Sumário

Introduction ...................................................................................................................... 5
Insomnia ........................................................................................................................ 16
Chronic Insomnia Disorder ................................................................................................... 17
Sleep Related Breathing Disorders .................................................................................. 38
Obstructive Sleep Apnea Disorders ..................................................................................... 40
Central Sleep Apnea Syndromes .......................................................................................... 52
Sleep Related Hypoventilation Disorders......................................................................... 58
Idiopathic Central Alveolar Hypoventilation ................................................................... 69
Sleep Related Hypoventilation Disorders......................................................................... 72
Isolated Symptoms and Normal Variants ......................................................................... 81
Central Disorders of Hypersomnolence ........................................................................... 86
Disorders .............................................................................................................................. 88
Narcolepsy Type 1 ............................................................................................................ 88
Narcolepsy Type 2 ............................................................................................................ 95
Idiopathic Hypersomnia ................................................................................................. 100
Kleine-Levin Syndrome ................................................................................................. 104
Hypersomnia Due to a Medical Disorder ....................................................................... 108
Hypersomnia Due to a Medication or Substance ........................................................... 112
Hypersomnia Associated with a Psychiatric Disorder ................................................... 115
Insufficient Sleep Syndrome .......................................................................................... 118
Isolated Symptoms and Normal Variants........................................................................... 122
Long Sleeper ...................................................................................................................... 122
Circadian Rhythm Sleep-Wake Disorders ...................................................................... 129
General Criteria for Circadian Rhythm Sleep-Wake Disorder ............................................ 129
Delayed Sleep-Wake Phase Disorder ................................................................................. 130
Advanced Sleep-Wake Phase Disorder .............................................................................. 136
Irregular Sleep-Wake Rhythm Disorder ............................................................................. 142
Non-24-Hour Sleep-Wake Rhythm Disorder ...................................................................... 147
Shift Work Disorder ............................................................................................................ 153
Jet Lag Disorder .................................................................................................................. 157
Circadian Sleep-Wake Disorder Not Otherwise Specified (NOS) ....................................... 161
Parasomnias ................................................................................................................. 165
NREM-Related Parasomnias.............................................................................................. 167
Disorders of Arousal (From NREM Sleep) .................................................................... 167
REM-Related Parasomnias ................................................................................................ 176
REM Sleep Behavior Disorder ....................................................................................... 176
Recurrent Isolated Sleep Paralysis ................................................................................. 182
Nightmare Disorder ........................................................................................................ 185
Other Parasomnias.............................................................................................................. 190
Exploding Head Syndrome ............................................................................................. 190
Sleep Related Hallucinations .......................................................................................... 193
Sleep Enuresis................................................................................................................. 196
Parasomnia Due to a Medical Disorder .......................................................................... 201
Parasomnia Due to a Medication or Substance .............................................................. 201
Parasomnia, Unspecified ................................................................................................ 203
Isolated Symptoms and Normal Variants........................................................................... 203
Sleep Talking...................................................................................................................... 203
Sleep Related Movement Disorders ............................................................................... 207
Disorders ............................................................................................................................ 207
Restless Legs Syndrome ................................................................................................. 208
Periodic Limb Movement Disorder ................................................................................ 215
Sleep Related Leg Cramps ............................................................................................. 221
Sleep Related Bruxism ................................................................................................... 224
Sleep Related Rhythmic Movement Disorder ................................................................ 231
Benign Sleep Myoclonus of Infancy .............................................................................. 235
Propriospinal Myoclonus at Sleep Onset........................................................................ 238
Sleep Related Movement Disorder Due to a Medical Disorder ..................................... 241
Sleep Related Movement Disorder, Unspecified ........................................................... 243
Isolated Symptoms and Normal Variants........................................................................... 243
Excessive Fragmentary Myoclonus ................................................................................ 243
Hypnagogic Foot Tremor and Alternating Leg Muscle Activation ............................... 246
Sleep Starts (Hypnic Jerks)............................................................................................. 249
Other Sleep Disorder ..................................................................................................... 254
Appendix A: Sleep Related Medical and Neurological Disorders ...................................... 256
Disorders ......................................................................................................................... 256
Introduction
Classification of disorders plays several key roles in medicine. The most

familiar of these is that is serves as a guide to clinicians in the identification of

specific disease states. In doing so, classification systems provide clinicians

with important information regarding numerous related factors including

pathogenesis, prognosis, course, and heritability. Moreover, therapeutic

interventions are largely guided by the nosological decisions made by

clinicians. In turn, information accrued regarding therapeutic response of these

disease states is utilized to further refine the nosology. Classification systems

also serve to define the domain of a given discipline, a factor of particular

importance for fields such as sleep medicine which cut across many related

specialties. Finally, by identifying areas of uncertainty and overlap among

related pathologies, these systems play a critical role in guiding future research

agendas which will enhance our knowledge and understanding of the clinical

features, pathophysiology and treatment response specific to each disorder.

Since its infancy 35 years ago, the field of sleep medicine has paid particular

attention to the issue of classification, beginning with the 1979 American Sleep

Disorders  Association’s  Diagnostic  Classification  of  Sleep  and  Arousal  

Disorders. Since that time, as our knowledge and understanding of sleep

disorders has grown, several different structural approaches have been utilized

in revisions of the classification system, culminating in the International

Classification of Sleep Disorders, 2nd Edition. The organization of that edition,

although not without its limitations, has proven effective and user-friendly and

has been maintained in the current revision.

Ideally, classification systems are based largely on pathophysiology. However,

such an approach is dependent on adequate knowledge concerning the various

pathophysiologies of disease or disorder within a given discipline. As is the case

with many diagnostic systems, our current knowledge and understanding of the

pathophysiology of many sleep disorders is inadequate. As a result,

International Classification of Sleep Disorders, 3rd Edition, not unlike its

predecessors, employs a hybrid approach which utilizes pathophysiology, where

known, but also relies heavily on phenomenology and organ system approaches.

Despite these shortcomings, this approach is one that has proven familiar and

workable for sleep medicine clinicians.

Recognizing the need for currency and relevance in a rapidly evolving field, the

American Academy of Sleep Medicine Board of Directors approved a revision

of International Classification of Sleep Disorders, 2nd Edition in 2011.

Following appointment of a chair/editor, a task force, consisting of individual

work group chairs for each major division of the manual, was selected, along

with two pediatric consultants. A focus group of experts was convened in June

2011 to obtain input on major structural and content issues. Based on this

feedback, individual work groups then set about to define the list of disorders to
be included within their sections as well as proposed criteria for each diagnosis.

This process included comprehensive literature searches for every potential

diagnosis as well as for their major features. The draft diagnostic criteria which

emanated from this work were then reviewed and modified by the task force

(consisting of the work group chairs and pediatric advisors), as well as by the

board of the AASM. The edited criteria were then distributed to external peer

reviewers with expertise in the respective areas, as well as to international

societies and membership sections of the AASM for comment. These reviews

were carefully considered and revisions made based on this input. Subsequent to

this, text revisions were begun and the same review process and modifications

were undertaken once text drafts were completed. Further modifications were

made based on recommendations from the AASM board before finalization of

the edition. At all points in this process, efforts were made to rely as heavily as

possible on available and current scientific evidence. However, due to the

paucity of available evidence in many areas, decisions regarding the nosology

were often made by consensus of the work groups, task force, and reviewers.

Using ICSD-3
As noted above, the general structure of the current edition closely parallels that

of the second edition. The major clinical divisions remain unchanged. As with

International Classification of Sleep Disorders, 2nd Edition, pediatric diagnoses

are fully integrated into the major clinical diagnoses, with the exception
of obstructive sleep apnea, pediatric. Where pediatric presentations call for

variation in the diagnostic criteria, those variations are noted within the criteria

section. In an effort to better identify those clinical features of a disorder which

are developmentally-specific, a text heading forDevelopmental Issues has been

added for each diagnosis. Specific ICD codes (9-CM and 10-CM) are listed at

the beginning of each diagnosis. Because of the complexities and differences

between International Classification of Sleep Disorders diagnoses and the ICD

system, assignment of codes is challenging. These issues are discussed further

under Coding below.

Although classification systems are, by their nature, intended to define disorders

in the most specific terms possible, clinicians must recognize that there is

inevitably some degree of variability in presentation which may result in

clinically significant conditions which do not meet all specific criteria for a

given diagnosis. Therefore, some degree of judgment is necessary in the

application of these criteria. Bearing this exception in mind, all listed criteria

should generally be met for establishment of a given diagnosis, unless otherwise

specified. Clinicians should note that most diagnoses within the International

Classification of Sleep Disorders include a criterion, or criteria, that connote

clinical significance (i.e., disturbing symptoms, significant consequences,

distress or impairment in one or more functional realms). These criteria are

particularly important because, without them, many phenomena related to sleep-

wake do not rise to a level that requires clinical attention and treatment. Users

should also pay particular attention to the Notes section (where included), as

these notes provide essential definitions and details concerning application of

the criteria.

Clinicians will note a number of significant content changes from the former

edition. The most apparent of these is the collapse of all previous chronic

insomnia diagnoses into a single chronic insomnia disorder diagnosis. The

rationale for this is described in the introductory section of Insomniadisorders.

A separate diagnosis is retained for short-term insomnia. Within the Central

Disorders of Hypersomnolence section, the nomenclature for narcolepsy has

been changed to narcolepsy type 1and type 2. This modification is discussed in

the introduction to that section. Users will also find several new diagnoses

within the Sleep Related Breathing Disorders. Within the Central Sleep Apnea

Syndromes, a diagnosis of treatment-emergent central sleep apnea now appears.

This term is preferred to the widely used term complex sleep apnea because it

describes a more specific and well-defined disorder in which the central apnea

arises in the context of positive airway pressure treatment for obstructive sleep

apnea and is not attributable to another cause. Central sleep apnea associated

with other identifiable etiologies such as Cheyne-Stokes breathing or substance-

induced central sleep apnea are not classified as treatment-emergent. Assigning

a diagnosis of a sleep related hypoventilation disorder requires demonstration

of elevated PaCO2 (by direct measure of arterial blood gas or, more commonly,

by proxy measures such as end-tidal or transcutaneous CO2determination). The

new diagnosis of sleep related hypoxemia disorder should be employed when

there is sustained drop in SaO2 but PaCO2 has not been measured. Within the

parasomnia section, a single set of general criteria and a unified text now

describe disorders of arousal from non-rapid eye movement sleep, although

additional, specific criteria and separate coding are maintained for the diagnoses

within this section (i.e., confusional arousal, sleepwalking and sleep terror).

Other, somewhat less consequential additions, deletions and reassignment of

diagnoses also appear in this edition. International Classification of Sleep

Disorders, 2nd Edition contained a separate chapter forIsolated Symptoms and

Normal Variants. A small number of these were felt to qualify as formal

diagnoses at this time and have been moved to relevant sections. Other

symptoms and variants appear at the conclusion of the chapter to which they are

most applicable (e.g., snoring to the Sleep Related Breathing Disorders, long

sleeper to Central Disorders of Hypersomnolence, and movement related

variants to the Sleep Related Movement Disorder section).

A wealth of information regarding each diagnosis is contained within the

separate text headings within each diagnostic section. The outline below details

some of the specific content to be found within each text heading. These terms

are not indexed in the hard copy version of this manual because they appear
throughout the document. Users should refer to the relevant text heading within

a specific diagnosis for information related to these terms:

Alternate Names
Diagnostic Criteria
Essential Features
Associated Features
Clinical and Pathophysiological Subtypes
Demographics
includes: • Prevalence • Gender bias • Racial / ethnic bias • Cultural issues
Predisposing and Precipitating Factors
includes: • Risk factors
Familial Pattern
includes: • Genetics • Familial clusters
Onset, Course and Complications
includes: • Medical • Neurological • Psychiatric / social
Developmental Issues
includes: • Pediatric • Geriatric
Pathology and Pathophysiology
Objective Findings
includes: • Sleep logs • Actigraphy • Questionnaires • Polysomnography
• Multiple sleep latency test • Neurological ° Electroencephalogram
° Cerebrospinal fluid ° Neuroimaging ° Electromyogram ° Autonomic
• Endocrine • Genetic testing • Physical findings • Respiratory ° Arterial
blood gas ° Pulmonary function ° Ventilatory response • Cardiac
° Electrocardiogram ° Echocardiogram ° Cardiac catheterization
• Serum chemistry

Relationship to Other Classification Systems

Historically, there have been three major classifications systems for sleep

disorders. Although the International Classification of Sleep Disorders system

has, for many years, been the primary nosology for sleep medicine specialists,

both the Diagnostic and Statistical Manual of Mental Disorders (DSM) of the

American Psychiatric Association and the International Classification of

Diseases (ICD) nosology of the World Health Organization have also classified

sleep disorders. Unfortunately, these competing systems have differed

significantly in structure and content over the years. Development of DSM-5

was ongoing during the development of this manual and an effort was

undertaken to achieve the greatest degree of concordance possible between

these two systems, recognizing that the International Classification of Sleep

Disorders will inevitably contain a greater level of detail than DSM due to

differences in their target users. This goal was largely achieved although some

differences will still exist. The major change to the Insomnia section (i.e.

establishment of a single chronic insomnia disorder diagnosis) within this new

system is paralleled in DSM-5. Central Disorders of

Hypersomnolence diagnoses are organized somewhat differently in the DSM

classification than in this manual and narcolepsy criteria differ

slightly. Circadian Rhythm Sleep-Wake Disorder diagnoses are identical within

the two systems with the exception that DSM does not include a jet lag

disorder. Sleep Related Breathing Disorders are significantly more detailed

within International Classification of Sleep Disorders than DSM-5, although the

organizational structures in this section are quite similar. Sleep Related

Movement Disorders and Parasomnias are likewise similar but with fewer

overall diagnoses within DSM-5.

With the publication of International Classification of Sleep Disorders, 2nd

Edition, a major effort to expand and reorganize sleep related diagnoses within

ICD-9-CM was undertaken. This effort resulted in the inclusion of many

additional sleep related diagnoses in ICD-9-CM (primarily within the Diseases

of  the  Nervous  System  section).  The  archaic  distinction  between  “organic”  and  

“non-organic”  disorders  has  historically  been  a  guiding  principle  of  ICD,  

resulting in dissemination of sleep diagnoses to both the neurological and

mental disorder categories. Clinicians familiar with the ICD-9-CM categories

which have been employed since the most recent changes will find general

concordance between the assigned diagnostic codes found herein and the most

current version of ICD-9-CM. These ICD-9-CM codes for sleep disorders are

essentially carried over to ICD-10-CM. However, certain content revisions in

International Classification of Sleep Disorders, 3rd Edition (e.g., chronic

insomnia) necessitates a significant departure from the coding approach utilized

in ICD-9-CM and International Classification of Sleep Disorders, 2nd Edition.

This is discussed further below.

Coding
Diagnostic codes for the relevant ICD-9-CM and ICD-10-CM diagnoses can be

found at the beginning of each diagnosis section of the book. In the United

States, the former codes (ICD-9-CM) should be employed until the

implementation date for ICD-10-CM which, at the time of this writing, is

October 1, 2014. Following that date, only the ICD-10-CM codes should be

used. As already stated, clinicians should recognize that there is not precise

concordance between the assigned codes for International Classification of

Sleep Disorders, 3rd Edition diagnoses and the diagnoses listed within ICD.

Changes to the International Classification of Sleep Disorders classification

system are not reflected in the ICD system for many years. Moreover, the ICD

classification of sleep disorders has historically been significantly less detailed

than ICSD (particularly for international users not employing the Clinical

Modification (CM) version used in the United States). Hence, clinicians will

find many areas in which assigned codes found in this manual do not

correspond as closely as one would like to ICD codes. Most notably, with the

collapse of chronic insomnia diagnoses into a single disorder in International

Classification of Sleep Disorders, 3rd Edition, the assigned codes for this

diagnosis within International Classification of Sleep Disorders, 3rd Edition are

307.42 (ICD-9-CM) – “Nonorganic  persistent  disorder  of  initiating  or  

maintaining  sleep”  and  F51.01  (ICD-10-CM) – “Primary  insomnia.”  A  variety  

of other insomnia diagnoses will continue to appear in the ICD system but, with

the classification and coding changes recommended herein, these become

essentially defunct for sleep medicine clinicians. In summary, the assigned

codes  in  this  edition  represent  “best  approximations”  to  the  corresponding  ICD  

codes, but some degree of discrepancy between the systems will exist in a

number of areas.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Insomnia
This section includes sleep disorders chiefly characterized by the complaint of insomnia. For
the purpose of this manual, insomnia is defined as a persistent difficulty with sleep
initiation, duration, consolidation, or quality that occurs despite adequate opportunity and
circumstances for sleep, and results in some form of daytime impairment. These three
components of insomnia—persistent sleep difficulty, adequate sleep opportunity, and
associated daytime dysfunction—are collectively implied by text references to the term
insomnia. Among adults with insomnia, sleep complaints most typically include difficulties
initiating or maintaining sleep. Concerns about lengthy periods of nocturnal wakefulness,
insufficient amounts of nocturnal sleep, or poor sleep quality often accompany these
complaints. Individuals who report these sleep related symptoms in the absence of daytime
impairment are not regarded as having an insomnia disorder that warrants clinical attention
other than education and reassurance. Insomnia among children is often reported by their
caretakers and characterized by bedtime resistance, frequent nighttime awakenings and/or
an inability to sleep independently. Regardless of the exact nature of the nocturnal sleep
concerns, daytime impairments are reported, presumably caused by the nighttime sleep
difficulties or by some common but unidentified mechanism during sleep and wakefulness.
Daytime symptoms typically include fatigue, decreased mood or irritability, general malaise,
and cognitive impairment. Among adults, chronic insomnia may impair social or vocational
functioning and reduce quality of life, whereas in children it may lead to poor school
performance, impaired attention, and behavioral disturbance. In some patients, physical
symptoms such as muscle tension, palpitations, or headache may also be attributed to the
insomnia. Others with more severe forms of insomnia may be at increased risk for motor
vehicle and work-site accidents as well as psychiatric and cardiovascular disorders. Insomnia
often accompanies comorbid medical illnesses, mental disorders, and other sleep disorders.
It may also arise in association with the use, abuse, or exposure to certain substances. When
insomnia occurs comorbid to these conditions and is persistent and prominent, a separate
insomnia diagnosis is warranted.

The insomnia nosology presented in this text represents a marked departure from the
previous International Classification of Sleep Disorders, 2nd Edition insomnia classification
system in terms of its conceptual framework and relative simplicity. The previous insomnia
nosology of the International Classification of Sleep Disorders promoted the concept that
insomnia can exist as a primary sleep disorder or arise as a secondary form of sleep
disturbance related to an underlying primarypsychiatric, medical, or substance abuse
disorder. However, many symptoms and associated features of so-called primary and
secondary insomnias are overlapping, thus making differentiation among such subtypes
difficult, if not impossible. There is increasing recognition that even when insomnia arises
“secondary”  to  another  condition,  it  often  develops an independent course over time and
may remain as a clinically significant condition, even if the so-called primary condition is
adequately treated. Evidence suggests that insomnia, if left untreated, may adversely affect
the outcome of these comorbid conditions. Moreover, it appears that treatment of the
insomnia may improve outcome of both the sleep disturbance and the comorbid conditions.
Given these observations, insomnia seems best viewed as a comorbid disorder that
warrants separate treatment attention.
In addition to the primary vs. secondary insomnia distinction, prior editions of the
International  Classification  of  Sleep  Disorders  delineated  multiple  putative  “primary  
insomnia”  diagnostic  subtypes.  Specifically,  both  the  original  1990  version of the
International Classification of Sleep Disorders and the International Classification of Sleep
Disorders, 2nd Edition described primary insomnia subtypes such as psychophysiological
insomnia, idiopathic insomnia, inadequate sleep hygiene, and paradoxical insomnia, as
discrete diagnostic entities. Experience suggests that, in practice, it is rare to encounter
patients who meet the diagnostic criteria for exclusively one of these subtypes. In fact,
many of the diagnostic criteria delineated for these subtypes represent generic
characteristics (e.g., engaging in sleep-disruptive habits; underestimation of sleep time,
evidence of conditioned arousal) of insomnia, per se, and do not facilitate discrimination
among these subtypes or between these subtypes and  those  presumed  to  have  “secondary”  
forms of insomnia.

Both clinical experience and a growing body of empirical findings have shown that the
diagnostic distinctions advocated by previous versions of the International Classification of
Sleep Disorders are difficult to reliably ascertain and are of questionable validity. In view of
such considerations, the current manual abandons the previously employed complex and
highly specific insomnia classification scheme described by the original International
Classification of Sleep Disorders and the 2nd Edition in favor of a more global and defensible
nosology.

The manual includes three diagnostic categories for insomnia: chronic insomnia disorder,
short-term insomnia disorder, and other insomnia disorder. These diagnoses apply to
patients with and without comorbidities regardless of whether those comorbidities are
viewed as potentially sleep disruptive. Chronic insomnia disorder is characterized by chronic
sleep onset and/or sleep maintenance complaints with associated daytime impairment, and
is reserved for individuals whose sleep difficulties exceed minimal frequency and duration
thresholds shown to be associated with clinically significant morbidity outcomes. Short-term
insomnia disorder is characterized by sleep/wake difficulties that fail to meet the minimal
frequency and duration criteria of chronic insomnia disorder. Nonetheless, short-term
insomnia disorder is associated with clinically significant sleep dissatisfaction or waking
impairment. Other insomnia disorders should be assigned to those rare cases that fail to
meet criteria for short-term insomnia disorder, yet are thought to have sufficient symptoms
of insomnia to warrant clinical attention.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Chronic Insomnia Disorder

ICD-9-CM code: 307.42

ICD-10-CM code: F51.01

Alternate Names
Chronic insomnia, primary insomnia, secondary insomnia, comorbid insomnia, disorder of
initiating and maintaining sleep, behavioral insomnia of childhood, sleep-onset association
disorder, limit-setting sleep disorder.

Diagnostic Criteria

Criteria A-F must be met

A. The patient reports, or the patient's parent or caregiver observes, one or more of the
following:1

1. Difficulty initiating sleep.

2. Difficulty maintaining sleep.

3. Waking up earlier than desired.

4. Resistance to going to bed on appropriate schedule.

5. Difficulty sleeping without parent or caregiver intervention.

B. The patient reports, or the patient's parent or caregiver observes, one or more of the
following related to the nighttime sleep difficulty:

1. Fatigue/malaise.

2. Attention, concentration, or memory impairment.

3. Impaired social, family, occupational, or academic performance.

4. Mood disturbance/irritability.

5. Daytime sleepiness.

6. Behavioral problems (e.g., hyperactivity, impulsivity, aggression).

7. Reduced motivation/energy/initiative.

8. Proneness for errors/accidents.

9. Concerns about or dissatisfaction with sleep.

C. The reported sleep/wake complaints cannot be explained purely by inadequate

opportunity (i.e., enough time is allotted for sleep) or inadequate circumstances (i.e., the
environment is safe, dark, quiet, and comfortable) for sleep.

D. The sleep disturbance and associated daytime symptoms occur at least three times per
week.
E. The sleep disturbance and associated daytime symptoms have been present for at least
three months2

F. The sleep/wake difficulty is not better explained by another sleep disorder.

Notes

1. Reports of difficulties initiating sleep, difficulties maintaining sleep, or waking up too early
can be seen in all age groups. Resistance going to bed on an appropriate schedule and
difficulty sleeping without parent or caregiver intervention is seen most commonly in
children and older adults who require the supervision of a caretaker due to a significant
level of functional impairment (e.g., those with dementia).

2. Some patients with chronic insomnia may show recurrent episodes of sleep/wake
difficulties lasting several weeks at a time over several years, yet not meet the three-month
duration criterion for any single such episode. Nonetheless, these patients should be
assigned a diagnosis of chronic insomnia disorder, given the persistence of their
intermittent sleep difficulties over time.

3. Some patients who use hypnotic medications regularly may sleep well and not meet the
criteria for an insomnia disorder when they take such medications. However, in the absence
of such medications these same patients may meet the above criteria. This diagnosis would
apply to those patients particularly if they present clinically and voice concerns about their
inability to sleep without their sleep medications.

4. Many comorbid conditions such as chronic pain disorders or gastroesophageal reflux

disease (GERD) may cause the sleep/wake complaints delineated here. When such
conditions are the sole cause of the sleep difficulty, a separate insomnia diagnosis may not
apply. However, in many patients such conditions are chronic and are not the sole cause of
sleep difficulty. Key determining factors in the decision to invoke a separate insomnia
diagnosis  include:  “How  much  of  the  time  does  the  sleep  difficulty  arise  as  a  result  of  factors  
directly  attributable  to  the  comorbid  condition  (e.g.,  pain  or  GERD)?”  or  “Are  there times
that  the  sleep/wake  complaints  occur  in  the  absence  of  these  factors?”  “Have  perpetuating  
cognitive or behavioral factors (e.g., negative expectations, conditioned arousal, sleep-
disruptive habits) arisen, suggesting an autonomous aspect to the ongoing  insomnia?”  If  
there is evidence that the patient's sleep/wake complaints are not solely caused by the
medical condition, and those sleep/wake complaints seem to merit separate treatment
attention, then a diagnosis of chronic insomnia disorder should be made.

Essential Features

The essential feature of chronic insomnia disorder is a frequent and persistent difficulty
initiating or maintaining sleep that results in general sleep dissatisfaction. The sleep
complaint is accompanied by distress about poor sleep and/or impairment in family, social,
vocational, academic, or other important areas of functioning. Furthermore, the sleep
disturbance and associated waking symptoms occur despite having adequate time and
circumstances each night to obtain necessary sleep. Chronic insomnia disorder can occur in
isolation or comorbidly with a mental disorder, medical condition, or substance use.

The sleep complaints that comprise chronic insomnia disorder may include difficulties
initiating sleep or difficulties maintaining sleep. The latter complaint may include waking up
during the night with difficulty returning to sleep or having a final awakening occurring too
early, well before the desired rising time. Chronic insomnia disorder may be characterized
solely by sleep onset or sleep maintenance complaints or, more commonly, by both types of
complaints occurring together. Individuals' sleep complaints may also change over time such
that those with solely sleep onset complaints may subsequently develop sleep maintenance
complaints and vice versa. Also, those who present initially with mixed sleep onset and
sleep maintenance difficulties may later evidence one or the other of these difficulties but
not both. Complaints about poor-quality, unrefreshing, or nonrestorative sleep often
accompany sleep onset and sleep maintenance complaints, but do not suffice to define
insomnia disorder when occurring as the sole sleep complaint.

The degree of sleep disturbance required to assign a chronic insomnia disorder diagnosis is
somewhat arbitrary in that it relies primarily on individuals' subjective sleep complaints.
Moreover, the degree of sleep disturbance required to connote clinical significance varies
across age groups. Nonetheless, sleep onset latencies and periods of wakefulness after
sleep onset > 20 minutes generally connote clinically significant sleep disturbances in
children and young adults. In middle and older aged adults, onset latencies and periods of
wakefulness during sleep > 30 minutes typically connote clinical significance. Complaints of
early morning awakening are less well defined, but typically entail the termination of sleep
at least 30 minutes before the desired rising time and a concomitant reduced total sleep
time compared with the usual premorbid sleep pattern. The exact time at which early
morning awakenings occur may vary considerably as a function of usual bedtimes. For
example, a final awakening at 4:00 a.m. is likely to connote clinical significance when the
usual bedtime is 11:00 p.m. but not when the usual bedtime occurs at 9:00 p.m.

Symptoms during wakefulness accompany the sleep difficulties and result in the impairment
of normal functioning. Common waking symptoms include fatigue; reduced motivation;
reduced concentration, attention, and memory functioning; and irritability or reduced
mood. Complaints of subjective daytime sleepiness are also common, although, in contrast
to patients with hypersomnolence conditions, many with this complaint are not able to nap
in the daytime and few show unintentional sleep episodes. Reports of reduced performance
at work or school or impaired social functioning also are common. Some affected individuals
attribute errors or accidents at work to their sleep difficulties. Somatic symptoms such as
headaches or gastrointestinal dysfunction are occasionally attributed to the ongoing sleep
difficulties as well.
The fatigue of insomnia sufferers is manifest mainly as a lack of energy and desire to reduce
or limit activity levels. This symptom should be differentiated from reports of subjective
sleepiness as well as from unintended sleep episodes. Insomnia sufferers commonly report
subjective sleepiness characterized by a sense of reduced alertness and enhanced need or
desire to sleep. However, they seldom fall asleep spontaneously without intending to do so.
Despite a desire to nap, many individuals with insomnia are unable to do so. Frequent,
unintentional daytime sleep episodes are more characteristic of other types of sleep
disorders such as sleep disordered breathing, narcolepsy, idiopathic hypersomnia, and the
like.

In young children, difficulty falling asleep, staying asleep, or both are often the result of
inappropriate sleep associations or inadequate limit setting. Inappropriate sleep
associations result from a child's dependency on specific stimulation, objects, or settings for
initiating sleep or returning to sleep following an awakening; in the absence of these
conditions, sleep onset is significantly delayed. This manifestation usually presents as
frequent nighttime awakenings and/or nighttime fears or anxiety about sleeping alone. The
process of falling asleep is associated with a specific form of stimulation (e.g., rocking,
watching television), object (e.g., bottle, excessive feedings), or setting (e.g., lighted room,
parents remaining in the room, or child taken to parents' bed). When such conditions are
absent, children with this disorder experience difficulty falling asleep at bedtime and
following normal nighttime arousals. If the conditions associated with falling asleep are
reestablished, the child usually resumes sleep relatively quickly. Because sleep-onset
associations are highly prevalent in young children, the phenomenon is defined as a
disorder only if (1) the associations are highly problematic or demanding (e.g., extended
rocking, car rides); (2) sleep onset is significantly delayed or sleep is otherwise disrupted in
the absence of the associated conditions; and (3) caregiver intervention is frequently
required to aid the onset or resumption of sleep. Limit-setting issues are characterized by
bedtime stalling or bedtime refusal that is met with and reinforced by inadequate limit
setting by a caregiver. Sleep problems occur when caregivers institute no or few limits or
when limits are instituted inconsistently or in an unpredictable manner. Limit-setting sleep
problems may also result in prolonged nocturnal awakenings, depending on caregiver
response during the night.

It also should be noted that some children's needs for specific conditions for sleeping or
their resistance to go to bed may reflect underlying anxiety or fears. Fear of sleeping alone,
being in the dark, or having nightmares may lead some children to demand certain sleep
promoting conditions (presence of parent in bedroom) or to repeatedly delay their
bedtimes.

Although transient and episodic forms of insomnia occur, the clinically significant daytime
consequences of insomnia and the longer term, more serious morbidity outcomes most
typically develop when the sleep difficulties occur at least three times per week and persist
for at least three months. For this reason, these frequency and duration criteria must be
met for the assignment of a chronic insomnia disorder diagnosis. However, it is recognized
that more acute and episodic forms of insomnia may cause significant distress and
functional impairment and require clinical attention. Cases that meet all criteria except the
frequency or duration criteria for chronic insomnia disorder should be assigned a diagnosis
of short-term insomnia disorder.

Associated Features

Individuals with chronic insomnia disorder typically note feelings of reduced well-being and
general malaise during the day. In addition, excessive focus on and worry about ongoing
sleep difficulties and their associated daytime consequences are common. Thoughts about
ongoing sleep difficulties may occur through the day and may be amplified as bedtime
approaches. Frank performance anxiety about sleep is common. Although many with
insomnia may appear anxious and worry-prone, their anxiety and worry are often focused
mainly on their sleep difficulties. When anxiety and worry are more pervasive and not solely
focused on sleep problems, a comorbid anxiety disorder may be present. Many with chronic
insomnia disorder show a pattern of conditioned arousal in response to environmental cues
in their bedrooms or conscious efforts to initiate sleep. Such individuals may fall asleep
easily in settings outside of their bedrooms when not trying to sleep, but show a pattern of
cognitive and physiological arousal when lying down in their beds with the intention to fall
asleep. Some patients with this pattern may report sleeping better when away from home
than when at home. Unlike noncomplaining normal sleepers, individuals with chronic
insomnia disorder often express conscious intentions and excessive effort to sleep, only to
find sleep difficult to initiate under such circumstances.

In children, the sleep disturbance may be accompanied by daytime behavioral problems and
limit-setting difficulties during the day. In addition, the nighttime sleep disturbance often
results in poor parental sleep and associated daytime impairment. Marital conflicts
regarding how to respond to or intervene with the ongoing sleep problem may arise.
Parents also may develop negative feelings toward the child who disrupts their sleep and
demands their attention during the night.

Clinical and Pathophysiological Subtypes

Various clinical and pathophysiological subtypes of insomnia have been described in

previous nosologies. Both the American Psychiatric Association's Diagnostic and Statistical
Manual, 4th Edition, Text Revision (DSM-IV-TR) and the International Classification of Sleep
Disorders, 2nd Edition describe independently occurring or primary forms of insomnia.
Within DSM-IV-TR, the global term, primary insomnia, is applied to all forms of insomnia
that are not better explained by a coincident psychiatric, medical or substance use/abuse
disorder. Within the International Classification of Sleep Disorders, 2nd Edition system,
multiple primary insomnia subtypes are delineated. The specific primary insomnia subtypes
listed in the previous International Classification of Sleep Disorders, 2nd Edition include the
following:

Psychophysiological insomnia is characterized primarily by heightened arousal and learned

sleep-preventing associations that result in a complaint of insomnia. Patients presumed to
have this type of insomnia often have sleep difficulty when trying to sleep in their usual
sleep setting at home but may fall asleep easily in a novel sleep setting or when not trying to
sleep. They also demonstrate excessive focus on and worry about sleep and suffer from
elevated levels of cognitive and somatic arousal, particularly at bedtime.

Idiopathic insomnia is characterized by a longstanding complaint of sleep difficulties with

insidious onset occurring during infancy or early childhood. It is presumed to arise in infancy
or early childhood without discernible cause and to persist over time without sustained
periods of remission. Given its early onset, stability over time, and lifelong course, this
disorder is thought to arise from either genetically determined or congenital aberrations in
the sleep-inducing or arousal systems in the brain, or both. No consistent genetic markers or
neural pathology have been identified among those presumed to suffer from this condition.

Paradoxical insomnia, which has previously been called sleep state misperception, is
described as a complaint of severe sleep disturbance without corroborative objective
evidence of the degree of sleep disturbance claimed. Those presumed to have this form of
sleep difficulty have a marked propensity to underestimate the amount of sleep they
actually are obtaining. In essence, they are thought to perceive much of the time they
actually sleep as wakefulness. Although many such patients routinely obtain normative
amounts of sleep, as documented by standard polysomnographic measures, they complain
of the common sleep/wake symptoms of other insomnia disorders. Some studies using
neuroimaging or sleep electroencephalograph (EEG) spectral analysis techniques have
suggested that an altered sleep/wake arousal system in such individuals may explain the
apparent mismatch between their conventional objective sleep measures and subjective
sleep reports.

Inadequate sleep hygiene is presumed to result from or be sustained by daily living

activities that are inconsistent with the maintenance of good-quality sleep and normal
daytime alertness. Patients with this form of insomnia have ongoing sleep/wake difficulties
as a function of practices such as daytime napping, maintaining a highly variable sleep/wake
schedule, routinely using sleep-disruptive products (caffeine, tobacco, alcohol) too close to
bedtime, engaging in mentally or physically activating or emotionally upsetting activities too
close to bedtime, routinely using the bed and bedroom for activities other than sleep, or
failing to maintain a comfortable environment for sleep.

Behavioral insomnia of childhood is presumed to result from improper sleep training or

limit setting by parents or caretakers. Within this broader diagnosis, several subtypes have
been described. Sleep-onset association type is characterized by the child's dependency on
specific stimulation, objects, or settings for initiating sleep or returning to sleep following an
awakening; in the absence of these conditions, sleep onset is significantly delayed. Limit-
setting type is characterized by bedtime stalling or bedtime refusal that is the result of
inadequate limit setting by a caregiver. Amixed type characterized by features of sleep-
onset association difficulties and bedtime resistance represents a third subtype within this
diagnostic category.

The DSM-IV-TR and International Classification of Sleep Disorders, 2nd Edition also describe
several so-called secondary insomnias, arising from co-occurring primary or causative
conditions. Among these are the following:

Insomnia due to (another) mental disorder is thought to be caused by or secondary to a co-

occurring psychiatric condition. Insomnia is a common complaint, particularly among
patients with mood disorders and anxiety disorders. Likewise, sleep disturbance is
commonly seen in those with psychotic spectrum disorders and various Axis II (personality)
disorders. Among those individuals presumed to have insomnia due to a mental disorder,
insomnia has historically been regarded as a secondary symptom, caused by the mental
disorder itself.

Insomnia due to (a) medical condition is thought to be caused by or secondary to a co-

occurring medical condition. Like the mental disorders, many medical conditions may have
an ongoing insomnia complaint associated with them. In particular, those conditions that
cause some form of ongoing pain or discomfort, mobility limitation, or breathing
disturbance commonly have insomnia complaints accompanying them. Among those
individuals presumed to have insomnia due to a medical disorder, insomnia has historically
been regarded as a secondary symptom, caused by the medical disorder itself.

Insomnia due to drug or substance is thought to be caused by or secondary to use of or

withdrawal from a drug or substance. Many forms of prescription and nonprescription
medications, street drugs, and other commonly used substances may produce sleep
disturbances either during periods of use or upon withdrawal. Given these effects, insomnia
complaints may arise either during periods when these substances are used or following
their discontinuance. Among those individuals presumed to have insomnia due to drug or
substance, insomnia has historically been regarded as a secondary symptom, caused by the
drug or substance itself.

Despite the heuristic appeal of these various subtypes, it is often difficult to discriminate
among them in clinical practice. Many of the defining features of the so-called primary
insomnia subtypes such as conditioned arousal, poor sleep hygiene practices, and
underestimation of sleep time are ubiquitous among insomnia sufferers, per se, and are not
specific to one subgroup. This is true whether the so-called primary insomnia subtypes are
considered in isolation or if all of the primary and secondary subtypes mentioned are
considered. There is substantial symptom overlap both within the group of primary
insomnias as well as among the primary and secondary insomnias. Furthermore, many
individuals with insomnia have multiple medical and psychiatric comorbidities, making it
difficult to assign causation to any single factor. As a result, discrimination among these
subtypes has proven difficult given their current definitions and available methods for their
ascertainment. Furthermore, it is not clear that insomnia is always the result of co-occurring
medical, mental, or substance use disorders. Often insomnia may precede the onset of such
conditions, and even when precipitated by such conditions, the insomnia may evolve and
develop partial or total independence over time. In such circumstances, the term secondary
insomnia seems inappropriate. Currently there is limited understanding of mechanistic
pathways in chronic insomnia, so it is not possible to draw firm conclusions about the
association or direction of causality between insomnia and such co-occurring conditions.
Furthermore, other than the differing treatments required for distinctive comorbidities,
efficacious treatments for insomnia generally are similar across the range of insomnia
subtypes. Finally, research has provided very limited support for the reliability and validity
of the various specific subtypes discussed.

International Classification of Sleep Disorders, 2nd Edition additionally delineates the

separate pediatric diagnosis, behavioral insomnia of childhood, characterized by sleep
difficulties resulting from inappropriate sleep associations or inadequate limit setting by
parents or caretakers. Although perhaps more common in young children, inappropriate
sleep associations can occur in older age groups. For example, adults with insomnia may
report intolerance for quiet and dark settings and may not be able to fall asleep unless the
television is on. Similarly, it is not clear that limit-setting issues are involved in the sleep
difficulties of only young children. Such difficulties also can manifest during adolescence as a
function of volitionally delaying bedtimes. Similarly, they may occur in older, cognitively
impaired adults when their caretakers allow liberal daytime napping that in turn results in
disruptive awakenings and night wandering. It is also clear that many of the features of
sleep/wake dysfunction assigned to this childhood insomnia subtype overlap substantially
with the global insomnia disorder. Given these considerations, a separate childhood
insomnia diagnosis is of questionable merit.

In addition to these various subtypes, a distinctive subtype of insomnia with objectively

short sleep duration has been recently described. This group is characterized by insomnia
complaints, along with an objectively documented average sleep time less than six hours
per night and elevated morbidity risk. Because evidence in support of this insomnia is
currently limited, it is premature to delineate a separate insomnia category for this
presentation at this juncture.

Given all of these considerations, a more global and defensible approach has been chosen
for the diagnosis of those with chronic insomnia complaints. Specifically, the single diagnosis
of chronic insomnia disorder is provided for all patients who have persistent and frequent
insomnia complaints whether they occur in the presence or absence of a potentially sleep-
disruptive comorbid psychiatric illness, medical disorder, or pattern of substance use.

Demographics

The full clinical syndrome of chronic insomnia disorder occurs in about 10% of the
population, but the prevalence of transient insomnia symptoms is much higher (30% to 35%
of the population). Chronic insomnia disorder is more common in women, those with
medical/psychiatric/substance disorders, and in people in lower socioeconomic strata. It
may occur at any age but is more commonly diagnosed in older adults, most likely due to
age-related deterioration in sleep continuity and increase in medical comorbidities and
medication use that increase insomnia risk.

Insomnia associated with requirements of parental/caregiver presence at bedtime and/or

during the night, along with insomnia due to limit-setting difficulties, are estimated to occur
in 10% to 30% of children, depending on the exact definitions used. Certain subgroups of
children, such as those suffering from chronic illnesses or neurodevelopmental disorders,
have a somewhat higher prevalence of insomnia symptoms. Because children are not
expected to sleep through the night with regularity until they are three to six months of age,
six months is a reasonable age to first consider a diagnosis of chronic insomnia disorder,
unless the sleeplessness is very marked at an earlier age. Furthermore, sleep-onset
associations and limit-setting problems are strongly associated with caregivers' behaviors,
bedtime interactions, and culture. Thus, the interpretation of the nighttime awakenings and
demands for parental contact should be considered in the context of the family and culture.
Identification of sleep problems in children and adolescents are often based on specific
cultural definitions. Studies on adolescents indicate prevalence rates of 3% to 12%,
depending on the diagnostic criteria utilized, with higher frequency in girls than boys after
puberty.

Predisposing and Precipitating Factors

Individuals who have difficulty sleeping during stressful times or who report being habitual
light sleepers appear to have elevated propensity to develop chronic insomnia. Prior
transient episodes of poor sleep elevate the risk for subsequent development of a chronic
insomnia disorder. Job-related stress and factors such as death of a loved one, divorce, a
marked change in work schedule, job loss, and other major life changes are often
precipitating circumstances for chronic insomnia disorder. Personality factors that produce
anxious overconcern about health, general well-being, or daytime functioning may serve as
predisposing characteristics because individuals with chronic insomnia disorder often
display excessive preoccupation with daytime consequences of insomnia, and they devote
particular effort to what they presume are sleep-promoting practices. A psychological style
characterized by the repression and internalization of disturbing affect is characteristic of
those with chronic insomnia disorder and also may represent a predisposing trait. Parents
who have unrealistic sleep expectations for their children may predispose them to insomnia
by putting them in bed too early or assigning them too much time in bed each night.

Comorbid psychiatric conditions, particularly mood and anxiety disorders, are associated
with increased risk for chronic insomnia disorder. Likewise, comorbid restless legs syndrome
or medical disorders such as GERD or those conditions that result in chronic pain, breathing
difficulties, or immobility also are associated with increased risk for chronic insomnia
disorder. A pattern of alcohol dependence/abuse as well as the excessive use of caffeine or
other stimulants may raise risk for chronic insomnia disorder. Insomnia in children is often
associated with difficult temperament, as well as other comorbid medical and psychiatric
conditions. Unstable home situations, safety concerns and domestic abuse are likewise
significant risk factors in both children and adults. Caregiver and relationship factors are also
important to consider. Furthermore, parents of children with a current or past history of
medical problems may have difficulty setting limits, whether because of guilt, a sense that
the  child  is  “vulnerable,”  or  concerns  about  doing  psychological harm. Environmental
factors such as the child sharing a room with a parent or with other siblings, the presence of
extended family or others in the home, and cramped living accommodations may contribute
to negative sleep-onset associations or poor limit setting.

Familial Patterns

The familial pattern of insomnia is not well documented. Nonetheless, the prevalence of
insomnia is higher among monozygotic twins relative to dizygotic twins; it is also higher in
first-degree relatives than in the general population. The association is stronger with
mothers and daughters. The extent to which familial aggregation represents shared genetic
predisposition, shared environment, learned behavior (e.g., by observations of parental
behavior), or a by-product of psychopathology remains undetermined.

Onset, Course, and Complications

Onset may be insidious or acute. In the former case, individuals often report symptoms of
insomnia in early life or young adulthood. Onset of insomnia is often associated with major
life events (e.g., separation, death of a loved one), minor daily stressors, or changes in sleep
schedule.

The course of insomnia can be situational, recurrent, or persistent. The specific type of sleep
complaint may also change over time. Individuals who complain of difficulty falling asleep at
one time may later complain of difficulty maintaining sleep, and vice versa. Although short-
term insomnia often remits when the precipitating event subsides or the individual adapts
to it, sleep difficulties may also persist over time even after the initial triggering factor has
disappeared. When left untreated, insomnia may persist and gradually lead to a vicious
cycle of poor sleep, daytime impairments, apprehension of insomnia, and further sleep
disturbances. Among predisposed individuals, insomnia can also follow an intermittent
course, with recurrent episodes of sleep difficulties associated with stressful life events.
Even in persistent insomnia, there is extensive night-to-night variability, with an occasional
good night's sleep intertwined with several poor night's sleep. Approximately 70% of
individuals with insomnia at a given time continue reporting insomnia a year later, and 50%
still have insomnia three years later. Complications of persistent insomnia include increased
risks for depression, hypertension, work disability, and prolonged use of prescription or
over-the-counter sleep aids.

Among children, chronic insomnia disorder may have its onset at any time during late
infancy through the childhood years. The course of chronic insomnia disorder in young
children varies and depends on the reasons for the sleeplessness. When limit-setting factors
and negative sleep associations resolve, sleep often improves. With age, independence and
privacy become more important, and sleep difficulties may decrease. Complications may
result from the consequent sleep loss and include irritability and decreased attention and
school performance. Increased family tensions and caregiver sleep loss may also result.
Some who develop insomnia during childhood may continue to suffer from chronic
insomnia disorder into adulthood.

Developmental Issues

Developmental issues during childhood, such as separation anxiety and age/developmental

milestones, may predispose a child to developing sleep problems. For example, limit-setting
issues are often more common after the child is old enough to climb out of the crib or is
moved into a bed, has increased verbal skills, and desires greater independence. Because
children are not expected to sleep through the night with regularity until they are three to
six months of age, six months is a reasonable age to first consider a diagnosis of insomnia
disorder, unless the sleeplessness is very marked at an earlier age. However, when sleep
difficulties are persistent and pronounced in infants, underlying medical causes should be
considered (e.g., sleep disordered breathing, GERD, pain).

The specific symptoms of chronic insomnia disorder, as well as precipitating and

perpetuating factors, may vary across the adult age range. These changes may in part reflect
developmental changes across adulthood, such as the phase delay of endogenous circadian
rhythms in adolescence and young adulthood, and the phase advance and increased
number of awakenings often seen even among healthy older adults. Epidemiological studies
confirm that sleep onset difficulties and nonrestorative sleep are most common among
young adults with chronic insomnia disorder, whereas sleep maintenance insomnia and
early morning awakening are more common in middle-aged and older adults. Objective
daytime sleepiness is uncommon in younger adults with insomnia, but more common in
older adults. However, older adults may have less sleep dissatisfaction than their younger
counterparts, despite objectively worse sleep continuity. Precipitating factors for chronic
insomnia disorder may also change across the adult age range, with medical and medication
factors assuming a larger role in older adults. Likewise, perpetuating factors may vary with
the life circumstances of adults of different ages. One common example is the option of
older adults to spend large amounts of time in bed after retirement, which may exacerbate
the effects of age on sleep continuity. Finally, medical disorders and symptoms (e.g., pain,
dyspnea, and impaired mobility) and medications often play a larger role in the insomnia of
older adults in comparison with younger adults. Hypnotic medications are
disproportionately prescribed to older adults, often with limited benefit and the potential
for rebound and withdrawal insomnia.

Pathology and Pathophysiology

Studies of the pathophysiology of chronic insomnia disorder have focused on one or more
dimensions of physiological hyperarousal during sleep and wakefulness. These studies
contrast groups of insomnia sufferers, typically those without significant comorbidities, with
healthy controls using a variety of physiological measures. Many of these studies are
characterized by small sample sizes and lack of replication. Collectively these studies suggest
increased physiological arousal among individuals with insomnia, characterized by measures
such as increased heart rate, altered heart rate variability, increased whole-body metabolic
rate, elevated cortisol, adrenocorticotropic hormone, and CRF levels (particularly near sleep
onset), increased body temperature and increased high-frequency electroencephalographic
(EEG) activity during nonrapid eye movement (NREM) sleep. These studies imply heightened
activity of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis across
sleep and wakefulness that is thought to perpetuate sleep/wake dysfunction. Some
evidence also suggests that physiological dysregulation may be more evident in certain
subgroups of individuals with insomnia (e.g., those with extreme subjective-objective sleep
discrepancies or those with insomnia and short objective sleep duration). There is also some
evidence that these findings may not generalize to insomnia comorbid with mental
disorders, which may have different pathophysiological findings.

No discrete structural brain pathology can be identified in most individuals with insomnia.
Patients with insomnia comorbid with neurological disorders such as stroke, brain trauma,
and multiple sclerosis may have identifiable brain lesions, but insomnia is rarely their sole
neurological symptom. Recent studies have provided conflicting evidence regarding the
finding of reduced hippocampal or anterior cingulate volume, with most studies reporting
negative findings.

Objective Findings

Although polysomnography is not indicated in the routine evaluation of insomnia, it may be

useful to rule out other sleep disorders (e.g., sleep-disordered breathing) among some
patients who appear to meet criteria for chronic insomnia disorder. In the absence of other
sleep disorders, results of polysomnographic sleep monitoring of patients with chronic
insomnia disorder may show increased sleep latency and/or increased wake time after sleep
onset coupled with reduced sleep efficiency in comparison with age-appropriate norms.
Sleep onset latency or wake time after sleep onset often exceeds 30 minutes, although one-
hour to two-hour periods of wakefulness in bed are not uncommon. A subset of patients
shows reduced sleep duration of less than six hours per night. Some patients show altered
sleep architecture with an increase in stage N1 sleep and a decrease in slow wave sleep.
Patients with a pronounced conditioned sleep difficulty in the home environment may show
a reverse first-night effect in the sleep laboratory (i.e., better sleep on the first vs. the
second recording night). However, some patients show normal sleep times and an absence
of sleep onset or sleep maintenance difficulties on standard polysomnographic (PSG)
measures. Some insomnia patients have alterations in power density measures of the sleep
EEG when compared with individuals without sleep complaints. Specifically, these patients
often show relatively greater power in the high frequency (beta and gamma ranges)
bandwidths. Some reports have shown that elevated high-frequency power is characteristic
of insomnia patients with marked subjective-objective discrepancies in sleep measures,
compared to insomnia patients with more obvious objective sleep disturbances or
individuals without sleep complaints.

Serial monitoring with PSG or actigraphy typically shows marked night-to-night variability in
all sleep measures as well as in recorded bed and rising times. This variability is typically
greater than that of comparison groups of good sleepers.

Many patients with insomnia underestimate the actual sleep time shown by
polysomnography, and some may provide sleep estimates that fall far short of actual PSG-
recorded sleep time. This latter group has previously been categorized as having subjective
insomnia, sleep state misperception, or paradoxical insomnia. In general, patients with
insomnia tend to underestimate sleep duration and overestimate sleep latency and
awakenings, whereas good sleepers tend to overestimate sleep duration and underestimate
sleep latency and awakenings relative to PSG. This subjective-objective mismatch may be
related to physiological hyperarousal, and may be one of the core features of insomnia.

Results of the Multiple Sleep Latency Test (MSLT) usually show normal daytime alertness. In
several studies, patients with insomnia have longer mean MSLT values than control subjects,
suggesting hyperalertness or hyperarousal. A minority of insomnia patients, particularly
older adults with insomnia, have reduced mean MSLT values indicating increased sleepiness.
Such a finding should prompt consideration of other concurrent sleep disorders such as
obstructive sleep apnea.

Young children typically show essentially normal sleep during PSG monitoring when the
caregiver is present and appropriate limits are set in the laboratory.

Although PSG and MSLT testing usually are not helpful in the establishment of an insomnia
disorder diagnosis, there are circumstances that may warrant such testing with selected
patients. PSG should be considered when there are reported symptoms or bed partner
observations of sleep disordered breathing or periodic limb movements during sleep.
Patients who present insomnia symptoms accompanied by excessive daytime sleepiness
may warrant PSG and MSLT testing, particularly if narcolepsy is suspected. Patients who
show acceptable adherence to trials of well-established insomnia therapies but fail to show
adequate treatment response may benefit by PSG to rule out a comorbid sleep disorder.

Finally, a small number of functional imaging studies have been conducted during sleep and
wakefulness in insomnia and control groups. These studies suggest regionally specific
increases of relative glucose metabolism in insomnia compared to controls. Specifically,
these studies show smaller wake to NREM decreases of relative glucose metabolism in
sleep/wake-regulating regions including thalamus, upper brainstem, anterior cingulate, and
limbic cortex in insomnia patients. Self-reported and objective sleep disruptions are related
to increased relative metabolism in these regions. These findings are similar to regional
activation patterns during sleep in an animal model of stress-induced insomnia. Other
studies using nuclear magnetic resonance spectroscopy have identified reduced gamma-
aminobutyric acid (GABA) signaling in sleep-regulating regions in insomnia that correlate
with objective measure of sleep continuity. Studies examining task-related changes in blood
flow using blood oxygenation level dependent functional magnetic resonance imaging
(BOLD fMRI) paradigms have shown reduced activation relative to baseline levels in
individuals with insomnia when compared to normal sleeping controls. Task-related
activation  changes  in  the  direction  of  “normalization”  following  cognitive  behavioral  
treatment.

Differential Diagnosis

A chronic insomnia disorder that presents as difficulty initiating sleep should be

differentiated fromdelayed sleep-wake phase disorder. In the latter condition, sleep
initiation is consistently later than desired because the individual's endogenous circadian
rhythm is delayed relative to the desired sleep schedule. Sleep-onset difficulties persist, and
sleep time is reduced whenever the individual chooses bedtimes and rising times that are
too early and out of phase with the endogenous circadian rhythm. However, patients with
delayed sleep-wake phase disorder are able to fall asleep with less difficulty, and sleep a
normal amount of time, when sleeping in phase with their delayed endogenous rhythm by
selecting late bed and rising times. By comparison, those with a chronic insomnia disorder
often feel sleepy at the desired bedtime but are unable to sleep regardless of the timing of
their bed and rise times. Furthermore, sleep problems tend to be more variable on a night-
to-night basis in insomnia disorder. Given the prevalence of delayed sleep-wake phase
disorder in teenagers and young adults, it is particularly important to consider the possibility
of this alternate or comorbid diagnosis when evaluating individuals from these age groups
presenting with sleep onset insomnia complaints.

A chronic insomnia disorder that presents as a difficulty maintaining sleep with premature
morning rise times also should be differentiated from advanced sleep-wake phase disorder.
The latter tends to be more common in older adults than it is in younger adults and children.
Among those with an advanced sleep phase pattern, sleep initiation is consistently earlier
than desired because the individual's endogenous circadian rhythm is advanced relative to
the desired sleep schedule. However, total sleep time is adequate when the individual
chooses early bed and rise times that coincide with the advanced endogenous circadian
rhythm. In contrast, those with chronic insomnia disorder may display sleep maintenance
difficulties and early morning rise time regardless of the sleep schedule they select.

There can be some overlap between chronic insomnia disorder and both delayed and
advanced sleep-wake phase disorders. Patients with a delayed sleep pattern may become
chronically frustrated or anxious about their inability to initiate sleep at their desired times,
and this frustration or anxiety may continue to disrupt sleep and delay sleep onset well
beyond the sleep onset time promoted by the endogenous rhythm. Early morning
awakenings may similarly have arousing sleep disruptive effects in the setting of an
advanced sleep phase. In such circumstances both a circadian rhythm sleep-wake disorder
diagnosis and a chronic insomnia disorder diagnosis may apply and should be assigned.

Chronic insomnia disorder should also be discriminated from situational sleep difficulties
arising fromsleep-disruptive environmental circumstances. A variety of environmental
factors including excessive noise or light and extreme temperatures will disrupt the sleep of
most individuals. Also, sleeping in an area where there is imminent threat or danger to one's
safety can also be disruptive to sleep. Bed partners who snore loudly, move excessively
during sleep, or have parasomnias may also disrupt one's sleep. When an individual reports
environmental circumstances that would be regarded as disruptive to the sleep of most
individuals, a chronic insomnia disorder should not be assigned. Chronic insomnia disorder
applies only when the individual reports sleep difficulty in the context of sleep-conducive
environment circumstances or when the insomnia symptoms show some independence
from the environmental factors. When environmental circumstances are a primary cause of
sleep disturbance and associated consequences, a diagnosis of other sleep disorder may be
considered.

Chronic insomnia disorder should also be differentiated from patterns of chronic volitional
sleep restriction (insufficient sleep syndrome). Some individuals show excessive daytime
sleepiness, fatigue, and reduced sleep at night as a result of electing overly demanding
daytime schedules or by volitionally delaying sleep in order to engage in desired
recreational or social activities. However, when allowing themselves sufficient time to sleep,
they are able to initiate and maintain sleep easily and for a normal duration. Those with
chronic insomnia disorder tend to have excessive wake time and reduced sleep time despite
routinely allotting sufficient time to sleep. Moreover, chronic insomnia disorder is not
typically associated with excessive daytime sleepiness and unintentional daytime sleep
episodes, which are often observed in those with patterns of volitional sleep restriction.

Insomnia symptoms may occur comorbid with another sleep disorder, such as sleep
apnea or restless legs syndrome. A chronic insomnia disorder diagnosis would apply only
when: (1) the insomnia symptoms show some independence in their onset or variation over
time from the other symptoms of the co-occurring sleep disorder; or (2) when insomnia
symptoms persist despite adequate treatment reflected by marked symptom improvement
in the coincident sleep disorder. A chronic insomnia disorder diagnosis would not apply
when effective treatment of the coincident sleep disorder resolves the insomnia symptoms.

Among children, sleep difficulties may be present when the child has to sleep alone in a
separate room, but absent when the child is allowed to sleep with parents or when a parent
is present in the child's bedroom. An absence of sleep difficulties under the latter
circumstances does not indicate the insomnia is resolved. Only when the child is able to
sleep consistently independently is there no longer an insomnia problem. In some children,
the persistence of sleep difficulties in the absence of parents may reflect underlying
conditions such as separation anxiety or an anxiety disorder.

In young children, sleep difficulties can be the result of medical issues, including
gastroesophageal reflux, as well as developmental milestones, such as motoric, language,
and cognitive development. Children, adolescents, and adults may develop a chronic
insomnia disorder comorbid with a medical or psychiatric disorder. Insomnia symptoms may
arise as a result of either another sleep disorder, a medical condition, or a psychiatric
disorder that has sleep-disruptive effects. A chronic insomnia disorder diagnosis would
apply when: (1) the insomnia symptoms show some independence in their onset or
variation over time from the other symptoms of the co-occurring sleep, medical ,or
psychiatric disorder; or (2) when insomnia symptoms persist despite adequate treatment
reflected by marked symptom improvement in the coincident sleep, medical, or psychiatric
disorder. Because insomnia symptoms often develop some independence over time, a
chronic insomnia disorder diagnosis usually will be warranted when those symptoms are
persistent in association with a chronic medical or psychiatric disorder. A chronic insomnia
disorder diagnosis would not apply when effective treatment of the coincident sleep,
medical, or psychiatric disorder resolves the insomnia symptoms.

Unresolved Issues and Further Directions

Much remains to be learned about the underlying pathophysiological pathways leading to

insomnia and whether insomnia should be classified as a unitary disorder or subdivided into
several subtypes. Clearly, these issues are closely linked. Further studies that clarify the
pathophysiological pathways leading to insomnia ultimately will reveal whether those
meeting current criteria for chronic insomnia disorder suffer from a single disease or
multiple separate diseases with similar outward presentations.

A related unresolved issue is whether the current global classification promotes a generic
approach to insomnia therapy that ultimately fails to benefit some insomnia subgroups.
Perhaps this global classification scheme will overlook distinctive insomnia subtypes with
specific treatment needs that vary from the generic treatments typically provided.
Previous editions of the International Classification of Sleep Disorders allowed for the
assignment of an insomnia diagnosis to patients who present exclusively with complaints of
nonrestorative sleep; that is, patients who complain only of sleep that is poor in quality or
unrefreshing, in the absence of sleep-onset or sleep maintenance complaints, could qualify
for an insomnia diagnosis in previous versions of this nosology. The current version of this
nosology excludes such patients from the insomnia diagnostic categories. This decision was
based on several considerations. Most insomnia patients present with complaints of sleep
initiation or maintenance difficulties. Although a small subset of patients present with
isolated complaints of nonrestorative sleep, this complaint more commonly arises in
association with other symptoms of insomnia, or in conjunction with sleep disordered
breathing, other sleep disorders or certain chronic medical conditions (e.g., fibromyalgia or
chronic fatigue syndrome). Although various epidemiological studies have identified
subgroups who are presumed to have an insomnia disorder and present solely with a
complaint that their sleep is nonrestorative or unrefreshing, such studies typically lack
polysomnography that would be needed to rule out other occult sleep disorders as a cause.
Finally, nonrestorative sleep remains a poorly defined construct that may reflect not only a
type of sleep disturbance, but also the daytime consequences of poor sleep such as fatigue
and anergia. This construct would benefit from further definitional efforts and research to
explore its clinical significance in the context of insomnia. Given these considerations, the
isolated complaint of nonrestorative sleep was not retained as part of the diagnostic
definition of the insomnia disorders delineated in this manual.

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Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Sumário
Sleep Related Breathing Disorders .......................................................................................... 38
Obstructive Sleep Apnea Disorders......................................................................................... 40
Obstructive Sleep Apnea, Adult.............................................................................................. 40
Obstructive Sleep Apnea, Pediatric ........................................................................................ 48
Central Sleep Apnea Syndromes ............................................................................................. 52
Central Sleep Apnea with Cheyne-Stokes Breathing.............................................................. 53
Sleep Related Hypoventilation Disorders ............................................................................... 58
Obesity Hypoventilation Syndrome ........................................................................................ 59
Congenital Central Alveolar Hypoventilation Syndrome ....................................................... 63
Late-Onset Central Hypoventilation with Hypothalamic Dysfunction ................................... 66
Idiopathic Central Alveolar Hypoventilation ......................................................................... 69
Sleep Related Hypoventilation Disorders ............................................................................... 72
Sleep Related Hypoventilation Due to a Medical Disorder .................................................... 73
Sleep Related Hypoxemia Disorder ......................................................................................... 77
Sleep Related Hypoxemia ......................................................................................................... 77
Isolated Symptoms and Normal Variants ............................................................................... 81
Snoring .................................................................................................................................... 81
Catathrenia .............................................................................................................................. 83
Sleep  Related  Breathing  Disorders
The sleep related breathing disorders are characterized by abnormalities of respiration during
sleep. In some of these disorders, respiration is also abnormal during wakefulness. The
disorders are grouped into obstructive sleep apnea (OSA) disorders, central sleep apnea
disorders, sleep related hypoventilation disorders, and sleep related hypoxemia
disorder. However, many patients will meet diagnostic criteria for more than one of these
groups. In particular, many patients have a combination of obstructive and central sleep
apnea. Although a diagnosis is often based on which disorder predominates, this may vary
from night to night as well as over time in individual patients. There is also overlap in
pathophysiology, as some central apneas are associated with a closed upper airway and many
obstructive apneas begin during a time of falling ventilatory drive.

In the sections that follow, individual respiratory events (e.g., apneas, hypopneas, and
hypoventilation) are not defined; rather, reference is made to the latest version of the
American Academy of Sleep Medicine (AASM) Manual for the Scoring of Sleep and
Associated Events for these definitions. The AASM Manual for the Scoring of Sleep and
Associated Events includes different scoring rules for adult and pediatric individuals,
definitions of obstructive and central apneas and hypopneas, and rules for scoring Cheyne-
Stokes breathing and hypoventilation.

The OSA disorders are separated into adult and pediatric categories, as the presentation,
diagnostic criteria, course, and complications differ significantly. These disorders are
characterized by upper airway narrowing or closure during sleep while respiratory effort
continues (at least during some portion of the event). The use of out-of-center sleep testing
(OCST) with limited channels (electroencephalogram [EEG] is not usually recorded) is now
included in the diagnostic criteria for adult OSA.

The central sleep apnea syndromes are characterized by reduction or cessation of airflow due
to absent or reduced respiratory effort. Central apnea or hypopnea may occur in a cyclical or
intermittent fashion. Patients with central sleep apnea of various etiologies may also exhibit
OSA.

In primary central sleep apnea, the cause of the disorder is unknown (idiopathic). The arterial
partial pressure of carbon dioxide (PaCO2) during wake in these patients is normal or low.
Patients do not meet diagnostic criteria for other central sleep apnea disorders. In central
sleep apnea with Cheyne-Stokes breathing, there is a cyclical pattern of crescendo-
decrescendo respiration separated by central apneas or central hypopneas. Most patients with
this disorder have congestive heart failure (reduced or preserved ejection fraction), although,
less commonly, others exhibit this breathing pattern following stroke or in association with
other neurological disorders. In high-altitude periodic breathing, the disorder is associated
with acute ascent to high altitude. Symptoms must be present to establish the diagnosis of
high-altitude periodic breathing, as this breathing pattern is an expected finding after ascent
to altitude. Central sleep apnea due to medical or neurological condition (not Cheyne-Stokes)
is usually due to a structural lesion in the central nervous system. These disorders should be
excluded before a diagnosis of primary central sleep apnea is made. In central sleep apnea
due to drug or substance, the patient demonstrates central apneas secondary to the effects of
potent opioids or other respiratory depressants on respiratory control centers.
Treatment-emergent central sleep apnea is a new addition to the International Classification
of Sleep Disorders. In this disorder, the patient exhibits predominantly obstructive events
during diagnostic sleep testing (e.g., obstructive or mixed apneas and obstructive hypopneas),
but central apneas or central hypopneas emerge or persist on positive airway pressure
treatment without a backup rate and are the predominant residual breathing abnormality (i.e.,
obstructive events have resolved). A diagnosis of treatment-emergent central sleep apnea is
made when the central sleep apnea component is not better explained by another diagnosis
(i.e., another central sleep apnea disorder).

Sleep related hypoventilation disorders are characterized by an abnormal increase in the

arterial PCO2 (PaCO2) during sleep. Adult and pediatric hypoventilation disorders are defined
by different criteria. For adults, an increase in the arterial PCO2 (or surrogate) to greater than
55 mm Hg for at least 10 minutes or an increase  ≥  10  mm  Hg  above  the  awake  value  to  a  
value of 50 mm Hg or greater for at least 10 minutes is required. In pediatric patients, the
PaCO2 (or surrogate) must be greater than 50 mm Hg for greater than 25% of total sleep time.

In this edition of the International Classification of Sleep Disorders, there are a number of
changes in the classification of sleep related hypoventilation disorders. The obesity
hypoventilation syndrome is listed as a separate disorder given that it is both prevalent and
has distinct clinical characteristics. In contrast to other sleep related hypoventilation
disorders, a diagnosis of obesity hypoventilation syndrome requires documentation of awake
(daytime) hypoventilation (PaCO2 > 45 mm Hg). For the other disorders in this category,
awake hypoventilation may or may not be present.

In the previous version of the International Classification of Sleep Disorders, a group of

disorders were listed under the category of sleep related hypoventilation/hypoxemia
disorders. In the International Classification of Sleep Disorders, 3rd Edition, disorders
manifesting hypoventilation are separated from disorders in which only a finding of
hypoxemia (arterial oxygen desaturation) during sleep is documented. Demonstrating sleep
related hypoventilation rather than simply hypoxemia has important diagnostic and treatment
consequences. Sleep related hypoxemia disorders are characterized by sustained periods of
significantly reduced oxyhemoglobin saturation during sleep. This diagnostic category is
used when sleep related hypoventilation is either not present or the status is unknown. Sleep
related hypoxemia can occur due to hypoventilation, ventilation-perfusion mismatch, low
partial pressure of oxygen, shunt, or a combination of these factors. Many diverse etiologies
can be associated with sleep related hypoxemia. There are no longer separate diagnostic
categories for the various types of medical and neurological pathology that may contribute to
hypoventilation or hypoxemia. In the International Classification of Sleep Disorders, 2nd
Edition, these included lower airway obstruction, pulmonary parenchymal and vascular
pathology, and neuromuscular and chest wall disorders. In the International Classification of
Sleep Disorders, 3rd Edition, the specific pulmonary or neurological disorder should be
diagnosed separately, in association with a diagnosis of sleep related hypoventilation due
medical or neurological condition or sleep related hypoxemia.

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Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Obstructive Sleep Apnea Disorders

Obstructive Sleep Apnea, Adult
Obstructive Sleep Apnea, Pediatric
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Obstructive Sleep Apnea, Adult

ICD-9-CM code: 327.23

ICD-10-CM code: G47.33

Alternate Names

OSA syndrome, sleep apnea, sleep apnea syndrome, obstructive apnea, sleep disordered
breathing, obstructive sleep apnea hypopnea syndrome.

The term upper airway resistance syndrome (UARS) is subsumed under this diagnosis
because the pathophysiology does not significantly differ from that of obstructive sleep
apnea. Use of the term Pickwickian syndrome is discouraged because not only has it been
applied to those with OSA, but also indiscriminately used to describe persons who are only
obese and those with obesity hypoventilation syndrome.

Diagnostic Criteria

(A and B) or C satisfy the criteria

A. The presence of one or more of the following:

1. The patient complains of sleepiness, nonrestorative sleep, fatigue, or insomnia
symptoms.
2. The patient wakes with breath holding, gasping, or choking.
3. The bed partner or other observer reports habitual snoring, breathing interruptions, or
both  during  the  patient’s  sleep.
4. The patient has been diagnosed with hypertension, a mood disorder, cognitive
dysfunction, coronary artery disease, stroke, congestive heart failure, atrial
fibrillation, or type 2 diabetes mellitus.
B. Polysomnography (PSG) or OCST1 demonstrates:
 1. Five or more predominantly obstructive respiratory events2 (obstructive and mixed
apneas, hypopneas, or respiratory effort related arousals [RERAs])3 per hour of sleep
during a PSG or per hour of monitoring (OCST).1
OR
C. PSG or OCST1 demonstrates:
1. Fifteen or more predominantly obstructive respiratory events (apneas, hypopneas, or
RERAs)3per hour of sleep during a PSG or per hour of monitoring (OCST).1
Notes

1. OCST commonly underestimates the number of obstructive respiratory events per hour as
compared to PSG because actual sleep time, as determined primarily by EEG, is often not
recorded. The term respiratory event index (REI) may be used to denote event frequency
based on monitoring time rather than total sleep time.
2. Respiratory events defined according the latest version of the AASM Manual for the
Scoring of Sleep and Associated Events.
3. RERAs and hypopnea events based on arousals from sleep cannot be scored using OCST
because arousals by EEG criteria cannot be identified.
Essential Features

OSA is characterized by repetitive episodes of complete (apnea) or partial (hypopnea) upper

airway obstruction occurring during sleep. These events often result in reductions in blood
oxygen saturation and are usually terminated by brief arousals from sleep. By definition,
apneic and hypopneic events last a minimum of 10 seconds. Most events are 10 to 30 seconds
in duration but occasionally persist for one minute or longer. Events can occur in any stage of
sleep but more frequently occur in stages N1, N2, and R sleep than in stage N3 sleep. Events
are usually longer and associated with more severe decreases in oxygen saturation when they
occur in stage R sleep and when the individual is sleeping supine. Oxygen saturation usually
returns to baseline values following resumption of normal breathing but may remain low if
the apneic or hypopneic events are very frequent and prolonged, or if there is underlying
pulmonary pathology. Snoring between apneas is typically reported by bed partners, as are
witnessed episodes of gasping or choking and body movements that disrupt sleep. Most
patients awaken in the morning feeling tired and unrefreshed regardless of the duration of
their time in bed. Apneas, hypopneas, and snoring may be exacerbated following the
ingestion of alcohol, use of sedating medications prior to sleep, or following an increase in
body weight.

Excessive sleepiness is a major presenting complaint in many but not all cases. The
sleepiness is most evident during relaxing or inactive situations. With extreme sleepiness,
sleep may occur while actively conversing, eating, walking, or driving. In women, excessive
sleepiness is a less prominent complaint. Additionally, reports of insomnia, poor sleep
quality, and fatigue are common, particularly among women. Quality of life generally is
adversely affected by unrefreshing sleep, sleepiness, and fatigue. Bed partners may also
report sleep disruption and associated consequences. The frequency of apneas and hypopneas
during sleep correlates poorly with daytime symptom severity and impact on quality of life.
In some cases, affected individuals will not endorse any symptoms or confirm any bed
partner observations.

Associated Features
Systemic hypertension is a common finding in patients with OSA. There is substantial
clinical and epidemiologic evidence implicating OSA as a significant risk factor for
development of systemic hypertension independent of other conditions such as obesity and
smoking. Additionally, OSA is frequently observed in patients with coronary artery disease,
atrial fibrillation, and stroke, and it may be an independent risk factor for these conditions.
OSA is also associated with type 2 diabetes, and there are accumulating data to suggest that it
is a risk factor for the development of type 2 diabetes. Patients with severe disease may be at
risk for developing pulmonary hypertension and cor pulmonale, although this is usually seen
only in patients with daytime hypercapnia due to comorbid conditions such as morbid obesity
or chronic obstructive pulmonary disease (COPD). When OSA coexists with dilated
cardiomyopathy or ischemic heart disease, there may be worsening of the underlying heart
disease and predisposition to congestive heart failure. Gastroesophageal reflux symptoms,
nocturia, mood disturbance, and erectile dysfunction are sometimes reported in patients with
OSA. The disorder can also be associated with the following motor parasomnias: OSA-
induced arousals from non-rapid eye movement (NREM) sleep mimicking a primary disorder
of arousal (confusional arousal, sleepwalking, or sleep terrors); OSA-induced arousals from
REM sleep mimicking REM sleep behavior disorder; disorders of arousal from NREM
associated with slow wave sleep rebound during initiation of nasal continuous positive airway
pressure (CPAP) therapy of OSA; OSA-induced arousals linked with sleep related eating
disorder; and OSA-induced nocturnal seizures or cerebral anoxic attacks with prominent
motor activity.

Severity of OSA as determined by the frequency of apneas and hypopneas and/or degree of
oxygen desaturation correlates poorly with symptomatic sleepiness. Different measures of
sleepiness, including self-reported severity of sleepiness, commonly used indices such as the
Epworth Sleepiness Scale, and objective measures such as the Multiple Sleep Latency Test
(MSLT), are not strongly correlated and, thus, assessment of sleepiness can be difficult and
relatively unreliable. In addition, patients may adapt to any level of sleepiness over time and
fail to view it as a reportable problem. Bed partner-observed breathing pauses and disruptive
snoring may not always be accompanied by patient complaints of sleepiness. Finally, it is
important to note that sleepiness is a condition with a number of possible etiologies and a
range of manifestations (see Differential Diagnosis).

Clinical and Pathophysiological Subtypes

Apneas and hypopneas are believed to have similar pathophysiology and consequences.
Therefore, from a clinical perspective, there is little importance in distinguishing patients who
have predominantly apnea from those who have predominantly hypopnea. Occasionally,
patients may demonstrate only REM-related apneas or hypopneas, but there is no consensus
to suggest that this is a distinct clinical or pathophysiological subtype.

Some patients have relatively few arterial oxygen desaturations but a significant number of
respiratory events characterized by narrowing of the upper airway resulting in brief arousals
from sleep. Depending on the definition of hypopnea employed, these events typically meet
criteria for either hypopneas associated with arousal but no desaturation, or for RERAs.
When initially described, this latter group was said to have UARS. Current data suggest that
this condition represents simply a variant of OSA in which obstructive events result in
arousal but minimal arterial oxygen desaturation. Patients with this condition commonly
snore and report daytime sleepiness or fatigue. However, there are some reports of patients
with frequent respiratory arousals in the absence of snoring. They tend to be less obese than
individuals who have respiratory event-associated arterial oxygen saturation. The prevalence
of this group of patients is unknown. When advanced technology is used to detect changes in
airflow (as described in the AASM Manual for the Scoring of Sleep and Associated Events),
most of these patients will be diagnosed as having OSA, as defined by the criteria listed
above.

COPD and OSA frequently coexist, but there is no common pathophysiologic relationship.
Nevertheless, individuals with both disorders have greater nocturnal oxygen desaturation and
daytime hypercapnia for the same degree of bronchial airflow obstruction, and greater risk of
developing pulmonary hypertension and right heart failure. The prevalence rate for having
both conditions has been estimated to be 1%.

Demographics

OSA can occur in any age group. Estimates of prevalence are very dependent on how sleep
related respiratory events are defined, as well as their frequency and other criteria used to
define disease. Nevertheless, general population-based studies from a number of countries
indicate that OSA associated with daytime sleepiness occurs in 3% to 7% of adult men and
2% to 5% of adult women. However, because many individuals with OSA do not endorse
daytime sleepiness, the prevalence of the disease is likely much higher. A major study
yielded prevalence rates as high as 24% in men and 9% in women using only an apnea-
hypopnea index (AHI) criterion of ≥  5/hour,  although  addition  of  a  daytime  sleepiness  
criterion reduced these estimates to 4% in males and 2% in females.

The prevalence of OSA increases with age, although it appears to plateau in the elderly. The
ratio of OSA in men compared to women is approximately two to one. This disparity may
decline in middle to older age as a result of a greater risk for OSA in women after
menopause.

OSA occurs in all racial and ethnic groups. In younger and elderly groups, but not in middle-
aged groups, OSA has been reported to be more prevalent in blacks than whites. The
prevalence of OSA in Asian patients is comparable to that of whites, despite having a
generally lower body mass index (BMI). Differences in craniofacial features that predispose
Asians to developing OSA are the likely explanation. Data comparing OSA prevalence rates
among Hispanics and Native Americans to other racial/ethnic groups are sparse, although it is
clear that OSA occurs commonly in these groups.

Predisposing and Precipitating Factors

The major predisposing factor for OSA is excess body weight. It has been estimated that
~60% of moderate to severe OSA is attributable to obesity. The risk of OSA increases as the
degree of additional weight increases, with an extremely high prevalence of OSA in people
with morbid obesity. OSA patients with normal or below-normal body weight are more likely
to have upper airway obstruction due to a localized structural abnormality such as a
maxillomandibular malformation or adenotonsillar enlargement. Increasing neck
circumference predicts higher AHIs; it is not, however, independent of BMI. Instability in
ventilatory control appears to increase risk of OSA. Those patients with an exaggerated
ventilatory response to a respiratory disturbance have a greater propensity for obstructive
events. Menopause is a risk factor for this disorder in women, even after adjustment for age
and BMI. However, use of hormone replacement therapy may be protective. There are
conflicting data concerning smoking as a risk factor for OSA. Various abnormalities of the
bony and soft tissue structures of the head and neck may predispose the individual to having
OSA. These may be hereditary (e.g., mandibular size, mandibular position, palatal height) or
acquired (e.g., enlarged adenoids and tonsils). Endocrine disorders such as acromegaly and
hypothyroidism are risk factors for OSA. Adults and children with Down syndrome also have
a high prevalence of OSA. OSA is common in patients with some neurologic disorders that
affect peripheral muscles, such as myotonic dystrophy. OSA is likely made worse following
alcohol consumption or use of sedating medications before sleep and by nocturnal nasal
restriction or congestion due to abnormal morphology, rhinitis, or both.

Familial Patterns

OSA is a heritable condition as demonstrated by familial clustering of OSA patients. First-

degree relatives of OSA patients are twice as likely to have OSA in comparison to those not
affected. Clustering of symptoms that are associated with OSA such as snoring, daytime
sleepiness, and snorting or gasping also occurs. Heritability explains approximately one third
of the variation in the AHI, with a substantial proportion of the heritability explained by
obesity. Other inherited traits that might predispose an individual to developing OSA include
craniofacial morphology and ventilatory control. Familial environmental factors such as
physical activity and eating habits may play a role as well. Nevertheless, genetic studies to
date have not identified a unique gene or genes responsible for OSA heritability.

Onset, Course, and Complications

As documented in longitudinal population studies, the severity of untreated OSA measured

by the AHI tends to slowly progress over time. OSA becomes more severe in patients whose
BMI increases, but may improve with weight reduction. However, the effect of weight gain
on increasing OSA severity is greater than the impact of weight loss on decreasing OSA
severity. Moreover, the consequences of weight change are more evident in men than women.

Substantial evidence implicates OSA as a risk factor for incident systemic hypertension,
coronary artery disease, congestive heart failure, stroke, and premature mortality. Data
suggest that these effects are more evident in men and middle-aged individuals. In addition,
there is accumulating evidence to suggest that OSA is a risk factor for the development of
type 2 diabetes mellitus independent of obesity. Various arrhythmias are commonly observed
in association with OSA. Evidence suggests that OSA is particularly related to the onset and
recurrence of atrial fibrillation.

OSA may increase the severity of depression. Because of daytime sleepiness, functional
impairment occurs commonly as manifested by poor job performance, loss of employment,
impaired family relationships, and reduction in overall quality of life. The risk of motor
vehicle accidents is significantly increased among those with OSA.

Developmental Issues

OSA can occur in any age group, but in adults, prevalence accelerates between young
adulthood and middle age, with a plateau reached after approximately age 65 years. Although
OSA occurs in the elderly, it is commonly observed with few symptoms. In addition, some
evidence suggests that risk of cardiovascular disease related to OSA may be less important in
the elderly. This has raised the possibility that its presence in this age group represents a
distinct clinical variant. Pediatric OSA is discussed in a separate section (below).
Pathology and Pathophysiology

The pathophysiology underlying upper airway narrowing during sleep is multifactorial.

Patients with OSA commonly have reduced cross-sectional area of the upper airway lumen
due to either excessive bulk of soft tissues (tongue, soft palate, and lateral pharyngeal walls)
or craniofacial anatomy, or both. During inspiration, negative pressure is generated in the
lumen of the upper airway, promoting closure. However, pharyngeal dilating muscles act to
maintain patency. The activity of these muscles decreases with sleep onset, but is normally
adequate to maintain an open airway. In persons with OSA, the activity of the pharyngeal
dilating muscles becomes insufficient to prevent narrowing and/or closure of the upper
airway. This state-dependent change is the major contributing factor leading to an obstructed
upper airway. There is a further reduction in tone and phasic activity of pharyngeal dilating
muscles during REM sleep, particularly in phasic REM, which likely contributes to apneas
and hypopneas that are longer and more pronounced. Decreased end-expiratory lung volume
and falling ventilatory drive associated with hypocapnia also predispose to upper airway
narrowing or closure. In the breaths leading up to obstructive apnea, end-expiratory upper
airway caliber progressively decreases. Smaller end-expiratory lung volume may result in
smaller upper airway size due to decreased downward traction (tracheal tug). Some patients
have unstable ventilatory control (high loop gain) with resulting periods of hypocapnia that
may also contribute to upper airway narrowing.

The mechanisms of apnea/hypopnea termination are controversial. Event termination may

occur with or without an associated arousal. Some events may resolve with augmentation of
upper airway muscle tone from chemical (low PaO2, high PaCO2) and mechanical (upper
airway mechanoreceptors) stimuli, whereas others may depend on a change of sleep state
(arousal) at either a cortical or subcortical level. Cortical arousals are associated with changes
detectable by EEG, whereas other changes of state may be detectable only by direct or
indirect measures of sympathetic tone. Even if arousals are not required for termination of all
obstructive events, sleep fragmentation from arousals is nevertheless believed to be a
significant cause of excessive daytime sleepiness. Apneas and hypopneas typically last
considerably longer in REM and, in some patients, are only present in this sleep stage. The
explanation for this finding is unknown.

As an apnea or hypopnea event progresses, the patient gradually becomes more hypoxemic;
the degree of oxygen desaturation is dependent not only on the duration of the event, but also
on  the  patient’s  baseline  oxygen  saturation  and  lung  volume  and  the  presence  of  comorbid  
lung conditions. Slight hypercarbia also occurs during apneas and hypopneas and is worse
during REM sleep.

Accumulating evidence indicates that persons with OSA have elevated levels of circulating
inflammatory mediators related to repetitive episodes of oxygen desaturation and increased
sympathetic nervous system activity. Both of these findings may be important in the
pathogenesis of hypertension and cardiovascular disease related to OSA.

Objective Findings

Obstructive apneas are documented by a cessation of airflow with ongoing respiratory efforts
during PSG or an OCST. When breathing effort is recorded with respiratory inductance
plethysmography, it typically shows paradoxical movement of the rib cage and abdomen. If
esophageal manometry is used, increasingly large swings between inspiratory and expiratory
efforts are observed. Obstructive hypopneas are a reduction rather than a cessation of airflow
with ongoing respiratory effort. Increasing respiratory effort with constant or reduced flow is
indicative of increased upper airway resistance. This state is most accurately identified with a
quantitative measurement of flow and esophageal manometry, although it can be inferred
when there is obvious inspiratory airflow limitation (flattening of the inspiratory flow) on a
nasal pressure recording. Although patients with OSA have predominantly obstructive events,
they may also have variable amounts of central apneas. In some patients, these resolve with
administration of positive airway pressure, whereas in others frequent central apneas either
persist or emerge, at least during the initial night of positive airway pressure treatment.

Oxygen saturation typically declines for a variable period of time following the onset of an
event (apnea or hypopnea), with the nadir usually occurring after normal breathing resumes.
The degree of oxygen desaturation may range from as little as 1% to 2%, up to 30% to 40%
or greater. If the baseline oxygen saturation is normal, there may be no discernible drop in
oxygen saturation despite evidence of airflow limitation followed by arousal. As a result,
some events associated with evidence of increased respiratory effort (and/or flattening of
inspiratory flow) and an arousal at event termination may not meet diagnostic criteria for
apnea or hypopnea. These events are defined as RERAs. These events are presumed to have
the same underlying pathophysiology as obstructive apneas and hypopneas (upper airway
obstruction) and are considered to be as much of a risk factor for symptoms of unrefreshing
sleep, daytime somnolence, and fatigue as frank apnea or hypopnea.

The EEG may provide evidence of a brief arousal from sleep, and the submental
electromyogram may demonstrate a burst of activity indicating upper airway dilating muscle
activation immediately preceding the resumption of normal breathing. Microphones may
record a sudden resumption of loud snoring. Obstructive apneas and hypopneas may be
accompanied by bradyarrhythmias, tachyarrhythmias, or both; however, the prevalence of
this finding in patients varies widely. At the time of arousals, there is often a surge in both
sympathetic nervous system activity and systemic blood pressure.

Differential Diagnosis

In contrast to patients with OSA, those with isolated snoring will not exhibit obstructive
apneas, hypopneas, or RERAs on PSG or OCST and do not have other sleep symptoms
attributable to breathing disturbance. However, because arousal-based hypopneas and RERAs
cannot be identified with OCST, OSA cannot be excluded if the OCST is negative.

Patients with central sleep apnea have predominantly central rather than obstructive apneas,
hypopneas, or RERAs as the primary finding on PSG or OCST. If mixed apneas are
predominant, a diagnosis of OSA should be made.

Patients with obesity hypoventilation syndrome will demonstrate daytime hypercapnia.

Snoring may not be a prominent feature, although daytime sleepiness can occur. Patients
with sleep related hypoventilation disorders may show episodes of oxygen desaturation
without evidence of airflow obstruction on PSG or OCST. Confirmation of nocturnal
hypercapnia will be diagnostic. However, if obstructive apneas or hypopneas are evident, a
diagnosis of OSA should be made instead of, or in addition to, the diagnosis of sleep related
hypoventilation.
OSA must be differentiated from other causes of sleepiness such as narcolepsy, idiopathic
hypersomnia, and insufficient sleep. These conditions often can be identified on the basis of
history, but PSG and/or MSLT may be required to confirm the diagnosis.

OSA should be distinguished from other causes of nocturnal dyspnea, such as nocturnal
panic attacks, nocturnal gastroesophageal reflux, asthma, paroxysmal nocturnal dyspnea from
congestive heart failure, and nocturnal angina pectoris. In many cases, absence of snoring and
daytime sleepiness will be highly suggestive of etiologies other than OSA. However, the
absence of obstructive apneas, hypopneas, or RERAs on PSG will definitively exclude OSA
as the diagnosis.

Unresolved Issues and Further Directions

Although substantial evidence implicates OSA as a risk factor for coronary artery disease and
stroke, it has not been clearly demonstrated that treatment mitigates this risk. This is
especially a concern for patients with mild OSA who are not hypersomnolent. The
pathophysiologic mechanisms linking OSA to increased risk of coronary artery disease,
stroke, and hypertension require further investigation. Although there is a clear association
between OSA and type 2 diabetes mellitus, further studies are needed to determine whether
OSA is an independent risk factor and what mechanisms are involved.

Bibliography

Berry RB, Brooks R, Gamaldo CE, Harding SM, Lloyd RM, Marcus CL and Vaughn BV for
the American Academy of Sleep Medicine. The AASM Manual for the Scoring of Sleep
and Associated Events: Rules, Terminology and Technical Specifications, Version 2.0.3.
www.aasmnet.org. Darien, IL: American Academy of Sleep Medicine, 2014
Berry RB. Dreaming about an open upper airway. Sleep 2006;29:429–30.
Budhiraja R, Budhiraja P, Quan SF. Sleep-disordered breathing and cardiovascular disorders.
Respir Care 2010;55:1322–32.
Iber C, Ancoli-Israel S, Chesson AL, Quan SF; for the American Academy of Sleep
Medicine. The AASM manual for the scoring of sleep and associated events: rules,
terminology and technical specifications. 1st ed. Westchester, IL: American Academy of
Sleep Medicine, 2007.
Pamidi S, Aronsohn RS, Tasali E. Obstructive sleep apnea: role in the risk and severity of
diabetes. Best Pract Res Clin Endocrinol Metab 2010;24:703–15.
Patel SR, Larkin EK, Redline S. Shared genetic basis for obstructive sleep apnea and
adiposity measures. Int J Obes (Lond) 2008;32:795–800.
Pepin JL, Guillot M, Tamisier R, Levy P. The upper airway resistance syndrome. Respiration
2012;83:559–66.
Peppard PE, Taheri S. Excess weight and sleep-disordered breathing. J Appl Physiol
2005;99:1592–9.
Punjabi NM. The epidemiology of adult obstructive sleep apnea. Proc Am Thorac Soc
2008;5:136–43.
White DP. Sleep apnea. Proc Am Thorac Soc 2006;3:124–8.
Younes M. Role of arousal in the pathogenesis of obstructive sleep apnea. Am J Respir Crit
Care Med 2004;169:623–33.
Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-
disordered breathing among middle-aged adults. N Engl J Med 1993;328:1230–5.
Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a population
health perspective. Am J Respir Crit Care Med 2002;165:1217–39.
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Obstructive Sleep Apnea, Pediatric

ICD-9-CM code: 327.23

ICD-10-CM code: G47.33

Alternate Names

Obstructive sleep apnea syndrome, sleep apnea, sleep apnea syndrome, obstructive apnea,
sleep disordered breathing, sleep hypopnea syndrome, obstructive hypoventilation, and upper
airway obstruction.

The term upper airway resistance syndrome (UARS) is subsumed under this diagnosis
because the pathophysiology does not significantly differ from that of OSA. Use of the term
Pickwickian syndrome is discouraged, as this term has been used loosely to cover a
constellation of conditions including OSA and central hypoventilation.

Diagnostic Criteria

Criteria A and B must be met

A. The presence of one or more of the following:

1. Snoring.
2.  Labored,  paradoxical,  or  obstructed  breathing  during  the  child’s  sleep.
3. Sleepiness, hyperactivity, behavioral problems, or learning problems.
B. PSG demonstrates one or more of the following:
1. One or more obstructive apneas, mixed apneas, or hypopneas, per hour of sleep.1
C. A pattern of obstructive hypoventilation, defined as at least 25% of total sleep time with
hypercapnia (PaCO2 > 50 mm Hg) in association with one or more of the following:
1. Snoring.
2. Flattening of the inspiratory nasal pressure waveform.
3. Paradoxical thoracoabdominal motion.
Notes

1. Respiratory events defined according to the latest version of the AASM Manual for the
Scoring of Sleep and Associated Events.
Essential Features

Pediatric criteria for OSA apply to patients younger than 18 years. However, for the purpose
of PSG scoring, the AASM Manual for the Scoring of Sleep and Associated Events states that
adult diagnostic criteria may be used for patients aged 13 to 18 years.
Pediatric OSA is characterized by intermittent complete or partial obstruction (obstructive
apnea or hypopnea); prolonged partial upper airway obstruction; or both prolonged and
intermittent obstructions that disrupt normal ventilation during sleep, normal sleep patterns,
or both. Children with OSA may demonstrate several breathing patterns during sleep. Some
children have cyclic episodes of obstructive apnea, similar to that of adults with the
syndrome. However, some patients, particularly younger children, have a pattern of
obstructive hypoventilation, which consists of long periods of persistent partial upper airway
obstruction associated with hypercapnia, arterial oxygen desaturation, or both. Some children
may manifest a pattern of UARS similar to that seen in adults, including snoring without
identifiable airflow obstruction and increasingly negative esophageal pressure swings and
cyclic arousals. In children, upper airway obstruction occurs predominantly during REM
sleep. Children often do not have cortical arousals in response to the upper airway
obstruction, although they may have movement or autonomic arousals. Perhaps as a result of
this higher arousal threshold, sleep architecture is usually normal, with normal amounts of
slow wave sleep. Even short obstructive apneas may be associated with severe hypoxemia
because children have a lower functional residual capacity and a higher metabolic rate than
adults.

Most children with OSA present with a history of snoring and difficulty breathing during
sleep. Snoring is usually loud and may be punctuated by pauses and gasps, with associated
movements or arousal from sleep. However, some patients, particularly infants and those
with neuromuscular weakness, may not snore. Patients with obstructive hypoventilation often
have continuous snoring without pauses or arousals. Children have a very compliant rib cage.
As a result, paradoxical breathing is a prominent sign in these patients (note that paradoxical
breathing during REM sleep is a normal phenomenon in young children up to at least age
three years). A pectus excavatum may be present. Thoracic retractions may be present.
Children may sleep in unusual positions, such as seated or with their neck hyperextended.
Diaphoresis may be observed. Morning headaches may also occur. Many parents of children
with OSA  are  so  concerned  about  their  child’s  breathing  that  they  sleep  with  their  child  or  
stimulate their child to terminate the apneas.

Excessive daytime sleepiness may be present, especially in older children and adolescents,
but is seen less commonly in children than in adults with OSA. Developmental, behavioral,
and learning issues are frequently present. These may include attention problems,
hyperactivity, moodiness, irritability, and impaired academic performance.

Associated Features

Hypoxemia and hypercapnia are often present during sleep and may be severe. A prominent
sinus arrhythmia is often seen, although other arrhythmias are rare. Secondary enuresis may
occur. Breathing during wakefulness is normal, although mouth breathing secondary to
adenoidal hypertrophy may be present. Other nonspecific daytime symptoms related to
adenotonsillar hypertrophy, such as frequent upper respiratory tract infections or dysphagia,
may occur. Although studies have shown that children with OSA generally have larger tonsils
and adenoidal tissue than do other children, the size of the tonsils and adenoidal tissue does
not predict disease in individual patients.

Clinical and Pathophysiological Subtypes

Clinical presentations include OSA, obstructive hypoventilation, and recurrent arousal
associated with increased respiratory effort (RERAs).

Demographics

The prevalence in children has been estimated at 1% to 4%, but the prevalence may currently
be higher due to the pediatric obesity epidemic. The prevalence in infants and adolescents is
unknown. In prepubertal children, the disease occurs equally among boys and girls; in
adolescents, data suggest the prevalence may be higher in males. There appears to be a higher
prevalence in black children than white children; the prevalence in other ethnic groups is
unknown. The disease can occur at any age, from the neonatal period to adolescence, but in
otherwise healthy children it is most common in the preschool age (in association with
adenotonsillar hypertrophy) and in adolescents (in association with obesity).

Predisposing and Precipitating Factors

Adenotonsillar hypertrophy and obesity are the most common predisposing/precipitating

factors. Children with craniofacial abnormalities, particularly micrognathia or midfacial
hypoplasia, are at risk. Those with Down syndrome are particularly at risk for having OSA.
Children with neuromuscular diseases often have upper airway muscle weakness, which
predisposes to airway collapse. Children with cerebral palsy may be predisposed to OSA
because of spasticity, weakness, or incoordination of the upper airway muscles. Infants with
gastroesophageal reflux may develop OSA due to upper airway edema or laryngospasm.
Other medical conditions such as mucopolysaccharidosis and sickle cell disease may
predispose to OSA. Pharyngeal flap operations, typically performed to improve speech
quality in patients with cleft palate, can result in OSA. Environmental tobacco smoke
exposure has been associated with snoring and OSA.

Familial Patterns

There is evidence for an increased risk of OSA in children with affected family members.
Potential mechanisms for familial aggregation include heritability of predisposing skeletal,
soft tissue, body habitus, or respiratory control characteristics. However, the relative roles of
genetic factors versus environmental factors have not been determined.

Onset, Course, and Complications

The exact course of pediatric OSA has not been well studied. Symptoms typically begin
within the first few years of life, although the disease may not be diagnosed until many years
later. The natural course of untreated OSA is not known. A few short-term studies suggest
that some children with mild disease may improve, or conversely, have worsening of the
condition; long-term studies are not available. Complications are frequent and may be severe.
In early childhood, OSA can cause growth failure, especially when associated with a
comorbid genetic or craniofacial disorder. Cognitive and behavioral complications are
common and may include developmental delay, poor school performance, attention deficit
hyperactivity disorder, inattention and impairment in concentration, and aggressive behavior.
Rarely, cases of severe asphyxial brain damage, seizures, and coma have been reported.
Cardiovascular complications include pulmonary hypertension, cor pulmonale, and systemic
hypertension.

Developmental Issues
Developmental issues are reviewed within individual sections.

Pathology and Pathophysiology

In children, as in adults, OSA results from a combination of abnormal neuromuscular control

and anatomical narrowing of the collapsible (supracartilaginous) portion of the upper airway.
During wakefulness, the patient with OSA compensates by augmenting upper airway muscle
tone to dilate the upper airway; thus, obstructive apnea does not occur. During sleep, there is
a decrease in ventilatory drive and in neuromuscular tone, facilitating upper airway collapse.
The resultant recurrent hypoxemia, hypercapnia, and sleep disruption may lead to
neurobehavioral, cardiovascular, and growth abnormalities. Childhood OSA has also been
associated with metabolic and inflammatory abnormalities.

In most children who are otherwise healthy, upper airway narrowing is primarily due to
adenotonsillar hypertrophy. Pediatric OSA also occurs in association with obesity, which is
becoming increasingly prevalent. Other causes for upper airway narrowing include
craniofacial anomalies, particularly those involving midface hypoplasia or
micrognathia/retrognathia. In addition, children with decreased upper airway muscle tone or
abnormal upper airway muscle function, such as children with muscular dystrophy or
cerebral palsy, are at increased risk for OSA.

Objective Findings

PSG demonstrates obstructive and mixed apneas, hypopneas, or periods of obstructive

hypoventilation. In children, obstructive apneas lasting two respiratory cycles or longer are
scored. In contrast to adults with OSA, EEG arousals may or may not be present following
apneas, especially in young children, although subcortical/autonomic arousals (as manifested
by body movements, tachycardia, or measurements of pulse transit time or arterial tonometry)
may occur. Possibly as a result of the higher arousal threshold, sleep architecture is usually
preserved. Apneas and hypopneas occur primarily during REM sleep, and breathing may be
totally normal during NREM sleep. Obstructive events are frequently associated with
desaturation and hypercapnia. Evaluation of the upper airway by endoscopy, radiography,
computed tomographic scans, or magnetic resonance imaging studies may show large tonsils
and adenoidal tissue and a narrow upper airway, although these tests are not performed
routinely. Echocardiography may show evidence of right, left, or biventricular hypertrophy.

Differential Diagnosis

Pediatric OSA must be differentiated from isolated snoring. Children with snoring but
without observed apnea, labored breathing during sleep, daytime behavioral issues,
sleepiness, or other symptoms of OSA may not require further laboratory investigation.
However, children who have snoring and symptoms of OSA need evaluation to determine
whether they have isolated snoring or OSA (N.B. this distinction cannot reliably be made
clinically but should be based on PSG). Children with primary snoring do not have apneas,
gas exchange abnormalities, or frequent arousals on PSG.Central sleep apnea can be
differentiated from OSA by the lack of chest or abdominal wall movement associated with
the central apneas. Mixed apneas may be seen and are included in the diagnosis of OSA.
Children with fixed upper airway obstruction due to structural abnormalities tend to obstruct
both awake and asleep, and have stridor rather than snoring. OSA in children must be
distinguished from nonobstructive alveolar hypoventilation. Children with lung or chest wall
disease may have desaturation and hypercapnia during sleep. It may be difficult to separate
nonobstructive hypoventilation and desaturation from OSA, especially because the two
conditions may coexist. In general, children with nonobstructive hypoventilation will not
snore and will not have paradoxical inward rib cage motion during inspiration, although the
latter may be present in children with neuromuscular disease. OSA must be differentiated
from other causes of sleepiness such asnarcolepsy, idiopathic hypersomnia, and insufficient
sleep. Sleep related epilepsy may mimic obstructive apnea during sleep and may be
indistinguishable from OSA without the appropriate EEG monitoring, especially in infants
who may have only subtle motor components of seizures.

Unresolved Issues and Further Directions

There is a need for further research in many aspects of pediatric OSA. Although studies of
prevalence have been performed in the past, the prevalence has probably increased in recent
years due to the increasing prevalence of childhood obesity. Further data regarding the
prevalence in infants and adolescents is needed. The natural course of the disease, the optimal
techniques for monitoring patients during PSG, the effects of mild OSA, and the threshold
necessitating treatment require further study. The role of genetic, ethnic, and anatomic factors
in the pathophysiology of childhood OSA also requires further study.

Bibliography

Arens R, Marcus CL. Pathophysiology of upper airway obstruction: a developmental

perspective. Sleep 2004;27:997–1019.
Arens R, McDonough JM, Costarino AT, et al. Magnetic resonance imaging of the upper
airway structure in children with obstructive sleep apnea syndrome. Am J Respir Crit
Care Med 2001;164:698–703.
Marcus CL, Brooks LJ, Davidson Ward S, et al.; American Academy of Pediatrics. Diagnosis
and management of childhood obstructive sleep apnea syndrome: technical report.
American Academy of Pediatrics. Pediatrics 2012;130:e714–55.
Marcus CL, Brooks LJ, Draper K, Gozal D, et al.; American Academy of Pediatrics.
Diagnosis and management of childhood obstructive sleep apnea syndrome: clinical
practice guideline. American Academy of Pediatrics. Pediatrics 2012;130:576–84.
Redline S, Tishler PV, Schluchter M, Aylor J, Clark K, Graham G. Risk factors for sleep-
disordered breathing in children. Associations with obesity, race, and respiratory
problems. Am J Respir Crit Care Med 1999;159:1527–32.
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Central Sleep Apnea Syndromes

Central Sleep Apnea with Cheyne-Stokes Breathing
Central Apnea Due to a Medical Disorder without Cheyne-Stokes Breathing
Central Sleep Apnea Due to High Altitude Periodic Breathing
Central Sleep Apnea Due to a Medication or Substance
Primary Central Sleep Apnea
Primary Central Sleep Apnea of Infancy
Primary Central Sleep Apnea of Prematurity
Treatment-Emergent Central Sleep Apnea
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Central Sleep Apnea with Cheyne-Stokes Breathing
ICD-9-CM code: 786.04

ICD-10-CM code: R06.3

Alternate Names

Cheyne-Stokes respiration.

Diagnostic Criteria

(A or B) + C + D satisfy the criteria

A. The presence of one or more of the following:

1. Sleepiness.

2. Difficulty initiating or maintaining sleep, frequent awakenings, or nonrestorative sleep.

3. Awakening short of breath.

4. Snoring.

5. Witnessed apneas.

B. The presence of atrial fibrillation/flutter, congestive heart failure, or a neurological disorder.

C. PSG (during diagnostic or positive airway pressure titration) shows all of the following:

1. Five or more central apneas and/or central hypopneas per hour of sleep.1

2. The total number of central apneas and/or central hypopneas is > 50% of the total number of apneas
and hypopneas.2

3. The pattern of ventilation meets criteria for Cheyne-Stokes breathing (CSB).1

D. The disorder is not better explained by another current sleep disorder, medication use (e.g.,
opioids), or substance use disorder.

Notes

1. As defined by the most recent version of the AASM Manual for the Scoring of Sleep and
Associated Events.

2. If criterion C2 is not met, CSB can be listed as a polysomnographic finding.

3. A diagnosis of central sleep apnea (CSA) with CSB does not exclude a diagnosis of OSA.

Essential Features
CSA-CSB is characterized by recurrent central apneas or central hypopneas alternating with a
respiratory phase exhibiting a crescendo-decrescendo pattern of flow (or tidal volume). The longer
cycle length (> 40 seconds; typically 45 to 60 seconds) distinguishes CSB from other central sleep
apnea types. The vast majority of patients with CSA-CSB have either systolic or diastolic heart
failure. In systolic heart failure the cycle length is longer (longer respiratory phase) than in patients
with diastolic heart failure, and there is often a delay in the nadir of the associated oxygen
desaturation. Patients with CSA-CSB have normal or low daytime arterial PCO2 (PaCO2). Some
patients with heart failure have a mixture of obstructive and central apneas with more central apneas
in the later part of the night or when the patient is placed on positive airway pressure (PAP). A
diagnosis of CSA-CSB requires that events be predominantly central apneas and hypopneas with an
average frequency of at least 5/hour during a diagnostic PSG or either the diagnostic or therapeutic
portion of a split-night study. For patients with a mixture of OSA and CSA-CSB, the central apneas
may appear only after elimination of obstruction on positive airway pressure. In patient with CSA-
CSB, arousal from sleep tends to occur at the zenith of respiratory effort between contiguous central
apneas or hypopneas. This can result in sleep fragmentation. However, patients may complain of
disturbed nocturnal sleep or nocturnal dyspnea rather than daytime sleepiness.

Associated Features

Presenting features of CSB pattern during sleep may include excessive daytime sleepiness, insomnia,
or nocturnal dyspnea. Because many patients with CSA-CSB have known heart failure, their
complaints of frequent awakenings or disturbed sleep may be falsely assumed to be entirely secondary
to heart failure. Because studies have shown that approximately 60% of patients with heart failure
have some form of sleep apnea, a high index of suspicion is indicated. A CSB pattern can also occur
during wakefulness and can be observed at bedside or in the clinic. Some studies suggest that the
presence of CSA-CSB during wakefulness is associated with a worse prognosis. Although heart
failure is the major cause of CSA-CSB, recent studies suggest that it can be noted after stroke. CSA-
CSB can rarely present in an idiopathic form or be associated with renal failure.

As in other forms of CSA, apneas and hypopneas are associated with absent or reduced ventilatory
effort, respectively, due to diminished central respiratory drive. Of interest, a longer respiratory phase
between apneas is associated with a longer circulation time and delay in the saturation nadir. The CSB
breathing pattern is characteristically observed during stages N1 and N2 and usually resolves or is
attenuated during REM sleep. In patients with both OSA and CSA-CSB, the relative amount of
central and obstructive apnea can vary over time or even within the same night.

Clinical and Pathophysiological Subtypes

Some patients have combined OSA and CSA, and the CSA-CSB may not manifest until the patient is
placed on positive airway pressure treatment. These patients are considered to have both OSA and
CSA with CSB. Patients with systolic or diastolic heart failure may have CSB, but the cycle length is
longer in those with systolic dysfunction. Patients with neurological disorders may have CSB, but the
characteristic cycle length is less well described.

Demographics

CSA with CSB generally is seen in subjects older than 60 years. The prevalence of this breathing
disorder in the setting of chronic congestive heart failure has been reported to be 25% to 40%,
depending on how patients are divided into those with predominant OSA and those with CSA. In
patients with heart failure there is a striking male predominance in the occurrence of CSA-CSB. Of
interest, the use of β-blockers and angiotensin-converting enzyme inhibitors for treatment of
congestive heart failure has not decreased the prevalence of CSA-CSB. Some form of sleep apnea is
reported in 50% to 70% of patients following stroke, depending on the AHI cutoff used for diagnosis.
Although OSA predominates, central sleep apnea is also common especially in the first few days
following stroke. CSA-CSB has been reported to occur in 26% to 50% of patients in the acute period
following stroke.

Predisposing and Precipitating Factors

The most important predisposing factors are the presence of congestive heart failure, stroke, and
possibly renal failure. Within the heart failure population, risk factors for CSB pattern during sleep
include male sex, age older than 60 years, the presence of atrial fibrillation, and daytime hypocapnia
(i.e., awake PaCO2 of 38 mm Hg or less). In general, greater pulmonary congestion (higher left
ventricular end-diastolic pressure) predicts lower PaCO2. Some studies suggest that CSA-CSB occurs
more commonly in the supine position. Although renal failure is often listed as a possible cause of
CSA-CSB, there is scant literature documenting this association.

Familial Patterns

Not applicable or known.

Onset, Course, and Complications

There are no definitive data concerning the onset. However, because it is seen in the setting of
congestive heart failure, stroke, and possibly renal failure, CSA with CSB most likely has its onset
following the development of one of these illnesses. In the setting of systolic congestive heart failure,
it is associated with a poor prognosis, as indicated by a greater adjusted relative risk for mortality-
cardiac transplantation compared to patients without CSB. These data suggest that CSB pattern during
sleep participates in the pathophysiology and progression of heart failure. Its clinical significance in
the setting of stroke or other neurological disorders remains less certain. In some patients with CSA
after stroke, the pattern can transition to one of OSA. The presence of obstructive apnea following
stroke has been found to be associated with a worse prognosis.

Developmental Issues

Although there are reports of CSB in children, the condition is extremely rare in this age group. Of
interest, one study of patients with congestive heart failure across all age groups found CSB to be
absent in children but present in 40% of the adult patients with congestive heart failure. A limitation
of the study was that only ten children with congestive heart failure were studied.

Pathology and Pathophysiology

CSA with CSB generally arises because of instability in the respiratory control system. A high
ventilatory drive and delay in chemoreceptor response to changes of PaCO2 and PaO2 (due to
increased circulation time) are likely the major factors. This breathing disorder tends to occur in
individuals with a chronically low PaCO2 when awake and asleep. Hyperventilation occurs due to an
increase in the responsiveness of the peripheral and central chemoreceptors. The increased
responsiveness is believed to be due to both increased sympathetic tone and stimulation of vagal
irritant receptors in the lungs by pulmonary congestion. The PaCO2 in individuals with CSB pattern
and heart failure is closer to their apneic threshold than in those without CSB pattern (primarily due to
a smaller sleep related rise in PaCO2 in those with CSB), so that even modest increases in ventilation
can drive PaCO2 below the apneic threshold. The most common trigger factor for central apnea is an
arousal from sleep, which abruptly augments ventilation and drives PaCO2 below the apneic
threshold.

The crescendo-decrescendo pattern of tidal volume results from prolonged lung-to-chemoreceptor

circulatory delay, such that changes in PaCO2 in the lung are transmitted only very slowly to the
chemoreceptors, resulting in a gradual buildup and falloff of ventilatory stimulation. The length of the
cycle is directly proportional to lung-to-chemoreceptor circulation time and inversely proportional to
cardiac output. Accordingly, whereas the length of the ventilatory-apneic cycle in primary CSA is
typically shorter than 40 seconds, in CSB pattern it is almost invariably longer than 40 seconds
(usually 45-90 seconds). One study of patients with varying degrees of heart failure found a
considerably shorter cycle time in patients with normal ejection fraction (e.g., diastolic heart failure).
The pathophysiology of CSB pattern in the setting of stroke and renal failure has not been examined
in any detail. However, apneas in association with these medical disorders are believed to be due to a
reduction in PaCO2 below the apneic threshold. In individuals with renal failure, pulmonary
congestion (volume overload) may play a role in stimulating hyperventilation.

Objective Findings

The polysomnographic hallmarks of CSB pattern are recurrent central apneas and central hypopneas
alternating with ventilatory periods having a prolonged crescendo-decrescendo pattern of airflow
(tidal volume). CSB pattern typically occurs at the transition from wakefulness to NREM sleep and
during stages N1 and N2. It tends to dissipate in stages N3 and R. In stage N3 sleep the sleeping
PaCO2is higher (further above the apneic threshold). During REM sleep the hypoxic and hypercapnic
ventilatory responses are lower, thereby reducing the tendency for an overshoot in ventilation which
may drive PaCO2 below the apneic threshold.

Arousals are frequently seen in association with CSB and are typically noted at or near the zenith in
respiratory effort (or airflow), although can occur at or near the onset of the respiratory phase pattern.
In contrast, arousals tend to occur at apnea termination in other CSA disorders. As noted above, a
longer respiratory phase (and cycle length) is associated with lower cardiac output and longer
circulation time.

Central hypopnea, rather than apnea, can occur at the nadir in respiratory effort in patients with CSB
and have been included in calculation of the central AHI in a substantial number of investigations.
Central hypopneas are characterized by the absence of snoring, flattening in the nasal pressure or PAP
device flow signal, and thoracoabdominal paradox.

Central apneas and central hypopneas are usually accompanied by modest oxyhemoglobin
desaturation; arterial oxygen saturation seldom falls below 80% to 85%. The combination of oxygen
desaturation and arousals from sleep leads to sleep fragmentation with reduced amounts of stage N3
sleep. Additionally, PaCO2 less than 40 mm Hg is typically observed during wakefulness. In patients
with both obstructive and central apneas, the proportion of central apneas tends to increase over the
night, and this is associated with a fall in the sleeping PaCO2. The lower sleeping PaCO2 is thought to
be due to an increase in pulmonary congestion during the night with stimulation of juxtacapillary (J)
receptors in the lung interstitium and a subsequent increase in ventilatory drive. As noted above, some
patients have more CSA-CSB in the supine position.

Differential Diagnosis
Primary CSA can usually be distinguished from CSB pattern by the absence of a history of heart
failure, stroke, or renal failure and by the absence of a crescendo-decrescendo breathing pattern
between central apneas. The cycle length (apnea + ventilatory phase) in primary CSA is typically less
than 40 seconds. High-altitude periodic breathing only occurs at high altitude and is not associated
with heart failure, stroke, or renal failure. Patients with CSA due to drug or substance have a history
of use of this type of medication, and an ataxic breathing pattern may be present. If patients with CSA
associated with opioids manifest periodic breathing, the respiratory phase does not have a crescendo-
decrescendo pattern and the cycle length is shorter. Patients with CSA due to a medical or
neurological disease without Cheyne-Stokes will have central apnea that does not have Cheyne-Stokes
morphology, as the name implies. Sleep related hypoventilation and hypoxemic syndromes can be
readily distinguished from CSA-CSB by documentation of an awake PaCO2 > 45 mm Hg and/or sleep
related hypoventilation. Patients with CSA-CSB usually have an awake PaCO2 < 40 mm Hg. In
patients with sleep related hypoventilation disorders, some central apneas may be present, but these
events do not have a Cheyne-Stokes morphology. Additionally, oxygen desaturation in sleep related
hypoventilation syndromes is generally more pronounced during REM sleep. OSA is distinguished by
the presence of respiratory efforts during apneas. A few central apneas or hypopneas at sleep onset or
during REM sleep are normal, especially in elderly subjects. These cease once sleep becomes stable.

Unresolved Issues and Further Directions

The pathophysiology and clinical significance of CSB pattern have not yet been elucidated in the
setting of stroke and renal failure. Less is also known about the importance of CSB in patients with
heart failure with a normal ejection fraction.

Bibliography

Dowdell WT, Javaheri S, McGinnis W. Cheyne-Stokes respiration presenting as sleep apnea

syndrome. Clinical and polysomnographic features. Am Rev Respir Dis 1990;141:871–9.

Hall M, Xie A, Rutherford R, Ando S, Floras J, Bradley T. Cycle length of periodic breathing in
patients with and without heart failure. Am J Respir Crit Care Med 1996;154:376–81.

Lanfranchi P, Braghiroli A, Bosimini E, et al. Prognostic value of nocturnal Cheyne-Stokes

respiration in chronic heart failure. Circulation 1999;99:1435–40.

MacDonald M, Fang J, Pittman SD, White DP, Malhotra A. The current prevalence of sleep
disordered breathing in congestive heart failure patients treated with beta-blockers. J Clin Sleep Med
2008;4:38–42.

Naughton M, Benard D, Tam A, Rutherford R, Bradley T. The role of hyperventilation in the

pathogenesis of central sleep apnea in patients with congestive heart failure. Am Rev Respir Dis
1993;148:330–8.

Peer A, Lorber A, Suraiya S, Malhotra A, Pillar G. The occurrence of Cheyne-Stokes respiration in

congestive heart failure: the effect of age. Front Psychiatry 2010;1:133.

Pressman MR, Benz RL, Schleifer CR, Peterson DD. Sleep disordered breathing in ESRD: acute
beneficial effects of treatment with nasal continuous positive airway pressure. Kidney Int
1993;43:1134–9.
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Eur Respir J 2005;25:829–33.

Sin D, Fitzgerald F, Parker J, Newton G, Floras J, Bradley T. Risk factors for central and obstructive
sleep apnea in 450 men and women with congestive heart failure. Am J Respir Crit Care Med
1999;160:1101–6.

Sin DD, Logan AG, Fitzgerald FS, et al. Effects of continuous positive airway pressure on
cardiovascular outcomes in Heart failure patients with and without Cheyne-Stokes Respiration.
Circulation 2000;102:61–6.

Wedewardt J, Bitter T, Prinz C, Faber L, Horstkotte D, Oldenburg O. Cheyne-Stokes respiration in

heart failure: cycle length is dependent on left ventricular ejection fraction. Sleep Med 2010;11:137–
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Xie A, Skatrud J, Puleo D, Rahko P, Dempsey J. Apnea-hypopnea threshold for CO2 in patients with
congestive heart failure. Am J Respir Crit Care Med 2002;165:1245–50.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Sleep Related Hypoventilation Disorders

Obesity Hypoventilation Syndrome
Congenital Central Alveolar Hypoventilation Syndrome
Late-Onset Central Hypoventilation with Hypothalamic Dysfunction
Idiopathic Central Alveolar Hypoventilation
Sleep Related Hypoventilation Due to a Medication or Substance
Sleep Related Hypoventilation Due to a Medical Disorder

The primary feature of these disorders is insufficient sleep related ventilation, resulting in
abnormally elevated arterial partial pressure of carbon dioxide (PaCO2) during sleep. In
addition, demonstration of daytime hypoventilation is required for a diagnosis of obesity
hypoventilation syndrome (OHS). Awake hypoventilation is defined as an arterial partial
pressure of carbon dioxide (PaCO2) greater than 45 mm Hg. In the sleep related
hypoventilation disorders other than OHS, daytime hypoventilation may or may not be
present. If hypoventilation is present during wakefulness, it worsens during sleep in all of
these disorders.

General Criteria Sleep Related Hypoventilation

Criterion A must be met

A. Sleep related hypoventilation, as defined by the most recent version of the AASM Manual
for the Scoring of Sleep and Associated Events, is present.1,2
Notes

1. Monitoring of arterial PCO2 during sleep is not practical. Acceptable surrogates include
end-tidal PCO2 or transcutaneous PCO2.
2. Arterial oxygen desaturation is often present but is not required for the diagnosis.
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Obesity Hypoventilation Syndrome

ICD-9-CM code: 278.03

ICD-10-CM code: E66.2

Alternate Names

Hypercapnic sleep apnea, sleep related hypoventilation associated with obesity.

Use of the term Pickwickian syndrome is discouraged because not only has it been applied to those
with OSA, but also indiscriminately used to describe persons who are only obese and those with OHS.

Diagnostic Criteria

Criteria A-C must be met

A. Presence of hypoventilation during wakefulness (PaCO2 > 45 mm Hg) as measured by arterial

PCO2, end-tidal PCO2, or transcutaneous PCO2.

B. Presence of obesity (BMI > 30 kg/m2; > 95th percentile for age and sex for children).

C. Hypoventilation is not primarily due to lung parenchymal or airway disease, pulmonary vascular
pathology, chest wall disorder (other than mass loading from obesity), medication use, neurologic
disorder, muscle weakness, or a known congenital or idiopathic central alveolar hypoventilation
syndrome.

Notes

1. PSG shows worsening of hypoventilation during sleep if PaCO2 or noninvasive estimate of the
PaCO2is measured.

2. OSA is often present and, in such cases, a diagnosis of both OSA and OHS should be made.

3. Arterial oxygen desaturation is usually present but is not required for the diagnosis.

Essential Features

OHS is characterized by obesity and daytime hypercapnia (arterial PaCO2 > 45 mm Hg) that cannot
be fully attributed to an underlying cardiopulmonary or neurologic disease. Hypercapnia worsens
during sleep and is often associated with severe arterial oxygen desaturation. Hypoventilation is often
worse during REM than during NREM sleep. The majority of OHS patients have comorbid OSA
(80% to 90%). In these patients, daytime hypercapnia may improve or even normalize with adequate
PAP treatment and sustained adherence to treatment. Those OHS patients without OSA exhibit
sustained or intermittent episodes of shallow breathing during sleep associated with worsening
hypoventilation and hypoxemia. Patients with OHS may have few, if any, sleep complaints, or may
present with considerable sleep disturbance including reduced sleep efficiency and frequent
awakenings. Hypercapnia and hypoxemia may remain unnoticed for quite some time until sudden
deterioration with cardiopulmonary arrest or severe decompensation (acute or chronic hypercapnic
respiratory failure) develops.

Associated Features

Patients with OHS commonly complain of hypersomnolence. The severity of hypersomnolence may
not correlate closely with degree of hypercapnia. Other symptoms include morning headaches,
fatigue, mood disturbance and impairments of memory or concentration. Physical examination may
reveal features suggestive of cor pulmonale or circulatory congestion, such as plethora, scleral
injection, and peripheral edema. Laboratory testing commonly shows polycythemia and elevated
serum CO2 on  electrolyte  testing  (≈  serum  bicarbonate), reduced forced vital capacity during
pulmonary function testing, right heart strain, right ventricular hypertrophy and right atrial
enlargement on electrocardiography and ventricular dysfunction on echocardiography. Consequences
of chronic hypercapnia and hypoxemia include pulmonary artery hypertension, cor pulmonale, and
neurocognitive dysfunction.

Clinical and Pathophysiological Subtypes

Not applicable or known.

Demographics

OHS may be underdiagnosed if CO2 analysis  (≈  serum  bicarbonate)  is  not performed in obese patients
presenting with complaints suggestive of OHS. The prevalence of OHS in populations of patients with
OSA varies across studies but is often in the range of 10% to 15% of obese patients with OSA.
Although the prevalence of OHS is higher in men than women the difference is not as prominent as in
OSA.

Predisposing and Precipitating Factors

Obesity is believed to be the primary pathophysiologic factor responsible for hypoventilation and
hypoxemia. Greater degrees of obesity are often associated with worse sleep related hypoventilation,
but individual variations in the severity of hypercapnia at similar weights may be seen. The use of
central nervous system depressants, such as alcohol, anxiolytics, and hypnotics, may further worsen
respiratory impairment. Patients who are hypercapnic and hypoxemic during wakefulness will
invariably become even more so during sleep, in particular REM sleep, but the relationship between
wake SaO2/PaCO2 and sleep related desaturation is not sufficiently strong to have substantial
predictive value in individual patients.

Familial Patterns

Not applicable or known.

Onset, Course, and Complications

Persons who are eventually diagnosed with OHS either present initially for evaluation of suspected
OSA or are identified following one or more episodes of severe hypercapnic respiratory failure. The
course can be variable but is generally slowly progressive. Many affected individuals with severe
hypercapnia and hypoxemia develop pulmonary hypertension, heart failure, cardiac arrhythmias, and
neurocognitive dysfunction. Polycythemia is common in those with chronic hypoxia. Although the
risk of increased morbidity and mortality appears to increase with worsening sleep related
hypoventilation/hypoxemia, the specific relationship between sleep related
hypoventilation/hypoxemia and morbidity and mortality is not well defined. Obesity, itself, can lead
to other respiratory complaints, including shortness of breath, dyspnea on exertion and orthopnea,
even in the absence of demonstrable elevation of daytime PaCO2. However, in one study of inpatients
with obesity, those with hypoventilation had an 18-month mortality of 23% compared with 9% in the
group with equivalent obesity but no hypoventilation. Many patients with OHS respond to CPAP or
bilevel PAP with improvement in daytime PaCO2. However, normalization of daytime PaCO2 occurs
in only a minority of patients. In one study, 34% of OHS patients using PAP more than 4.5 hours per
night had normalization of the PaCO2. In contrast hypercapnia may worsen with oxygen therapy alone
for the associated hypoxia.

Pathology and Pathophysiology

The etiology of hypoventilation is not completely understood. Although comorbid OSA is common,
hypercapnia and hypoxemia are not entirely a function of upper airway obstruction. The importance
of various factors leading to hypoventilation likely varies among patients. It has been postulated that
sustained nocturnal hypercapnia results from the development of short (due to apnea-hypopnea) or
longer (secondary to hypoventilation) periods of hypercapnia accompanied by inadequate
compensation (i.e., CO2 unloading) during periods of ventilation between obstructive events.
Abnormal ventilatory control (blunted hypercapnic ventilatory response) allows hypercapnia to persist
into wakefulness after the cause of acute hypercapnia is no longer present. A chronic hypercapnic
state would produce an elevation of bicarbonate. Although this blunts the degree of acidosis due to an
elevated PaCO2, it reduces the compensatory CO2 ventilatory response. Impaired renal bicarbonate
excretion rate, as seen in hypoxia, heart failure, or diuretic-related chloride deficiency, may contribute
to the persistence of hypercapnia. Obesity itself is also associated with several factors that predispose
to CO2 retention. Obesity itself increases CO2 production. There is an increased work of breathing due
to mass loading from the additional weight on the respiratory pump as well as resistive loading due to
intermittent upper airway obstruction during sleep. Numerous factors impair CO2 elimination
including altered lung volumes and mechanics, ventilation-perfusion abnormalities secondary to
atelectasis or pulmonary congestion, reduced chemosensitivity and load responsiveness, and
suppression of respiratory drive due to obesity-related humoral factors, such as resistance to the
elevated leptin levels that occur in patients with the OHS (leptin is a respiratory stimulant). The
importance of these factors likely varies from patient to patient.

Objective Findings

Arterial blood gas testing during wakefulness shows hypercapnia and often hypoxemia in untreated
patients. Even with effective treatment most OHS patients continue to exhibit some degree of daytime
hypoventilation. The characteristic polysomnographic finding is sleep related hypoventilation and
arterial oxygen desaturation during sleep with or without obstructive apneas and hypopneas.
Worsening hypoventilation during sleep can be documented by an arterial blood gas measurement of
PaCO2 during sleep (rarely performed) or transcutaneous or end-tidal PCO2 measurements. Periods of
decreased tidal volume lasting up to several minutes with sustained arterial oxygen desaturation are
usually present. Intermittent arousals may be observed. OSA is present in the majority of OHS
patients, during at least a portion of the night. The transient ventilation between obstructive events
(even if associated with arousal from the preceding obstructive event) is not sufficient to prevent
worsening hypoventilation during sleep. Severe arterial oxygen desaturation is usually associated with
the obstructive events. Chronic hypoxia can be associated with polycythemia. Electrocardiography,
chest radiography, and echocardiography may demonstrate evidence of pulmonary hypertension.

The serum bicarbonate level is usually elevated due to renal compensation for chronic respiratory
acidosis (hypercapnia). In one study, a serum bicarbonate level threshold > 27 mEq/L had a sensitivity
of 92% and a specificity of 50% of identifying OHS in obese patients suspected of having OSA. This
suggests that the serum bicarbonate level may be useful to screen patients for possible OHS.
However, an arterial blood gas is required for diagnosis of OHS, as the serum bicarbonate level may
be elevated due to metabolic alkalosis.

Differential Diagnosis

The differential diagnosis includes any disorder that can give rise to hypoventilation during
wakefulness and sleep. This includes pulmonary airway and parenchymal disorders, pulmonary
vascular pathology, neuromuscular and chest wall disorders, severe untreated hypothyroidism, use of
respiratory suppressants, and congenital or idiopathic central alveolar hypoventilation
syndromes.OSA and CSA syndromes can be distinguished from sleep related hypoventilation by the
periodic alterations in airflow and accompanying periodic fluctuations in SaO2. In contrast, oxygen
desaturation due to sleep related hypoventilation is generally more sustained, usually several minutes
or longer in duration. When more than one disorder is believed to be responsible for the ventilatory
insufficiency during sleep, all pertinent diagnoses should be coded.

Unresolved Issues and Further Directions

Future research into the pathogenesis of this disorder, including renal bicarbonate homeostasis, is
needed. Because it is clinically impractical to routinely obtain arterial blood samples during sleep in
most persons suspected of this disorder, other techniques of measuring CO2 levels must be
investigated. The degree and duration of hypercapnia/hypoxemia necessary to produce adverse
consequences, such as pulmonary hypertension, in individual patients is not well defined. Little
information is available regarding the effect of oxygen therapy or noninvasive ventilation on the
course of the underlying disease. Studies are needed to determine the optimal time to initiate these
interventions and the specific subpopulations of patients who will benefit most from these therapies.

Bibliography

Berger KI, Goldring RM, Rapoport DM. Obesity hypoventilation syndrome. Semin Respir Crit Care
Med 2009;30:253.

Budweiser S, Riedl SG, Jörres RA, et al. Mortality and prognostic factors in patients with obesity-
hypoventilation syndrome undergoing noninvasive ventilation. J Intern Med 2007;261:375–83.

Littleton SW, Mokhlesi B. The pickwickian syndrome-obesity hypoventilation syndrome. Clin Chest
Med 2009;30:467–78, vii-viii.

Mokhlesi B; Tulaimat A; Evans AT et al. Impact of adherence with positive airway pressure therapy
on hypercapnia in obstructive sleep apnea. J Clin Sleep Med 2006;2:57–62.

Mokhlesi B. Obesity hypoventilation syndrome: a state-of-the-art review. Respir Care 2010;55:1347–

62.
Nowbar S, Burkart KM, Gonzales R, et al. Obesity-hypoventilation in hospitalized patients:
prevalence, effects, and outcome. Am J Med 2004;116:1–7.

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Respir Crit Care Med 2011;183:292–8.

Piper AJ. Obesity hypoventilation syndrome--the big and the breathless. Sleep Med Rev 2011;15:79–
89.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Congenital Central Alveolar Hypoventilation Syndrome

ICD-9-CM code: 327.25

ICD-10-CM code: G47.35

Alternate Names

Congenital central hypoventilation syndrome.

The term Ondine’s  curse  is  no  longer  recommended  due  to  its  negative  connotations.

Diagnostic Criteria

Criteria A and B must be met

A. Sleep related hypoventilation is present.

B. Mutation of the PHOX2B gene is present.

Notes

1. Sleep related hypoventilation may be associated with either daytime hypoventilation (PaCO2 > 45
mm Hg) or normal daytime PaCO2 levels. In either case, the PaCO2 is higher during sleep and meets
criteria for sleep related hypoventilation.

2. PSG monitoring demonstrates severe hypercapnia and arterial oxygen desaturation. Some central
apneas may occur but the predominant pattern is reduced flow/tidal volume.

3. Although the condition is termed congenital, some patients with a PHOX2B genotype may present
phenotypically later in life (and even in adulthood), especially in the presence of a stressor such as
general anesthesia or a severe respiratory illness.

Essential Features

Congenital central alveolar hypoventilation syndrome (CCHS) is a syndrome of autonomic

dysfunction, primarily the failure of automatic central control of breathing, due to a mutation of
the PHOX2B gene. CCHS is characterized by the onset of hypoventilation, usually at birth. The
hypoventilation is worse during sleep than wakefulness and is unexplained by primary pulmonary,
neurological, or metabolic disease. CCHS typically presents in an otherwise normal-appearing infant
who is noted to have cyanosis, feeding difficulties, hypotonia or, less commonly, central apnea. Some
children are diagnosed following cardiovascular collapse. The infant requires intubation and then
cannot be weaned from mechanically assisted ventilation, despite appearing vigorous and having a
normal chest radiograph. Some infants may appear to breathe adequately on clinical examination but
experience episodes of hypoventilation (not necessarily apnea) characterized by hypoxemia and
hypercapnia. Patients with CCHS may occasionally present later in life with cyanosis, an apparent
life-threatening event, cor pulmonale, or hypoxic neurological damage. CCHS has been diagnosed in
adults who present with respiratory failure following anesthesia or in association with a minor
respiratory illness; these patients usually have a mild mutation, and may have evidence of
longstanding hypoxemia including cognitive deficits. Most patients with CCHS have sufficiently
severe hypoventilation during sleep that they require mechanically assisted ventilation, although this
state-dependent difference may not be apparent during early infancy. Some patients (~15%)
hypoventilate during wakefulness as well as during sleep and require continuous ventilatory support.
However, most patients with CCHS do not require ventilatory support during wakefulness but may
have subtle abnormalities in gas exchange when physically inactive or during vigorous exercise.

Associated Features

Associated autonomic abnormalities include Hirschsprung disease in approximately 16% of patients

with CCHS, autonomic dysfunction (e.g., decreased heart rate variability or hypotension), neural
tumors (e.g., ganglioneuromas or ganglioneuroblastomas), swallowing dysfunction during the early
years, and ocular abnormalities (e.g., strabismus). Most patients are cognitively normal, although
developmental delay may be present, especially in patients in whom the hypoventilation has not been
well controlled.

Clinical and Pathophysiological Subtypes

Research suggests that severity of illness is related to the type of mutation present. Most patients have
a polyalanine expansion mutation; those with more polyalanine repeats are more likely to have severe
disease including waking hypoventilation. Patients with a point mutation or frame shift mutations are
at greater risk for neural tumors.

Demographics

The prevalence of CCHS is not known, but the disease is rare. The condition occurs equally among
both sexes and all ethnic/racial groups.

Predisposing and Precipitating Factors

This is a congenital genetic syndrome.

Familial Patterns

CCHS usually occurs as a de novo mutation, but siblings with the condition have been reported. As
the gene is dominant, patients are at risk of having children with CCHS.

Onset, Course, and Complications

The condition is genetic and is therefore present from birth, but some patients may present later in
life. The physiological abnormalities of CCHS persist for life and are not ameliorated over time.
However, the clinical consequences of hypoventilation can be prevented by providing adequate
ventilatory support. If untreated, death usually results from cor pulmonale or complications of apnea
or severe hypoventilation. Patients with poorly controlled CCHS may develop mental retardation,
growth failure, seizures, or cor pulmonale. When treated, infants with CCHS may improve over the
first six to 12 months. Some patients who initially require ventilatory support 24 hours a day may
progress to adequate ventilation during wakefulness. However, patients continue to require ventilatory
support during sleep. Conversely, some patients may develop the need for continuous ventilatory
support. It is unclear whether these patients had conditions that worsened, were not adequately
evaluated and treated initially, or were associated with changing ventilatory demands. Even with
treatment, patients with CCHS require close monitoring, particularly during infancy. Minor medical
illnesses, such as upper respiratory tract illnesses or diarrhea, may precipitate bouts of respiratory
failure. Edema and lethargy are often early signs of impending respiratory failure. The clinical signs
of hypoxemia and hypoventilation in these patients may be subtle, as the children do not show signs
of distress or increased work of breathing, such as retractions and nasal flaring. As a result, gas
exchange abnormalities may progress for some time without notice until the child appears to
deteriorate suddenly with cardiopulmonary arrest or severe decompensation.

Developmental Issues

Not applicable.

Pathology and Pathophysiology

The exact pathophysiology of CCHS is unknown. Radiologic and postmortem studies have not shown
gross central nervous system abnormalities. The PHOX2B gene plays a role in the development of the
autonomic system. Functional MRI and physiologic studies have shown widespread cerebral
abnormalities in response to stimuli such as exogenous hypercapnia.

Objective Findings

Hypoxemia and hypercapnia are present on PSG during sleep. Central apneas may be present, but
hypoventilation associated with decreased tidal volume and respiratory rate is more common. In
contrast to most types of sleep disordered breathing in children, abnormalities may be more severe
during NREM than during REM sleep. Patients may not arouse from sleep despite severe gas
exchange abnormalities. Paradoxical breathing and snoring do not typically occur.

Patients with CCHS have flat rebreathing hypoxic and hypercapnic responses, although they may
respond to transient ventilatory challenges of the peripheral chemoreceptors. Arterial blood gases may
be normal during wakefulness but will be abnormal if obtained from an arterial line during sleep. In
patients with chronically untreated or poorly controlled CCHS, a compensated respiratory acidosis
may be present. In these patients, polycythemia may be present and the serum bicarbonate level may
be elevated. Computed tomography and MRI scans of the head are normal. Electrocardiography,
echocardiography, or cardiac catheterization may reveal evidence of pulmonary hypertension.
Pulmonary function tests may be normal or show evidence of mild obstructive or restrictive lung
disease resulting from associated conditions such as tracheitis.

Differential Diagnosis

CCHS must be distinguished from other forms of central hypoventilation, such as central
hypoventilation due to Chiari malformation, other causes of central nervous system disturbance such
as trauma or tumors, metabolic conditions such as Leigh disease, or obesity hypoventilation
syndrome. CCHS must also be distinguished from hypoventilation secondary to muscle weakness due
to conditions such as diaphragmatic paralysis or muscular dystrophy. Infants presenting with apnea or
an apparent life-threatening event due to causes such as gastroesophageal reflux may be thought to
have CCHS. However, these infants typically have intermittent episodes of apnea rather than
sustained hypoventilation, and the episodes typically resolve once the primary cause has been treated.
CCHS patients presenting with cor pulmonale may be misdiagnosed as having congenital heart
disease.

Unresolved Issues and Further Directions

There are many unresolved issues regarding CCHS, including prevalence data, precise genotype-
phenotype correlations, effect of aging on patients with CCHS, long-term outcome of children with
CCHS born to parents with CCHS, and the exact nature of the gene-encoded deficit.

Bibliography

Amiel J, Laudier B, Attie-Bitach T, et al. Polyalanine expansion and frameshift mutations of the
paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome. Nat Genet
2003;33:459–61.

Gozal D, Marcus CL, Shoseyov D, Keens TG. Peripheral chemoreceptor function in children with the
congenital central hypoventilation syndrome. J Appl Physiol 1993;74:379–87.

Macey PM, Woo MA, Macey KE, et al. Hypoxia reveals posterior thalamic, cerebellar, midbrain, and
limbic deficits in congenital central hypoventilation syndrome. J Appl Physiol 2005;98:958–69.

Marcus CL, Jansen MT, Poulsen MK, Keens SE, Nield TA, Lipsker LE et al. Medical and
psychosocial outcome of children with congenital central hypoventilation syndrome. J Pediatr
1991;119:888–95.

Paton JY, Swaminathan S, Sargent CW, Hawksworth A, Keens TG. Ventilatory response to exercise
in children with congenital central hypoventilation syndrome. Am Rev Respir Dis 1993;147:1185–91.

Paton JY, Swaminathan S, Sargent CW, Keens TG. Hypoxic and hypercapnic ventilatory responses in
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Weese-Mayer DE, Berry-Kravis EM, Ceccherini I, Keens TG, Loghmanee DA, Trang H. An official
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and management. Am J Respir Crit Care Med 2010;181:626–44.

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congenital central hypoventilation syndrome. Respir Physiol Neurobiol 2005;149:73–82.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Late-Onset Central Hypoventilation with Hypothalamic Dysfunction

ICD-9-CM code: 327.26

ICD-10-CM code: G47.36

Alternate Names

Late-onset central hypoventilation syndrome; rapid-onset obesity with hypothalamic

dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD).

Diagnostic Criteria

Criteria A-E must be met

A. Sleep related hypoventilation is present.

B. Symptoms are absent during the first few years of life.
C. The patient has at least two of the following:
1. Obesity.
2. Endocrine abnormalities of hypothalamic origin.
3. Severe emotional or behavioral disturbances.
4. Tumor of neural origin.
D. Mutation of the PHOX2B gene is not present.
E. The disorder is not better explained by another sleep disorder, medical or neurological
disorder, medication use, or substance use disorder.
Notes

1. Central apneas may occur but the predominant pattern is reduced flow/tidal volume
associated with hypoventilation and arterial oxygen desaturation.
Essential Features

Late-onset central hypoventilation with hypothalamic dysfunction is a disorder of central

control of ventilation. Patients are usually healthy until early childhood (often 2-3 years of
age) when they develop hyperphagia and severe obesity, followed by central hypoventilation,
which often presents as respiratory failure. The respiratory failure may be precipitated by a
mild respiratory illness or anesthesia. Patients require ventilatory support during sleep; most
patients breathe adequately during wakefulness but some need ventilatory support during
both wakefulness and sleep. The hypoventilation persists even if the patients lose weight,
differentiating the condition from obesity hypoventilation syndrome. Patients often develop
hypothalamic endocrine dysfunction characterized by increased or decreased hormone levels,
which may include one or more of the following: diabetes insipidus, inappropriate
antidiuretic hormone hypersecretion, precocious puberty, hypogonadism, hyperprolactinemia,
hypothyroidism, and decreased growth hormone secretion. Mood and behavior abnormalities,
sometimes severe, have frequently been reported. Developmental delay or autism may be
present, but many patients are cognitively normal. Other symptoms of hypothalamic
dysfunction, such as temperature dysregulation, have been reported.

Associated Features

Tumors of neural origin such as ganglioneuroma may occur.

Clinical and Pathophysiological Subtypes

None known.
Demographics

There are no prevalence data. The disorder seems to occur equally among males and females.

Familial Patterns

Familial cases have not been reported.

Predisposing and Precipitating Factors

Unknown. Patients do not have the PHOX2B genetic mutation of congenital central
hypoventilation syndrome.

Onset, Course, and Complications

Patients are typically normal at birth. Obesity often begins in early childhood, perhaps
because the child is old enough to walk around and obtain his/her own food. Respiratory
failure typically presents several years after the onset of obesity, and requires ventilatory
support via face mask or tracheostomy. The respiratory failure does not improve over time.
Death has been reported from respiratory failure, cor pulmonale, or hypernatremia secondary
to diabetes insipidus; case series have reported a high mortality.

Developmental Issues

Not applicable.

Pathology and Pathophysiology

The cause of the disorder is not known. The brain typically appears normal on imaging or at
autopsy, or may show secondary signs of hypoxemia.

Objective Findings

Hypoxemia and hypercapnia are present on PSG during sleep. Central apneas may be present,
but hypoventilation associated with decreased tidal volume and respiratory rate is more
common. Obstructive apneas may occur but are not the primary abnormality.

Patients have flat hypoxic and hypercapnic responses. Oxygen and carbon dioxide
determinations may be normal during wakefulness but will demonstrate hypoxemia and
hypercapnia during sleep. In patients with chronically untreated or poorly controlled
hypoventilation, a compensated respiratory acidosis may be present, with elevated serum
bicarbonate levels. In these patients, polycythemia may be present. Serum tests may show
evidence of endocrine abnormalities; hypernatremia is common. Computed tomography and
MRI scans of the head are normal. Electrocardiography, echocardiography, or cardiac
catheterization may reveal evidence of pulmonary hypertension. Pulmonary function tests
may be normal or show evidence of mild obstructive or restrictive lung disease resulting from
associated conditions such as tracheitis.

Differential Diagnosis
The disorder can be distinguished from late presentation of congenital central
hypoventilation syndrome by testing for the PHOX2B gene. Genetic testing may also be
useful in distinguishing the disorder from Prader-Willi syndrome, which is characterized by a
known genetic abnormality. Most children with Prader-Willi syndrome have hypotonia at
birth and more severe developmental delay. The disorder can be distinguished from obesity
hypoventilation syndrome by the presence of endocrine abnormalities and other associated
hypothalamic abnormalities, and by the persistence of hypoventilation despite weight loss. In
addition, the patients typically have a totally flat hypercapnic ventilatory response rather than
the blunted response seen in children with obesity hypoventilation syndrome. The disorder
should be distinguished from isolated hypopituitarism or other hypothalamic disease without
hypoventilation, and from obesity-related OSA.

Unresolved Issues and Further Directions

The etiology of the disorder is not known. Although the disorder shares some features of
congenital central hypoventilation syndrome, including the presence of neural tumors, it does
not share the same gene. Little information is available on prevalence or long-term prognosis.

Bibliography

Ize-Ludlow D, Gray JA, Sperling MA, et al. Rapid-onset obesity with hypothalamic
dysfunction, hypoventilation, and autonomic dysregulation presenting in childhood.
Pediatrics 2007;120:e179–88.
Katz ES, McGrath S, Marcus CL. Late-onset central hypoventilation with hypothalamic
dysfunction: a distinct clinical syndrome. Pediatr Pulmonol 2000;29:62–8.
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Idiopathic Central Alveolar Hypoventilation

ICD-9-CM code: 327.24

ICD-10-CM code: G47.34

Alternate Names

Alveolar hypoventilation, central alveolar hypoventilation, idiopathic central alveolar

hypoventilation, nonapneic alveolar hypoventilation, primary alveolar hypoventilation.

Diagnostic Criteria

Criteria A and B must be met

A. Sleep related hypoventilation is present.

B. Hypoventilation is not primarily due to lung parenchymal or airway disease, pulmonary
vascular pathology, chest wall disorder, medication use, neurologic disorder, muscle
weakness, or obesity or congenital hypoventilation syndromes.
Notes
1. The predominant respiratory pattern is one of reduced tidal volume or ataxic breathing
with associated arterial oxygen desaturation. Although OSA may be present, it is not
believed to be the major cause of hypoventilation. When criteria are met, a diagnosis of
both OSA and idiopathic central alveolar hypoventilation may be made.
2. Arterial oxygen desaturation is often present but is not required for the diagnosis.
Essential Features

Idiopathic central alveolar hypoventilation is defined as the presence of decreased alveolar

ventilation resulting in sleep related hypercapnia and hypoxemia in individuals with
presumed normal mechanical properties of the lung and respiratory pump. Thus, chronic
hypoventilation during sleep exists without any readily identifiable impairments of
respiration, such as pulmonary airway or parenchymal conditions, neurologic, neuromuscular
or chest wall abnormalities, severe obesity, other sleep related breathing disorder, or use of
respiratory depressant medications or substances. Diurnal as well as nocturnal
hypoventilation is believed to be due primarily to blunted chemoresponsiveness to CO2 and
O2. However, reported cases are few and not studied in enough detail to conclusively
establish a well-defined etiology. Alternatively, these cases may represent a mixed group of
patients with varied underlying conditions erroneously deemed idiopathic as a result of
incomplete diagnostic work-up. Patient may complain of morning headaches, fatigue,
neurocognitive decline and sleep disturbance, or may be entirely asymptomatic. Frequent
episodes of shallow breathing may be noted to occur during sleep.

Associated Features

Consequences of chronic hypercapnia and hypoxemia include pulmonary artery hypertension,

cor pulmonale, and neurocognitive dysfunction. Patients with other comorbid sleep related
breathing disorders are likely to experience greater severity and duration of sleep related
hypoventilation than are patients with isolated idiopathic central hypoventilation.

Clinical and Pathophysiological Subtypes

Not applicable or known.

Demographics

Not known. It is likely that some patients with this diagnosis may have an underlying
anatomic or functional defect affecting respiratory mechanics and ventilatory drive which
remains undiagnosed.

Predisposing and Precipitating Factors

The use of central nervous system depressants, such as alcohol, anxiolytics, and hypnotics,
may further worsen hypercapnia/hypoxemia. Patients who are hypercapnic and hypoxemic
during wakefulness will generally become even more so during sleep, in particular REM
sleep, but the relationship between wake SaO2/PaCO2 and sleep related desaturation is not
sufficiently strong to have substantial predictive value in individual patients.

Familial Patterns

Not applicable or known.

Onset, Course, and Complications

The onset of the condition is variable, often presenting in adolescence or early adulthood. The
disorder is generally slowly progressive. Many affected individuals with severe hypercapnia
and hypoxemia develop respiratory impairment, pulmonary hypertension, heart failure,
cardiac arrhythmias, and neurocognitive dysfunction. Polycythemia is common in those with
chronic hypoxia. Although the risk of increased morbidity and mortality appears to increase
with worsening sleep related hypoventilation/hypoxemia, the specific relationship between
sleep related hypoventilation/hypoxemia and morbidity and mortality is not well defined.

Pathology and Pathophysiology

The etiology of hypoventilation in these patients is not understood. Chronic hypercapnia and
hypoxemia in idiopathic central alveolar hypoventilation is believed to be due to defective
CO2 and O2homeostasis, with impaired CO2 unloading, reduced chemoresponsiveness to
CO2 and O2, and suppression of respiratory drive. Imaging of the central nervous system does
not document a structural defect. Hypoventilation worsens during sleep compared to waking
levels due to a further reduction in chemosensitivity and decreased activity of the ventilatory
muscles. Additionally, daytime hypoxemia, if sufficiently severe, may place the patient near
or on the steep portion of the oxyhemoglobin dissociation curve where even relatively small
decrements in arterial oxygen tension result in large decrements in oxyhemoglobin saturation.
Thus, sleep related hypoventilation in these patients may have a relatively great impact on
oxyhemoglobin saturation.

Objective Findings

The characteristic polysomnographic finding is demonstration of sleep related

hypoventilation (determination of PaCO2 by arterial blood gas or by a surrogate measure
[end-tidal CO2 or transcutaneous CO2]). Periods of decreased tidal volume lasting up to
several minutes, with sustained arterial oxygen desaturation, are usually present. Intermittent
arousals may be observed. Daytime arterial blood gases may be normal or show hypoxia and
hypercapnia. Chronic hypoxia can be associated with polycythemia. Electrocardiography,
chest radiography, and echocardiography may demonstrate evidence of pulmonary
hypertension. Central nervous system imaging is generally unremarkable.

Differential Diagnosis

The differential diagnosis includes any disorder that can cause hypoventilation during sleep.
This includes obesity hypoventilation syndrome, pulmonary airway and parenchymal
disorders, pulmonary vascular pathology, neuromuscular and chest wall disorders, severe
untreated hypothyroidism, and use of respiratory suppressants. CCHS is associated with an
abnormal PHOX2Bgene. Unlike patients with late-onset central hypoventilation with
hypothalamic dysfunction, patients with idiopathic central hypoventilation do not have
evidence of hypothalamic dysfunction. It is essential to excluded medical and neurological
disorders that are associated with hypoventilation before a diagnosis of idiopathic central
hypoventilation can be made. OSA and CSA syndromes can be distinguished from sleep
related hypoventilation by the periodic alterations in airflow and accompanying periodic
fluctuations in SaO2. In contrast, oxygen desaturation due to sleep related hypoventilation is
generally more sustained, usually several minutes or longer in duration. When more than one
disorder is believed to be responsible for the ventilatory insufficiency during sleep, all
pertinent diagnoses should be coded.
Unresolved Issues and Further Directions

A better understanding of the etiology of idiopathic central alveolar hypoventilation is

essential to guide preventive and treatment measures. Because it is clinically impractical to
routinely obtain arterial blood samples during sleep in most persons suspected of this
disorder, other techniques of measuring CO2 levels must be investigated. The degree and
duration of hypercapnia/hypoxemia necessary to produce adverse consequences, such as
pulmonary hypertension, in individual patients is not well defined. Little information is
available regarding the effect of oxygen therapy or noninvasive ventilation on the course of
the underlying disease. Studies are needed to determine the optimal time to initiate these
interventions and the specific subpopulations of patients who will benefit most from these
therapies.

Bibliography

Brown LK. Hypoventilation syndromes. Clin Chest Med 2010;31:249–70.

Casey KR, Cantillo KO, Brown LK. Sleep-related hypoventilation/hypoxemic syndromes.
Chest 2007;131:1936–48.
Chebbo A, Tfaili A, Jones SF. Hypoventilation syndromes. Med Clin North Am
2011;95:1189–202.
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Sleep Related Hypoventilation Disorders

Obesity Hypoventilation Syndrome
Congenital Central Alveolar Hypoventilation Syndrome
Late-Onset Central Hypoventilation with Hypothalamic Dysfunction
Idiopathic Central Alveolar Hypoventilation
Sleep Related Hypoventilation Due to a Medication or Substance
Sleep Related Hypoventilation Due to a Medical Disorder

The primary feature of these disorders is insufficient sleep related ventilation, resulting in
abnormally elevated arterial partial pressure of carbon dioxide (PaCO2) during sleep. In
addition, demonstration of daytime hypoventilation is required for a diagnosis of obesity
hypoventilation syndrome (OHS). Awake hypoventilation is defined as an arterial partial
pressure of carbon dioxide (PaCO2) greater than 45 mm Hg. In the sleep related
hypoventilation disorders other than OHS, daytime hypoventilation may or may not be
present. If hypoventilation is present during wakefulness, it worsens during sleep in all of
these disorders.

General Criteria Sleep Related Hypoventilation

Criterion A must be met

A. Sleep related hypoventilation, as defined by the most recent version of the AASM Manual
for the Scoring of Sleep and Associated Events, is present.1,2
Notes

1. Monitoring of arterial PCO2 during sleep is not practical. Acceptable surrogates include
end-tidal PCO2 or transcutaneous PCO2.
2. Arterial oxygen desaturation is often present but is not required for the diagnosis.
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Sleep Related Hypoventilation Due to a Medical Disorder

ICD-9-CM code: 327.26

ICD-10-CM code: G47.36

Alternate Names

Alveolar hypoventilation, nonapneic alveolar hypoventilation, secondary alveolar

hypoventilation, sleep related hypoventilation.

Diagnostic Criteria

Criteria A-C must be met

A. Sleep related hypoventilation is present.

B. A lung parenchymal or airway disease, pulmonary vascular pathology, chest wall disorder,
neurologic disorder, or muscle weakness is believed to be the primary cause of
hypoventilation.
C. Hypoventilation is not primarily due to obesity hypoventilation syndrome, medication use,
or a known congenital central alveolar hypoventilation syndrome.
Notes

1. Arterial desaturation is often present but is not required for the diagnosis.
2. Although OSA or CSA may be present, they are not believed to be the major cause of
hypoventilation. The predominant respiratory pattern is one of reduced tidal volume or
ataxic breathing and associated arterial oxygen desaturation. When criteria are met, a
diagnosis of both OSA and CSA due to medical or neurological condition as well as sleep
related hypoventilation due to a medical disorder may be made.
3. Hypoventilation may be present during wakefulness but is not required for the diagnosis.
Essential Features

Lung airway or parenchymal disease, chest wall disorders, pulmonary hypertension,

neurologic and neuromuscular disorders, if sufficiently severe, can result in ventilatory
impairment and chronic hypercapnia and hypoxemia. Acute exacerbations of respiratory
disorders can accentuate the severity of hypoventilation. Sleep related hypoventilation is
present and is usually most severe during REM sleep. In some patients, hypercapnia may also
be present during wakefulness. Patients can either be asymptomatic or present with
complaints of dyspnea, chest tightness, or fatigue. Polycythemia is often noted with severe
chronic hypoxemia. Specific respiratory disorders are associated with abnormal findings on
pulmonary function testing, radiographic imaging, echocardiography, and pulmonary artery
catheter measurements. Suspected neurologic or neuromuscular causes of hypoventilation
may be investigated using central nervous system imaging or measures of peripheral nerve or
muscular function.

Associated Features

Consequences of chronic hypercapnia and hypoxemia arising as a result of medical and

neurologic disorders include pulmonary artery hypertension, cor pulmonale, and
neurocognitive dysfunction. Some of these disorders are prevalent diseases and commonly
overlap. Patients with multiple disorders are likely to experience greater severity and duration
of sleep related hypoventilation than are patients with either disorder alone.

Clinical and Pathophysiological Subtypes

The clinical presentation varies with the underlying disorder responsible for the sleep related
hypoventilation. Chronic obstructive pulmonary disease is characterized by generally fixed
and not fully reversible lower airways obstruction, and includes chronic bronchitis,
emphysema, cystic fibrosis, and bronchiectasis. Chronic bronchitis is a clinical entity defined
by the presence of chronic productive cough for at least three months of the year, for at least
two consecutive years, in the absence of other identifiable etiologies. Emphysema is
characterized by destruction of lung tissue and the dilation of peripheral airspaces without
evident fibrosis. Emphysema and chronic bronchitis often coexist. Alpha-1 antitrypsin
deficiency is a genetic cause of chronic obstructive pulmonary disease. Both bronchiectasis
and cystic fibrosis are characterized by lower airway inflammation and destruction of airways
and lung parenchyma. Patients with chronic lower airways obstruction are increasingly
predisposed to developing hypoventilation as the severity of the underlying lower airways
obstruction increases.

Parenchymal lung disease associated with restrictive ventilatory dysfunction (e.g., interstitial
lung disease) can also be associated with sleep related hypoventilation. Neurologic,
neuromuscular, and chest wall disorders can produce hypoventilation due to an abnormal
ventilatory pump (secondary to reduced muscle strength or anatomic distortion of the chest
wall structures) that is unable to meet the ventilatory requirements for maintaining PaCO2 at
or below 45 mm Hg. In addition, some of these patients have reduced central neural
chemoresponsiveness. Last, hypoxemia may be worsened by the development of atelectasis
or aspiration due to defective swallowing associated with some neurologic and
neuromuscular conditions.

Demographics

The demographics of sleep related hypoventilation due to a medical disorder are a function of
the prevalence, clinical characteristics, and degree of severity of the underlying conditions.
Thus, prevalence may be higher in patients with greater perturbations of pulmonary function
or neuromuscular weakness. Individuals with chronic hypercapnia during wakefulness will
experience even greater decrements of alveolar ventilation during sleep.

Predisposing and Precipitating Factors

Greater impairments of respiratory function are associated with greater risk for sleep related
hypoventilation and hypoxemia. However, there is no recognized threshold of pulmonary
parenchymal or vascular disease severity that adequately predicts the risk of sleep related
hypoventilation in individual patients. Reduced chemosensitivity may be present in some
neuromuscular disorders. The use of central nervous system depressants, such as alcohol,
anxiolytics, and hypnotics, may further worsen respiratory impairment. Patients who are
hypercapnic and hypoxemic during wakefulness will generally become even more so during
sleep, in particular REM sleep, but the relationship between wake SaO2/PaCO2 and sleep
related desaturation is not sufficiently strong to have substantial predictive value in individual
patients.

Familial Patterns

Genetic patterns for many of the disorders are not known. Alpha-1 antitrypsin deficiency is a
genetic disorder characterized by defective production of the enzyme inhibitor; severe forms
of deficiency can lead to emphysema. Genetic causes of bronchiectasis include primary
ciliary dyskinesia and cystic fibrosis. Muscular dystrophies are genetically inherited. The
familial patterns of sleep related hypoventilation due to these disorders reflect those of the
underlying inherited conditions.

Onset, Course, and Complications

Onset and course of the hypoventilation parallels the presence and severity of the underlying
medical or neurological disorders that impair respiration although substantial variability in
course is observed even within the same underlying condition. Many affected individuals
with severe hypercapnia and hypoxemia develop respiratory impairment, pulmonary
hypertension, heart failure, cardiac arrhythmias, and neurocognitive dysfunction.
Polycythemia is common in those with chronic hypoxia. Although the risk of increased
morbidity and mortality appears to increase with worsening sleep related hypoventilation, the
specific relationship between sleep related hypoventilation and morbidity and mortality is not
well defined. Many patients respond to assisted ventilation, whereas hypercapnia may worsen
with oxygen therapy alone.

Pathology and Pathophysiology

Pulmonary parenchymal diseases are characterized by altered lung volumes (e.g., reduced
functional residual capacity) and abnormal ventilation/perfusion relationships, which can
result in hypercapnia and hypoxemia during wakefulness. Decreased lung volume is
associated with reduced oxygen reserves that increase the risk of hypoxemia. In addition,
sleep may be associated with an altered pattern of ventilatory-muscle activation, particularly
during REM sleep when, due to reduced activation of the intercostal and accessory muscles,
there is a disproportionate ventilatory burden placed on the diaphragm. This may lead to
hypoventilation in patients with chest wall abnormalities or in those with chronic obstructive
pulmonary disease. In the latter, lung hyperinflation creates a mechanical disadvantage to the
diaphragm. Many neurologic and neuromuscular disorders are associated with impaired
respiratory mechanics and reduced CO2 chemosensitivity. Finally, daytime hypoxemia, if
sufficiently severe, may place the patient near or on the steep portion of the oxyhemoglobin
dissociation curve, where even relatively small decrements in arterial oxygen tension result in
large decrements in oxyhemoglobin saturation. Thus, sleep related hypoventilation in these
patients may have a relatively great impact on oxyhemoglobin saturation.

Objective Findings

The characteristic polysomnographic finding is demonstration of sleep related

hypoventilation (by arterial PaCO2, transcutaneous PCO2, or end-tidal PCO2). Sustained
oxygen desaturation during sleep that is unexplained by discrete apnea and hypopnea events
is common but is not sufficient to establish a diagnosis of sleep related hypoventilation.
Intermittent arousals associated with hypoxemia may be observed. Many medical and
neurologic disorders are associated with significant sleep disturbances and changes in sleep
architecture, including prolonged sleep onset latency, reduced sleep efficiency, and decreased
sleep stages N3 and REM, may be present. Obstructive and central apneas, when present, will
further disturb sleep and accentuate sleep related oxyhemoglobin desaturation. Daytime
arterial blood gases may be normal or show hypoxia and hypercapnia. Chronic hypoxia
(especially when present during the day as well as at night) can be associated with
polycythemia. Electrocardiography, chest radiography, and echocardiography may
demonstrate evidence of pulmonary hypertension.

In patients with neuromuscular weakness or restrictive chest wall disorders spirometry shows
a restrictive ventilatory dysfunction with the forced vital capacity (FVC) often less than 50%
of predicted. However, significant nocturnal desaturation can occur with FVC values greater
than 50% of predicted.

Differential Diagnosis

The differential diagnosis includes all disorders which can give rise to hypoventilation during
sleep. This includes OHS, use of medications or substances that can suppress respiratory
drive, andcongenital or idiopathic central alveolar hypoventilation
syndromes. OSA and CSA can be distinguished from sleep related hypoventilation by the
periodic alterations in airflow and accompanying periodic fluctuations in SaO2. In contrast,
oxygen desaturation due to sleep related hypoventilation is generally more sustained, usually
several minutes or longer in duration. When more than one disorder is believed to be
responsible for the ventilatory insufficiency during sleep, all pertinent diagnoses should be
coded.

Unresolved Issues and Further Directions

Thresholds of impairments of ventilation and respiratory drive producing

hypercapnia/hypoxemia need to be identified. The degree and duration of
hypercapnia/hypoxemia necessary to produce adverse consequences, such as pulmonary
hypertension, in individual patients is not well defined. The value of routinely measuring
PaCO2 during sleep in these patients is not clear. Additionally, because it is clinically
impractical to routinely obtain arterial blood samples during sleep in most persons suspected
of this disorder, other techniques of measuring CO2 levels must be investigated. Little
information is available regarding the effect of oxygen therapy or noninvasive ventilation on
the course of the underlying disease. Studies are needed to determine the optimal time to
initiate these interventions and the specific subpopulations of patients who will benefit most
from these therapies.

Bibliography

Ambrosino N, Carpenè N, Gherardi M. Chronic respiratory care for neuromuscular diseases

in adults. Eur Respir J 2009;34:444–51.
Beuther DA. Hypoventilation in asthma and chronic obstructive pulmonary disease. Semin
Respir Crit Care Med 2009;30:321–9.
Biering-Sørensen F, Jennum P, Laub M. Sleep disordered breathing following spinal cord
injury. Respir Physiol Neurobiol 2009;169:165–70.
Castriotta RJ, Murthy JN. Hypoventilation after spinal cord injury. Semin Respir Crit Care
Med 2009;30:330–8.
Dhand UK, Dhand R. Sleep disorders in neuromuscular diseases. Curr Opin Pulm Med
2006;12:402–8.
Donath J, Miller A. Restrictive chest wall disorders. Semin Respir Crit Care Med
2009;30:275–92.
Fathi M, Lundberg IE, Tornling G. Pulmonary complications of polymyositis and
dermatomyositis. Semin Respir Crit Care Med 2007;28:451–8.
Glass GA, Josephs KA, Ahlskog JE. Respiratory insufficiency as the primary presenting
symptom of multiple-system atrophy. Arch Neurol 2006;63:978–81.
Kennedy JD, Martin AJ. Chronic respiratory failure and neuromuscular disease. Pediatr Clin
North Am 2009;56:261–73, xii.
Taylor-Cousar JL. Hypoventilation in cystic fibrosis. Semin Respir Crit Care Med
2009;30:293–302.
Toussaint M, Chatwin M, Soudon P. Mechanical ventilation in Duchenne patients with
chronic respiratory insufficiency: clinical implications of 20 years published experience.
Chron Respir Dis 2007;4:167–77.
Vazquez-Sandoval A, Huang EJ, Jones SF. Hypoventilation in neuromuscular disease. Semin
Respir Crit Care Med 2009;30:348–58.
Wider C, Wszolek ZK. Rapidly progressive familial parkinsonism with central
hypoventilation, depression and weight loss (Perry syndrome)--a literature review.
Parkinsonism Relat Disord 2008;14:1–7.
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Sleep Related Hypoxemia Disorder

Sleep Related Hypoxemia
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Sleep Related Hypoxemia

ICD-9-CM code: 327.26

ICD-10-CM code: G47.36

Alternate Names

Nocturnal oxygen (or oxyhemoglobin) desaturation, low nocturnal oxygen saturation,

nocturnal hypoxemia, sleep related hypoxemia, sleep related oxygen desaturation.

Diagnostic Criteria

Criteria A and B must be met

A. PSG, OCST or nocturnal oximetry shows the arterial oxygen saturation (SpO2) during
sleep  of  ≤  88%  in  adults  or  ≤  90%  in  children  for  ≥  5  minutes.
B. Sleep related hypoventilation is not documented.1
Notes

1. If sleep related hypoventilation is documented (as measured by arterial blood gas,

transcutaneous PCO2, or end-tidal CO2 sensors), the disorder is classified as sleep related
hypoventilation.
2. OSA or CSA may be present, but these are not believed to be the major cause of
hypoxemia.
3. Physiological causes, if known, should be indicated (e.g., shunt, ventilation-perfusion
[V/Q] mismatch, low mixed venous oxygen, and/or high altitude).
Essential Features

Significant hypoxemia during sleep is present and is believed to be secondary to a medical or

neurological disorder. The presence of hypoxemia is not better explained by another sleep
related breathing disorder (e.g., OSA). Although some amount of obstructive or central apnea
may be present, these disorders are not thought to be primarily responsible for the hypoxemia
during sleep. Some patients with sleep related hypoxemia also exhibit hypoxemia during
wakefulness. Sleep related hypoventilation has not been documented (if so, a diagnosis of
sleep related hypoventilation is made). The presentation of patients with sleep related
hypoxemia varies with the underlying medical or neurological disorders. Chronic hypoxemia
can arise from airway or parenchymal pulmonary disease, chest wall disorders, pulmonary
hypertension, or neurologic and neuromuscular disorders. Acute exacerbations of respiratory
disorders can accentuate the severity of hypoxemia. Hypoxemia due to underlying lower
airway obstructive disease, pulmonary parenchymal disease, vascular pathology, and other
causes of hypoventilation is generally sustained (several minutes or longer), whereas
sawtooth fluctuations of oxygen saturation (typically less than one minute) characterize
hypoxemia due to OSA or CSA. Patients can either be asymptomatic or present with
complaints of nocturnal dyspnea, impaired sleep quality, chest tightness, or fatigue.
Polycythemia is often noted with severe chronic hypoxemia.

Associated Features

Consequences of chronic hypercapnia and hypoxemia include pulmonary artery hypertension,

cor pulmonale, and neurocognitive dysfunction. Some of the disorders causing hypoxemia
are prevalent diseases and not uncommonly overlap. Patients with multiple breathing
disorders are likely to experience greater severity and duration of sleep related hypoxemia
than are patients with a single disorder.

Clinical and Pathophysiological Subtypes

Specific variations in the sleep related findings have not been described for the various
etiologies.

Demographics

The demographics of sleep related hypoxemia are a function of the prevalence, clinical
characteristics and degree of severity of the underlying conditions. Thus, prevalence may be
higher in patients with greater perturbations of pulmonary function or neuromuscular
weakness. Individuals with chronic hypoxemia during wakefulness will experience even
greater decrements of oxygenation during sleep.

Predisposing and Precipitating Factors

Greater impairments of respiratory function are associated with greater risk for sleep related
hypoxemia. However, there is no recognized threshold of pulmonary parenchymal or
vascular disease severity or extent of neuromuscular weakness that adequately predicts the
risk of sleep related hypoxemia in individual patients. Patients who are hypoxemic during
wakefulness will generally become even more so during sleep, especially REM sleep. Among
the best predictors of sleep related hypoxemia are reduced baseline wake SaO2 and
hypercapnia. Patients with wake hypercapnia should be suspected of sleep related
hypoxemia. However, the relationship between wake SaO2/PaCO2 and sleep related
desaturation is not sufficiently strong to have substantial predictive value in individual
patients.

Familial Patterns

Genetic patterns for many of the disorders are not known. Alpha-1 antitrypsin deficiency is a
genetic disorder characterized by defective production of the enzyme inhibitor; severe forms
of deficiency can lead to emphysema. Genetic causes of bronchiectasis include primary
ciliary dyskinesia and cystic fibrosis. Muscular dystrophies are genetically inherited. The
familial patterns of sleep related hypoxemia due to these disorders reflect those of the
underlying inherited conditions.

Onset, Course, and Complications

Onset and course of sleep related hypoxemia parallel the presence and severity of the
underlying medical or neurological disorders that impair respiration, although substantial
variability in course is observed even within the same underlying condition. Many affected
individuals with severe hypercapnia and hypoxemia develop respiratory impairment,
pulmonary hypertension, heart failure, cardiac arrhythmias, and neurocognitive dysfunction.
Polycythemia is common in those with chronic hypoxia. Higher rates of painful crises
accompany hypoxemia in children with sickle cell disease. Although the risk of increased
morbidity and mortality appears to increase with worsening sleep related hypoxemia, the
specific relationship between sleep related hypoxemia and morbidity and mortality is not well
defined. Many patients respond to oxygen therapy; in some, hypercapnia may worsen with
oxygen therapy alone for hypoxia.

Pathology and Pathophysiology

Hypoxemia may arise from a shunt physiology, ventilation-perfusion [V/Q] mismatching,

low mixed venous oxygen, and/or high altitude. Hypoventilation also gives rise to
hypoxemia; however, when hypoventilation has been documented, a diagnosis of sleep
related hypoventilation should be assigned, rather than sleep related hypoxemia. Pulmonary
parenchymal diseases are characterized by altered lung volumes (e.g., reduced functional
residual capacity) and abnormal ventilation/perfusion relationships, which can result in
hypercapnia and hypoxemia during wakefulness. Decreased lung volume is associated with
reduced oxygen reserves that increase the risk of hypoxemia. In addition, sleep may be
associated with an altered pattern of ventilatory muscle activation, particularly during REM
sleep when, due to reduced activation of the intercostal and accessory muscles, there is a
disproportionate ventilatory burden placed on the diaphragm. This may lead to
hypoventilation in patients with chest wall abnormalities or chronic obstructive pulmonary
disease. In the latter, lung hyperinflation creates a mechanical disadvantage to the diaphragm.
In sickle cell anemia, decreased oxyhemoglobin affinity may partly contribute to hypoxemia.
Many neurologic and neuromuscular disorders are associated with impaired respiratory
mechanics and reduced CO2 chemosensitivity. Finally, daytime hypoxemia, if sufficiently
severe, may place the patient near or on the steep portion of the oxyhemoglobin dissociation
curve where even relatively small decrements in arterial oxygen tension result in large
decrements in oxyhemoglobin saturation. Thus, sleep related hypoventilation in these patients
might have a relatively great impact on oxyhemoglobin saturation.

Objective Findings

Various patterns of oxygen desaturation (sustained, intermittent, or episodic) may be

observed during sleep. The diagnosis is generally made on the basis of overnight oximetry
(alone or as a component of PSG or OCST); less commonly, arterial blood gas measurements
are indicated, especially if concomitant hypoventilation is suspected. PSG may demonstrate
normal sleep architecture or frequent arousals, increased wakefulness after sleep onset and
reduced sleep efficiency; however, the contribution of sleep related hypoxemia to the altered
sleep architecture, if present, is uncertain. Daytime arterial blood gases may be normal or
show hypoxia and hypercapnia. Nocturnal oximetry usually shows sustained periods of
reduced arterial oxygen but clusters of more severe drops in the arterial oxygen saturation can
occur every one to two hours due to worsening of breathing during REM sleep. A sawtooth
pattern of briefer desaturations (typically less than one minute) suggests the presence of
discrete events (apneas or hypopneas). Some sawtooth changes may be superimposed on low
baseline oxygen saturation but are not the predominant pattern. Chronic hypoxia can be
associated with polycythemia. Electrocardiography, chest radiography, and echocardiography
may demonstrate evidence of pulmonary hypertension.

Differential Diagnosis

The differential diagnosis encompasses all disorders which can give to hypoxemia during
sleep. This includes pulmonary airway and parenchymal disorders, pulmonary vascular
pathology, neuromuscular and chest wall disorders, OHS, use of medications or substances
that can suppress respiratory drive, and congenital or idiopathic central alveolar
hypoventilation syndromes. OSA andCSA syndromes can be distinguished from sleep related
hypoxemia by the periodic alterations in airflow and accompanying periodic fluctuations in
SaO2. In contrast, oxygen desaturation associated with sleep related hypoxemia is generally
more sustained, usually several minutes or longer in duration. In cases when more than one
disorder is believed to be responsible for the ventilatory insufficiency during sleep, all
pertinent diagnoses should be coded.

Unresolved Issues and Further Directions

The degree and duration of hypercapnia/hypoxemia necessary to produce adverse

consequences, such as pulmonary hypertension, in individual patients is not well defined. The
value of routinely measuring arterial blood gases or SaO2 during sleep is not clear. With the
exception of COPD, little information is available regarding the effect of oxygen therapy on
the course of the underlying disease. Even less is understood regarding the consequences of
isolated sleep related hypoxemia and the need for oxygen supplementation in patients with
normal daytime wake oxygen levels. Studies are needed to determine the optimal time to
initiate oxygen therapy and the specific subpopulations of patients who will benefit most
from this intervention.

Bibliography

Berry RB, Sriram P. Evaluation of hypoventilation. Semin Respir Crit Care Med
2009;30:303–14.
Brown LK. Hypoventilation syndromes. Clin Chest Med 2010;31:249–70.
Casey KR, Cantillo KO, Brown LK. Sleep-related hypoventilation/hypoxemic syndromes.
Chest 2007;131:1936–48.
Chebbo A, Tfaili A, Jones SF. Hypoventilation syndromes. Med Clin North Am
2011;95:1189–202.
Mogri M, Desai H, Webster L, Grant BJ, Mador MJ. Hypoxemia in patients on chronic opiate
therapy with and without sleep apnea. Sleep Breath 2009;13:49–57.
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Isolated Symptoms and Normal Variants

Snoring
Catathrenia
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Snoring
ICD-9-CM code: 786.09

ICD-10-CM code: R06.83

Snoring is a respiratory sound generated in the upper airway during sleep that typically
occurs during inspiration but may also occur in expiration; the snoring described here occurs
without episodes of apnea, hypopnea, RERAs or hypoventilation. The intensity of snoring
may vary and often will disturb  the  bed  partner’s  sleep  and  even  awaken  the  patient.  Snoring  
in this context does not cause symptoms of daytime sleepiness or insomnia in the patient.
This type of snoring has variously been referred to as habitual, primary or simple snoring.

Snoring is a cardinal symptom of obstructive sleep apnea. A designation of habitual

snoring cannot be made in those who exhibit symptoms (daytime sleepiness/fatigue or other
related symptoms) or report possible breathing pauses, without objective measurement of
breathing during sleep. In addition, those individuals with snoring and comorbid
cardiovascular disease (especially pulmonary or systemic hypertension, coronary artery
disease, or atrial fibrillation) are at increased risk for the presence of OSA even in the
absence of complaints of daytime sleepiness. Therefore, PSG or OCST isrequired in order to
effectively rule out OSA in such populations. It should also be noted that patients who initially
have isolated snoring may be at risk for developing OSA with aging or weight gain.

Occasional snoring is almost universal. Estimates on snoring vary widely depending on its
definition. The incidence of snoring in children is reported to be 10% to 12%. The Wisconsin
cohort study reports habitual snoring in about 24% of adult women and 40% of adult men.
Prevalence of snoring increases with age in both sexes, except that the prevalence of reported
snoring starts to decrease again in men after 70 years of age. Some have hypothesized that his
may be due to decreased hearing acuity in older individuals.

Snoring is most common in adult men and is also linked to obesity. Nasal obstruction
increases the risk of snoring. Ingestion of alcohol, muscle relaxants, narcotics, or other
substances that decrease upper airway muscle tone predisposes an individual to snoring.
Smoking, particularly in males, has also been shown to be a risk factor. Snoring has also been
shown to increase during pregnancy. In children, an association has been reported between
snoring and adenotonsillar hypertrophy. During snoring there is vibration of the uvula and
soft palate, although it may also involve the faucial pillars, pharyngeal walls, and lower
structures. Snorers have been shown to have morphologic derangements of the palate
consistent with neurogenic lesions. These are thought to be due to trauma from vibration. If
PSG is performed, snoring tends to be loudest during stage N3 sleep or REM sleep.

Epidemiologic studies are difficult to interpret if sleep apnea was not excluded by PSG.
Based on the current literature, habitual snoring in children may be associated with worse
school performance, but conclusive evidence for this is lacking. Some studies have suggested
that adult snorers may have a higher prevalence of cardiovascular disease, including
hypertension, stroke, and ischemic heart disease. However, a large observational study in
which all subjects underwent PSG found no increased risk of cardiovascular morbidity or
mortality with habitual snoring. Of interest, one study found that snoring was associated with
atherosclerosis of the carotid artery, but this has not been confirmed by other studies. As
snoring tends to increase during pregnancy, the impact of snoring on maternal health is of
great interest. A study found that pregnancy-onset habitual snoring (but not chronic [pre-
conceptual] snoring) was associated with increased risk of gestational hypertension and
preeclampsia. Further studies are needed in this area.

Bibliography

Cho JG, Witting PK, Verma M, et al. Tissue vibration induces carotid artery endothelial
dysfunction: a mechanism linking snoring and carotid atherosclerosis? Sleep
2011;34:751–7.
Kezirian EJ, Chang JL. Snoring without OSA and health consequences: the jury is still out.
Sleep 2013;36:613.
Lee SA, Amis TC, Byth K, et al. Heavy snoring as a cause of carotid artery atherosclerosis.
Sleep 2008;31:1207–13.
Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men
with obstructive sleep apnoea-hypopnoea with or without treatment with continuous
positive airway pressure: an observational study. Lancet 2005;365:1046–53.
Mason RH, Mehta Z, Fonseca AC, Stradling JR, Rothwell PM. Snoring and severity of
symptomatic and asymptomatic carotid stenosis: a population-based study. Sleep
2012;35:1147–51.
O’Brien  LM,  Bullough  AS,  Owusu  JT,  et  al.  Pregnancy-onset habitual snoring, gestational
hypertension, and preeclampsia: prospective cohort study. Am J Obstet Gynecol
2012;207:487.e1–9.
Rich J, Raviv A, Raviv N, Brietzke SE. An epidemiologic study of snoring and all-cause
mortality. Otolaryngol Head Neck Surg 2011;145:341–46.
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Catathrenia
Catathrenia, also known as sleep related groaning, is included in the SRBD section because it
appears to be associated with prolonged expiration, usually during REM sleep. However,
some studies have documented catathrenia during NREM sleep. Typically, a deep inspiration
is followed by prolonged expiration and a monotonous vocalization resembling groaning. The
pattern is sometimes called bradypnea (low respiratory rate). The affected individual is
usually unaware of the problem, but clinical evaluation is sought due to complaints of the bed
partner or family members. The recurrent bradypneic episodes may resemble central apnea
except that central apneas are not typically associated with vocalization. Catathrenia is
thought to be rare and more common in men. Several episodes may occur nightly and often in
clusters. The long-term consequences of catathrenia are unknown, but the disorder is
primarily a social problem for the affected individual. The episodes of catathrenia are not
associated with sleep talking or body movement. No association with psychiatric disorders
has been demonstrated. The onset of catathrenia has recently been reported in patients taking
sodium oxybate for narcolepsy with cataplexy. The clinical significance of this finding is
unclear.

Bibliography

Abbasi AA, Morgenthaler TI, Slocumb NL, et al. Nocturnal moaning and groaning-
catathrenia or nocturnal vocalizations. Sleep Breath 2012;16:367–73.
Pevernagie DA, Boon PA, Mariman ANN, Verhaeghen DB, Pauwels RA. Vocalization
during episodes of prolonged expiration: a parasomnia related to REM sleep. Sleep Med
2001;2:19–30.
Poli F, Ricotta L, Vandi S, et al. Catathrenia under sodium oxybate in narcolepsy with
cataplexy. Sleep Breath 2012;16:427–34.
Vetrugno  R,  Lugaresi  E,  Plazzi  G,  Provini  F,  D’Angelo  R,  Montagna  P.  Catathrenia  
(nocturnal groaning): an abnormal respiratory pattern during sleep. Eur J Neurol
2007;14:1236–43.
Vetrugno R, Provini F, Plazzi G, Vignatelli L, Lugaresi E, Montagna P. Catathrenia
(nocturnal groaning): a new type of parasomnia. Neurology 2001;56:681–3.
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Sumário
Central Disorders of Hypersomnolence ............................................................................ 86
Disorders ........................................................................................................................ 88
Narcolepsy Type 1 .................................................................................................................. 88
Narcolepsy Type 2 .................................................................................................................. 95
Idiopathic Hypersomnia ........................................................................................................ 100
Kleine-Levin Syndrome ........................................................................................................ 104
Hypersomnia Due to a Medical Disorder ............................................................................. 108
Hypersomnia Due to a Medication or Substance .................................................................. 112
Hypersomnia Associated with a Psychiatric Disorder .......................................................... 115
Insufficient Sleep Syndrome ................................................................................................. 118
Isolated Symptoms and Normal Variants ................................................................... 122
Long Sleeper ............................................................................................................... 122
Central  Disorders  of  Hypersomnolence
Adequate alertness is necessary for well-being and performance in modern society.
Sleepiness predisposes an individual to developing serious performance decrements in
multiple areas of function, as well as to potentially life-threatening domestic, occupational,
and vehicular accidents. This section includes a group of disorders in which the primary
complaint is daytime sleepiness not caused by disturbed nocturnal sleep or misaligned
circadian rhythms. Other sleep disorders may be present, but they must be adequately treated
before a diagnosis in this category can be established. In this nosology, the term
hypersomnolence is used to describe the symptom of excessive sleepiness, whereas
hypersomnia refers to specific disorders, such as idiopathic hypersomnia.

Daytime sleepiness is defined as the inability to stay awake and alert during the major waking
episodes of the day, resulting in periods of irrepressible need for sleep or unintended lapses
into drowsiness or sleep. Sleepiness may vary in severity and is more likely to occur in
sedentary, boring, and monotonous situations that require little active participation. Some
patients are aware of increasing sleepiness before falling asleep, whereas others can fall
asleep  with  little  or  no  prodromal  symptoms  (“sleep  attacks”).  This  group  of  patients  
sometimes can present following motor vehicle accidents attributable to sleepiness. In some
forms of hypersomnolence, sleepiness is associated with large increases in total daily amount
of sleep without any genuine feeling of restoration. In others, sleepiness can be alleviated
temporarily by naps but reoccurs shortly thereafter. In young children, sleepiness may
express itself as excessively long night sleep or with the recurrence of previously
discontinued daytime napping. Children may paradoxically present with inattentiveness,
emotional lability, hyperactive behavior, or decreased performance in school. In most cases,
excessive sleepiness is a chronic symptom. It must occur for at least three months prior to
diagnosis.

The severity of daytime sleepiness can be quantified subjectively using severity scales such
as the Epworth Sleepiness Scale and objectively using the Multiple Sleep Latency Test
(MSLT). These measures do not always correlate with each other and must be used with
appropriate clinical judgment. When applied in clinical settings, the MSLT is sensitive to
sleep deprivation and circadian effects. It has not been validated as a diagnostic test in people
who are habitually awake throughout the night and sleep during the day. Normal and
abnormal ranges of sleep latencies have not been established when this test is administered at
times other than the hours between 8:00 a.m. and 6:00 p.m.

Normative data are not available for children younger than six years.

The MSLT measures the physiological tendency to fall asleep in quiet situations. In the
context of diagnosing central disorders of hypersomnolence, the MSLT should be conducted
according to standardized procedures, as defined in the American Academy of Sleep
Medicine (AASM) practice parameters. In particular, patients should be encouraged to sleep
as much as possible during the week and, especially, during the night prior to the MSLT.
Delaying wake-up time and subsequent MSLT start time may be appropriate in some patients
with delayed sleep phase syndrome. It is strongly recommended that adequate sleep be
documented by sleep log and, whenever possible, actigraphy for a period of one to two weeks
prior to the MSLT. MSLT mean sleep latencies should be considered a continuum with
values below five minutes generally considered as indicative of sleepiness and those over 10
minutes generally considered indicative of normal alertness. In this section, a mean MSLT
sleep latency of less than eight minutes is used to define sleepiness for diagnostic purposes.
This value has been shown to be the best cutoff in the context of diagnosing narcolepsy, with
approximately 90% of patients with narcolepsy having a latency below this level. The
presence of multiple sleep onset rapid eye movement periods (SOREMPs) during the MSLT
is a more specific finding in narcolepsy than is a mean sleep latency less than or equal to
eight minutes, although SOREMPs can also be seen in the presence of insufficient sleep,
circadian rhythm disorders (including delayed sleep phase disorder or shift work), sleep
related breathing disorders or, occasionally, normal subjects. The results of an MSLT should
be carefully interpreted in the context of the patient's history and the complaint of daytime
sleepiness.

The maintenance of wakefulness test is a measure of the ability to remain awake during the
daytime in a darkened, quiet environment and is usually administered to assess response to
treatment. It should not be used for diagnostic purposes.

A 24-hour continuous sleep recording or an actigraphic recording of at least one week is

useful in the diagnosis of some patients with idiopathic hypersomnia. In all cases in which a
diagnosis of hypersomnolence is to be made, a review of other sleep, medical, and psychiatric
disorders, as well as substance and medication use, should be performed.

In this edition of International Classification of Sleep Disorders the preferred names of

certain central disorders of hypersomnolence have been changed. In particular, narcolepsy
has been divided into narcolepsy type 1 and narcolepsy type 2 rather than narcolepsy with
and without cataplexy. This change is predicated on the concept that absence of hypocretin
(orexin) is a fundamental marker of the most precisely defined category of the disorder.
Because some patients without cataplexy will also have low cerebrospinal fluid (CSF)
hypocretin-1  levels,  the  use  of  the  term  “narcolepsy  with  cataplexy”  or  “narcolepsy-
cataplexy”  is  inappropriate.  The  change  is  not  intended  to  imply  that  the  presence  or  absence  
of cataplexy is unimportant clinically nor that measuring CSF hypocretin-1 levels is
obligatory. The motivation behind the decision to eliminate the subcategories of idiopathic
hypersomnia is discussed in the appropriate section. The decision to use Kleine-Levin
syndrome as the preferred name in place of recurrent hypersomnia is based on data
suggesting that the condition is fairly homogeneous, as well as the lack of definite evidence
for other major subcategories of the disorder.

Bibliography
Arand D, Bonnet M, Hurwitz T, Mitler M, Rosa R, Sangal RB. A Review by the MSLT and
MWT Task Force of the Standards of Practice Committee of the American Academy of
Sleep Medicine. The clinical use of the MSLT and MWT. Sleep 2005;28:123–44.
Aurora RN, Lamm CI, Zak RS, et al. Practice parameters for the non-respiratory indications
for polysomnography and multiple sleep latency testing for children. Sleep
2012;35:1467–73.
Littner MR, Kushida C, Wise M, et al.; Standards of Practice Committee of the American
Academy of Sleep Medicine. Practice parameters for clinical use of the multiple sleep
latency test and the maintenance of wakefulness test. Sleep 2005;28:113–21.
Mignot E, Lin L, Finn L, et al. Correlates of sleep-onset REM periods during the Multiple
Sleep Latency Test in community adults. Brain 2006;129:1609–23.
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Central Disorders of Hypersomnolence ››

Disorders
Narcolepsy Type 1
Narcolepsy Type 2
Idiopathic Hypersomnia
Kleine-Levin Syndrome
Hypersomnia Due to a Medical Disorder
Hypersomnia Due to a Medication or Substance
Hypersomnia Associated with a Psychiatric Disorder
Insufficient Sleep Syndrome
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Central Disorders of Hypersomnolence ›› Disorders ››

Narcolepsy Type 1

ICD-9-CM code: 347.01

ICD-10-CM code: G47.411

Alternate Names

Hypocretin deficiency syndrome, narcolepsy-cataplexy, narcolepsy with cataplexy.

Diagnostic Criteria

Criteria A and B must be met

A. The patient has daily periods of irrepressible need to sleep or daytime lapses into sleep
occurring for at least three months.1
B. The presence of one or both of the following:
1. Cataplexy (as defined under Essential Features) and a  mean  sleep  latency  of  ≤  8  
minutes and two or more sleep onset REM periods (SOREMPs) on an MSLT
performed according to standard techniques. A SOREMP (within 15 minutes of sleep
onset) on the preceding nocturnal polysomnogram may replace one of the SOREMPs
on the MSLT.2
2. CSF hypocretin-1  concentration,  measured  by  immunoreactivity,  is  either  ≤  110  pg/mL  
or <1/3 of mean values obtained in normal subjects with the same standardized assay.
Notes

1. In young children, narcolepsy may sometimes present as excessively long night sleep or as
resumption of previously discontinued daytime napping.
2. If narcolepsy type I is strongly suspected clinically but the MSLT criteria of B1 are not
met, a possible strategy is to repeat the MSLT.
Essential Features

Narcolepsy type 1 is a disorder primarily characterized by excessive daytime sleepiness and

signs of REM-sleep dissociation, the most specific of which is cataplexy. It has now been
firmly established that narcolepsy type 1 is caused by a deficiency of hypothalamic
hypocretin (orexin) signaling. Patients with low or undetectable concentrations of hypocretin-
1 in the CSF compose a specific disease population with a single etiology and relatively
homogenous clinical and polysomnographic features. Patients with sleepiness and low or
absent CSF hypocretin-1 levels are classified as having narcolepsy type 1, even if they do not
manifest cataplexy.

Excessive daytime sleepiness is the cardinal symptom, and often the most disabling. Patients
with narcolepsy type 1 experience repeated daily episodes of an irrepressible need to sleep or
lapses into sleep. Most patients awaken refreshed after a sleep episode but begin to feel
sleepy again after variable times. Sleepiness is most likely to occur in monotonous situations
that require no active participation; for example, watching television or riding in a car.
Physical activity may temporarily suppress the urge to sleep. In some cases sleepiness
manifests  as  sudden  irresistible  sleep  “attacks”  that  may  occur  in  unusual  situations such as
eating or walking. Often, such sleep attacks occur on a background of overall sleepiness.
Even when seemingly awake, many narcolepsy patients have lapses in vigilance, sometimes
in combination with automatic behavior, such as writing gibberish or interrupting a
conversation with a completely different topic. Sleepiness generally has a serious impact on
the ability of the patient to function in educational, social, and occupational situations.

Because patients are rarely examined during an attack of cataplexy, its presence needs to be
established based on the clinical interview alone. Cataplexy is defined as more than one
episode of generally brief (< 2 minutes), usually bilaterally symmetrical sudden loss of
muscle tone with retained consciousness. The episodes are precipitated by strong emotions,
usually positive, with almost all patients reporting some episodes precipitated by emotions
associated with laughter. The finding of transient reversible loss of deep tendon reflexes
during an attack, if observed, is a strong diagnostic finding. In children (and rarely adults),
cataplexy may present close to disease onset as facial (or generalized) hypotonia with droopy
eyelids, mouth opening, and protruded tongue, or gait unsteadiness, which clearly are not
related to emotion. Facial and masticatory movements may occur. In children, anticipation of
a reward is a common precipitant. It is important to use child-appropriate contexts and
language when trying to elicit a history of cataplexy in children.

The cataplexy phenotype differs widely between patients, ranging from sporadic partial
attacks triggered by laughter, to frequent complete attacks of collapse brought about by a
variety of emotions. In the vast majority of attacks, cataplexy is bilateral, although patients
sometimes report one side of the body to be more affected than the other. Partial attacks can
be  very  subtle  and  sometimes  only  recognized  by  experienced  observers  such  as  the  patient’s  
partner. Neck weakness, producing head drop, is a common complaint, whereas facial
weakness may lead to sagging of the jaw and dysarthria. Respiratory muscles are not
involved although patients sometimes describe shortness of breath when symptomatic.
Attacks start abruptly and usually build up over several seconds, especially in attacks
producing complete peripheral weakness and collapse. Positive motor phenomena are not
uncommon, with muscle twitching or small jerks, particularly of the face. Although many
emotions can potentially lead to cataplexy, those associated with mirth are usually the most
potent. Laughing out loud, telling a joke, and making a witty remark are typical examples.
The frequency of cataplexy is variable, ranging from less than one attack per month to more
than 20 attacks per day. Cataplexy is generally short-lived, lasting a matter of seconds, with
the vast majority of attacks lasting less than two minutes. However, if a particular trigger
continues, consecutive attacks may merge together to form what seems to be one long
episode. Sudden withdrawal of anticataplectic medication, especially antidepressants, can
result  in  “status  cataplecticus”  in  which  long-lasting attacks happen virtually continuously.

Associated Features

In addition to sleepiness and cataplexy, patients with narcolepsy type 1 often report several
other symptoms, none of which are specific for the disorder. Many patients report disruption
of nocturnal sleep, which can sometimes be of major concern. Although sleep onset is rarely
a problem, an inability to maintain continuous sleep is very common. 33% to 80% of
narcolepsy patients have hypnagogic hallucinations and/or sleep paralysis. Hypnagogic
hallucinations are defined as vivid dreamlike experiences occurring at the transition from
wake to sleep. Typically, hypnagogic hallucinations  have  a  multimodal  or  “holistic”  
character, often combining visual, auditory, and tactile phenomena. Hypnopompic
hallucinations are similar but occur at sleep to wake transitions. Sleep paralysis describes the
disturbing temporary inability to move voluntary muscles at sleep-wake transitions. Despite
being awake and conscious of the sleeping environment, it is impossible for subjects to move
their limbs or even open their eyes. The experience may last for several minutes and can be
very distressing. Other symptoms may include ptosis, blurred vision, and diplopia,
presumably as a result of sleepiness.

Epidemiological studies have shown that obesity is a common symptom of narcolepsy.

Around disease onset, an unexplained increase in body weight is often observed. Obesity
(defined  as  a  body  mass  index  ≥  30  kg/m2) occurs more than twice as often in narcoleptic
populations as in control groups. An increased frequency of several other sleep abnormalities
has been described in narcolepsy, including sleep talking, periodic limb movements of sleep,
sleep disordered breathing, and REM sleep behavior disorder. There is an increased
prevalence of depressive symptoms, although there are conflicting reports on how often these
symptoms qualify as a clinical depression. Recent studies point to a high level of anxiety
disorders in patients with narcolepsy, with panic attacks or social phobias in about 20%.
More than half of patients report severe fatigue, which can be distinct from sleepiness.

Clinical and Pathophysiological Subtypes

Narcolepsy type 1 due to a medical condition: This condition is primarily associated with
central nervous system (CNS) disorders, including autoimmune or paraneoplastic disorders
associated with anti-Ma2 or antiaquaporin4 antibodies, and tumors or other lesions of the
hypothalamus. In addition, undetectable hypocretin-1 levels have been reported in association
with sleepiness after severe head trauma. The condition must fulfill criteria for narcolepsy
type 1 and be attributable to another medical disorder.

Narcolepsy without cataplexy with low CSF Hcrt-1 levels: Narcolepsy type 1 should be
diagnosed, even in the absence of cataplexy, if diagnostic criteria A and B2 are fulfilled.

Demographics

Narcolepsy with cataplexy occurs in 0.02% to 0.18% of the United States and western
European populations. A lower prevalence has been reported in Israel, whereas narcolepsy
with cataplexy may be slightly more common in Japan (0.16% to 0.18%). Both sexes are
affected, with a slight preponderance of males.

Predisposing and Precipitating Factors

Several unproven precipitating factors have been suggested in case reports, including head
trauma, sustained sleep deprivation, unspecified viral illness, and sudden changes in sleep-
wake patterns. Several studies have pointed to seasonal patterns in the onset of narcolepsy,
which may point to a specific environmental trigger. Recent studies have shown an increase
in antibodies against beta-hemolytic streptococcus, which were strongest around onset of
narcolepsy and decreased with disease duration, suggesting that streptococcal infections may
constitute an environmental trigger. There have been reports of narcolepsy type 1 occurring
after vaccination against H1N1 associated influenza, but a definite causal association has not
yet been established. Tribbles homolog 2 antibodies, found in some patients with
autoimmune uveitis, have been described in 14% to 26% of narcolepsy patients, but the
significance is uncertain.

Familial Patterns

At the genetic level, narcolepsy with cataplexy is closely associated with the human
leukocyte antigen (HLA) subtypes DR2/DRB1*1501 and DQB1*0602. These two subtypes
are always found together in whites and Asians, but in blacks, DQB1*0602 is more
specifically associated with narcolepsy. Almost all patients with cataplexy are positive for
DQB1*0602, compared with 12% to 38% of the general population who have this HLA
subtype. Other subtypes also have less striking associations. For example, DQB1*0301 is
associated with increased susceptibility to narcolepsy, whereas subtypes such as DQB1*0501
and DQB1*0601, are protective in the presence of DQB1*0602. Genomewide studies have
found associations between narcolepsy and polymorphisms in T cell receptor alpha, tumor
necrosis factor (TNF)-alpha 2, and TNF receptor 2 as well as the purinergic receptor P2Y11
genes.

There is a low prevalence of familial cases; the risk of narcolepsy type 1 in first-degree
relatives of affected individuals is approximately 1% to 2%. When compared to the
population prevalence, this indicates a tenfold to fortyfold increase in risk. This increased risk
cannot be explained solely by HLA gene effects, suggesting the existence of other genetic
factors. Multiplex families with more than two affected members are uncommon. In most
cases, normal CSF hypocretin levels have been found in these families, and the association
with HLA DQB1*0602 is much weaker compared to sporadic narcolepsy. So far, only a
single case of narcolepsy type 1 has been described in association with a preprohypocretin
mutation.

Onset, Course, and Complications

Onset usually occurs after five years of age and most typically between ages 10 and 25 years.
However, a bimodal distribution in the age at onset has been described in some populations
with a first peak occurring at adolescence (age 15 years) and a second at the age of 35 years.
Recent studies highlight the fact that narcolepsy, and especially cataplexy, in young children
may present somewhat differently, resulting in delayed diagnosis and erroneously high
estimates of age of onset.

Sleepiness is usually the first symptom to manifest. Cataplexy most often occurs within one
year of onset but in rare cases, may precede the onset of sleepiness or commence up to 40
years later. Hypnagogic hallucinations, sleep paralysis, and disturbed nocturnal sleep often
manifest later in the course of the disease.
When left untreated, narcolepsy type 1 is often socially disabling and isolating. Patients have
a tendency to fail in school and are often dismissed from their jobs. Driving may be avoided
for fear of a motor vehicle accident. The inability to sleep at night may further contribute to a
loss of control these patients have over their schedule. Depression and weight gain also are
common.

In most cases, symptoms gradually develop over several years. When the clinical picture has
fully developed, there are usually only minor fluctuations in severity. Cataplexy may lessen
with age, or occasionally increase in frequency and severity.

Developmental Issues

In recent years, increasing attention has been given to the clinical presentation of narcolepsy
in childhood. Narcolepsy with cataplexy is infrequent prior to the age of four years. In
addition, the clinical presentation in children may be different from that of adults. In young
children, sleepiness may be difficult to assess, and may express itself as excessively long
night sleep, or the recurrence of previously discontinued daytime napping. Moreover,
children may paradoxically present with hyperactive behavior, behavioral problems or
decreased performance in school. Inattentiveness, lack of energy, insomnia, bizarre
hallucinations, or a combination thereof can lead to a psychiatric misdiagnosis of
schizophrenia or depression. In this population, the presence of ancillary symptoms such as
sleep paralysis or hypnagogic hallucinations may also be difficult to confirm, depending on
the  child’s  verbal  ability.  Precocious  puberty  and  obesity  may  also  develop  around  the  time  
of symptom onset. REM sleep behavior disorder or REM sleep without atonia may also be
manifest at the time of symptom onset.

Cataplexy may be very severe around disease onset and appear phenotypically different from
typical episodes seen in adulthood. In addition to typical attacks triggered by positive
emotions, children can also present with weakness involving the face, eyelids, and mouth not
clearly associated with emotion. Together with tongue protrusion, this characteristic pattern
has been termed a cataplectic facies. Children with cataplexy may also display positive motor
phenomena, ranging from perioral dyskinetic or dystonic movements to frank stereotypies. In
children, anticipation of reward may also be a precipitant.

The diagnosis of narcolepsy type 1 in children may be complicated because of difficulties

performing the MSLT, and lack of normative values in children younger than six years. If the
MSLT shows equivocal results, repeating it after a time interval may be helpful. Given these
difficulties, CSF hypocretin-1 measurements are of particular value, as hypocretin-1 levels
are low or undetectable very shortly after disease onset in children as well.

Pathology and Pathophysiology

It is now firmly established that narcolepsy type 1 is caused by deficiencies in hypocretin

signaling, most likely due to a selective loss of hypothalamic hypocretin producing neurons.
Several animal models lacking hypocretin neurotransmission demonstrate narcolepsy,
indicating a causal relationship. The vast majority of patients (90% to 95%) with narcolepsy
and cataplexy have undetectable or low (< 110 pg/mL) levels of hypocretin-1 in the CSF.
Patients without cataplexy can be hypocretin deficient as well, although at a much lower
frequency, and are thus also classified as narcolepsy type 1. The strong HLA association in
narcolepsy has led to the hypothesis that autoimmunity is a likely etiological mechanism,
potentially explaining the selectivity of neuronal destruction in the hypothalamus. However,
definitive proof for autoimmunity has not been obtained.

Objective Findings

Narcolepsy type 1 is essentially defined as a hypocretin deficiency syndrome, which is

reflected in the need for objective measurements in the clinical criteria. This requirement is
further driven by the fact that many patients require lifelong treatment with potentially
addictive medications, underscoring the importance of objective confirmation of the
diagnosis.

It is strongly recommended that the MSLT be preceded by at least one week of actigraphic
recording with a sleep log to establish whether the results could be biased by insufficient
sleep, shift work, or another circadian sleep disorder. In patients with narcolepsy type 1, the
MSLT demonstrates a mean sleep latency of less than eight minutes and typically less than
five minutes. Meta-analysis shows mean sleep latencies in narcoleptic patients with cataplexy
of 3.1 ± 2.9 minutes. In addition, two or more SOREMPs must be present. Recent data
suggest that a SOREMP within 15 minutes of onset of nocturnal sleep is a highly specific
finding in the absence of another sleep disorder, but with low sensitivity. Therefore, the
criteria  for  narcolepsy  type  1  allow  the  “replacement”  of  one  SOREMP in the MSLT with a
SOREMP on the preceding polysomnogram. For the correct interpretation of MSLT findings,
the recordings should be performed with the following conditions: (1) the patient must be free
of drugs that influence sleep for at least 14 days (or at least five times the half-life of the drug
and longer-acting metabolite), confirmed by a urine drug screen; (2) the sleep-wake schedule
must have been standardized and, if necessary, extended to a minimum of seven hours in bed
each night (longer for children) for at least seven days before polysomnography (preferably
documented by sleep log and, whenever possible, actigraphy); and (3) nocturnal
polysomnography should be performed on the night immediately preceding the MSLT to rule
out other sleep disorders that could mimic the diagnostic features of narcolepsy type 1. Sleep
time during polysomnography should be curtailed as little as possible with the goal of at least
seven hours asleep. The overnight polysomnogram may demonstrate an increase in the
amount of stage N1 sleep, and there may be a disruption of the normal sleep pattern, with
frequent awakenings. REM sleep without atonia may be present.

Measuring CSF levels of hypocretin-1 is a highly specific and sensitive test for the diagnosis
of narcolepsy type 1. Hypocretin-1 can be measured in crude CSF, using a commercially
available radioimmunoassay. When using the Stanford reference sample, values less than 110
pg/mL are highly specific. Alternatively, a laboratory may elect to obtain control data
themselves, in which case a level of less than 33% of mean control values is considered
abnormal. Issues concerning the standardization of CSF hypocretin measurements remain,
but extensive protocols are available. Low CSF hypocretin values are occasionally observed
in seriously ill patients with other disorders and should be interpreted within the clinical
context.

HLA typing of narcoleptic patients with cataplexy almost always shows the presence of HLA
DQB1*0602 (and DR2 or DRB1*1501 in whites and Asians), but this is not diagnostic for
narcolepsy. Approximately 25% of the normal Caucasian population, 12% of the Japanese
population, and 38% of the black population are positive for DQB1*0602. HLA typing could
be considered when a spinal tap is contemplated to assess hypocretin-1 values: if the patient
is HLA-negative, hypocretin-1 levels are most likely normal.
Differential Diagnosis

In the absence of cataplexy, narcolepsy type 1 can be diagnosed based on the presence of
hypersomnolence and low CSF hypocretin-1 levels. When cataplexy is absent and CSF
hypocretin-1 levels are normal or unknown, narcolepsy type 2 should be diagnosed.

Cataplexy must be differentiated from cataplexy-like episodes that are occasionally observed
in normal individuals. For example, feelings of muscle weakness are sometimes reported
when healthy subjects laugh out loud. In genuine cataplexy, episodes most often occur with a
significant frequency, and are associated with loss of muscle tone. Cataplexy should be
differentiated from hypotension, transient ischemic attacks, drop attacks, akinetic seizures,
neuromuscular disorders, vestibular disorders, psychological or psychiatric disorders, and
sleep paralysis. Clear improvement with antidepressant medications may favor a diagnosis of
cataplexy in difficult cases.

Sleepiness may be secondary to obstructive sleep apnea, insufficient sleep syndrome, shift
work, the effects of substances or medications, or other sleep disorders. Many of these
conditions can result in early onset REM sleep as well. When cataplexy is present, these
disorders do not preclude a diagnosis of narcolepsy type 1. When there is a questionable
history of cataplexy in such cases, either comorbid conditions should be adequately treated
before performing an MSLT or CSF hypocretin-1 should be measured.

Idiopathic hypersomnia is differentiated from narcolepsy type 1 by the absence of cataplexy

and the lack of two or more SOREMPS on the MSLT. In contrast with patients who have
narcolepsy, patients with idiopathic hypersomnia generally have high sleep efficiency, sleep
drunkenness, and long, unrefreshing naps.

In insufficient sleep syndrome, there is no cataplexy, and normalizing sleep time eliminates
the daytime sleepiness. Chronic fatigue syndrome and depression may mimic narcolepsy but
do not show the typical MSLT findings. Malingering and substance abuse disorder should be
considered in patients who try to mislead the clinician in order to obtain stimulant
medications.

Unresolved Issues and Further Directions

Ten percent of patients with narcolepsy with cataplexy have normal hypocretin-1 levels in the
CSF, which suggests that CSF levels either do not perfectly reflect brain hypocretin
neurotransmission or that narcolepsy with cataplexy can be caused by factors other than
hypocretin deficiency. The cause of the hypocretin cell destruction remains unknown,
although an autoimmune-mediated mechanism is suspected. Levels of hypocretin-1 have
been reported in the blood of some subjects. The development of serum tests to determine
hypocretin deficiency would provide a less invasive diagnostic approach.

Bibliography

Andlauer O, Moore H, Jouhier L, et al. Nocturnal REM sleep latency for identifying patients
with narcolepsy/hypocretin deficiency. JAMA Neurol 2013;6:1–12.
Aran A, Einen M, Lin L, Palazzi G, Nishino S, Mignot E. Clinical and therapeutic aspects of
childhood narcolepsy-cataplexy: a retrospective study of 51 children. Sleep
2010;33:1457–64.
Arii J, Kanbayashi T, Tanabe Y, et al. CSF hypocretin-1 (orexin-A) levels in childhood
narcolepsy and neurologic disorders. Neurology 2004;63:2440–2.
Bourgin P, Zeitzer JM, Mignot E. CSF hypocretin-1 assessment in sleep and neurological
disorders. Lancet Neurol 2008;7:649–62.
Dauvilliers Y, Gosselin A, Paquet J, Touchon J, Billiard M, Montplaisir J. Effect of age on
MSLT results in patients with narcolepsy-cataplexy. Neurology 2004;62:46–50.
Dauvilliers Y, Arnulf I, Mignot E. Narcolepsy with cataplexy. Lancet 2007;369:499–511.
Kotagal S, Krahn LE, Slocumb N. A putative link between childhood narcolepsy and obesity.
Sleep Med 2004;5:147–50.
Mignot E, Lammers GJ, Ripley B, et al. The role of cerebrospinal fluid hypocretin
measurement in the diagnosis of narcolepsy and other hypersomnias. Arch Neurol
2002;59:1553–62.
Mignot E, Lin L, Finn L, et al. Correlates of sleep-onset REM periods during the Multiple
Sleep Latency Test in community adults. Brain 2006;129:1609–23.
Nevsimalova S, Prihodova I, Kemlink D, Lin L, Mignot E. REM sleep behavior disorder
(RBD) can be one of the first symptoms of childhood narcolepsy. Sleep Med
2007;8:784–6.
Overeem S, van Nues SJ, van der Zande WL, Donjacour CE, van Mierlo P, Lammers GJ. The
clinical features of cataplexy: a questionnaire study in narcolepsy patients with and
without hypocretin-1 deficiency. Sleep Med 2011;12:12–8.
Pizza F, Franceschini C, Peltola H, et al. Clinical and polysomnographic course of childhood
narcolepsy with cataplexy. Brain 2013 Oct 18. [Epub ahead of print]
Plazzi G, Parmeggiani A, Mignot E, et al. Narcolepsy-cataplexy associated with precocious
puberty. Neurology 2006;66:1577–9.
Serra L, Montagna P, Mignot E, Lugaresi E, Plazzi G. Cataplexy features in childhood
narcolepsy. Mov Disord 2008;23:858–65.
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Central Disorders of Hypersomnolence ›› Disorders ››

Narcolepsy Type 2

ICD-9-CM code: 347.00

ICD-10-CM code: G47.419

Alternate Names

Narcolepsy without cataplexy.

Diagnostic Criteria

Criteria A-E must be met

A. The patient has daily periods of irrepressible need to sleep or daytime lapses into sleep occurring
for at least three months.

B.  A  mean  sleep  latency  of  ≤  8  minutes  and  two  or  more  sleep  onset  REM  periods  (SOREMPs) are
found on a MSLT performed according to standard techniques. A SOREMP (within 15 minutes of
sleep onset) on the preceding nocturnal polysomnogram may replace one of the SOREMPs on the
MSLT.

C. Cataplexy is absent.1

D. Either CSF hypocretin-1 concentration has not been measured or CSF hypocretin-1 concentration
measured by immunoreactivity is either > 110 pg/mL or > 1/3 of mean values obtained in normal
subjects with the same standardized assay.2

E. The hypersomnolence and/or MSLT findings are not better explained by other causes such as
insufficient sleep, obstructive sleep apnea, delayed sleep phase disorder, or the effect of medication or
substances or their withdrawal.

Notes

1. If cataplexy develops later, then the disorder should be reclassified as narcolepsy type 1.

2. If the CSF Hcrt-1  concentration  is  tested  at  a  later  stage  and  found  to  be  either  ≤  110  pg/mL  or  <  
1/3 of mean values obtained in normal subjects with the same assay, then the disorder should be
reclassified as narcolepsy type 1.

Essential Features

Narcolepsy type 2 is characterized by excessive daytime sleepiness and abnormal manifestations of

REM sleep on polysomnography/MSLT. Cataplexy is absent, although some atypical sensations of
weakness triggered by unusual emotions such as stress and anger may be reported. Refreshing
daytime naps are characteristic.

An essential feature of the diagnosis is the presence of a mean sleep latency less than or equal to eight
minutes and two or more SOREMPs on an MSLT (or one SOREMP on an MSLT and one on the
preceding nocturnal polysomnogram). The presence of CSF hypocretin-1  concentrations  ≤  110  pg/mL  
or less than one third of mean values obtained in normal subjects with the same assay excludes the
diagnosis, but most patients with narcolepsy type 2 will not have undergone CSF examination.

Associated Features

Sleep paralysis, hypnagogic hallucinations, or automatic behavior may be present. Memory lapses,
automatic behavior, ptosis, blurred vision, and diplopia may occur in association with sleepiness.
REM sleep behavior disorder and nonrapid eye movement (NREM) parasomnias may occur.
Nocturnal sleep disruption with frequent awakenings may be present.

Clinical and Pathophysiological Subtypes

Narcolepsy type 2 due to a medical condition: This condition fulfills criteria for narcolepsy type 2
and is attributable to another medical disorder. Neurologic disorders associated with narcolepsy type 2
include tumors or sarcoidosis of the hypothalamus, autoimmune or paraneoplastic disorders
associated with anti-Ma-2 or anti-aquaporin-4 antibodies, multiple sclerosis, myotonic dystrophy,
Prader-Willi syndrome, Parkinson disease, and head trauma. In disorders associated with both sleep
apnea and narcolepsy type 2, such as myotonic dystrophy or Prader-Willi syndrome, a diagnosis of
narcolepsy type 2 should only be made if abnormal MSLT findings persist after the sleep apnea is
adequately treated. In all cases, especially with complex problems such as head trauma, clinical
judgment should be used to determine if the development of narcolepsy was a mere coincidence or
was triggered by the event or disorder.

Demographics

The exact prevalence of narcolepsy type 2 is uncertain. Cases of narcolepsy without cataplexy
represent 15% to 25% of the clinic narcoleptic population. A population-based study suggested a
higher percentage (36%), corresponding to a point prevalence of 20.5/100,000. Population-based
studies have shown that approximately 4% to 9.5% of adults may have multiple SOREMPs during
random MSLTs, but shift workers and subjects with sleep deprivation or sleep apnea were included in
the studies. Although both sexes can be affected, the prevalence may be slightly higher in men. The
age of onset mirrors that of narcolepsy type 1.

Predisposing and Precipitating Factors

As discussed below, about 24% of patients with narcolepsy but no cataplexy will have low CSF Hcrt-
1 levels and almost all of these will be positive for the HLA DQB1*0602 antigen. These patients
probably share a common pathogenesis with narcolepsy with cataplexy and should be classified as
narcolepsy type 1. Underlying genetic and environmental factors associated with other patients with
narcolepsy type 2 are unknown. Environmental precipitating factors are suspected from case reports
but have never been proven to trigger narcolepsy without cataplexy. Among the most commonly
reported triggers are head trauma and unspecified viral illnesses.

Familial Patterns

The detailed genetic pattern of narcolepsy type 2 is unknown. Relatives of patients with narcolepsy
type 1 may be more likely to experience partial narcolepsy symptoms compatible with the diagnosis
of narcolepsy type 2.

Onset, Course, and Complications

Onset typically occurs during adolescence. In about 10% of patients, cataplexy will develop later in
the course of the disease, necessitating a change in diagnosis to narcolepsy type 1. Most of these
patients will, if tested, have absent or intermediate levels of CSF Hcrt-1. In a cohort of patients with
narcolepsy without cataplexy in whom CSF Hcrt-1 status was known, 33% of those with low levels
later developed cataplexy, compared with 18% with intermediate levels and only 1% with normal
levels. When left untreated, narcolepsy type 2 is socially disabling and isolating. Patients have a
tendency to fail in school and are often dismissed from their jobs. Driving may be avoided for fear of
a motor vehicle accident. The inability to sleep at night may further contribute to a loss of control
these patients have over their schedule. Depression and weight gain also are common.

Developmental Issues

Children with narcolepsy type 2 will typically present with a reappearance of regular daytime napping
after naps had been discontinued. In all pediatric cases, one should consider the possibility of an
evolving disorder with the development of cataplexy over time. Once the patient develops clear
cataplexy, the diagnosis should be changed to narcolepsy type 1. Limited information is available on
narcolepsy type 2 prior to adolescence. Descriptions of the experience of sleep paralysis or
hypnagogic hallucinations are very difficult to evoke in young patients, and normative data are not
available for the MSLT in children younger than six years of age. In peripubertal children and
adolescents, the diagnosis is often challenging. The most common causes of short sleep latencies,
often with multiple SOREMPs on the MSLT, are chronic sleep deprivation and delayed sleep phase
disorder. Behavioral problems may be associated with the onset of the disorder, and symptoms may
be hidden by the patient. Inattentiveness, lack of energy, insomnia, bizarre hallucinations, or a
combination thereof can lead to a psychiatric misdiagnosis of schizophrenia or depression. If the
MSLT shows equivocal results, repeating it after a time interval may be helpful, as SOREMPs often
emerge later in children.

Pathology and Pathophysiology

Narcolepsy type 2 is most likely a heterogeneous disorder. Approximately 24% of narcoleptic patients
without cataplexy have a low CSF Hcrt-1 concentration, and another 8% have intermediate levels (>
110  pg/mL  but  ≤  200  pg/mL).  The  CSF  Hcrt-1 status of most patients with narcolepsy type 2 is
unknown (those patients who are known to have absent CSF Hcrt-1 levels are classified as narcolepsy
type 1). Therefore, there will be a subgroup of about one fourth to one third of narcolepsy type 2
patients who will have hypocretin deficiency, presumably from loss of the hypocretin-producing
neurons. This group of patients cannot be accurately separated clinically or by laboratory tests (other
than CSF Hcrt-1 level) from the majority of patients without cataplexy who have normal CSF Hcrt-1
levels. Although those with low CSF Hcrt-1 levels have a younger age of onset and their MSLT
shows shorter mean sleep latency with more SOREMPs in comparison with those with normal levels,
there is too much overlap between the groups for these differences to be helpful diagnostically in
individual patients. One hundred percent of patients with low CSF Hcrt-1 levels are positive for HLA
DQB1*0602. About 26% of patients with normal levels are also HLA positive, a percentage not
higher than that seen in the normal population. The underlying pathophysiology of the remainder of
patients who have normal CSF Hcrt-1 levels is unknown. It is possible some may have partial
hypocretin deficiency severe enough to cause sleepiness but not severe enough to result in cataplexy
or low CSF Hcrt-1 levels. However, support for this hypothesis is lacking in that there are no major
differences in clinical or polysomnographic findings in those positive or negative for HLA
DQB1*0602. In the only postmortem study of a case of narcolepsy without cataplexy (CSF Hcrt-1
status unknown), the number of hypocretin cells was decreased but not as much as in cases of
narcolepsy with cataplexy.

Objective Findings

It is strongly rcommended that the MSLT be preceded by at least one week of actigraphic recording
with a sleep log to establish whether the results could be biased by insufficient sleep, shift work, or
another circadian sleep disorder. The MSLT demonstrates a mean latency of less than eight minutes,
typically less than five minutes, with two or more SOREMPs or one SOREMP together with a
SOREMP on the preceding polysomnogram. Meta-analysis shows mean sleep latencies in narcoleptic
patients with cataplexy of 3.1 ± 2.9 minutes. Recent data suggest that a SOREMP within 15 minutes
of onset of nocturnal sleep is a highly specific finding in the absence of another sleep disorder, but
with low sensitivity. Therefore, the criteria for narcolepsy  type  2  allow  the  “replacement”  of  one  
SOREMP in the MSLT with a SOREMP on the preceding polysomnogram. For the correct
interpretation of MSLT findings, the recordings should be performed with the following conditions:
(1) the patient must be free of drugs that influence sleep for at least 14 days (or at least five times the
half-life of the drug and longer-acting metabolite), confirmed by a urine drug screen; (2) the sleep-
wake schedule must have been standardized and, if necessary, extended to a minimum of seven hours
in bed each night (longer for children) for at least seven days before polysomnography (preferably
documented by sleep log and, whenever possible, actigraphy); and (3) nocturnal polysomnography
should be performed on the night immediately preceding the MSLT to rule out other sleep disorders
that could mimic the diagnostic features of narcolepsy type 2. Sleep time during polysomnography
should be curtailed as little as possible, with the goal of at least seven hours asleep. The overnight
polysomnogram may demonstrate an increase in the amount of stage N1 sleep, and there may be a
disruption of the normal sleep pattern, with frequent awakenings. REM sleep without atonia may be
present.

About 45% of narcolepsy type 2 cases have been reported to be HLA DQB1*0602 positive, compared
with 12% to 38% of controls. Whereas essentially all patients who have low CSF Hcrt-1 levels will be
positive, about 25% of those with normal levels will also be positive. Assuming that 24% of patients
with narcolepsy but no cataplexy will have low CSF Hcrt-1 levels, the probability that an HLA-
positive patient will have low Hcrt-1 levels is only 0.56. Therefore the HLA status of a patient cannot
be used to diagnose narcolepsy type 2 nor to predict with high probability  the  patient’s  CSF  Hcrt-1
levels. However, if lumbar puncture is contemplated to measure CSF Hcrt-1 levels, HLA typing
should be performed first; if the patient is HLA negative, CSF Hcrt-1 levels will almost certainly be
normal and the lumbar puncture will be unnecessary.

Approximately 24% of narcoleptic patients without cataplexy have a low CSF Hcrt-1 concentration
and  another  8%  have  intermediate  levels  (>  110  pg/mL  but  ≤  200  pg/mL).  If  the  CSF  Hcrt-1 levels of
such patients are known to be low, they are classified as narcolepsy type 1, but the CSF Hcrt-1 status
will not be known for most of these patients. Possible indications for considering measuring CSF
Hcrt-1 levels as a diagnostic procedure would be the presence of disorders such as obstructive sleep
apnea or the use of psychotropic medications that may complicate interpretation of an MSLT.

Differential Diagnosis

Narcolepsy type 1 is diagnosed if cataplexy is present or the CSF hypocretin levels are known to be
low even in the absence of cataplexy. Patients with idiopathic hypersomnia may have mean sleep
latencies on MSLT similar to those of narcolepsy type 2, but have fewer than two SOREMPs on
MSLT and the preceding polysomnogram combined. In contrast to narcolepsy, patients
with idiopathic hypersomnia generally have high sleep efficiency, sleep drunkenness, and long,
unrefreshing naps. Sleepiness may be secondary to obstructive sleep apnea (OSA), insufficient sleep
syndrome, shift work, the effects of substances or medications, or other sleep disorders. Many of these
conditions can result in early-onset REM sleep, so their clinical and polysomnographic exclusion is
essential before a diagnosis of narcolepsy type 2 is made. However, the presence of other sleep
disorders does not preclude a diagnosis of narcolepsy type 2 if daytime sleepiness and REM
abnormalities persist after adequate treatment of the initial disorder. Chronic fatigue
syndrome and depression may mimic narcolepsy but do not show the typical MSLT
findings. Malingering and substance abuse disordershould be considered in patients who try to
mislead the clinician in order to obtain stimulant medications.

Unresolved Issues and Further Directions

Excluding the minority of patients with definite hypocretin deficiency, the underlying biology of
narcolepsy without the presence of cataplexy is unknown. It is not established whether narcolepsy
type 2 is a homogeneous or heterogeneous condition. It is uncertain whether or not some patients have
partial hypocretin deficiency not identifiable from CSF measurements. Further advances in
classification will depend on answers to these unknowns. Further studies on the natural history of
narcolepsy type 2 are needed to determine the cause of the hypersomnolence and the risk of
development of cataplexy over time.

Bibliography

Andlauer O, Moore IV H, Hong SC, et al. Predictors of hypocretin (orexin) deficiency in narcolepsy
without cataplexy. Sleep 2012;35:1247–55.

Bourgin P, Zeitzer JM, Mignot E. CSF hypocretin-1 assessment in sleep and neurological disorders.
Lancet Neurol 2008;7:649–62.

Mignot E, Lin L, Finn L, et al. Correlates of sleep-onset REM periods during the Multiple Sleep
Latency Test in community adults. Brain 2006;129:1609–23.

Oka Y, Inoue Y, Kanbayashi T, et al. Narcolepsy without cataplexy: 2 subtypes based on CSF
hypocretin-1/orexin-A findings. Sleep 2006;29:1439–43.

Sasai T, Inoue Y, Komada Y, Sugiura T, Matsushima E. Comparison of clinical characteristics among

narcolepsy with and without cataplexy and idiopathic hypersomnia without long sleep time, focusing
on HLA-DRB1(*)1501/DQB1(*)0602 finding. Sleep Med 2009;10:961–6.

Silber MH, Krahn LE, Olson EJ, Pankratz VS. The epidemiology of narcolepsy in Olmsted County,
Minnesota: a population-based study. Sleep 2002;25:197–202.

Takei Y, Komada Y, Namba K, et al. Differences in findings of nocturnal polysomnography and

multiple sleep latency test between narcolepsy and idiopathic hypersomnia. Clin Neurophysiol
2012;123:137–41.

Thannickal TC, Nienhuis R, Siegel JM. Localized loss of hypocretin (orexin) cells in narcolepsy
without cataplexy. Sleep 2009;32:993–8.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Central Disorders of Hypersomnolence ›› Disorders ››

Idiopathic Hypersomnia

ICD-9-CM code: 327.11

ICD-10-CM code: G47.11

Alternate Names

Idiopathic CNS hypersomnolence.

Diagnostic Criteria
Criteria A-F must be met

A. The patient has daily periods of irrepressible need to sleep or daytime lapses into sleep occurring
for at least three months.1

B. Cataplexy is absent.

C. An MSLT performed according to standard techniques shows fewer than two sleep onset REM
periods or no sleep onset REM periods if the REM latency on the preceding polysomnogram was less
than or equal to 15 minutes.2

D. The presence of at least one of the following:

1.  The  MSLT  shows  a  mean  sleep  latency  of  ≤  8  minutes.

2. Total 24-hour  sleep  time  is  ≥  660  minutes  (typically  12–14 hours)3 on 24-hour polysomnographic
monitoring (performed after correction of chronic sleep deprivation), or by wrist actigraphy in
association with a sleep log (averaged over at least seven days with unrestricted sleep).4

E. Insufficient sleep syndrome is ruled out (if deemed necessary, by lack of improvement of
sleepiness after an adequate trial of increased nocturnal time in bed, preferably confirmed by at least a
week of wrist actigraphy).

F. The hypersomnolence and/or MSLT findings are not better explained by another sleep disorder,
other medical or psychiatric disorder, or use of drugs or medications.

Notes

1. Severe and prolonged sleep inertia, known as sleep drunkenness (defined as prolonged difficulty
waking up with repeated returns to sleep, irritability, automatic behavior, and confusion) and/or long
(> 1 hour), unrefreshing naps are additional supportive clinical features.

2.  A  high  sleep  efficiency  (≥  90%)  on  the  preceding  polysomnogram  is  a  supportive  finding  (as  long  
as sleep insufficiency is ruled out).

3. The total 24-hour sleep time required for diagnosis may need to be adapted to account for normal
changes in sleep time associated with stages of development in children and adolescents as well as for
variability across cultures in all age groups.

4. Occasionally, patients fulfilling other criteria may have an MSLT mean sleep latency longer than 8
minutes and total 24-hour sleep time shorter than 660 minutes. Clinical judgment should be used in
deciding if these patients should be considered to have idiopathic hypersomnia (IH). Great caution
should be exercised to exclude other conditions that might mimic the disorder. A repeat MSLT at a
later date is advisable if the clinical suspicion for IH remains high.

Essential Features

IH is characterized by excessive daytime sleepiness that occurs in the absence of cataplexy, is

accompanied by no more than one SOREMP on MSLT and preceding polysomnogram combined, and
is not adequately explained by another disorder. Other disorders causing sleepiness must be carefully
considered and excluded, especially insufficient sleep syndrome. Objective evidence of
hypersomnolence  must  be  demonstrated  by  an  MSLT  showing  a  mean  sleep  latency  of  ≤  8  minutes  or  
by polysomnography or wrist actigraphy showing a total 24-hour  sleep  time  of  ≥  660  minutes.  A  
prolonged and severe form of sleep inertia, historically known as sleep drunkenness, consists of
prolonged difficulty waking up with repeated returns to sleep, irritability, automatic behavior, and
confusion. It is reported in 36% to 66% of patients with IH in different series. Subjects typically do
not easily awaken to alarm clocks and frequently use special devices or procedures to wake up. Naps
are generally long, often more than 60 minutes, and described as unrefreshing by 46% to 78% of
patients. Sleep efficiency on polysomnogram is usually high (mean 90% to 94%). Self-reported total
sleep  time  is  longer  than  in  controls  and  is  ≥  10  hours  in  at  least  30%  of  patients.

Associated Features

Associated symptoms which suggest a dysfunction of the autonomic nervous system may be present.
These symptoms include headache, orthostatic disturbance, perception of temperature dysregulation,
and peripheral vascular complaints (Raynaud-type phenomena with cold hands and feet). Sleep
paralysis and hypnagogic hallucinations may also be reported, but the frequency is uncertain (4% to
40% in different series).

Clinical and Pathophysiological Subtypes

The 2005 2nd edition of the International Classification of Sleep Disorders divided IH into two
disorders: IH with long sleep time, and IH without long sleep time. IH is likely a heterogeneous
condition, the pathophysiology of which is currently unknown. However, recent studies suggest that a
division of the disorder based on the length of nocturnal sleep lacks validity. Comparison of patients
with  ≥  10  hours  of  sleep  to  those  with  <  10  hours  show  no  differences  in  Epworth  Sleepiness  Scale  
scores, MSLT mean sleep latencies, or percentage with sleep drunkenness, unrefreshing naps,
hypnagogic hallucinations, or sleep paralysis. The only reported differences are that the group with
long sleep is somewhat younger and thinner, with lower Horne-Ostberg scores and marginally higher
sleep efficiency. If MSLT mean sleep latencies are not used as a diagnostic criterion, the distribution
of latencies is unimodal, suggesting no separate subtypes. In addition, an actigraphy study has shown
that patients with IH tend to overestimate their sleep time by a mean of 0.99 hours, thus making the
fundamental criterion for distinguishing between patients with long and shorter sleep inaccurate.
Clinicians may wish to continue to note sleep duration as an important clinical feature, but the caveats
discussed above should be clearly considered. Any future separation of IH into distinct conditions
must await advances in understanding the underlying biology.

Demographics

Prevalence and incidence of IH are not known. Some studies have suggested a higher prevalence in
women.

Predisposing and Precipitating Factors

In contrast to narcolepsy, the disorder is not known to be HLA associated, and no consistent
precipitating factor has been identified.

Familial Patterns

A familial predisposition to hypersomnia has been reported but rigorous studies have not been
performed.

Onset, Course, and Complications

The mean age of onset of IH in different series is 16.6–21.2 years. Once established, the disorder is
generally stable in severity and long lasting, although a spontaneous remission rate of 14% has been
reported in one series. Complications are mostly social and professional, and include poor work or
school performance, reduced earnings, and loss of employment.

Developmental Issues

IH frequently develops in adolescence. Exclusion of other causes of hypersomnolence in that age

group, including delayed sleep-wake phase disorder, obstructive sleep apnea, insufficient sleep
syndrome, and use of recreational drugs, is essential. Early in the development of narcolepsy,
SOREMPs may not be present on MSLT; therefore, some patients may need to be reclassified later as
narcolepsy type 2. If the 24-hour total sleep time is used to confirm the diagnosis of IH in a child or
adolescent, normal values may need to be adapted to account for changes in sleep time associated
with stages of development.

Pathology and Pathophysiology

The pathophysiology of IH is unknown. Neurochemical studies measuring monoamine metabolites in

the CSF have been inconclusive. CSF hypocretin-1 concentrations in patients with IH are normal.
CSF histamine levels have been reported to be low in patients with narcolepsy and IH, but a recent
study did not confirm these findings.

Objective Findings

Polysomnographic monitoring generally demonstrates NREM and REM sleep in expected proportions
with normal REM latency. Total sleep time is often prolonged. Sleep apnea should be either absent or
adequately treated before diagnosing this disorder, with special attention paid to excluding significant
respiratory effort related arousals. The MSLT should not show more than one SOREMP (or none if a
SOREMP  was  observed  on  the  preceding  night’s  polysomnogram  (PSG)).  The  mean  sleep  latency  on  
the MSLT is usually shorter than in controls but longer than in most patients with narcolepsy,
averaging 8.3 and 7.8 minutes in two large studies.

In patients with MSLT mean latencies > 8 minutes, prolonged sleep monitoring should be performed
by polysomnography (24 hours) or wrist actigraphy (7 days with unrestricted sleep) after correction of
sleep deprivation, exclusion of other sleep disorders, and discontinuation of sedating medication as
required for an MSLT (see Narcolepsy–Objective Findings). Total 24-hour sleep time in adults (major
sleep  episode  plus  naps)  must  be  ≥  660  minutes  (note  that  the  use  of  24-hour PSG monitoring for the
diagnosis of IH has been validated against controls, but the use of seven days of actigraphic
monitoring still awaits validation).

Differential Diagnosis

IH may be confused with OSA, especially when respiratory-related arousals (rather than apneas or
hypopneas) are present. Narcolepsy type 2 is distinguished from IH by the presence of two or more
sleep onset REM periods on the MSLT or preceding PSG. Insufficient sleep syndrome must be
carefully  excluded  by  extending  the  patient’s  sleep  before  testing.  Historical  information, physical
examination, and, if indicated, laboratory testing including brain imaging should help rule
out hypersomnolence due to a medical disorder. In particular, posttraumatic hypersomnolence,
residual hypersomnolence following adequate treatment of sleep apnea, and sleep fragmentation due
to pain may mimic IH.Hypersomnolence due to a medication or substance must be considered and
ruled out by discontinuation of possible causative agents, if clinically appropriate. Hypersomnia
associated with a psychiatric disorder should be considered in patients with a psychiatric condition,
most typically depression. The complaint of excessive sleepiness and prolonged sleep may be rather
similar to that of patients with IH, except that it may vary from day to day and is often associated with
poor sleep at night. The MSLT in hypersomnia associated with a psychiatric disorder does not
demonstrate a short mean sleep latency. Chronic fatigue syndrome is characterized by persistent or
relapsing fatigue that does not resolve with sleep or rest. Patients clearly complain of fatigue rather
than excessive daytime sleepiness, and the mean MSLT sleep latency is normal. Long sleepers feel
fully refreshed and do not experience daytime sleepiness if they are allowed to sleep as long as they
need, in contrast with patients with IH who continue to feel sleepy regardless of prior sleep duration.

Unresolved Issues and Further Directions

There is a paucity of knowledge regarding the neurobiology of IH. Further research in this area, as
well as more precise characterization of clinical characteristics and treatment response, is required.

Bibliography

Ali M, Auger RR, Slocumb NL, Morgenthaler TI. Idiopathic hypersomnia: clinical features and
response to treatment. J Clin Sleep Med 2009;5:562–8.

Anderson KN, Pilsworth S, Sharples RD, Smith IE, Shneerson JM. Idiopathic hypersomnia: a study of
77 cases. Sleep 2007;30:1274–81.

Bassetti C, Aldrich MS. Idiopathic hypersomnia: a series of 42 patients. Brain 1997;120:1423–35.

Dauvilliers Y, Delallee N, Jaussent I, et al. Normal cerebrospinal fluid histamine and tele-
methylhistamine levels in hypersomnia conditions. Sleep 2012;35:1359–66.

Kanbayashi T, Kodama T, Kondo H, et al. CSH histamine contents in narcolepsy, idiopathic

hypersomnia and obstructive sleep apnea syndrome. Sleep 2009;32:181–7.

Vernet C, Arnulf I. Idiopathic hypersomnia with and without long sleep time: a controlled series of 75
patients. Sleep 2009;32:753–9.

Vernet C, Leu-Semenescu S, Buzare MA, Arnulf I. Subjective sleepiness in idiopathic hypersomnia:

beyond excessive sleepiness. J Sleep Res 2010;19:525–34.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Central Disorders of Hypersomnolence ›› Disorders ››

Kleine-Levin Syndrome

ICD-9-CM code: 327.13

ICD-10-CM code: G47.13

Alternate Names
Recurrent hypersomnia, periodic hypersomnolence.

Diagnostic Criteria

Criteria A-E must be met

A. The patient experiences at least two recurrent episodes of excessive sleepiness and sleep duration,
each persisting for two days to five weeks.

B. Episodes recur usually more than once a year and at least once every 18 months.

C. The patient has normal alertness, cognitive function, behavior, and mood between episodes.

D. The patient must demonstrate at least one of the following during episodes:

1. Cognitive dysfunction.

2. Altered perception.

3. Eating disorder (anorexia or hyperphagia).

4. Disinhibited behavior (such as hypersexuality).

E. The hypersomnolence and related symptoms are not better explained by another sleep disorder,
other medical, neurologic, or psychiatric disorder (especially bipolar disorder), or use of drugs or
medications.

Essential Features

Kleine-Levin syndrome is characterized by relapsing-remitting episodes of severe hypersomnolence

in association with cognitive, psychiatric, and behavioral disturbances. A typical episode lasts a
median 10 days (range, 2.5–80 days), with rare episodes lasting several weeks to months. The first
episode is often triggered by an infection or alcohol intake, with further episodes recurring every 1–12
months (median three months) for years. During episodes, patients may sleep as long as 16 to 20
hours per day, waking or getting up only to eat and void (incontinence is not observed). They remain
rousable, but are irritable if prevented from sleeping. When they are awake during episodes, most
patients are exhausted, apathetic, confused, and slow in speaking and answering. Anterograde
amnesia is typical. Almost all report a dreamlike, altered perception of the environment
(derealization). Less commonly, patients eat ravenously (66%, although one third eat less), are
hypersexual (53%, principally men), childish, depressed (53%, predominantly women), and anxious
at being left alone and seeing strangers, and experience hallucinations and delusions (30%). Patients
are remarkably normal between episodes with regard to sleep, cognition, mood, and eating. The
disease typically resolves after a median of 14 years, except in adult-onset cases, when the course may
be more prolonged. The simultaneous occurrence of all these symptoms is the exception rather than
the rule, with hypersomnolence being more characteristic at the disease onset and during the first part
of the episodes, and disinhibited behaviors being evident during only a few episodes. In occasional
cases, isolated recurrent hypersomnolence may be the only symptom. Amnesia, transient dysphoria,
or elation with insomnia may signal the termination of an episode.

Associated Features
Physical examination is unremarkable, except for general psychomotor slowing. Social and
occupational impairment during attacks is often severe, with teenagers bedridden for days, but can be
variable depending on the frequency, severity, and duration of episodes.

Clinical and Pathophysiological Subtypes

Menstrual-related Kleine-Levin syndrome (alternate name: menstrual-related hypersomnia): This

descriptor is used when episodes are exclusively associated with menstruation (occurring just before
or during menses), a condition reported in only 18 women worldwide. Hypersomnolence episodes in
these cases have been associated with compulsive eating in 65%, sexual disinhibition in 29%, and
depressive mood in 35%. Episodes last 3 to 15 days and recur less than three times a year. One boy
with Kleine-Levin syndrome is reported to have a sister affected by menstrual-related
hypersomnolence. Menstrual-related hypersomnia may be a variant of Kleine-Levin syndrome,
although response to contraceptive doses of estrogen and progesterone, reported in some cases,
suggests a reproductive endocrine disturbance.

Demographics

Kleine-Levin syndrome is rare, with a prevalence estimated around 1 to 2 cases per million. Roughly
500 cases have been reported to date in the literature, from all countries in which the disease has been
investigated. The disease starts during the second decade in 81% of patients, with a male/female ratio
of 2:1. Adults and younger children may also be affected.

Predisposing and Precipitating Factors

Birth and developmental problems, as well as Jewish heritage, are risk factors for developing the
syndrome. The frequency of the HLA DQB1*02 was increased compared with controls in a
retrospective, multicenter series of 30 patients with Kleine-Levin syndrome, but not in another larger
prospective series (n = 108). A flu-like illness or an infection of the upper airway (and more rarely
gastroenteritis) is often reported immediately prior to the onset of the first episode, and more rarely
before relapses. Other less frequently reported triggering events include alcohol consumption, head
trauma, travel, or exposure to anesthesia.

Familial Patterns

Familial cases of Kleine-Levin syndrome are found in 5% of patients, including twins, parent-child,
siblings, and uncle-nephew associations. There is no increased history of mood disorders in family
members of patients.

Onset, Course, and Complications

Early adolescence (second decade) is the usual age of onset. The course of Kleine-Levin syndrome is
characterized by recurrent episodes of severe sleepiness, lasting up to several weeks, with normal
functioning between episodes. Several long-term studies suggest an often-benign course, with
episodes lessening in duration, severity, and frequency over a median course of 14 years. Male sex,
age at onset younger than 12 years or older than 20 years, as well as the presence of hypersexuality
during episodes, predict longer disease duration. Complications are mainly social and occupational. In
rare cases, subjects have been reported to choke while eating voraciously, to have suicidal thoughts,
or to be involved in a car accident. A reduced long-term working memory capacity following episodes
was reported in eight patients with Kleine-Levin syndrome.
Developmental Issues

Adolescents are affected in most cases. However, the onset of the condition has been reported in
children as young as four years.

Pathology and Pathophysiology

Postmortem examination of the central nervous system has been performed in only four cases, with
inconsistent findings. One subject showed significant perivascular lymphocytic infiltrations in the
hypothalamus, amygdala, and the grey matter of the temporal lobes; a second demonstrated similar
infiltrations in the thalamus; and a third in the diencephalon and the midbrain with a suggestion of
mild localized encephalitis. In the fourth case, a smaller locus coeruleus and decreased pigmentation
in the substantia nigra were reported. Magnetic resonance imaging was unremarkable. In contrast,
functional brain imaging studies during episodes are frequently abnormal, showing hypometabolism
in the thalamus, hypothalamus, mesial temporal lobe, and frontal lobe. Some of these abnormalities
persist during asymptomatic periods in half of the patients. An autoimmune basis for the disorder is
suggested clinically (onset occurs during adolescence, often in conjunction with an infection) and by
the occasional association with HLA DQB1*02.

Objective Findings

Routine electroencephalograms obtained during episodes have shown general slowing of background
electroencephalographic activity and often paroxysmal—0.5-2.0-second—bursts of bisynchronous,
generalized, moderate- to high-voltage 5- to 7-Hz waves. Polysomnography studies are often difficult
to interpret, and results are dependent on the duration of recording (overnight vs. 24-hour monitoring)
as well as the timing (at the beginning versus the end of episodes or at onset of the disease or later in
its course). Twenty-four-hour polysomnography demonstrates prolonged total sleep time (a mean 11–
12 hours), and 18 hours or more in some reports. During nocturnal polysomnography in 17 children,
nighttime slow wave sleep percentage was decreased during the first half of the episodes, and REM
sleep decreased  during  the  second  half.  Results  of  the  MSLT  are  highly  dependent  on  the  subjects’  
willingness to comply with the procedure, and may either be normal or abnormal, showing short
latencies or multiple SOREMPs. CSF cytology and protein are normal. CSF levels of hypocretin-1
were within normal range in 16 patients, although intraepisodic levels are lower than interepisodic
levels. Computed tomography scans and magnetic resonance imaging are normal. Brain functional
imaging is abnormal in most cases, with hypoperfusion of the left or right temporal and frontal lobes
as well as the diencephalon. These abnormalities are present during the episode of hypersomnolence
and sometimes between episodes. Hormone levels are normal, as are 24-hour secretory patterns.

Differential Diagnosis

Recurrent waxing and waning episodes of sleepiness may be secondary to structural insults of the
central nervous system. Tumors within the third ventricle (such as colloid cysts, pedunculated
astrocytomas, or, in some cases, craniopharyngiomas) may produce intermittent obstructions of
ventricular flow, leading to headaches, vomiting, vague sensorial disturbances, and a paroxysmal
impairment of alertness. Encephalitis, hyperammonemic encephalopathy, multiple sclerosis, head
trauma, porphyria, Lyme disease, basilar migraine, and complex partial status epilepticus less
frequently mimic symptoms of Kleine-Levin syndrome. Recurrent episodes of sleepiness also are
reported in the context of psychiatric disorders, such as depression, bipolar disorder, seasonal
affective disorder, and somatoform disorder. However, the onset and offset of symptoms are less
abrupt than in Kleine-Levin syndrome and persist to some extent between episodes. Other differential
diagnoses include excessive sleepiness due to a medication or substance, OSA, narcolepsy,
IH, and insufficient sleep. In these disorders, however, the complaint of excessive sleepiness occurs
daily and is usually not recurrent or periodic. There is no evidence that Kleine-Levin syndrome occurs
as a result of a seizure disorder.

Unresolved Issues and Further Directions

The pathophysiology of this disorder is not known. Evidence to date suggests that a localized but
multifocal encephalopathy occurs during episodes of Kleine-Levin syndrome, as functional imaging
and electroencephalography (EEG) slowing indicate thalamic, temporal, and frontal lobe involvement.
The cause of these episodic abnormalities may be genetic, autoimmune, inflammatory, or metabolic.

Bibliography

Arnulf I, Lin L, Gadoth N, et al. Kleine-Levin syndrome: a systematic study of 108 patients. Ann
Neurol 2008;63:482–93.

Arnulf I, Zeitzer JM, File J, Farber N, Mignot E. Kleine-Levin syndrome: a systematic review of 186
cases in the literature. Brain 2005;128:2763–76.

Billiard M, Jaussent I, Dauvilliers Y, Besset A. Recurrent hypersomnia: a review of 339 cases. Sleep
Med Rev 2011;15:247–57.

Dauvilliers Y, Mayer G, Lecendreux M, et al. Kleine-Levin syndrome. An autoimmune hypothesis

based on clinical and genetic analyses. Neurology 2002;59:1739–45.

Engström M, Vigren P, Karlsson T, Landtblom A. Working memory in 8 Kleine-Levin syndrome

patients: An fMRI study. Sleep 2009;32:681–8.

Gadoth N, Kesler A, Vainstein G, Peled R, Lavie P. Clinical and polysomnographic characteristics of

34 patients with Kleine-Levin syndrome. J Sleep Res 2001;10:337–41.

Huang Y, Lin Y, Guilleminault C. Polysomnography in Kleine-Levin syndrome. Neurology

2008;70:795–801.

Huang Y, Guilleminault C, Lin K, Hwang F, Liu F, Kung Y. Relationship between Kleine-Levin

Syndrome and upper respiratory infection in Taiwan. Sleep 2012;35:123–9.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Central Disorders of Hypersomnolence ›› Disorders ››

Hypersomnia Due to a Medical Disorder

ICD-9-CM code: 327.14

ICD-10-CM code: G47.14

Alternate Names

Not applicable.

Diagnostic Criteria

Criteria A-D must be met

A. The patient has daily periods of irrepressible need to sleep or daytime lapses into sleep occurring
for at least three months.

B. The daytime sleepiness occurs as a consequence of a significant underlying medical or

neurological condition.

C.  If  an  MSLT  is  performed,  the  mean  sleep  latency  is  ≤  8  minutes,  and  fewer  than two sleep onset
REM periods (SOREMPs) are observed.1

D. The symptoms are not better explained by another untreated sleep disorder,2 a mental disorder, or
the effects of medications or drugs.

Notes

1. In the subtype of residual hypersomnolence after treatment of obstructive sleep apnea, the MSLT
mean latency may be > 8 minutes.

2. Should criteria for narcolepsy be fulfilled, a diagnosis of narcolepsy type 1 or type 2 due to a
medical condition should be used rather than hypersomnia due to a medical condition.

3. In patients with severe neurological or medical disorders in whom it is not possible or desirable to
perform sleep studies, the diagnosis can be made by clinical criteria.

Essential Features

Patients with this disorder have excessive nocturnal sleep, daytime sleepiness, or excessive napping
that is attributable to a coexisting medical or neurological disorder. Daytime sleepiness may be of
variable severity and may resemble that of narcolepsy (i.e., refreshing naps) or idiopathic
hypersomnia (i.e., long periods of unrefreshing sleep). Sleep paralysis, hypnagogic hallucinations, or
automatic behavior may be present, but if the patient has cataplexy, the MSLT shows two or more
SOREMPs, or CSF Hcrt-1 levels are low, then narcolepsy (type 1 or type 2) due to a medical
condition should be diagnosed. In patients with both sleep related breathing disorders and
hypersomnia due to a medical disorder, the latter diagnosis should be made only if the
hypersomnolence persists after adequate treatment of the sleep disordered breathing. Hypersomnia
due to a medical disorder is only diagnosed if the medical condition is judged to be directly causing
the excessive sleepiness. Hypersomnolence has been described in association with a large range of
conditions, including metabolic encephalopathy, head trauma, stroke, brain tumors, encephalitis,
systemic inflammation (e.g., chronic infections, rheumatologic disorders, cancer), genetic disorders,
and neurodegenerative diseases.

Associated Features

Not applicable or known.

Clinical and Pathophysiological Subtypes

Many medical conditions can cause hypersomnolence.

Hypersomnia secondary to Parkinson disease: Significant hypersomnolence documented by MSLT

has been reported in some cases of Parkinson disease. Hypersomnia in Parkinson disease may be due
to insufficient control of nocturnal symptoms, resulting in insufficient sleep and daytime sleepiness. If
so, the diagnosis should be insomnia disorder. Cases of hypersomnolence that are due to the side
effects of dopaminergic agents should be coded as hypersomnia due to a medication or substance. In
other cases, however, hypersomnolence is likely of central origin and should be classified in this
section. Parkinson disease patients with an MSLT profile consistent with narcolepsy should be coded
as narcolepsy due to a medical condition.

Posttraumatic hypersomnia: Hypersomnolence appears to be common after traumatic brain injury

(TBI), with one meta-analysis suggesting a frequency of 28% of TBI patients. In some cases this may
be caused by injury to the hypocretin/orexin neurons or other wake-promoting neural systems.
However, the prevalence of sleep related breathing disorder (SRBD) in patients with head trauma is
high (frequency 23% to 25%). The nature of the relationship between TBI and OSA remains
undefined. Therefore, control of other potential sleep disorders is necessary prior to making a
diagnosis of hypersomnia due to a medical disorder (posttraumatic hypersomnia).

Genetic disorders associated with primary central nervous system somnolence: Genetic disorders
such as Niemann Pick type C disease and Norrie disease have been associated with daytime
somnolence. Prader-Willi syndrome, myotonic dystrophy, Moebius syndrome, and fragile X
syndrome are other examples of centrally mediated sleepiness. A number of genetic disorders have
been reported to be associated with both sleep disordered breathing and hypersomnolence (e.g.,
myotonic dystrophy and Prader-Willi syndrome). In these cases, hypersomnia due to a medical
disorder should be diagnosed only if the excessive sleepiness is still present after adequate treatment
of the SRBD. Smith-Magenis syndrome is a neurodevelopmental disorder characterized by
dysmorphic facial features, behavioral disturbance with onset in early childhood, daytime
somnolence, and night awakenings in association with reversal in the timing of the melatonin
secretion pattern (i.e., the serum levels of melatonin are high during the daytime and low at night).

Hypersomnia secondary to brain tumors, infections, or other central nervous system

lesions: Strokes, infections, tumors, sarcoidosis, or neurodegenerative lesions of the brain, especially
in the hypothalamus or rostral midbrain, may produce daytime sleepiness. In patients with brain
tumors, the sleepiness may be due to the tumor itself or the effects of treatment.

Hypersomnia secondary to endocrine disorder: Hypothyroidism is the most recognized example of

this condition.

Hypersomnia secondary to metabolic encephalopathy: Hepatic encephalopathy, chronic renal

insufficiency, adrenal or pancreatic insufficiency, exposure to toxins, and certain inherited metabolic
disorders in childhood may result in hypersomnolence.

Residual hypersomnia in patients with adequately treated OSA: Some patients with SRBDs report
persistent sleepiness despite apparently adequate amounts of sleep and optimal treatment of their sleep
apnea and other known sleep disorders. They may have moderately elevated Epworth Sleepiness
Scale scores, but most have mean sleep latencies > 8 minutes on MSLT. They also report more
fatigue, apathy, and depression. It is essential that sleep disordered breathing be fully treated for at
least three months, and that control of the SRBD be confirmed by: (1) a download of positive airway
pressure (PAP) machine compliance data demonstrating optimal usage (preferably at least 7 hours a
night); and (2) a polysomnogram demonstrating elimination of essentially all sleep disordered
breathing. Other causes of sleepiness, such as insufficient sleep syndrome, psychiatric disorders, or
hypersomnolence related to medications or drugs must be eliminated. Animal studies have suggested
this residual sleepiness could be caused by hypoxic injury to monoamine systems. Obesity itself may
also contribute, and more research is needed to understand the underlying mechanism.

Demographics

Demographics reflect those of the underlying condition.

Predisposing and Precipitating Factors

Predisposing and precipitating factors reflect those of the underlying condition.

Familial Patterns

Familial patterns reflect those of the underlying condition.

Onset, Course, and Complications

Onset, course, and complications reflect those of the underlying condition.

Developmental Issues

Daytime naps are normal in children younger than 3-4 years; thus, it is difficult to differentiate
physiologic napping from hypersomnolence in children younger than this age. Inattentiveness, mood
swings, and learning difficulties often accompany childhood daytime sleepiness. Reference values for
the MSLT in children differ from those of adults, and this issue should be considered during the
evaluation process. Special attention should be paid to genetic disorders in children.

Pathology and Pathophysiology

Pathology and pathophysiology reflect those of the underlying condition.

Objective Findings

Nocturnal polysomnography may show normal or moderately disturbed sleep. In patients with a
metabolic encephalopathy, EEG abnormalities may be present, such as an increase in the amount of
slow wave sleep. MSLT must show fewer than 2 SOREMPs and usually will show a mean sleep
latency less than eight minutes. If clinically significant sleep disordered breathing or periodic limb
movements are present, they should be treated prior to diagnosing hypersomnia due to a medical
disorder.

Differential Diagnosis

See the differential diagnosis in previous hypersomnolence sections. The major challenge in
establishing a diagnosis of hypersomnia due to a medical disorder is determining whether the
associated medical or neurological disorder is truly causing the hypersomnolence.

Unresolved Issues and Further Directions

This area is understudied. Multiple complex neurological, metabolic, endocrine, and medication-
related interactions may be present. Further studies are needed to define the reciprocal relationships
between sleep disorders and other diseases.

Bibliography

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sleep disorders in traumatic brain injury. J Clin Sleep Med 2007;3:349–56.

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Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Central Disorders of Hypersomnolence ›› Disorders ››

Hypersomnia Due to a Medication or Substance

ICD-9-CM code: 292.85 (drug-induced); 291.82 (alcohol-induced)

ICD-10-CM code: F11-F19 (see table in Appendix B for detailed coding instructions)

Alternate Names
Hypersomnia due to substance abuse, hypersomnia due to stimulant withdrawal, hypersomnia due to
sedative abuse, toxic hypersomnia, toxic encephalopathy.

Diagnostic Criteria

Criteria A-C must be met

A. The patient has daily periods of irrepressible need to sleep or daytime lapses into sleep.

B. The daytime sleepiness occurs as a consequence of current medication or substance use or

withdrawal from a wake-promoting medication or substance.

C. The symptoms are not better explained by another untreated sleep disorder, medical or
neurological disorder, or mental disorder.

Essential Features

Patients with this disorder have excessive nocturnal sleep, daytime sleepiness, or excessive napping
that is attributable to sedating medications, alcohol, or drugs of abuse. This diagnosis also includes
hypersomnolence associated with withdrawal from amphetamines and other drugs. If narcolepsy or
hypersomnolence existed prior to stimulant abuse, the diagnosis of hypersomnia due to a medication
or substance should not be used.

Associated Features

Associated features reflect those of the medications or substances responsible.

Clinical and Pathophysiological Subtypes

Hypersomnia due to sedating medications: Sedation is a common side effect of many prescription
medications including benzodiazepines, nonbenzodiazepine hypnotics, opioids, barbiturates,
anticonvulsants, antipsychotics, anticholinergics, and some antidepressants and antihistamines.
Sleepiness also can occur with some dopamine agonists such as pramipexole or ropinirole, and with
many antiseizure medications. Though less common, sleepiness can also occur with nonsteroidal anti-
inflammatory drugs, some antibiotics, antispasmodics, antiarryhthmics, and beta-blockers. Over-the-
counter medications, such as valerian and melatonin, can produce sedation. Excessive sleepiness is
especially common when these drugs are used in elderly patients or those with multiple medical
conditions, or in combination. Some tolerance to the sedative effects can occur with time.

Hypersomnia due to substance abuse: Daytime sleepiness can occur with abuse of alcohol,
benzodiazepines, barbiturates, gamma hydroxybutyrate, opiates, and marijuana.

Hypersomnia due to stimulant withdrawal: Daytime sleepiness is common with abrupt

discontinuation of stimulants. In chronically heavy amphetamine users, sleepiness is most severe in
the first week of withdrawal and can persist for up to three weeks; individuals may have an increase in
total sleep and daytime napping, but sleep may seem fragmented and nonrestorative. Significant
depression often accompanies the hypersomnolence. Infrequently, sleepiness may be a residual
complaint in those who have used stimulants in the past but have been abstinent for many years. In
people who regularly consume coffee or other sources of caffeine, discontinuation can produce
sleepiness, fatigue, and inattentiveness for two to nine days.
Demographics

Patients of any age can experience sleepiness from sedating medications. Stimulant abuse and the
consequent sleepiness during withdrawal are most common in adolescents and young adults.

Predisposing and Precipitating Factors

Sleepiness from sedating medications may be more common in older patients and in those with
multiple medical problems.

Familial Patterns

Not applicable or known.

Onset, Course, and Complications

Onset, course, and complications reflect those of the medications or substances responsible.

Pathology and Pathophysiology

Not applicable or known.

Objective Findings

Polysomnography is generally unnecessary unless a concomitant sleep disorder is suspected.

Polysomnography and MSLT results vary depending on the specific substance in question and the
timing of the most recent intake. With stimulant withdrawal, nocturnal polysomnography may show
normal sleep, whereas the MSLT typically demonstrates a short mean sleep latency with or without
multiple SOREMPs. A urine toxicology screen may be positive for the suspected substance. The
diagnosis is often confirmed if symptoms resolve after the causal agent is removed.

Differential Diagnosis

Major sleep disorders that are associated with excessive sleepiness, especially SRBDs, periodic limb
movement disorder, narcolepsy, IH, and insufficient sleep syndrome should be ruled out. A urine drug
screen should routinely accompany an MSLT as the use of or withdrawal from some medications or
substances may affect MSLT test results.

Although many psychotropic medications may result in daytime sleepiness, it is important for
clinicians to recognize that many psychiatric disorders also are associated with increased prevalence
of other sleep disorders (e.g., insomnia, SRBD, circadian disorders, and movement disorders).
Although sedative effects of the psychotropic agents may contribute to sleepiness, clinicians must
maintain a high index of suspicion for other sleep related etiologies. When other sleep disorders are
identified, multiple diagnoses may be appropriate.

Unresolved Issues and Further Directions

Sedatives can worsen sleep related breathing disorders, and more research is needed to understand and
manage this interaction.

Bibliography
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España RA, Scammell TE. Sleep neurobiology from a clinical perspective. Sleep 2011;34:845–58.

Gillin JC, Smith TL, Irwin M, Butters N, Demodena A, Schuckit M. Increased pressure for rapid eye
movement sleep at time of hospital admission predicts relapse in nondepressed patients with primary
alcoholism at 3-month follow-up. Arch Gen Psychiatry 1994;51:189–97.

Guilleminault C, Brooks SN. Excessive daytime sleepiness: a challenge for the practicing neurologist.
Brain 2001;124:1482–91.

Juliano LM, Griffiths RR. A critical review of caffeine withdrawal: empirical validation of symptoms
and signs, incidence, severity, and associated features. Psychopharmacology (Berl) 2004; 176:1–29.

McGregor C, Srisurapanont M, Jittiwutikarn J, Laobhripatr S, Wongtan T, White JM. The nature,

time course and severity of methamphetamine withdrawal. Addiction 2005;100:1320–9.

Mogri M, Desai H, Webster L, Grant BJ, Mador MJ. Hypoxemia in patients on chronic opiate therapy
with and without sleep apnea. Sleep Breath 2009;13:49–57.

Punjabi NM. The epidemiology of adult obstructive sleep apnea. Proc Am Thorac Soc 2008;5:136–
43.

Qureshi A, Lee-Chiong T. Medications and their effects on sleep. Med Clin North Am 2004;88:751–
66.

Roehrs T, Roth T. Sleep, sleepiness, and alcohol use. Alcohol Res Health 2001;25:101–9.

Roehrs T, Bonahoom A, Pedrosi B, Zorick F, Roth T. Nighttime versus daytime hypnotic self-
administration. Psychopharmacology 2002;161:137–42.

Schweitzer P. Drugs that disturb sleep and wakefulness. In: Kryger MH, Roth T, Dement WC, eds.
Principles and practice of sleep medicine, 5th ed. St Louis: Elsevier Saunders, 2011:542–60.

William Ishak W, Ugochukwu C, Bagot K, Khalili D, Zaky C. Energy drinks: psychological effects
and impact on well-being and quality of life-a literature review. Innov Clin Neurosci 2012;9:25–34.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Hypersomnia Associated with a Psychiatric Disorder

ICD-9-CM code: 327.15

ICD-10-CM code: F51.13

Alternate Names

Hypersomnia not due to substance or known physiological condition, nonorganic hypersomnia,

pseudohypersomnia, or pseudonarcolepsy.
Diagnostic Criteria

Criteria A-C must be met

A. The patient has daily periods of irrepressible need to sleep or daytime lapses into sleep occurring
for at least three months.

B. The daytime sleepiness occurs in association with a concurrent psychiatric disorder.

C. The symptoms are not better explained by another untreated sleep disorder, a medical or
neurological disorder, or the effects of medications or drugs.

Essential Features

Patients with hypersomnia associated with a psychiatric disorder may report excessive nocturnal
sleep, daytime sleepiness, or excessive napping. In addition, they often feel their sleep is of poor
quality and nonrestorative. Patients are often intensely focused on their hypersomnolence, and
psychiatric symptoms may become apparent only after prolonged interviews or psychometric testing.
Associated psychiatric conditions include mood disorders, conversion or undifferentiated somatoform
disorder, and less frequently other mental disorders such as schizoaffective disorder, adjustment
disorder, or personality disorders.

Associated Features

Poor work attendance, spending full days in bed several times a week, or abruptly leaving work
because of a perceived need to sleep are common symptoms. Patients may also have social
withdrawal, apathy, and feelings of low energy.

Clinical and Pathophysiological Subtypes

Hypersomnia associated with mood disorder: Hypersomnolence in the context of depression is a

frequent feature of atypical depression and bipolar II disorder (recurrent major depressive episodes
with hypomanic episodes). In seasonal affective disorder, daytime fatigue, loss of concentration,
increased appetite for carbohydrates, and weight gain are reported. MSLT results are usually normal,
but long hours spent in bed are reported.

Hypersomnia associated with a conversion disorder or somatic symptom

disorder:Pseudohypersomnia or pseudonarcolepsy, sometimes with pseudocataplexy, has been
described.

Demographics

Hypersomnia associated with a psychiatric disorder accounts for 5% to 7% of hypersomnolence cases.

Women are more susceptible than men, and the typical age range is between 20 and 50 years. In
patients with major depression, the prevalence of hypersomnolence ranges from 5% to over 50%
depending on how hypersomnolence is defined. Hypersomnolence affects over 50% of patients with
seasonal affective disorder.

Predisposing and Precipitating Factors

Not applicable or known.

Familial Patterns

Not known, except for the familial patterns of certain psychiatric disorders (e.g., bipolar II disorder).

Onset, Course, and Complications

The mean age of onset is usually in the third decade in both sexes. With major depression,
hypersomnolence may persist even after the depressive episode improves, and persistent
hypersomnolence is associated with increased risk of recurrent depression. Complications are mostly
social and occupational.

Developmental Issues

Hypersomnolence occurs in 10% to 20% of children with major depression, sometimes in

combination with insomnia, but sleep quality appears normal. Although sleep problems may develop
at any stage of depression, they are most pronounced during the acute phase. Children and adolescents
with depression who manifest either insomnia or hypersomnolence generally manifest more
pronounced symptoms, such as anhedonia and weight loss.

Pathology and Pathophysiology

The underlying cause is unknown. Although patients with this disorder report sleepiness, sleep studies
reveal little or no evidence of increased propensity to sleep. In some patients, fragmented nighttime
sleep may contribute to their daytime sleepiness. Because of uncertainty about the nature of the
relationship,  the  term  “hypersomnia associated with a  psychiatric  disorder”  is  preferred  to  
“hypersomnia due to a  psychiatric  disorder.”

Objective Findings

Nocturnal polysomnography typically shows a prolonged total time in bed with fragmented sleep.
Sleep latency is prolonged, wake time after sleep onset is increased, awakenings may be frequent and
prolonged, and sleep efficiency is low. REM sleep latency may be shortened in the case of untreated
depression. Sleep latencies on the MSLT are often within normal limits, a result contrasting with the
subjective complaint of daytime sleepiness and an elevated score on the Epworth Sleepiness Scale.
24-hour continuous sleep-recording studies typically show considerable time spent in bed during day
and night, a behavior sometime referred to as clinophilia. Psychiatric interviews and evaluations are
essential to diagnose the underlying psychiatric condition.

Differential Diagnosis

As there are no definitive tests for diagnosing hypersomnolence associated with a psychiatric
disorder, it is essential to rule out other common causes of sleepiness such as insufficient sleep,
sedation from medications or substances, SRBD, periodic limb movement disorder, and IH. Chronic
fatigue syndrome is characterized by persistent or relapsing fatigue that does not resolve with sleep or
rest, but the main complaint is usually fatigue rather than sleepiness. Insufficient sleep syndrome is
associated with excessive daytime sleepiness, impaired concentration, and lowered energy level, but a
detailed  history  of  the  subject’s  current  sleep  schedule  reveals  chronic  sleep  deprivation.

Unresolved Issues and Further Directions

The lack of concordance between subjective and objective findings raises multiple issues. It is unclear
to what extent these patients are objectively sleepy or, instead, suffer from decreased energy and lack
of interest that confines them to bed. More research is needed to create an effective definition of
hypersomnolence in this population and to develop tools for measuring it. Finally, future efforts
should define the mechanism through which some patients express their psychiatric symptoms as
excessive sleepiness.

Bibliography

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Brain 2001;124:1282–91.

Kaplan KA, Harvey AG. Hypersomnia across mood disorders: a review and synthesis. Sleep Med Rev
2009;13:275–85.

Kotagal S. Hypersomnia in children: interface with psychiatric disorders. Child Adolesc Psychiatr
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phenomenology and comorbidity in childhood depression. Sleep 2007;30:83–90.

Nofzinger EA, Thase ME, Reynolds CF 3rd, et al. Hypersomnia in bipolar depression: a comparison
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Partonen T, Lönnqvist J. Seasonal affective disorder. Lancet 1998;352:1369–74.

van den Berg JF, Luijendijk HJ, Tulen JH, Hofman A, Neven AK, Tiemeier H. Sleep in depression
and anxiety disorders: a population-based study of elderly persons. J Clin Psychiatry 2009;70:1105–
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Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Insufficient Sleep Syndrome

ICD-9-CM code: 307.44

ICD-10-CM code: F51.12

Alternate Names

Behaviorally induced insufficient sleep syndrome, insufficient nocturnal sleep, chronic sleep
deprivation, sleep restriction.

Diagnostic Criteria
Criteria A-F must be met

A. The patient has daily periods of irrepressible need to sleep or daytime lapses into sleep or, in the
case of prepubertal children, there is a complaint of behavioral abnormalities attributable to
sleepiness.

B. The patient's sleep time, established by personal or collateral history, sleep logs, or actigraphy1 is
usually shorter than expected for age.2

C. The curtailed sleep pattern is present most days for at least three months.

D. The patient curtails sleep time by such measures as an alarm clock or being awakened by another
person and generally sleeps longer when such measures are not used, such as on weekends or
vacations.

E. Extension of total sleep time results in resolution of the symptoms of sleepiness.

F. The symptoms are not better explained by another untreated sleep disorder, the effects of
medications or drugs, or other medical, neurologic, or mental disorder.

Notes

1. If there is doubt about the accuracy of personal history or sleep logs, then actigraphy should be
performed, preferably for at least two weeks.

2. In the case of long sleepers, reported habitual sleep periods may be normal based on age. However,
these sleep periods may be insufficient for these patients.

Essential Features

Insufficient sleep syndrome occurs when an individual persistently fails to obtain the amount of sleep
required to maintain normal levels of alertness and wakefulness. The individual is chronically sleep
deprived as a result of failure to achieve necessary sleep time due to reduced time in bed. There is a
U-shaped relationship between age and average sleep time, with the minimum in middle-aged
individuals. Examination reveals unimpaired or above-average ability to initiate and maintain sleep,
with little or no psychopathology. Physical examination reveals no medical explanation for the
patient’s  sleepiness.  A  detailed  history  of  the  sleep  pattern reveals a substantial disparity between the
need for sleep and the amount actually obtained. The significance of this disparity often goes
unappreciated by the patient. Sleep time that is markedly extended on weekend nights or during
holidays compared to weekday nights is also suggestive of this disorder. A therapeutic trial of a longer
major sleep episode can reverse the symptoms. In individuals with physiologic sleep requirements
significantly  in  excess  of  seven  to  eight  hours,  reported  “average”  amounts of sleep (e.g., seven
hours/night) may, in fact, be insufficient. Additional symptoms such as sleep paralysis and
hypnagogic hallucinations may occur.

Associated Features

Depending upon chronicity and extent of sleep loss, individuals with this condition may show
irritability, concentration and attention deficits, reduced vigilance, distractibility, reduced motivation,
anergia, dysphoria, fatigue, restlessness, uncoordination, and malaise. Secondary symptoms may
become the main focus of the patient, serving to obscure the primary cause of the difficulties.
Psychologically and somatically normal individuals who chronically obtain less sleep than they
physiologically require typically experience daytime sleepiness. Situational factors such as demands
of the family and work schedule may, on occasion, make it very difficult to obtain adequate sleep.

Clinical and Pathophysiological Subtypes

Not applicable or known.

Demographics

Insufficient sleep syndrome affects all ages and both sexes. It may be more frequent in adolescence,
when sleep need is high, but social pressure and tendency to delay sleep often lead to chronic
restricted sleep. Cultural factors may also influence sleep duration, with students from different
countries reporting sleep time varying between six and eight hours per night.

Predisposing and Precipitating Factors

Social and psychological factors may impact nocturnal sleep length and daytime sleepiness. Cultural
habits such as the siesta may enhance evening alertness at the expense of reducing nocturnal sleep
efficiency. Also, the evening preference chronotype predisposes to complaints of insomnia and
insufficient sleep. The association of eveningness with insufficient sleep persists after controlling for
variables such as sex, age, and sleep duration.

Familial Patterns

Not applicable or known.

Onset, Course, and Complications

This condition results in increased daytime sleepiness, concentration problems, lowered energy level,
and malaise. If unchecked, insufficient sleep syndrome may predispose to depression and other
psychological difficulties, as well as poor work performance and withdrawal from family and social
activities. Abuse of stimulants may also occur. Traffic accidents or injury at work may result.

Developmental Issues

Insufficient sleep syndrome is a common problem in adolescents. It should be differentiated from

delayed sleep phase disorder, the effects of recreational drug use, and school avoidance behavior.
Increased predisposition to substance use and accidents in teens may be consequent to insufficient
sleep.

Pathology and Pathophysiology

Symptoms are due to normal physiological and psychological responses to sleep deprivation. Sleep
restriction studies in normal volunteers have shown that even mild sleep restriction (for example, six
hours of nocturnal sleep per night) results in a corresponding decrease in performance and increased
sleepiness. Sleep restriction to four hours per night (i.e., extension of wakefulness to 20 hours per
day) will likely lead to greater buildup of homeostatic sleep drive during the waking hours and greater
likelihood of impaired performance on a psychomotor vigilance task. The effects of sleep deprivation
on neurobehavioral performance measures may vary with the nature of the task being considered.
In some long sleepers, it is important to be aware that extending sleep to nine or more hours often
results in improved performance. The diagnosis of insufficient sleep syndrome may be especially
difficult to make in subjects who have a physiologic need for unusually large amounts of sleep.

Objective Findings

Actigraphy combined with sleep diaries maintained for a 2- to 3-week period may be helpful by
documenting total time in bed, sleep latency, total sleep time, and sleep efficiency. Polysomnography
and MSLT are not required to establish a diagnosis of insufficient sleep syndrome. Rather, sleep time
is extended first, and the patient is reevaluated. If a therapeutic trial with a longer sleep episode
eliminates the symptoms, insufficient sleep syndrome is diagnosed.

Polysomnography, when performed, reveals reduced sleep onset latency, and high (greater than 90%)
sleep efficiency. When extended sleep is permitted, prolonged sleep time with slow wave rebound
may be seen. Noting a disparity between reported sleep at home and observed total sleep time in the
sleep laboratory can be helpful. The MSLT reveals excessive sleepiness, with stage N1 sleep
occurring in most naps, with short sleep latency. Stage N2 sleep occurs in more than 80% of MSLT
naps. SOREMPs can occur.

Differential Diagnosis

Insufficient sleep syndrome may be confused with narcolepsy or other hypersomnolence

disordersbecause an abnormal MSLT (even with two SOREMPs) can be observed as the result of
acute or chronic sleep deprivation. The confusion may be most frequently encountered in adolescents
or young adults. The differential diagnosis of insufficient sleep syndrome includes numerous other
conditions that may result in daytime sleepiness or shortening of nocturnal sleep duration. These
include other central disorders of hypersomnolence, long sleeper or short sleeper, SRBD, circadian
rhythm sleep disorders, insomnia disorder, affective disorder, and periodic limb movement disorder.

Unresolved Issues and Further Directions

The correlation between subjectively reported sleepiness, performance-test decrements, and MSLT-
measured sleepiness after sleep deprivation is poor. Short sleepers often have a higher NREM sleep
pressure, as measured by EEG delta power, than long sleepers, even if they do not complain of
daytime sleepiness. There is interindividual susceptibility to sleep deprivation, with some people
being consistently more tired and experiencing greater performance decrement after even a mild
degree of sleep deprivation.

Bibliography

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1979;48:495–506.

Habeck C, Rakitin BC, Moeller J, et al. An event related fMRI study of the neurobehavioral impact of
sleep deprivation on performance of a delayed match to sample task. Cogn Brain Res 2004;18:306–
21.

Merikanto I,Kronholm E, Peltonen M, Laatikainen T, Lahti T, Partonen T. Relation of chronotype to

sleep complaints in the general Finnish population. Chronobiol Int 2012;29:311–7.
Mont TH, Buysse DJ, Carrier J, Bart BD, Rose  LR.  Effects  of  afternoon  “siesta”  naps  on  sleep,  
alertness, performance, and circadian rhythms in the elderly. Sleep 2001;24:680–7.

Mu Q, Mishory A, Johnson KA, et al. Decreased brain activation during a working memory task at
rested wakefulness is associated with vulnerability to sleep deprivation. Sleep 2005;28:433–46.

Roehrs T, Zorick F, Sicklesteel J, Wittig R, Roth T. Excessive daytime sleepiness associated with
insufficient sleep. Sleep 1983;6:319–25.

Taylor DJ, Bramoweth AD. Patterns and consequences of inadequate sleep among college students:
substance use and motor vehicle accidents. J Adolesc Health 2010;46:610–2.

Tucker AM, Whitney P, Belenky G, Hinson JM, Van Dongen HPA. Effects of sleep deprivation on
dissociated components of executive functioning. Sleep 2010;33:47–57.

Van Dongen HP, Maislin G, Mullington JM, Dinges DF. The cumulative cost of additional
wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic
sleep restriction and total sleep deprivation. Sleep 2003;26:117–26.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Isolated Symptoms and Normal Variants

Long Sleeper

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Long Sleeper
A long sleeper is an individual who consistently sleeps substantially more in 24 hours than
does the typical person of his or her age group. For adults, the usually accepted figure is 10
hours or more, but many epidemiologic studies have used sleep times of 8–10 hours. For
children and adolescents, the entity should be considered if sleep time is more than two hours
longer than age-specific norms. Sleep, although long, is basically normal in architecture and
physiology. Sleep efficiency and timing are normal. A consistent daily pattern, documented
by a carefully kept sleep log (preferably confirmed by actigraphy), showing 10 or more hours
of sleep per night over a minimum of seven days is desirable for the identification of the long
sleeper. In general, long sleepers seek medical help when they develop sleepiness as a result
of being forced to curtail their sleep time to less than their required amounts. Usually, the
long sleep pattern began in childhood, is well established by early adolescence, and persists
throughout life. Many long sleepers, because of occupational or educational demands,
function with reasonable success on nine hours of sleep per night during the work or school
week, with increases to 12 or more hours on weekends and holidays.

About 2% of men and 1.5% of women report sleeping at least 10 hours per night.
Epidemiologic studies have consistently found an increased mortality (and sometimes
increased body mass index, lower glucose tolerance, higher prevalence of type 2 diabetes and
coronary heart disease) associated with long sleep, compared to average-duration sleep, but it
is not clear whether most of the subjects were naturally long sleepers or had disorders
resulting in excessive duration of sleep. In subjects older than 60 years, sleep duration longer
than 9.5 hours is associated with male sex, low education, no physical exercise, and more
physical diseases. Long (> nine hours) sleep duration has a high heritability (44%) and
concordance between monozygotic twins, which is higher if they live together. Genomewide
studies favor a polygenic origin of sleep duration, with influence of clock and other genes
(DEC2, K+ channel regulatory proteins genes). Long sleepers presumably represent the
extreme high end of the normal sleep duration continuum.

Long sleepers, like short sleepers, have normal absolute amounts of stage N3 sleep, unless
there is chronic sleep restriction preceding polysomnography, in which case the absolute
amount of N3 stage is increased. Amounts of stages N2 and REM sleep are somewhat higher
than normal. The individual has no problem with time distortion or ability to be accurate
about the quantity or quality of sleep. Assuming that individuals have obtained their usual
sleep amounts for several nights before the procedure, no sleepiness is evident on the MSLT.
It is important to differentiate the long sleeper from patients with narcolepsy, idiopathic
hypersomnia, sleep disordered breathing, or medical causes of hypersomnolence. Many
pathologic causes of increased sleep have an acute or subacute onset, may not be present
since childhood, and rarely show the stable course of the long sleeper. Nevertheless,
differentiation from pathologic conditions of hypersomnolence may be difficult in the child
or adolescent because the normal continuum of sleep duration is somewhat higher in these
age groups than in adults. The correct determination is often made by exclusion of specific
diagnostic features associated with other conditions and by the absence of complaints
concerning  the  quality  of  the  individual’s  awake-state functioning when adequate sleep is
obtained (e.g., during prolonged holidays). In particular, the differentiation of a genuine long
sleeper from a patient with idiopathic hypersomnia may be difficult. In the genuine long
sleeper, sleeping long hours is refreshing, and sleepiness disappears when long hours of
nocturnal sleep are enforced.

Bibliography

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short sleepers and long sleepers. Am J Physiol 1996;270:R41–53.

Hartmann E, Baekeland F, Zwilling GR. Psychological differences between long and short
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Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Sumário
General Criteria for Circadian Rhythm Sleep-Wake Disorder ................................................... 129
Delayed Sleep-Wake Phase Disorder ...................................................................................... 130
Advanced Sleep-Wake Phase Disorder.................................................................................... 136
Irregular Sleep-Wake Rhythm Disorder .................................................................................. 142
Non-24-Hour Sleep-Wake Rhythm Disorder ........................................................................... 147
Shift Work Disorder .................................................................................................................. 153
Jet Lag Disorder ........................................................................................................................ 157
Circadian Sleep-Wake Disorder Not Otherwise Specified (NOS) ............................................ 161
Circadian  Rhythm  Sleep-Wake  Disorders
Circadian rhythms are endogenous, near-24-hour biological rhythms that exist in all living
organisms. The internal near-24-hour circadian clock is entrained or synchronized to the 24-
hour light-dark cycle. In humans, the endogenous period of the circadian oscillation is
genetically determined and typically is slightly longer than 24 hours. In order to maintain
entrainment, the endogenous rhythm must be reset each day to the 24-hour clock time. For
optimal sleep, the actual sleep time should match the timing of the circadian rhythm of
sleep and wake propensity. Therefore, a recurrent or chronic pattern of sleep and wake
disturbance may result from disruption of the internal circadian timing system or a
misalignment between the timing of the individual's circadian sleep-wake propensity and
the 24-hour social and physical environments (e.g., sleep episodes scheduled entirely or in
part during a phase of circadian alertness promotion). As used herein, a circadian rhythm
sleep-wake disorder (CRSWD) is defined by the following criterion: The disorder is caused by
alterations of the circadian time-keeping system, its entrainment mechanisms, or a
misalignment of the endogenous circadian rhythm and the external environment.

Most CRSWDs arise when a substantial misalignment exists between the internal rhythm
and the required timing of the patient's school, work, or social activities. Therefore,
measurement of endogenous circadian timing is important for the accurate diagnosis of
CRSWDs. In addition to the history, multiple tools are available to assess sleep-wake
patterns. Sleep log and actigraphy are essential instruments in the evaluation of CRSWDs
and should be conducted for at least seven days, preferably for 14 days, to capture work
and non-work days. Circadian chronotype (Morningness-Eveningness Questionnaires) and
physiological measures of endogenous circadian timing (salivary or plasma dim light
melatonin onset and urinary 6-sulfatoxymelatonin) also can provide important diagnostic
information. Circadian chronotype is a reflection of an individual's optimal timing of sleep
and wake propensity, as well as other physiological and mental functions. Several
questionnaires  can  be  used  to  assess  chronotype  of  “eveningness”  or  “morningness”  (e.g.,  
Munich Chronotype Questionnaire, or Morningness-Eveningness Questionnaire).

The most common presenting symptoms of CRSWDs are difficulty initiating and maintaining
sleep, and excessive sleepiness, but their impact extends to adverse health outcomes,
impairments in social, occupational and educational performance, and safety concerns.
Important advances have been made in the identification of clinical CRSWD subtypes,
particularly in the area of pediatrics. However, the challenge remains to develop more
precise and clinically practical tools to improve diagnostic accuracy for CRSWDs.

General Criteria for Circadian Rhythm Sleep-Wake Disorder

Criteria A-C must be met

A. A chronic or recurrent pattern of sleep-wake rhythm disruption primarily due to

alteration of the endogenous circadian timing system or misalignment between the
 endogenous circadian rhythm and the sleep-wake schedule desired or required by an
individual’s  physical  environment  or  social/work  schedules.
B. The circadian rhythm disruption leads to insomnia symptoms, excessive sleepiness, or
both.
C. The sleep and wake disturbances cause clinically significant distress or impairment in
mental, physical, social, occupational, educational, or other important areas of
functioning.

All disorders described in the ensuing section imply a sleep difficulty that meets each of the
above criteria. The specific features that characterize each type of CRSWD are included
within the individual diagnostic criteria.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Circadian Rhythm Sleep-Wake Disorders ›› Disorders ››

Delayed Sleep-Wake Phase Disorder

ICD-9-CM code: 327.31

ICD-10-CM code: G47.21

Alternate Names

Delayed sleep phase syndrome, delayed sleep phase pattern, motivated delayed sleep
phase disorder.

Diagnostic Criteria

Criteria A-E must be met

A. There is a significant delay in the phase of the major sleep episode in relation to the
desired or required sleep time and wake-up time, as evidenced by a chronic or recurrent
complaint by the patient or a caregiver of inability to fall asleep and difficulty awakening
at a desired or required clock time.
B. The symptoms are present for at least three months.
C. When patients are allowed to choose their ad libitum schedule, they will exhibit improved
sleep quality and duration for age and maintain a delayed phase of the 24-hour sleep-
wake pattern.
D. Sleep log and, whenever possible, actigraphy monitoring for at least seven days
(preferably 14 days) demonstrate a delay in the timing of the habitual sleep period. Both
work/school days and free days must be included within this monitoring.
E. The sleep disturbance is not better explained by another current sleep disorder, medical
or neurological disorder, mental disorder, medication use, or substance use disorder.
Notes
1. Standardized chronotype questionnaires are useful tools to assess the chronotype of
eveningness and morningness. Individuals with this disorder typically score as evening
types. This tool can also be useful in determining whether an eveningness circadian
preference contributes to sleep initiation difficulties among those who do not meet full
criteria for the disorder.
2. Demonstration of a delay in the timing of other circadian rhythms, such as melatonin
(measured by dim light melatonin onset or urinary 6-sulfatoxymelatonin sampled across
a 24-hour period), is desirable to confirm the delayed circadian phase.
Essential Features

Delayed sleep-wake phase disorder (DSWPD) is characterized by habitual sleep-wake timing

that is delayed, usually more than two hours, relative to conventional or socially acceptable
timing. Affected individuals complain of difficulty falling asleep at a socially acceptable time,
as required to obtain sufficient sleep duration on a school or work night. Once sleep onset
occurs, it is reportedly of normal duration. These individuals also experience difficulty
arising at a socially acceptable wake time, as required to prepare for school or work. When
allowed  to  follow  his  or  her  preferred  schedule,  the  patient’s  timing  of  sleep  is  delayed.

Associated Features

Individuals with DSWPD may demonstrate excessive sleep inertia (extreme difficulty
awakening and confusion) in the morning as a result of curtailed sleep time and awakening
during a circadian phase of high sleep propensity. Individuals with this disorder as well as
normal sleepers with evening chronotypes may have increased rates of mental
disturbances, such as Diagnostic and Statistical Manual of Mental Disorders (DSM) Axis I
disorders or symptoms (e.g., mood disorders or depressive symptoms). In some individuals
with DSWPD, there may be an overlap with non-24-hour sleep-wake disorder, or an
alternation between symptoms of the two disorders. Attempts to cope with the inability to
fall asleep earlier may result in the development of insomnia disorder. Individuals may use
alcohol, sedatives, hypnotics, or stimulant substances to alleviate symptoms of insomnia
and excessive sleepiness, thereby perpetuating their underlying sleep disorder.

Clinical and Pathophysiological Subtypes

Motivated delayed sleep-wake phase disorder is a subtype typically composed of

adolescents who have little intrinsic motivation to successfully complete treatment and
thereby resume a normal lifestyle (regular school attendance, developmentally appropriate
peer interactions, etc). A history of mood or anxiety disorder (especially school phobia and
separation and social anxiety) or other factors (e.g., learning disabilities, attention deficit
hyperactivity disorder) are often present and may motivate the patient (sometimes
unconsciously) to avoid a return to normal adolescent activities, especially regular school
attendance. It is not uncommon that ill-defined medical issues (e.g., chronic fatigue,
recurrent mononucleosis episodes, pain syndromes) trigger the onset or complicate the
course of the disorder. Important clues, in addition to the existence of premorbid mental
disorders,  include  exaggerated  presenting  symptoms  (e.g.,  “can’t  wake  up  even  if  I  throw  
cold  water  on  him”)  and  failure  to  comply  with  basic  straightforward  treatment  
recommendations (e.g., refusal or inability to stop napping during the day).
Although social, psychological, and environmental factors may play a significant role in the
development of delayed sleep-wake phase, International Classification of Sleep Disorders,
3rd Edition has chosen to list only a single delayed sleep-wake phase diagnosis, with the
recognition that most cases reflect variable chronobiologic and behavioral contributions.

Demographics

The exact prevalence of DSWPD in the general population is unknown. The condition is
more common among adolescents and young adults, with a reported prevalence of 7% to
16%. It is estimated that DSWPD is seen in approximately 10% of patients presenting in
sleep clinics with recurrent insomnia complaints. There have been no studies assessing
racial/ethnic differences in DSWPD.

Predisposing and Precipitating Factors

Most individuals with DSWPD are evening chronotypes. Many adolescents experience a
biological endogenous shift towards later bedtimes beginning around puberty. Genetic
factors such as polymorphism in the circadian clock gene hPer3 are associated with DSWPD.
Environmental factors, including decreased exposure to light during the phase advance
region of the phase response curve (PRC) (i.e., in the morning on days with early wake
times) or increased exposure to bright light during the phase delay portion of the PRC (i.e.,
late in the evening) may exacerbate the delayed circadian phase. Individuals may have
increased sensitivity in the phase delay region or decreased sensitivity in the phase advance
region of the phase response curve to light. Maladjustment to changes in work and social
schedules, travel across time zones, and shift work can precipitate this disorder. Individuals
may consume excessive caffeine and other stimulants, which may further delay sleep onset
and thus exacerbate the delayed sleep time.

Social and behavioral factors play an important role in the development and maintenance of
the delayed sleep patterns for many affected individuals. Personal, social, and occupational
activities that continue into the late evening may perpetuate and exacerbate the sleep
phase delay. In adolescents, the role of school avoidance, social maladjustment, and family
dysfunction should be considered as contributing factors. Individuals with a psychiatric
disorder, such as a mood disorder (major depression or bipolar disorder), severe obsessive-
compulsive disorder, attention deficit hyperactivity disorder, or other neurodevelopmental
disorders may have a delayed sleep phase.

Familial Patterns

A positive family history has been reported in approximately 40% of individuals with
DSWPD. In one pedigree, DSWPD was suggested to segregate as an autosomal dominant
trait. Polymorphisms inhPer3, arylalkylamine N-acetyltransferase, human leukocyte antigen,
and Clock have been suggested to be associated with DSWPD.

Onset, Course, and Complications

A delayed sleep pattern typically begins during adolescence. Onset in early childhood is also
described, especially in familial cases; the onset may follow psychological, medical, or
environmental stressors. Without treatment, DSWPD is a chronic condition that may last
into late life. However, with increasing age across adulthood, the timing of the sleep-wake
cycle may advance, thereby decreasing the propensity to delayed sleep phase.
Phototherapy, as well as behavioral and pharmacologic treatments, can advance the timing
of sleep hours, but there is usually a continual tendency and preference for delayed sleep
hours, and recurrence is high. Use of alcohol, sedatives, hypnotics, or stimulants to treat
symptoms of insomnia and sleepiness during normal waking hours may lead to substance
abuse.

Developmental Issues

DSWPD may be encountered in any age group but is especially prevalent among adolescents
and young adults. In addition to the clinical features described elsewhere, DSWPD may
present in older children and adolescents with chief complaints of truancy, repeated school
absences, chronic tardiness and/or school failure, rather than sleep complaints per se. In
severe cases, school attendance is completely curtailed and the patient may have failed to
attend school regularly for many months. Extreme difficulty in morning awakening,
requiring intensive parental involvement, may also be the presenting concern. An increased
risk of motor vehicle accidents has been associated with delayed sleep onset and resultant
insufficient  sleep  in  adolescents;  thus,  the  occurrence  of  a  car  crash  or  “near-miss”  incident  
should alert the clinician to probe for additional evidence of circadian pathology.
Adolescents may also present primarily with mood complaints (depression, suicidal
ideation). Chronic insomnia is commonly associated with and may be the chief presenting
complaint in adolescents with DSWPD as a result of repeated attempts and failures to
achieve sleep onset at their desired bedtime.

In younger children, the condition may be associated with delays in other markers of
circadian phase, including the typical presleep surge in alertness referred to as the
“forbidden  zone”  or  “second  wind  phenomenon.”  Thus,  especially  in  younger  children,  
DSWPD may present primarily as bedtime resistance, as caregivers attempt to establish
bedtimes  that  directly  conflict  with  the  child’s  circadian-mediated readiness for sleep.

Several pediatric populations appear to have an increased vulnerability to DSWPD and sleep
disturbances, likely of multifactorial etiology. These include children with attention deficit
hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Several studies have
examined melatonin onset in children with ADHD and reported significant delays in
comparison with typically developing children, as well as successful treatment with
melatonin. Children with ASD have a high prevalence (up to 80%) of sleep disturbances,
including delayed sleep onset, night and early morning awakenings, and irregular sleep
patterns, at least some of which appear associated with circadian abnormalities. These
children reportedly have a number of alterations in melatonin synthesis, levels, amplitude,
and patterns of secretion.

Little is known about the natural history of the clinical entity of DSWPD in the pediatric
population, including the impact of various treatment modalities, the likelihood of
spontaneous resolution of symptoms, or long-term consequences.
There is increasing evidence to suggest that the evening chronotype is associated in both
children and adolescents with a number of adverse consequences, including decreased
health-related quality of life, higher rates of behavioral/emotional problems including
depression and suicidality, decreased sleep duration and increased daytime sleepiness,
more sleep complaints, impairments in academic functioning, and increased likelihood of
substance use. Thus, eveningness may confer an increased risk for physical and mental
health problems.

Pathology and Pathophysiology

The exact mechanisms responsible for DSWPD are unknown. An abnormal interaction
between the endogenous circadian rhythm and the sleep homeostatic process that
regulates sleep and wakefulness may play an essential role in the pathophysiology of
DSWPD. Early studies reported an altered phase relationship between the sleep-wake cycle
and circadian phase, whereas more recent studies have failed to support this finding. In
these patients, sleep onset, sleep offset, and phase of circadian markers such as core body
temperature and melatonin are delayed relative to clock time when compared with
controls. Although this condition may be predominantly due to a misalignment between
circadian timing and the external environment, alterations in the length of the circadian
period or an altered homeostatic process (indicated by decreased sleep propensity in
response to sleep deprivation) also may be contributing factors. In children and adults,
voluntary behaviors such as staying awake late at night and waking up late in the morning or
afternoon may result in an abnormal relationship between the endogenous circadian
rhythm and the sleep homeostatic process that regulates sleep and wakefulness. Delayed
bedtimes and wake times may increase exposure to bright light in the late evening (a delay
signal for the circadian clock) and decrease exposure to light in the early morning (an
advance signal for the circadian clock), thereby promoting and perpetuating the delay in the
circadian sleep phase. Given a sufficient discrepancy between early and late wake times,
early wake times may be associated with bright light exposure during the maximal phase
delay region, perpetuating the circadian phase delay and the disorder. Individuals may have
alterations in sensitivity to the phase shifting effects of light. For example, partial sleep
deprivation encountered with this disorder can also attenuate the ability to phase-advance
the circadian system, further perpetuating the delayed circadian phase.

Objective Findings

Recordings of sleep logs and actigraphy over an interval of at least seven (and preferably
fourteen) consecutive days demonstrate delayed sleep onset and sleep offset (typically
greater than two hours) relative to socially acceptable times. Though clock times may be
culture dependent, for many affected individuals sleep onset is typically delayed until 1:00
a.m. to 6:00 a.m., (though may be earlier based on age and developmental status), and
wake time occurs in the late morning or afternoon. Daily demands and schedules may result
in an earlier than desired wake-up time during work or school days, but a delay in bedtime
and wake-up time is almost always seen during free days and vacation. Polysomnography
(though not routinely indicated nor required for the diagnosis), when performed at
preferred (delayed) sleep times, is essentially normal for age. If a conventional bedtime and
wake-up time are enforced, however, polysomnographic recording may show prolonged
sleep latency and decreased total sleep time. Laboratory measures of circadian timing
generally show the expected phase delay in the timing of the nadir of the core body
temperature rhythm and dim-light melatonin onset (DLMO). Several questionnaires are
useful in assessing the chronotype, the degree of eveningness or morningness (e.g.,
“Morningness-Eveningness  Questionnaire,”  “Munich  Chronotype  Questionnaire”).  
Individuals with DSWPD, typically score high as evening types, though normal sleepers can
also score high on eveningness. Elevations are expected in self-report of daytime sleepiness,
such as on the Epworth Sleepiness Scale.

The results of polysomnography and other diagnostic tools in younger age groups are similar
to those seen in adults. Actigraphy and/or sleep logs are useful in the diagnosis of DSWPD in
the pediatric population. Several validated instruments are available for assessing phase
preference  in  the  pediatric  and  adolescent  populations.  These  include  the  Children’s  
Chronotype Questionnaire (CCTQ) (parent-report), the Morningness-Eveningness Scale for
Children (self-report), and the Morningness-Eveningness Questionnaire for Children and
Adolescents. These surveys have been used to assess chronotype in the pediatric population
and may be useful in clinical settings.

Differential Diagnosis

Delayed sleep-wake phase disorder must be distinguished  from  “normal”  sleep  patterns,  
particularly in adolescents and young adults who maintain delayed schedules regularly or
intermittently, without distress or impaired functioning. DSWPD must be distinguished from
other causes of difficulty initiating sleep, including chronic insomnia disorder. In DSWPD,
sleep initiation and maintenance are improved when the patient is allowed to sleep on the
preferred schedule. When individuals with DSWPD must arise before the desired wake time,
excessive sleep inertia and excessive daytime sleepiness may be evident. Other forms of
excessive daytime sleepiness, from which this must be distinguished, do not generally
exhibit the pronounced circadian pattern and do not abate with alterations in the sleep-
wake schedule. The development of DSWPD may be influenced by alterations in circadian
physiology as well as behavioral factors.

Inadequate sleep hygiene and insufficient sleep syndrome must also be considered in the
differential.

Unresolved Issues and Further Directions

There is limited knowledge of the underlying pathophysiology of DSWPD. Recent evidence

suggests that alteration in the homeostatic regulation of sleep and alertness may play an
important role. The intrinsic circadian period may be abnormally long. Recent advances in
the understanding of the molecular basis for the generation and entrainment of circadian
rhythms, together with the identification of a familial form of DSWPD, will lead to improved
understanding of the mechanisms responsible for this condition, as well as targeted,
evidence-based therapies.

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Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Circadian Rhythm Sleep-Wake Disorders ›› Disorders ››

Advanced Sleep-Wake Phase Disorder

ICD-9-CM code: 327.32

ICD-10-CM code: G47.22

Alternate Names

Advanced sleep phase type, advanced sleep phase disorder, advanced sleep phase
syndrome.

Diagnostic Criteria

Criteria A-E must be met

A. There is an advance (early timing) in the phase of the major sleep episode in relation to
the desired or required sleep time and wake-up time, as evidenced by a chronic or recurrent
complaint of difficulty staying awake until the required or desired conventional bedtime,
together with an inability to remain asleep until the required or desired time for awakening.

B. Symptoms are present for at least three months.

C. When patients are allowed to sleep in accordance with their internal biological clock,
sleep quality and duration are improved with a consistent but advanced timing of the major
sleep episode.

D. Sleep log and, whenever possible, actigraphy monitoring for at least seven days
(preferably 14 days) demonstrate a stable advance in the timing of the habitual sleep
period. Both work/school days and free days must be included within this monitoring.

E. The sleep disturbance is not better explained by another current sleep disorder, medical
or neurological disorder, mental disorder, medication use, or substance use disorder.

Notes

1. Standardized chronotype questionnaires are useful tools to assess the chronotype of

eveningness and morningness. Individuals with advanced sleep phase score as morning
types.

2. Demonstration of an advance (typically greater than two hours) in the timing of other
circadian rhythms such as DLMO or urinary 6-sulfatoxymelatonin is desirable to confirm the
advanced circadian phase.

Essential Features

Advanced sleep-wake phase disorder (ASWPD) is characterized by a stable advance (earlier

timing) of the major sleep episode, such that habitual sleep onset and offset occur typically
two or more hours prior to required or desired times. Affected individuals complain of early
morning or maintenance insomnia and excessive evening sleepiness. When affected
individuals are allowed to maintain an advanced schedule, sleep quality and quantity are
improved.

Associated Features
Individuals with ASWPD may experience chronic partial sleep loss due to early morning and
maintenance insomnia, particularly if sleep is resisted during early evening.

Clinical and Pathophysiological Subtypes

Familial patterns are discussed below.

Demographics

The prevalence of ASWPD in the general population is unknown. In one large survey study
involving middle-aged adults (40-64 years), the population prevalence was estimated at 1%,
although it is unclear what proportion of these subjects would deem their schedule to be
significantly troublesome so as to warrant clinical attention. Until the identification of
familial cohorts (see below), only four cases were described in the literature. There is no
known sex difference.

Predisposing and Precipitating Factors

Advanced age appears to be a risk factor. Among a cohort aged 20 to 59 years, older age
was associated with increased morningness, which was determined to be a significant
mediator of numerous age-sleep  relationships.  A  patient’s  ability  to  sleep  at  an  abnormal  
circadian phase (phase tolerance) also impacts the degree to which adverse symptoms are
experienced, and this adaptability varies among individuals. Conflicting results have been
obtained with respect to the relationship between age and phase tolerance, with some
suggesting that age decreases phase tolerance, and others suggesting that age may actually
be protective. Methodological differences preclude direct comparisons of the investigations,
as do wide variations in the age groups studied. Genetic factors also can influence the
development of the condition, as has been definitively demonstrated among select familial
cohorts (see Pathology and Pathophysiology section). Environmental influences may
precipitate, maintain, or exacerbate the advanced circadian phase, but this has not been
proven. ASWPD has been reported in children with neurodevelopmental disorders. In
particular, studies in children with autism spectrum disorders and Smith-Magenis syndrome
have shown profound alterations in melatonin secretion profiles, which may manifest as a
phase advance with very early morning waking.

Familial Patterns

Various groups have described kindreds with familial ASWPD. These cases may be
characterized by an earlier age of onset. It is not clear whether the familial or nonfamilial
variety of the condition is more common.

Onset, Course, and Complications

Repetitive attempts to resume sleep with awakenings may result in the development of a
comorbid chronic insomnia disorder. Individuals may use alcohol, other sedatives, and/or
stimulants to alleviate symptoms, potentially exacerbating the underlying sleep/wake
disorder. The impact on caregivers of children with neurodevelopmental disorders and
ASWPD may be particularly profound.

Developmental Issues

ASWPD is most frequently encountered among older age groups. An early age of onset of
ASWPD should prompt further probing for a familial pattern. Caregivers may report that a
child  wakes  “too  early”  in  the  morning,  which  is  disruptive  to  the  household  routine  and  
may curtail parental sleep. This is particularly true for younger children, who may require
adult supervision once they are awake. However, this complaint regarding the waking
pattern is often more related to unrealistic caregiver expectations regarding an
“appropriate”  wake  time  for  a  young  child  and/or  a  developmentally  inappropriate  early  
bedtime resulting in prolonged time in bed, rather than to a true advance in sleep onset and
offset. In some cases, children are motivated to wake up earlier than desired because they
are reinforced for this behavior by parental attention or the opportunity to watch television
or  utilize  other  media  upon  waking.  The  complaint  that  a  child  “falls  asleep  too  early”  in  the  
evening, especially in adolescence, is rare and should raise concerns regarding the
possibility of chronically insufficient sleep and/or a sleep disorder resulting in increased
sleep needs. The rarity of observations of advanced sleep onset and offset times among
young children may also be due in part to societal expectations of earlier bed and wake
times for this age group; thus, a misalignment with circadian preference is less likely.

Pathology and Pathophysiology

Possible etiologies include: (1) an alteration in the ability of the circadian clock to phase
delay; (2) a dominant phase advance region of the light phase response curve to entraining
agents; (3) altered strength of entraining agents, such as light exposure at the appropriate
circadian time (voluntarily or involuntarily induced); or (4) a shortened endogenous
circadian period of the pacemaker. Among these proposed mechanisms, only the latter has
been definitively demonstrated among select familial ASWPD subjects. Genetic analyses
revealed a missense mutation in a casein kinase (CK1ε) binding region of a Period gene
(hPer2), culminating in hypophosphorylation by CK1ε in vitro. Hypophosphorylation of the
Period protein results in promotion of its transcription and, ultimately, a decrease in the
period length of the clock. However, genetic heterogeneity is apparent within familial
ASWPD, as demonstrated by the fact that other cohorts from this same study and another
study did not reveal mutations in hPer2. A separate report of a Japanese familial ASWPD
cohort described a missense mutation in a different casein kinase gene (CKIδ), which also
resulted in decreased enzymatic activity in vitro. Yet another group described associations
between hPer1 and hPer2polymorphisms and extreme morningness circadian preferences
(questionnaire-based), in the absence of discrete ASWPD.

Objective Findings
Among patients with familial ASWPD, laboratory measures to determine the phase of
circadian rhythms reliably show the expected phase advance in the timing of the nadir of
the temperature rhythm and the dim light melatonin onset, in comparison with unaffected
controls. Among those with nonfamilial ASWPD, a wider range of timing of circadian
markers is found, with some values approaching those of unaffected controls.

Polysomnography (though not routinely indicated nor required for the diagnosis), when
performed at preferred (advanced) sleep times, is essentially normal for age. If a
conventional bedtime and wake-up time is enforced, however, polysomnographic recording
may show short sleep latency and early awakening with curtailment of total sleep time.

Differential Diagnosis

ASWPD  must  be  distinguished  from  “normal”  sleep  patterns,  particularly  among  the  elderly  
or very young, who often maintain advanced schedules without distress or impaired
functioning. ASWPD must also be distinguished from other causes of early awakening,
including chronic insomnia disorder.Poor sleep hygiene practices, particularly evening
napping among the elderly, and irregularity of the sleep-wake schedule should also be
considered.  The  possibility  of  a  “free-running”  (nonentrained)  circadian  rhythm  also  merits  
consideration, but patients with this condition are most commonly blind and report only
periodic complaints of insomnia depending on the relative relationship between the internal
rhythm and that of the light/dark cycle. Major depressive disorder is a common cause of
early awakening that must be considered. These patients do not typically manifest the early
evening sleepiness that is characteristic of ASWPD. As with any sleep disturbances that
persists over time, insomnia can develop secondarily. The Horne-Östberg questionnaire (or
other chronotype questionnaire) may assist in determining the contribution of a
morningness circadian preference to the presenting sleep/wake complaint. The presence of
more than one contributing variable seems to be the norm, and each entity needs to be
treated accordingly.

Unresolved Issues and Further Directions

The existing literature suggests that clinicians are unlikely to encounter patients with
stringently defined ASWPD. Until the identification of familial cohorts, only four cases were
described. Various treatment trials also support this contention with demonstration of
objectively conventional sleep and wake times despite study entry based on subjective
reports of advanced sleep phase. Select studies of patients with sole complaints of
maintenance insomnia/early-morning awakenings have demonstrated marked advances
(earlier timing) of physiologically measured circadian rhythms. The absence of the early
evening sleepiness complaint may be due to the fact that the timing of sleep onset can be
more readily modified than wake time, and is likely to be more actively resisted due to its
propensity to conflict with social or family obligations. Alternatively, evening sleep that
occurs prior to entering the bed/bedroom may not be reported as such. If it is definitively
demonstrated that the evening sleepiness complaint is not present or is not prominent, the
term advance-related sleep complaints may be used in lieu of ASWPD. If this broader term is
used, the condition is observed more commonly (~7% of respondents in a study of
individuals aged 40-64 years). There is limited knowledge of the pathophysiology of ASWPD
(or advance-related sleep complaints) beyond those associated with select cases of familial
ASWPD. Increased use of physiologic circadian assessments will require the development of
normative values to guide practitioners. Knowledge gaps are even more prominent within
pediatric and adolescent populations.

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Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Circadian Rhythm Sleep-Wake Disorders ›› Disorders ››

Irregular Sleep-Wake Rhythm Disorder

ICD-9-CM code: 327.33

ICD-10-CM code: G47.23

Alternate Names

Irregular sleep-wake cycle disorder, irregular sleep-wake rhythm type.

Diagnostic Criteria

Criteria A-D must be met

A. The patient or caregiver reports a chronic or recurrent pattern of irregular sleep and
wake episodes throughout the 24-hour period, characterized by symptoms of insomnia
during the scheduled sleep period (usually at night), excessive sleepiness (napping) during
the day, or both.

B. Symptoms are present for at least three months.

C. Sleep log and, whenever possible, actigraphy monitoring for at least seven days,
preferably 14 days, demonstrate no major sleep period and multiple irregular sleep bouts
(at least three) during a 24-hour period.

D. The sleep disturbance is not better explained by another current sleep disorder, medical
or neurological disorder, mental disorder, medication use, or substance use disorder.

Essential Features

Irregular sleep-wake rhythm disorder (ISWRD) is characterized by lack of a clearly defined

circadian rhythm of sleep and wake. The chronic or recurring sleep-wake pattern is
temporally disorganized so that sleep and wake episodes are variable throughout the 24-
hour cycle. Individuals have symptoms of insomnia and excessive sleepiness, depending on
the time of day and their particular sleep-wake pattern.

Associated Features

ISWRD is more commonly observed in neurodegenerative disorders, such as dementia, and

in children with developmental disorders. Individuals typically present with insomnia or
excessive sleepiness, depending on the time of day. Sleep and wake episodes across the 24-
hour cycle are fragmented, with the longest sleep bout being typically less than four hours.
Individuals or caregivers report frequent naps throughout the daytime. Total sleep time
across the 24 hours may be normal for age.

Clinical and Pathophysiological Subtypes

Older adults with Alzheimer disease who experience sundowning may represent a clinical
subtype with more severe sleep fragmentation and lower circadian rhythm amplitude than
those who do not experience sundowning.

Demographics

Demographic patterns generally parallel those of associated risk factors such as

neurodevelopmental and neurodegenerative disorders.

Predisposing and Precipitating Factors

Neurodegenerative disorders such as Alzheimer disease, Parkinson disease, and Huntington

disease increase the risk for ISWRD. Children with developmental disorders also are at
increased risk for ISWRD.

Poor sleep hygiene and lack of exposure to external synchronizing agents such as light,
activity, and social schedules may be predisposing as well as precipitating factors involved in
the development of ISWRD, particularly in the institutionalized elderly.

Familial Patterns
Not applicable or known.

Onset, Course, and Complications

Onset of the condition may occur at any age. Little is known regarding the course and
complications of ISWRD in adults. Due to the multiple awakenings and, in the elderly,
nocturnal  wandering,  falls  can  be  an  indirect  complication.  In  addition  to  the  patient’s  sleep-
wake dysfunction, the caregiver’s  sleep  is  often  disrupted.  The  sleep  and  wake  disruption  
associated with ISWRD is a common cause of institutionalization.

Developmental Issues

Caregivers may report that a child with ISWRD has difficulty falling asleep at the desired
bedtime or “falls  asleep  too  early”  in  the  evening,  wakes  “too  early”  or  has  difficulty  waking  
in the morning, and/or exhibits developmentally inappropriate napping behavior during the
day. Parents may complain that their child sleeps too much or too little or at inappropriate
times. Attempts to keep the child awake during the day, especially during sedentary
activities, are often unsuccessful. The key characteristics that distinguish ISWRD from other
sleep complaints or circadian sleep wake disorders are the lack of prolonged consolidated
sleep periods, the often seemingly random distribution in sleep periods across the 24-hour
day, and the marked day-to-day and week-to-week variability with little in the way of a
clearly predictable major sleep-wake pattern. The impact  on  caregivers’  sleep  and  daytime  
functioning is likely to be particularly profound.

There may be phenotypes of ISWRD in children, with differences regarding symptom

presentation and severity and chronicity that are related to the underlying condition. For
example, it is possible that children with chronic neurologic conditions such as autism or
chromosomal syndromes characterized by developmental delays may have a more
intractable and treatment resistant pattern compared with children with more self-limited
conditions (e.g., postconcussion).

Although ISWRD appears to be rare in typically developing children, it may be

environmentally or behaviorally induced. This may be seen in children with irregular or
fragmented sleep and wake schedules because of a chaotic household. Children with
developmental disorders are at increased risk for ISWRD. For example, children with autism,
Asperger syndrome, or pervasive developmental disorder not otherwise specified often
have highly irregular sleep patterns. In addition, these children often have circadian rhythm
abnormalities which are both more severe and chronic and they are at increased risk for
relapse.

Both ISWRD and non-24-hour sleep-wake rhythm disorder are also common in Angelman
syndrome, a neurodevelopmental disorder associated with an abnormality of chromosome
15q11-q13, and have been reported in children with Williams syndrome, a
neurodevelopmental genetic disorder characterized by physical abnormalities and a
distinctive cognitive profile with intellectual disabilities and learning difficulties. Studies in
children and adults with autism spectrum disorders and in children with Smith-Magenis
syndrome have shown profound alterations in melatonin secretion profiles. Smith-Magenis
syndrome is a developmental disorder caused by an abnormality in the short (p) arm of
chromosome 17. It is characterized by mild to moderate intellectual disability, distinctive
facial features, sleep disturbances, and behavioral problems. Decreased concentrations of
melatonin and its metabolites and daytime elevation and abnormal rhythm/decreased
amplitude of melatonin secretion have been reported in these populations. These findings
may be due to polymorphisms in melatonin enzymes synthesis or variants in genes coding
for melatonin receptors. Other postulated mechanisms for circadian rhythm disturbances,
particularly ISWRD, in these populations include clock gene polymorphisms and decreased
levels of entrainment by social/environmental cues.

There may also be medical conditions that predispose typically developing children and
adolescents to ISWRD. These include traumatic brain injury and chronic fatigue syndrome.
Brain tumor survivors, especially patients who have experienced disruption in the
hypothalamic-pituitary axis, may have an increased prevalence of circadian rhythm
disorders, including ISWRD.

There is very little literature on ISWRD in the pediatric population; prevalence, sex, and
racial/ethnic differences are unknown. Little is known about the natural history of the
clinical entity of ISWRD in the pediatric population, including the impact of various
treatment modalities, the likelihood of spontaneous resolution of symptoms, or long-term
consequences. The impact on caregivers of children with neurodevelopmental disorders and
ISWRD may be particularly profound.

The prevalence of ISWRD increases with advancing age, but it is likely that age-related
increase in neurodegenerative disorders, rather than aging per se, explains this relationship.

Pathology and Pathophysiology

The etiology of ISWRD is likely multifactorial. Anatomic or functional abnormalities of the

circadian clock can result in an arrhythmic pattern of rest and activity. Decreased exposure
to environmental-entraining agents, such as light and structured physical and social
activities (common in institutionalized elderly, and children with developmental disorders),
also can contribute to the development of an irregular sleep-wake cycle.

Objective Findings

In addition to a careful sleep history, sleep log and actigraphy monitoring show the expected
lack of a clearly defined circadian rhythm of the sleep-wake cycle, which, instead, is
characterized by multiple irregular sleep and wake bouts throughout the 24-hour period.
The use of sleep log and actigraphy is indicated for the identification of irregular sleep wake
rhythm. The irregular sleep-wake pattern is defined as having multiple sleep bouts (typically
2–4 hours) during a 24-hour period. The pattern may vary from day to day, thus monitoring
for at least seven days and preferably 14 days may be needed to differentiate the irregular
pattern from other circadian rhythm sleep-wake disorders.

Polysomnography is not required to establish the diagnosis. Polysomnography may be

useful for the diagnosis of other comorbid sleep disorders. Monitoring of other circadian
rhythms, such as core body temperature and melatonin for at least 24 hours, may also show
a loss of clear circadian rhythmicity or a low amplitude rhythm.

Differential Diagnosis

Poor sleep hygiene and voluntary maintenance of irregular sleep schedules should be
distinguished from irregular sleep-wake pattern. Individuals with irregular sleep-wake
rhythms may present with complaints of insomnia. Careful analysis of sleep logs or
actigraphy will demonstrate multiple irregular periods of sleep throughout the 24-hour
cycle. In both adults and children, other causes of sleep fragmentation and daytime
napping, including comorbid medical and psychiatric disorders, other sleep
disorders, or medication should be identified and treated.

Unresolved Issues and Further Directions

There is limited knowledge of the pathophysiology and natural history, response to

treatment, and complications of the disorder in adults and children. Further research into
the relative contribution of alterations in environmental synchronizing agents, such as light
and activity, versus a dysfunction of the endogenous circadian clock in the development of
irregular sleep and wake patterns will lead to improved understanding of this condition.

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Sleep Med Clin 2009;4:213–8.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Circadian Rhythm Sleep-Wake Disorders ›› Disorders ››

Non-24-Hour Sleep-Wake Rhythm Disorder

ICD-9-CM code: 327.34

ICD-10-CM code: G47.24

Alternate Names

Free-running disorder, nonentrained disorder, hypernychthemeral syndrome.

Diagnostic Criteria

Criteria A-D must be met

A. There is a history of insomnia, excessive daytime sleepiness, or both, which alternate with
asymptomatic episodes, due to misalignment between the 24-hour light-dark cycle and the
non-entrained endogenous circadian rhythm of sleep-wake propensity.

B. Symptoms persist over the course of at least three months.

C. Daily sleep logs and actigraphy for at least 14 days, preferably longer for blind persons,
demonstrate a pattern of sleep and wake times that typically delay each day, with a
circadian period that is usually longer than 24 hours.

D. The sleep disturbance is not better explained by another current sleep disorder, medical
or neurological disorder, mental disorder, medication use, or substance use disorder.

Notes
1. Patients may present with a progressively delaying sleep-wake pattern and intermittent
insomnia and excessive sleepiness. Individual symptoms will depend on when an individual
tries to sleep in relation to the circadian rhythm of sleep-wake propensity. The magnitude of
the daily delay will depend on the endogenous circadian period, and may range from less
than 30 minutes (when the period is close to 24 hours) to more than an hour (when the
period is longer than 25 hours).

2. The symptomatic episode will typically begin with a gradual increase in sleep latency and
delayed sleep onset. As the sleep propensity rhythm shifts into the daytime, patients will
have difficulty falling asleep at night and staying awake during the day. As the sleep-wake
propensity rhythm drifts further, patients will eventually complain of late afternoon and
evening sleepiness and naps as well as an early sleep onset time and short sleep latency.

3. Other circadian rhythms, such as the DLMO or urinary 6-sulfatoxymelatonin rhythm

obtained at two time points 2-4 weeks apart (i.e., to allow sufficient time for the drift to be
apparent) is desirable to confirm the nonentrained rhythm.

Essential Features

Non-24-hour sleep-wake disorder (N24SWD) is characterized by symptoms of insomnia or

excessive sleepiness that occur because the intrinsic circadian pacemaker is not entrained to
a 24-hour light/dark cycle. The non-24-hour period can be shorter or, more typically, longer
than 24 hours. Because the endogenous circadian rhythm is not aligned to the external 24-
hour environment, symptoms will depend on when an individual tries to sleep in relation to
the circadian rhythm of sleep and wake propensity. Individuals typically present with
episodes of difficulty falling asleep or staying asleep, excessive sleepiness or both,
alternating with short asymptomatic periods. The severity of individual sleep-wake
symptoms can be variable. Starting with the asymptomatic period when the individual's
endogenous rhythm is aligned to the external environment and required sleep-wake times,
sleep latency will gradually increase and the individual will complain of sleep-onset
insomnia. As the sleep phase continues to drift so that maximal endogenous sleep
propensity is now in the daytime, individuals will have trouble staying awake during the day
(exhibiting multiple daytime naps) and complain of sleepiness.

Associated Features

Most individuals with nonentrained circadian rhythms are totally blind, and the failure to
entrain circadian rhythms is related to the lack of photic input to the circadian pacemaker. A
small proportion of totally blind people may retain functional circadian photoreception and
entrained rhythms if their blindness is due exclusively to an outer retina disorder (rod and
cone layer) with retention of functional, intrinsically photosensitive retinal ganglion cells and
the retinohypothalamic pathway. Some blind people may also be able to entrain to
nonphotic cues (e.g., the timing of physical activity), producing entrainment at an adverse
phase in some cases. In sighted people, social and behavioral factors also play an important
role in the development and maintenance of the disorder, as there is an increased incidence
of psychiatric disorders. Occasionally, the disorder is associated with developmental
intellectual disability or dementia. In sighted individuals, there is often a history of delayed
sleep phase, and decreased exposure to light and structured social and physical activity.
Some sighted individuals with N24SWD also demonstrate increased sleep duration.

Demographics

It is thought that over half of totally blind individuals have non-24-hour circadian rhythms;
50% to 80% of blind individuals complain of sleep disturbances. The prevalence, sex, and
racial/ethnic differences of N24SWD in adults and children are unknown.

Predisposing and Precipitating Factors

Total blindness is the most common predisposing condition. In sighted people, the disorder
can be induced by certain environmental conditions, such as decreased or inappropriately
timed exposure to circadian entraining agents, particularly light. Delayed sleep-wake phase
disorder may predispose to N24SWD in sighted persons. The condition has developed after
chronotherapy for DSWPD. This disorder has also been reported in adults following
traumatic brain injury.

Familial Patterns

Not applicable or known.

Developmental Issues

Caregivers may report that a child has difficulty falling asleep at the desired  bedtime  or  “falls  
asleep  too  early”  in  the  evening,  wakes  “too  early”  or  has  difficulty  waking  in  the  morning  
and staying awake during the day. Parents may complain that their child sleeps too much or
too little or at inappropriate times. The key characteristics that distinguish N24SWD from
other sleep complaints or circadian sleep wake disorders are twofold: (1) the predictable
pattern  of  misalignment  between  the  child’s  sleep  patterns  and  the  light-dark 24-hour cycle
(progressive delay in sleep onset-offset across days to weeks); and (2) periods of apparent
“symptom  remission”  during  those  transient  intervals  when  the  child’s  circadian  sleep-wake
propensity  coincides  with  the  desired  bed  and  wake  times.  The  impact  on  caregivers’  sleep  
and daytime functioning is often profound.

Although N24SWD is extremely rare in typically developing or sighted children, it has been
reported with some frequency in children with intellectual disabilities and blindness. For
example, children with optic nerve hypoplasia due to a variety of underlying causes,
especially those children with hypoplastic corpus callosum and comorbid severe intellectual
and visual impairments, have been reported to have features of N24SWD. N24SWD has also
been described in pediatric patients with Rett syndrome (a genetic disorder occurring
almost exclusively in girls, characterized by severe developmental regression, language
delays, and limited social interactions), autism spectrum disorders, and Angelman
syndrome, a neurodevelopmental disorder associated with an abnormality of chromosome
15q11-q13. The common mechanism in all of these disorders is postulated to be lack of
entrainment to the 24-hour day that results from the failure to perceive and/or attend to
social/environmental zeitgebers (time cues). There have also been several case reports
which describe the emergence of N24SWD in intellectually normal sighted children or
adolescents who have limited or inappropriate exposure to environmental and other
entraining cues (e.g., decreased light during the day and/or excessive light exposure in the
evening). These individuals are likely to have significant psychiatric impairments that
predispose them to avoidance of social interactions (e.g., anxiety) or medical conditions that
involve enforced prolonged periods of inactivity (traumatic brain injury, chronic fatigue).

Little is known about the natural history of the clinical entity of N24SWD in the pediatric
population, including the impact of various treatment modalities, the likelihood of
spontaneous resolution of symptoms, or long-term consequences.

There may be varying phenotypes of N24SWD in children, with differences in regard to

symptom presentation, severity, and chronicity that are related to the underlying condition.
For example, it is likely that children with chronic neurologic conditions such as blindness or
neurodevelopmental disabilities have a more intractable and treatment resistant pattern
compared to children with more self-limited conditions (e.g., traumatic brain injury).

Onset, Course, and Complications

Onset may occur at any age in blind individuals, coincident with loss of light perception, and,
in congenitally blind children, onset can occur from birth or during infancy. If untreated, the
course is chronic. Attempts to regulate sleep and wake times may involve the use of alcohol,
sedatives-hypnotics, and stimulants, which in turn can exacerbate the underlying sleep
disorder. Depressive symptoms and mood disorders can be comorbid conditions,
particularly in sighted patients. The adverse effects on school or work performance, as well
as other psychosocial complications, due to a lack of predictable sleep and wake times and
excessive daytime sleepiness, are key motivations for seeking treatment.

Pathology and Pathophysiology

The intrinsic period of the human circadian pacemaker is usually longer than 24 hours and
requires daily input from the environment to maintain synchrony to the 24-hour day. The
light-dark cycle is the most important environmental time cue (zeitgeber) in humans (as in
other species), although nonphotic time cues also play a role in normal entrainment. A lack
of photic input to the circadian pacemaker is clearly the cause of nonentrained rhythms in
totally blind people. It has been suggested that, in sighted individuals, a systematic delay
due to inadequate exposure to light may contribute to the development of N24SWD. In
addition, the disorder may be caused by an extremely prolonged endogenous circadian
period that is outside of the range for entrainment to the 24-hour cycle or by an alteration
in the response of the circadian clock to the entraining effects of light.

Objective Findings

Sleep studies yield different results depending on the degree of synchrony between sleep
times and the circadian pacemaker at the time when the sleep study is performed.
Recording of sleep log and actigraphy over prolonged periods (at least 14 days, but ideally
longer in blind individuals) demonstrate the lack of a stable relationship between the timing
of the sleep-wake cycle and the 24-hour day. When sleep schedules follow the endogenous
circadian propensity for sleep and wake, sleep onset and wake times are typically delayed
each day. Serial measurements of circadian rhythms, such as melatonin, usually show a
progressive daily delay of the phase of the rhythm consistent with a period that is longer
than 24 hours.

Clinical and Pathophysiological Subtypes

Totally blind patients with N24SWD are clinically different than sighted patients. In sighted
patients with N24SWD, the circadian period is often 25 hours or longer, whereas in totally
blind patients with the disorder, the circadian period follows an average period length which
is often closer to 24 hours and rarely may be shorter than 24 hours.

Differential Diagnosis

Some individuals with severe DSWPD may demonstrate progressive delay of their sleep
period by 30 minutes or more for several days, and their symptoms may be confused with
N24SWD.

Behavioral factors and psychiatric disorders, as well as medical and neurological disorders
(especially blindness, but also dementia or mental retardation), may play a role in the
development of N24SWD. In many of these cases, however, multiple physiologic,
behavioral, and environmental factors contribute to the condition. In the majority of these
cases, the disorder should be coded as N24SWD. This includes non-24-hour sleep-wake
patterns that are associated with blindness.

Unresolved Issues and Further Directions

There is only limited knowledge of the underlying pathophysiology of sighted persons with
N24SWD. The primary risk factor in sighted persons appears to be a long circadian period
that is beyond the range of entrainment to a 24-hour cycle or a progressive delay due to
inappropriate exposure to light. This risk may explain the overlap between DSWPD and
N24SWD. Future studies are needed to understand the role of genetic predisposition,
environmental or social cues and traumatic brain injury in the development of N24SWD, and
to delineate other health consequences of the condition. There are substantial knowledge
gaps regarding the prevalence, pathophysiology, clinical presentation, natural history,
effective treatment strategies, and prognosis of N24SWD in children and adolescents
compared with adults.

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Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Circadian Rhythm Sleep-Wake Disorders ›› Disorders ››

Shift Work Disorder

ICD-9-CM code: 327.36

ICD-10-CM code: G47.26

Alternate Names

Shift work sleep disorder.

Diagnostic Criteria

Criteria A-D must be met

A. There is a report of insomnia and/or excessive sleepiness, accompanied by a reduction of

total sleep time, which is associated with a recurring work schedule that overlaps the
usual time for sleep.
B. The symptoms have been present and associated with the shift work schedule for at least
three months.
C. Sleep log and actigraphy monitoring (whenever possible and preferably with concurrent
light exposure measurement) for at least 14 days (work and free days) demonstrate a
disturbed sleep and wake pattern.
D. The sleep and/or wake disturbance are not better explained by another current sleep
disorder, medical or neurological disorder, mental disorder, medication use, poor sleep
hygiene, or substance use disorder.
Essential Features

Shift work disorder is characterized by complaints of insomnia or excessive sleepiness that

occur in association with work hours that occur, at least in part, during the usual sleep
episode. There are several types of shift-work schedules, including evening shifts, night
shifts, early morning shifts, rotating shifts, split shifts, on-call overnight duty, and long
duration work shifts that include work hours at night. The sleep disturbance is most
commonly reported in association with night shifts, early morning shifts, and rotating shifts.
Total sleep time is typically curtailed by one to four hours, and sleep quality is perceived as
unsatisfactory in night, early morning, and rotating shift workers as well as in those who
work long-duration shifts. In addition to impairment of performance at work, reduced
alertness may also be associated with consequences for safety during the work schedule
and on the commute to and from work. The sleep disorder occurs despite attempts to
optimize environmental conditions for sleep. The condition usually persists only for the
duration of the shift work schedule. However, in some individuals, the sleep disturbance
may persist beyond the duration of shift work.

Associated Features

Early morning work shifts starting between 4:00 a.m. and 7:00 a.m. can also be associated
with complaints of difficulty in sleep initiation as well as difficulty awakening. Permanent
evening shifts may be primarily associated with sleep maintenance difficulty. Excessive
sleepiness usually occurs during work shifts (mainly night, early morning, and rotating
shifts), often accompanied by the need to nap and by impaired mental ability due to the
reduced alertness. Reduced alertness and increased fatigue throughout the waking period
may be associated with reduced performance capacity, and with consequences for safety.
Also, major portions of free time may have to be used for recovery of sleep, resulting in
adverse social consequences. When compared with shift workers without shift work
disorder, patients with shift work disorder report greater mood problems, such as
impatience, avoidance of interaction with coworkers, a higher risk of depression, impaired
social functioning, and lower coping skills. Patients with shift work disorder also have a
higher risk of subjective health complaints, ulcers, and substance abuse. Risk for sleepiness-
related errors and accidents are highest at night, especially in the early morning hours.
Drowsy driving accident risk is highest in the morning hours when night shift workers
commute home and early morning workers commute to work.

Clinical and Pathophysiological Subtypes

There are substantial individual differences in the ability to adjust to shift work. However,
mechanisms underlying these individual differences are not known.

Requirement of extended work hours, such as on-call overnight duty and long-duration
work shifts that include work hours at night, represents a specific clinical subtype. In
addition to the circadian misalignment (having to work during the night), sleep loss and
fatigue associated with prolonged continuous work may increase the severity of excessive
sleepiness and performance impairments.

Demographics

The prevalence of shift work disorder depends on the prevalence of shift work in the
population. It has been estimated that approximately 20% of the workforce in industrialized
countries is employed in a job that requires shift work. Although the actual prevalence of
clinically significant sleep disturbance and excessive daytime sleepiness due to work
schedules is unknown, the total number of night-shift workers suggests that an estimated
prevalence of 2% to 5% of the general population is reasonable. The prevalence of shift
work disorder among rotating- and night-shift workers has been estimated to be between
~10% and 38%. These figures do not, however, include individuals with early morning or
split shift work, which may be other at-risk groups. There is no known sex or racial
difference in vulnerability.

Predisposing and Precipitating Factors

Depending on the type of shift, circadian preference may influence the ability to adjust to or
tolerate shift work. For example, individuals described as morning types obtain shorter
daytime sleep after a night shift. Persons with comorbid medical, psychiatric, and other
sleep disorders such as sleep apnea and individuals with a strong need for stable hours of
sleep may be at particular risk. Social pressures before and after a work shift also contribute
to short sleep durations in shift workers (e.g., social interactions with family and friends,
domestic obligations, a second job, and leisure activities). Social pressures also diminish the
desire or willingness to maintain a consistent daytime sleep schedule on days off, thereby
reducing the likelihood of circadian adjustment.

Familial Patterns

Not applicable or known.

Onset, Course, and Complications

The condition is closely linked to work schedules and typically remits when the major sleep
episode is scheduled at a conventional time. Because there are so many different work
schedules, ranging from an occasional overnight shift to regular night work, the course is
quite variable. Because shift work is often combined with extended hours of duty, fatigue
can be a complicating factor. Circadian adaptation is often counteracted by exposure to light
at the wrong time of the day and the tendency of most workers to resume full daytime
activities and nighttime sleep during weekends and vacations. It has been hypothesized that
in some individuals, the condition may lead to chronic sleep disturbances. Complications
may include exacerbation of gastrointestinal, metabolic, reproductive, neoplastic, and
cardiovascular disorders. Disruptions of social and family life are frequent. Drug and alcohol
dependency may result from attempts to improve the sleep and wakefulness disturbances
produced by shift work. Fatigue and excessive sleepiness due to the combination of sleep
loss and circadian misalignment pose important safety concerns. The level of alertness
required of the worker, in addition to the intensity of symptoms, needs to be taken into
account when evaluating the disorder. For example, the threshold for intervention may be
lower for workers whose performance is critical for personal or public safety (for example,
health care workers or nuclear power plant or public transport operators).

Developmental Issues

Not applicable or known.

Pathology and Pathophysiology

The condition is thought to be directly related to circadian misalignment and sleep loss. The
sleep disturbance is generated by a circadian alerting process that corresponds with the
time that the worker needs to sleep. The excessive sleepiness during the night and early
morning appears to be partly related to cumulative sleep loss and partly due to a decreased
circadian alerting signal that corresponds with the work time and the commute to and from
work. Tolerance to night work varies considerably and may involve differences in the degree
of  circadian  adaptation  (“clock  resetting”)  to  a  night-work, day-sleep schedule. Alternatively,
tolerance may be related to individual differences in response to circadian and homeostatic
influences on sleep and wakefulness regulation. Environmental and social factors may
exacerbate sleep loss associated with shift work schedules.

Objective Findings

The condition can usually be diagnosed by history. Sleep logs and actigraphy are
recommended to demonstrate a disrupted sleep-wake pattern consistent with shift work
disorder. Polysomnographic recordings, while not required for the diagnosis, are useful if
the etiology of the sleep disturbance is in question (for example to rule out sleep apnea or
narcolepsy). Polysomnography during a typical daytime sleep episode after a work shift also
can be useful to determine the severity of the sleep disruption, although this is undertaken
almost exclusively for research studies of shift work disorder. Polysomnography may
demonstrate impaired sleep quality, with prolonged sleep latency, sleep maintenance
difficulty, or shortened total sleep time, depending on the timing of the sleep episode in
relation to the underlying phase of the circadian timing system. The sleep episode may be
fragmented, with frequent arousals and awakenings. The Multiple Sleep Latency Test
(MSLT) may demonstrate excessive sleepiness during the time of the work shift. If available,
measures of the unmasked melatonin rhythm are useful to indicate the degree of circadian
misalignment.

Differential Diagnosis

The excessive sleepiness should be differentiated from that caused by other primary sleep
disorders such as obstructive sleep apnea or narcolepsy. Insufficient sleep related to
conflicting daytime activities (for example, child care) or from environmental interference
with sleep (for example, daytime noise) often contributes to sleepiness. Sometimes patients
with DSWPD may adopt a night-work schedule that is more congruent with their sleep
preferences. Insomnia and excessive sleepiness may also suggest other persistent circadian
rhythm sleep-wake disorders. However, historical information on the relation between the
occurrence of disturbed sleep and work-hour distribution should provide sufficient
information to indicate the correct diagnosis. Increasing frustration, negative expectations,
and poor sleep hygiene may predispose the person to the development of coexisting chronic
insomnia disorder that could persist beyond the shift work schedule (i.e., shift work may
represent a precipitating event that leads to chronic problems with insomnia). Drug and
alcohol abuse or dependency may result from efforts to treat the sleep disturbance.

Unresolved Issues and Further Directions

Although there is sufficient information regarding the prevalence of shift work in

industrialized populations, less information is available regarding the actual prevalence of
shift work disorder and its impact on health and safety. Further research is needed to
improve the definition of what constitutes shift work disorder, to develop diagnostic tools
for shift work disorder, to determine the prevalence of shift work disorder using diagnostic
criteria, to elucidate the burden of shift work disorder over and above that which may be
due to shift work in general, to investigate mechanisms underlying the health and safety
consequences of shift work disorder, and to determine which shift workers are at greatest
risk of shift work disorder. Furthermore, there is limited information on the role of age, sex,
and circadian chronotype on the vulnerability to shift work disorder.

Bibliography

Akerstedt T. Shift work and disturbed sleep/wakefulness. Occup Med 2003;53:89–94.

Ancoli-Israel S, Cole R, Alessi C, Chambers M, Moorcroft W, Pollak C. The role of actigraphy
in the study of sleep and circadian rhythms. Sleep 2003;26:342–92.
Boggild H, Knutsson A. Shift work, risk factors and cardiovascular disease. Scand J Work
Environ Health 1999;25:85–99.
Costa G. Shift work and occupational medicine: an overview. Occup Med 2003;53:83–8.
Drake CL, Roehrs T, Richardson G, Walsh JK, Roth T. Shift work sleep disorder: prevalence
and consequences beyond that of symptomatic day workers. Sleep 2004;27:1453–62.
Drake CL, Wright KP Jr. Shift work, shift work disorder, and jet lag. In: Kryger MH, Roth T,
Dement WC, eds. Principles and practice of sleep medicine, 5th ed. Philadelphia:
Elsevier Saunders, 2011:784–98.
Flo E, Pallesen S, Magerøy N, et al. Shift work disorder in nurses--assessment, prevalence
and related health problems. PLoS One 2012;7:e33981.
Folkard S, Tucker P. Shift work, safety and productivity. Occup Med 2003;53:95–101.
Horne J, Reyner L. Vehicle accidents related to sleep: a review. Occup Environ Med
1999;56:289–94.
Knutsson A. Health disorders of shift workers. Occup Environ Med 2003;53:103–8.
Swanson LM, Arnedt JT, Rosekind MR, Belenky G, Balkin TJ, Drake C. Sleep disorders and
work performance: findings from the 2008 National Sleep Foundation Sleep in America
poll. J Sleep Res 2011;20:487–94.
Waage S, Moen BE, Pallesen S, et al. Shift work disorder among oil rig workers in the North
Sea. Sleep 2009;32:558–65.
Wright KP Jr, Bogan RK, Wyatt JK. Shift work and the assessment and management of shift
work disorder (SWD). Sleep Med Rev 2013;17:41–54.
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Circadian Rhythm Sleep-Wake Disorders ›› Disorders ››

Jet Lag Disorder

ICD-9-CM code: 327.35

ICD-10-CM code: G47.25

Alternate Names

Jet lag, time zone change syndrome, jet lag syndrome, jet lag type.

Diagnostic Criteria

Criteria A-C must be met

A. There is a complaint of insomnia or excessive daytime sleepiness, accompanied by a

reduction of total sleep time, associated with transmeridian jet travel across at least two
time zones.
B. There is associated impairment of daytime function, general malaise, or somatic
symptoms (e.g., gastrointestinal disturbance) within one to two days after travel.
C. The sleep disturbance is not better explained by another current sleep disorder, medical
or neurological disorder, mental disorder, medication use, or substance use disorder.
Essential Features

Jet lag disorder is characterized by a temporary mismatch between the timing of the sleep
and wake cycle generated by the endogenous circadian clock and that of the sleep and wake
pattern required by a change in time zone. Individuals complain of disturbed sleep,
sleepiness and fatigue, and impaired daytime function. The severity and duration of
symptoms is dependent on the number of time zones traveled, the ability to sleep while
traveling, exposure to appropriate circadian times cues in the new environment, tolerance
to circadian misalignment when awake during the biological night, and the direction of the
travel. Eastward travel (requiring advancing circadian rhythms and sleep-wake hours) is
usually more difficult to adjust to than westward travel.

Associated Features

In addition to sleep disturbance and decreased daytime alertness, associated features may
include general malaise and gastrointestinal symptoms. Numerous other variables related to
travel, such as sleep loss, decreased mobility, and alcohol and/or caffeine intake, contribute
to the overall fatigue. Daytime sleepiness can lead to memory difficulties, problems
concentrating, driving and flying, and to impaired decision-making. Sleepiness, sleep
disturbance and circadian misalignment associated with jet lag may also impair athletic
performance. Effects of jet lag not only affect travelers, but also can have significant
consequences for airline pilots and flight attendants.

Clinical and Pathophysiological Subtypes

There are individual differences in the ability to adjust to rapid shifts in time zones;
however, specific clinical subtypes have not been identified.

Demographics
Jet lag affects all age, sex, and racial groups. Limited available data suggest that older
individuals may experience fewer jet lag symptoms compared with younger individuals.
However, the data have limitations and further research is needed to better define the
relationship between age and the development of jet lag disorder.

There are no studies on the prevalence of jet lag disorder.

Predisposing and Precipitating Factors

Disturbed sleep and/or shortened sleep duration before and during travel contribute to jet
lag symptoms. Prolonged uncomfortable sitting positions, air quality and pressure, stress,
and excessive caffeine and alcohol consumption may increase the severity of insomnia and
impaired alertness and function associated with transmeridian travel.

Eastward travel often leads to difficulties with sleep onset as attempts to sleep are made at
an earlier  internal  circadian  time  when  the  travelers’  biological  clock  is  promoting  alertness  
(i.e., biological day). Difficulty awakening and daytime sleepiness and fatigue occur because
wake time also occurs at an earlier biological time when the circadian clock is still promoting
sleep  (i.e.,  during  the  travelers’  biological  night).

Westward jet travel often leads to sleepiness and fatigue in the evening hours of the new
time zone as the internal circadian clock of the traveler is promoting sleep (i.e., biological
night). Sleep disturbance in the new time zone is typically manifest as a sleep maintenance
issue with early morning awakenings and difficulty returning to sleep because the internal
circadian clock of the traveler is promoting wakefulness during the sleep episode (i.e.,
biological day).

Basic circadian science principles suggest that inappropriately timed exposure to light and
darkness during and immediately after jet travel can shift the circadian clock in the wrong
direction, thereby increasing the duration of jet lag symptoms. Time at destination upon
arrival may also influence jet lag symptoms with fewer symptoms reported following
midday arrivals after eastward travel.

An individual's innate circadian preference may also confer a greater or lesser ability to
adjust to a particular time shift, but this finding has not been systematically assessed. Jet lag
is often reported to be worse after eastward than westward travel. Westward travel may
generally be easier because the genetically determined period of the circadian clock in
humans is on average longer than 24 hours. A circadian period longer than 24 hours is
associated with a circadian drive or physiological tendency for bed and wake times to be
later, thus making it easier to shift the circadian clock during westward travel to more
delayed sleep and wake times. However, 20% to 25% of humans have circadian periods that
are near to, or shorter than, 24 hours, and these individuals may find it easier to adapt to
eastward travel.

Familial Patterns

Not applicable or known.

Onset, Course, and Complications

Jet lag is usually a temporary condition. Symptoms begin approximately one to two days
after air travel across at least two time zones and are self-limited. The severity and duration
of symptoms are usually in proportion to the number of time zones traveled and the
direction of travel. It is estimated that it takes one day per time zone for circadian rhythms
to adjust to the local time. However, if traveling more than six time zones, circadian rhythms
may shift in the opposite direction, resulting in a prolonged period of adjustment that may
last up to several weeks and increased severity of jet-lag symptoms. Exposure to light at
inappropriate times may prolong the time of adjustment by shifting the circadian rhythms in
the opposite direction. Menstrual and reproductive problems have been associated with
frequent transmeridian travel in female airline personnel. Poor sleep hygiene practices may
perpetuate sleep/wake complaints, and repetitive failed attempts to initiate or maintain
sleep at desired times may predispose to the development of insomnia disorder.

Developmental Issues

The effect of age on the development or severity of jet lag disorder symptoms is unknown.

Pathology and Pathophysiology

The symptoms of jet lag disorder are due to both desynchronization of endogenous
circadian rhythms with local time and sleep disturbance. The severity of symptoms can be
influenced by the environment and behaviors of the traveler. Factors inherent to jet travel,
including prolonged time spent sitting in a confined space, ability to sleep on long-haul
flights, decreased physical activity, and a low oxygen environment, may influence severity.

Objective Findings

Objective laboratory testing usually is not indicated. When performed, polysomnography or

actigraphy shows disturbed sleep and a loss of a normal sleep-wake pattern or a mismatch
between the timing of sleep and wakefulness with the desired sleep-wake pattern of the
local time.

Differential Diagnosis

A thorough history and physical examination should be performed to exclude other mental,
physical, or sleep disorders. Somatic complaints of gastrointestinal symptoms may indicate
an underlying medical condition. When jet lag symptoms persist, increasing frustration,
negative expectations, and poor sleep hygiene may predispose the individual to the
development of chronic insomnia disorder.

Unresolved Issues and Further Directions

Understanding mechanisms of individual differences in vulnerability and tolerance to

disturbed sleep and wakefulness during jet lag is necessary. Development of effective and
practical strategies to combat jet-lag symptoms and improve sleep, performance and safety
are needed.
It is unknown how expression of the disorder varies across the life span.

Bibliography

Auger RR, Morgenthaler TI. Jet lag and other sleep disorders relevant to the traveler. Travel
Med Infect Dis 2009;7:60–8.
Burgess HJ, Crowley SJ, Gazda CJ, Fogg LF. Eastman CI. Preflight adjustment to eastward
travel: 3 days of advancing sleep with and without morning bright light. J Biol Rhythms
2003;18:318–28.
Daan  S,  Lewy  AJ.  Scheduled  exposure  to  daylight:  a  potential  strategy  to  reduce  “jet  lag”  
following transmeridian flight. Psychopharmacol Bull 1984;20:566–8.
Dawson D, Campbell SS. Timed exposure to bright light improves sleep and alertness during
simulated night shifts. Sleep 1991;14:511–6.
Drake CL, Wright KP Jr. Shift work, shift work disorder, and jet lag. In: Kryger MH, Roth T,
Dement WC, eds. Principles and practice of sleep medicine, 5th ed. Philadelphia:
Elsevier Saunders, 2011; 784–98.
Eastman CI, Gazda CJ, Burgess HJ, Crowley SJ, Fogg LF. Advancing circadian rhythms before
eastward flight: a strategy to prevent or reduce jet lag. Sleep 2005;28:33–44.
Moline ML, Pollak CP, Monk TH, et al. Age-related differences in recovery from simulated jet
lag. Sleep 1992;15:28–40.
Muhm, JM, Rock PB, McMullin DL, et al. Effect of aircraft-cabin altitude on passenger
discomfort. N Engl J Med 2007;357:18–27.
Sack R, Auckley D, Auger RR, et al. Circadian rhythm sleep disorders: part i, basic principles,
shift work and jet lag: An American Academy of Sleep Medicine Review. Sleep
2007;30:1456–79.
Suhner A, Schlagenhauf P, Höfer I, Johnson R, Tschopp A, Steffen R. Effectiveness and
tolerability of melatonin and zolpidem for the alleviation of jet lag. Aviat Space Environ
Med 2001;72:638–46.
Tresguerres JA, Ariznavarreta C, Granados B, et al. Circadian urinary 6-sulphatoxymelatonin,
cortisol excretion and locomotor activity in airline pilots during transmeridian flights. J
Pineal Res 2001;31:16–22.
Waterhouse  J,  Edwards  B,  Nevill  A,  et  al.  Identifying  some  determinants  of  “jet  lag”  and  its  
symptoms: a study of athletes and other travellers. Br J Sports Med 2002;36:54–60.
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Circadian Rhythm Sleep-Wake Disorders ›› Disorders ››

Circadian Sleep-Wake Disorder Not Otherwise Specified (NOS)

ICD-9-CM code: 327.30

ICD-10-CM code: G47.20

Patients who meet all of the general diagnostic criteria for a CRSWD but do not meet criteria
for one of the specific types of circadian rhythm sleep-wake disorders are classified here.
This diagnosis is intended primarily for patients with alterations in circadian sleep-wake
patterns due to underlying medical, neurologic, and psychiatric disorders. The underlying
neurological, psychiatric, or medical condition is typically the precipitating factor. Patients
may present with a variety of symptoms, including disturbed nocturnal sleep and excessive
sleepiness. The sleep-wake pattern may range from alterations in the phase of the sleep-
wake cycle to irregular sleep-wake pattern. Recordings of sleep logs and actigraphy over a
period of at least seven days, preferably for 14 days or longer, demonstrate sleep onsets
and sleep offsets that may be delayed or advanced relative to conventional times, irregular
or non-24-hour.

Sleep-wake disturbances are common in patients with neurodegenerative disorders

(Alzheimer disease, Parkinson disease, Huntington disease), as well as neurodevelopmental
disorders. Sleep-wake disturbances associated with these disorders may exhibit some
features of irregular sleep-wake patterns, but do not have a consistent pattern of at least
three sleep periods per day. The particular features of this disorder vary with the type of
underlying medical, psychiatric, or neurological condition. The disruption of the sleep-wake
cycle has been implicated in the etiology of sundowning and nocturnal wandering in older
adults with dementia. Patients with Parkinson disease may exhibit various types of
circadian-rhythm alterations. In addition, motor fluctuations can exhibit marked diurnal
fluctuation in patients with Parkinson disease.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Sumário
Parasomnias............................................................................................................................. 165
NREM-Related Parasomnias ................................................................................................. 167
Disorders of Arousal (From NREM Sleep) .......................................................................... 167
REM-Related Parasomnias .................................................................................................... 176
REM Sleep Behavior Disorder ............................................................................................. 176
Recurrent Isolated Sleep Paralysis ........................................................................................ 182
Nightmare Disorder .............................................................................................................. 185
Other Parasomnias ................................................................................................................. 190
Exploding Head Syndrome ................................................................................................... 190
Sleep Related Hallucinations ................................................................................................ 193
Sleep Enuresis ....................................................................................................................... 196
Parasomnia Due to a Medical Disorder ................................................................................ 201
Parasomnia Due to a Medication or Substance ..................................................................... 201
Parasomnia, Unspecified....................................................................................................... 203
Isolated Symptoms and Normal Variants ................................................................................. 203
Sleep Talking ............................................................................................................................ 203
Parasomnias
Parasomnias are undesirable physical events or experiences that occur during entry into sleep,
within sleep, or during arousal from sleep. Parasomnias may occur during non-rapid eye
movement sleep (NREM), rapid eye movement sleep (REM), or during transitions to and
from sleep.

Parasomnias encompass abnormal sleep related complex movements, behaviors, emotions,

perceptions, dreams, and autonomic nervous system activity. Parasomnias are clinical
disorders because of the resulting injuries, sleep disruption, adverse health effects, and
untoward psychosocial effects. The clinical consequences of the parasomnias can affect the
patient, the bed partner, or both.

Human consciousness consists of three essential states: Wake, NREM sleep, and REM sleep.
The three states are modulated by a host of influences including the degree of aminergic and
cholinergic neurochemical bias, central nervous system (CNS) activation, and the degree of
endogenous versus exogenous input. Under normal physiologic conditions, which include
homeostatic drive and circadian rhythmicity, the process of state declaration is maintained in
a stable and predictable fashion throughout a 24-hour period. However, as the sleep-wake
cycle oscillates, the normally distinct states of consciousness may be rendered into a state that
is not fully declared, resulting in a temporary unstable state of dissociation. Thus, sleep and
wake can be viewed as occurring on a spectrum rather than being entirely dichotomous states.

Parasomnias are the result of such state dissociation. Recent research has shown that
combinations of one or more of these states do occur and may result in unstable states of
altered consciousness manifesting as parasomnias. Disorders of arousal, such as
sleepwalking, sleep terrors, and confusional arousals are an admixture of wakefulness and
NREM sleep. Higher cognitive function is severely impaired, if not absent, while the
potential for motor capacity has, for the most part, been retained. REM sleep behavior
disorder (RBD) is an admixture of REM sleep coupled with waking or NREM sleep levels of
tonic EMG activity. All three states may be present in the same individual as an overlap of
disorders.

The comingling of basic states of consciousness is the result of different forms of

pathophysiology. In disorders of arousal, no identifiable neuropathology is present, but
functional changes in cerebral activity during NREM sleep are present, essentially resulting
in a brain in which certain areas are deactivated (asleep) and others remain activated (awake).
This CNS activation, with concomitant skeletal muscle and autonomic nervous system
activation, is believed to reflect a functional disabling of, or damage to, brain areas usually
responsible for the inhibition of these activities during sleep. Additionally, sleep inertia, sleep
state instability, and locomotor/central pattern generators are thought to contribute to the
occurrence of NREM parasomnias.

NREM disorders of arousal frequently appear to involve the disinhibition  of  “basic  drive  
states”  such  as  feeding,  sex,  and  aggression.  Here,  it  has  been  postulated  that  central  pattern  
generators elicit primal fixed action patterns that would otherwise have been inhibited by the
prefrontal cortex during wake. In this regard, aggression is typically abrupt in onset and
characterized by apparent instinctual defensive posturing as opposed to behaviors that are
complex and procedural. These can emerge in pathologic forms with the parasomnias, as seen
with sleep related aggression and locomotion, sleep related eating disorder (SRED), and
abnormal sleep related sexual behaviors.

In contrast, RBD often results from serious neuropathology. Initially, this neuropathology
affects the area of the brain responsible for inhibiting muscle tone during REM sleep. As a
result, dreams may be enacted. In the case of REM-related behaviors, the experience and
activity reflect the actual, often aggressive content of a dream. It is frequently possible to
correlate observed movements with later descriptions of the dream. The initial appearance of
RBD symptoms is often followed years later by the development of neurodegenerative
disorders, particularly Parkinson disease and related synucleinopathies.

Abnormal sleep related movements comprise a separate category of disorders, which is

detailed in the sleep related movement disorders section. Unlike the parasomnias, which
typically entail more complex movements and behavior, the movement disorders encompass
a broad range of predominantly simple motoric activities: myoclonic, repetitive, rocking,
rhythmic, grinding, cramping, fragmentary, dystonic, or dyskinetic movements or tremors,
which are not usually associated with dream mentation or experiential concomitants.

Parasomnias involve sleep related behaviors and experiences over which there is no
conscious deliberate control. There are ten core categories of parasomnias listed in the
International Classification of Sleep Disorders, 3rd Edition. Only one of the core categories,
RBD, requires video-polysomnographic documentation as one of the essential diagnostic
criteria. However, for most of the other parasomnias, polysomnographic monitoring can
provide corroborative documentation in support of the clinical diagnosis.

Considerable advances have taken place in understanding the neurophysiologic aspects of

abnormal arousals from slow wave sleep associated with the disorders of arousal. Advances
in the clinical understanding of these NREM sleep parasomnias have occurred as well,
particularly in regard to their prevalence and severity in adults. In regard to RBD, long-term
delayed emergence of neurodegeneration has frequently been found in middle-aged and older
adults following onset of RBD. When combined with thorough clinical interviews, video-
polysomnography a powerful discriminating tool for identifying the cause of sleep related
injury in adults.

Bibliography

Cramer Bornemann MA, Mahowald MW. Sleep forensics. In: Kryger MH, Roth T, Dement
WC, eds. Principles and practice of sleep medicine, 5th ed. Philadelphia: Elsevier
Saunders, 2010.
Hobson JA. REM sleep and dreaming: towards a theory of protoconsciousness. Nat Rev
Neurosci 2009;10:803–13.
Ohayon M, Caulet M, Priest R. Violent behavior during sleep. J Clin Psychiatry
1997;58:369–76.
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nocturnal wandering in the US adult general population. Neurology 2012;78:1583–9.
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in fronto-limbic seizures and in parasomnias. A neuroethologic approach. Neurol Sci
2005;26:s225–32.
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Parasomnias ››

NREM-Related Parasomnias
Disorders of Arousal (From NREM Sleep)
Confusional Arousals
Sleepwalking
Sleep Terrors
Sleep Related Eating Disorder
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Parasomnias ›› NREM-Related Parasomnias ››

Disorders of Arousal (From NREM Sleep)

This group of NREM-related disorders, which includes confusional arousals, sleepwalking, and
sleep terrors, arise as a result of incomplete arousals from deep sleep. The conditions share: (1)
similar genetic and familial patterns; (2) similar pathophysiology of partial arousals from deep sleep;
and (3) similar priming by sleep deprivation and biopsychosocial stressors. Disorders of arousal are:
(1) not secondary to psychiatric disorders; (2) not generally secondary to neuropathology or head
injury; (3) associated with absent or minimal cognitive functioning; (4) associated with amnesia for
the prior episode; and (5) may be triggered by sound, touch, or other stimuli.

General Diagnostic Criteria for Disorders of Arousal

Criteria A-E must be met

A. Recurrent episodes of incomplete awakening from sleep.1

B. Inappropriate or absent responsiveness to efforts of others to intervene or redirect the
person during the episode.
C. Limited (e.g., a single visual scene) or no associated cognition or dream imagery.
D. Partial or complete amnesia for the episode.
E. The disturbance is not better explained by another sleep disorder, mental disorder, medical
condition, medication, or substance use.
Notes

1. The events usually occur during the first third of the major sleep episode.
2. The individual may continue to appear confused and disoriented for several minutes or
longer following the episode.

See the following pages for ICD codes, Alternate Names, and Diagnostic Criteria specific
to: Confusional Arousals, Sleepwalking, and Sleep Terrors.

Essential Features

Disorders of arousal consist of complex behaviors that are usually initiated during partial
arousals from slow wave (N3) sleep. Most episodes are brief, but they may last as long as 30
to 40 minutes in some children. Sleep talking and shouting may accompany these events. The
eyes are usually open during an episode and, not uncommonly, are wide open with a
confused  “glassy”  stare.  The  patient  with  a  disorder  of  arousal  may  be  very  difficult  to  
awaken and, when awakened, is often confused. There is usually amnesia for these episodes,
although adults may remember fragments of episodes. Dream-like mentation is sometimes
reported in adults. Other high-level cognitive functions such as attention, planning, social
interaction, and intent are absent. Because disorders of arousal usually originate from slow
wave sleep, they most often emerge in the first third or first half of the typical sleep period.
They may occur during other times of increased slow wave sleep, such as during recovery
sleep following sleep deprivation. They rarely arise from a daytime nap.

Disorders of arousal are encountered most commonly in children and typically resolve by
puberty but may persist (or, infrequently, arise de novo) in adolescence or adulthood.

Confusional Arousals: Confusional arousals, unlike sleepwalking, occur with the patient in bed.
When the patient leaves the bed, sleepwalking has been initiated. Confusional arousals often start with
the individual sitting up in bed and looking about in a confused manner.

Sleepwalking: Sleepwalking episodes typically begin as confusional arousals. Sleepwalking episodes

can  also  begin  with  the  individual  immediately  leaving  the  bed  and  walking  or  even  “bolting”  from  
the bed and running. Highly inappropriate, agitated, resistive, belligerent, or violent behavior can also
occur. Behaviors can be simple and non–goal-directed, or complex and protracted, and may involve
inappropriate sexual activity with oneself or an individual in close proximity such as a bed partner.
The ambulation may terminate spontaneously, at times in inappropriate places, or the sleepwalker
may return to bed, lie down, and continue to sleep without reaching conscious awareness at any point.
The sleepwalking individual is disoriented in time and place, with slow speech, with severely
diminished mentation, and blunted response to questions or requests. There is often prominent
anterograde and retrograde memory impairment. Despite diminished external perception as a result of
blockade of sensory input, the individual may appear to be awake during some or most of a disorder
of arousal with reduced vigilance and impaired cognitive response.

Sleep Terrors: Sleep terrors differ from other disorders of arousal in that the events are often
accompanied by a cry or piercing scream, accompanied by autonomic nervous system and behavioral
manifestations of intense fear. There is often intense autonomic discharge, with tachycardia,
tachypnea, flushing of the skin, diaphoresis, mydriasis, and increased muscle tone. The person usually
sits up in bed; is unresponsive to external stimuli; and, if awakened, is confused and disoriented.
However, bolting out of bed and running is not uncommon in adults and also can be associated with
violent behaviors, particularly if attempts are made to block or restrain the individual. The sleep terror
episode may be accompanied by incoherent vocalizations. Sometimes there is prolonged
inconsolability associated with a sleep terror in children or adults.
Associated Features

Disorders of arousal are devoid of higher cognitive functions such as planning, memory from
before an incident, formation of a memory during an incident, true social interaction, or
recognition of others. Patients exhibiting disorders of arousal are not consciously aware and
behaviors are often  thought  to  be  “automatic”  in  nature.  Self-injury may occur as well as
injury to others in close proximity.

Disorders of arousal, in particular sleepwalking, can involve normal, routine behaviors that are
inappropriate only in regard to their timing. More often, however, sleepwalking involves
inappropriate behaviors, such as urinating in a wastebasket, moving furniture around haphazardly, or
climbing out a window. Sleepwalkers are sometimes able to navigate in familiar surroundings, but are
prone to bumping into objects or falling down. A sudden arousal consistent with sleep terrors may
segue rapidly into agitated sleepwalking and panicky running and other potentially dangerous
behaviors. Self-injury is not unusual and when resulting in death has been given the term of
“parasomnia  pseudosuicide.”  Cuts,  bruises,  and  other  injuries  may  occur—often to the surprise of the
sleepwalker once awake. Sleepwalkers are reported to have a high tolerance for pain. Knife cuts,
burns, and other self-injury sustained during sleepwalking may not awaken them.Violence to others
also can occur with adult sleepwalking, especially in men. The sleepwalker does not generally seek
out the eventual victim of violence. More typically, a person attempting to block, grab, restrain,
redirect or awaken a sleepwalker during an episode may be violently attacked, even if they are family
members or friends. This may result in a form of primitive defensive aggression including pushing,
hitting, kicking, or throwing objects. This pattern also has been reported in the sleep laboratory when
technical personnel have attempted to return sleepwalking patients to bed. In extreme cases, victims
have been stabbed with knives or blunt objects. Such inappropriate and antisocial behaviors have legal
and forensic implications, as sleepwalkers have been arrested and charged with assault and battery,
attempted homicide, homicide, and sexual assault with indecency.

The  child  with  calm  sleepwalking  may  quietly  walk  toward  a  light  or  to  the  parents’  
bedroom. Occasionally, children will walk toward a window or door or even go outside, with
obvious attendant risk.

Clinical and Pathophysiological Subtypes

Sleep related abnormal sexual behaviors are primarily classified as confusional arousals in
that they typically occur without any behaviors outside of the bed (or chosen sleeping
accommodation), but have also been less commonly associated with sleepwalking. Other
terms  for  this  condition  include  “atypical sexual behavior during sleep,”  “sexsomnia,”  and  
“sleep sex.”  Sleep related abnormal sexual behaviors often have major interpersonal, clinical,
and occasional criminal consequences. The set of abnormal sexual behaviors during
disordered arousals includes prolonged or violent masturbation, sexual molestation and
assaults (of minors and adults), initiation of sexual intercourse irrespective of the menstrual
status of the bed partner (in contrast to waking intercourse for those individuals), and loud
(sexual) vocalizations during sleep—followed by morning amnesia. The preponderance of
patients have also been diagnosed with a NREM sleep parasomnia, most often confusional
arousals alone but on occasion with sleepwalking, sleep related driving, or sleep related
eating disorder. Obstructive sleep apnea (OSA) is another recognized precipitant of sleep
related abnormal sexual behaviors.
The presence of an overlap disorder, in which RBD and a partial arousal disorder
(sleepwalking or sleep terrors) are comorbid in a patient, may complicate diagnosis of each
condition. Careful review of history and use of polysomnography may facilitate identification
of this presentation.

Demographics

There is no sex difference with disorders of arousals. They are especially prevalent among
children and adults younger than 35 years. The prevalence rate of confusional arousals and
sleepwalking are similar.

The prevalence of confusional arousals in children three to 13 years of age in a large

population-based study was 17.3%. Lifetime prevalence of confusional arousals has recently
been reported as 18.5% (16.1-20.9 confidence interval). The prevalence among adults older
than 15 years is 2.9% to 4.2%.

The  lifetime  prevalence  of  sleepwalking  is  as  high  as  18.3%.  A  recent  study  of  “nocturnal  
wandering”  that  likely  included  a  large  percentage  of  sleepwalkers reported a lifetime
prevalence of 29.2%. A Swedish study of children aged 6-16 years found the incidence of
sleepwalking to be 40%. Up to 4.3% of adults sleepwalk. In one series, one third of 54 adult
patients with injurious sleepwalking (with or without night terrors) began sleepwalking after
16 years of age.

The prevalence of sleep terrors has not been studied as thoroughly. Prevalence rates of 1% to
6.5% in children and 2.2% in adults have been reported, with a virtually constant prevalence
rate of 2.3% to 2.6% in the 15-year-old to 64-year-old age group, before falling to 1% in the
older than 65 years age group. Other studies have reported the intermittent appearance of
sleep terrors in 25% of children younger than five years.

Predisposing and Precipitating Factors

Disorders of arousal are most often evaluated in terms of predisposing, priming, and
precipitating (triggering) factors. Most often a simultaneous co-occurrence of these factors is
thought necessary in order for a disorder of arousal occur. However, the reason a disorder of
arousal occurs on one night and not others is not fully understood.

A genetic predisposition has been hypothesized and several studies have identified different
genetic loci and modes of inheritance (see Familial Pattern, below). In childhood, disorder of
arousal can usually be considered an expected and normal developmental sleep phenomenon,
apart from those cases with clinical consequences. However, disorders of arousal that persist
beyond adolescence or begin in adulthood can often be problematic and may require clinical
attention.

Many priming factors for disorders of arousal, in particular sleepwalking, have been
identified. Sleep deprivation and situational stress are the most potent factors.
Hyperthyroidism, migraines, head injury, encephalitis, stroke, and other conditions have also
been reported much more rarely as potential priming factors.

OSA and other sleep related respiratory events are increasingly recognized precipitants of
disorders of arousal in both children and adults. Treatment of these comorbid conditions may
reduce or eliminate the occurrence of disorders of arousal. Disorders of arousal may also be
triggered by environmental stimuli such as telephone calls, pagers, messaging from electronic
devices, and a host of other stimuli. It is clinically important to note that first responders,
physicians, and others on call may be vulnerable to such stimuli, increasing the potential for
inappropriate responses and behavior.

Travel, sleeping in unfamiliar surroundings, febrile states in children, physical or emotional

stress in adults, the premenstrual period in women, as well as the use of psychotropic
medications such as lithium carbonate, phenothiazines, anticholinergic agents, and
sedative/hypnotic agents have been associated with the onset of sleepwalking, but a causal
relationship has yet to be established. Alcohol has been identified in previous reports as a
potential sleepwalking trigger. However, the amnesia associated with disorders of arousal
makes these reports unreliable. More recent evidence-based reviews have found no
compelling relationship between alcohol and disorders of arousal. Internal stimuli, such as a
distended bladder, or external stimuli, such as noise or light, can also precipitate episodes.

There is no significant association between childhood disorders of arousal and

psychopathology. In adult sleepwalking, although a considerable number of patients may
have a past or current history of nonpsychotic depressive and anxiety disorders, it does not
appear that the psychiatric disorder and sleepwalking, in particular, are tightly linked. In
addition, when the two conditions emerge in close temporal proximity, control of the
psychiatric disorder often does not control the parasomnia, for which separate treatment is
required.

Familial Patterns

Genetic factors appear to play an important role in all of the disorders of arousal. However,
published research data exist primarily for patients who sleepwalk. Sleepwalking has a
familial pattern. The rate of childhood sleepwalking increases in relation to the number of
affected parents: 22% when neither parent has the disorder, 45% if one parent is affected, and
60% when both are affected. Population-based studies of monozygotic and dizygotic twins
suggest that genetic factors play a role in 65% of cases of sleepwalking. Different models of
modes of inheritance including multifactorial, recessive with incomplete penetrance, and
autosomal dominant trait with reduced penetrance have been proposed, based primarily on
analysis of family histories. However, these finding are not sufficiently specific to be used for
diagnostic testing. Further, the mechanisms by which a genetic predisposition for confusional
arousal or other related disorders contributes to their occurrence are not known.

Onset, Course, and Complications

Confusional arousals most often appear in early childhood around the age of two years. This
childhood form of confusional arousals is typically benign, but may cause concern in parents.
Confusional arousals of early childhood diminish in occurrence after the age of five years.

Sleepwalking can begin as soon as a child is able to walk but may begin at almost any time in
the life cycle, including as late as the seventh decade. Sleepwalking is often preceded by
confusional arousals. Childhood sleepwalking usually disappears spontaneously around
puberty but may persist into adolescence. Episodes can occur sporadically or with high
frequency, such as multiple times nightly for several consecutive nights. Sleepwalking may
occur for the first time in adulthood or may recur in adulthood during periods of sleep
deprivation or stress.
Sleep terrors usually emerge in children aged four to 12 years (but can also emerge in
adulthood) and tend to resolve spontaneously by early adolescence, as does sleepwalking.
Social embarrassment over the sleep terrors can impair social relationships in children and
adults. Serious or even lethal injuries can occur.

Developmental Issues

As noted above, disorders of arousal most often occur initially in childhood and decrease in
occurrence steadily until young adulthood. However, they may occur for the first time in
adulthood or reappear after many asymptomatic years, often related to stress, sleep
deprivation, or development of another sleep disorder.

Pathology and Pathophysiology

The overwhelming majority of individuals with disorders of arousal do not have neurological
or psychological pathology. There are rare reported cases of confusional arousals associated
with brain lesions in areas subserving arousal, such as the posterior hypothalamus, midbrain
reticular area, and periventricular gray matter. However, data from a single patient with
confusional arousals suggest that they may be due to a functional abnormality in the brain
that leaves some regions, such as hippocampus and frontal associative cortices, asleep, while
other parts of the brain such as motor, cingulate, insular, amygdala, and temporopolar
cortices, are active or awake.

It is generally considered that disorders of arousal represent a dissociation of different regions

of the brain in addition to activation of locomotor centers/central pattern generators,
accompanied by sleep inertia and sleep state instability.

Objective Findings

Although not routinely indicated for the evaluation of typical, uncomplicated, and
noninjurious parasomnias, polysomnographic studies demonstrate that disorders of arousal
typically begin after an arousal from slow wave sleep, most commonly toward the end of the
first or second episode of slow wave sleep. Occasionally, disorders of arousal can emerge
from stage N2 sleep. Heart rate acceleration, increased muscle tone, and muscle twitching
may rarely be observed before a slow wave sleep arousal.

Diagnostic polysomnography may note high-amplitude hypersynchronous delta waves and

frequent arousals from slow wave sleep. However, these findings have a low specificity and
have been reported to occur in other disorders such as OSA and in asymptomatic individuals.
On rare occasions, polysomnography can provide support for the clinical diagnosis by
documenting arousals from slow wave sleep accompanied by behaviors typical of
confusional arousals. Out-of-bed behaviors are very rare in the sleep laboratory. Changes
between the home and sleep laboratory environment, timing, habits, and other factors may
serve to decrease the likelihood of sleepwalking in the laboratory. Time-synchronized video-
polysomnographic (vPSG) recording is essential if polysomnography (PSG) is to be used as
support for the diagnosis. However, a normal PSG does not rule out the diagnosis of a
disorder of arousal. In adults in whom there are only one or two episodes per year, there is a
very low likelihood of occurrence in the sleep laboratory. However, the sleep study may
assist in ruling out disorders with similar presentations, such as RBD or nocturnal epilepsy.
PSG may further be useful by identifying potential triggers, such as sleep related breathing
disorder or periodic leg movements that are currently present. Provocative sleep studies using
sleep deprivation and acoustic stimuli have been used for research purposes, with success.
However, the sensitivity and specificity of these techniques for clinical purposes are
unknown.

Postarousal EEG recordings in children and adults with sleepwalking often demonstrate a
partial or virtually complete persistence of sleep, with diffuse, rhythmic delta activity; diffuse
delta and theta activity; mixed delta, theta, alpha, and beta activity; or at times alpha and beta
activity.

PSG also may be helpful in excluding the diagnosis of RBD by demonstration of normal
muscle atonia in REM sleep (assuming adequate amounts of REM sleep are observed).
Although  the  “macrostructure”  of  sleep  (i.e.,  the  cycling  of  various  NREM  and  REM  sleep  
stages and the relative distributions of these sleep stages) is generally preserved with
sleepwalking,  the  “microstructure”  of  sleep  can  be  perturbed.  Power  spectral  analyses  of  slow  
wave activity in adult sleepwalkers have revealed several forms of slow wave sleep
dysregulation, including high amounts of slow wave sleep fragmentation (particularly during
the first NREM-REM sleep cycle), a significant increase in delta power just prior to an
arousal, and increased slow wave activity across all NREM sleep cycles.

Differential Diagnosis

Disorders of arousal should be carefully distinguished from other disorders with similar
presentations, but different pathophysiologies, courses, and treatments. Other disorders to be
considered includeRBD, sleep related epilepsy, sleep related dissociative disorders, alcohol
and drug related behaviors,and OSA.

RBD typically presents as dream-enacting behaviors during the second half of the night and
usually affects middle-aged men, but also can affect women and virtually any age group.
Because sleepwalking in adults can also present as dream-enacting behaviors that emerge
during any time of the night, vPSG may be necessary to distinguish sleepwalking from RBD.
In contrast to disorders of arousal, signs of RBD, particularly tonic/phasic EMG activity
during REM sleep, are almost always present during sleep studies. If sleepwalking (or sleep
terrors) occurs with RBD in the same patient, both should be diagnosed. This has been
referred to as a parasomnia overlap disorder.

Other sleep disorders, such as OSA, can precipitate disorders of arousal. Therefore, a careful
history must be obtained to identify other sleep disorders. Sleep related epilepsy can manifest
with wandering behavior or with frenzied walking or running. In adults, a diagnosis
of malingering also should be considered. If a neurologic or medical disorder is identified as
the precipitant of a disorder of arousal, then the sleepwalking should be diagnosed
as parasomnia due to a medical disorder.

Disorders of arousal should not be diagnosed in the presence of alcohol intoxication. The
behavior of the alcohol-intoxicated individual may superficially resemble that of the
sleepwalker. However, the sleepwalker is typically severely cognitively impaired, but with
only limited motor impairment. The alcohol-intoxicated  individual’s  level  of  cognitive  
functioning may be reduced, but not absent, whereas motor behavior is often severely
impaired. In alcoholic blackouts, where anterograde amnesia is, by definition, the cardinal
manifestation, it is important to note that outward motor behavior and cognitive function may
not be impaired and may be perceived as normal. Thus, the importance of appreciating the
neuroscience of alcoholic blackouts and its potential role in the explanation of unusual and
bizarre nocturnal behaviors cannot be understated because these can mimic parasomnias. The
former are exponentially more prevalent and thus should be given appropriate weight when
attributing likely causation in cases with criminal allegations.

Unresolved Issues and Further Directions

With the development of sophisticated genetic testing and neuroimaging, direct research into
the causes and mechanisms of disorders or arousals is anticipated. Further investigations that
aid in the characterization of the pathophysiology are necessary. Further development of
sleep laboratory-based techniques for provoking episodes of sleepwalking would improve
diagnostic accuracy.

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Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Parasomnias ››
REM-Related Parasomnias
REM Sleep Behavior Disorder
Recurrent Isolated Sleep Paralysis
Nightmare Disorder
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Parasomnias ›› REM-Related Parasomnias ››

REM Sleep Behavior Disorder

ICD-9-CM code: 327.42

ICD-10-CM code: G47.52

Alternate Names

None.

Diagnostic Criteria

Criteria A-D must be met

A. Repeated episodes of sleep related vocalization and/or complex motor behaviors.1,2

B. These behaviors are documented by polysomnography to occur during REM sleep or,
based on clinical history of dream enactment, are presumed to occur during REM sleep.
C. Polysomnographic recording demonstrates REM sleep without atonia (RWA)3
D. The disturbance is not better explained by another sleep disorder, mental disorder,
medication, or substance use.
Notes

1. This criterion can be fulfilled by observation of repetitive episodes during a single night of
video polysomnography.
2. The observed vocalizations or behaviors often correlate with simultaneously occurring
dream  mentation,  leading  to  the  frequent  report  of  “acting  out  one's  dreams.”
3. As defined by the guidelines for scoring PSG features of RBD in the most recent version of
the American Academy of Sleep Medicine (AASM) Manual for the Scoring of Sleep and
Associated Events.
4. Upon awakening, the individual is typically awake, alert, coherent, and oriented.
5. On occasion, there may be patients with a typical clinical history of RBD with dream-
enacting behaviors, who also exhibit typical RBD behaviors during vPSG, but do not
demonstrate sufficient RWA, based on the current evidence-based data, to satisfy the PSG
criteria for diagnosing RBD. In such patients, RBD may be provisionally diagnosed,
based on clinical judgment. The same rule applies when vPSG is not readily available.
6. Medications may unmask latent RBD with preexisting RWA, according to current expert
opinion. Therefore, medication-induced RBD can be diagnosed as RBD, using clinical
judgment, pending future longitudinal studies.
Essential Features

RBD is characterized by abnormal behaviors emerging during REM sleep that may cause
injury or sleep disruption. RBD is also associated with EMG abnormalities during REM
sleep. The EMG demonstrates an excess of muscle tone during REM sleep, and/or an excess
of phasic EMG twitch activity during REM sleep.

A complaint of sleep related injury is common with RBD, which usually manifests as an
attempted enactment of unpleasant, action-filled, and violent dreams in which the individual
is being confronted, attacked, or chased by unfamiliar people or animals. Typically, at the end
of an episode, the individual awakens quickly, becomes rapidly alert, and reports a dream
with a coherent story. The dream action corresponds closely to the observed sleep behaviors.

Sleep and dream-related behaviors reported by history and documented during vPSG include
both violent and (less commonly) nonviolent behaviors: talking (including giving speeches),
smiling, laughing, singing, whistling, shouting, swearing profanities, crying, chewing,
gesturing, reaching, grabbing, arm flailing, clapping, slapping, punching, kicking, sitting up,
leaping from bed, crawling, running, or dancing. Walking, however, is quite uncommon with
RBD, and leaving the room is especially rare, because the eyes are usually closed, precluding
attention to the environment. There can be rare occurrences of smoking a fictive cigarette,
masturbation-like behavior, pelvic thrusting, and mimics of eating, drinking, urinating, and
defecating. The eyes usually remain closed during an RBD episode, with the person attending
to the dream action and not to the actual environment.

Medical attention is usually sought after sleep related injury has occurred to either the person
or the bed partner, and rarely because of sleep disruption. Because RBD occurs during REM
sleep, it usually appears at least 90 minutes after sleep onset, unless there is coexisting
narcolepsy, in which case RBD can emerge shortly after sleep onset during a sleep onset
rapid eye movement period (SOREMP). There is an acute form of RBD that emerges during
intense REM sleep rebound states, such as during withdrawal from alcohol and sedative-
hypnotic agents, or in association with certain medication use, drug intoxication, or relapsing
multiple sclerosis.

Associated Features

PLMs during NREM sleep are very common with RBD and may disturb the sleep of the bed
partner. Daytime tiredness or sleepiness is uncommon, unless narcolepsy is also present.
There is typically no history of irritable, aggressive, or violent behavior during the day. There
may be a longstanding prodromal history of sleeptalking, yelling, limb twitching, and jerking
during sleep that may or may not be dream related.

Clinical and Pathophysiological Subtypes

Parasomnia overlap disorder is a condition in which patients have both RBD and either a
disorder of arousal, sleep related eating disorder, sexsomnia, or rhythmic movement disorder.
This condition is male predominant, but less so than isolated RBD. Most cases begin during
childhood or adolescence. Virtually all age groups can be affected. It can be idiopathic or
symptomatic of a broad set of disorders, including narcolepsy, multiple sclerosis, brain tumor
(and therapy), rhombencephalitis (right pontine tegmentum/medulla lesion), brain trauma,
congenital Moebius syndrome, agrypnia excitata, Machado-Joseph disease, various
psychiatric disorders and their pharmacotherapies, and substance abuse disorders and
withdrawal states.

Status dissociatus can be classified as a subtype of RBD that manifests as an extreme form of
state dissociation without identifiable sleep stages, but with sleep and dream-related
behaviors that closely resemble RBD. Status dissociatus represents a major breakdown of the
polysomnographic markers for REM sleep, NREM sleep, and wakefulness, with admixtures
of these states being present, but with conventional sleep stages not being identifiable during
polysomnographic monitoring. There is abnormal behavioral release that can be associated
with disturbed dreaming, strongly suggestive of dream-enacting behaviors that closely
resemble RBD. Not uncommonly, the individual thinks he is awake when observers presume
he is asleep and attempting to act out a dream, or vice versa. An underlying neurologic or
medical condition, spanning a broad range of pathology, is virtually always present.

Dream  enactment  (“oneirism”)  that  is  REM  sleep  related  or  related  to  a  dissociated  REM  
sleep-wakefulness state can be a core feature of a pathologic condition called agrypnia
excitata that is characterized by generalized motor overactivity, impaired ability to initiate
and  maintain  sleep  (with  “wakeful  dreaming”),  loss  of  slow  wave  sleep,  and  marked  motor  
and autonomic sympathetic activation. Agrypnia excitata is found with such diverse
conditions as delirium tremens, Morvan syndrome, and fatal familial insomnia. Thus,
agrypnia excitata manifests as both a severe parasomnia and a severe insomnia.

Demographics

RBD is a male predominant disorder that usually emerges after age 50 years. Cases of RBD
from early childhood up to age 88 years have been reported. RBD emerging in adults before
age 50 years tends to have different demographics and associated features, including greater
sex parity and increased rates of idiopathic RBD and parasomnia overlap disorder (POD),
comorbid narcolepsy, antidepressant medication use, and possibly autoimmune diseases. In
addition, the clinical presentation of RBD in younger adults differs from that in older adults
in being less aggressive and violent, presumably due to greater female representation and
higher rates of comorbid narcolepsy (which manifests with milder RBD behaviors).

RBD associated with neurologic disorders and other symptomatic forms of RBD are as male
predominant as idiopathic RBD, with the exception of narcolepsy (as described below) and
multiple system atrophy. Of note, RBD may not be the presenting complaint to a sleep
disorders center. Therefore, systematic questioning for RBD should be included for all newly
evaluated patients at a sleep center. RBD in children is virtually never idiopathic and is
usually associated with narcolepsy (at times emerging months before the emergence of
narcoleptic symptoms), brainstem tumors, antidepressant medications, neurodevelopmental
disorders, and various rare conditions.

The prevalence is not known with much certainty, although a prevalence of 0.38% to 0.5% is
reported in the elderly and the general population. A 2.1% prevalence of current sleep related
violence has been reported; 38% of these events have associated dream enactment,
suggesting a prevalence of RBD as high as 0.8%.

Predisposing and Precipitating Factors

The major predisposing factors are male sex, age 50 years or older, and an underlying
neurological disorder, particularly Parkinson disease, multiple system atrophy, dementia with
Lewy bodies, narcolepsy, or stroke. A recent multicenter case-control study of environmental
risk factors of RBD found that smoking, head injury, pesticide exposure, and farming were
significant risk factors. Medications, particularly the antidepressants venlafaxine, serotonin-
specific reuptake inhibitors (SSRIs), mirtazapine, and other antidepressant agents (but not
bupropion) are an increasingly recognized precipitating factor. Beta-blockers (bisoprolol,
atenolol), anticholinesterase inhibitors, and selegiline can also trigger RBD. Psychiatric
disorders involving depression (that require antidepressant pharmacotherapy) may comprise a
predisposing factor, particularly in adults younger than 50 years. RBD may also be associated
with posttraumatic stress disorder.

Familial Patterns

A recent multicenter controlled study revealed a significantly increased positive family

history of dream enactment, raising the possibility of a genetic contribution to RBD.

Onset, Course, and Complications

Onset of chronic RBD can be gradual or rapid, and the course is often progressive.
Complications include sleep related injuries to self and/or bed partner that at times are life
threatening, and disruption of the bed partner's sleep that can be severe. Marital discord due
to the RBD is uncommon but can be severe when present, due to repeated injury and/or
disruption of the bed partner's sleep.

Delayed emergence of a neurodegenerative disorder, often more than a decade after the onset
of idiopathic RBD, is very common in men 50 years of age and older. These disorders
include Parkinson disease (PD), multiple system atrophy (MSA), and dementia with Lewy
bodies (DLB). Two recently reported series found 81% and 82% eventual conversion rates
from idiopathic RBD to parkinsonism/dementia (and also mild cognitive impairment in the
latter study). Conversely, RBD is present in >90% of reported cases of MSA, in
approximately 50% of reported cases of DLB, and in up to 46% of reported patients with PD.

Developmental Issues

As stated previously, RBD can emerge in children, usually in association with narcolepsy-
cataplexy, brainstem tumors, or antidepressant medications.

Pathology and Pathophysiology

Current evidence suggests a selective association between RBD and neurodegenerative

disorders. The synucleinopathies comprise a set of neurodegenerative disorders that share a
common pathologic lesion composed of aggregates of insoluble α-synuclein protein in
selectively vulnerable populations of neurons and glial cells. These pathologic aggregates
appear to be closely linked to the onset and progression of clinical symptoms and the
degeneration of affected brain regions in neurodegenerative disorders. The major
synucleinopathies include PD, DLB, and MSA.

RBD can be strongly linked with narcolepsy (almost always narcolepsy type 1), representing
another form of REM sleep motor-behavioral dyscontrol. The RBD may be precipitated or
worsened by the pharmacologic treatment of cataplexy. RBD associated with narcolepsy is
now considered to be a distinct phenotype of RBD, characterized by lack of sex
predominance, less complex and more elementary movements in REM sleep, less violent
behavior in REM sleep, earlier age of onset, and hypocretin deficiency (that is characteristic
of narcolepsy type 1). The presence of RBD in pediatric patients may be an initial
manifestation of narcolepsy type 1.

Other reported etiologic associations of RBD with neurologic disorders include ischemic or
hemorrhagic cerebrovascular disease, multiple sclerosis, progressive supranuclear palsy,
Guillain-Barré syndrome, brainstem neoplasms (including cerebellopontine angle tumors),
Machado-Joseph disease (spinocerebellar ataxia type 3), mitochondrial encephalomyopathy,
normal pressure hydrocephalus, Tourette syndrome, group A xeroderma, and autism.

The pathophysiology of human RBD is presumed to correspond to the findings from an

animal model of RBD with respect to interruption of the REM atonia pathway and/or
disinhibition of brainstem motor pattern generators.

Objective Findings

Polysomnography demonstrates an excessive amount of sustained or intermittent loss of

REM atonia and/or excessive phasic muscle twitch activity of the submental and/or limb
EMGs during REM sleep. Some patients have almost exclusively arm and hand behaviors
during REM sleep, indicating the need for both upper and lower extremity EMG monitoring
in fully evaluating for RBD. Some patients preserve most of their REM atonia but have
excessive EMG twitching during REM sleep. The most current evidence-based data for
detecting RWA in the evaluation of RBD indicate that any (tonic/phasic) chin EMG activity
combined with bilateral phasic activity of the flexor digitorum superficialis muscles in >27%
of REM sleep (scored in 30-second epochs) reliably distinguishes RBD patients from
controls. Autonomic nervous system activation (such as tachycardia) is uncommon during
REM sleep motor activation in RBD, in contrast to the disorders of arousal. Approximately
75% of patients have PLMs during NREM sleep; a low percentage of these movements is
associated with EEG signs of arousal. Increased percentages of slow wave sleep and
increased delta power in RBD have been found in controlled and uncontrolled studies, but
this can be a highly variable finding in RBD, depending on the clinical population. Sleep
architecture and the customary cycling among REM and NREM sleep stages are usually
preserved in RBD, although some patients show a shift toward N1 sleep.

Validated RBD screening questionnaires that can assist in the process of diagnosing RBD are
currently available.

Differential Diagnosis

RBD is one of several disorders that can manifest as complex, injurious, and violent sleep
related and dream-related behaviors in adults. Other disorders that can mimic RBD in adults
and/or children include sleepwalking, sleep terrors, OSA, nocturnal seizures (nocturnal
frontal lobe epilepsy; nocturnal complex partial seizures); rhythmic movement disorders;
sleep related dissociative disorders, frightening hypnopompic
hallucinations, and posttraumatic stress disorder; a diagnosis of malingeringalso should be
considered.
In general, RBD involves attempted enactment of unpleasant, aggressive dreams that usually
occurs two or more hours after sleep onset, with rapid awakening from an episode. In
contrast, sleepwalking and sleep terror episodes often emerge within two hours after sleep
onset, are not usually associated with rapid alertness, and are rarely associated with dreaming
in children. Adults can have dreams associated with disorders of arousal, but they are usually
more fragmentary and limited than RBD dreams. Sleep related seizures usually present with
repetitive, stereotypical behaviors.

Parasomnia overlap disorder can be distinguished from status dissociatus in several ways: if
there is an awakening after an episode of RBD, sleepwalking, or sleep terror, there is the
realization of having just been asleep; status dissociatus, however, is more likely to manifest
with confusion over whether one is asleep, awake, or dreaming. vPSG in overlap conditions
shows the typical findings for both RBD and disorders of arousal, whereas with status
dissociatus, there is an inability to discern sleep stages. Also, patients with status dissociatus
do not walk far during an episode, and their behavioral repertoire more closely resembles that
of RBD than that of the disorders of arousal.

Unresolved Issues and Further Directions

Numerous questions related to the vPSG evaluation of RBD remain unresolved. These
include issues of defining and quantifying RWA and RBD activity such as: (1) What is the
minimum REM sleep percentage of total sleep time (and minimum absolute REM sleep time)
needed to diagnose RWA or rule out RWA? (2) What is the minimum number of REM sleep
epochs and minimum duration of REM sleep epochs necessary to diagnose RWA or rule out
RWA? (3) What guidelines can be developed for diagnosing or ruling out RWA in the setting
of disrupted REM sleep continuity associated with conditions such as obstructive sleep apnea
and with medications? (4) What are the minimal amounts of true RBD behaviors documented
by vPSG needed to identify RBD in patients without sufficient RWA?

It is unclear why there is a male predominance of this disorder in middle-aged and older
adults. It is unknown if RBD subgroups other than men age 50 years or older demonstrate
increased risk for development of parkinsonism or dementia. One such subgroup comprises
patients with antidepressant-triggered RBD for whom the potential risk for future
parkinsonism and dementia is unclear. New antidepressant or other psychotropic agents being
developed for clinical use should be assessed for their immediate and long-term effects on
REM atonia, REM phasic activity, REM sleep behavioral release, and proclivity to
precipitate dream-enacting behaviors.

Bibliography

Boeve BF. REM sleep behavior disorder: Updated review of the core features, the REM sleep
behavior disorder-neurodegenerative disease association, evolving concepts,
controversies, and future directions. Ann N Y Acad Sci 2010;1184:15–54.
Dauvilliers Y, Jennum P, Plazzi G. REM sleep behaviour disorder and REM sleep without
atonia in narcolepsy. Sleep Med 2013;14:775–81.
Frauscher B, Gschliesser V, Brandauer E, et al. REM sleep behavior disorder in 703 sleep-
disorder patients: the importance of eliciting a comprehensive sleep history. Sleep Med
2010;11:167–71.
Frauscher B, Iranzo A, Gaig C, et al. Normative EMG values during REM sleep for the
diagnosis of REM sleep behavior disorder. Sleep 2012;35:835–47.
Iranzo A, Santamaria J. Severe obstructive sleep apnea/hypopnea mimicking REM sleep
behavior disorder. Sleep 2005;28:203–6.
Iranzo A, Santamaria J, Tolosa E. The clinical and pathophysiological relevance of REM
sleep behavior disorder in neurodegenerative diseases. Sleep Med Rev 2009;13:385–401.
Iranzo A, Tolosa E, Gelpi E, et al. Neurodegenerative disease status and post-mortem
pathology in isolated rapid-eye-movement sleep behaviour disorder: an observational
cohort study. Lancet Neurol 2013;12:443–53.
Ju YE. Rapid eye movement sleep behavior disorder in adults younger than 50 years of age.
Sleep Med 2013;14:768–74.
Lloyd R, Tippman-Peikert M, Slocumb N, Kotagal S. Characteristics of REM sleep behavior
disorder in childhood. J Clin Sleep Med 2012:15:127–31.
Olson E, Boeve B, Silber M. Rapid eye movement sleep behavior disorder: demographic,
clinical, and laboratory findings in 93 cases. Brain 2000;123:331–9.
Oudiette D, De Cock VC, Lavault S, Leu S, Vidailhet M, Arnulf I. Non-violent elaborate
behaviors may also occur in REM sleep behavior disorder. Neurology 2009;72:551–7.
Postuma RB, Gagnon JF, Vendette M, Fantini ML, Massicotte-Marquez J, Montplaisir J.
Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior
disorder. Neurology 2009;72:1296–300.
Schenck CH, Mahowald MW. REM sleep behavior disorder: clinical, developmental, and
neuroscience perspectives 16 years after its formal identification in SLEEP. Sleep
2002;25:120–38.
Schenck CH, Boeve BF, Mahowald MW. Delayed emergence of a parkinsonian disorder or
dementia in 81% of older males initially diagnosed with idiopathic REM sleep behavior
disorder (RBD): 16 year update on a previously reported series. Sleep Med 2013;14:744–
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Schenck CH, Howell MJ. Spectrum of RBD (overlap between RBD and other parasomnias).
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Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Parasomnias ›› REM-Related Parasomnias ››

Recurrent Isolated Sleep Paralysis

ICD-9-CM code: 327.43

ICD-10-CM code: G47.51

Alternate Names

Hypnagogic and hypnopompic paralysis, predormital and postdormital paralysis, kanashibari

(Japan).

Diagnostic Criteria

Criteria A-D must be met

A. A recurrent inability to move the trunk and all of the limbs at sleep onset or upon
awakening from sleep.
B. Each episode lasts seconds to a few minutes.
C. The episodes cause clinically significant distress including bedtime anxiety or fear of
sleep.
D. The disturbance is not better explained by another sleep disorder (especially narcolepsy),
mental disorder, medical condition, medication, or substance use.
Essential Features

Recurrent isolated sleep paralysis is characterized by an inability to perform voluntary

movements at sleep onset (hypnagogic or predormital form) or on waking from sleep
(hypnopompic or postdormital form) in the absence of a diagnosis of narcolepsy. The event
consists of an inability to speak or to move the limbs, trunk, and head. Respiration is usually
unaffected. Consciousness is preserved, and full recall is present. An episode of sleep
paralysis lasts seconds to minutes. It usually resolves spontaneously but can be aborted by
sensory stimulation, such as being touched or spoken to, or by the patient making intense
efforts to move.

Associated Features

At least during the initial episodes, intense anxiety is usually present. Hallucinatory
experiences accompany the paralysis in about 25% to 75% of patients. These may include
auditory, visual, or tactile hallucinations, or the sense of a presence in the room. Some
patients experience predormital or postdormital hallucinations at separate times from
episodes of sleep paralysis.

Clinical and Pathophysiological Subtypes

A familial form of sleep paralysis has been described (see below).

Demographics

Estimates of the prevalence of sleep paralysis vary widely due to differences in the definition
used, the age of the population sampled, and possibly cultural and ethnic factors. Most
prevalence studies of sleep paralysis (usually of students younger than 30 years) have
investigated the occurrence of one or more episodes without requirement of recurrence or
distress. These suggest a 15% to 40% prevalence of at least one episode of sleep paralysis.
Two notable exceptions are a 1962 study of mostly college students that reported a
prevalence of 5%, and a 1999 study of all adult ages that found a prevalence of 6%. No
consistent sex differences have emerged from multiple studies. The mean age of onset is 14
to 17 years, although onset earlier and later in life has been reported.

Predisposing and Precipitating Factors

Sleep deprivation and irregular sleep-wake schedules have been identified as predisposing
factors to episodes of sleep paralysis. Mental stress has been reported as a precipitating factor
in some but not other studies. Sleep paralysis appears to be more common with sleep in the
supine position. Personality factors have not been shown to play a major role, although one
study found a higher score on the paranoia scale of the Minnesota Multiphasic Personality
Inventory in patients with sleep paralysis compared to controls. Other factors that have been
noted on regression analysis include an association with bipolar disorder, the use of
anxiolytic medication, and sleep related leg cramps.

Familial Patterns

Two families with apparent familial sleep paralysis occurring over three and four generations
have been reported. A maternal form of transmission has been postulated.

Onset, Course, and Complications

Onset is usually in adolescence. Most events appear to occur in the second and third decades,
but may continue later in life. There are no known complications, apart from anxiety over the
episodes.

Developmental Issues

Though sleep paralysis may be present as part of the narcolepsy tetrad in children, there is no
information currently available about childhood presentation of recurrent isolated sleep
paralysis.

Pathology and Pathophysiology

Episodes of sleep paralysis elicited by awakening patients from nocturnal sleep appear to
arise from REM sleep. Sleep paralysis is an example of state dissociation with elements of
REM sleep persisting into wakefulness. Early-onset REM sleep after forced awakenings has
been shown to predispose an individual to having sleep paralysis. It may be that subjects with
less tolerance to sleep disruption are more likely to experience the phenomenon.

Objective Findings

Analysis of sleep paralysis after forced awakenings during PSG studies reveals the event to
be a dissociated state with the persistence of REM-related electromyographic atonia into
conscious wakefulness. Hallucinatory experiences may be present but are not essential for the
diagnosis.

Differential Diagnosis

Cataplexy produces similar generalized paralysis of skeletal muscles but occurs during
wakefulness and is precipitated by emotion. Atonic seizures occur during
wakefulness. Nocturnal panic attacks are not usually associated with paralysis. Familial
periodic paralysis syndromes, especially hypokalemic periodic paralysis, may occur at rest
and on awakening. However, the episodes usually last hours, may be associated with
carbohydrate intake, and are usually accompanied by hypokalemia. There are
also hyperkalemic and normokalemic periodic paralysis syndromes.

Unresolved Issues and Further Directions

Not applicable or known.

Bibliography
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Harsh J, eds. Sleep onset: normal and abnormal processes. Washington: American
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New York: Spectrum, 1976:97–124.
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sleep paralysis in the general population. Neurology 1999;52:1194–200.
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isolated sleep paralysis elicited during a multi-phasic sleep-wake schedule. Sleep
2002;25:89–96.
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sleep interruption. Sleep 1992;15:217–25.
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Parasomnias ›› REM-Related Parasomnias ››

Nightmare Disorder
ICD-9-CM code: 307.47

ICD-10-CM code: F51.5

Alternate Names

Nightmares, REM nightmares, recurrent nightmares, dream anxiety disorder, anxiety dreams.

Diagnostic Criteria

Criteria A-C must be met

A. Repeated occurrences of extended, extremely dysphoric, and well-remembered dreams that usually
involve threats to survival, security, or physical integrity.

B. On awakening from the dysphoric dreams, the person rapidly becomes oriented and alert.

C. The dream experience, or the sleep disturbance produced by awakening from it, causes clinically
significant distress or impairment in social, occupational, or other important areas of functioning as
indicated by the report of at least one of the following:

1. Mood disturbance (e.g., persistence of nightmare affect, anxiety, dysphoria).

2. Sleep resistance (e.g., bedtime anxiety, fear of sleep/subsequent nightmares).

3. Cognitive impairments (e.g., intrusive nightmare imagery, impaired concentration, or memory).

4. Negative impact on caregiver or family functioning (e.g., nighttime disruption).

5. Behavioral problems (e.g., bedtime avoidance, fear of the dark).

6. Daytime sleepiness.

7. Fatigue or low energy.

8. Impaired occupational or educational function.

9. Impaired interpersonal/social function

Notes

1. Nightmare disorder in children is most likely to occur in those exposed to severe psychosocial
stressors. Because childhood nightmares often resolve spontaneously, the diagnosis should be given
only if there is persistent distress or impairment.

Essential Features

Nightmare disorder is characterized by recurrent, highly dysphoric dreams, which are disturbing
mental experiences that generally occur during REM sleep and that often result in awakening. Given
that these experiences are most often associated with REM sleep, the episodes have a greater tendency
to occur during the second half of the major sleep episode when the REM pressure is most
pronounced. Nightmares involve an internally generated conscious experience or dream sequence that
seems vivid and real. They have a tendency to become increasingly more disturbing as they unfold.
Emotions are characteristically negative and most frequently involve anxiety, fear, or terror but may
also involve anger, rage, embarrassment, and disgust. Nightmare content most often focuses on
imminent physical danger to the individual but may also involve other distressing themes. Ability to
detail  the  nightmare’s  contents  upon  awakening  is  common  in  nightmare  disorder.  Multiple  
nightmares within a single sleep episode may occur and may bear similar themes. Because nightmares
typically arise during REM sleep, they may occur at any moment that REM pressure is high.

Nightmares are very common in children. They typically occur in the last third of the night and result
in a complete awakening, after which the child can often provide a detailed description of the
frightening scenario. However, clear distinction from confusional arousals and sleep terrors in young
children is often not possible.

Associated Features

Postawakening anxiety and difficulty returning to sleep may be present. Nightmares are more
common in those with higher levels of anxiety. Additionally, nightmares are commonly seen in those
who have been physically or sexually abused and in those suffering from posttraumatic stress
disorder.

Nightmares arising either immediately following a trauma (acute stress disorder [ASD]) or one month
or more after a trauma (posttraumatic stress disorder [PTSD]) have been described during NREM
sleep, especially N2, as well as during REM sleep and at sleep onset. Posttraumatic nightmares may
take the form of a realistic reliving of a traumatic event or may depict only some of its elements or
emotional content.

Clinical and Pathophysiological Subtypes

None known.

Demographics
Occasional nightmares are very common in children, occurring in 60% to 75% of children, beginning
as young as 2.5 years of age. The occurrence of occasional nightmares in children does not constitute
a nightmare disorder. However, frequent nightmares are uncommon, occurring in 1% to 5% of
preadolescent children. It is estimated that 10% to 50% of children aged three to five years have at
least occasional nightmares severe enough to disturb their parents. Nightmares appear to be a trait-like
characteristic that persists over time during childhood. The best predictor of recurrent nightmares at
an older age is recurrent nightmares in childhood. Approximately 2% to 8% of the general population
has a current problem with nightmares, and this frequency is higher in clinical populations. Trauma-
related nightmares are the most consistent problem reported by patients with PTSD. Nightmares
beginning within three months of a trauma are present in up to 80% of patients with PTSD. Although
approximately 50% of PTSD cases resolve within three months, posttraumatic nightmares may persist
throughout life.

Predisposing and Precipitating Factors

Frequent nightmares are associated with enduring personality characteristics and psychopathologies;
they are inversely correlated with measures of well-being. Associations with psychopathology have
been identified for adults and adolescents, but research on children is largely absent other than for
assessments of PTSD. Measures of nightmare distress are much more robustly associated with
psychopathology than are measures of nightmare frequency.

The clinical use of pharmacologic agents affecting the neurotransmitters norepinephrine, serotonin,
and dopamine is associated with the complaint of nightmares. A majority of these agents are
antidepressants, antihypertensives, and dopamine-receptor agonists. Agents affecting the
neurotransmitters gamma-aminobutyric acid (GABA), acetylcholine, and histamine, and the
withdrawal of REM sleep suppressive agents also can be associated with the complaint of nightmares.
Of note, nightmares are a common reaction in varenicline, which is an agent that blocks α-4-β-2
nicotinic acetylcholine receptors.

Familial Patterns

Twin-based studies have identified persistent genetic predisposition to nightmares in childhood

(reported retrospectively by adults) and adulthood as well as genetic influences on the co-occurrence
of nightmares and some other parasomnias, such as sleeptalking (somniloquy).

Onset, Course, and Complications

Nightmares usually start between ages three years and six years. The proportion of children reporting
nightmares reaches a peak between six and ten years of age and decreases thereafter. A subgroup of
children continue to have nightmares into adolescence or adulthood and may become lifelong
nightmare sufferers. Nightmares generally diminish in frequency and intensity over the course of
decades, but some patients still describe frequent episodes at the age of 60 or 70 years. Nightmare
disorder can lead to sleep avoidance and deprivation, and thereby to more intense nightmares, which
can produce insomnia.

ASD and PTSD associated nightmares can develop at any age after physical or emotional trauma.
Individuals with PTSD are at risk for developing mood disorders and depression, social and
employment consequences, self-destructive and impulsive behavior, and substance abuse; it is not
known to what extent the nightmares symptomatic of PTSD contribute to these complications.
Developmental Issues

As stated above, nightmares are very common in children but the occurrence of occasional nightmares
does not constitute nightmare disorder. Population studies have revealed that the prevalence and
frequency of nightmares increases through childhood into adolescence. For example, preschoolers
seldom  report  “bad  dreams.”  Furthermore,  in  regard  to  the  prevalence  of  nightmares,  children  appear  
to exhibit a sex divergence over time, with girls demonstrating higher prevalence by late adolescence.

Pathology and Pathophysiology

Not applicable or known.

Objective Findings

PSG recordings during actual nightmares are few in number and, in some instances, have shown
abrupt awakenings from REM sleep preceded by accelerated heart and respiratory rates. Highly
disturbing dream content frequently contrasts strikingly with relatively minor autonomic changes.
Distinctive anomalies in nightly sleep architecture have not been demonstrated; brainstem and
auditory-evoked potentials appear normal. Recordings during posttraumatic nightmares are few but
have been recorded from both REM and NREM sleep. PSG recordings of sleep in patients with PTSD
have provided widely variable results.

PSG evaluation is not routinely performed but may be indicated in some circumstances to exclude
other parasomnias such as disorders of arousal and sleep-associated seizures. A PSG is particularly
appropriate if patients report nightmares in conjunction with sleep behaviors that are repetitive or
stereotyped or are injurious to self or others.

Differential Diagnosis

Nightmare disorder must be distinguished from dream disturbances associated with certain other
neurological and sleep disorders. Rare cases of seizures presenting  only  as  “nightmares”  have  been  
reported and should be considered in the differential diagnosis, particularly in those patients who
present with a history of central nervous system disease. PSG or continuous video EEG may be
necessary to identify nightmares associated with nocturnal seizures. Nightmares differ from sleep
terrors in having detailed recollection of dreaming in contrast to fragments of dreams or no dream
recall, presenting no or minimal overt movement or autonomic activity, occurring late in the night,
being followed by rapid awakening and difficulty returning to sleep, and most often arising from
REM sleep. RBD occurs more often in late middle-aged men and is more often associated with violent
explosive movements and a history of nocturnal injuries. The dream disturbance of RBD usually
involves being threatened or attacked by unfamiliar people or animals and is controlled in tandem
with the sleep behavioral disturbance by appropriate medication. Nightmares occur at any age and are
not typically associated with movements, overt behaviors, or injuries. Anxiety may accompany
episodes of sleep paralysis occurring either at sleep onset (hypnagogic) or offset (hypnopompic),
when the individual feels conscious but unable to move, speak, and, at times, breathe properly.
Anxiety may be further worsened if disturbing hypnagogic hallucinations or dream sequences
accompany the paralysis. Nightmares, although they may involve some degree of movement
inhibition or some degree of apparent wakefulness, are usually not accompanied by feelings of either
total paralysis or complete waking consciousness.
Patients with narcolepsy often report nightmares; these may occur at sleep onset. However,
narcolepsy and nightmare disorder are clearly distinguishable by other clinical symptoms. Nocturnal
panic attacks occur either during or immediately after nocturnal awakenings from NREM sleep,
usually in the first four hours of the sleep episode. Although frequency of panic attacks is correlated
with frequency of nightmares and many patients report that dysphoric dreams precede their attacks,
there may be no dream recall reported on awakening with a panic attack.

Sleep related dissociative disorders comprise a sleep related variant of the dissociative disorders as
defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V). These
include dissociative identity disorder (formerly called multiple personality disorder) and dissociative
fugue, in which individuals meeting waking criteria for these diagnoses may at times experience the
recall  of  actual  physical  or  emotional  trauma  as  a  “dream”  during  periods  of  EEG-documented
nocturnal waking.

Nightmares that occur intermittently during the course of ASD or PTSD are an expected symptom of
those mental disorders and do not always require independent coding as nightmare disorder. However,
as is often the case, when the frequency and/or severity of posttraumatic nightmares is such that they
require independent clinical attention, then a diagnosis of nightmare disorder should be applied. In
some cases, other symptoms of PTSD may have largely resolved while the nightmares persist.
Nightmare disorder should be coded in these cases as well. It is clinically important to establish
whether nightmares are associated with PTSD or ASD because the evaluation, course, complications,
and treatment differ significantly for these groups.

Unresolved Issues and Further Directions

Basic  pathophysiologic  studies  are  still  needed,  especially  studies  contrasting  “idiopathic”  nightmare  
disorder and nightmares associated with PTSD. In particular, determining whether posttraumatic
nightmares arise from sleep or primarily from wakefulness would be an important distinguishing
feature particularly when determining effective clinical interventions. The PSG correlates of
nightmare disorder and posttraumatic nightmares as well as the variables affecting dream mentation
and recall require further definition and delineation.

The distinction between nightmares and sleep terrors is difficult when assessed only by
questionnaires. It still remains unclear to what degree and level of complexity sleep mentation is
associated with sleep terrors. The topic of NREM sleep dream disturbances (other than disturbed
mentation that may occur with sleep terrors) also needs formal investigation, including whether or not
the term NREM sleep nightmare should be utilized.

The optimal methods for assessing nightmare frequency and nightmare distress are still unclear.
Standardized scales assessing nightmare distress should be developed and utilized. Retrospective
questionnaire-based evaluations of nightmares are problematic inasmuch as they underestimate
nightmare frequencies relative to home logs, whereas home logs may selectively increase recall of
nightmares.

Bibliography

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nightmare sufferers. Biol Psychiatry 2003;54:1092–8.
Hobson J. REM sleep and dreaming: towards a theory of protoconsciousness. Nat Rev Neurosci
2009;10:803–13.

Hublin C, Kaprio J, Partinen M, Koskenvuo M. Nightmares: familial aggregation and association with
psychiatric disorders in a nationwide twin cohort. Am J Med Genet 1999;88:329–36.

Lavie P. Sleep disturbances in the wake of traumatic events. N Engl J Med 2001;345:1825–32.

Levin R, Fireman G. Nightmare prevalence, nightmare distress, and self-reported psychological

disturbance. Sleep 2002;25:205–12.

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Nielsen T, Zadra A. Idiopathic nightmares and dream disturbances associated with sleep-wake
transitions. In: Kryger MH, Roth T, Dement WC, eds. Principles and practice of sleep medicine, 5th
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Pagel J, Helfter P. Drug induced nightmares—an etiology based review. Hum Psychopharmacol
2003;18:59–67.

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Abnorm Psychol 2000;109:273–81.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Parasomnias ››

Other Parasomnias
Exploding Head Syndrome
Sleep Related Hallucinations
Sleep Enuresis
Parasomnia Due to a Medical Disorder
Parasomnia Due to a Medication or Substance
Parasomnia, Unspecified
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Parasomnias ›› Other Parasomnias ››

Exploding Head Syndrome

ICD-9-CM code: 327.49

ICD-10-CM code: G47.59

Alternate Names

Sensory sleep starts, sensory sleep shocks.

Diagnostic Criteria

Criteria A-C must be met

A. There is a complaint of a sudden loud noise or sense of explosion in the head either at the
wake-sleep transition or upon waking during the night.
B. The individual experiences abrupt arousal following the event, often with a sense of fright.
C. The experience is not associated with significant complaints of pain.
Essential Features

Exploding head syndrome is characterized by a sudden, loud imagined noise or sense of a

violent explosion in the head occurring as the patient is falling asleep or waking during the
night.

The event is variously described as a painless loud bang, an explosion, a clash of cymbals, or
a bomb exploding, but occasionally may be a less alarming sound. It is usually associated
with a sense of fright, and many patients believe they are having a stroke. In a minority of
cases a flash of light or myoclonic jerk may accompany the event. The abnormal sensation
lasts a few seconds and may recur during further attempts at sleeping. The number of attacks
varies—from many on a single night to infrequent—with some patients reporting clustering
of attacks over several nights followed by a gap of weeks to months. A high level of clinical
distress can be associated with recurrent attacks, with concern about their underlying cause.

Associated Features

A flash of light may accompany the sound, and a myoclonic jerk may sometimes occur.
Although the event is typically painless, a simultaneous stab of pain in the head has
occasionally been reported. An insomnia complaint may develop as a result of the recurring
arousals and anxiety regarding the events.

Clinical and Pathophysiological Subtypes

None known.

Demographics

The prevalence is unknown. Exploding head syndrome is reported to be more common in

women than in men. The median age of onset is 58 years, but onset at all ages has been
reported, including the first and eighth decades.

Predisposing and Precipitating Factors

Most patients do not detect precipitating factors, but some report increased numbers of
attacks when under personal stress or overtired.

Familial Patterns

Occasional cases of exploding head syndrome occurring in the same family have been
reported, although it is not clear whether this represents a true familial pattern.

Onset, Course, and Complications

The course is benign with no reported neurologic sequelae. Frequent events on a single night
can result in insomnia. Clinical levels of anxiety may result from patient concern about a
serious medical basis for the exploding head syndrome. The condition may also exacerbate a
comorbid migraine disorder. In many patients, the symptoms appear to remit spontaneously
over some years.

Developmental Issues

Not known or applicable.

Pathology and Pathophysiology

The events occur most frequently during a period of drowsiness preceding sleep. Some events
are reported to occur upon waking during the night, but may actually be occurring during
reinitiating sleep. The condition appears to be a sensory variant of the better-known transient
motor phenomenon of sleep starts or hypnic jerks occurring at wake-sleep transition. The
neurophysiologic mechanisms underlying these hypnagogic phenomena are unknown.

Objective Findings

VPSG in a small sample of patients found that events arose from early drowsiness with
predominant alpha rhythm interspersed with some theta activity. In one patient, events arose
during transition from N1 sleep, in another patient from N1 sleep to wakefulness, and in a
third patient from N2 sleep to wakefulness. Events occurring in the N1/N2 to wake transition
have been recorded during both nocturnal vPSG and MSLTs. Slow eye movements were
present in the only tracing reproduced in the report of a patient with exploding head
syndrome emerging during wake to N1 sleep transition. Arousals occurred immediately
following the episodes. No epileptiform discharges accompany the event.

Differential Diagnosis

Exploding head syndrome should be distinguished from sudden onset-headache syndromes.

“Idiopathic  stabbing  headache”  (ice-pick headache) is a benign syndrome of brief stabs of
pain on the side of the head. Although they can occur at sleep onset, they are more common
during wakefulness.“Thunderclap  headache” is a very severe sudden onset headache
characteristic of subarachnoid hemorrhage but also resulting from other causes and
occasionally occurring as a benign symptom. It does not usually occur at sleep
onset. “Hypnic  headache  syndrome” affects older people who regularly awaken 4-6 hours
after sleep onset, with a diffuse headache that lasts 30-60 minutes and is often associated with
nausea but no autonomic symptoms. Other conditions to be considered include sleep related
migraines, cluster headaches, and nocturnal paroxysmal hemicrania. In contrast to headache
syndromes, exploding head syndrome is usually painless. Simple partial seizures can present
with sensory phenomena but do not usually occur predominantly at sleep onset. Nocturnal
panic attackscan waken a person from sleep, but are not usually associated with a sense of
noise or explosion.Recurrent nightmares are characterized by recall of more complex and
longer-lasting visual imagery.Sleep starts occur at wake-sleep transition but are
predominantly a motor phenomenon with sudden myoclonic jerks rather than an emphasis on
sensory symptoms.

Unresolved Issues and Further Directions

The neurophysiologic basis of these events requires further study.

Bibliography
Chakravarty A. Exploding head syndrome: report of two new cases. Cephalalgia
2008;28:399–400.
Evans RW. Exploding head syndrome followed by sleep paralysis: a rare migraine aura.
Headache 2006;46:682–3.
Kallweit U, Khatami R, Bassetti CL. Exploding head syndrome - more  than  “snapping  of  the  
brain”?  Sleep  Med  2008;;9:589.
Palikh GM, Vaughn BV. Topiramate responsive exploding head syndrome. J Clin Sleep Med
2010;6:382–3.
Pearce JM. Clinical features of the exploding head syndrome. J Neurol Neurosurg Psychiatry
1989;52:907–10.
Sachs C, Svanborg E. The exploding head syndrome: polysomnographic recordings and
therapeutic suggestions. Sleep 1991;14:263–6.
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Parasomnias ›› Other Parasomnias ››

Sleep Related Hallucinations

ICD-9-CM code: 368.16

ICD-10-CM code: H53.16

Alternate Names

Hypnagogic hallucinations, hypnopompic hallucinations, complex nocturnal visual

hallucinations.

Diagnostic Criteria

Criteria A-C must be met

A. There is a complaint of recurrent hallucinations that are experienced just prior to sleep
onset or upon awakening during the night or in the morning.
B. The hallucinations are predominantly visual.
C. The disturbance is not better explained by another sleep disorder (especially narcolepsy),
mental disorder, medical disorder, medication, or substance use.
Essential Features

Sleep related hallucinations are hallucinatory experiences that occur at sleep onset or on
awakening from sleep. Sleep related hallucinations are predominantly visual but may include
auditory, tactile, or kinetic phenomena. Hallucinations at sleep onset (hypnagogic
hallucinations) may be difficult to differentiate from sleep onset dreaming. Hallucinations on
waking in the morning (hypnopompic hallucinations) may arise out of a period of REM
sleep, and patients also may be uncertain whether they represent waking or dream-related
experiences. Complex nocturnal visual hallucinations may represent a distinct form of sleep
related hallucinations. They typically occur following a sudden awakening, without recall of
a preceding dream. They usually take the form of complex, vivid, relatively immobile images
of people or animals, sometimes distorted in shape or size. These hallucinations may remain
present for many minutes but usually disappear if ambient illumination is increased. Patients
are clearly awake but often initially perceive the hallucinations as real and frightening.

Associated Features

Sleep related hallucinations may be associated with episodes of sleep paralysis, either at the
same time or on different nights. Patients with complex nocturnal visual hallucinations may
jump out of the bed in terror, sometimes injuring themselves. Some patients may experience
other parasomnias, such as sleep talking or sleepwalking, separate from the hallucinations;
some patients may also experience similar complex hallucinations during the day,
unassociated with sleep.

Clinical and Pathophysiological Subtypes

Dream-like hypnagogic and hypnopompic hallucinations appear to differ in clinical features

and pathogenesis from complex nocturnal visual hallucinations arising in wakefulness after
sudden arousals during the night. Sleep related hallucinations are common in narcolepsy and
also occur as occasional phenomena in a high percentage of the general population. In
contrast, complex nocturnal visual hallucinations appear to be rare and occur in the setting of
a range of neurologic and visual disorders (see Differential Diagnosis) as well as in an
idiopathic form. However, further work is needed to establish whether or not these forms of
hallucinations represent different entities.

Demographics

In large European population studies, sleep related hallucinations have been reported to occur
with a prevalence of 25% to 37% for hypnagogic hallucinations, whereas the equivalent
reported prevalence for hypnopompic hallucinations is 7% to 13%. Both hypnagogic and
hypnopompic hallucinations are more common in younger persons and occur slightly more
frequently in women than in men.

Predisposing and Precipitating Factors

Multivariate analyses in large population studies have suggested that sleep related
hallucinations are associated with younger age, current drug use, past alcohol use, anxiety,
mood disorder, sleep onset insomnia, and perceived insufficient sleep.

Familial Patterns

Not applicable or known.

Onset, Course, and Complications

Sleep related hallucinations appear to be more common in adolescence and early adulthood.
In many patients, the frequency appears to decrease with age. The natural history of complex
nocturnal visual hallucinations depends on the underlying cause.

Developmental Issues
Not known or applicable.

Pathology and Pathophysiology

It is presumed that most sleep related hallucinations are due to dream ideation of REM sleep
intruding into wakefulness, but this has not been firmly established. Infrequent hallucinations
of this type may be within the limits of normal sleep-wake transition. Complex nocturnal
visual hallucinations may in some cases be release phenomena in which loss of visual input
or decreased reticular activating system activity results in the visual cortex generating
aberrant images.

Objective Findings

Hypnagogic hallucinations appear to arise predominantly from sleep onset REM periods.
However, the very few reports of polysomnography in complex nocturnal visual
hallucinations suggest an onset from NREM sleep. MRI scans of the brain, PSG, EEG, and
neuropsychological testing may help in the differential diagnosis and in identifying
underlying disorders.

Differential Diagnosis

Nightmares are frightening dreams awakening the patient from sleep. They are clearly
recognized as dreams and do not persist into wakefulness. Exploding head syndrome consists
of a sudden sensation of an explosion in the head, usually at sleep onset and sometimes
accompanied by a noise or flash of light. It does not involve complex visual imagery and lasts
only seconds. In RBD, the patient acts out dreams during REM sleep. If not awakened by an
observer, the person usually has little recollection of dream content. Sleepwalking may
occasionally be associated with dream ideation, but the patient recognizes that the dream
occurred during sleep. Visual hallucinations can be due to epileptic seizures but are usually
brief, stereotyped, and fragmentary in such cases. Occasionally, complex visual
hallucinations may be associated with migraine but are usually followed by a headache.

Complex nocturnal visual hallucinations may be seen in patients with narcolepsy, PD, DLB,
visual loss (Charles Bonnet hallucinations), and midbrain and diencephalic pathology
(peduncular hallucinosis),as well as with the use of β-adrenergic receptor-blocking
medications. Anxiety disorders have been noted in some patients.

Unresolved Issues and Further Directions

In contrast to the extensive study of sleep paralysis, little work has been reported on sleep
related hallucinations. It is uncertain whether they represent normal variants or pathologic
entities. It is unclear whether they are always associated with REM sleep intruding into
wakefulness. It is uncertain how frequently complex nocturnal visual hallucinations are an
independent entity, as opposed to representing a final common pathway of a range of other
disorders. Further work is needed to determine from which stages of sleep they arise.

Bibliography

Barnes  J,  David  AS.  Visual  hallucinations  in  Parkinson’s  disease:  a  review  and  
phenomenological survey. J Neurol Neurosurg Psychiatry 2001;70:727–33.
Kavey N, Whyte J. Somnambulism associated with hallucinations. Psychosomatics
1993;34:86–90.
Mahowald M, Woods S, Schenck C. Sleeping dreams, waking hallucinations, and the central
nervous system. Dreaming 1998;8:89–102.
Manford M, Andermann F. Complex visual hallucinations. Clinical and neurobiological
insights. Brain 1998;121:1819–40.
Ohayon M. Prevalence of hallucinations and their pathological associations in the general
population. Psychiatry Res 2000;97:153–64.
Ohayon M, Priest R, Caulet M, Guilleminault C. Hypnagogic and hypnopompic
hallucinations: pathological phenomena? Br J Psychiatry 1996;169:459–67.
Silber MH, Hansen M, Girish M. Complex nocturnal visual hallucinations. Sleep Med
2005;6:363–6.
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Parasomnias ›› Other Parasomnias ››

Sleep Enuresis
ICD-9-CM code: 788.36

ICD-10-CM code: N39.44

Alternate Names

Enuresis nocturna; nocturnal bedwetting; primary, familial, functional, idiopathic,

monosymptomatic, or essential enuresis; night wetting; sleep related enuresis.

Diagnostic Criteria

Primary Sleep Enuresis – Criteria A-D must be met

A. The patient is older than five years.

B. The patient exhibits recurrent involuntary voiding during sleep, occurring at least twice a
week.
C. The condition has been present for at least three months.
D. The patient has never been consistently dry during sleep.

Secondary Sleep Enuresis – Criteria A-D must be met

A. The patient is older than five years.

B. The patient exhibits recurrent involuntary voiding during sleep, occurring at least twice a
week.
C. The condition has been present for at least three months.
D. The patient has previously been consistently dry during sleep for at least six months.
Essential Features

Sleep enuresis (SE) is characterized by recurrent involuntary voiding that occurs during
sleep. In primary SE, recurrent involuntary voiding occurs at least twice a week during sleep
after five years of age in a patient who has never been consistently dry during sleep for six
consecutive months. SE is considered secondary in a child or adult who had previously been
dry for six consecutive months and then began wetting at least twice a week. Both primary
and secondary enuresis must be present for a period of at least three months. Though primary
and secondary enuresis share the common symptom of voiding during sleep, they are
understood as distinct phenomena with different etiologies.

SE is associated with difficulty arousing from sleep in response to an urge to urinate and may
occur during any sleep stage. Sleep disorders that fragment sleep such as sleep apnea are
associated with SE, and treatment of these disorders may cure or reduce their incidence.

Associated Features

Involuntary voiding during wakefulness may be associated with SE and, if present, generally
points toward a physiological etiology. Psychosocial problems are considered a relatively rare
cause in primary SE, though it does occur more commonly in children with attention deficit
hyperactivity disorder and in children living in disorganized families. Secondary SE is seen
more commonly in children who have recently experienced a significant psychosocial stress,
such as parental divorce, physical or sexual abuse, or neglect. Chronic constipation and
encopresis (fecal soiling) often occur in children with secondary SE.

SE can occur in association with diabetes and urinary tract infection. It may occur in
individuals with nocturnal epilepsy. Among older adults, SE may be associated with
symptoms of congestive heart failure, OSA, depression, and dementia.

SRBD is reported in 8% to 47% of children with enuresis, compared to an overall prevalence

of 1% to 2%. PLMS have been reported in patients with refractory SE. A large epidemiology
study of children aged 6-10 years found that a current complaint of SE was significantly
associated with increased ORs (2.7-3.4) for subjectively high arousal threshold, night terrors,
nocturia, and confusion when awakened from sleep. Other studies have found mouth
breathing, nasal congestion, snoring, and restless sleep to be highly related to enuresis in
children.

Clinical and Pathophysiological Subtypes

The most important distinction is between primary and secondary SE.

Demographics

SE occurs in 15% to 20% of 5-year-olds. It is three times more common in boys than in girls.
SE is reported by 2.1% of community-dwelling older adults and is more common among
women than men.

Predisposing and Precipitating Factors

The etiology of SE is complex. The factors that precipitate SE on a particular night and at a
particular time remain unknown. One popular model hypothesizes that SE consists of three
interrelated factors: large nocturnal urine volume production, nocturnal bladder overactivity,
and difficulty arousing from sleep. Several studies suggest difficulty arousing from sleep is
most important in primary enuresis, whereas bladder instability/overactivity is more
important in secondary enuresis.
Children  with  enuresis  are  often  described  by  their  families  as  “deep  sleepers”  and  very  
difficult to arouse. A high arousal threshold has been objectively confirmed in these children.

It has been reported that fragmentation of sleep by disorders such as sleep apnea is highly
correlated with SE. Sleep fragmenting disorders such as sleep apnea and PLMS have been
previously reported to be proximal triggers for the occurrence of disorders of arousal—
sleepwalking, confusional arousals, and night terrors. Successful treatment of sleep apnea in
these disorders has been reported to result in reduction or elimination of disorders of arousal.
Similarly, surgical treatment of sleep apneas by adenotonsillectomy has been reported to cure
nocturnal enuresis in 60% or more of patients, although this is not a consistent result. Several
studies have noted the presence of sleep related breathing disorder in > 40% of enuresis
patients studied. However, not all sleep studies have noted SRBD in patients with enuresis.
Those without SRBD were still found to have high arousal threshold from sleep.

Primary SE is a disorder that occurs when an individual fails to arouse from sleep in response
to bladder sensations or fails to inhibit a bladder contraction. These are developmentally
acquired skills, and, as such, there is a range in the ages of their acquisition. A small
proportion of children with primary SE lack the normal increase in vasopressin release during
sleep, leading to a high urinary volume that exceeds the bladder capacity. If these children do
not arouse to the sensation of a full bladder, primary SE is the result. Secondary SE can be
caused by, or be associated with, any one of the following identifiable problems: (1) an
inability to concentrate urine due to diabetes mellitus, diabetes insipidus, nephrogenic
diabetes insipidus (idiopathic or pharmacologic [e.g., secondary to the use of lithium
carbonate]), or sickle cell disease; (2) increased urine production secondary to the ingestion
of caffeine, diuretics, or other agents; (3) urinary tract pathology, such as urinary tract
infections, irritable bladder, malformations of the genitourinary tract (e.g., ectopic ureter); (4)
chronic constipation and encopresis; (5) neurologic pathology, such as seizures or neurogenic
bladder; or (6) psychosocial stressors, such as parental divorce, neglect, physical or sexual
abuse, and institutionalization. The mechanisms by which secondary SE is associated with
these problems are often not understood.

Familial Patterns

Hereditary factors are suspected in children with primary enuresis. There is often a high
prevalence of enuresis among the parents, siblings, and other relatives of the child with
primary enuresis. The reported prevalence is 77% when both parents were enuretic as
children and 44% when one parent has a history of enuresis. Recent linkage studies support
the hypothesis of genetic and phenotypic heterogeneity of SE. A putative linkage of SE to a
region on chromosomes 22q, 13q, and 12q across different families has been reported.

Onset, Course, and Complications

Voiding is a spinal reflex during wakefulness and sleep during infancy, until about 18 months
of age. Between 18 months and three years of age, the child is able to delay voiding with a
full bladder, first during wakefulness and at a later age during sleep. The primary determinant
of the age at which this skill is acquired is developmental maturation. Somewhat arbitrarily,
primary SE is defined as a problem if it persists beyond five years of age. The spontaneous
cure  rate  is  15%  per  year.  The  primary  complication  of  SE  is  to  the  child’s  self-esteem. How
well  the  child’s  family  deals  with  the  symptom  is  an  important  determinant  of  whether  
complications develop. Secondary SE can occur at any age. Complications of secondary SE
are determined by the problem leading to the enuresis.

Developmental Issues

The developmental pattern of enuresis is similar to NREM parasomnias, although its first
occurrence in adulthood is uncommon.

Pathology and Pathophysiology

SE is a heterogeneous disorder with various underlying pathophysiological mechanisms,

resulting in a mismatch between nocturnal bladder capacity and the amount of urine produced
during sleep, in association with a simultaneous failure of arousal from sleep in response to
the sensation of bladder fullness. SE can be seen in association with sleep fragmentation
disorders including SRBD, which in children is most often secondary to adenotonsillar
hypertrophy.

Objective Findings

In primary and secondary SE, enuretic episodes can occur in all sleep stages, during nocturnal
wakefulness, and in association with transient arousals. Sleep stages have not been found to
be different on nights when enuresis occurs versus nights on which it does not occur. The
results of polysomnographic studies of children with enuresis compared to normal controls
have been inconsistent. A computerized power analysis of sleep data suggested an increase in
delta power, whereas the majority of other studies have reported no differences. However, a
recent study found those age 6-14 years had elevated light stage N1 sleep and reduced N3
sleep and REM sleep compared to normal controls. The population with enuresis had a
significantly elevated arousal index.

SRBD has been reported in 8% to 47% of children with SE. SE and sleep apnea are highly
correlated with an increasing prevalence of enuresis as the respiratory disturbance index
(RDI) increases. In addition to SRBD, PLMS (range of 3.9 to 38.6 per hour of sleep) have
been reported in a group of children with treatment-resistant SE.

Recent studies have demonstrated that patients with enuresis are subjectively sleepier than
normal controls. This has been hypothesized to result from fragmented nocturnal sleep and is
consistent with a large body of sleep research in other areas.

Differential Diagnosis

Enuresis may be caused by a variety of medical or neurological disorders such as diabetes

mellitus, diabetes insipidus, epilepsy, sickle cell disease, bowel or bladder dysfunction,
anatomical abnormalities or infection of the urinary tract, neurological/developmental
disorders or other sleep disorders, especially OSA. Organic pathology of the urinary tract is
more prevalent in children who, in addition to sleep enuresis, also exhibit daytime enuresis,
abnormalities in the initiation of micturition, or abnormal urinary flow.

Evaluation of sleep enuresis should include complete enuresis history, sleep history, physical
examination and laboratory studies (as indicated) to exclude these etiologies. When signs and
symptoms of sleep apnea are present—mouth breathing, snoring, adenotonsillar hypertrophy,
daytime sleepiness, hyperactivity—a sleep study should be conducted.
Unresolved Issues and Further Directions

Recent advances suggest that the terms primary and secondary enuresis may be overly
simplistic. Further work is necessary to understand the genetic and clinical aspects of SE.

Other sleep disorders are common in children with SE. Though it may be possible that the
apneas, hypopneas, and snoring-related arousals in children with SRBD could be the trigger
of SE, many children with SE do not have a sleep disorder. In such cases, the underlying
bladder overactivity may be the stimulus for arousal.

Studies of the relationship of sleep, sleep disorders, and sleep fragmentation to SE performed
to date have been inconsistent. This is likely due to differing definitions of enuresis and
varying research methodologies. Further sophisticated sleep laboratory studies are necessary
to elucidate the relationship. In particular, the proximal trigger for episodes of SE has not
been determined. Some studies suggest enuresis is spontaneous, whereas others suggest a
relationship to sleep disorders that result in arousals—similar to findings in disorders of
arousal.

Bibliography

Burgio K, Locher J, Ives D, Hardin J, Newman A, Kuller L. Nocturnal enuresis in

community-dwelling older adults. J Am Geriatr Soc 1996;44:139–43.
Brooks LJ, Topol HI. Enuresis in children with sleep apnea. J Pediatr 2003;142:515–8.
Chandra M, Saharia R, Hill V, Shi QH. Prevalence of diurnal voiding symptoms and difficult
arousal from sleep in children with nocturnal enuresis. J Urol 2004;172:311–6.
Cohen-Zrubavel V, Kushnir B, Kushnir J, Sadeh A. Sleep and sleepiness in children with
nocturnal enuresis. Sleep 2011;34:191–4.
Dhondt K, Raes A, Hoebeke P, Van Laecke E, Van Herzeele C, Vande Walle J. Abnormal
sleep architecture and refractory nocturnal enuresis. J Urol 2009;182:1961–5.
Jeyakumar A, Rahman SI, Armbrecht ES, Mitchell R. The association between sleep-
disordered breathing and enuresis in children. Laryngoscope 2012 Aug;122:1873–7.
Neveus T. The role of sleep and arousal in nocturnal enuresis. Acta Paediatr 2003;92:1118–
23.
Kalorin CM, Mouzakes J, Gavin JP, et al. Tonsillectomy does not improve bedwetting:
results of a prospective controlled trial. J Urol 2010;184:2527.
Neveus T, Stenberg A, Lackgren G, Tuvemo T, Hetta J. Sleep of children with enuresis: A
polysomnographic study. Pediatrics 1999;103:1193–7.
Norgaard JP, Hansen JH, Nielsen JB, Petersen BS, Knudsen N, Djurhuus JC. Simultaneous
registration of sleep-stages and bladder activity in enuresis. Urology 1985;26:316–9.
Sakellaropoulou AV, Hatzistilianou MN, Emporiadou MN, et al. Association between
primary nocturnal enuresis and habitual snoring in children with obstructive sleep
apnoea-hypopnoea syndrome. Arch Med Sci 2012;8:521–7.
Stone J, Malone PS, Atwill D, et al. Symptoms of sleep-disordered breathing in children with
nocturnal enuresis. J Pediatr Urol 2008;4:197.
Weissbach A, Leiberman A, Tarasiuk A, Goldbart A, Tal A. Adenotonsillectomy improves
enuresis in children with obstructive sleep apnea syndrome. Int J Pediatr
Otorhinolaryngol 2006;70:1351–6.
Wolfish N. Sleep arousal function in enuretic males. Scand J Urol Nephrol Suppl
1999;202:24–6.
Wolfish NM, Pivik RT, Busby KA. Elevated sleep arousal thresholds in enuretic boys:
clinical implications. Acta Paediatr 1997;86:381–4.
Yeung CK, Chiu HN, Sit FK. Sleep disturbance and bladder dysfunction in enuretic children
with treatment failure: fact or fiction? Scand J Urol Nephrol Suppl 1999;202:20–3.
Yeung CK, Diao M, Sreedhar B. Cortical arousal in children with severe enuresis. N Engl J
Med 2008;359;22–4.
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Parasomnias ›› Other Parasomnias ››

Parasomnia Due to a Medical Disorder

ICD-9-CM code: 327.44

ICD-10-CM code: G47.54

The essential feature of this diagnosis is the presence of a parasomnia that is attributable to an
underlying neurological or medical condition. RBD is the parasomnia most commonly
associated  with  an  underlying  neurological  condition  (“symptomatic  RBD”).  However,  when  
diagnostic criteria for RBD are met, the more specific diagnosis of REM sleep behavior
disorder should be made.

Complex nocturnal sleep related (hypnagogic and hypnopompic) visual hallucinations can
occur with neurological disorders such as narcolepsy, PD, DLB, visual loss (Charles Bonnet
hallucinations), andmidbrain and diencephalic pathology (peduncular hallucinosis).
Dreaming and sleep paralysis may or may not be associated with these hallucinations.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Parasomnias ›› Other Parasomnias ››

Parasomnia Due to a Medication or Substance

ICD-9-CM code: 292.85 (drug-induced); 291.82 (alcohol-induced)

ICD-10-CM code: F11-F19 (see table in Appendix B for detailed coding instructions)

The essential feature of this diagnosis is the close temporal relationship between exposure to
a drug, medication, or biological substance and the onset of the signs and symptoms of that
disorder. A likely causal relationship can be inferred if signs and symptoms of the
parasomnia disappear when the drug or substance is withdrawn.

The emergent parasomnia can be a de novo parasomnia, the aggravation of a chronic

intermittent parasomnia, or the reactivation of a previous parasomnia. As discussed
previously, a variety of medications and biological substances, including selective serotonin
reuptake inhibitors, venlafaxine, tricyclic antidepressants, monoamine oxidase inhibitors,
mirtazapine, bisoprolol, selegiline, or cholinergic treatment for Alzheimer disease, have been
reported to be associated with acute or chronic RBD. Acute RBD can also be seen during
states of withdrawal from cocaine, amphetamine, alcohol, barbiturate, and meprobamate
abuse. Caffeine and chocolate abuse have been implicated in causing or unmasking RBD.
However, when diagnostic criteria for RBD are met, the more specific diagnosis of REM
sleep behavior disorder should be made.

The use of medications such as β-adrenergic receptor-blocking agents can be associated with
sleep related hallucinations. When the clinical presentation suggests a direct relationship
between a drug or substance and sleep related hallucinations, a diagnosis of parasomnia due
to a medication or substance should be employed.

Sedative-hypnotics such as zolpidem and zopiclone have been associated with apparent
NREM parasomnias including SRED and sleep driving. It has been suggested that sleep
driving is an overlap behavior in which the sedative-hypnotic increases the arousal threshold
during sleep at the beginning of the behavior, while later behavior is due to the CNS
depressing effects of the drug while awake. It has not been determined if drug-related NREM
parasomnias are associated with the same genetic predisposition, priming factors, and triggers
observed in disorders of arousal. When clinical presentation suggests a direct relationship
between disorders of arousal and use of a drug or substance, a diagnosis of parasomnia due to
a medication or substance should be employed.

Alcohol has often appeared on lists of potential sleepwalking triggers without a basis in
reliable empirical scientific research. Recent evidence-based reviews have found no
relationship between alcohol and sleepwalking. The behavior of the alcohol-intoxicated
individual may superficially resemble that of the sleepwalker. However, the sleepwalker is
typically severely cognitively impaired, but with only limited motor impairment. The
alcohol-intoxicated  individual’s  level  of  cognitive  functioning  may  be  reduced, but not
absent, whereas motor behavior is severely impaired.

Proponents of the theory of alcohol related sleepwalking suggest that the effects of alcohol
are similar to that of sleep deprivation—that is, alcohol increases deep sleep. However, this
claim in not substantiated by sleep laboratory-based studies in normal controls, and no
empirical sleep studies of alcohol and sleepwalking have ever been conducted.

There is no scientific evidence that complex behaviors occurring during the sleep period
following alcohol ingestion are anything other than the nocturnal wandering of an alcohol-
intoxicated individual. Unconsciousness, intoxication, and sleep are very different states of
consciousness. Parasomnias should be easily distinguished from alcohol intoxication by the
presence of significant alcohol ingestion prior to bedtime.

The association of therapeutic doses of sedative hypnotic drugs and apparent parasomnias
should be carefully distinguished from the expected effects of drug abuse or misuse that
result in CNS depression. Investigations of drivers who had accidents attributed to drug-
related sleep driving are reported to show that (1) blood levels of prescribed sedative
hypnotics exceeded therapeutic ranges; (2) the individuals failed to take the medication at the
correct time or remain in bed for sufficient time following ingestion; and/or (3) the
individuals combined sedative-hypnotics with other CNS depressants and/or alcohol. Driving
with a high blood level of a sedative-hypnotic can result in significant cognitive and motor
impairment. Serious accidents can result. Sleep driving and other complex behaviors in this
population are more likely to have resulted from drug misuse and abuse rather than true
parasomnias.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Parasomnias ›› Other Parasomnias ››

Parasomnia, Unspecified
ICD-9-CM code: 327.40

ICD-10-CM code: G47.50

This diagnosis is intended for parasomnias that cannot be classified elsewhere or for cases in
which the physician has a clinical suspicion of a parasomnia but is unable to establish a
specific  diagnosis.  In  many  cases,  “parasomnia,  unspecified”  will  be  a  temporary  diagnosis.  
However, in other patients, an underlying condition may not ever be established, and in those
patients,  “parasomnia,  unspecified”  should  remain  an  ongoing  diagnosis.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Parasomnias ››

Isolated Symptoms and Normal Variants

Sleep Talking
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Parasomnias ›› Isolated Symptoms and Normal Variants ››

Sleep Talking
Alternate Names

Somniloquy.

The essential feature is talking, with varying degrees of comprehensibility, during sleep.
Sleep talking may occur during REM or NREM sleep. Sleep talking can be idiopathic or
associated with parasomnias such as RBD or disorders of arousal such as confusional arousal.
Sleep talking may follow arousals from sleep or more rarely cause them. Sleep talking is
highly prevalent. A recent cross-sectional epidemiologic study found the lifetime prevalence
of sleep talking to be 66% and current prevalence—in the past three months—to be 17%.
There is no apparent sex difference. Onset and course are unknown.

Complications usually arise when sleep talking is very frequent or loud or if the content is
objectionable to others. Sleep talking is usually reported by the bed partner or someone
sleeping in the same room or sleeping area as the affected individual. Sleep talking can
disrupt the sleep of a bed partner, roommate, or others in a group-sleeping situation (such as
college dormitories, military barracks, fire stations, or a tent while camping). The content of
sleep talking has not been shown to reflect actual prior waking behavior or memories. The
sleep talker is rarely aware of his or her sleep talking.
Nocturnal vocalization, including frank sleep talking, is often seen in patients with RBD and
subclinical RBD. A recent report notes that sleep talking may be a useful diagnostic marker
for differentiating DLB from Alzheimer disease and other types of dementia. The
vocalizations of RBD may be loud, emotional, profane, and associated with behaviors that
correlate with remembered dream mentation. Nocturnal seizures may be associated with
vocalization that tends to be stereotypic. The vocalizations associated with sleep terrors are
emotionally laden and associated with behaviors of intense arousal and agitation. In PTSD,
increased vocalizations during sleep have been described.

Bibliography

Arkin AM, Toth MF, Baker J, Hastey JM. The frequency of sleep talking in the laboratory
among chronic sleep talkers and good dream recallers. J Nerv Ment Dis 1970;151:369–
74.
Bjorvatn B, Grønli J, Pallesen S. Prevalence of different parasomnias in the general
population. Sleep Med 2010;11:1031–4.
Honda K, Hashimoto M, Yatabe Y, et al. The usefulness of monitoring sleep talking for the
diagnosis of Dementia with Lewy bodies. Int Psychogeriatr 2013;25:851–8.
Hublin C, Kaprio J, Partinen M, Koskenvuo M. Sleeptalking in twins: epidemiology and
psychiatric comorbidity. Behav Genet 1998;28:289–98.
Reimao RN, Lefevre AB. Prevalence of sleep-talking in childhood. Brain Dev 1980;2:353–7.
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Sumário
Sleep Related Movement Disorders....................................................................................... 207
Disorders .................................................................................................................................. 207
Restless Legs Syndrome ....................................................................................................... 208
Periodic Limb Movement Disorder ...................................................................................... 215
Sleep Related Leg Cramps .................................................................................................... 221
Sleep Related Bruxism .......................................................................................................... 224
Sleep Related Rhythmic Movement Disorder ...................................................................... 231
Benign Sleep Myoclonus of Infancy ..................................................................................... 235
Propriospinal Myoclonus at Sleep Onset .............................................................................. 238
Sleep Related Movement Disorder Due to a Medical Disorder ............................................ 241
Sleep Related Movement Disorder, Unspecified .................................................................. 243
Isolated Symptoms and Normal Variants ............................................................................. 243
Excessive Fragmentary Myoclonus ...................................................................................... 243
Hypnagogic Foot Tremor and Alternating Leg Muscle Activation ...................................... 246
Sleep Starts (Hypnic Jerks) ................................................................................................... 249
Sleep  Related  Movement  Disorders
Sleep related movement disorders are primarily characterized by relatively simple, usually
stereotyped, movements that disturb sleep or its onset. Restless legs syndrome (RLS) is an
exception in that patients typically engage in walking or nonstereotypic limb movement to
reduce leg discomfort. However, RLS is closely associated with periodic limb movements
(PLMs), which are usually simple and stereotyped within a series. Nocturnal sleep
disturbance or complaints of daytime sleepiness or fatigue are a prerequisite for a diagnosis
of a sleep related movement disorder. For example, many normal sleepers exhibit episodes of
periodic limb movements of sleep (PLMS) but have no complaint of a sleep disturbance, nor
do they show a significant objective disturbance of their sleep as a result of the movements.
Such persons should not be classified as having periodic limb movement disorder (PLMD),
but instead, the presence of PLMS should simply be noted. Similar considerations relate to
the distinction between rhythmic movement disorder and the presence of rhythmic
movements.

Body movements that disturb sleep also are seen in many other sleep disorder categories
(e.g., in parasomnias such as sleepwalking, sleep terrors, and rapid eye movement (REM)
sleep behavior disorder (RBD)). However, these parasomnias differ from the simple
stereotyped movements categorized as sleep related movement disorders in that they involve
complex behaviors during the sleep period. Parasomnia-related movements may appear
purposeful and goal directed, but are outside the conscious awareness of the individual.
Parasomnias are listed in a separate section from the sleep related movement disorders.

Although the history may be diagnostic, polysomnography is sometimes necessary to make a

firm diagnosis of sleep related movement disorders and distinguish them from parasomnias.
In these cases, it is necessary to add all-night video recording to the polysomnographic
recording and to correlate the documented movements with the technician's description of the
patient's behavior and level of consciousness in order to establish a diagnosis. There are some
movement disorders that may occur during both sleep and wakefulness. If the presentation
during sleep is significantly different from that during wakefulness, or if the movement is
entirely confined to sleep, then the movement disorder is classified here (e.g., the occurrence
of bruxism exclusively in sleep).

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Sleep Related Movement Disorders ››

Disorders
Restless Legs Syndrome
Periodic Limb Movement Disorder
Sleep Related Leg Cramps
Sleep Related Bruxism
Sleep Related Rhythmic Movement Disorder
Benign Sleep Myoclonus of Infancy
Propriospinal Myoclonus at Sleep Onset
Sleep Related Movement Disorder Due to a Medical Disorder
Sleep Related Movement Disorder Due to a Medication or Substance
Sleep Related Movement Disorder, Unspecified
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Sleep Related Movement Disorders ›› Disorders ››

Restless Legs Syndrome

ICD-9-CM code: 333.94

ICD-10-CM code: G25.81

Alternate Names

Willis-Ekbom disease.

Diagnostic Criteria

Criteria A-C must be met

A. An urge to move the legs, usually accompanied by or thought to be caused by uncomfortable and
unpleasant sensations in the legs.1,2 These symptoms must:

1. Begin or worsen during periods of rest or inactivity such as lying down or sitting;

2. Be partially or totally relieved by movement, such as walking or stretching, at least as long as the
activity continues;3 and

3. Occur exclusively or predominantly in the evening or night rather than during the day.4

B. The above features are not solely accounted for as symptoms of another medical or a behavioral
condition (e.g., leg cramps, positional discomfort, myalgia, venous stasis, leg edema, arthritis,
habitual foot tapping).

C. The symptoms of RLS cause concern, distress, sleep disturbance, or impairment in mental,
physical, social, occupational, educational, behavioral, or other important areas of functioning.5

Notes

1. Sometimes the urge to move the legs is present without the uncomfortable sensations, and
sometimes the arms or other parts of the body are involved in addition to the legs.

2.  For  children,  the  description  of  these  symptoms  should  be  in  the  child’s  own  words.

3. When symptoms are very severe, relief by activity may not be noticeable but must have been
previously present.

4. As a result of severity, treatment intervention, or treatment-induced augmentation, the worsening in

the evening or night may not be noticeable but must have been previously present.

5. For certain research applications, such as genetic or epidemiological studies, it may be appropriate
to omit criterion C. If so, this should be clearly stated in the research report.

Essential Features
RLS is a sensorimotor disorder characterized by a complaint of a strong, nearly irresistible urge to
move the limbs. This urge to move is often but not always accompanied by other uncomfortable
sensations felt deep inside the limbs or by a feeling that is simply difficult or impossible to describe.
Although  the  legs  are  most  prominently  affected,  “restless  legs”  is  a  misnomer,  in  that 21% to 57% of
individuals with RLS describe some arm sensations. The most common adult RLS descriptors in
English  are  “restless,”  “uncomfortable,”  “twitchy,”  “need  to  stretch,”  “urge  to  move,”  and  “legs  want  
to  move  on  their  own.”  About  half  express  their  RLS  sensations  as  painful.  “Numb”  and  “cold”  are  
very uncommon descriptors for RLS.

Criteria A1-3 specify the necessary characteristics of the RLS sensations: worse at rest, better with
movement, and predominant occurrence in the evening or night. The separation of worsening at rest
(criterion A1) from worsening in the evening/night (criterion A3) is based on circadian rhythm studies
that show an increase at night, independent of activity level. RLS must be differentiated from other
conditions that can mimic RLS (criterion B). Clinically significant RLS is defined by RLS symptoms
causing substantial distress, sleep disturbance, or impairment of function (criterion C).

Associated Features

Disturbed sleep is a common, prominent, and distressing aspect of RLS. Sleep onset and maintenance
complaints in individuals with RLS are notably higher than in controls, with odds ratios (OR) between
1.7 and 3.5. In clinical populations, disturbed sleep is reported in 60% to 90% of individuals with
RLS, is typically the most troubling symptom, and is often the primary reason for seeking medical
care. The Medical Outcomes Study Sleep Questionnaire scores for sleep quantity, sleep disturbance,
sleep adequacy, and sleep problems are significantly worse for RLS patients than controls. Daytime
fatigue and daytime sleepiness are also common complaints; however, the sleepiness is not as severe
as expected for the degree of sleep disruption, implying hyperarousal in RLS. In contrast to
obstructive sleep apnea, Epworth Sleepiness Scale scores in RLS are typically in the normal range,
and either no different or marginally elevated when compared to normal controls. Clinical sleep
disturbance correlates with both severity of RLS and health impact of RLS. Some individuals with
RLS may choose to work at night, thereby shifting quiet activities and their sleep schedule away from
the circadian peak of their RLS symptoms.

PLMs, a family history of RLS, and response to dopaminergic therapy are supportive of the diagnosis.
Periodic limb movements can occur in sleep (PLMS) or wakefulness (PLMW). PLMW occur during
quiet rest and frequently at the transition between waking and sleep, disrupting sleep onset or the
return to sleep. PLMS are frequently associated with arousal from sleep. RLS sensory and motor
features respond initially to treatment with dopaminergic therapy in almost all cases.

Multiple clinic-based and population-based studies have shown an increased prevalence of mood and
anxiety disorders in individuals with RLS. Most controlled studies using validated assessments have
shown significantly increased ORs for moderately or highly elevated depressive symptoms (OR 1.95
and 3.67), major depression (OR 2.6), major depressive disorder (OR 2.57 and 4.7), generalized
anxiety disorder (OR 3.5), panic disorder (OR 4.7, 12.9, and 18.9), and posttraumatic stress disorder
(OR 3.76). In addition, a positive correlation has been found between the severity of RLS and
depression/anxiety symptoms. Relevant to the RLS-depression relationship is the emerging evidence
that treatment of RLS improves depressive symptoms.

Similarly, increased rates of attention deficit hyperactivity disorder (ADHD) have been found in RLS,
both in pediatric and adult studies. Emerging data indicate that about one fourth of individuals with
RLS have ADHD symptoms, and conversely, that 12% to 35% of those with ADHD meet criteria for
RLS. Other medical conditions for which there is some evidence for greater-than-chance association
include narcolepsy, migraine, chronic obstructive pulmonary disease, Parkinson disease, multiple
sclerosis, peripheral neuropathy, obstructive sleep apnea, diabetes mellitus, fibromyalgia, rheumatoid
arthritis, nocturnal eating, obesity, thyroid disease, and heart disease.

Clinical and Pathophysiological Subtypes

Evidence in the literature is not sufficient to support well-defined subtypes of RLS. Early-onset RLS
(prior to age 45 years) is more familial and associated with slower progression than late-onset RLS. In
addition,  the  classification  of  “secondary”  RLS  has  been  suggested  when  the  condition  occurs  in  
association with iron deficiency, pregnancy, and chronic renal failure, but this construct has been
challenged based on pathophysiological, family history, genetic, and clinical course data.

Demographics

The overall prevalence of RLS has been estimated at 5% to 10% in European and North American
population-based studies. However, in Asian countries, studies thus far indicate a lower prevalence.
Prevalence is about twice as high in women than in men. In most studies, prevalence increases with
age up to 60-70 years, except in Asian populations where an age-related increase has not been found.
Various measures of clinical significance such as frequency (1-2 times/week), severity (moderate to
severe distress), differential diagnosis, and impact have been applied to population-based studies.
These analyses indicate the prevalence of clinically significant RLS to be 2% to 3% in Europe and
North America, but lower in Asia. Annual incidence rates have been reported as 0.8% to 2.2%.

Pediatric prevalence rates are 2% to 4% in UK/US and Turkish studies, with moderate to severe RLS
in about 0.5% to 1%. Adolescents are more likely to have moderate to severe RLS symptoms than
younger children—one half of 12- to 17-year-olds compared to one fourth of 8- to 11-year-olds with
RLS. Boys are affected as often as girls, with the sex difference not emerging until the late teens or
twenties.

Predisposing and Precipitating Factors

A positive family history of RLS, the genetic variants noted below, and female sex confer increased
risk for RLS. The best characterized precipitating factors are iron deficiency, certain medications,
pregnancy, chronic renal failure, and prolonged immobility. Mild iron deficiency, characterized by
serum ferritin below 50 µg/L, has been associated with increased severity of RLS, and repletion of
iron stores from below 50-75 µg/L has been found to diminish RLS symptoms. Medications that may
precipitate or aggravate RLS and/or PLMS include sedating antihistamines, some centrally active
dopamine receptor antagonists, and most antidepressants. An exception is the antidepressant
bupropion, with its dopamine-promoting activity.

The prevalence of RLS during pregnancy is two to three times greater than in the general population.
There is a peak in the number of women affected by RLS in the third trimester, with resolution of
symptoms for most, but not all, by one month after delivery. Independent predictors of RLS during
pregnancy are a family history of RLS (OR 8.43), a history of RLS in prior pregnancy (OR 53.74), a
history  of  RLS  in  the  past  (OR  12.91),  and  hemoglobin  ≤11  g/dL  (OR  2.05).  Parity,  the  number  of  
previous pregnancies, appears to account for the 2:1 sex difference between women and men in the
general population prevalence of RLS.
In chronic renal failure patients, the prevalence of RLS is two to five times greater than in the general
population. This represents prevalence rates of 11% to 58% in US and European chronic renal failure
clinics. Compared to patients with chronic renal failure without RLS, those with RLS have greater
sleep disturbance, report poorer quality of life, and more frequently discontinue dialysis prematurely.
Typically, RLS symptoms improve dramatically within one month after kidney transplantation but
become severe again with transplant failure.

There is limited or contradictory evidence for sleep deprivation, peripheral neuropathy, radiculopathy,
pain, caffeine, tobacco, or alcohol as exacerbating factors for RLS.

Familial Patterns

Early-onset RLS is highly familial, with 40% to 92% of cases reporting affected family members.
High concordance rates are observed in monozygotic twins. The risk of RLS is two to six times
greater for first-degree relatives of patients with RLS than for those from the general population.
Although an autosomal dominant model of RLS is suggested by many family studies, recent
genomewide linkage and association studies suggest a more complex gene-environment pattern.
Linkage analyses have reported several different gene loci associated with RLS but, to date, no single
causative gene. However, genomewide association studies have identified single nucleotide
polymorphisms in RLS, four of which have been replicated: BTBD9, MEIS1,
MAP2K5/LBXCOR, and PTPRD. Nonetheless, the relationship between familial RLS and these
findings remains to be determined.

Onset, Course, and Complications

Onset of RLS symptoms occurs at all ages, from childhood to late adult life. Mean age of onset for
familial RLS is in the third or fourth decade, with onset prior to age 21 years in about one third of
cases. The clinical course of RLS differs based on age of onset. In early-onset RLS (before age 45
years), slow progression of symptoms is found in about two thirds of cases. Most of the remaining one
third report stable symptoms over time, although remission has been described. In late-onset RLS,
rapid progression is typical and aggravating factors are common.

Significant impairment of health-related quality of life (HRQoL) has been found in moderate to
severe RLS. Both physical health and mental health scores have consistently been found to be lower
for individuals with RLS, using standard QoL assessment tools. The HRQoL impairments are strongly
associated with severity of RLS and remain after controlling for age, sex, and disease comorbidity. In
addition, patients with cancer, type 2 diabetes, or renal failure who also have RLS have been shown to
have poorer quality of life than those without RLS. Overall, RLS accounts for a major disease burden
on those who suffer from it, demonstrated to be similar to or worse than that associated with
osteoarthritis, congestive heart failure, depression, Parkinson disease, or stroke.

Large population-based studies have found positive associations between RLS and cardiovascular
disease, including coronary heart disease and stroke. Repetitive surges in heart rate and blood pressure
associated with PLMS are a potential mediator in the physiology of these relationships. Only limited
mortality data are available, suggesting increased risk of mortality in women and in chronic renal
failure patients with RLS.

Developmental Issues
The accurate diagnosis of RLS in children and adolescents requires understanding of developmental
language and cognitive skills. Adequate verbal skills are needed for children to communicate the
sensory  component  of  RLS  and  description  must  be  in  “the  child's  own  words,”  rather  than  by  a  
parent  or  caretaker.  For  criterion  A,  children  rarely  use  or  understand  the  word  “urge.”  Instead  they
describe  that  their  legs  “need  to”  “have  to”  or  “got  to”  move.  Descriptors  for  the  discomfort  include:  
bugs, ants, weird/funny feelings, tingle, wiggly, and shaky. Younger children often use the word
“kick”  rather  than  “move,”  e.g.,  “my  legs  want  to  kick.”  Similar  to  adults,  children  report  arm  
involvement in almost half of cases. Sitting in class, lying in bed, reading a book, and riding in a car
are situations where children report onset or worsening of their symptoms. Relief is typically achieved
by moving around, walking, rubbing, kicking, or distraction. Perhaps as a result of prolonged periods
of sitting in class, two thirds of children and adolescents with RLS report daytime leg sensations.
Because of this, for diagnostic criterion A3 (worse in the evening/night), it is important to compare
equal duration of sitting or lying down in the day to sitting or lying down in the evening/night.
However, even with such comparisons, a significant subset of children do not report worsening at
evening/night, yet meet all other diagnostic criteria and have supportive features for RLS, including a
positive family history. Children who are age six years or older and developmentally normal have
been shown to report detailed, adequate descriptors for RLS symptoms. For children who are too
young to adequately describe RLS sensations or are developmentally delayed, a PLMD diagnosis may
be the initial diagnosis, with full RLS symptomatology evident over time. Diagnosis by observational
techniques has been suggested but not yet validated.

The differential diagnosis of pediatric RLS includes positional discomfort, sore leg muscles,
joint/tendon injury, and bruises, all of which are common mimics. In childhood, RLS is frequently
misdiagnosed  as  “growing  pains.”  Four  specific  domains that are affected in pediatric RLS are sleep,
daily activities, mood, and energy/vitality. Difficulties with sleep onset, sleep maintenance, and sleep
quality are common. Negative influence of RLS on waking activities includes academic impact due to
disruption of schoolwork, homework, and ability to concentrate. Severity assessment of pediatric RLS
has thus far been limited to simple measures of self-reported frequency and intensity.

Because pediatric RLS is highly familial, the presence of RLS in a first-degree relative helps to
increase diagnostic certainty in childhood RLS. Similarly, the presence of PLMS or a history of
PLMD is quite helpful in supporting an RLS diagnosis in children. As in adults, approximately 70%
of children with RLS demonstrate  PLMS  ≥  5/hour  on  a  single  night  and  nearly  90%  when  multiple  
nights  are  sampled.  PLMS  ≥  5/hour  are  uncommon  in  pediatric  normative  samples.  As  noted  above,  
pediatric RLS is comorbid with ADHD in about one fourth of cases, and, as in adults, higher rates of
anxiety and depressive symptoms are found. RLS is common in pediatric chronic kidney disease.

Prevalence rates of RLS increase with age until late adulthood then stabilize or decrease slightly in the
elderly. However, strong associations with anxiety, mood disorders, and decreased QoL measures
remain in the elderly. Diagnostic criteria for RLS in the cognitive-impaired elderly have been
suggested but not validated.

Pathology and Pathophysiology

Brain iron deficiency, central nervous system dopamine regulation, and genetics appear to be primary
factors in the pathophysiology of RLS. Iron is important in brain dopamine production and synaptic
density, as well as in myelin synthesis and energy production. A connection between RLS and low
brain iron is supported by autopsy data, MRI, brain sonography, and cerebrospinal fluid analysis.
Evidence for central nervous system dopaminergic system involvement comes mainly from multiple
randomized clinical trials that have clearly demonstrated the effect of dopaminergic drugs for RLS
and PLMS. In addition, an altered dopaminergic profile in RLS is supported by functional MRI,
positron emission tomography, and autopsy data. Association of gene variants BTBD9, MEIS1,
MAP2K5/LBXCOR,and PTPRD with RLS has been replicated, indicating a genetic substrate upon
which environmental factors might act. BTBD9 is estimated to confer a population attributable risk
(PAR) of 50% for RLS. Together, BTBD9, MEIS1, and MAP2K5/LBXCOR account for 70% of the
PAR for RLS in individuals with European ancestry. Thus far, two of the
variants, BTBD9 and MEIS1, appear to influence expression of PLMS, as well as iron homeostasis.
However, the full role of RLS gene variants has not been adequately defined.

Objective Findings

Although polysomnography is not routinely indicated in the evaluation of RLS, polysomnographic

studies demonstrate significant objective sleep abnormalities in RLS, with increased latency to
persistent sleep and higher arousal index as the most consistent differences in sleep architecture.
PLMS  ≥5/hour  occur  in  70%  to  80%  of  adults  with  RLS  on  single-night testing but in >90% when
multiple nights are sampled. In adult RLS, PLMS are more prominent during the first half of the night
and vary in frequency from night to night. About one third of PLMS are associated with cortical
arousals, and most have associated autonomic arousals. PLMS are not influenced by placebo effect.
PLMS arousals contribute to the primary RLS morbidity of sleep disturbance. Furthermore, RLS
sensory symptoms impair return to sleep, and thereby result in more prolonged awakening.

The Suggested Immobilization Test (SIT) evaluates PLMW and related sensory components of RLS
during resting wakefulness. A standard polysomnogram recording without respiratory measures is
used for one hour before the usual bedtime while the subject sits comfortably awake and upright in
bed with the legs outstretched. RLS diagnosis is supported by a finding of more than 40 PLMW/hour.

Activity monitors with high-frequency sampling and body-position monitoring may be attached to the
ankle or foot to provide an alternate measure of PLMs. Recordings assess the frequency and
variability of PLMs from night to night, typically over three to five nights.

Differential Diagnosis

The differentiation of RLS from other conditions that may have characteristics of RLS is essential,
because approximately 40% of individuals without RLS will report some urge or need to move the
legs while at rest. Fulfilling diagnostic criteria A2 (better with movement) and A3 (worse in the
evening/night) improves specificity for an RLS diagnosis to only about 70%, based on studies that
have used structured diagnostic interviews. However, differentiating RLS from leg
cramps and positional discomfort improves specificity to 94%, emphasizing the importance of
differential  diagnosis.  The  most  important  “mimics”  of  RLS  are leg cramps, positional discomfort,
arthralgias/arthritis, myalgias, leg edema, peripheral neuropathy, radiculopathy, and habitual foot
tapping. Not characteristic of  RLS  are:  “knotting”  of  the  muscle  (cramps),  relief  with  a  single  postural  
shift (positional discomfort), limitation to joints (arthritis), soreness to palpation (myalgias), and other
abnormalities on physical examination. Less common conditions to be differentiated from RLS
include neuroleptic-induced akathisia, myelopathy, symptomatic venous insufficiency, peripheral
artery disease, eczema, orthopedic problems, painful legs and moving toes, and anxiety-induced
restlessness. Neuroleptic-induced akathisia differs from RLS in that akathisia is associated with the
need to move the entire body and occurs in association with use of dopamine-receptor antagonists.
Painful legs and moving toes have neither a clear circadian pattern nor the sense of an urge to move.
Pain involving the legs occurs with numerous conditions, including arthritis, vascular problems,
sports/orthopedic injuries, and neuropathy. These pains can have a nocturnal presentation and may be
worse at rest, but improvement with movement either does not occur or entails more exercise than
simple movement of the leg. The urge to move, if present at all, usually stems from awareness that
movement produces relief rather than the strong primary urgency of movement felt with RLS. The
presence of pain, however, does not exclude a diagnosis of RLS, because about 50% of patients with
RLS report their RLS symptoms as painful.

Although it is important that RLS symptoms not be attributable solely to another medical or
behavioral condition, it should also be appreciated that any of these mimics can occur in an individual
who also has RLS. For example, some subjects may have both RLS and leg cramps. When the
diagnosis of RLS is not certain, evaluation for the supportive features such as the presence of PLMS
or a family history of RLS may be helpful. Diagnostic interviews that include differential diagnosis
have been validated for RLS. These demonstrate sensitivity and specificity of > 90%.

Unresolved Issues and Further Directions

The diagnosis of RLS relies on the subjective report of sensory symptoms that lie outside the range of
common sensory experience. Many patients have difficulty describing the sensations. Further studies
of the biological bases for RLS may lead to better classification of RLS and possibly to objective tests
for diagnosis. Iron, dopamine, and genetic research hold particular promise. Additional
epidemiological and genetic studies outside the US and Europe are needed to explore apparent
population differences. The diagnostic standards and severity assessment for children and cognitively
impaired adults require further development. Clarification of the natural course and potential
exacerbating factors is needed. Better understanding of RLS with comorbidities such as mood
disorders and attention deficit hyperactivity disorder might lead to improved outcomes in those
disorders. Further evaluation of long-term complications is important, including clarification of
associations with hypertension, cardiovascular disease, and stroke.

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Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Sleep Related Movement Disorders ›› Disorders ››

Periodic Limb Movement Disorder

ICD-9-CM code: 327.51

ICD-10-CM code: G47.61

Alternate Names

Periodic movement disorder of sleep, sleep myoclonus syndrome, nocturnal myoclonus syndrome.

Diagnostic Criteria

Criteria A-D must be met

A. Polysomnography demonstrates PLMS, as defined in the latest version of the American Academy
of Sleep Medicine (AASM) Manual for the Scoring of Sleep and Associated Events.

B. The frequency is > 5/hour in children or > 15/hour in adults.1

C. The PLMS cause clinically significant sleep disturbance or impairment in mental, physical, social,
occupational, educational, behavioral, or other important areas of functioning.2,3

D. The PLMS and the symptoms are not better explained by another current sleep disorder, medical or
neurological disorder, or mental disorder (e.g., PLMS occurring with apneas or hypopneas should not
be scored).4,5

Notes

1. The PLMS Index must be interpreted in the context of a patient's sleep related complaint. In adults,
normative values greater than five per hour have been found in studies that did not exclude respiratory
event-related arousals (using sensitive respiratory monitoring) and other causes for PLMS. Data
suggest a partial overlap of PLMS Index values between symptomatic and asymptomatic individuals,
emphasizing the importance of clinical context over an absolute cutoff value.
2. If PLMS are present without clinical sleep disturbance or daytime impairment, the PLMS can be
noted as a polysomnographic finding, but criteria are not met for a diagnosis of PLMD.

3. The presence of insomnia or hypersomnia with PLMS is not sufficient to establish the diagnosis of
PLMD. Studies have shown that in most cases the cause of the accompanying insomnia or
hypersomnia is something other than the PLMS. To establish the diagnosis of PLMD, it is essential to
establish a reasonable cause-and-effect relationship between the insomnia or hypersomnia and the
PLMS. This requires that other causes of insomnia such as anxiety or other causes of hypersomnia
such as obstructive sleep apnea or narcolepsy are ruled out. PLMS are common, but PLMD is thought
to be rare in adults.

4. PLMD cannot be diagnosed in the context of RLS, narcolepsy, untreated obstructive sleep apnea, or
REM sleep behavior disorder; PLMS occur commonly in these conditions but the sleep complaint is
more readily ascribed to the accompanying disorder. The diagnosis of RLS takes precedence over that
of PLMD when potentially sleep-disrupting PLMS occur in the context of RLS. In such cases, the
diagnosis of RLS is made and the PLMS are noted.

5. When it is reasonably certain that the PLMS have been induced by medication, and full criteria for
PLMD  are  met,  it  is  preferred  that  the  more  specific  diagnosis  of  PLMD  be  used,  rather  than  “Sleep  
related  movement  disorder  due  to  a  medication  or  substance.”

Essential Features

PLMD is characterized by periodic episodes of repetitive, highly stereotyped limb movements that
occur during sleep (PLMS), in conjunction with clinical sleep disturbance or fatigue that cannot be
accounted for by another primary sleep disorder or other etiology.

PLMS occur most frequently in the lower extremities. They typically involve extension of the big toe,
often in combination with partial flexion of the ankle, the knee, and sometimes, the hip. Similar
movements can occur in the upper limbs. Individual movements may be associated with an autonomic
arousal, a cortical arousal, or an awakening. Typically, the patient is unaware of the limb movements
or the frequent sleep disruption. An arousal may precede, coincide with, or follow the limb
movement, suggesting that a central generator may give rise to both the periodic movements and the
related sleep disturbance.

A clinical history of sleep onset problems, sleep maintenance problems, or unrefreshing sleep
attributable to the PLMS is needed for a diagnosis of PLMD. These symptoms have most consistently
been associated with PLMS, and the presence of these clinical symptoms differentiates PLMD from
asymptomatic PLMS. Although excessive daytime sleepiness has been reported with PLMD in the
past, newer data do not find significantly elevated Epworth Sleepiness Scale scores or Multiple Sleep
Latency Test (MSLT) values in subjects with PLMS. If the only complaint is sleep disruption for the
bed partner, then PLMD should not be diagnosed but the sleep disturbance of the bed partner can be
noted.

The PLMS index should exceed five per hour in children and 15 per hour in adult cases for a
diagnosis of PLMD. This is based on substantial normative data in children. In adults, there is a
significant increase in sleep disturbance symptoms with PLMS >15/hour.

The PLMS and the symptoms of sleep disturbance or nonrestorative sleep should not be better
explained by another etiology. Most important in the differential diagnosis are RLS, REM sleep
behavior disorder (RBD), and narcolepsy. Research studies indicate that five or more PLMS per hour
occur in 80% to 90% of patients with RLS, in about 70% with RBD, and in 45% to 65% with
narcolepsy. In RBD, PLMS are often present without arousals during nonrapid eye movement sleep
(NREM) sleep but can also continue into REM sleep, which is unusual in all other settings. If
significant daytime sleepiness and PLMS are present, a diagnosis of narcolepsy should be considered.
PLMD should not be diagnosed when criteria for one of these three disorders is met. However, the
primary  disorder  “with  PLMS”  can  be  specified  (e.g.,  “RLS  with  PLMS”).

A sensitive technique, such as pressure transducer airflow monitoring or esophageal manometry,

should be used to monitor breathing during polysomnography to reasonably exclude sleep related
breathing disorders (SRBDs) as the direct cause of the PLMS. When independent PLMS are present
in patients with SRBDs, a separate diagnosis of PLMD may be considered if the PLMS persist despite
adequate treatment of the SRBD and otherwise unexplained sleep disturbance remains. Ideally,
polysomnography for the diagnosis of PLMD should be performed after the biologic effect of a
medication or substance, such as an antidepressant known to induce or aggravate PLMS, has ended.

Associated Features

Higher rates of mood disorders, anxiety, attention deficits, oppositional behaviors, and parasomnias
have been reported in some studies of patients with PLMD. In children with PLMD, a family history
of RLS is common. A sustained clinical response to dopaminergic therapy is supportive of the
diagnosis of PLMD. Although PLMD symptoms may be responsive to benzodiazepines,
benzodiazepine responsiveness is not supportive of the diagnosis due to the nonspecific effect of
benzodiazepines on sleep.

Clinical and Pathophysiological Subtypes

Not applicable or known.

Demographics

Although PLMD is thought to be rare, the exact prevalence is not known. PLMD has been reported in
both children and adults. PLMS >5/hour are very uncommon in children and adults younger than the
age of 40 years, but then increase markedly with advancing age, occurring in over 45% of the elderly.
The population prevalence of PLMS >15/hour has been estimated at 7.6% of 18- to 65-year-olds, with
4.5% of the total population also reporting sleep disturbance or excessive sleepiness. However, RLS
and medication-induced PLMS were not exclusionary criteria in this population, suggesting much
lower rates for PLMD. The increase in PLMS with age may occur as a partial expression of familial
or genetic factors associated with RLS, based on data that show very little increase in PLMS with age
when individuals who have RLS or first-degree relatives with RLS are excluded. PLMS are less
common in black adults and children than in whites. No sex difference has been described for PLMS
or PLMD.

Predisposing and Precipitating Factors

A positive family history of RLS confers increased risk for PLMS and PLMD. The genetic variants
noted below may be a mediator of this risk. Precipitation or aggravation of PLMS has been reported
with the use of several medications. Selective serotonin reuptake inhibitor antidepressants, tricyclic
antidepressants, lithium, and dopamine receptor antagonists have most often been associated with this
effect.
Low brain iron, as reflected by serum ferritin level, may worsen PLMS via the role of iron in
dopamine function. Less evidence is available for obstructive sleep apnea (OSA), alcohol, pain, and
sleep deprivation as factors that worsen PLMS.

Familial Patterns

The familial pattern of PLMD has not been studied in detail. Families with RLS have been found to
include first-degree relatives without RLS but with increased rates of PLMS or PLMD, raising the
possibility that PLMD is an attenuated manifestation or a precursor to RLS. The gene
variants BTBD9and MEIS1, which were found in genomewide studies of RLS, appear to influence the
expression of PLMS.

Onset, Course, and Complications

Although the typical age of onset is not known, PLMD occurs in both children and adults, with onset
as early as infancy. The natural history has not been described in detail, but some pediatric cases of
PLMD progress to RLS. Incidence and remission rates are unknown. Impaired performance in a
simulated driving task has been found in patients with PLMD. Increased PLMS have been associated
with a higher risk of cardiovascular disease, stroke, and mortality in some studies. PLMS-related
overactivity of the sympathetic nervous system is postulated to be a potential mechanism for these
associations.

Developmental Issues

Given the low background rates of PLMS in children, PLMD has emerged as a useful diagnostic
category in pediatric sleep medicine. Pediatric PLMD has important clinical and polysomnographic
correlates that are comparable in severity to pediatric OSA. However, PLMS and PLMD normative
data remain sparse for children younger than two years.

In the elderly, frequent occurrence of other conditions that can account for sleep disturbance and
fatigue makes application of PLMD criteria difficult, even though PLMS are common.

Pathology and Pathophysiology

Dopaminergic impairment has been implicated in the pathophysiology of PLMS and PLMD. The
study of PLMS in RLS and in children also suggests genetic diathesis and iron status as factors.
Cyclic alternating pattern, a marker of nonrestorative sleep, is increased in individuals with PLMS
and may influence the periodicity of PLMS. Cortical arousals can precede, coincide with, or follow
PLMS, indicating that PLMS do not cause the arousals. In addition, PLMS can be dissociated from
arousals pharmacologically, suggesting an indirect relation, possibly mediated by a central generator.
The autonomic arousals associated with PLMS are characterized by significant heart rate and blood
pressure surges, a mechanism for possible increased cardiovascular and cerebrovascular disease risk.

Objective Findings

PLMS can appear immediately with the onset of stage N1 sleep, are frequent during stage N2 sleep,
decrease in frequency in stage N3, and are usually absent during stage R sleep. PLMS typically occur
in discrete episodes that last from a few minutes to an hour. Both lower limbs should be monitored for
the presence of limb movements. Movements of the upper limbs may be sampled if clinically
indicated. The anterior tibialis electromyogram (EMG) shows repetitive contractions, each lasting 0.5
to 10 seconds. The movements may affect one or, more typically, both of the lower limbs, but not
necessarily in a symmetric or simultaneous pattern. Specific scoring criteria for PLMS are described
in the AASM Manual for the Scoring of Sleep and Associated Events.

Self-reports, bed partner observations, or parental reports for children have not been found to have
sufficient specificity or sensitivity to replace objective testing for PLMS.

Care must be taken to discriminate PLMS from other movements such as a simple change in body
position, stretching of a limb, or a muscle cramp. PLMS are longer in duration than myoclonic jerks,
which, by definition, are typically 50 to 150 milliseconds long. Movements associated with
respiratory events, hypnagogic foot tremor, or alternating leg muscle activation during sleep (ALMA)
should not be included in the PLMS index.

PLMS may be associated with electroencephalographic (cortical) arousals or with awakenings.

Autonomic arousals—measured by a change in heart rate, blood pressure, or pulse transit time—have
been shown to be more frequent than cortical arousals. In some cases, periodic arousals may persist
even though the PLMS have subsided. The arousals are typically more difficult to measure than are
the PLMS, and their clinical significance is a topic of ongoing debate. As with obstructive sleep
apnea, the associated cortical arousal index has not proven more useful than the PLMS index in
making clinical decisions. Although a subjective report of excessive daytime sleepiness is present in
some patients with PLMD, mean sleep latency measured by MSLT has not been found to be
consistently abnormal or to correlate with the PLMS cortical arousal index.

The movements should be reported as an index of total sleep time, called the PLMS index. The PLMS
index is the number of periodic limb movements per hour of total sleep time, as determined by
polysomnography. The PLMS arousal index is the number of PLMS associated with a cortical
arousal, expressed per hour of total sleep time. Other parameters for the description of PLMS include
periodicity index, intermovement interval distribution, and time of night distribution. These features
have been shown to help differentiate PLMS patterns in different conditions (e.g., a finding of the
highest periodicity indices in adult RLS and PLMD).

Leg actigraphy has been validated against PSG for the measurement of PLMS and provides a
methodology to assess PLMS in large populations, as well as night-to-night variability.

Differential Diagnosis

As described in the essential features section, PLMD is a diagnosis of exclusion and it is important to
differentiate it from other conditions in which PLMS occur, particularly RLS, RBD,
narcolepsy, andSRBDs. Increased rates of PLMS have also been reported in multiple system atrophy,
dopa-responsive dystonia, sleep related eating disorder, spinal cord injury, end-stage renal disease,
congestive heart failure, Parkinson disease, sickle cell disease, posttraumatic stress disorder,
Asperger syndrome, Williams syndrome, and multiple sclerosis. Dopaminergic impairment and/or
diminished inhibition of the central pattern generator for PLMS have been proposed as common
factors linking various disorders and PLMS.

Sleep starts (hypnic jerks) need to be differentiated from PLMS. Sleep starts typically are limited to
the transition from wakefulness to sleep, are not periodic, and are briefer (20 to 100 milliseconds)
than PLMS. Normal phasic REM activity is limited to REM sleep, typically occurs in 5- to 15-second
clusters, and is usually associated with bursts of REMs. Phasic REM EMG twitches are more variable
in duration and do not have the periodicity of PLMS. Fragmentary myoclonus is characterized by
EMG activity that is briefer (75 to 150 milliseconds), more variable in duration, less periodic than
PLMS, and has little or no associated visible movement. Also, PLMS must be differentiated from
movements associated withnocturnal epileptic seizures and myoclonic epilepsy and from a number of
forms of myoclonus seen while awake, such as in Alzheimer disease, Creutzfeldt-Jakob
disease, and other neuropathologic conditions. However, in these disorders, the involuntary
movements are prominent during the daytime, often do not disappear with activity, are prominent in
the arms and other body parts in addition to the legs, and do not display the periodicity seen with
PLMS.

Unresolved Issues and Further Directions

There has been controversy over the clinical significance of PLMS. To date, the interpretation of most
studies has been confounded by multiple factors that include: imprecise diagnostic criteria; confusion
between PLMS and PLMD; inadequate monitoring for subtle SRBDs; a lack of consideration of
medications known to induce, worsen, or suppress PLMS; and inadequate measurement of the known
night-to-night variability of PLMS. Newer respiratory monitoring techniques for polysomnography
and the use of actigraphy monitors over several nights should help address a number of these issues.
The role of associated arousals in relation to clinical symptoms is yet to be determined, but the
appreciation of autonomic arousals as well as cortical arousals might be critical. It is possible that
PLMS are a measurable marker of unstable sleep, related to genetic diathesis and dopaminergic
impairment.

Bibliography

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Hornyak M, Feige B, Riemann D, Voderholzer U. Periodic leg movements in sleep and periodic limb
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Pennestri MH, Whittom S, Adam B, Petit D, Carrier J, Montplaisir J. PLMS and PLMW in healthy
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periodic limb movement disorder: parent-child pairs. Sleep Med 2009;10:925–31.

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Scofield H, Roth T, Drake C. Periodic limb movements during sleep: population prevalence, clinical
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Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Sleep Related Movement Disorders ›› Disorders ››

Sleep Related Leg Cramps

ICD-9-CM code: 327.52

ICD-10-CM code: G47.62

Alternate Names

Leg  cramps,  “charley  horse,”  nocturnal  leg  cramps.

Diagnostic Criteria

Criteria A-C must be met

A. A painful sensation in the leg or foot associated with sudden, involuntary muscle hardness or
tightness, indicating a strong muscle contraction.

B. The painful muscle contractions occur during the time in bed, although they may arise from either
wakefulness or sleep.

C. The pain is relieved by forceful stretching of the affected muscles, thus releasing the contraction.

Essential Features

Sleep related leg cramps are painful sensations caused by sudden and intense involuntary contractions
of muscles or muscle groups during which there is muscle spasm and hardness for several seconds.
These painful sensations are usually in the calf or small muscle of the foot. Occurring during the time
in bed, sleep related leg cramps may arise from either wakefulness or sleep.

Sleep related leg cramps usually start abruptly but may in some cases be preceded by a less painful
warning sensation. The muscle contractions last for a few seconds up to several minutes and then
remit spontaneously. The frequency of sleep related leg cramps varies considerably from less than
yearly to multiple episodes every night.

The cramps can be relieved by strongly stretching the affected muscle and sometimes also by local
massage, application of heat, or movement of the affected limb. Leg cramps can be present primarily
during the daytime.

Associated Features

The muscle cramp affects sleep. The pain from the cramp itself and from the activities used to relieve
it commonly disturb sleep onset or cause an awakening from sleep. Often the presenting complaint is
insomnia, at times severe.
Tenderness and discomfort in the muscle may persist for several hours after the cramping. Persisting
discomfort after the cramping episode often delays subsequent return to sleep.

Clinical and Pathophysiological Subtypes

Sleep related leg cramps are known to be either idiopathic or secondary to other medical conditions,
but there have been no indications of significant differences in the clinical features of the disorder
related to the cause.

Demographics

Sleep related leg cramps are common. It has been suggested that nearly every adult older than 50
years has experienced sleep related leg cramps at least once. Both the prevalence and the frequency of
the events increase with age. Sleep related leg cramps have been reported to occur at least
occasionally in about 7% of children and adolescents, 33% in adults older than 60 years, and 50% in
adults older than 80 years, with both older groups reporting a symptom frequency of at least once
every two months. Nightly leg cramps have been reported in 6% of adults older than 60 years. No
definitive sex information has been reported, though a single study reported a higher prevalence in
women.

Predisposing and Precipitating Factors

Predisposing factors include diabetes mellitus, amyotrophic lateral sclerosis, cramp fasciculation
syndrome, peripheral vascular disease, hypokalemia, hypocalcemia, hypomagnesemia, and metabolic
disorders. The disorder can be associated with prior vigorous exercise, prolonged standing at work,
dehydration, fluid and electrolyte disturbances, endocrine disorders, neuromuscular disorders,
disorders of reduced mobility, vascular disease, cirrhosis, and hemodialysis. Medications that have
been associated with sleep related leg cramps include oral contraceptives, intravenous iron sucrose,
teriparatide, raloxifene, diuretics, long-acting β-agonists, and statins. Sleep related leg cramps occur in
about 40% of pregnant women and generally resolve after delivery.

Familial Patterns

Not known.

Onset, Course, and Complications

Sleep related leg cramps have not been reported in infancy, nor in children younger than eight years.
The peak onset is usually in adulthood, but the condition may be seen for the first time in old age. The
natural history of leg cramps is not well understood. Many patients describe a waxing and waning
course  of  many  years’  duration.  Complications  include  muscle  tenderness,  insomnia,  and  occasional
daytime fatigue due to interrupted sleep. No marked mental or social dysfunction has been described
due to sleep related leg cramps alone.

Pathology and Pathophysiology

Many sleep related leg cramps appear to be idiopathic. Although leg cramps involve abnormal muscle
tone, they are generally considered not to involve agonist-antagonist co-contractions and, thus, are not
classified as dystonias. Some nocturnal leg cramps, particularly those in the feet, may resemble
dystonias but, unlike classic dystonias, sleep related leg and foot cramps are relieved by stretching the
affected muscle or muscles.
Electrophysiologic recordings show that the cramps typically start with spontaneous firing of anterior
horn cells followed by motor unit discharges for contractions at rates up to 300 Hz (considerably more
than with voluntary muscle contractions). The pain may result from local metabolite accumulations or
from local ischemia.

Muscle and tendon shortening due to age or lack of stretching exercise is thought to contribute to the
development of sleep related leg cramps. Exercise involving stretching the affected muscles is thought
to help prevent or reduce the occurrence of sleep related leg cramps.

Objective Findings

Polysomnographic studies of patients with chronic sleep related leg cramps reveal nonperiodic bursts
of gastrocnemius EMG activity. Episodes arise from sleep without any specific preceding physiologic
changes during sleep.

Differential Diagnosis

Sleep related leg cramps are common in chronic myelopathy, peripheral neuropathy, muscular pain
fasciculation syndrome, and disorders of calcium metabolism. These causes should be differentiated
by clinical history and physical examination. RLS is sometimes confused with sleep related leg
cramps because both can present with leg discomfort during the sleep period and RLS patients
sometimes complain of a cramping sensation. However, if patients meet the diagnostic criteria for
RLS and do not describe an actual cramp or hardening of the muscle, the diagnosis should be RLS.
Because leg cramps can mimic RLS and meet all the criteria for RLS, the description of an actual
spasm or hardening of the muscle is a critical differentiating factor. A leg cramp is also a much briefer
event than the typical symptoms of RLS, which can persist for hours. However, RLS and leg cramps
may sometimes be seen in the same individual.

Dystonia is ongoing daily spasm of muscles and is distinguished electrophysiologically from leg
cramps by ongoing co-contraction of agonist and antagonist muscles. Dystonia can be focal, as in the
case  of  muscles  of  the  neck  (torticollis)  or  hand  (writer’s  cramp),  or  generalized  as  in  the  case  of  
torsion dystonia.

Unresolved Issues and Further Directions

Sleep related leg cramps are common and can affect sleep. Their association with other disorders and
different medications hinder accurate epidemiological data and underestimate their effect on sleep and
on quality of life. Instruments to quantify the severity of the disorder and its impact are needed to
adequately address clinical relevance, treatment, and the potential occupational hazards. Effective
treatments for sleep related leg cramps have yet to be developed. The prophylactic benefits of
stretching exercises remain to be adequately validated.

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Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Sleep Related Movement Disorders ›› Disorders ››

Sleep Related Bruxism

ICD-9-CM code: 327.53

ICD-10-CM code: G47.63

Alternate Names

Nocturnal bruxism, nocturnal tooth grinding, tooth clenching.

Diagnostic Criteria

Criteria A and B must be met

A. The presence of regular or frequent tooth grinding sounds occurring during sleep.

B. The presence of one or more of the following clinical signs:

1. Abnormal tooth wear consistent with above reports of tooth grinding during sleep.

2. Transient morning jaw muscle pain or fatigue; and/or temporal headache; and/or jaw locking upon
awakening consistent with above reports of tooth grinding during sleep.

Notes

1. Although polysomnography is not required for the diagnosis, sleep bruxism, as described in the
latest version of the AASM Manual for the Scoring of Sleep and Associated Events, is ideally
recorded with masseter muscle activity with audio-video signal to increase diagnostic reliability.

Essential Features

Bruxism is defined as a repetitive jaw-muscle activity characterized by clenching or grinding of the

teeth and/or by bracing or thrusting of the mandible. Bruxism has been divided into its two distinct
circadian manifestations: sleep bruxism and awake bruxism.

In sleep, jaw muscle contractions are frequently repeated over time and are termed rhythmic
masticatory muscle activity (RMMA). These contractions can take two forms on electromyographic
traces: a series of repetitive activity (phasic muscle contractions) or isolated sustained jaw clenching
(tonic contractions). These contractions during sleep produce tooth-grinding sounds and are referred
to as sleep related bruxism.

Sleep related bruxism can lead to abnormal tooth wear, tooth pain, jaw muscle pain, and temporal
headache. Severe sleep related bruxism may also result in sleep disruption. This may involve not only
the individual affected, but also the bed partner, because the sounds made by the friction of the teeth
are usually perceived as being unpleasant and can be quite loud and disturbing to those nearby.

The disorder is typically brought to dental or medical attention because of the tooth damage, pain, or
disturbing sounds. Less commonly, it may present as a cause of disturbed sleep. Young and otherwise
healthy individuals with sleep related bruxism appear to have normal sleep structure and homeostasis.
The majority of RMMA episodes during sleep occur in association with sleep arousal.

Jaw muscle pain, tenderness in the masseter and temporalis muscle regions, morning headache, or
fatigue can arise due to sleep related bruxism.

Associated Features

Additional symptoms include a variety of unpleasant muscle and tooth sensations, limitation of jaw
movements, orofacial pain, and temporal/tension headaches. Tooth wear, fractured teeth, and buccal
lacerations also can occur. These symptoms may be induced by sleep related bruxism, but the
connection may not be apparent to the affected individual and diagnostic discrimination is weak.

Headaches are frequently reported by both adults and children with sleep related bruxism. The
headache usually involves the temporal regions and it has the characteristics of a tension headache. It
is reported either in the morning (more frequently) or during the day (with wake bruxism). The
estimated OR for headache in individuals with sleep related bruxism is > 4 compared to controls.

There is high individual variability in the intensity and duration of sleep related bruxism, but in the
most severe cases, hundreds of events can occur during a night of sleep. However, no direct
relationship has been observed between the severity of sleep related bruxism and the appearance of
clinical signs and symptoms. Indeed, individuals with a mild to moderate index of sleep bruxism (2 to
4 RMMA episodes/hour of sleep) have a higher risk of reporting painful jaw upon awakening (OR
3.9), and masticatory muscle fatigue (OR 5.1) compared to individuals with severe sleep related
bruxism (> 4 RMMA episodes/hour of sleep).

Psychosocial components may also be linked to sleep related bruxism. The psychological assessment
of otherwise healthy adults with sleep related bruxism suggests a correlation (not yet proven as a
causality) between bruxism and stress/anxiety. Moreover, both children and adults with sleep related
bruxism seem to have higher scores in stress, anxiety, and psychiatric scales compared to control
individuals.

Clinical and Pathophysiological Subtypes

Sleep related bruxism without clear cause is termed primary or idiopathic.

Forms of sleep related bruxism associated with the use of psychoactive medications, recreational
drugs, or a variety of medical disorders (e.g., Parkinson disease, RBD, Down syndrome) are defined
assecondary sleep related bruxism. Treatment-induced sleep related bruxism is also
termediatrogenic.

Although the primary form of sleep related bruxism is most often reported in healthy children and
adults, secondary sleep related bruxism is observed in children with cerebral palsy and mental
retardation and in adult patients with abnormal movements such as in oromandibular
myoclonus/facio-mandibular myoclonus or with sleep related breathing disorders. OSA and sleep
related bruxism commonly co-occur.

Tooth grinding and clenching also can occur during wakefulness, as an oral parafunctional activity
known as awake bruxism. Awake bruxism is considered a different disorder, probably with different
diagnostic criteria and pathophysiology; its association with sleep bruxism is still under debate.
However, the two oral activities may coexist in the same individual.

Demographics

The prevalence of sleep related bruxism, based on reports from parents or sleep partner, is highest in
childhood (approximately 14% to 17%) and then decreases over the life span. In teenagers to young
adults, prevalence is in the 12% range. In young to middle-aged adults, it is approximately 8% but as
little as 3% in older persons. The reported reduction in tooth grinding in the elderly probably
overestimates the actual reduction, because edentulism, use of dentures, and changes in sleeping
behaviors (i.e., in isolation) may influence reporting. There is no reported sex difference for the
prevalence of sleep related bruxism.
Predisposing and Precipitating Factors

Predisposing factors include personality types; for example, individuals who are highly motivated or
characteristically maintain high vigilance may have an increased prevalence of sleep related bruxism.

Genetic predisposition is plausible but still under investigation. As described below, there is some
familial predisposition due to environmental or shared genetic factors. Recently, a serotonin gene was
described in bruxism patients but the absence of distinction between the wake and sleep forms in this
report preclude firm conclusions.

Precipitating factors can include anxiety related to current life events, tasks requiring high levels of
performance, and repetitive tasks with short deadlines. The use of cigarettes or caffeine in the hours
before sleep also can contribute to the occurrence of sleep related bruxism (probably due to the
increased arousals and sleep instability).

The  role  of  dental  morphologic  “defects”  (occlusal  interferences)  remains  controversial  in  the  etiology  
of sleep related bruxism. Tooth contacts do not usually set in motion a bruxism episode; they are
usually late in the series of events occurring during sleep related bruxism/tooth grinding. Hence, the
causality link between tooth contact and sleep related bruxism is not supported by the temporal
sequence.

Familial Patterns

Sleep related bruxism tends to occur in families; approximately 20% to 50% of affected individuals
have at least one direct family member with a history of tooth grinding, and childhood sleep related
bruxism appears to persist into adulthood in two thirds of reported cases. However, no genetic
variants or genetic inheritance patterns so far have been associated with sleep related bruxism.

Onset, Course, and Complications

The onset of sleep related bruxism may occur during childhood, adolescence, or adulthood. It is
difficult to establish the time of onset with precision because it is mainly based on the awareness of
the individual or his/her family members who report the disorder.

Sleep related bruxism in childhood has been reported by parents to begin as soon as both upper and
lower teeth have erupted. Secondary sleep related bruxism may occur at any age, but is more common
in younger and middle-aged adults.

Even without a tooth grinding history or complaints, RMMA may be observed in most normal
sleepers (on average, one episode per hour of sleep) across the life span. However, in individuals with
sleep related bruxism, jaw-muscle contractions are more frequent and more intense. This may explain
the secondary tooth damage and the occurrence of pain and other symptoms.

The night-to-night variability in episodes of audible tooth grinding sounds is large (greater than 50%
coefficient of variation). In-laboratory polysomnographic recordings indicate that the corresponding
variability in frequency of RMMA is smaller (approximately 25%), although ambulatory recording
has suggested somewhat higher RMMA variability. First-night effect on RMMA index is minimal.

Dental damage and abnormal tooth wear are the most frequent signs of the disorder. However, they
are not a direct proof of current sleep related bruxism and many contributing factors have to be ruled
out (e.g., type of diet in the occurrence of abnormal tooth wear). Diagnostic discriminative strength of
these dental findings is weak; severity of wear cannot account for the index (i.e., frequency of
RMMA). Sleep related bruxism could lead to temporomandibular joint disorders (e.g., pain, joint
sound [click], or jaw movement limitations), although recent evidence does not support this
association. Transient morning orofacial pain, including temporal headaches, is not uncommon, as
described above. Hypertrophy of the masseter and temporalis muscles can occur, but the diagnostic
specificity of this finding for sleep related bruxism is also weak.

The natural course of this sleep disorder is usually benign. Many individuals with sleep related
bruxism remain asymptomatic for most of their lives. Others can experience associated symptoms
(i.e., pain) that may interfere with their quality of life and/or sleep and may require treatments. Further
diagnostic investigations and assessment are recommended if sleep related bruxism is associated with
other more severe sleep or medical disorders (e.g., SRBD, RBD, epilepsy).

Developmental Issues

Sleep related bruxism is frequently reported in childhood but decreases with age. However, some
individuals may experience it every night for most of their lives.

Conceptualizations of sleep related bruxism in children vary. Some consider this a physiological oral
parafunction while teeth are erupting or exfoliating, whereas others view this as a sleep disorder with
many associated signs and symptoms. Sleep related bruxism, especially in children, has been
associated with attention deficit hyperactivity disorder, parasomnias, SRBD, snoring, and many
psychological and medical conditions.

In the elderly, sleep related bruxism has been observed in association with movement disorders (e.g.,
Parkinson disease or oral tardive dyskinesia persisting during sleep), RBD, and dementia.

Pathology and Pathophysiology

The majority of RMMA episodes during sleep (up to 80%) occur in association with sleep arousals.
Sleep related bruxism episodes typically follow a clear arousal sequence, starting with increased
sympathetic-cardiac activity and fast electroencephalographic (EEG) waves in the minutes to seconds
preceding the onset of an RMMA episode. The jaw muscle contractions are then followed by, or are
concomitant with, an increase in blood pressure and ventilation. RMMA episodes sometimes
conclude with swallowing. Other causes of sleep bruxism onset are unknown, although potential
candidates include airway resistance and oropharyngeal dryness.

In the majority of individuals with sleep related bruxism, the frequency of sleep arousals is within the
normal range. However, they may have an exaggerated responsiveness to ongoing sleep arousals or an
increased magnitude of arousal. Individuals with sleep related bruxism show more CAP phase A3 (as
described by the scoring and analysis of cyclic alternating pattern (CAP) during sleep) than controls,
an expression of increased arousal pressure and increased sleep instability. This increased sleep
instability  seems  to  be  the  “permissive  window”  for  occurrence  of  RMMA  during  sleep.

Objective Findings

Polysomnographic (PSG) monitoring of individuals with sleep related bruxism demonstrates

increased masseter and temporalis muscle activity during sleep, along with grinding sounds. RMMA
episodes can occur during all sleep stages, but are most common in sleep stages N1 and N2 (more
than 80% of episodes), whereas fewer than 10% of RMMA episodes occur during REM sleep.
However, in some individuals, sleep related bruxism occurs predominantly in REM sleep.

As described above, the majority of sleep related bruxism episodes are temporally associated with
sleep arousal and are preceded by signs of autonomic/cardiac activation (e.g., increased heart rate and
blood pressure).

Three subtypes of the EMG pattern of sleep related bruxism have been described: phasic activity at 1
Hz frequency with EMG bursts lasting 0.25 to 2 seconds; sustained tonic activity lasting longer than 2
seconds; or a mixed pattern. An episode begins after at least a three-second interval with no muscle
activity.

Polysomnography is not usually performed in otherwise healthy individuals with sleep related
bruxism in routine clinical settings. However, PSG may be indicated to demonstrate the disorder and
to rule out associated respiratory disturbances, gastroesophageal reflux, RBD, night terrors,
faciomandibular myoclonus, or epilepsy. The sensitivity of polysomnographic study in detecting sleep
related bruxism in severe cases is moderate to high; in milder cases, however, it may be low due to the
night-to-night variability in RMMA and tooth grinding.

Ambulatory home monitoring may be used for screening, diagnosis, and treatment outcome
assessment by studying the individual in his/her usual environment, but it is characterized by lower
diagnostic specificity due to the absence of audiovisual recordings (i.e., 20% overestimation in
RMMA frequency is expected due to poor capacity to exclude concomitant nonspecific activities).

To record and score sleep related bruxism activity (i.e., RMMA), there must be a minimum of one
masseter muscle monitor, ideally with audiovisual recording, to associate muscular activity with
grinding sound production. Video monitoring helps distinguish bruxism from other orofacial and
masticatory movements that normally occur during sleep (e.g., swallowing, coughing) and from
specific movement disorders (RBD, epilepsy and tooth tapping, oromandibular myoclonus).

For the best level of diagnostic specificity and sensitivity, bilateral masseter and temporalis muscle
EMG recordings, referenced to ear, mastoid, or zygomatic bone, are advisable.

Differential Diagnosis

The disorder seldom poses diagnostic problems. Evaluation for temporomandibular disorders and
damage to dentition is indicated.

Sleep related bruxism needs to be differentiated from other faciomandibular activities occurring
during sleep, such as faciomandibular myoclonus, SRBD, RBD, abnormal swallowing, gastro-
esophageal reflux, night terrors, confusional arousals, dyskinetic jaw movements persisting in sleep
(dystonia, tremor, chorea, dyskinesia), and, rarely, sleep related epilepsy.

Oromandibular or faciomandibular myoclonus has been observed in approximately 10% of

individuals with severe sleep related bruxism, but it can also occur in individuals without abnormally
increased RMMA events. As opposed to sleep related bruxism, faciomandibular myoclonus consists
of EMG bursts of brief duration (less than 250 milliseconds in length) in the facial muscles; these can
occur either as isolated bursts or as a cluster of regularly or irregularly occurring brief bursts. A high
index of oromandibular myoclonus in sleep has been observed in idiopathic RBD patients.
Rhythmic jaw movements also have been observed in association with partial complex or generalized
seizure disorders. Epilepsy needs to be considered in the differential diagnosis, although the
presentation of epilepsy as relatively isolated sleep related bruxism is very rare.

Unresolved Issues and Further Directions

An  expert  bruxism  international  group  has  proposed  a  diagnostic  grading  system  of  “possible,”  
“probable,”  and  “definite”  for  both  sleep  and  awake  bruxism.  Such  a  clinical  tool  will  help  to  
discriminate sleep bruxism from awake bruxism, although further validation is required for clinical
and research purposes in all relevant dental and medical domains. In summary, this group suggests
that  a  rating  of:  (1)  “possible”  is  given  if  based  on  self-report, by means of questionnaires, and/or the
anamnestic  part  of  a  clinical  examination;;  (2)  “probable”  sleep  or  awake  bruxism  is  given  if  based  on  
self-report and supportive physical  findings;;  (3)  “definite”  sleep  bruxism  if  based  on  self-report,
physical findings, and a polysomnographic recording, preferably with audiovisual recordings.

The clinical relevance of sleep related bruxism in cases of comorbidity with other medical problems
such as snoring, sleep related breathing disorder, RBD, attention deficit hyperactivity disorder,
headache, and orofacial pain needs to be assessed in order to distinguish primary benign forms of
sleep related bruxism from those that represent an epiphenomenon of other more severe sleep and
medical disorders.

Sleep related bruxism may be concomitant to breathing disorders, including any level of severity of
OSA; further research is in progress to assess the specificity and validity of this association.

There is currently no evidence supporting the possibility that patients with sleep related bruxism, in its
primary form, are at increased risk of neurological disorders; such a risk factor assessment needs
long- term study before any conclusion can be drawn.

Investigation of genetic associations to sleep related bruxism require large sample sizes, using valid
tools to assess the specificity of RMMA versus other oromandibular activities and to discriminate
gene candidates specific for bruxism from those related to its comorbidities such as stress or other
related triggers of RMMA.

Bibliography

Abe S, Yamaguchi T, Rompré PH, De Grandmont P, Chen YJ, Lavigne GJ. Tooth wear in young
subjects: a discriminator between sleep bruxers and controls? Int J Prosthodont 2009;22:342–50.

Carra MC, Macaluso GM, Rompre PH, et al. Clonidine has a paradoxical effect on cyclic arousal and
sleep bruxism during NREM sleep. Sleep 2010;33:1711–6.

Hublin C, Kaprio J, Partinen M, Koskenvuo M. Sleep bruxism based on self-report in a nationwide

twin cohort. J Sleep Res 1998;7:61–7.

Lavigne G, Guitard F, Rompre P, Montplaisir J. Variability in sleep bruxism activity over time. J
Sleep Res 2001;10:237–44.

Lavigne G, Manzini C, Huynh NT. Sleep bruxism. In: Kryger MH, Roth T, Dement WC, eds.
Principles and practice of sleep medicine, 5th ed. St. Louis: Elsevier Saunders, 2011:1129–39.
Lobbezoo F, Ahlberg J, Glaros AG, et al. Bruxism defined and graded: An international consensus. J
Oral Rehab 2013;40:2–4.

Ohayon M, Li K, Guilleminault C. Risk factors for sleep bruxism in the general population. Chest
2001;119:53–61.

Rompre PH, Daigle-Landry D, Guitard F, Montplaisir JY, Lavigne GJ. Identification of a sleep
bruxism subgroup with a higher risk of pain. J Dent Res 2007;86:837–42.

Vetrugno R, Provini F, Plazzi G, et al. Familial nocturnal facio-mandibular myoclonus mimicking

sleep bruxism. Neurology 2002;58:644–7.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Sleep Related Movement Disorders ›› Disorders ››

Sleep Related Rhythmic Movement Disorder

ICD-9-CM code: 327.59

ICD-10-CM code: G47.69

Alternate Names

Body rocking, head banging, head rolling, body rolling, jactatio capitis nocturna, jactatio corporis
nocturna, rhythmie du sommeil.

Diagnostic Criteria

Criteria A-D must be met

A. The patient exhibits repetitive, stereotyped, and rhythmic motor behaviors involving large muscle
groups.

B. The movements are predominantly sleep related, occurring near nap or bedtime, or when the
individual appears drowsy or asleep.

C. The behaviors result in a significant complaint as manifest by at least one of the following: 1

1. Interference with normal sleep.

2. Significant impairment in daytime function.

3. Self-inflicted bodily injury or likelihood of injury if preventive measures are not used.

D. The rhythmic movements are not better explained by another movement disorder or epilepsy.

Notes

1. When there are no clinical consequences of the rhythmic movements, the rhythmic movements are
simply noted but the term rhythmic movement disorder is not employed.
Essential Features

Sleep related rhythmic movement disorder (RMD) is characterized by repetitive, stereotyped, and
rhythmic motor behaviors (not tremors) that occur predominantly during drowsiness or sleep and
involve large muscle groups. The occurrence of significant clinical consequences differentiates RMD
from developmentally normal sleep related movements.

Typically seen in infants and children, but also in adults, RMD comprises several subtypes. Body
rocking may involve the entire body, with the individual on hands and knees, or it may be limited to
the torso, with the individual sitting. Head banging often occurs with the person prone, repeatedly
lifting the head or entire upper torso, and forcibly banging the head back down into the pillow or
mattress. Alternately, the individual may sit with the back of the head against the headboard or wall,
repeatedly banging the occiput. Combining head banging and body rocking, they may rock on hands
and knees, banging the vertex or frontal region of the head into the headboard or wall. Head rolling
consists of side-to-side head movements, usually with the child (or adult) in the supine position. Less
common rhythmic movement forms include body rolling, leg banging, or leg rolling. Rhythmic
humming or inarticulate sounds often accompany the body, head, or limb movements and may be
quite loud.

Episodes often occur near sleep onset, although they also may occur at any time during the night and
even during quiet wakeful activities, such as listening to music or traveling in vehicles. The
movement frequency can vary, but the rate is usually between 0.5 per second and two per second.
Duration of the individual movement clusters also varies but generally is less than 15 minutes.
Cessation of movements may occur following environmental disturbance or being spoken to. Children
who have sufficient language development to be asked about event recall in the morning are typically
amnestic for the episodes. Rarely, adults will report a volitional component.

Sleep related rhythmic movements are common in normal infants and children. Without evidence for
significant consequences, the movements alone should not be considered a disorder. Sleep related
rhythmic movements should be considered a disorder only if the behaviors significantly interfere with
normal sleep, cause significant impairment in daytime function, or result in self-inflicted bodily injury
(or would result in injury if preventive measures are not used).

Associated Features

The vast majority of infants and children with sleep related rhythmic movements are otherwise
developmentally and intellectually normal, as are most adolescents and adults.

Clinical and Pathophysiological Subtypes

Body Rocking: The whole body is rocked while on the hands and knees.

Head Banging: The head is forcibly moved, striking an object.

Head Rolling: The head is moved laterally, typically while in a supine position.

Other: Includes body rolling, leg rolling, and leg banging.

Combined: Involves two or more of the individual types.

Demographics
At nine months of age, 59% of all infants have been reported to exhibit one or more of the following
sleep related rhythmic movements: body rocking (43%), head banging (22%), or head rolling (24%).
At 18 months, the overall prevalence has been reported to decline to 33%, and by five years, to only
5%. Most pediatric studies have found no sex difference.

Over 50 cases of RMD have been reported in adolescents and adults, with a male preponderance
found in adults.

Predisposing and Precipitating Factors

The soothing effect of vestibular stimulation has been proposed as the initiating factor in infants and
toddlers. Environmental stress and lack of environmental stimulation have also been proposed as
factors. One study found higher anxiety scores in children with body rocking than in controls. Self-
stimulation has been suggested as a factor, particularly in intellectually disabled, autistic, and
emotionally disturbed children. Rhythmic movements have been postulated to be a calming technique
employed by children to combat insomnia.

Rhythmic movements have been reported in association with RLS, OSA, narcolepsy, RBD, and
ADHD. Rhythmic movements may be used as a conscious strategy to relieve the urge to move or the
uncomfortable sensations associated with RLS. OSA-associated RMD often improves with positive
airway pressure. Individuals with narcolepsy may initiate rhythmic movements to terminate episodes
of sleep paralysis.

In older children or adults, stereotypic movements may be associated with intellectual disability or
autism spectrum disorder. However, in most of these cases, the movements are not predominantly
sleep related, and an additional diagnosis of RMD is not indicated.

Familial Patterns

A familial pattern has been reported rarely, as has occurrence in identical twins.

Onset, Course, and Complications

The onset of sleep related rhythmic movements is typically in early childhood. Body rocking has a
mean age of onset of six months, head banging of nine months, and head rolling of ten months. The
condition may rarely present at an older age following central nervous system trauma. Sleep related
rhythmic movements commonly resolve in the second or third year of life. Persistence at five years of
age occurs in about 5% of children. Sleep related movements rarely continue into adolescence and
adulthood. Worsening or spontaneous onset in adults is very rare. In some adult cases the chief
concern is disturbance of the bed partner's sleep. Most adolescents and adults have one form of RMD,
although some have two or more.

Head banging is the most disturbing form of the problem. Typical cases in infants and toddlers pose
little risk of serious injury. Vigorous rhythmic movements can produce loud noises when the patient
hits the bed frame or when the bed bangs against the wall or floor. The noises can be very disturbing
to other family members. Parental concern is common, and psychosocial consequences in the older
individual can be distressing. It is important to discuss appropriate safety precautions with the
patient's caretakers. Under extraordinary circumstances, particularly in the developmentally disabled,
injury to soft tissues or bone has been reported.

Developmental Issues
Because age-related factors are a critical dimension for RMD, developmental issues are discussed
under Essential Features and other sections.

Pathology and Pathophysiology

In infants and young children, rhythmic movements have been hypothesized to promote motor
development by stimulation of the vestibular system. More recently, the role of inhibitory control on
the central motor pattern generator has been suggested as a physiologic mechanism to explain both
pediatric and adult forms of sleep related rhythmic movements.

Objective Findings

Polysomnographic scoring rules for RMD are defined in the AASM Manual for the Scoring of Sleep
and Associated Events. Video-polysomnographic studies have shown rhythmic movements to occur
most often in association with stages N1 and N2 sleep; 46% occur while falling asleep or during
NREM sleep; 30% during both NREM and REM sleep; and 24% only during REM sleep. The
exclusively REM-related rhythmic movements occur more frequently in adults. Although an epileptic
etiology has been reported in one individual, most EEG studies have shown normal activity between
episodes of rhythmic behavior.

Differential Diagnosis

RMD must be distinguished from other repetitive movements involving restricted small muscle
groups, such as sleep related bruxism, thumb sucking, and rhythmic sucking of a pacifier or the lips, as
well as other specifically defined rhythmic movements of sleep, such as hypnagogic foot tremor.

In adults, RMD can be misdiagnosed as RBD or be comorbid with RBD. Video polysomnography is
particularly helpful in these cases. Rhythmic movements may occur as a conscious or unconscious
strategy to relieve RLS symptoms. If the rhythmic movements are clearly in response to RLS
sensations, then a separate diagnosis of RMD is not needed. However, RMD may be diagnosed if
RMD criteria are met and RLS does not adequately explain the presence or extent of rhythmic
movements.

Children with autism spectrum disorder often exhibit repetitive behaviors, but these movements
typically occur during wakefulness and are not predominantly sleep related. Stereotypic movement
disorder is a Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnosis that is typically
seen with intellectual disability and is not predominantly sleep related. In children with autism
spectrum disorder or intellectual disability, an additional diagnosis of RMD should be made only if
the movements are predominantly sleep related. Akathisia is seen as a complication of neuroleptic
medication and is not predominantly sleep related.

Autoerotic or masturbatory behaviors may involve body rocking or other repetitive body movements,
but the primary focus is genital stimulation as is evident by direct genital contact. Rarely, RMD needs
to be differentiated from epilepsy, tic disorders, or involuntary movements associated with other
neurological conditions.

Unresolved Issues and Further Directions

There is controversy about the classification of hypnagogic foot tremor as a separate entity or as a
subtype of sleep related rhythmic movements. Many aspects of sleep related rhythmic movements
deserve further study, including the relationship of the typical form seen in otherwise normal infants
and young children to the rhythmic movements seen in children with intellectual disability and autism
spectrum disorder. The pathophysiology of persistent RMD is poorly understood, as is the association
with other sleep disorders in adults.

Bibliography

Dyken M, Lin-Dyken D, Yamada T. Diagnosing rhythmic movement disorder with video-

polysomnography. Pediatr Neurol 1997;16:37–41.

Kohyama J, Matsukura F, Kimura K, Tachibana N. Rhythmic movement disorder: polysomnographic

study and summary of reported cases. Brain Dev 2002;24:33–8.

Laberge L, Tremblay R, Vitaro F, Montplaisir J. Development of parasomnias from childhood to

early adolescence. Pediatrics 2000;106:67–74.

Manni R, Terzaghi M. Rhythmic movements during sleep: a physiological and pathological profile.
Neurol Sci 2005;26:s181–5.

Mayer G, Wilde-Frenz J, Kurella B. Sleep related rhythmic movement disorder revisited. J Sleep Res
2007;16:110–6.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Sleep Related Movement Disorders ›› Disorders ››

Benign Sleep Myoclonus of Infancy

ICD-9-CM code: 327.59

ICD-10-CM code: G47.69

Alternate Names

Benign neonatal sleep myoclonus.

Diagnostic Criteria

Criteria A-E must be met

A. Observation of repetitive myoclonic jerks that involve the limbs, trunk, or whole body.

B. The movements occur in early infancy, typically from birth to six months of age.

C. The movements occur only during sleep.

D. The movements stop abruptly and consistently when the infant is aroused.

E. The disorder is not better explained by another sleep disorder, medical or neurological disorder, or
medication use.

Essential Features
Benign sleep myoclonus of infancy (BSMI) is characterized by repetitive myoclonic jerks that occur
during sleep in neonates and infants. Although BSMI is benign and relatively rare, it is included in the
sleep related movement disorders section because it is commonly confused with epilepsy. However,
unlike the jerks of myoclonic seizures and myoclonic encephalopathy, the jerks of BSMI occur
exclusively during sleep. The jerks are often bilateral and massive, typically involving large muscle
groups. The movements can occur in the whole body or exclusively in the limbs, the trunk, or rarely,
the face.

Associated Features

Not applicable or known.

Clinical and Pathophysiological Subtypes

Most infants with BSMI are neurologically normal, born to mothers with no history of illicit drug use.
However, BSMI has been described in more than half of infants with neonatal opioid withdrawal
syndrome, suggesting a subtype with this specific etiology. It must be stressed, however, that some
cases of neonatal abstinence syndrome do not follow a benign clinical course. Whether such cases
should be included with those of BSMI is an unresolved matter.

Demographics

The prevalence is unknown. The incidence has been estimated at 3.7 per 10,000 live births. More than
200 cases have been described in the literature. Males are affected more than females by a ratio of
about 2:1. The typical age range is birth to six months of age.

Predisposing and Precipitating Factors

Predisposing factors have not been delineated. Rocking or repetitive noises may precipitate individual
episodes of BSMI.

Familial Patterns

Familial occurrence has been described.

Onset, Course, and Complications

Onset is usually noted between birth and one month of age in a neurologically normal infant. The
course is self-limited and benign. The disorder may be present for only a few days or may last for
several months. Maximum expression is typically between 15 and 35 days of age. BSMI resolves by
three months of age in 64% of affected infants, by six months in 95%, and by 12 months in 97% with
persistence rarely into the second year of life or later. There are no known complications. Long-term
follow-up in a limited number of children has shown normal psychomotor development and normal
cognitive function at five to 10 years of age. There is no evidence for an increased risk of seizures.

Developmental Issues

Because age-related factors are a critical dimension for BSMI, developmental issues are discussed
throughout this section.

Pathology and Pathophysiology

The presence of a generator in the cervical spinal cord that is not adequately inhibited due to
immature myelination of descending pathways has been hypothesized.

Objective Findings

Video-polysomnographic EEG and EMG monitoring has demonstrated paroxysmal muscle activity,
without ictal or interictal EEG abnormalities. BSMI occurs predominantly during quiet sleep but also
may be present during active sleep. The muscle jerks are usually seen in clusters of four or five jerks
per second, each jerk lasting 40 to 300 milliseconds. BSMI clusters typically repeat in irregular series
for one to 15 minutes, but, in some cases, the clusters may recur for up to 60 minutes or longer and be
mistaken for status epilepticus. One study showed 30% of the jerks to involve the whole body, 20% to
involve the abdominal or proximal muscles, and 50% to involve only the arms or the legs. The arms
are usually more involved than the legs. Activity is symmetrical in over 90% of cases but can be
lateralized. The myoclonus is not associated with arousals, awakenings, or sleep stage transitions.

Spontaneous or provoked awakening of the infant leads to prompt, abrupt, and consistent cessation of
the movements. Gentle rocking of the infant or the infant's crib has been shown to provoke the
myoclonus. This may be a useful maneuver during EEG monitoring when differentiation from
seizures is of concern. In contrast to jitteriness and other nonepileptic etiologies, BSMI will often
increase rather than be suppressed by gentle restraint. Neuroimaging studies are normal.

Differential Diagnosis

BSMI should be distinguished from myoclonic seizures; misdiagnosis may lead to unnecessary
diagnostic testing or medication use. The absence of episodes while awake in infants with BSMI is the
single most helpful clinical feature. In addition, BSMI will stop abruptly and consistently when the
infant is aroused. Neonatal seizures are often seen in the context of perinatal disorders such as
hypoxic-ischemic encephalopathy, infection, or metabolic abnormalities, whereas BSMI is typically
present in neurologically normal infants. Infantile spasms (West syndrome) are most often seen after
the first month of life but sometimes occur earlier. Infantile spasms are usually manifest by sudden
head flexion with arm extension and lower extremity flexion. They are usually associated with a
hypsarrhythmic EEG pattern. Pyridoxine-dependency seizures are responsive to treatment with
vitamin B6. In cases that are difficult to differentiate, an EEG obtained during sleep will show normal
patterns when BSMI is elicited by gentle rocking. Anticonvulsant medications are ineffective and
unnecessary in BSMI.

BSMI also should be distinguished from other disorders that occur during wakefulness,
includingmyoclonic encephalopathies, hyperekplexia (startle disease), drug
withdrawal, and jitteriness. Benign myoclonus of early infancy usually occurs after the third month of
life and only occurs during wakefulness.

PLMD can occur in infants but typically has a distinctly different duration and frequency. The muscle
activity is of longer duration (0.5 to 10 seconds) and recurs at a more regular and longer interval
(typically 20 to 40 seconds). PLMD can be associated with EEG arousals, whereas BSMI is not.
BSMI is more often seen in the arms than the legs, whereas PLMD predominantly occurs in the lower
limbs.

Phasic-REM muscle activity typically involves smaller muscle groups and can be linked to observable
eye movements. Sleep starts occur at the wake-sleep transition and typically are not
repetitive.Propriospinal myoclonus at sleep onset is a rare disorder that has not been reported in
children and is characterized by jerks involving the abdominal and truncal muscles at the transition
from wakefulness to sleep. Fragmentary myoclonus has been described in adults and is primarily a
nonspecific EMG finding with little or no visible movement.

Unresolved Issues and Further Directions

The prevalence, incidence, and pathophysiology of BSMI warrant further study.

Bibliography

Alfonso I, Papazian O, Aicardi J, Jeffries HE. A simple maneuver to provoke benign neonatal sleep
myoclonus. Pediatrics 1995;96:1161–3.

Di Capua M, Fusco L, Ricci S, Vigevano F. Benign neonatal sleep myoclonus: clinical features and
video-polygraphic recordings. Mov Disord 1993;8:191–4.

Held-Egli K, Rüegger C, Das-Kundu S, Schmitt B, Bucher HU. Benign neonatal sleep myoclonus in
newborn infants of opioid dependent mothers. Acta Paediatrica 2009;98:69–73.

Hrastovec A, Hostnik T, Neubauer D. Benign convulsions in newborns and infants: Occurrence,

clinical course and prognosis. Eur J Paediatr Neurol 2012;16:64–73.

Maurer VO, Rizzi M, Bianchetti MG, Ramelli GP. Benign neonatal sleep myoclonus: a review of the
literature. Pediatrics 2010;125:e919–24.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Sleep Related Movement Disorders ›› Disorders ››

Propriospinal Myoclonus at Sleep Onset

ICD-9-CM code: 327.59

ICD-10-CM code: G47.69

Alternate Names

Spinal myoclonus, plurisegmental myoclonus, intersegmental myoclonus, axial myoclonus.

Diagnostic Criteria

Criteria A-E must be met

A. The patient complains of sudden jerks, mainly of the abdomen, trunk, and neck.

B. The jerks appear during relaxed wakefulness and drowsiness, as the patient attempts to fall asleep.

C. The jerks disappear upon mental activation and with onset of a stable sleep stage.

D. The jerks result in difficulty initiating sleep.

E. The disorder is not better explained by another sleep disorder, medical or neurological disorder,
mental disorder, medication use, or substance use disorder.

Notes

1. Although there is no current definitive evidence that propriospinal myoclonus confined to sleep
onset is associated with significant structural lesions of the spinal cord, propriospinal myoclonus that
is persistent during the day has been linked to structural spinal cord pathology in 16% to 20% of
cases.

Essential Features

Propriospinal myoclonus at sleep onset (PSM) consists of sudden myoclonic jerks occurring in the
transition from wakefulness to sleep and, rarely, during intrasleep wakefulness and upon awakening in
the morning. The jerks arise mainly in the axial muscles and spread rostrally and caudally according
to propriospinal propagation. The jerks may be of variable intensity; they are isolated, recurring in
quasi-periodic fashion for variable durations, or may be repeated in brief clusters of a few movements,
separated by longer intervals. Jerks involve the abdominal and truncal muscles first and are then
propagated to proximal muscles of the limbs and the neck. The pattern of movement is usually flexor
but may be an extension of the trunk. Vocalization rarely occurs. The jerks are most often
spontaneous but, in some cases, can be evoked by external stimulations. The jerks appear to be related
to the recumbent position and a state of relaxed wakefulness, particularly when the patient tries to fall
asleep. Any mental activation makes the jerks disappear. The jerks eventually disappear at sleep onset
and remain absent throughout all stages of sleep, even though they sometimes reappear during
intrasleep wakefulness.

Associated Features

PSM often is associated with severe sleep-onset insomnia due to the inability of the patient to fall
asleep because of the recurrent disturbing muscular activity.

Clinical and Pathophysiological Subtypes

PSM may be considered a variant of the more generally described propriospinal myoclonus seen
during the daytime. In daytime PSM, myoclonic jerks involve the thoracoabdominal/paraspinal or
cervical muscles and spread caudally or rostrally to the other myotomes. The jerks are provoked or
worsened by the recumbent position and cannot be voluntarily suppressed. They are often preceded by
premonitory sensations, are stable over time, and respond unpredictably to drug treatment. The
frequent presleep worsening of daytime PSM (around 50% of the cases) suggests that patients with
PSM may have a milder or variant form of a single clinical and neurophysiologic entity.

Demographics

Epidemiologic data are lacking. PSM is probably a rare condition. A higher prevalence in men is
reported. The disorder affects adults and has not been reported in children.

Predisposing and Precipitating Factors

Not applicable or known.

Familial Patterns
Not applicable or known.

Onset, Course, and Complications

PSM arises in adulthood and is usually a chronic, unremitting condition. Patients may develop a fear
of falling asleep, anxiety, and depression. Intense myoclonic jerks may cause injury to the patient or
the bed partner.

Pathology and Pathophysiology

The pathophysiology of PSM is unknown. PSM is thought to originate from a focal spinal pattern
generator, set into motion by supraspinal dysfacilitatory influences typical of the state of relaxed
wakefulness and drowsiness. PSM is presumed to propagate up and down the spinal cord via slowly
conducting, long propriospinal (intersegmental) pathways. A focal spinal generator thus is able to
recruit muscles from multiple segments.

Objective Findings

Polysomnography demonstrates brief myoclonic EMG bursts recurring nonperiodically with alpha
activity present on the EEG and, in particular, when alpha activity spreads from the posterior to the
anterior brain regions. Epileptic EEG discharges are not observed in PSM. Jerks disappear either with
EEG desynchronization, due to mental activation, or with appearance of sleep spindles and K-
complexes. Jerks remain absent throughout sleep but may occasionally reappear upon awakening and
during intrasleep wakefulness. Polysomnography with extended EMG recording demonstrates that the
jerks arise first in spinal innervated muscles and then propagate to more caudal and rostral muscles
according to a propriospinal pattern of propagation. Detailed analysis of the jerks shows that the EMG
activity originates in muscles innervated by thoracic or cervical spinal segments (sternocleidomastoid,
paraspinalis, rectus abdominis) and then spreads to more rostrally and caudally innervated muscles at
a slow velocity (2 to 16 milliseconds; around 5 milliseconds on average). Back-averaging of the EEG
does not show any jerk-locked cortical activity. MRI of the brain is normal. In a recent review of
PSM, only one patient with exacerbation at sleep onset had a hypersignal at T10-T11 and a
nonspecific medullary cone lesion. The remaining patients had no signs on spinal cord MRI at sleep
onset.

MRI of the spine is usually normal but demonstrates a focal lesion in around 20% of the cases. The
causal relationship of PSM with these spinal lesions is unclear, although magnetic resonance diffusion
tensor imaging with fiber tracking may demonstrate spinal tract disorganization.

Differential Diagnosis

PSM shows features similar to those of the syndrome of intensified sleep starts. However, sleep starts
(hypnic jerks) usually appear during the transition between wakefulness and sleep and during light
NREM sleep, whereas PSM may sometimes be present during relaxed wakefulness. Unlike PSM,
sleep starts (hypnic jerks) sometimes affect only one or a few body segments; propriospinal
propagation is not present in neurophysiological studies of sleep starts. Phasic REM twitches, which
are a normal phenomenon during REM sleep, involve the distal muscles of the hands and face, often
without displacement of the body segment. Fragmentary myoclonus resembles physiological hypnic
myoclonus, but in an enhanced form, and persists throughout all stages of NREM and REM sleep.
Both physiological hypnic myoclonus and fragmentary myoclonus are EMG findings not associated
with overt muscular activity and do not involve muscles acting across large joints. Epileptic
myoclonus is not confined to relaxed wakefulness and may be associated with epileptic discharges on
the EEG.PLMS are longer in duration, involve mainly the lower limbs, and usually spare truncal and
abdominal muscles. PLMs may begin during presleep wakefulness but generally occur during NREM
sleep. Some patients with RLS may have prominent PLMs in wakefulness while sitting or lying down.
However, prominent leg discomfort is usually present in these patients. Occasionally PSM may be
present in RLS/PLMS patients in wake before sleep, but the EMG morphology is different. In
addition, when myoclonic jerks involving leg muscles appear, the PSM disappears. Psychogenic
myoclonus may simulate PSM but the muscle recruitment pattern, the spread velocity, and the
recording of cortical premovement activity observed before voluntary movements may be useful to
differentiate the two types of jerks.

Unresolved Issues and Further Directions

Future studies are needed to better define the distinctions between PSM and related conditions such as
sleep starts (hypnic jerks) and, in particular, the syndrome of intensified sleep starts. Also,
neuroimaging and possibly postmortem studies may detect the neural structures responsible for the
initiation of the myoclonic jerks.

Bibliography

Montagna P, Provini F, Plazzi G, Liguori R, Lugaresi E. Propriospinal myoclonus upon relaxation and
drowsiness: a cause of severe insomnia. Mov Disord 1997;12:66–72.

Montagna P, Provini F, Vetrugno R. Propriospinal myoclonus at sleep onset. Neurophysiologique

clinique 2006;36:351–5.

Roze E, Bounolleau P, Ducreux D, et al. Propriospinal myclonusmyoclonus revisited. Clinical,

neurophysiologic, and neuroradiologic findings. Neurology 2009;72:1301–9.

Tison F, Arne P, Dousset V, Paty J, Henry P. Propriospinal myoclonus induced by relaxation and
drowsiness. Rev Neurol (Paris) 1998;154:423–5.

Vetrugno R, Provini F, Meletti S, et al. Propriospinal myoclonus at the sleep-wake transition: a new
type of parasomnia. Sleep 2001;24:835–43.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Sleep Related Movement Disorders ›› Disorders ››

Sleep Related Movement Disorder Due to a Medical Disorder

ICD-9-CM code: 327.59

ICD-10-CM code: G47.69

Diagnostic Criteria

Criteria A-C must be met

A. The patient manifests sleep related movements that disturb sleep or its onset.
B. The movement disorder occurs as a consequence of a significant underlying medical or
neurological condition.

C. The symptoms are not better explained by another sleep related movement disorder, other
untreated sleep disorder, substance use, or mental disorder.

This diagnosis is intended for sleep related movement disorders due to an underlying medical or
neurologic condition that do not meet criteria for another specific movement disorder. Many
neurological conditions may be associated with movement abnormalities that are evident in wake and
sleep. In some cases, the nocturnal manifestations of the movement abnormalities may be apparent
before  establishment  of  a  firm  neurological  diagnosis.  Thus,  in  some  cases,  “sleep  related  movement  
disorder  due  to  a  medical  disorder”  is  a  temporary  diagnosis, given when a sleep diagnosis is required
before the underlying medical or neurological condition can be fully diagnosed. Once the presence of
a medical or neurological condition is clearly established, that becomes the sole diagnosis unless the
sleep complaint is the focus of independent clinical attention.

When a movement disorder that is listed elsewhere in the sleep related movement disorder section of
the International Classification of Sleep Disorders, 3rd Edition is caused or exacerbated by a medical
or neurological condition (e.g., restless legs syndrome), it is preferred that the more specific diagnosis
(e.g.,  RLS)  be  used  rather  than  “sleep  related  movement  due  to  a  medical  disorder,”  with  annotation  
of the relationship to the medical or neurological disorder.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Sleep Related Movement Disorders ›› Disorders ››

Sleep Related Movement Disorder Due to a Medication or Substance

ICD-9-CM code: 292.85 (drug-induced); 291.82 (alcohol-induced)

ICD-10-CM code: F11-F19 (see table in Appendix B for detailed coding instructions)

Diagnostic Criteria

Criteria A-C must be met

A. The patient manifests sleep related movements that disturb sleep or its onset.

B. The movement disorder occurs as a consequence of current medication or substance use or

withdrawal from a wake-promoting medication or substance.

C. The symptoms are not better explained by another sleep related movement disorder, other
untreated sleep disorder, or medical, neurological, or mental disorder.

This diagnosis is intended for sleep related movement disorders due to a medication or substance
(toxin or other bioactive substance) that do not meet criteria for another specific movement disorder.
Many substances may be associated with movement abnormalities that are evident in wake and sleep.
To the extent that the movement abnormality is an expected complication of the substance(s) involved
(e.g., tardive dyskinesia or akathisia associated with neuroleptic usage), this diagnosis is unnecessary
unless the sleep related aspects of the movement abnormality or its sequelae, are the focus of
independent clinical attention.

When a movement disorder that is listed elsewhere in the sleep related movement disorder section of
the International Classification of Sleep Disorders, 3rd Edition is caused or exacerbated by drugs or
substances (e.g., restless legs syndrome), it is preferred that the more specific diagnosis (e.g., RLS) be
used  rather  than  “Sleep  related  movement  disorder  due  to  a  medication  or  substance,”  with  annotation  
of the relationship to drug or substance.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Sleep Related Movement Disorders ›› Disorders ››

Sleep Related Movement Disorder, Unspecified

ICD-9-CM code: 327.59

ICD-10-CM code: G47.69

This diagnosis is assigned when patients have a sleep related movement disorder that cannot be
classified elsewhere or is suspected to be associated with an underlying psychiatric condition. In some
cases,  “sleep  related  movement  disorder,  unspecified”  is  a  temporary  diagnosis  prior  to  establishment  
of an underlying psychiatric condition that may explain the sleep related movement (e.g., movements
associated with posttraumatic stress disorder nightmares prior to firm establishment of the psychiatric
diagnosis). Once the psychiatric diagnosis is established, that becomes the sole diagnosis unless the
sleep complaint is the focus of independent clinical attention.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Sleep Related Movement Disorders ››

Isolated Symptoms and Normal Variants

Excessive Fragmentary Myoclonus
Hypnagogic Foot Tremor and Alternating Leg Muscle Activation
Sleep Starts (Hypnic Jerks)
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Sleep Related Movement Disorders ›› Isolated Symptoms and Normal Variants ››

Excessive Fragmentary Myoclonus

Excessive fragmentary myoclonus (EFM) is a largely incidental polysomnographic finding
on EMG, characterized by small movements of the corners of the mouth, fingers, or toes, or
by no visible movement at all. The finding is associated with no known clinical consequence.
Large limb movements across large joint spaces are not characteristic of EFM and, if present,
should exclude the diagnosis of EFM. Scoring of EFM is described in the most recent version
of the AASM Manual for the Scoring of Sleep and Associated Events. The condition is a
NREM phenomenon and the movements resemble the phasic twitches seen in normal REM
sleep except that they are more universally dispersed throughout a sleep epoch than phasic
REM twitches, which are generally clustered within small groups in a sleep epoch. Its
importance lies in that it is within the differential diagnosis of other sleep related movement
disorders.

Patients usually are not aware of the twitch-like movements. Patients may have other
coexistent sleep disorders, but EFM does not appear to contribute to the symptoms of these
sleep disorders.

EFM, a NREM phenomenon, is less common than phasic REM twitches, which occur in
REM sleep in normal individuals without sleep complaints. Most cases have been reported in
adults. EFM is predominantly found in males. A recent study found EFM in 100% of 62
patients with a variety of sleep disorders, bringing into question the specificity of EFM.

Numerous causes of chronic sleep fragmentation may be associated with EFM. The condition
has been described with obstructive sleep apnea and primary central sleep apnea, sleep
related hypoxemic/hypoventilation syndromes, narcolepsy, PLMD, and various causes of
insomnia. In apneic patients, the twitching intensifies during periods of increased hypoxemia.
One report has found excessive fragmentary myoclonus to be very common in children with
Niemann-Pick disease, type C. No specific precipitating factors have been reported. The
contribution of EFM to the symptomatology of any of these disorders is unknown.

The course is not well studied but appears to be benign and non-progressive. The disorder
may be the sole abnormality in some cases of excessive daytime sleepiness, but causality is
questionable. No other serious consequences of the disorder have been described when it
occurs in isolation.

In some cases, EFM is present in normal individuals. Its relatively benign course suggests
that it is not associated with a neurodegenerative process. In most reported cases, there have
been associated sleep abnormalities and sleep disruption, suggesting that EFM may be due to
disruptions of normal motor-control mechanisms during sleep. Whether there is a genetic or
other basis predisposing individuals to develop the condition is unknown. In any case, it
would appear to result from intensification of an otherwise normal motor phenomenon. The
predominant topographic distribution of EFM in distal and facial muscles suggests that
cortical motor centers participate in its generation.

EFM is detected as isolated, very brief (usually 75 to 150 milliseconds), asymmetrical,

asynchronous EMG potentials in various muscles of the face, trunk, arms, and legs. The
amplitude varies from approximately 50 to several hundred microvolts; the taller amplitudes
are often associated with visible movement of the fingers, toes, or corners of the mouth,
whereas the smaller ones may resemble fasciculation potentials and be without overt
movement. Large movements across large joint spaces preclude a diagnosis of EFM. Small
twitch-like movements may be observed on video recording. Episodes of these myoclonic
potentials typically last from 10 minutes to several hours. They often appear at sleep onset
and continue through the NREM sleep stages, including slow wave sleep. The presence of
EFM in REM is difficult to determine because it is superimposed on the normal phasic
clusters of physiological phasic REM twitches. EFM is electromyographically similar to the
latter. Occasionally, the EMG activity also persists during EEG periods of wakefulness
within the sleep period or is present in drowsiness prior to sleep onset. The EEG usually
shows no changes at the time of the movements, although high-amplitude EMG potentials
may be associated with a K complex or even with transient EEG arousal. There are no ocular
or autonomic accompaniments. It seems possible that, depending on the digitalization rates,
digital systems may record less fragmentary myoclonus than earlier paper records. No
laboratory tests other than polysomnography (optimally with multiple EMG leads) have been
reported to be helpful in assessing EFM.

EFM generally has a maximum burst duration of only 150 milliseconds and does not recur
periodically. It can be distinguished from PLMS because PLMS are characterized by a longer
burst duration (typically 0.5 to 10 seconds) and a long period between bursts (5-90 seconds).
EFM, which occurs in NREM, must also be differentiated from normal physiological phasic
REM twitches, which have a similar burst duration but are limited to the REM state and tend
to occur in clusters within an epoch, as opposed to EFM in which bursts tend not to cluster
within a particular epoch. Larger body movements across the large joints are not a feature of
excessive fragmentary myoclonus. The presence of such movements suggests other disorders.

Further investigation is necessary to determine whether EFM occurs as a consequence of

sleep disruption or whether it is an independent cause of sleep disruption and daytime
symptoms in its own right. It must also be determined whether there are any physiological
differences that distinguish fragmentary myoclonus seen in many normal individuals from
EFM. It is not known whether some additional pathophysiological element is required to
increase fragmentary myoclonus into an abnormal range. The current threshold for the
diagnosis of EFM should be further investigated because the scoring criteria lack specificity.
The apparent strong predominance in males also remains unexplained.

Bibliography

Broughton R. Pathological fragmentary myoclonus, intensified sleep starts and hypnagogic

foot tremor: three unusual sleep-related disorders. In: Koella WP, Schulz OF, Visser P,
eds. Sleep 1986. Stuttgart: Fischer-Verlag, 1988:240–3.
Broughton R, Tolentino MA. Fragmentary pathological myoclonus in NREM sleep.
Electroencephalogr Clin Neurophysiol 1984;57:303–9.
Broughton R, Tolentino MA, Krelina M. Excessive fragmentary myoclonus in NREM sleep:
a report of 38 cases. Electroencephalogr Clin Neurophysiol 1985;61:123–33.
Frauscher B, Kunz A, Brandauer E, Ulmer H, Poewe W, Hogl B. Fragmentary myoclonus in
sleep revisited: A polysomnographic study in 62 patients. Sleep Med 2011;12:410–5.
Goyal MK, Kumar G, Sivaraman M. Sahota P. Teaching neuroimages: excessive fragmentary
hypnic myoclonus. Neurology 2011;77:e59–e60.
Lins O, Castonguay M, Dunham W, Nevsimalova S, Broughton R. Excessive fragmentary
myoclonus: time of night and sleep stage distributions. Can J Neurol Sci 1993;20:142–6.
Vankova J, Stepanova I, Jech R, et al. Sleep disturbances and hypocretin deficiency in
Niemann-Pick disease type C. Sleep 2003;26:427–30.
Vetrugno R, Plazzi G, Provini F, Liguori R, Lugaresi E, Montagna P. Excessive fragmentary
hypnic myoclonus: clinical and neurophysiological findings. Sleep Med 2002;3:73–6.
Montagna P, Liguori R et al. Physiological hypnic myoclonus Electroencephalogr Clin
Neurophysiol 1988;70:172–6.
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Sleep Related Movement Disorders ›› Isolated Symptoms and Normal Variants ››
Hypnagogic Foot Tremor and Alternating Leg Muscle Activation
Hypnagogic foot tremor (HFT) is rhythmic movement of the feet or toes that occurs at the
transition between wake and sleep or during light NREM sleep (stages N1 and N2).
Alternating leg muscle activation (ALMA) consists of brief activation of the anterior tibialis
in one leg in alternation with similar activation in the other leg during sleep or arousals from
sleep. HFT may be a relatively common and normal finding. Affected individuals move the
feet or the toes rhythmically for seconds to minutes during drowsy wakefulness or lighter
stages of sleep. It can be pathologically exaggerated in some patients. ALMA is defined by a
polysomnographic pattern with unknown clinical manifestations, but frequency of muscle
activations, length of activations, and occurrence primarily with arousals suggest that ALMA
may be similar to HFT or represent an EMG manifestation of some episodes of HFT. The
original case series that described ALMA did not link it with movement of the lower
extremity, but a subsequent report did. HFT and ALMA are considered together because the
relationship between them remains to be clarified, and the similarity in a number of their
features suggests they may not be fully independent entities.

Associated features of HFT and ALMA are similar. Most cases of HFT have been reported in
persons with other sleep disorders, such as RLS or SRBDs. ALMA has been identified
mainly in patients with SRBD or PLMs. Seventy-five percent of patients with ALMA in the
original series used antidepressant medication. In that study, patients with ALMA
complained of sleepiness, insomnia, or restless of the legs, but only one reported patient had
more specific complaints of sudden nocturnal muscle contractions in his legs and a sensation
that his legs were vibrating. A separately reported case of a patient with ALMA documented
absence of any SRBD, PLMs, or use of antidepressant medication. This patient complained
of frequent and easily provoked awakenings, as well as excessive daytime sleepiness. The
ALMA and symptoms responded to treatment with pramipexole.

The single series in which HFT was studied found that it occurs in 7.5% of patients in whom
a polysomnogram was performed for other reasons. Affected individuals range in age from
14 to 72 years, with a majority in the middle-age range (40 to 65 years). Men and women are
equally affected. It is possible that the frequency of these movements may be increased in
individuals with disorders such as RLS or SRBD, but it can occur in individuals with
otherwise normal sleep. The prevalence of the condition in the general population and its
frequency in affected individuals remains uncertain. The initial series reporting ALMA found
that it occurs in 1.1% of unselected studies from a sleep disorder center. Patients with ALMA
were mostly male (11:5) and ranged in age from 12 to 70 years, with most aged 35 to 55
years (mean age 41 years). Therefore, the age ranges of both conditions are similar, with both
males and females affected. These distributions may be due to the incidental discovery of
both entities during routine sleep studies for other sleep complaints.

No predisposing factors are known for HFT. The use of antidepressant medication may
increase risk for ALMA.

No longitudinal studies have been performed for either entity. In some individuals, HFT is an
occasional finding, but others appear to manifest the rhythmic movements on many nights
and over a span of at least months. ALMA showed some tendency to persist between two
different recordings in the originally reported series. Because most individuals are unaware of
the presence of the HFT movements, and patients with ALMA may have no associated
complaint or awareness of the phenomenon, the evolution of HFT and ALMA may be
difficult to follow except in the sleep laboratory or with home monitoring. Although usually
an incidental and benign finding, HFT may cause sleep disruption and sleep-onset insomnia if
sufficiently prolonged or severe.

In HFT, the patient typically reports foot movements (directly experienced or observed by
others) that occur at the transition between wake and sleep or during light sleep. On occasion,
movement has not been observed but HFT is seen as an incidental finding on sleep study
conducted for other indications. Polysomnography demonstrates a pattern of brief, repeated
activation of the anterior tibialis in one leg. The minimum frequency is 0.3 Hz; the maximum
4.0 Hz. Multiple leg activations in a single leg occur in a train of at least four movements.
EMG recordings of the foot or leg muscles or video recordings of movement may show trains
of recurrent 1-Hz to 2-Hz EMG potentials or movements. Typical associated EMG bursts are
300 to 700 milliseconds in duration, and the typical duration of trains is 10 to 15 seconds,
although longer bursts and trains have been reported. In morbid conditions, trains may persist
much longer. Events are recorded at the transition into sleep and during stages N1 and N2
sleep. Distribution over the night has not been fully investigated. Persistent HFT has been
found in about half of the individuals who have had multiple studies. Alternation between
legs has not been described, but its potential occurrence is suggested in two published studies
of HFT.

In ALMA, polysomnography demonstrates a pattern of brief, repeated activation of the

anterior tibialis in one leg alternating with similar activation in the other leg. At a minimum, a
single leg muscle activation in one leg is followed sequentially by a similar single activation
in the other leg, reactivation in the original leg, and then reactivation in the alternate leg, with
some continued alternation beyond this minimal sequence in most instances. The minimum
frequency of alternating EMG bursts is 0.5 Hz, and the maximum frequency is 3.0 Hz. The
patient may report foot movements (directly experienced or observed by others) that occur at
the transition between wake and sleep or during light sleep. As noted above, there is
frequently no observation of movement reported but alternating leg muscle activation is
recorded as an incidental finding on polysomnography.

ALMA can be demonstrated by polysomnography if the surface EMG is recorded

independently from both right and left anterior tibialis muscles. A sequence of ALMA may
begin with one to several lengthy activations (one to two seconds) in one or both legs. Some
patients show unilateral activity at times. ALMA usually closely precedes or follows an
arousal or awakening and gradually diminishes as sleep returns. However, ALMA can also
emerge without arousals from any sleep stage. Proclivity for any specific portion of the
nocturnal sleep cycle has not been identified. Leg muscle activations during REM sleep, in
comparison to NREM sleep, are often briefer and somewhat less regular. Sequences of
ALMA sometimes recur at intervals similar to those of PLMs. Extensor forearm EMG study
may suggest alternating muscle activity in the upper extremities, though it is less prominent
than activation in the legs. ALMA shows some night-to-night consistency. Repeat studies are
likely to show persistent ALMA. The number of sequences recorded, on average, and the
timing of ALMA with respect to arousals tends to remain constant.

The specific polysomnographic criteria for HFT during sleep and ALMA are defined in the
latest version of the AASM Manual for the Scoring of Sleep and Associated Events.

Presentation of HFT or ALMA with other concurrent sleep disorders is common.

Because of the similar frequency, duration, and body part involvement of the movements,
HFT and ALMA may represent variants of the same disorder. Insufficient scientific evidence
has accumulated to make this a certainty. Thus, these entities are listed sequentially but
separately.

Of note, some have questioned whether HFT and ALMA might represent a variant of
rhythmic movement disorder in which movements are confined to the legs and an older
population is affected.

HFT and ALMA should be distinguished from other sleep-onset

movements: PLMD (especially the polyclonic form), PSM, and sleep related RMD.
Movement disorders that should be distinguished from HFT and ALMA include dyskinetic
movements of the foot, such as painful legs and moving toes; tremors or rhythmic
movements of other cause (Parkinson disease, clonus); and neuroleptic-induced akathisia.
None of these conditions involves regular alternation between sides, as seen in ALMA, or an
association with the use of antidepressant medication.

Whether HFT should be distinguished from ALMA is not known. Potential differences based
on existing reports include the presence of clear movement in HFT as opposed to some
uncertainty whether ALMA must involve movement. ALMA, in contrast to HFT, alternates
between sides, occurs in any sleep stage, can occur without arousal, and is associated with the
use of antidepressants.

High-frequency leg movements (HFLM) also have been described as a repetitive anterior
tibialis, polysomnographic activation phenomenon, possibly showing some association with
RLS, and with potential overlap with HFT and ALMA. In contrast to HFT, however, HFLM
occur in all sleep stages, and are mostly unilateral rather than bilateral. In contrast to ALMA,
HFLM are mostly unilateral rather than alternating, and often show sequences that last longer
than those reported for ALMA. The reported HFLM may be more common than ALMA, and
the possibility exists that ALMA represents a subtype of HFLM in which leg alternation
occurs.

The degree to which these movements are quasi-voluntary remains to be determined because
some are suppressible. Whether HFT and ALMA are merely alternate forms of the same
underlying motor mechanism is also unclear. As reports of these movements have arisen from
reviews of sleep center records, nothing is known about their manifestation in the general
population. The associations noted may be due to biased sampling caused by a skewing of the
population toward those with sleep disorders, especially respiratory disorders. The degree to
which HFT and ALMA have clinical significance remains uncertain.

Bibliography
Berry RB. A woman with rhythmic foot movements. J Clin Sleep Med 2007;3:749–51.
Broughton R. Pathological fragmentary myoclonus, intensified sleep starts and hypnagogic
foot tremor: three unusual sleep-related disorders. In: Koella WP, Schulz OF, Visser P,
eds. Sleep 1986. Stuttgart: Fischer-Verlag, 1988:240–3.
Chervin RD, Consens FB, Kutluay E. Alternating leg muscle activation during sleep and
arousals: a new sleep-related motor phenomenon? Mov Disord 2003;18:551–9.
Consentino FI, Iero I, Lanuzza B, Tripodi M, Ferri R. The neurophysiology of the alternating
leg muscle activation (ALMA) during sleep: Study of one patient before and after
treatment with pramipexole. Sleep Med 2006;7:63–71.
Cunningham SL, Winkelman JW, Dorsey CM, et al. An electromyographic marker for
neuroleptic-induced akathisia: preliminary measures of sensitivity and specificity. Clin
Neuropharmacol 1996;19:321–32.
Wichniak A, Tracik F, Geisler P, Ebersbach G, Morrissey SP, Zulley J. Rhythmic feet
movements while falling asleep. Mov Disord 2001;16:1164–70.
Yang C, Winkelman JW, White DP. The effects of antidepressants on leg movements
(abstract) Sleep 2004;27(Abst Suppl):A311–2.
Yang C, Winkelman JW. Clinical and polysomnographic characteristics of high frequency
leg movements. J Clin Sleep Med 2010;6:431–8.
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Sleep Related Movement Disorders ›› Isolated Symptoms and Normal Variants ››

Sleep Starts (Hypnic Jerks)

Sleep starts, also known as hypnic jerks, are sudden, brief, simultaneous contractions of the
body or one or more body segments occurring at sleep onset. Sleep starts (or hypnic jerks)
usually consist of a single contraction that often affects the body asymmetrically. The jerks
may be either spontaneous or induced by stimuli. The motor activity is often associated with
a sensory component, which may be somesthetic, often an impression of falling or less
commonly pain or tingling; auditory, such as banging, snapping or crackling noises; or visual,
including flashing lights, hypnagogic dreams, or hallucinations. A sharp cry may occur. The
patient may not recall a jerk that was noted by a bed partner if the sleep start does not cause
awakening. Multiple jerks occasionally occur in succession, usually early in the sleep period.
When sleep starts or hypnic jerks are frequent, intense, or repetitive, they may lead to sleep-
onset insomnia.

Purely sensory sleep starts are subjective, localized, sensory impressions that occur at sleep
onset  and  are  not  associated  with  motor  activity.  The  term  “Intensified  sleep  starts”  has  been  
applied to both the motor and purely sensory forms when a complaint of difficulty falling
asleep as a result of the starts is present.

A prevalence of 60% to 70% has been reported, but with a highly sporadic occurrence. Sleep
starts affect all ages and both sexes.

Excessive caffeine or other stimulant intake, prior intense physical work or exercise, sleep
deprivation, and emotional stress can increase the frequency and severity of sleep starts.

Sleep starts are an essentially universal component of the sleep-onset process, although they
are often not recalled. Hypnic jerks may occur at any age, as a subjective complaint;
however, they are usually encountered in adulthood. The course is usually benign. Intensified
sleep starts may lead to avoidance/delay of sleep, a fear of falling asleep and chronic anxiety.
As a result, acute and chronic sleep deprivation may occur. Sleep-onset insomnia may result
either from repeated awakenings induced by the starts or from anxiety about falling asleep.
Injury, such as bruising a foot against a bedstead or kicking a sleeping companion, may
occasionally occur.
The physiological mechanisms underlying sleep starts are uncertain. No pathologic finding
has been described except for a single case of auditory sleep starts associated with a
brainstem lesion. Hypnic jerks are hypothetically caused by sudden descending volleys
originating in the brainstem reticular formation activated by the system instability at the
transition between wake and sleep. However, the similarity between sleep starts and the
startle response has led some to postulate that abnormalities of sensory processing are
primary, with secondary motor manifestations involving the reticulospinal tract. Sleep starts
are a prominent symptom in hereditary hyperekplexia, some cases of which are caused by
mutations in the glycine receptor. It has also been postulated that sleep starts are a response to
hypnagogic imagery.

Polysomnographic monitoring shows that hypnic jerks occur during transitions from
wakefulness to sleep, mainly at the beginning of the sleep episode. Superficial EMG
recordings of the involved muscles show brief (generally 75-millisecond to 250-millisecond)
high-amplitude potentials, either singly or in succession. The EEG typically shows
drowsiness or stage N1 sleep patterns, sometimes with a negative-vertex sharp wave
occurring at the time of the jerk. Autonomic activation, including tachycardia, tachypnea or
irregular breathing, and sudomotor activation may follow an intense jerk. After the jerk, a
brief arousal or a return to sustained wakefulness may occur. Physical and neurological
examinations and routine laboratory tests are otherwise normal. Although polysomnography
is not necessary for diagnosis in most individuals, it may be indicated in occasional cases
with complaints of insomnia and frequent movements.

Hypnic jerks must be differentiated from a number of physiological or pathologic movements

that occur at sleep onset or during sleep. Physiological partial hypnic myoclonus consists of
small, isolated contractions of a muscle or part thereof, occurring sporadically in distal
muscles and resembling fasciculation potentials. The contractions are particularly evident
during stage N1 and REM sleep.

Fragmentary myoclonus consists of profuse, brief, small-amplitude muscle twitches that

occur in an asynchronous, symmetrical, and bilateral manner, especially in distal muscles.
Fragmentary myoclonus occurs at sleep onset as well as within all sleep stages. Contrary to
the massive jerks of the sleep starts or hypnic jerks, the small muscle twitches of
physiological partial hypnic myoclonus and of fragmentary myoclonus often represent only
an EMG finding and are not associated with overt movements at the joints. Normal body
movements are complex, with body postural shifts usually at the transition between one sleep
stage and another. Benign sleep myoclonus of infancy consists of myoclonic jerks at the
elbow, fingers, toes, and face during sleep in infants.

PSM is characterized by jerks, usually spontaneous, but sometimes also evoked, arising first
in spinal innervated axial muscles of the trunk, neck, or abdomen and then propagated at slow
velocity to more rostral and caudal muscles. PSM is present during relaxed wakefulness,
characterized by diffuse EEG alpha activity, and disappears with sleep onset or mental
activation. PSM is usually a chronic condition associated with sleep-onset insomnia.

Excessive startling and hypnic jerks may occur as part of the hyperekplexia syndrome, in
which generalized myoclonus is readily elicited by stimuli during either wakefulness or sleep.
The major form of this condition is also characterized by stiffness and falls. Brief epileptic
myoclonus can be differentiated by coexistent EEG discharge, the presence of other features
of epileptic seizures, and the occurrence of the myoclonus in both wakefulness and during
sleep rather than only at sleep onset.

The muscle contractions of PLMD are much longer in duration, involve mainly the feet and
lower legs, show periodicity, and occur within sleep. RLS consists of slower and repetitive
semivoluntary movements at sleep onset that are associated with deep, unpleasant, and
sometimes unbearable sensations, which are temporarily relieved by getting up and
exercising.

Bibliography

Broughton R. Pathological fragmentary myoclonus, intensified sleep starts and hypnagogic

foot tremor: three unusual sleep-related disorders. In: Koella WP, Schulz OF, Visser P,
eds. Sleep 1986. Stuttgart: Fisher Verlag; 1988:240–3.
Kennard MA, Schwartzman AE, Millar TP. Sleep, consciousness, and the alpha
electroencephalographic rhythm. Arch Neurol Psychiatry 1958;79:328–35.
Montagna P, Liguori R, Zucconi M, et al. Physiological hypnic myoclonus.
Electroencephalgr Clin Neurophysiol 1988;70:172–6.
Oswald I. Sudden bodily jerks on falling asleep. Brain 1959;82:92–103.
Salih F, Klingebiel R, Zschenderlein R, et al. Acoustic sleep starts with sleep-onset insomnia
related to a brainstem lesion. Neurology 2008;70:1935–7.
Sander HW, Geisse H, Quinto C, Sachdeo R, Chokroverty S. Sensory sleep starts. J Neurol
Neurosurg Psychiatry 1998;64:690.
Vetrugno R, Montagna P. Sleep-to-wake transition movement disorders. Sleep Med
2011;12:S11–6.
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Sumário
Other Sleep Disorder ................................................................................................................ 254
Appendix A: Sleep Related Medical and Neurological Disorders ........................................... 256
Disorders............................................................................................................................... 256
Fatal Familial Insomnia .................................................................................................... 256
Sleep Related Epilepsy ..................................................................................................... 259
Sleep Related Headaches ................................................................................................. 264
Sleep Related Laryngospasm ........................................................................................... 269
Sleep Related Gastroesophageal Reflux .......................................................................... 272
Sleep Related Myocardial Ischemia ................................................................................. 277
Other  Sleep  Disorder
ICD-9-CM code: 327.8

ICD-10-CM code: G47.8

Sleep disorders that cannot be classified elsewhere in the International Classification of

Sleep Disorders, 3rd Edition are listed here. This may be due to the fact that the sleep
disorder overlaps more than one category or, more often, when insufficient data have been
collected to firmly establish another diagnosis. It is also possible that new sleep disorders
that do not fall within any of the current major categories will be discovered during the
lifetime of the International Classification of Sleep Disorders, 3rd Edition. When a specific
diagnosis cannot yet be determined but the presenting problem clearly falls into a specific
category (e.g., a circadian rhythm sleep-wake  disorder),  the  “unspecified”  diagnosis  within  
that category (e.g., circadian rhythm sleep-wake disorder, unspecified) is preferred.

The International Classification of Sleep Disorders, 2nd Edition included a specific diagnosis
of environmental sleep disorder within this section. This diagnosis is infrequently employed
in the clinical setting and significant controversy exists regarding whether environmentally
induced sleep disturbance represents a clinical disorder per se. The condition is typically
characterized by complaints of sleep initiation and/or maintenance that are the direct result
of an environmental factor. Associated daytime symptoms such as sleepiness, fatigue, or
cognitive or emotional disturbance may be present. The environmental disturbance may be
a physical stimulus such as noise (e.g., vehicular traffic, aircraft, bed partner snoring), light,
temperature, movement (e.g., bed partner movement disorder or parasomnia), an
emotional stimulus such as environmental danger (e.g., combat setting or disaster area), or
an environmental requirement (such as caring for an infant or elderly family member).
Hospitalization is often cited as a precipitant of environmental sleep disturbance although
many additional factors (e.g., anxiety or pain) may also contribute to sleep disturbance in
this setting. If the clinician determines that an environmental factor is the primary cause of
a sleep disturbance, a diagnosis of Other Sleep Disorder may be employed.

It is the physical aspects of the environment, rather than their psychological meaning, which
account for the sleep complaint. Unlike insomnia disorder, the sleep disturbance is
dependent on the presence of the environmental factor. In the absence of the stimulus,
sleep is normal.

The prevalence of environmentally induced sleep disturbances is not known although, as

noted, the diagnosis is not commonly reported in sleep centers. Some individuals may be
more susceptible to environmental disturbances but little is known about specific
characteristics that might predispose to this condition.

Although environmental factors may play a contributing role in some cases of chronic
insomnia disorder, multiple other factors account for that condition, which is typically
evident even in the absence of the offending environmental stimulus. Distinguishing an
insomnia disorder from an environmentally induced sleep disturbance may pose a challenge
in certain clinical encounters and providers must use clinical judgment in establishing the
diagnosis.

In behavioral insomnia of childhood, the child may require certain environmental

circumstances in order to sleep (e.g., a pacifier, music, lights, television, or a parent). It is the
absence of these circumstances that results in sleep initiation or maintenance problems. In
such cases, a diagnosis of chronic insomnia disorder (behavioral insomnia of childhood –
sleep-onset association type) is indicated.

Bibliography

Basner M, Griefahn B, Berg MV. Aircraft noise effects on sleep: mechanisms, mitigation and
research needs. Noise Health 2010;12:95–109.
Hume KI, Brink M, Basner M. Effects of environmental noise on sleep. Noise Health.
2012;14:297–302.
Thiessen G, Lapointe A. Effect of continuous traffic noise on percentage of deep sleep,
waking, and sleep latency. J Acoust Soc Amer 1983;73:225–9.
Yilmaz M, Sayin Y, Gurler H. Sleep quality of hospitalized patients in surgical units. Nurs
Forum 2012;47:183–92.
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Appendix A: Sleep Related Medical and Neurological Disorders
The disorders presented in this section may have a unique presentation during the sleep
period or may present exclusively in association with sleep. Some of these disorders (e.g.,
sleep related epilepsy and sleep related headache) may be encountered during evaluation
for other sleep disorders. In addition, some of these disorders are in the differential
diagnosis of other sleep-wake disorders. Sleep related epilepsy must be considered in the
differential diagnosis of certain movement disorders and parasomnias. Sleep related
headaches may be a clue to the presence of sleep apnea. Sleep related gastroesophageal
reflux may either be a precipitant of a sleep apnea episode or be triggered by sleep apnea
with aspiration pneumonia as its most serious consequence. Sleep related myocardial
ischemia is an important consideration because myocardial infarction has a predilection for
the early morning hours during the latter phase of the sleep period and may be precipitated
by episodes of sleep apnea. It is important to be aware of sleep related laryngospasm as a
potentially life-threatening consequence of neurodegenerative diseases such as multiple
system atrophy. Fatal familial insomnia, although rare, presents with severe insomnia and
has a well-understood neuropathology.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Appendix A: Sleep Related Medical and Neurological Disorders ››

Disorders
Fatal Familial Insomnia
Sleep Related Epilepsy
Sleep Related Headaches
Sleep Related Laryngospasm
Sleep Related Gastroesophageal Reflux
Sleep Related Myocardial Ischemia
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Appendix A: Sleep Related Medical and Neurological Disorders ›› Disorders ››

Fatal Familial Insomnia

Alternate Names

Fatal progressive insomnia with dysautonomia, familial thalamic degeneration of the

anterior and dorsomedial thalamic nuclei, thalamic insomnia.

Essential Features

Fatal familial insomnia is a very rare, progressive disorder characterized by initial difficulties
in falling asleep and maintaining sleep, spontaneous lapses from quiet wakefulness into a
sleep state with enacted dreams (oneiric stupor), and loss of slow wave sleep features. In
later stages of the disease, it may not be possible to identify any distinct sleep stages.

Although loss of temporal and spatial orientation develops, cognitive function is retained
until impaired alertness makes testing impossible. The disorder progresses to unarousable
coma, and finally, death.
Associated Features

Bronchopulmonary and other infections may also be present. There is a loss of the circadian
rhythmicity of endocrine rhythms. Autonomic hyperactivity (e.g., pyrexia, salivation,
hyperhidrosis, tachycardia, tachypnea, and dyspnea) is present. The disorder includes
somatomotor disturbances, with dysarthria, dysphagia, tremor, spontaneous and reflex
myoclonus, dystonic posturing, ataxia, and a positive Babinski sign. Hallucinations may be
present.

Clinical and Pathophysiological Subtypes

None.

Demographics

Age of onset is usually in adulthood, between 36 and 62 years of age. The disorder is rare.
There are no sex differences.

Predisposing and Precipitating Factors

Not known or applicable.

Familial Patterns

Fatal familial insomnia (FFI) is transmitted according to an autosomal dominant pattern.

Patients harbor a missense GAC to AAC mutation at codon 178 of the prion protein
gene PRNP located on chromosome 20, cosegregating with the methionine polymorphism
at codon 129 of the same gene on the mutated allele (D178N 129M). The clinical syndrome
varies by the M129V genotype. Patients who are methionine homozygous at the 129 codon
are younger and display a shorter disease course than do patients who are methionine-
valine heterozygous at codon 129.

Onset, Course, and Complications

The disorder is always fatal, usually within eight to 72 months. The course is one of
relentless worsening of symptoms. Patients may die after a short (less than 12 months) or
long (12 to 72 months) disease course. The younger age at disease onset and, consequently,
a lower rate of comorbidity, may explain the generally more prolonged disease course in FFI
in comparison to other prion diseases. Complications include infections (in particular of the
lungs and bladder) that develop during the course of the disease, especially in the late
stages, and represent the usual cause of death. Other frequent complications include skin
ulcers when patients become bedridden and aspiration of food due to the severe dysphagia;
the latter may require nasogastric or gastrostomy feeding.

Pathology and Pathophysiology

Severe bilateral loss of neurons, with reactive gliosis of the anterior and dorsomedial
thalamic nuclei and severe neuronal loss and reactive astrogliosis in the inferior olives, are
found. Spongiform changes in cortical layers in cases with a prolonged course have been
described. Deposition of proteinase K-resistant prion protein type 2 in the grey matter but
not the white matter occurs in both familial and sporadic fatal insomnia. Both familial and
sporadic fatal insomnia have been transmitted to transgenic animals by intracerebral
inoculum of brain homogenates.

Objective Findings

In early stages of FFI, periods of relaxed wakefulness alternate with episodes of

electroencephalographic (EEG) desynchronization, rapid eye movement (REM) bursts, loss
of antigravity muscle tone, and irregular myoclonic and tremor-like limb-muscle activities
associated with vivid dreams (oneiric stupor). Sleep spindles and features of slow wave
sleep are absent or progressively lost throughout the course of the illness. In the final stages
of the disorder, the EEG becomes unreactive and progressively flattens until death occurs; it
may display periodic spike discharges.

Positron emission tomography (PET) with (18F)-2-fluorodeoxy-D-glucose shows thalamic

hypometabolism. Magnetic resonance spectroscopy with multisequences can detect prion-
induced gliosis in vivo. Circadian rhythms of body temperature, systemic blood pressure,
and heart and respiratory rate and endocrine rhythms of growth hormone, prolactin,
luteinizing hormone, follicle-stimulating hormone, and adrenocorticotropic hormone may
be lost. Serum catecholamine and cortisol values are elevated, with low or undetectable
adrenocorticotropic hormone levels. Pathologic examination demonstrates degeneration of
the anterior and dorsomedial thalamic nuclei and atrophy of the inferior olivary nucleus.
Deposition of proteinase K-resistant prion protein type 2 is found in the brain.

Differential Diagnosis

This disorder must be differentiated from REM sleep behavior disorder (RBD), which is not
associated with autonomic hyperactivity or a familial pattern. The differential diagnosis
includes dementia, familial Creutzfeldt-Jakob disease with the 178 codon mutation in the
PRNP cosegregating with the valine polymorphism at codon 129 on the mutated
allele, Morvan fibrillary chorea, delirium tremens, or even schizophrenia. A sporadic form of
fatal insomnia has also been reported.

Unresolved Issues and Further Directions

Not applicable or known.

Bibliography

Cortelli P, Perani D, Parchi P, et al. Cerebral metabolism in fatal familial insomnia: relation to
duration, neuropathology, and distribution of protease-resistant prion protein.
Neurology 1997;49:126–33.
Goldfarb L, Petersen R, Tabaton M, et al. Fatal familial insomnia and familial Creutzfeldt-
Jakob disease: disease phenotype determined by a DNA polymorphism. Science
1992;258:806–8.
Haik S, Galanaud D, Linguraru MG, et al. In vivo detection of thalamic gliosis. A
pathoradiologic demonstration in familial fatal insomnia. Arch Neurol 2008;65:545–9.
Krasnianski A, Bartl M, Sanchez Juan PJ, et al. Fatal familial insomnia: clinical features and
early identification. Ann Neurol 2008;63:658–61.
Lugaresi E, Medori R, Montagna P, et al. Fatal familial insomnia and dysautonomia with
selective degeneration of thalamic nuclei. N Engl J Med 1986;315:997–1003.
Monari L, Chen S, Brown P, et al. Fatal familial insomnia and familial Creutzfeldt-Jakob
disease: different prion proteins determined by a DNA polymorphism. Proc Natl Acad Sci
U S A 1994;91:2839–42.
Montagna P, Cortelli P, Gambetti P, Lugaresi E. Fatal familial insomnia: sleep,
neuroendocrine and vegetative alterations. Adv Neuroimmunol 1995;5:13–21.
Montagna P, Gambetti P, Cortelli P, Lugaresi E. Familial and sporadic fatal insomnia. Lancet
Neurol 2003;2:167–76.
Sforza E, Montagna P, Tinuper P, et al. Sleep-wake cycle abnormalities in fatal familial
insomnia. Evidence of the role of the thalamus in sleep regulation. Electroencephalogr
Clin Neurophysiol 1995;94:398–405.
Telling G, Parchi P, DeArmond S, et al. Evidence for the conformation of the pathologic
isoform of the prion protein enciphering and propagating prion diversity. Science
1996;274:2079–82.
Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.
Appendix A: Sleep Related Medical and Neurological Disorders ›› Disorders ››

Sleep Related Epilepsy

Alternate Names

Sleep epilepsy, nocturnal seizure, sleep related seizures.

Essential Features

A seizure is a paroxysmal event resulting from a sudden excessive discharge of the neurons
of the cerebral cortex, whereas epilepsy is a condition of recurrent unprovoked seizures.
Sleep facilitates epileptic activity and seizures. The characteristics of specific subtypes of
sleep related epilepsy are discussed in the Clinical and Pathologic Subtypes section below.

Associated Features

The different types of nocturnal frontal lobe epilepsy (NFLE) may cause severe sleep
disruption, affecting both macrostructure and microstructure of sleep, resulting in poor
sleep quality, daytime fatigue, and sleepiness in some patients. The movements also may be
so severe that injuries can occur. From one third to one half of patients with sleep related
epilepsy also have occasional attacks during the day, although these are not necessarily of
the same type as those occurring at night.
Neurocognitive impairment is typically diagnosed in almost all cases of continuous spike
waves during NREM sleep (CSWS). Motor impairment in the form of a unilateral deficit is
sometimes seen as an associated feature of CSWS.

Clinical and Pathophysiological Subtypes

Clinical and EEG criteria are used to define a variety of sleep related epilepsy subtypes.

Several types of epileptic syndromes have a marked tendency to manifest only or

predominantly during sleep, or after arousal from sleep. These include NFLE, benign
epilepsy of childhood with centrotemporal spikes (BECT), benign epilepsy with occipital
paroxysms (BEOP), early-onset or late-onset childhood occipital epilepsy, juvenile myoclonic
epilepsy (JME), generalized tonic-clonic seizures on awakening, certain forms of temporal
lobe epilepsy, tonic seizure (as a component of Lennox-Gastaut syndrome), Landau-Kleffner
syndrome, and continuous spike waves during NREM sleep (CSWS).

NFLE may present in three distinct ways: (1) nocturnal paroxysmal arousal, (2) nocturnal
paroxysmal dystonia, or (3) episodic nocturnal wanderings.

BECT can present with focal clonic facial twitching that is often preceded by perioral
numbness. These seizures are more often seen in drowsiness and sleep than wakefulness.
The clinical course is often benign with disappearance of the seizures in adulthood.

BEOP is characterized by focal seizures marked by deviation of the eyes and vomiting. Sleep
is the main precipitating factor, with most of the seizures occurring soon after sleep onset or
in the early hours of the morning. There is frequent evolution to secondary generalized
attacks. The clinical evolution of the early-onset type is benign, whereas in the late-onset
type with visual seizures, the prognosis is uncertain.

JME is characterized by massive bilaterally synchronous myoclonic jerks, which are most
frequently noted on awakening.

CSWS (formerly known as electrical status epilepticus of sleep [ESES]) is characterized by

continuous and diffuse slow spike-and-wave complexes persisting through NREM sleep (at
least 85% of the duration), as well as neuropsychological and motor impairment. Despite
the continuous presence of epileptic spike-wave activity on EEG in sleep, there may be no
associated visible sleep related movement. However, clinical epileptic seizures are
sometimes seen in the daytime.

Demographics

There is no significant sex predominance.

Predisposing and Precipitating Factors

Stress, sleep deprivation, irregularities of the sleep-wake rhythm, other sleep pathologies,
and the use of stimulant drugs or other drugs that modify sleep architecture may predispose
an individual to having seizures. Perinatal or prenatal problems, congenital hemiparesis, and
prior encephalopathy may be considered antecedents of the syndrome of CSWS. OSA may
exacerbate sleep related seizures and complicate their treatment.

Familial Patterns

The idiopathic generalized epilepsies form the largest category of epilepsies that appear to
be heritable but show no clear mendelian mode of transmission. Juvenile myoclonic
epilepsy and idiopathic generalized epilepsy with adolescent onset appear to be genetically
heterogeneous. Among the partial epilepsies, BECT shows a familial pattern. A form of
autosomal dominant NFLE with 70% to 80% penetrance has been reported in many
countries, and a genetic heterogeneity also has been reported. Genetic factors have not
been established in CSWS and seem to play a minor role. Familial antecedents of epilepsy
(including febrile convulsions) have been found in 15% of cases.

Onset, Course, and Complications

Idiopathic generalized epilepsies and partial epilepsy may start at any age. The onset of
benign epilepsies of childhood with centrotemporal or occipital spikes is between 4 and 12
years of age. The onset of NFLE is generally from age 10 to 16 years, mostly before the age
of 20 years. The average age of recognition of CSWS is between 4 and 14 years, but the
appearance of the first seizure is early, typically between two months and 12 years of age.
Most patients with recurrent sleep related epilepsy continue to have seizures restricted to
sleep. In some cases, they may have seizures during both sleep and wakefulness. For focal
epilepsies (excluding BECT and the early-onset type of BEOP), the prognosis is less favorable
compared to generalized epilepsies. At least 35% of the focal seizures confined to sleep are
resistant to antiepileptic drugs.

Definitive data on the natural history of NFLE are not available, although a high prevalence
of parasomnias has been documented in NFLE patients.

CSWS resolves in many cases within three years after onset, and in almost all cases by the
mid-teen years. Despite normalization of the EEG and elimination of seizures,
neuropsychological impairment may persist. Interictal paroxysmal activity may induce
prolonged cognitive and motor impairment. Hyperkinesias, aggressiveness, and psychotic
states may appear. OSA may exacerbate sleep related seizures and complicate their
treatment.

Pathology and Pathophysiology

In idiopathic generalized epilepsy, genetic factors are contributory. Pathogenic markers,

associated neurologic deficits, or characteristic brain imaging findings have not been
identified. However, microdysgenesis has been described in some forms of idiopathic
generalized epilepsy. EEG recordings with sphenoidal or zygomatic leads may show epileptic
activity over the mesiotemporal regions in partial complex seizures.

Video-polysomnographic (vPSG) analysis confirms that the motor pattern of NFLE resembles
that noted in orbital and mesial frontal seizures. Nocturnal frontal lobe seizures involve a
large neuronal network, and some of their clinical expressions are possible consequences of
disinhibition of innate motor patterns produced by the central pattern generator. Recent
reports derived from stereo-EEG studies seem to show that in some cases, the seizures (in
particular nocturnal wanderings) may arise from temporal or insular regions (rather than
frontal regions) with a secondary spread to the cingulate regions. They may sometimes
mimic parasomnias.

Secondary bilateral synchrony is the mechanism generating CSWS. This hypothesis is

supported by EEG, intracranial recordings, EEG with coherence computer-assisted analysis,
and metabolic (positron emission tomography [PET] and single-photon emission computed
tomography [SPECT]) studies. CSWS associated with Landau-Kleffner syndrome (an acquired
epileptic aphasia) is probably secondary to an alteration of function over the temporal area.

Objective Findings

Patients with suspected sleep related epilepsy often need to be evaluated in the sleep
laboratory with video and full-head EEG monitoring in order to obtain the correct diagnosis.
The characteristic interictal epileptiform activity in idiopathic generalized epilepsies usually
increases during NREM sleep, whereas it decreases during REM sleep and wakefulness.
Interictal epileptiform activity may be associated with phasic arousals.

In partial epilepsies, the interictal epileptiform activity occurs in a localized distribution with
an increase in spike frequency in stages N2 and N3 compared to REM sleep. Most of the
seizures are activated in stage N2 sleep. Monitoring may also detect transient autonomic
alterations in cardiac rhythm, blood pressure, and respiration during seizures. If epilepsy is
suspected, a standard daytime 16-channel to 20-channel EEG (with partial or total sleep
deprivation the night before, as indicated) should be performed. Ambulatory 24-hour EEG
recordings may be useful to detect distribution of interictal epileptiform activity during the
sleep-wake cycle.

Nocturnal vPSG is the gold standard test for NFLE. Most of the seizures appear during NREM
sleep, with preponderance in NREM stages N1 and N2 (greater than 60%). Rarely do they
emerge from REM sleep. In some cases, particularly in paroxysmal arousals, the motor
attacks may show a periodicity (every 20 seconds to two minutes). Due to the fact that the
discharges originate deep in the frontal lobe and are not visible using scalp EEG, the EEG
during the attacks is uninformative in almost half of the cases. In a few cases, recording
using intracranial or depth electrodes confirms the paroxysms during or preceding the
motor components. The interictal sleep EEG is generally normal, but in 30% to 40% of
subjects, focal epileptic abnormalities are seen, predominantly in the anterior regions. The
video recording of the different types of attacks in NFLE permits categorization of the
seizures and characterization of the main features.

During CSWS, diffuse spike waves at two to 2.5 Hz occur in bursts, with or without clinical
manifestations. The discharges are continuous and occupy from 85% to 100% of NREM
sleep stages. Abnormalities arise as soon as the patients fall asleep and disappear abruptly
on awakening. REM sleep is typically preserved, and the frequency of spike-wave discharges
significantly decreases but the frontal predominance of the infrequent bursts may become
more prominent. In general, EEG patterns during REM sleep are similar to those in the
awake records. The sleep structure is normal, but the presence of almost continuous spike-
wave discharges makes the recognition of normal NREM sleep EEG elements (such as K
complexes, spindles, or vertex sharp transients) difficult.

Differential Diagnosis

NFLE may be mistaken for a disorder of arousal from NREM such as sleepwalking,
confusional arousal,or sleep terror. Ictal and interictal EEGs are often normal because the
focus for the epileptic discharge may be deep in the brain. Disorders of arousal show a
different pattern of episodes in that they occur out of stage N3 sleep, are not stereotyped,
often have a sustained autonomic component, and are frequently seen during the first part
of the night. Partial arousal disorders tend to disappear or decrease in frequency after
adolescence. VPSG is often useful. Sleep talking, bruxism, and rhythmic movement
disorders can be differentiated from nocturnal seizures by history and vPSG
recordings.Benign neonatal sleep myoclonus may be confused with clonic or myoclonic
seizures during sleep. In the elderly (older than 60 years), the main differentiation
from RBD is by vPSG recording. PLMD, sleep starts, and propriospinal myoclonus at sleep
onset do not show EEG epileptiform activity and belong in the category of movement
disorders during sleep. Jerks, dyskinesias, or arousal on resumption of breathing in patients
with OSA also enter into the differential diagnosis of sleep related epilepsy. Rare cases of
anoxic syncope with some clonic jerks at the end of a prolonged (longer than two
minutes)obstructive event have been described.

Unresolved Issues and Further Directions

Not applicable or known.

Bibliography

Bazil C, Malow B, Sammaritano M. Sleep and epilepsy: the clinical spectrum. Amsterdam:
Elsevier Science; 2002.
Dinner D, Luders H. Relationship of epilepsy and sleep: an overview. In: Dinner D, Luders H,
eds. Epilepsy and sleep: physiological and clinical relationships. San Diego: Academic Press,
2001:2–18.

Malow B. Paroxysmal events in sleep. J Clin Neurophysiol 2002;19:522–34.

Nobili L, Cossu M, Mai R. Sleep-related hyperkinetic seizures of temporal lobe origin.

Neurology 2004;62:482–5.

Oldani A, Zucconi M, Ferini-Strambi L, Bizzozero D, Smirne S. Autosomal dominant nocturnal

frontal lobe epilepsy: electroclinical picture. Epilepsia 1996;37:964–76.

Provini F, Plazzi G, Tinuper P, Vandi S, Lugaresi E, Montagna P. Nocturnal frontal lobe

epilepsy. A clinical and polygraphic overview of 100 consecutive cases. Brain
1999;122:1017–31.

Scheffer I, Bhatia K, Lopes-Cendes I, et al. Autosomal dominant nocturnal frontal lobe

epilepsy. A distinctive clinical disorder. Brain 1995;118:61–73.

Shouse M, Martins da Silva A, Sammaritano M. Circadian rhythm, sleep, and epilepsy. J Clin
Neurophysiol 1996;13:32–50.

Tassinari C, Dravet C, Roger J. CSWS: Encephalography related to electrical status epilepticus

during slow sleep. Electroencephalogr Clin Neurophysiol 1977;43:529–30.

Tinuper P, Provini F, Bisulli F, et al. Movements disorders in sleep: guideline for

differentiating epileptic from non-epileptic motor phenomena arising from sleep. Sleep Med
Rev 2007;11:255–67.

Zucconi M. Sleep-related epilepsy. Handb Clin Neurol 2011;99:1109–37.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Appendix A: Sleep Related Medical and Neurological Disorders ›› Disorders ››

Sleep Related Headaches

Alternate Names

Various (see Clinical and Pathologic Subtypes).

Essential Features

Sleep related headaches are a group of unilateral or bilateral cephalalgias of varying severity
and duration that occur during sleep or upon awakening from sleep. It is a heterogenous
group of different headache entities with the common feature of occurrence during sleep or
upon awakening. The characteristics of specific subtypes of sleep related headache are
discussed in the Clinical and Pathologic Subtypes section below.

Associated Features

Individual features associated with specific sleep related headache types are discussed in
the following section.

Clinical and Pathophysiological Subtypes

Most sleep related headaches are daytime headache conditions that also may occur during
sleep. These include the primary headaches such as migraine, cluster headache, and chronic
paroxysmal hemicrania. There are other primary headaches that occur solely with sleep; for
example, hypnic headaches. In addition, secondary headaches related to medical,
neurological, psychiatric, and sleep disorders can cause sleep related headaches.

Migraines are common recurrent headaches of moderate to severe intensity that last
between four and 72 hours. Pain is typically unilateral and pulsating, aggravated by routine
physical activity and associated with nausea, and/or photophobia or phonophobia. They
occur during the day or during sleep; approximately 50% of migraine attacks occur between
4:00 a.m. and 9:00 a.m. Migraine headaches do not have a fixed association with a
particular sleep stage. The patient may awaken with a migraine out of REM sleep, or the
headaches  may  occur  in  relationship  to  stage  N3  sleep.  A  “classic  migraine”  headache  is  
preceded by an aura (if the patient is awake), which usually lasts four to 60 minutes and
typically consists of homonymous visual field defects and scintillating scotomas. In some
patients, the aura may continue or even begin during the headache phase. In contrast,
“common  migraine”  does  not  start  with  an  aura.  Other  signs  of  neurological  dysfunction
may include unilateral paresthesias, weakness, and aphasia. Features of brainstem
involvement may include vertigo, tinnitus, dysarthria, decreased hearing, diplopia, ataxia,
bilateral paresthesias, and impaired level of consciousness. A familial syndrome with
hemiplegia is well described. The hemiplegia is ipsilateral or contralateral to the side of the
headache.

Cluster headaches are severe, unilateral, periorbital or temporal headaches that start
quickly and peak within 10 to 15 minutes. They have a relatively shorter duration, usually
lasting 15 minutes to three hours (mean, 60 minutes). The headaches occur daily during
cluster periods—usually one to three attacks per day over a period of one to two months.
Most patients have one cluster period per year, though this can vary from patient to
patient. The headaches tend to occur at the same hour each day, with 75% of cluster
episodes reported to occur between 9:00 p.m. and 10:00 a.m. One or more cranial
autonomic features (e.g., ipsilateral conjunctival injection, lacrimation, nasal congestion,
rhinorrhea, forehead and facial sweating, miosis, ptosis, or eyelid edema) invariably
accompany attacks of cluster headaches. A strong predilection for attacks to occur during
sleep is well recognized, and these attacks are strongly related to REM sleep.

Chronic paroxysmal hemicrania closely resembles cluster headaches and consists of severe
unilateral orbital, supraorbital, or temporal pain associated with one or more cranial
autonomic features. However, the attacks are usually of shorter duration (lasting two to 30
minutes) and occur more frequently, most often at a frequency of more than five per day. In
contrast to cluster headaches, chronic paroxysmal hemicrania is exquisitely sensitive to
indomethacin. Attacks are also strongly associated with REM sleep.

Hypnic headaches are an uncommon type of headache that awakens the patient from sleep
with a generalized or lateralized headache that lasts at least 15 minutes (range, one to 180
minutes) with a frequency of at least 15 times per month. Onset is typically after the age of
50, although similar headaches are described rarely in younger individuals, including
children. In comparison to cluster headaches, hypnic headaches are less severe, often
bilateral and not associated with cranial autonomic features. Isolated nausea, photophobia,
or phonophobia may be present. They may occur one to three times during the night, with
many patients reporting that the headaches occur at the same time of the night. The
headaches tend to occur during REM sleep. However, they also have been reported to occur
during stage N3 sleep. A positive therapeutic response to lithium, indomethacin, and
caffeine has been reported in many patients.

Other medical (e.g., hypertension), neurologic (e.g., brain tumors, arteriovenous

malformations, cerebral venous thrombosis and trauma), psychiatric (e.g., depression), and
sleep disorders (e.g., snoring and OSA) also can give rise to headaches that may occur during
sleep or upon awakening from sleep. Patients with increased intracranial pressure (due, for
example, to brain tumor, hematoma, arteriovenous malformations, or cerebral venous
thrombosis) may complain of headache in the morning or headache that starts after
recumbence and improves after the patient is up for 30 to 60 minutes. Nausea, vomiting,
signs of focal neurological deficits, and papilledema may be present. The headache may
worsen with bending down or sneezing or with other activities that may cause further
increase in intracranial pressure.

Sleep related headaches can disrupt nocturnal sleep, although the exact prevalence of this
complication is unknown.

Demographics

The exact prevalence of sleep related headaches is not known. One study from a headache
clinic suggested that 17% of all headache patients complain of nocturnal or early morning
headaches, and roughly half of these were related to an identifiable sleep disorder.
However, many primary headache disorders can occur during sleep as well. Sleep related
migraines have been reported to increase in frequency with age.
Predisposing and Precipitating Factors

Migraine headaches have several predisposing factors that vary from patient to patient.
However, stress, relaxation, changes in weather and barometric pressure, changes in sleep
pattern, hypoglycemia, and specific foods (e.g., chocolate, Chinese food, alcohol) have been
known to trigger migraine headaches. Alcohol can also predispose an individual to having
cluster headache and chronic paroxysmal hemicrania. OSA and attendant hypoxia have
been reported to be a trigger for cluster headache. However, sleep apnea may also
predispose a person to having other types of headache and may independently lead to
morning headaches. Change of sleep pattern and insomnia can predispose the patient to
developing headaches.

Familial Patterns

There is a positive family history for migraine in up to 80% of patients with this disorder.
Familial hemiplegic migraine is inherited in an autosomal dominant pattern with a variety of
genetic mutations identified on chromosomes 1 and 19. Cluster headache does not have as
strong of a familial disposition as migraine headache, but first-degree relatives of probands
with cluster headache are seven times more likely to develop cluster headaches, and the
concordance rates in monozygotic twins is 100%. The inheritance patterns of hypnic
headache are not known.

Onset, Course, and Complications

Migraine headache usually starts in the second or third decade of life, with a slightly earlier
onset in men than in women. The mean age of onset of cluster headache is 28 years.
Chronic paroxysmal hemicrania has a wide range of onset, from childhood to old age. Most
patients with hypnic headache are elderly, with the age of onset from 40 to 82 years. Brain
tumors are more prevalent in the elderly, most occurring from the fifth decade to late life.

Most sleep related headaches are benign and tend to decrease in frequency with age. There
may be spontaneous remissions that last from months to years. Pregnancy has a variable
effect on these headaches. Migraines tend to decrease with age and, in women, may stop
after menopause. Cluster headaches, as the name suggests, occur in clusters and are
accompanied by pain-free intervals lasting months to a couple of years. They also tend to
decrease with age. Hypnic headache occurs infrequently. Headaches in patients with brain
tumors are related to an increase in intracranial pressure and tend to improve with
treatment of the primary lesion and a decrease in intracranial pressure. Some patients with
OSA report improvement of the headache after treatment of the apnea.

The sleep related headaches can cause sleep disruption and insomnia with decreased sleep
efficiency. Cluster headaches occurring regularly in sleep can also lead to transient
situational insomnia that may resolve after the remission or the treatment of the cluster
headache. Depending on the etiology of the sleep related headache (e.g., brain tumor),
other complications may occur.

Developmental Issues

Not applicable or known.

Pathology and Pathophysiology

Several anatomic areas are common to the physiology of both sleep and headaches; these
include the brainstem and diencephalon, specifically the ventrolateral periaqueductal gray
and the posterior hypothalamus. From a neurochemical perspective, adenosine, melatonin,
and orexin also are involved in both the regulation of sleep and the evolution of headaches.
Dysfunction of REM sleep and arousal mechanisms are common to many headache
disorders. Data from transgenic models indicate that disruption of sleep occurs in two forms
of familial migraine. However, current mechanistic explanations of the relationship between
sleep and headache are speculative.

Objective Findings

Polysomnographic aspects of sleep related headaches need to be better defined. Migraine

headache is reported to occur in association with REM sleep or stage N3 sleep. An excess of
stage N3 sleep also has been reported in patients with migraine. However, large controlled
studies are not available. Fifty percent of cluster headaches and a majority of chronic
paroxysmal hemicrania are associated with REM sleep. OSA and hypoxia during sleep may
aggravate other sleep related headaches or may be an independent cause of headache.
Hypnic headache occurs during sleep, with recent reports of headache during REM sleep
and uncommonly during stage N3 sleep. Thus, the majority of sleep related headaches seem
to have some relationship with REM sleep, but there are no defining or pathognomonic
polysomnographic aspects of individual headache syndromes.

Neuroimaging studies (computed tomography or magnetic resonance imaging head scans or

angiography) may be performed to rule out structural, vascular, or infectious disease
processes that may cause headaches.

Differential Diagnosis

Sleep related headaches are a heterogeneous group of different headache entities with a
common expression of occurrence during sleep. They need to be differentiated from other
headache conditions that are not sleep related. These include tension-type
headaches and headaches associated with paranasal sinus inflammation, tooth infection,
ear infection, febrile illness, benign intracranial hypertension, intracranial hypotension,
vasculitis, head trauma, alcohol intoxication, orbruxism. Although the initial presentation
may be one of headache, detailed history and examination will identify one of these
contributing conditions.
Tension-type headaches are bilateral headaches with a feeling of a band-like tightening
sensation around the head. In patients older than 50 years, giant cell arteritis may present
with lateralized or bilateral headache with tenderness over the temporal area, accompanied
by polymyalgia rheumatica and visual problems, including loss of vision.

Exploding head syndrome is in the differential diagnosis of headache because it may occur in
association with the sleep period. Patients report hearing an explosion in the head which is
unaccompanied by pain.

Unresolved Issues and Further Directions

Not applicable or known.

Bibliography

Brennan KC, Charles A. Sleep and headache. Semin Neurol 2009;29:406–17.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Appendix A: Sleep Related Medical and Neurological Disorders ›› Disorders ››

Sleep Related Laryngospasm

Alternate Names

Stridor, laryngeal dysfunction.

Essential Features

Sleep related laryngospasm is a disorder in which tracheal muscle dysfunction or

paratracheal soft-tissue swelling causes stridor or interruption of airflow, with associated
awakening from sleep. Patients may have total or near-total cessation of airflow while
asleep, and suddenly arouse. This brief respiratory blockage (lasting an estimated five to 45
seconds) is often followed by a period of stridor that lasts several minutes and gradually
evolves to normal breathing. Episodes are associated with panic and fear of suffocation;
cyanosis may be observed. In some cases of laryngospasm during sleep, patients may have
frequent laryngeal stridor (which may be difficult for families to differentiate from snoring),
associated tachypnea, and intermittent upper airway blockage.

Associated Features

Fear and panic upon awakening often accompany events and may, at times, lead to
insomnia. In some cases of sleep related laryngospasm, gastroesophageal reflux has been
identified. Less commonly, sleep related laryngospasm has been related to underlying OSA.
Clinical and Pathophysiological Subtypes

Sleep related laryngospasm may be associated with multisystem atrophy, a

neurodegenerative disorder.

Demographics

Prevalence data do not exist. Typical age of onset is unknown, although when the condition
is due to multisystem atrophy, affected individuals are typically older.

Predisposing and Precipitating Factors

Sleep related laryngospasm may be associated with gastroesophageal reflux. Laryngeal

dysfunction seen in other disorders, including laryngeal tumors and multisystem atrophy,
may cause sleep related stridor and intermittent laryngospasm. Precipitating factors include
use of hypnotic or other central nervous system depressant medications. Tonic-clonic
seizures may be a rare cause of sleep related laryngospasm in children.

Familial Patterns

Not applicable or known.

Onset, Course, and Complications

Laryngospasm is a common cause of death in multiple system atrophy.

Developmental Issues

Not known.

Pathology and Pathophysiology

When not associated with neurodegenerative disorders of known pathology (e.g.,

multisystem atrophy), the pathology and pathophysiology is uncertain. Sleep related
laryngospasm can be related to tracheal muscle dysfunction, postnasal drip, or reflux of
gastroesophageal contents causing irritation of soft tissue in the upper airway. Laryngeal
tumors and multisystem atrophy can cause laryngeal dysfunction, resulting in sleep related
laryngospasm.

Objective Findings

Sleep related laryngospasm may be observed on PSG with accompanying audio recording. It
is seen in all stages of sleep but is most severe in REM sleep. Laryngospasm can appear to be
similar to snoring on the polysomnographic snoring channel, but the audio recording will
confirm the high-pitched inspiratory sound as laryngospasm. OSA has also been detected in
some cases. Patients or family members may mistake laryngospasm for snoring or sleep
apnea. PSG evaluation may be necessary to distinguish these disorders. In children, PSG or
sleep-deprived EEG may demonstrate seizures that manifest solely as nocturnal
laryngospasm. Endoscopy of the upper airway is necessary to examine vocal cord function
and to exclude upper airway pathology. Gastroesophageal studies may reveal evidence of
reflux.

Differential Diagnosis

OSA may cause awakenings, with choking or gasping for air, excessive daytime somnolence,
restlessness, or insomnia. If OSA is a diagnostic consideration, sleep study is
warranted. Sleep related gastroesophageal reflux may result in coughing or choking
episodes during the night without true laryngospasm. However, these episodes usually are
described  in  the  setting  of  chest  pain  or  “heartburn.” One possible cause of sleep related
laryngospasm may be occult acid reflux into the upper airway, causing irritation or
swelling. Sleep terrors may be associated with sensations of impaired breathing or choking,
rapid heartbeat, and agitation. However, sleep terrors are most common in children, and
most patients do not focus on upper airway choking. Panic disorder can involve abrupt
awakening with respiratory distress, signs of sympathetic activity, and fear of dying.
However, most patients also have daytime episodes of panic. Nocturnal asthma can result in
sleep related coughing, wheezing, or shortness of breath. REM sleep behavior disorder
(RBD) may be in the differential diagnosis of laryngospasm, but is generally recognizable by
polysomnographic features of RBD and a history of dream enactment.

Unresolved Issues and Further Directions

Published reports generally have been limited to case series. Clarification of the relationship
between laryngospasm, sleep related breathing disorders, and gastroesophageal reflux is
needed.

Bibliography

Aloe F, Thorpy M. Sleep-related laryngospasm. Arq Neuropsiquiatr 1995;53:46–52.

Campbell A, Pierce R. Brief upper airway dysfunction. Respir Med 1994;88:125–9.

Guilleminault C, Eldridge F, Phillips J, Dement W. Two occult causes of insomnia and their
therapeutic problems. Arch Gen Psychiatry 1976;33:1241–5.

Iriarte J, Urrestarazu E, Alegre M, Goni C, Viteri C, Artieda J. Sleep-related laryngospasm: A

video polysomnographic recording. Epileptic Disord 2006;8:70–2.

Kavey N, Whyte J, Blitzer A, Gidro-Frank S. Sleep-related laryngeal obstruction presenting as

snoring or sleep apnea. Laryngoscope 1989;99:851–4.

Roland MM, Baran AS, Richert AC. Sleep related laryngospasm caused by gastroesophageal
reflux. Sleep Med 2008;9:451–3.
Thorpy M, Aloe F. Choking during sleep. Sleep Res 1989;18:314.

Thorpy M, Aloe F. Sleep related laryngospasm. Sleep Res 1989;18:313.

Thurnheer R, Henz S, Knoblauch A. Sleep-related laryngospasm. Eur Respir J 1997;10:2084–

6.

Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Appendix A: Sleep Related Medical and Neurological Disorders ›› Disorders ››

Sleep Related Gastroesophageal Reflux

Alternate Names

Gastroesophageal reflux, nocturnal gastroesophageal reflux, supine gastroesophageal

reflux, nocturnal heartburn, reflux esophagitis, esophagitis, heartburn.

Essential Features

Sleep related gastroesophageal reflux (GER) occurs when gastric contents cross the lower
esophageal sphincter (LES) into the esophagus and, potentially, into more proximal sites
during sleep time. Symptoms are usually noticed during arousals or awakenings. Symptoms
may include heartburn, substernal burning, chest discomfort, a sour or bitter taste in the
mouth, regurgitation, water brash, coughing, choking, or unexplained excessive daytime
sleepiness, even in the absence of typical reflux symptoms. Sleep related GER is associated
with sleep onset and sleep maintenance insomnia, early morning awakenings, sleep
disturbances, arousals, unrefreshing sleep, daytime functioning difficulties, and excessive
daytime sleepiness. GER is a potential asthma trigger, predisposes to aspiration, and is a
cause of cough. GER commonly coexists in patients with chronic obstructive pulmonary
disease, cystic fibrosis, idiopathic pulmonary fibrosis, and bronchiolitis obliterans syndrome
in lung transplant recipients. Sleep related GER is associated with sleep related
laryngospasm and is prevalent in patients with OSA.

Associated Features

Associated features of this disorder include dysphagia, odynophagia, laryngopharyngitis,

laryngospasm, epigastric burning, chronic cough, wheezing, or chest pain that may mimic
angina. Other associated features of sleep related GER include sleep onset and sleep
maintenance insomnia, excessive daytime sleepiness, daytime fatigue, poor daytime
functioning, and reduced work productivity. Patients with sleep related GER also have a
decrease in health-related quality of life and more health care visits.

Clinical and Pathophysiological Subtypes

Not applicable or known.

Demographics

GER symptoms affect up to 44% of adults in the United States monthly, and 20% weekly.
Among patients with weekly heartburn, 79% report GER symptoms during sleep time, 57%
report waking up during sleep, and 40% report that GER during sleep time affected their
ability to work the next day. Among the 15,315 subjects of the Sleep Heart Health Study,
25% reported heartburn during sleep. In a review of 5 large population studies, the mean
prevalence of heartburn during sleep time was 54% ± 22% (standard deviation). In patients
with OSA, sleep related reflux symptoms are present in up to 62%. Furthermore, in a trial
examining consecutive asthmatics, 50% had awakenings from sleep because of heartburn.
Thus, GER symptoms during sleep time are common. There is no known predilection for
men or women. However, men are more likely than women to develop Barrett esophagus.

Predisposing and Precipitating Factors

Predisposing factors for sleep related GER include eating within two hours of bedtime, an
elevated body mass index, erosive esophagitis, and hiatal hernia. Predictors of heartburn
during sleep include consumption of alcohol or carbonated beverages, or the use of
benzodiazepines before sleep time. Other predictors of heartburn during sleep include the
presence of insomnia, hypertension, asthma, snoring, or daytime sleepiness. The
relationship between GER and sleep disturbance is bidirectional. Sleep related GER is
associated with short sleep duration, difficulty falling asleep, arousals, poor sleep quality,
and early morning awakenings. Conversely, sleep deprivation induces a state of esophageal
hyperalgesia to acid, thus worsening heartburn symptoms.

Familial Patterns

Not applicable or known.

Onset, Course, and Complications

GER occurs in all age groups, including infants and children. Sleep disruption occurs more
frequently in infants and children with GER, compared to infants and children without GER.
The incidence of GER increases with age. GER may be more severe and is associated with
more complications in older adults.

GER is a chronic disease which is rarely cured, but it may be controlled with lifestyle, and
medical and/or surgical therapies. In patients with sleep related GER, medical GER therapy
improved sleep disturbances and daytime functioning in placebo-controlled trials. Long-
term outcome data are currently lacking. If GER is left untreated, the disease generally
progresses and can be associated with many complications. Esophageal complications
include esophagitis, esophageal erosions, esophageal stricture, ulcerations with stricture,
and Barrett esophagus, which is thought to be a precursor to esophageal adenocarcinoma.
Reflux can also result in dysphagia, weight loss, and upper gastrointestinal bleeding. Sleep
related GER is more commonly associated with erosive esophagitis, stricture, Barrett
esophagitis, and esophageal adenocarcinoma, compared to diurnal reflux. Extraesophageal
complications include pulmonary complications previously discussed in the Essential
Features section.

Pathology and Pathophysiology

Two major pathophysiologic mechanisms cause individual reflux episodes. Transient LES
relaxations (LES relaxations occurring without esophageal contractions) account for 53% to
74% of GER episodes. Transient LES relaxations decrease the LES pressure to the gastric
pressure gradient, facilitating the retrograde flow of gastric contents. An LES pressure of 10
mm Hg or less is the second mechanism by which intra-abdominal pressure overcomes the
LES pressure, resulting in the retrograde flow of gastric contents into the esophagus.

Pathophysiology of sleep related GER is similar to diurnal GER (i.e., transient LES relaxations
and a low LES pressure). However, sleep impacts esophageal physiology through the
impairment of esophageal acid clearance mechanisms when GER events occur. With sleep
onset, the upper esophageal sphincter (UES) pressure decreases and is lowest during N3
sleep, thus predisposing to aspiration. The UES contractile reflex remains intact during
sleep, including REM sleep. Lower esophageal sphincter (LES) pressure remains unchanged
during sleep. Sleep increases the vagal threshold for triggering transient LES relaxations, so
they usually do not occur during stable sleep and are usually confined to arousals. When
GER events occur during sleep, esophageal refluxate clearance is prolonged and an arousal
is required. Sleep facilitates proximal refluxate migration toward the UES. Saliva secretion,
with its acid-neutralizing bicarbonate, ceases during sleep. Swallowing, required for
esophageal peristalsis and refluxate clearance, does not occur during sleep and is
dependent on an arousal. Sleep also delays gastric emptying by disrupting gastromyoelectric
function. Events causing arousals, including periodic limb movements and apneas, could
trigger transient LES relaxations and thus GER events. Because refluxate clearance requires
an arousal, medications decreasing the arousal response (including benzodiazepines and
zolpidem) may prolong refluxate clearance and increase the risk of aspiration during sleep.

The pathology of GER includes abnormal esophageal manometry, endoscopy, and

esophageal biopsy findings. Esophageal manometry findings include an increased frequency
of transient LES relaxations, altered or decreased esophageal peristaltic contraction
amplitude, and a decrease in LES pressure. Endoscopic findings include changes ranging
from mild erythema, erosions, and ulcerations to severe erosions with stricture. Barrett
esophagus is identified when columnar tissue replaces the normal squamous epithelium of
the distal esophagus.

Objective Findings
Diagnostic testing is not required for sleep related GER. The diagnosis can be made if typical
symptoms of heartburn and/or regurgitation are present during sleep time. PSG is not
indicated. Esophageal pH monitoring, which may be combined with esophageal impedance,
objectively measures individual GER events. Esophageal monitoring is recommended in
difficult, refractory cases, or when symptoms continue despite therapy.

Sleep related GER is more likely to occur during the first two hours of sleep time.
Furthermore, in studies using combined esophageal pH monitoring with actigraphy, acid
reflux events occurred primarily during the recumbent-awake period, versus the recumbent-
asleep period. Reflux events are more likely to occur in the right side down and supine
positions than in the left side down position.

PSG without esophageal pH or impedance monitoring reveals arousals that are often
associated with swallows and a notable increase in chin EMG tone. Esophageal pH
monitoring detects acid reflux events and can be integrated with PSG. Esophageal pH
monitoring should be performed over a 24-hour  period  to  improve  the  test’s sensitivity and
specificity, which approximate 90%. The distal pH probe is placed 5 cm above the LES. A
proximal pH probe is often placed near the UES. An acid reflux event is defined when the pH
drops to less than 4.0, and this variable is reported as time (%) where pH is less than 4.0.
The percent time where pH is less than 4 is reported over the total recording time, upright
time and supine time. Note that supine (in this testing) is defined as the period of time that
the patient is in bed. Symptom correlation is also helpful using the event marker on the
device  or  diaries.  Normal  esophageal  pH  times  during  the  “supine”  or  sleep  period  are:  1)  
distal pH < 4 - less than 3.5% of the time; and 2) proximal pH < 4 - less than 0.6% of the time.
If esophageal pH monitoring is integrated with polysomnography, esophageal acid events
can be correlated with sleep events, including arousals, apneas, laryngospasm, and
increased chin EMG tone. Esophageal pH monitoring also can be performed simultaneously
with actigraphy to correlate acid reflux events with sleep and wake periods. Catheter-free
wireless pH systems are also available and are deployed into the esophagus, usually by
endoscopy.

Esophageal impedance monitoring can be combined with pH probes detecting liquid, gas, or
liquid gas in the esophagus, and can assess both acid and nonacid reflux events. Use of
esophageal impedance monitoring is often performed in esophageal centers, and this
technique would be difficult to integrate with polysomnography.

Other objective measures include esophageal endoscopy with or without biopsy in order to
evaluate for esophagitis and other esophageal complications. A histologic evaluation is
required to establish a diagnosis of Barrett esophagus.

Differential Diagnosis
The differential diagnosis is primarily with peptic ulcer disease and angina. The chest pain
associated with GER is sometimes indistinguishable from that of angina. Duodenal ulcer
disease is commonly associated with a burning epigastric pain, and this can sometimes be
similar to the pain experienced by patients with GER. Other conditions that may be
associated with GER include OSA, sleep related abnormal swallowing, and sleep related
laryngospasm. PSG evaluation with respiratory and pH monitoring can differentiate these
disorders.

Unresolved Issues and Further Directions

Not applicable or known.

Bibliography

Allen L, Poh CH, Gasiorowska A, et al. Increased oesophageal acid exposure at the beginning
of the recumbent period is primarily a recumbent-awake phenomenon. Aliment Pharmacol
Ther 2010;32:787–94.

Bajaj JS, Bajaj S, Dua KS, et al. Influence of sleep stages on esophago-upper esophageal
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Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.

Appendix A: Sleep Related Medical and Neurological Disorders ›› Disorders ››

Sleep Related Myocardial Ischemia

Alternate Names

Unstable angina, coronary insufficiency-acute, nocturnal angina, angina decubitus, variant

angina, Prinzmetal angina, vasospastic angina, angina pectoris, atherosclerotic heart
disease, asymptomatic cardiac ischemia, silent ischemia.

Essential Features

Sleep related myocardial ischemia is characterized by nocturnal reduction of blood flow to

the myocardium, typically during sleep. The symptoms of sleep related myocardial ischemia
are very similar to those that characterize episodes of cardiac ischemia during the daytime.
Classically, there is a feeling of chest pressure or pain that awakens the patient from sleep
and  may  be  described  as  a  “viselike”  discomfort.  The  discomfort  may  radiate  to  the  chin  and  
jaw and to the arm, especially the left arm.

Associated Features

Acute episodes of sleep related myocardial ischemia sometimes elicit atrial or ventricular
arrhythmias. Other associated presentations include acute onset of shortness of breath that
wakes the patient from sleep and that may be secondary to left ventricular diastolic
dysfunction or ischemic mitral regurgitation. Other related features depend on the trigger
for the cardiac ischemia. Ischemic events related to OSA may present during those times of
sleep when nocturnal desaturation is most severe. Cardiac ischemia related to
hemodynamic changes or vasospasm occurring during REM sleep may present in the early
hours of the morning, around the time of waking, when REM sleep is most likely to occur.
Ischemia associated with nocturnal hypotension is most likely to occur during slow wave
(N3) sleep, when blood pressure is lowest.

Clinical and Pathophysiological Subtypes

None known.

Demographics

The specifics of prevalence, sex ratios, and age ranges have not been comprehensively
evaluated. Some insights into demographics can be extrapolated, depending on the cause of
nocturnal angina. For sleep related myocardial ischemia triggered by OSA, the
preponderance of OSA in men suggests that middle-aged men with severe OSA are more
likely to experience nocturnal angina, particularly if they have more severe coronary artery
disease. Variant angina (also referred to as vasospastic or Prinzmetal angina) more
commonly affects younger populations, particularly women and those of Asian descent.
Cardiac ischemia secondary to nocturnal hypotension is more commonly manifested in
older individuals, particularly those with severe vasculopathy who are taking multiple
antihypertensive medications, and especially those in whom autonomic dysfunction (related
to either age or diabetes) may impair blood pressure homeostatic mechanisms.

Predisposing and Precipitating Factors

Predisposing factors include established coronary artery disease or valvular disease such as
aortic stenosis. Because coronary filling occurs during diastole, conditions associated with
reduced diastolic blood pressure, such as severe aortic regurgitation, may elicit nocturnal
angina, particularly in the presence of preexisting coronary artery disease. Similarly, any
predisposition to hypotension, which is most likely to occur during slow wave (N3) sleep,
may heighten risk. Usual risk factors for coronary artery disease that predispose an
individual to the development of sleep related myocardial ischemia include hypertension,
diabetes mellitus, cigarette smoking, and hyperlipidemia.

Retrospective and prospective studies suggest that OSA may be a trigger for myocardial
infarction and sudden death that occurs at night. Deeper oxyhemoglobin desaturations,
which may be encountered in REM, particularly with coexisting pulmonary disease or
truncal-abdominal obesity, are more likely to trigger cardiac ischemia. In patients with
vasospastic angina, use of nonselective β-adrenergic receptor-blocking agents may
theoretically increase the likelihood of vasospasm. In patients with nocturnal angina
secondary to hypotension, an excess of antihypertensive medications, as well as long-acting
nitroglycerin administered prior to sleep, may contribute. Finally, in the proper clinical
context, abuse of drugs such as amphetamine, cocaine, and other stimulants, needs to be
considered in the evaluation of myocardial ischemia.

Familial Patterns

Familial patterns reflect those of the underlying disease process.

Onset, Course, and Complications

For angina related to OSA, the first presentation of nocturnal angina may occur only when
the severity of both the sleep apnea and the coronary artery disease are sufficient to elicit
sleep related myocardial ischemia. This is likely to be most common in middle-aged to older
men, particularly those who are overweight, although several studies have documented life-
threatening OSA related cardiac ischemia in women. It is notable that several studies have
reported cardiac ischemia in patients with OSA even in the absence of severe coronary
artery stenosis. ST segment changes occurring as a result of OSA would be expected to
resolve with treatment of the OSA. Regardless of the underlying etiology, potential
complications of sleep related myocardial ischemia include acute left ventricular
dysfunction, ischemic mitral regurgitation and pulmonary edema, arrhythmias, and even
progression to myocardial infarction and death.

Pathology and Pathophysiology

For sleep related myocardial ischemia related to OSA, the apnea-related hypoxemia and
surges in blood pressure and heart rate at termination of apnea may all result in relative
myocardial oxygen deficiency. A substrate of preexisting severe coronary artery disease is
expected to exacerbate this problem. Variant angina may be more likely to occur during
sleep because of the significant and abrupt fluctuations in cardiovascular neural control
during REM sleep. For nocturnal angina related to hypotension, perfusion of the coronary
arteries during diastole makes maintenance of diastolic pressures during sleep important for
adequate myocardial perfusion. Autonomic insufficiency due to old age, diabetes, and
medication effects blunts the ability of the cardiovascular system to maintain adequate
blood pressure.
Objective Findings

Electrocardiographic monitoring during sleep reveals horizontal or downsloping ST segment

depression of greater than or equal to 1 mm, or ST segment elevation of 1 mm or more. The
electrocardiographic evidence of sleep related coronary artery ischemia is sometimes
unaccompanied by chest discomfort or other symptoms (silent ischemia) and may be
incidentally noted on either Holter monitoring or telemetry.

In general, ST segment abnormalities indicative of myocardial ischemia are 1 mm or more

horizontal or down-sloping depression or ST segment elevation, which may be detected on
the single lead electrocardiogram (ECG) employed in most sleep laboratories. However,
because the sensitivity of single-lead ECG in detecting ischemic changes is poor, the patient
with symptoms compatible with angina with a normal-appearing single ECG channel should
be further evaluated with multichannel ECG.

Sleep related myocardial ischemia in patients without sleep related breathing disorders may
be associated with REM sleep. Slow wave sleep with a fall in blood pressure and heart rate
can be associated with ischemia. Sleep related breathing disorders, particularly OSA, may
elicit oxygen desaturation and consequent sleep related myocardial ischemia. The presence
of cardiac arrhythmias should prompt an evaluation for nocturnal ischemia.

Differential Diagnosis

Sleep related myocardial ischemia must be differentiated from gastroesophageal reflux,

which may also be associated with chest discomfort. The nature of the pain, associated
symptoms and prior history are helpful in making a distinction, although 12-lead ECG may
be necessary in some cases.Nocturnal panic attacks may be associated with chest wall pain
and respiratory distress. Although the majority of patients with nocturnal panic will have a
history of daytime panic attacks, a small percentage have only nocturnal events. Nocturnal
panic attacks typically occur during transition from N2 to N3 sleep.

Other causes of nocturnal respiratory distress, including heart failure and pulmonary
disease, may be confused with myocardial ischemic episodes, although typical anginal chest
pain is not evident in these cases.

Chest pain due to thoracic mass, pleuritic pain, aortic aneurysm, or other thoracic
disease should be considered in the differential diagnosis. Chest wall pain may be secondary
to a variety of causes such as trauma, muscle spasm, or immobility.

Unresolved Issues and Further Directions

More comprehensive data are needed to identify the prevalence and demographics of the
various causes of sleep related myocardial ischemia. Further information is also needed to
explore the relationship between sleep related myocardial ischemia and the circadian
variation in myocardial infarction and sudden death, particularly the role of treatment on
outcomes.

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Copyright © 2014 by American Academy of Sleep Medicine. All Rights Reserved.