 years, daytime symptoms such as
sleepiness and behavioral problems (e.g., impulsivity and hyperactivity), attention-deficit/
hyperactivity disorder, learning  difficulties, and morning head aches are more often the focus
of concern. Children with obstructive sleep apnea hypopnea also may present with failure to


of concern. Children with obstructive sleep apnea hypopnea also may present with failure to
thrive and developmental delays. In young children, obesity is a less common risk factor,
while delayed growth and “failure to thrive” may be present.
Risk and Prognostic Factors
Genetic and physiological. The major risk factors for ob structive sleep apnea hypopnea
are obesity and male gender. Others include maxillary-mandi bular retrognathia or micro-
gnathia, positive family history of sleep apnea, genetic syndromes that reduce upper
airway patency (e.g., Down’s syndrome, Trea cher Collin’s syndrome), adenotonsillar hy-


gnathia, positive family history of sleep apnea, genetic syndromes that reduce upper
airway patency (e.g., Down’s syndrome, Trea cher Collin’s syndrome), adenotonsillar hy-
pertrophy (especially in youn g children), menopause (in fema les), and various endocrine
syndromes (e.g., acromegaly). Compared with  premenopausal females, males are at in-
creased risk for obstruct ive sleep apnea hypopnea, possibly reflecting the influences of sex
hormones on ventilatory control and body fat distribution, as well as because of gender
differences in airway structure. Medication s for mental disorders and medical conditions
that tend to induce somnolence may worsen the course of apnea symptoms if these med-
ications are not managed carefully.


Obstructive Sleep Apnea Hypopnea 381
Obstructive sleep apnea hypopnea has a strong  genetic basis, as evidenced by the sig-
nificant familial aggregation of the apnea hy popnea index. The prevalence of obstructive
sleep apnea hypopnea is approximately twice as high among the first-degree relatives of
probands with obstructive sleep apnea hypopn ea as compared with members of control
families. One-third of the variance in the apnea hypopnea index is explained by shared fa-
milial factors. Although genetic markers with diagnostic or prognostic value are not yet
available for use, eliciting a family history of obstructive sleep apnea hypopnea should in-
crease the clinical suspicion for the disorder.
Culture-Related Diagnostic Issues
There is a potential for sleepiness and fatigue to  be reported differently across cultures. In
some groups, snoring may be considered a si gn of health and thus may not trigger con-
cerns. Individuals of Asian ancestry may be at increased risk for obstructive sleep apnea
hypopnea despite relatively low BMI, possibly reflecting the influence of craniofacial risk
factors that narrow the nasopharynx.
Gender-Related Issues
Females may more commonly report fatigue rather than sleepiness and may underreport
snoring.
Diagnostic Markers
Polysomnography provides quan titative data on frequency of sleep-related respiratory
disturbances and associated changes in oxygen saturation and sleep continuity. Polysom-
nographic findings in children differ from th ose in adults in that children demonstrate
labored breathing, partial obst ructive hypoventilation with cyclical desaturations, hyper-
capnia and paradoxical movements. Apnea hy popnea index levels as low as 2 are used to
define thresholds of abnormality in children.


define thresholds of abnormality in children.
Arterial blood gas measurements while the in dividual is awake are usually normal, but
some individuals can have waking hypoxemia or  hypercapnia. This pattern should alert the
clinician to the possibility of coexisting lung disease or hypoventilation. Imaging procedures
may reveal narrowing of the u pper airway. Cardiac testing ma y show evidence of impaired
ventricular function. Individuals with severe no cturnal oxygen desaturation may also have el-
evated hemoglobin or hematocrit values. Vali dated sleep measures (e.g., multiple sleep la-
tency test [MSLT], maintenance of wake fulness test) may identify sleepiness.
Functional Consequences of
Obstructive Sleep Apnea Hypopnea
More than 50% of individuals with moderate  to severe obstructive sleep apnea hypopnea
report symptoms of daytime sleepiness. A twof old increased risk of occupational accidents
has been reported in association with sympto ms of snoring and slee piness. Motor vehicle
crashes also have been reported to be as mu ch as sevenfold higher among individuals with
elevated apnea hypopnea index values. Clinicians should be cognizant of state govern-
ment requirements for reporting this disorder , especially in relati onship to commercial
drivers. Reduced scores on measures of health -related quality of life are common in individ-
uals with obstructive sleep apnea hypopnea, wi th the largest decrements observed in the
physical and vitality subscales.
Differential Diagnosis
Primary snoring and other sleep disorders. Individuals with obstructive sleep apnea
hypopnea must be differentiat ed from individuals with primary snoring (i.e., otherwise


382 Sleep-Wake Disorders
asymptomatic individuals who snore and do not have abnorm alities on overnight polysom-
nography). Individuals with obstructive sl eep apnea hypopnea may additionally report
nocturnal gasping and choking. The presence of sleepiness or other daytime symptoms
not explained by other etiolo gies suggests the diagnosis of obstructive sleep apnea hypop-
nea, but this differentiation requires polysomnography. Defi nitive differential diagnosis
between hypersomnia, central sleep apnea, sleep-related hypoventilation, and obstructive
sleep apnea hypopnea also requ ires polysomnographic studies.
Obstructive sleep apnea hypopnea must be diff erentiated from other causes of sleepi-
ness, such as narcolepsy, hypersomnia, and ci rcadian rhythm sleep d isorders. Obstructive
sleep apnea hypopnea can be differentiated from  narcolepsy by the absence of cataplexy,
sleep-related hallucinations, and sleep paraly sis and by the presence of loud snoring,
gasping during sleep, or observed apneas in  sleep. Daytime sleep episodes in narcolepsy
are characteristically shorter,  more refreshing, and more of ten associated with dreaming.
Obstructive sleep apnea hypopnea shows characteristic apneas and hypopneas and oxy-
gen desaturation during nocturnal polysomnog raphic studies. Narcolepsy results in mul-
tiple sleep-onset rapid eye movement (REM) periods during the MS LT. Narcolepsy, like
obstructive sleep apnea hypopnea, may be asso ciated with obesity, and some individuals
have concurrent narcolepsy and obstructive sleep apnea hypopnea. A diagnosis of narco-


lepsy does not exclude the di agnosis of obstructive sleep apnea hypopnea, as the two con-
ditions may co-occur.
Insomnia disorder. For individuals complaining of difficulty initiating or maintaining
sleep or early-morning awakenings, insomnia disorder can be differen tiated from obstruc-
tive sleep apnea hypopnea by the absence of sn oring and the absence of the history, signs,
and symptoms characteri stic of the latter disorder. However, insomnia and obstructive
sleep apnea hypopnea may coexist, and if so , both disorders may need to be addressed
concurrently to improve sleep.
Panic attacks. Nocturnal panic attacks may include symptoms of gasping or choking
during sleep that may be difficult to distinguish clinically from obst ructive sleep apnea hy-
popnea. However, the lower frequency of episo des, intense autonomic arousal, and lack of
excessive sleepiness differentiate nocturnal pa nic attacks from obstructive sleep apnea hy-
popnea. Polysomnography in individuals with nocturnal panic attacks does not reveal the
typical pattern of apneas or oxygen desaturation characteristic of obstructive sleep apnea
hypopnea. Individuals with obstructive slee p apnea hypopnea do not provide a history of
daytime panic attacks.
Attention-deficit/hyperactivity disorder. Attention-deficit/hyperact ivity disorder in chil-
dren may include symptoms of inattention, academic impairment, hyperactivity, and in-
ternalizing behaviors, all of which may also  be symptoms of chil dhood obstructive sleep
apnea hypopnea. The presence of other symptoms and signs of childhood obstructive
sleep apnea hypopnea (e.g., labored breathing or snoring during sleep and adenotonsillar


hypertrophy) would suggest the presence of obstructive sl eep apnea hypopnea. Obstruc-
tive sleep apnea hypopnea and attention-de ficit/hyperactivity disorder may commonly
co-occur, and there may be causal links between  them; therefore, risk factors such as en-
larged tonsils, obesity, or a family history of sleep apnea may help alert the clinician to
their co-occurrence.
Substance/medication-induced  insomnia or hypersomnia. Substance use and substance
withdrawal (including medications) can prod uce insomnia or hypersomnia. A careful his-
tory is usually sufficient to identify the relevant substa nce/medication, and follow-up
shows improvement of the sleep  distur bance after discontinuation of the substance/med-


tory is usually sufficient to identify the relevant substa nce/medication, and follow-up
shows improvement of the sleep  distur bance after discontinuation of the substance/med-
ication. In other cases, the use of a substanc e/medication (e.g., alcohol, barbiturates, ben-
zodiazepines, tobacco) has been shown to exacerbate obst ructive sleep apnea hypopnea.
An individual with sy mptoms and signs cons istent with obstructive sleep apnea hypop-


Central Sleep Apnea 383
nea should receive that diagnosis, even in th e presence of concurrent substance use that is
exacerbating the condition.
Comorbidity
Systemic hypertension, coronary artery disease, heart failure, stroke, diabetes, and increased
mortality are consistently asso ciated with obstructive slee p apnea hypopnea. Risk esti-
mates vary from 30% to as much as 300% for moderate to severe obstructive sleep apnea
hypopnea. Evidence of pulmonary hypertensi on and right heart fa ilure (e.g., cor pulmo-
nale, ankle edema, hepatic congestion) are ra re in obstructive sleep apnea hypopnea and
when present indicate either very severe di sease or associated hypoventilation or cardio-
pulmonary comorbidities. Obstructive sleep apnea hypopnea also may occur with in-
creased frequency in association with a number of medical or neurological conditions (e.g.,
cerebrovascular disease, Parkinson’s disease). Physical findings refl ect the co-occurrence of
these conditions.
As many as one-third of individuals referred  for evaluation of obstructive sleep apnea
hypopnea report symptoms of depression, with  as many of 10% having depression scores
consistent with moderate to severe depressi on. Severity of obstructive sleep apnea hypop-
nea, as measured by the apnea hypopnea index,  has been found to be correlated with se-
verity of symptoms of depression. This a ssociation may be stronger in males than in
females.
Relationship to Internat ional Classification of
Sleep Disorders
The International Classification of Sleep Disorders,  2nd Edition (ICSD-2), differentiates 11 sub-
types of “sleep-related breath ing disorders,” including primary central sleep apnea, ob-


types of “sleep-related breath ing disorders,” including primary central sleep apnea, ob-
structive sleep apnea, and sle ep-related hypoventilation.
Central Sleep Apnea
Diagnostic Criteria
A. Evidence by polysomnography of five or more central apneas per hour of sleep.
B. The disorder is not better explained by another current sleep disorder.
Specify whether:
327.21 (G47.31) Idiopathic central sleep apnea:  Characterized by repeated epi-
sodes of apneas and hypopneas during sleep caused by variability in respiratory effort
but without evidence of airway obstruction.
786.04 (R06.3) Cheyne-Stokes breathing: A pattern of periodic crescendo-
decrescendo variation in tidal volume that results in central apneas and hypopneas at
a frequency of at least five events per hour, accompanied by frequent arousal.
780.57 (G47.37) Central sleep apnea comorbid with opioid use:  The pathogenesis
of this subtype is attributed to the effects of opioids on the respiratory rhythm genera-
tors in the medulla as well as the differential effects on hypoxic versus hypercapnic re-
spiratory drive.
Coding note  (for 780.57 [G47.37] code only): When an op ioid use disorder is present, first
code the opioid use disorder: 305.50 (F11.10) m ild opioid use disorder or 304.00 (F11.20)
moderate or severe opioid use disorder; then code 780.57 (G47.37) central sleep apnea
comorbid with opioid use. When an opioid use disorder is not present (e.g., after a one-


time heavy use of the substance), code only 780.57 (G47.37) central sleep apnea comor-
bid with opioid use.


384 Sleep-Wake Disorders
Note:  See the section “Diagnostic Features” in text.
Specify current severity:
Severity of central sleep apnea is graded according to the frequency of the breathing
disturbances as well as the extent of associated oxygen desaturation and sleep frag-
mentation that occur as a consequence of repetitive respiratory disturbances.
Subtypes
Idiopathic central sleep apnea and Cheyne-Stokes breathing are characterized by increased
gain of the ventilatory contro l system, also referred to as high loop gain,  which leads to in-
stability in ventilation and PaCO2 levels. This instability is termed periodic breathing and
can be recognized by hyperventilation alternating with hypoventilation. Individuals with
these disorders typically have pCO2 levels while awake that are slightly hypocapneic or
normocapneic. Central sleep apnea may also mani fest during initiation of treatment of ob-
structive sleep apnea hypopnea or may occur in association with obstructive sleep apnea
hypopnea syndrome (termed complex sleep apnea ). The occurrence of central sleep apnea in
association with obstructive slee p apnea is also considered to be due to high loop gain. In
contrast, the pathogenesis of central sleep apnea comorbid wi th opioid use has been at-
tributed to the effects of opioids on the re spiratory rhythm generators in the medulla as
well as to its differential effects on hypoxic versus hypercapneic respiratory drive. These
individuals may have elevated pCO2 levels while awake. Individuals receiving chronic
methadone maintenance therapy have been no ted to have increased somnolence and de-
pression, although the ro le of breathing disorders associated with opioid medication in caus-
ing these problems has not been studied.
Specifiers


ing these problems has not been studied.
Specifiers
An increase in the central apnea index (i.e., number of central apneas per hour of sleep) re-
flects an increase in severity of central sleep apnea. Sleep continuity and quality may be
markedly impaired with reductions in restor ative stages of non–rapid eye movement (REM)
sleep (i.e., decreased slow-wav e sleep [stage N3]). In indi viduals with severe Cheyne-
Stokes breathing, the pattern can also be ob served during resting wakefulness, a finding
that is thought to be a poor prognostic marker for mortality.
Diagnostic Features
Central sleep apnea disorders ar e characterized by repeated episodes of apneas and hy-
popneas during sleep caused by variability in respiratory effort. These are disorders of
ventilatory control in which resp iratory events occur in a peri odic or intermittent pattern.
Idiopathic central sleep apnea  is characterized by sleepiness, insomnia, and awakenings due
to dyspnea in association with five or more  central apneas per hour of sleep. Central sleep
apnea occurring in individuals with heart failu re, stroke, or renal failure typically have a
breathing pattern called Cheyne-Stok es breathing,  which is characterized by a pattern of
periodic crescendo-decrescendo 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. Central and obstru ctive sleep apneas may coexist; the ratio of
central to obstructive apneas/hypopneas may be  used to identify which condition is pre-
dominant.
Alterations in neuromuscular control of br eathing can occur in association with med-


Alterations in neuromuscular control of br eathing can occur in association with med-
ications or substances used in individuals with mental health conditions, which can cause
or exacerbate impairme nts of respiratory rhythm and ventilation. Individuals taking these
medications have a sleep-related breathing diso rder that could contribute to sleep distur-
bances and symptoms such as sleepiness, confusion, and depression. Specifically, chronic


Central Sleep Apnea 385
use of long-acting opioid medications  is often associated with im pairment of respiratory con-
trol leading to central sleep apnea.
Associated Features Supporting Diagnosis
Individuals with central sleep apnea hypopneas can manifest with sleepiness or insomnia.
There can be complaints of sleep fragment ation, including awakening with dyspnea.
Some individuals are asymptomatic. Obstruct ive sleep apnea hypopnea can coexist with
Cheyne-Stokes breathing, and thus snoring and abruptly terminating apneas may be ob-
served during sleep.
Prevalence
The prevalence of idiopathic central sleep apnea is unknown but thought to be rare. The
prevalence of Cheyne-Stokes breathing is high in individuals with depressed cardiac ven-
tricular ejection fraction. In individuals with an ejection fraction of less than 45%, the prev-
alence has been reported to be 20% or high er. The male-to-female ratio for prevalence is
even more highly skewed toward males than for obstructive sleep apnea hypopnea. Prev-
alence increases with age, and most patients are older than 60 years. Cheyne-Stokes breath-
ing occurs in approximately 20% of individu als with acute stroke. Central sleep apnea
comorbid with opioid use occurs in approxim ately 30% of individuals taking chronic opi-
oids for nonmalignant pain and similarly in individuals receiving methadone mainte-
nance therapy.
Development and Course
The onset of Cheyne-Stokes breathing appears tied to the deve lopment of heart failure. The
Cheyne-Stokes breathing pattern is associated with oscillations in heart rate, blood pres-
sure and oxygen desaturation, and elevated sy mpathetic nervous system activity that can