Physiology, Neurobiology, Disorders, Effect of Drugs on Sleep, Evaluation of Sleep Disorders, Management of Sleep Disorders, History of Sleep research

1. SLEEP
Physiology & Disorders
Presenter : Dr. Arpit Koolwal
Resident,
Department of Psychiatry
Subharti Medical College,
Meerut

2. Introduction
• Universal behavior
• Occupies 1/3rd of human life
• Exact functions are still unknown – But clearly
necessary for survival.
• Particular relevance to psychiatry.

3. Ancient Greeks
HYPNOS
MORPHEUS

4. A Brief History of Sleep Research
• Henri Pieron - “Le probleme physiologique du
sommeil” (1913)
• Nathaniel Kleitman - Father of American sleep
research
• Crucial work - Studies on sleep characteristics in
different populations ;and the effects of sleep
deprivation
• In 1953, along with one of his students, Eugene
Aserinsky, discovered REM during sleep

5. Nathaniel Kleitman
& the first Sleep Lab
(1950s)

6. A Brief History of Sleep Research
• William C. Dement - Cyclical nature of sleep in
1955
• Published a paper in 1958 that created an
explosion of fundamental research that led
Michel Jouvet to identify REM sleep as an
independent state of alertness.

7. What is sleep?
Natural periodic state of rest for the mind and body,
in which the eyes usually close, and consciousness is
completely or partly lost, so that there is a decrease
in bodily movement or external stimuli.
– Not the absence of waking
– Not due to lack of sensory input
– An active process
• Distinguished from wakefulness - decreased ability to
react to stimuli.
• Distinguished from coma - unconsciousness from
which the person cannot be aroused.

8. • Twilight State - Where the patient is relaxed
and "sleepy", able to follow simple directions
by the doctor, and is responsive.

9. Sleep Physiology
• Types of Sleep States
• EEG Waves
• Sleep Stages & Architecture
• Changes in sleep with age
• Functions of Sleep
• Requirement of Sleep

10. Types of Sleep States
• Physiologically - 1. NREM Sleep
2. REM Sleep
• Alternate cyclically – Function of cycling
unknown
• Irregular cycling/absent sleep stages - Can
result in sleep disorders.

11. NREM
• Composed of Stage 1 through 4.
• Constitutes about 75-80% of total sleep time.
• Normal state of entry into sleep.
• Most physiological functions including brain activity markedly lower than
wakefulness – Peaceful state relative to waking.
• Arousal can result in disorganised thinking, disorientation and amnesia for
period of arousal.
• Deepest portions (Stage 3 & 4) – Slow wave sleep
• Dreaming occurs but is abstract, disorganised, unreal and not
remembered.
• Associated with –
1. Night terrors
2. Somnambulism
3. Somniloquy
4. Enuresis
5. Bruxism

12. REM
• Polysomnographic measures – Irregular patterns sometimes close
to aroused waking patterns – PARADOXICAL SLEEP.
• Constitutes 20-25% of total sleep time.
• High brain activity
• Paralysis of voluntary muscles – Preventing acting out on dreams.
• Physiologic arousal including complete or partial penile erection.
• Altered thermoregulation
• Dreaming – the ones that are remembered
• Important for memory consolidation.
• Has two components – 1. Phasic REM – Sympathetically driven state
characterised by rapid eye movements, muscle twitches and
respiratory variability.
2. Tonic REM – Parasympathetically driven
state with no eye movements.
• REM period length and density of eye movements increases
throughout the cycle.

13. Physiological Process NREM REM
Brain activity Decreases from wakefulness
Increases in motor and sensory
areas, while other areas are similar
to NREM
Heart rate Slows from wakefulness
Increases and varies compared
to NREM
Blood pressure Decreases from wakefulness
Increases (up to 30 percent) and
varies from NREM
Sympathetic nerve activity Decreases from wakefulness
Increases significantly from
wakefulness
Muscle tone Similar to wakefulness Absent
Blood flow to brain Decreases from wakefulness
Increases from NREM, depending on
brain region
Respiration Decreases from wakefulness
Increases and varies from NREM, but
may show brief stoppages; coughing
suppressed
Airway resistance Increases from wakefulness
Increases and varies from
wakefulness
Body temperature
Is regulated at lower set point than
wakefulness; shivering initiated at
lower temperature than during
wakefulness
Is not regulated; no shivering or
sweating; temperature drifts toward
that of the local environment
Sexual arousal Occurs infrequently Greater than NREM
Physiological Changes During NREM and REM Sleep

14. EEG
waves

15. 1) Alpha waves
 Seen in all age groups but are most common in adults.
 Most marked in the parieto-occipital area.
 Occur rhythmically on both sides of the head but are often
slightly higher in amplitude on the nondominant side,
especially in right-handed individuals
 Occur with closed eyes , relaxation, wondering mind.
 Disappear normally with attention (eg, mental arithmetic,
stress, opening eyes, any form of sensory stimulation), then
become replaced with irregular low voltage activity.

16. 2) Beta waves
• Seen in all age groups.
• Small in amplitude , usually symmetric and more
evident anteriorly.
• Drugs, such as barbiturates and benzodiazepines,
augment beta waves.

17. 3)Theta waves
• Normally seen during sleep at any age.
• In awake adults, these waves are abnormal if
they occur in excess.
• Theta and delta waves are known collectively
as slow waves.

18. 4)Delta waves
• Slow waves, have a frequency of ≤ 3Hz or less.
• Normally seen in deep sleep in adults as well as
in infants and children.
• Delta waves are abnormal in the awake adult.
• Often, have the largest amplitude of all waves.
• Delta waves can be focal (local pathology) or
diffuse (generalized dysfunction).

19. Sleep spindles
• Groups of waves that occur during many sleep
stages but especially in stage 2.
• Have frequencies in the upper levels of alpha or
lower levels of beta.
• Lasting for a second or less, they increase in
amplitude initially and then decrease slowly. The
waveform resembles a spindle.
• They usually are symmetric and are most obvious
in the parasagittal regions.

20. Sleep Stages & Architecture
• According to EEG criteria -
1. NREM :
– Stage 1 NREM
– Stage 2 NREM
– Stage 3 NREM
– Stage 4 NREM
2. REM

21. Stage 1 NREM
• Transitional role in sleep-stage cycling.
• Occurs at sleep onset or following arousal from
another stage of sleep.
• Except – Newborns and Narcolepsy
• 1 to 7 minutes in the initial cycle
• 2 to 5% of total sleep
• Easily interrupted
• EEG – Transitions from wakefulness (rhythmic
alpha waves) to low voltage, mixed frequency
waves .

22. Stage 2 NREM
• Lasts 10 to 25 minutes in initial cycle and
lengthens with each successive cycle.
• 45 to 55% of the total sleep period.
• Arousal requires more intense stimuli than
stage 1.
• EEG – Low voltage, mixed frequency activity
characterised by the presence of sleep
spindles and K-complexes.

23. Stage 3 NREM
• Lasts only for a few minutes.
• 3-8% of total sleep.
• EEG – High voltage, slow wave activity.

24. Stage 4 NREM
• Lasts 20-40 minutes in the first cycle.
• 10-15% of total sleep.
• Arousal threshold is highest.
• EEG – high voltage slow wave activity – delta waves.
• Together with Stage 3 NREM – Slow Wave Sleep
(SWS)
• Now, combined with Stage 3 NREM into single entity
– N3 Stage

25. REM
• Desynchronised (low voltage, mixed
frequency) brain wave activity.
• “Sawtooth” waveforms. Theta activity and
slow alpha activity also characterise REM
sleep.
• 1-5 minutes in initial cycle.
• Progressively prolonged as sleep progresses.

26. • 4-5 cycles of these sequential stages
• Each cycle – 90-110 mins
• As sleep progresses delta sleep decreases and
REM sleep increases.
• REM in initial cycle is only 5-10 mins but in last
cycle can be as long as 40 mins
• As sleep progresses Stage 2 predominates in
NREM sleep and Stage 3 & 4 sometimes
disappear altogether.

28. Distribution of Sleep Stages

29. Changes in sleep with Age
1. Average amount of sleep per day -
• Newborn - up to 18 hours
• 1–12 months - 14–18 hours
• 1–3 years -12–15 hours
• 3–5 years - 11–13 hours
• 5–12 years - 9–11 hours
• Adolescents - 9-10 hours
• Adults, elder - 7–8 (+) hours
• Pregnant women -8 (+) hours

30. 2. NREM sleep - overall decrease across the life span.
• Decrease begins in early adolescence and continues
throughout adulthood.
3. Proportion of REM sleep - decrease from 50% or more of total
sleep time in the Nero born to 20-25% by 2 years.
• This figure remains finely constant throughout the rest of life.
• The high level of REM sleep in very early life suggests a role in
general maturation.
4. NREM - REM sleep cycles:- Occur at intervals of 50 to 60 min
in infract who often enter REM at the start of their sleep
period.
• This interval between sleep cycles remains until adolescence
when the periodicity changes to 90 to 100 min, which persists
into adult life.
• The amount of NREM and REM in each sleep cycle is about
equal in early infancy. After words NREM sleep predominates
in the earlier cycles & REM sleep in the later cycles.

31. 5. Continuity of sleep :- Is greatest in early
childhood and least at the extremes of age.
• Infants are easily wakened and so are the elderly
who also wake spontaneously more often
[Fragmentation of sleep by brief arousals without
actual waking is described as particularly
common in the elderly]
• Gradual increase in brief arousals in healthy
subjects from teenage to old age.
6. Circadian sleep wake rhythms :- Change
considerably in early development
• Full term neonates show 3 h to 4 h sleep wake
cycles.
• Sleep periods have shift to night

32. Sleep changes over the lifespan
 Continuous
REM in
gestation
 Sleep quality
changes with
age:
Amount of time in
slow wave and
REM sleep
decreases with age

33. Sleep architecture over the lifespan

34. Sleep over the lifespan – A single day

35. Functions of Sleep
1. Restorative Function:- Wound healing has been shown to
be affected by sleep.
• Studies have confirmed that sleep deprivation affects the
immune system.
• It has yet to be proven that sleep duration affects somatic
growth, however, it has been shown that slow wave sleep
does affect growth hormone levels in adult men.
2. Ontogenesis:- According to ‘ontogenetic hypothesis of
REM sleep’, the activity occurring drug neonatal REM
sleep seems to be particularly important for the
developing organism.
• Sleep deprivation early in life can result in behavioral
problems, permanent sleep disruption, decreased brain
mass and an abnormal amount of nominal cell death.
• REM sleep appears to be imp. for dev. of the brain.

36. 3. Memory Processing:- Turner et al - working memory
was shown to be adversity affected by sleep
deprivation.
• Memory seems to be affected differently by certain
stage of sleep e.g. procedural memory benefits from
late, REM rich sleep, whereas declarative memory
benefits from early SWS rich sleep.
4. Preservation:- The ‘Preservation and protection’
theory holds that sleep serves an adaptive function.
• It protects the animal during that portion of the 24 hr
day in which being awake, and hence roaming
around, would place the individual at greatest risk.

37. 5. Dreaming - Perceived experience of sensory
images & sounds during sleep, in a sequence
which the dreamer usually perceives more as an
apparent participant than as an observer.
• Mostly occurs during the REM phase of sleep.
Hobson and McCarley’s ‘Activation Synthesis
theory’ - Dreams are caused by the random firing
of neurons in the cerulean cortex during the
during the REM period.
• Forebrain then creates a story in an attempt to
reconcile & make sense of the nonsensical
information presented to it; hence the odd
nature of many dreams.

38. Sleep Requirement
• Normal Adult – 7-9hrs
• <6hrs – Short sleepers
• >9hrs – Long sleepers
• Long sleepers have increased no. of cycles and
increased no. of REMs – REM Density – which
is considered a measure of intensity of REM
sleep.
• “Sleep Debt”

39. SLEEP DISORDERS
Primary sleep disorders are subdivided into -
1. Dyssomnias (characterized by abnormalities
in the amount, quality, or timing of sleep)
2. Parasomnias (characterized by abnormal
behavior or physiological events occurring in
association with sleep, specific sleep stages,
or sleep-wake transitions).

40. PRIMARY SLEEP DISORDERS
DYSSOMNIAS
• Dyssomnias are primary disorders of initiating or
maintaining sleep or of excessive sleepiness and
are characterized by a disturbance in the amount,
quality, or timing of sleep.
• This part includes Primary Insomnia, Primary
Hypersomnia, Narcolepsy, Breathing-Related
Sleep Disorder, Circadian Rhythm Sleep Disorder,
and Dyssomnia Not Otherwise Specified.

41. PRIMARY INSOMNIA
• Individuals with Primary Insomnia most often report a
combination of difficulty falling asleep and intermittent
wakefulness during sleep.
• A diagnosis of Primary Insomnia should be reserved for
those individuals with significant distress or
impairment.
• A marked preoccupation with and distress due to the
inability to sleep may contribute to the development of
a vicious cycle: the more the individual strives to sleep,
the more frustrated and distressed he or she becomes
and the less he or she is able to sleep (Paradoxical
Insomnia).

42. • Chronic Insomnia may lead to decreased
feelings of well-being during the day (e.g.,
deterioration of mood and motivation; and an
increase in fatigue).
• Although individuals often have the subjective
complaint of daytime fatigue,
polysomnographic studies usually do not
demonstrate an increase in physiological signs
of sleepiness.

43. Diagnostic Criteria for Primary
Insomnia
A. The predominant complaint is difficulty initiating
or maintaining sleep, or non restorative sleep,
for at least 1 month.
B. The sleep disturbance (or associated daytime
fatigue) causes clinically significant distress or
impairment in social, occupational, or other
important areas of functioning.
C. The sleep disturbance does not occur exclusively
during the course of Narcolepsy, Breathing-
Related Sleep Disorder. Circadian Rhythm Sleep
Disorder, or a Parasomnia.

44. D. The disturbance does not occur exclusively
during the course of another mental disorder
(e.g ., Major Depressive Disorder. Generalized
Anxiety Disorder, a delirium).
E. The disturbance is not due to the direct
physiological effects of a substance (e.g ., a
drug of abuse, a medication) or a general
medical condition.

45. ASSOCIATED FEATURES AND
DISORDERS
-Many individuals with Primary Insomnia have a
history of “light” or easily disturbed sleep prior to
the development of more persistent sleep
problems.
-Interpersonal, social and occupational problems
may develop as a result of overconcern with
sleep, increased daytime irritability, and poor
concentration.
-Individuals with severe insomnia have greater
functional impairment, lower productivity, and
increased health care utilization.

46. -Individuals with Primary Insomnia may have a
history of mental disorders, particularly Mood
Disorders and Anxiety Disorders.
-Individuals with Primary Insomnia sometimes use
medications inappropriately: hypnotics or alcohol
to help with night time sleep, anxiolytics to
combat tension or anxiety, and caffeine or other
stimulants to combat excessive fatigue. In some
cases, this type of substance use may progress to
Substance Abuse or Substance Dependence.

47. SPECIFIC AGE AND GENDER FEATURES
•Complaints of insomnia are more prevalent with
increasing age and among women.
•The increasing prevalence of insomnia complaints with
age may be attributable partly to the increased rates of
physical health problems in the elderly.
•Paradoxically, despite the greater prevalence of
insomnia complaints among elderly women,
polysomnographic studies generally indicate better
preservation of sleep continuity and slow-wave sleep in
elderly females than in elderly males

48. PREVALENCE
•Population surveys indicate a 1-year prevalence of
insomnia complaints of 30%-45% in adults.
•The prevalence of Primary Insomnia is
approximately 1%-10% in the general adult
population and up to 25% in the elderly.
•In clinics specializing in sleep disorders,
approximately 15%-25% of individuals with
chronic insomnia are diagnosed with Primary
Insomnia.

49. COURSE
•Most cases have a fairly sudden onset at a time of
psychological, social, or medical stress.
•Primary Insomnia often persists long after the original
causative factors resolve, due to the development of
heightened arousal and negative conditioning. For
example, a person with a painful injury who spends a
great deal of time in bed and has difficulty sleeping
may then develop negative associations for sleep.
Negative associations, increased arousal, and
conditioned awakenings may then persist beyond the
convalescent period, leading to Primary Insomnia.

50. •Primary Insomnia typically begins in young
adulthood or middle age and is rare in childhood
or adolescence.
•In exceptional cases, the insomnia can be
documented back to childhood.
•Approximately 50%-75% of individuals with
insomnia complaints have chronic symptoms
lasting for more than 1 year, and previous
insomnia is the strongest single risk factor for
current insomnia

51. PRIMARY HYPERSOMNIA
• In individuals with Primary Hypersomnia, the
duration of the major sleep episode (for most
individuals, nocturnal sleep) may range from 8
to 12 hours and is often followed by difficulty
awakening in the morning. The actual quality
of nocturnal sleep is normal.
• Excessive sleepiness during normal waking
hours takes the form of intentional naps or
inadvertent episodes of sleep.

52. • Daytime naps tend to be relatively long (often
lasting an hour or more), are experienced as
unrefreshing, and often do not lead to improved
alertness.
• Unintentional sleep episodes typically occur in
low- stimulation and low-activity situations (e.g.,
while attending lectures, reading, watching tv, or
driving long distances).
• Prolonged nocturnal sleep and difficulty
awakening can result in difficulty in meeting
morning obligations.

53. • Unintentional daytime sleep disorders can be
embarrassing and even dangerous, if , for
instance, the individual is driving or operating
machinery when the episode occurs.

54. SPECIFIER
• RECURRENT - This specified is used if there
are periods of excessive sleepiness that last at
least 3 days occurring several times a year for
at least 2 years.

55. • In the recurrent form of Primary Hypersomnia known as
Kleine-Levin syndrome, individuals may spend 18- 20 hours
asleep or in bed.
• The recurrent periods of sleepiness are associated with
other characteristic clinical features indicating disinhibition.
Indiscriminate hypersexuality including inappropriate
sexual advances and overt masturbation can be seen in
males (and less often in females). Compulsive overeating
with acute weight gain may occur.
• Irritability, depersonalization, depression, confusion, and
occasional hallucinations have been described in some
individuals, and impulsive behaviors can also occur.

56. DIAGNOSTIC CRITERIA FOR PRIMARY
HYPERSOMNIA
A. The predominant complaint is excessive sleepiness for at
least 1 month (or less if recurrent) as evidenced by either
prolonged sleep episodes or daytime sleep episodes that
occur almost daily.
B. The excessive sleepiness causes clinically significant distress
or impairment in social, occupational, or other important
areas of functioning.
C. The excessive sleepiness is not better accounted for by
insomnia and does not occur exclusively during the course
of another Sleep Disorder (e.g., Narcolepsy, Breathing-
Related Sleep Disorder, Circadian Rhythm Sleep Disorder,
or a Parasomnia) and cannot be accounted for by an
inadequate amount of sleep.

57. D. The disturbance does not occur exclusively
during the course of another mental disorder.
E. The disturbance is not due to the direct
physiological effects of a substance (e.g., a drug
of abuse, a medication) or a general medical
condition.
Specify if:
Recurrent: if there are periods of excessive
sleepiness that last at least 3 days occurring
several times a year for at least 2 years

58. ASSOCIATED FEATURES AND
DISORDERS
Individuals with this disorder fall asleep quickly
and have good sleep efficiency, but may have
difficulty waking up in the morning,
sometimes appearing confused or combative.
- This prolonged impairment of alertness at the
sleep- wake transition is often referred to as
“sleep drunkenness.”

59. -Persistent daytime sleepiness can lead to
automatic behavior (usually of a very routine,
low-complexity type) that the individual
carries out with little or no subsequent recall.
- For example, individuals may find themselves
having driven several miles from where the
thought they were, unaware of the
“automatic” driving they did in the preceding
minutes.

60. -Many individuals with Primary Hypersomnia
have symptoms of depression that may meet
criteria for a Mood Disorder. This may be
related to the psychosocial consequences of
excessive sleepiness.
-Individuals with hypersomnia are also at risk for
Substance-Related Disorders, particularly
related to self-medication with stimulants.

61. SPECIFIC AGE OR GENDER FEATURES
• Kleine-Levin syndrome affects males about
three times more often than it affects females.

62. PREVALENCE
-Approximately 5%-10% of individuals who
present to sleep disorders clinics with
complaints of daytime sleepiness are
diagnosed as having Primary Hypersomnia.
-The recurrent form of Primary Hypersomnia
known as Kleine-Levin syndrome is rare.

63. • The lifetime prevalence of clinically significant
hypersomnia is at least 16%, and the
incidence over approximately a 4-year interval
is about 8%.

64. COURSE
-Primary Hypersomnia typically begins between
ages 15 and 30 years, with a gradual
progression over weeks to months.
-For most individuals, the course is then chronic
and stable, unless treatment is initiated.
-Kleine-Levin syndrome also begins during
adolescence and may continue its periodic
course for decades, although it often resolves
during middle age.

65. NARCOLEPSY
-Episodes of sleepiness in Narcolepsy are often
described as irresistible, resulting in
unintended sleep in appropriate situations
(e.g., while driving an automobile, attending
meetings, or carrying on a conversation).
-Sleep episodes generally last 10-20 minutes but
can last up to an hour if uninterrupted.
- Dreaming is frequently reported.

66. -Individuals have varying abilities to “fight off”
these sleep attacks. Some individuals take
naps intentionally in order to manage their
sleepiness
-Individuals with Narcolepsy typically have 2-6
episodes of sleep (intentional and
unintentional) per day when untreated.

67. -Cataplexy often develops several years after
the onset of daytime sleepiness and occurs in
approximately 70% of individuals with the
disorder.
-The loss of muscle tone with cataplexy may be
subtle, leading to a sagging jaw or drooping
eyelids, head, or arms not noticeable to
observers.

68. Cataplexy can also be more dramatic, and the
individual may drop objects being carried, buckle
at the knees, or actually fall to the ground.
Episodes are followed by a full return of normal
muscle strength. Individuals can clearly describe
events and have no confusion before or after the
episode.
-Cataplexy is usually triggered by a strong
emotional stimulus (e.g., anger, surprise,
laughter).

69. -Approximately 20%-40% of individuals with
Narcolepsy also experience intense dreamlike
imagery just before falling asleep (hypnagogic
hallucinations) or just after awakening
(hypnopompic hallucinations). The
hallucinations may also be auditory (e.g.,
hearing intruders in the home) or kinetic (e.g.,
sensation of flying).

70. Diagnostic Criteria for Narcolepsy
A. Irresistible attacks of refreshing sleep that occur daily over at least
3 months.
B. The presence of one or both of the following:
(1) cataplexy (i.e., brief episodes of sudden bilateral loss of muscle
tone, most often in association with intense emotion)
(2) recurrent intrusions of elements of rapid eye movement (REM)
sleep into the transition between sleep and wakefulness, as
manifested by either hypnopompic or hypnagogic hallucinations
or sleep paralysis at the beginning or end of sleep episodes
C. The disturbance is not due to the direct physiological effects of a
substance (e.g ., a drug of abuse, a medication) or another general
medical condition.

71. ASSOCIATED FEATURES AND
DISORDERS
- Individuals with Narcolepsy may describe being
able to sleep at any time in any situation.
- Automatic behavior, in which the individual
engages in activity without full awareness, can
occur as a result of profound sleepiness.
Individuals may drive, converse, or even work
during episodes of automatic behavior.
- Individuals with Narcolepsy ay hesitate to engage
in social activities because they fear falling asleep
or having an episode of cataplexy.

72. -Narcolepsy can severely limit daytime
functioning because of repeated,
uncontrollable sleep attacks, automatic
behavior, and episodes of cataplexy.
- The most common associated disorders with
Narcolepsy are Mood Disorders (primarily
Major Depressive Disorder and Dysthymic
Disorder), followed by Substance-Related
Disorders and Generalized Anxiety Disorder.

73. SPECIFIC AGE FEATURES
- Hyperactivity may be one of the presenting
signs in children with daytime sleepiness.
- The core clinical features and laboratory
finding in Narcolepsy in children are similar to
those n adults.
- Cataplexy and mild daytime sleepiness maybe
more difficult to identify in children than in
adults.

74. PREVALENCE
• Epidemiological studies indicate a prevalence
of 0.02%-0.16% for Narcolepsy in the adult
population, with equal rates in females and
males.

75. COURSE
-Onset after age 40 is unusual.
-Cataplexy may develop concurrently with
sleepiness but often appears months, years, or
even decades after the onset of sleepiness.
-The excessive sleepiness of Narcolepsy has a stable
course over time.
-Cataplexy usually has a stable course as well,
although some individuals report decreased
symptoms or even complete cessation of
symptoms after many years.

76. BREATHING-RELATED SLEEP DISORDER
-Sleepiness results from frequent arousals
during nocturnal sleep as the individual
attempts to breathe normally.
-Some individuals may complain of difficulty
breathing while lying or sleeping.

77. -Abnormal respiratory events during sleep in
Breathing-Related Sleep Disorder include
1. apneas (episodes of breathing cessation),
2. hypopneas (abnormally slow or shallow
respiration), and
3. hypoventilation (abnormal blood oxygen and
carbon dioxide levels).

78. 3 Forms of Breathing-Related Sleep Disorder
1.Obstructive sleep apnea syndrome
2.Central sleep apnea syndrome
3.Central alveolar hypoventilation syndrome

79. • An older term, Pickwickian Syndrome, has
been used to describe obese individuals with a
combination of obstructive sleep apnea
syndrome and waking hypoventilation as well
as sleep- related hypoventilation.

80. OBSTRUCTIVE SLEEP APNEA
SYNDROME
• Most common form of Breathing- Related
Sleep Disorder characterized by repeated
episodes of upper-airway obstruction (apneas
and hypopneas) during sleep usually occurs in
overweight individuals and leads to a
complaint of excessive sleepiness

81. -characterized by loud snores or brief gasps that
alternate with episodes of silence that usually
last 20-30 seconds
-snoring is caused by breathing through a
partially obstructed airway; silent periods are
caused by obstructive apneas, with the
cessation in breathing caused by complete
airway obstruction.

82. -the termination of the apneic event can be
associated with loud “resuscitative” snores,
gasps, moans or mumbling, or whole-body
movements.
-most affected individuals are unaware of the
loud snoring, breathing difficulty, and
frequent arousals

83. CENTRAL SLEEP APNEA SYNDROME
-characterized by episodic cessation of
ventilation during sleep (apneas and
hypopneas) without airway obstruction
-not associated with continued chest wall and
abdominal breathing movements and occur
more commonly in elderly persons as a result
of cardiac or neurological conditions that
affect ventilator regulation -may have mild
snoring

84. CENTRAL ALVEOLAR
HYPOVENTILATION
-characterized by an impairment in ventilatory
control that results in abnormally low arterial
oxygen levels further worsened by sleep
-most commonly occurs in very overweight
individuals and can be associated with a
complaint of either excessive sleepiness or
insomnia

85. Diagnostic Criteria for Breathing-
Related Sleep Disorder
A. Sleep disruption, leading to excessive
sleepiness or insomnia, that is judged to be
due to a sleep-related breathing condition
(e.g., obstructive or central sleep apnea
syndrome or central alveolar hypoventilation
syndrome).

86. B. The disturbance is not better accounted for
by another mental disorder and is not due to
the direct physiological effects of a substance
(e.g., a drug of abuse, a medication) or
another general medical condition (other than
a breathing-related disorder)

87. ASSOCIATED FEATURES AND
DISORDERS
•The individual with Breathng-Related Sleep
Disorder may complain of nocturnal chest
discomfort, choking, suffocation, or intense
anxiety in association with apneic events or
hypoventilation.
•Individuals with Breathing-Related Sleep Disorder
are often described as restless sleepers.
•Individuals with this disorder typically feel
unrefreshed on awakening and may describe
feeling more tired in the morning than when they
went to sleep.

88. •They may also experience sleep drunkenness
(i.e., extreme difficulty awakening, confusion,
and inappropriate behavior).
•Severe dryness of the mouth is common and
often leads the person to drink water during
the night of on awakening in the morning.

89. •The sleepiness can lead to memory disturbance,
poor concentration, irritability, and personality
changes.
•Mood disorders (particularly Major Depressive
Disorder and Dysthymic Disorder), Anxiety
Disorders (particularly Panic Disorder), and
Dementia are commonly associated with
Breathing-Related Sleep Disorder.
•Individuals can also have reduced libido and
erectile ability.

90. SPECIFIC AGE AND GENDER FEATURES
•In children, unusual sleep postures, such as
sleeping on the hands and knees, commonly
occur.
•Daytime mouth breathing, difficulty in
swallowing, and poor speech articulation are
also common features in children.

91. •The obstructive sleep apnea syndrome is most
common in middle-aged, overweight males
and prepubertal children with enlarged
tonsils.
•In adults, the male-to-female ratio of
obstructive sleep apnea syndrome ranges
from 2:1 to 4:1. There is no sex difference
among prepubertal children.

92. • In adults, central apneic events appear to be
more prevalent in males than in females,
although this difference is less apparent after
menopause.

93. PREVALENCE
•The prevalence of Breathing-Related Sleep
Disorder associated with obstructive sleep
apnea is estimated to be approximately 1%-
10% in the adult population but may be higher
in elderly individuals.

94. •The prevalence of central sleep apnea
syndrome is not precisely known but is
estimated to be 10% of the rate of obstructive
sleep apnea syndrome.

95. COURSE
-The obstructive sleep apnea syndrome can occur
at any age, but most individuals present for
evaluation when they are between ages 40 and
60 years (with females more likely to develop
obstructive sleep apnea after menopause).
-Central sleep apnea is more commonly seen in
elderly individuals with central nervous system or
cardiac disease.

96. -The central alveolar hypoventilation syndrome
and central sleep apnea syndrome can
develop at any age.
- Breathing-Related Sleep Disorder usually has
an insidious onset, gradual progression, and
chronic course. Most often, the disorder will
have been present for years by the time it is
diagnosed.

97. CIRCADIAN RHYTHM SLEEP DISORDER
(FORMERLY SLEEP-WAKE SCHEDULE
DISORDER)

98. Subtypes
Delays Sleep Phase Type----
•Individuals with this subtype are hypothesized to have an
alteration in the usual alignment of sleep with other
circadian rhythms. These individuals are “locked in” to
habitually late sleep hours and have great difficulty shifting
these sleep hours forward to an earlier time.
•There is concomitant difficulty awakening at socially
acceptable hours (e.g., multiple alarm clocks are often
unable to arouse the individual). Many individual with this
disorder will be chronically sleep deprived as a result of the
need to awaken for social and occupational obligations in
the morning.

99. • Jet Lag Type ------
•The disturbance arises from conflict between the
pattern of sleep and wakefulness generated by the
circadian system and the pattern of sleep and
wakefulness required by a new time zone.
•The severity of symptoms is proportional to the number
of time zones travelled, with maximal difficulties often
noted after traveling through 8 or more time zones in
less than 24 hours.
•Eastward travel (advancing sleep-wake hours) is typically
more difficult for most individuals to tolerate than
westward travel (delaying sleep-wake hours).

100. • Shift Work Type
-Insomnia durng the major sleep period or
excessive sleepiness during the major awake
period associated with night shift work or
frequently changing shift work

101. • Unspecified Type (e.g., advanced sleep phase,
non-24 hour sleep-wake pattern, irregular
sleep-wake pattern or other unspecified
pattern)

102. Diagnostic Criteria for
Circadian Rhythm Sleep Disorder
A. A persistent or recurrent pattern of sleep disruption leading
to excessive sleepiness or insomnia that is due to a
mismatch between the sleep-wake schedule required by a
person's environment and his or her circadian sleep-wake
pattern.
B. The sleep disturbance causes clinically significant distress or
impairment in social, occupational, or other important
areas of functioning.
C. The disturbance does not occur exclusively during the
course of another Sleep Disorder or other mental disorder.
D. The disturbance is not due to the direct physiological
effects of a substance (e.g., a drug of abuse, a medication)
or a general medical condition.

103. Delayed Sleep Phase Type: a persistent pattern of late
sleep onset and late awakening times, with an inability
to fall asleep and awaken at a desired earlier time
Jet Lag Type: sleepiness and alertness that occur at an
inappropriate time of day relative to local time,
occurring after repeated travel across more than one
time zone
Shift Work Type: insomnia during the major sleep period
or excessive sleepiness during the major awake period
associated with night shift work or frequently changing
shift work
Unspecified Type

104. ASSOCIATED FEATURES AND
DISORDERS
-Individuals with any Circadian Rhythm Sleep
Disorder may use increased amounts of
alcohol, sedative-hypnotic, or stimulants in an
attempt to control their inappropriately
phased sleep-wake tendencies. The use of
these substances may in turn exacerbate the
Circadian Rhythm Sleep Disorder.

105. -Delayed Sleep Phase Type has been associated
with schizoid, schizotypal, and avoidant
personality features, particularly in
adolescents, as well as with depressive
symptoms and Depressive Disorders.

106. SPECIFIC AGE FEATURES
-The onset of Delayed Sleep Phase Type most
often occurs between late childhood and early
adulthood.
-Shift work and jet lag symptoms are often
reported to be more severe, or more easily
induced in laboratory settings, in late-middle-
aged and elderly individuals compared with
young adults

107. PREVALENCE
-Prevalence figures for the Delayed Sleep Phase
Type from population surveys have varied
widely, ranging from 0.1% to 4% in adults and
up to 7% in adolescents.
-Up to 60% of night shift workers may have Shift
Work Type.

108. COURSE
-Delayed Sleep Phase Type typically begins during
adolescence and may follow a psychosocial
stressor. Without intervention, Delayed Sleep
Phase Type typically lasts for years or decades but
may “correct” itself given the tendency for
endogenous circadian rhythm phase to advance
with age.
-Shift Work Type persists for as long as the
individual works that particular schedule.
Reversal of symptoms generally occurs within 2
weeks of a return to a normal schedule.

109. • Experimental and field data concerning jet lag
indicate that it takes approximately 1 day per
time zone traveled for the circadian system to
resynchronize itself to the new local time.
Different circadian rhythms (such as core body
temperature, hormonal level, alertness, and
sleep patterns) may readjust at different rates.

110. Dyssomnia Not Otherwise Specified
The Dyssonmia Not Otherwise Specified category is
for insomnias, hypersomnias, or circadian rhythm
disturbances that do not meet criteria for any
specific Dyssomnia.
Examples include -
l. Complaints of clinically significant insomnia or
hypersomnia that are attributable to
environmental factors (e.g., noise, light, frequent
interruptions).
2. Excessive sleepiness that is attributable to
ongoing sleep deprivation.

111. Restless Legs Syndrome

112. Brief History
• The term was first introduced in 1945 by
Karl-Axel Ekbom
• A common movment disorder with
sensorimotor symptoms that are felt
during quiet wakefulness and getting to
sleep
• Earliest description of this disease was in
1672 by Thomas Willis, an English
physician

113. Prevalence
• Before 1995, Ekbom estimated that 5% of the
general population was affected by this
disorder
• Since then, studies have improved and
suggested that the prevalence is from 5-15%
in the white population

114. Possible Causes
• Iron deficiency anaemia
43% of patients with iron deficiency may have RLS
• Studies have shown reduced CSF ferritin and raised transferrin
levels in idiopathic RLS, suggesting a low brain iron content
(Earley et al. 2000)
• Using MRIs in five RLS patients, it was reported that iron
concentration was significantly lower in the putamen and
substantia nigra
• There is some evidence to suggest that serum iron levels have
a drop up to 50% at night when symptoms are most obvious
(Garcia-Borreguero et al. 2002)

115. Possible Causes
• During pregnancy, RLS has been reported in 11-27% of
women, usually during the third trimester (Goodman et al.
1988)
• However, RLS often resolves following delivery
• 20-57% of renal dialysis patients have RLS
• May also be associated with hypothyroidism and diabetes
mellitus.
• RLS has also been reported in up to 25% of patients with
rheumatoid arthritis and Sjogren’s syndrome

116. Pathophysiology
• The underlying cause of RLS during sleep is not known,
although the most likely would be central dopaminergic or
opioid dysfunction
• The dysfunction of the dopaminergic and/or dopamine linked
premotor circuits and the hypothalamic A11 dopamine cells
which converge and descend on the spinal flexor reflexes,
disinhibit as a result
• The final common pathway is influenced by other supraspinal
influences such as the reticulospinal, opioid, and monoamine
pathways.

117. Symptoms Described by Patients
• Like an electric current
• Crazy legs
• Like Coca-Cola bubbling through my veins
• Aching in my bones
• Pulling
• Tearing
• Throbbing
• Creepy crawly
• Pain/Growing Pains
• Itching Bones

118. Diagnostic Criteria: Restless Legs
Syndrome
A. The patient has a complaint of an unpleasant sensation in
the legs at night or difficulty in initiating sleep.
B. Disagreeable sensations of “creeping” inside the calves are
present and are often associated with general aches and
pains in the legs.
C. The discomfort is relieved by movement of the limbs.
D. Polysomnographic monitoring demonstrates limb
movements at sleep onset.
E. There is no evidence of any medical or mental disorders that
account for the movements.
F. Other sleep disorders may be present but do not account for
the symptom.

119. Associated Features
• The disorder can be associated with pregnancy, anemia,
and uremia. When associated with pregnancy, restless legs
syndrome usually appears after the 20th week of the
pregnancy.
• Most, if not all, patients with restless legs syndrome show
periodic leg movements during sleep. Unlike patients with
only periodic limb movements, patients with both
syndromes may show involuntary limb movements even
while awake.
• Patients may experience features of intense anxiety and
depression in association with restless legs syndrome. In
some patients, the emotional distress may be severe and
associated with psychosocial dysfunction.

120. SPECIFIC AGE FEATURES
• Restless legs syndrome has rarely been
reported to begin in infancy and may be seen
for the first time in advanced old age. The
peak onset is usually in middle age.

121. Periodic Limb Movement Disorder
• Characterized by periodic episodes of repetitive and highly stereotyped
limb movements that occur during sleep.
• The movements usually occur in the legs and consist of extension of the
big toe in combination with partial flexion of the ankle, knee, and
sometimes hip.
• Similar movements can occur in the upper limbs.
• The movements are often associated with a partial arousal or awakening;
however, the patient is usually unaware of the limb movements or the
frequent sleep disruption.
• Between the episodes, the legs are still.
• There can be marked nightly variability in the number of movements.
• There may be a history of frequent nocturnal awakenings and
unrefreshing sleep.
• Patients who are unaware of the sleep interruptions may have symptoms
of excessive sleepiness.
• It is probable that the nature of the patient’s complaint is affected by the
frequency of the movement as well as the associated awakenings.

122. Associated Features
• The disorder can produce anxiety and
depression related to the chronicity of the
sleep disturbance.

123. Course
• The natural history is not known. Periodic
limb movement disorder appears to increase
in prevalence with advancing age

124. Prevalence
• It appears to be rare in children and
progresses with advancing age to become a
common finding in up to 34% of patients over
the age of 60 years.
• It has been reported to occur in 1% to 15% of
patients with insomnia

125. Age of Onset
• Appears to be most prevalent in middle
adulthood and is rarely seen in children.

126. Diagnostic Criteria: Periodic Limb
Movement Disorder
A. The patient has a complaint of insomnia or excessive sleepiness. The
patient occasionally will be asymptomatic, and the movements are
noticed by an observer.
B. Repetitive highly stereotyped limb muscle movements are present;
in the leg, these movements are characterized by extension of the
big toe in combination with partial flexion of the ankle, knee, and
sometimes hip.
C. Polysomnographic monitoring demonstrates:
1. Repetitive episodes of muscle contraction (0.5 to 5 seconds in
duration) separated by an interval of typically 20 to 40 seconds
2. Arousal or awakenings may be associated with the movements
D. The patient has no evidence of a medical or mental disorder that
can account for the primary complaint.
E. Other sleep disorders (e.g., obstructive sleep apnea syndrome) may
be present but do not account for the movements.

127. PARASOMNIAS
-are disorders characterized by abnormal
behavior or physiological events occurring in
association with sleep, specific sleep stages, or
sleep- wake transitions.

128. •Parasomnias represent the activation of
physiological systems at inappropriate times
during the sleep-wake cycle
•These disorders involve activation of the
autonomic nervous system, motor system, or
cognitive processes during sleep or sleep-
wake transitions.

129. • Individuals with parasomnias usually present
with complaints of unusual behavior during
sleep rather than complaints of insomnia or
excessive daytime sleepiness.

130. NIGHTMARE DISORDER (FORMERLY
DREAM ANXIETY DISORDER)
-nightmares typically occur in a lengthy,
elaborate dream sequence that is highly
anxiety provoking or terrifying.
-dream content most often focuses on imminent
physical danger to the individual (e.g., pursuit,
attack, injury)

131. •on awakening, individuals with this disorder can describe the
dream sequence and content in detail
•individuals may report multiple nightmares within a given
night, often with a recurrent theme
•nightmares arise almost exclusively during rapid eye
movement
•Nightmare Disorder causes significant subjective distress
more often than it causes demonstrable social or
occupational impairment.
•If the individual avoids sleeping because of fear of
nightmares, the individual may experience excessive
sleepiness, poor concentration, depression, anxiety, or
irritability that can disrupt daytime functioning.

132. Diagnostic Criteria for Nightmare
Disorder
A. Repeated awakenings from the major sleep period or naps with
detailed recall of extended and extremely frightening dreams,
usually involving threats to survival, security, or self-esteem. The
awakenings generally occur during the second half of the sleep
period.
B. On awakening from the frightening dreams, the person rapidly
becomes oriented and alert (in contrast to the confusion and
disorientation seen in Sleep Terror Disorder and some forms of
epilepsy).
C. The dream experience, or the sleep disturbance resulting from the
awakening, causes clinically significant distress or impairment in
social, occupational, or other important areas of functioning .
D. The nightmares do not occur exclusively during the course of
another mental disorder (e.g., a delirium, Posttraumatic Stress
Disorder) and are not due to the direct physiological effects of a
substance (e.g., a drug of abuse, a medication) or a general
medical condition.

133. ASSOCIATED FEATURES AND
DISORDERS
• In individuals with Nightmare Disorder, mild
autonomic arousal (e.g., sweating) maybe evident
on awakening.
• Individuals who have had frequent nightmares
since childhood tend to show elevated rates of
general psychopathology on symptom measures.
• Depressive and anxiety symptoms that do not
meet criteria for a specific diagnosis are common
among individuals with Nightmare Disorder.

134. SPECIFIC CULTURE, AGE, AND GENDER
FEATURES
-The significance attributed to nightmare may vary
with cultural background. For instance, some
cultures may relate nightmares to spiritual or
supernatural phenomena, whereas others may
view nightmares as indicators of mental or
physical disturbance.
-Nightmare Disorder is most likely to appear n
children exposed to severe psychosocial
stressors.
-Females report having nightmares more often than
do men, at a ratio of approximately 2:1 to 4:1.

135. PREVALENCE
-Between 10% and 50% of children ages 3-5 years
have nightmares of sufficient intensity to disturb
their parents.
-In the adult population, as many as 50% of
individuals may report at least an occasional
nightmare.
-In young adults, at least 3% report having
nightmares frequently or always.
-The actual prevalence of Nightmare Disorder is
unknown.

136. COURSE
• Nightmares often begin between ages 3 and 6
years.
• When the frequency is high (e.g., several per
week),the dreams may become a source of
concern and distress to both children and
parents.
• Adults with chronic nightmares report similar
degrees of subjective disturbance as those who
have had nightmares for less than 6 months.

137. SLEEP TERROR DISORDER
-Sleep terrors are also called “night terrors” or
pavor nocturnes
-During a typical episode, the individual abruptly
sits up in bed screaming or crying, with a
frightened expression and autonomic signs of
intense anxiety (e.g. rapid breathing, flushing of
the skin, sweating, dilation of the pupils,
increased muscle tone).
-The individual is usually unresponsive to the efforts
of others to awaken or comfort him or her.

138. Diagnostic Criteria for Sleep Terror
Disorder
A. Recurrent episodes of abrupt awakening from sleep, usually
occurring during the first third of the major sleep episode and
beginning with a panicky scream.
B. Intense fear and signs of autonomic arousal, such as tachycardia.
rapid breathing,and sweating, during each episode.
C. Relative unresponsiveness to efforts of others to comfort the
person during the episode.
D. No detailed dream is recalled and there is amnesia for the
episode.
E. The episodes cause clinically significant distress or impairment in
social, occupational, or other important areas of functioning.
F. The disturbance is not due to the direct physiological effects of a
substance (e.g., a drug of abuse, a medication) or a general
medical condition.

139. ASSOCIATED FEATURES AND
DISORDERS
• The episode is usually accompanied by yelling,
screaming, crying, or incoherent vocalizations.
The individual may actively resist being held or
touched or even demonstrate more elaborate
motor activity (e.g., swinging, punching, rising
from the bed or fleeing).
• Episodes that simultaneously include features
of sleep terror and sleepwalking can occur.

140. • Alcohol or sedative use, sleep deprivation,
sleep- wake schedule disruptions, fatigue or
physical or emotional stress increase the
likelihood of episodes.

141. AGE AND GENDER FEATURES
• Among children, Sleep Terror Disorder is more
common in males than in females.
• Among adults, the sex ratio is even.

142. PREVALENCE
• There are limited data on Sleep Terror
Disorder in the general population.
• The prevalence of sleep terror episodes (as
opposed to Sleep Terror Disorder in which
there is recurrence and distress or
impairment) has been estimated at 1%-6%
among children and at less than 1% of adults.

143. COURSE
-The episodes most commonly occur for the first
time between ages 4 and 8 years. The peak
prevalence occurs at about age 12.
-Episodes rarely occur for the first time in adults,
although some associated behaviors such as
nocturnal eating may begin several years after
the sleepwalking itself.
-Sleepwalking in childhood usually disappears
spontaneously during early adolescence, typically
by age 15 years. Less commonly, episodes may
have a recurrent course, with return of episodes
in early adulthood after cessation of episodes in
late childhood.

144. Parasomnia Not Otherwise Specified
• The Parasonmia Not Otherwise Specified category is for disturbances that
are characterized by abnormal behavioral or physiological events during
sleep or sleep-wake transitions, but that do not meet criteria for a more
specific Parasomnia.
• Examples include -
1. REM sleep behavior disorder: motor activity, often of a violent nature,
that arises during rapid eye movement (REM) sleep. Unlike sleepwalking,
these episodes tend to occur later in the night and are associated with
vivid dream recall.
2. Sleep paralysis: an inability to perform voluntary movement during the
transition between wakefulness and sleep. The episodes may occur at
sleep onset (hypnagogic) or with awakening (hypnopompic). The
episodes are usually associated with extreme anxiety and, in some cases,
fear of impending death. Sleep paralysis occurs commonly as an ancillary
symptom of Narcolepsy and, in such cases, should not be coded
separately.
3. Situations in which the clinician has concluded that a Parasonmia is
present but is unable to determine whether it is primary, due to a
general medical condition, or substance induced.

145. Neurobiology of Sleep

146. • First investigations – 1930s.
• Bremer – transected cat brain stem – Sleep/wake
cycles remained intact after a low medullary level
transection whereas transection betweeen pons
and mid brain yielded chronic drowsiness.
• Electrical stimulation of the mid brain reticular
formation caused alerting of the cortex.
From these observations – Forebrain was kept alert
by tonic activity in the reticular formation.

147. In contrast...
• Transecting pons rostral to the trigeminal
nerve induced constant wakefulness.
• Suggested that input from a sleep centre in
the lower pons or medulla inhibited a
wakefulness centre in the rostral pons.
• Hence, it was established that sleep is an
active state of the brain.
• But identity of this lower brainstem sleep
centre remained a mystery.

148. • Von Economo – Through lesion studies after WW1 - the
posterior hypothalamus is important for the
maintenance of the wakefulness and the anterior
hypothalamic region is important for sleep induction.
• Sleep active neurons – were described in the basal
forebrain, particularly the substantia innominata and
the horizontal limb of the diagonal band of broca.
• Subsequent studies identified the GABAergic Ventro-
lateral preoptic area (VLPO) and Median Preoptic Area
(MnPO) as being sleep active neuronal populations
that project to and inhibit wake-active cell groups.

149. • Histaminergic neurons in Tuberomamillary
nuclei have been found to be wake promoting
and project widely throughout the brain.
• They are inhibited by the inhibitory neurons
from the VLPO neurons.
Sleep results from functional blockade of a
posterior hypothalamic waking centre.

150. REM Sleep – Role of Pons & ACh
• First described by – Aserinsky & Kleitman
• 1960s & 70s – firing rates of cells in specific brain
regions were characterised across arousal continuum –
1. Monoaminergic cell groups decrease their firing from
wakefulness to REM – REM-off cells.
2. Smaller set of brainstem regions had maximal firing
rates during REM – REM-on cells
• Hobson and McCarley – NREM/REM cycle arises from
a reciprocal interaction between these aminergic
REM-off cells and cholinergic REM-on cells in the
Medial Pons.

151. • Pons – Both necessary and sufficient to
generate REM sleep – Dorsolateral Pons is
particularly crucial for genesis of REM sleep.
• Neurons in Dorsolateral Pons have REM-on
profile.
• Activation of Dorsolateral Pons during REM
sleep –
Responsible for physiological manifestations,
REM and atonia.

152. Muscle Atonia in REM sleep
• Pathway - Cholinoceptive dorsolateral pontine neurons
project to the ventral medulla – form synapses with
inhibitory neuronal populations – project to inhibit
motorneurons in spinal chord.
• Lesions of Dorsolateral Pons – Produced REM sleep
without atonia in cats – Movements as if acting out in
dreams.
• Similar condition in humans – REM behavior disorder.
• Narcolepsy/Cataplexy – Cataplexy is triggered by
positive emotional stimuli – processed by limbic system
– these stimuli seem to converge on the muscle atonia
pathway, likely through prefrontal cortex and
amygdala.

153. Hypocretin/Orexin System
• Hypocretin 1 & 2 (Hcrt1 & Hcrt2) – Also k/a Orexin A & B – Independently described by
two groups in 1998.
• Hcrt neuorns – Found exclusively in PLH.
• Directly excites cellular systems involved in waking and arousal –
 Histaminergic cells of Tuberomammillary nuclei
 5HT cells of Dorsal Raphe Nuclei
 Noradrenergic cells of Locus Ceruleus
 Cholinergic cells of Laterdorsal Tegmental Nuclei, Pedunculopontine tegmentum nuclei,
& basal forebrain.
• Afferents –
 Lateral Septal nucleus
 Bed nucleus of the stria terminalis
 Preoptic area
 Dorsomedial, ventromedial and posterior hypothalamic nuclei
 Substantia nigra & Ventral tegmental area
 Dorsal raphe nuclei
• Anatomy suggests – Involvement in numerous physiological functions –
 Sleep-wake
 Feeding
 Thermoregulation
 BP
 Neuroendocrine regulation

154. • Hcrt1 increases arousal when infused into the
brain.
• Optogentic stimulation or inhibition of Hcrt
signaling increases or decreases wakefulness,
respectively.
• Hcrt receptor antagonists – Promote sleep and
?without cognitive deficits and dependence.

155. Hypocretin System & Narcolepsy
• HLA class II antigen HLA DQB1*0602 - >85% of
narcoleptic patients with cataplexy but only 12 – 38%
of general population - ??Narcolepsy may be an
autoimmune disease.
• Undetectable levels of Hcrt1 in CSF.
• Post mortem studies –
1. Absence of preproHcrt mRNA
2. 85 to 95% reduction in the no. of Hcrt containing cells
3. Increased staining for glial fibrillary protein in the PLH
of narcoleptic brains

156. Model for Arousal State Regulation
• Relative activation of wake active systems – BF, LDT/PPT, LC, DRN &
TM – and sleep-actve systems – VLPO & MnPO.
• During wakefulness – Monoaminergic projections from ARAS
activate wake promoting regions en route to cerebral cortex while
inhibiting sleep promoting neurons.
• During NREM sleep - GABAergic output forom VLPO, MnPO, & PZ
inhibit these populations.
• During REM sleep – Increased brainstem cholinergic activity (REM-
on) and inhibition of aminergic (REM-off) populations.
• Hcrt signaling promotes waking by activating brainstem abd
forebrain wake-active populations.
• Flip-Flop Switch Model of REM-NREM – Hcrt consolidates waking
and sleep states by stabilising transitions between sleep and
wakefulness as well as REM and NREM.
• Dysfunctional Hcrt system – Narcolepsy – extended periods of
wakefulness and sleep cannot be maintained and instead there is
rapid shift between these states.

157. Neurotransmitters in Sleep
Serotonin :-
• Prevention of serotonin synthesis or
destruction of the dorsal raphe nucleus of the
brain stem, which contains nearly all the
brain's serotonergic cell bodies, reduces sleep
for a considerable time
• Ingestion of L-tryptophan (which influences
serotonin synthesis) in large amount reduces
sleep latency and nocturnal awakenings.
• Conversely L-tryptophan deficiency is
associated with less time spent in REM sleep.

158. Nor epinephrine :-
• Nor epinephrine containing neurons with cell
bodies located in the locus cerulean play an
important role in controlling normal sleep
patterns.
• Drugs and manipulations that increase the firing
of these neurons markedly reduce REM sleep
(REM off neurons) and increase wakefulness.
• NE is lower during REM sleep

159. Acetylcholine:- Brain acetylcholine is also
involved in sleep, particularly in the
production of REM sleep.
• Disturbances in central cholinergic activity are
associated with sleep changes observed in
major depressive disorder.
• Higher during REM sleep
• Ratio of ACh & NE is the biochemical trigger
for REM sleep.

160. • Depression can be associated with an
underlying super sensitivity to ACH.
• Loss of cholinergic neurons in the basal
forebrain is associated with sleep disturbances
such as reduced REM & slow wave sleep as
seen in pt. Alzheimer's.

161. Dopamine :-
• Evidence shows that dopamine has are
alerting effect.
• Drugs that increase dopamine concentrations
in the brain tend to produce arousal and
wakefulness.

162. Sleep Homeostasis and the Timing of
Sleep and Wakefulness
• Sleep is a homeostatically regulated response.
• 2-process Model Of Sleep Regulation –
Homeostatic sleep related process S integrates input from the
circadian system (process C) to gate occurrence of sleep and
wakefulness throughout the day.
Process S – Proposed to be the neurochemical processes that begin to
build up at the onset of wakefulness and once the threshold value is
reached sleep will ensue but only if the process C is in appropriate
circadian phase.
• Delta waves – Increase in proportion to prior wake duration –
NREM delta power (NRD), also k/a EEG slow wave activity.
• NRD is suggested to reflect the cortical manifestation of the
recovery from prior waking activities – Quantitative measurement
of the Process S.

163. Anatomic Substrates of the 2-process
Model
Process C – Suprachiasmatic Nucleus (SCN)
• Not clear whether SCN specifically promotes
wakefuleness, sleep or both.
• More recently – Hcrt was proposed as the point
of integration between circadian and homeostatic
mechanisms – Based on CSF Hcrt1 levels assayed
throughout the day.
• But it is not clear to what extent the change in
levels is due to regulation (circadian or
homestatic) or is passively driven by increased
locomotor acitivity.

164. • Process S – Substrate has proven difficult to
identify –
1. GABAergic neurons in MnPO
2. Cortical neurons expressing neuronal nitric
oxide synthase (nNOS)

165. Other Neurochemicals involved in
sleep/wake control
• Melatonin
• Cytokines – IL-1, TNF-α
• Peptides –
 Wake promoting – CRF, ACTH, TRH, Neuropetide
Y
 Sleep promoting – GH, CCK-8, α-melanocyte
stimulating hormone, insulin, IGF-1
• Adenosine
• PGD2
• Gonadal Steroids

166. Melatonin
• Produced by Pineal gland during the night in both dirunal and nocturnal
species.
• Specific Receptors – Found in –
1. Cortex
2. SCN
3. Hypothalamic regions involved in thermo-regulation
• Function – Helps synchronise circadian rhythms.
• Use –
1. Physiologic dose – 0.03 mg – can help in sleep onset processes when
sleep initiation is attempted at abnormal times.
2. Pharmacologic dose - 1-10mg – May work through nonmelatonin
receptors.
• Limitaions –
1. Evidence to support the efficacy as general sleep aid is limited.
2. Proper dosage to be used in treatment of insomnia is not weel
dileanated – Lack of rigorous dose-response studies.

167. Approach to & Evaluation of
Sleep Disorders

168. Sleep History
• Central Component
• Supplemented by bed partner, family member,
or room-mate

169. Which symptoms can a pt. present
with??
• Insomnia –
1. Psychiatric disorders
2. Psychophysiological insomnia
3. Obstructive sleep apnea
4. Inadequate sleep hygiene
5. Idiopathic insomnia
6. RLS
7. Environmental sleep disorder
8. Adjustment insomnia
9. Delayed sleep phase disorder
10. Medications
11. Medical Disorders

170. • Hypersomnia
1. Insufficient sleep syndrome
2. Obstructive sleep apnea
3. PLMD
4. Medications
5. Narcolepsy
6. Idiopathic Hypersomnia
7. Mood disorders
• Unusual sleep behaviors
1. Sleepwalking
2. Sleep terrors
3. REM sleep behavior disorder
4. Sleep related epilepsy
5. PLMD
• Disturbance in timing of sleep –
1. Jet lag
2. Shift work sleep disorder
3. Advanced sleep phase disorder
4. Delayed sleep phase disorder

172. • Sleepiness vs. Fatigue
• Daytime sleepiness – Situations
• Insomnia – Difficulty with sleep initiation or maintenance, waking too
early, or sleep that is non-restorative, despite ample opportunity to sleep.
• “3P Model” –
a) Predisposing Factors –
1. Personality traits
2. Preferred sleeping times
b) Precipitating Factors – Major life transitions
c) Perpetuating Factors –
1. Perceived association between sleeping environment and inability to sleep
2. Excessive caffeine consumption
• Nocturnal behaviors – Posing risk to the patient or the bed partner

173. Physical Examination
• Measurement of –
1. Height
2. Weight
3. BMI
4. Neck circumference
5. Blood pressure
6. Heart rate
• Auscultation
• Peripheral oedema
• Mental status examination
• Neurological examination – DM with RLS

174. Head & Neck Examination
• Facial Morphology –
a. Long face syndrome –
1. Infra-orbital darkening
2. Mouth breathing
3. Elongated midface
4. Nasal atrophy
b. Mandibular Retrognathia
• Nasal Airway
1. Symmentry of the nares
2. Nasal Septal Deviation
3. Nasal turbinate hypertrophy
4. Collapse of the nasal alae on inspiration

177. • Oral Airway –
1. Low soft palate
2. Large or boggy uvula
3. Erythematous pillars
4. Tonsillar hypertrophy
5. High, narrow hard palate
6. Neck circumference
7. Macroglossia
8. Worn occlusives surfaces

183. • Neck circumference –
• Patients with OSA have significantly increased
neck circumference as compared to non-apneic
snorers.
• Greater distribution of neck fat may contribute to
mass loading on the upper airway in the patients
with OSA.
• Measured at the superior border of cricothyroid
membrane.
• >40 cm – predictive of OSA with 61% sensitivity
and 93% specificity, regardless of sex.

184. • American Academy of Sleep Medicine –
1. Increased neck circumference - Greater than 43.2 cm (17 in) in men,
greater than 40.6 cm (16 in) in women,
2. BMI 30 kg/m2 or greater,
3. modified Mallampati classification of III or IV,
4. Retrognathia,
5. Lateral peritonsillar narrowing,
6. Macroglossia,
7. Tonsillar hypertrophy,
8. Elongated/ enlarged uvula,
9. High-arched/narrow hard palate,
10. Nasal abnormalities – e.g. polyps, deviation, valve abnormalities, and
turbinate hypertrophy
11. Overjet

185. Subjective Assessment
1. Epworth Sleepiness Scale – Subjective assessment of the patient’s daytime sleep
propensity in recent times.
• Can be easily incorporated into the clinical evaluation - Should not be used as a substitute
for objective measurement of sleepiness.
• May correlate to a limited extent with the presence and severity of OSA - Some studies
have failed to find any statistically significant association with mean sleep latency on
multiple sleep latency tests, or with severity of OSA.
• Most advantageous use – to follow an individual’s self-assessment of sleepiness
longitudinally, and it may also serve as an indicator of treatment response.
2. Patient Reported Outcomes Measurement Information System (PROMIS) - An NIH-
supported system of measures for patient-reported health status and includes questions
on sleep disturbance.
3. Pittsburgh Sleep Quality Index (PSQI) - Inquires about sleep quality and disturbances over
the previous month.
4. Pediatric Sleep Questionnaire – Parent completed, assess risk for SDB in children.
5. STOP-BANG questionnaire - Sensitive screening tool for OSA.
6. International Restless Legs Syndrome Study Group Rating Scale (IRLS) - Assessment of
disease severity for patients with restless legs syndrome.
7. Insomnia Severity Index (ISI) – Patient’s perceived level of insomnia.

186. Sleep Diary
• Chart daily sleep and wake times and should be maintained
for at least 2 consecutive weeks.
• Review of this information allows the clinician to estimate
the total amount of sleep the patient obtains in a 24-hour
period.
• Sleep Pattern –
1. Is sleep obtained at the same times every day?
2. Is the patient’s sleep consolidated or fragmented across
24 hours?
3. Does the patient sleep and wake at conventional times, or
does he or she appear to be a ‘‘night owl’’ or ‘‘morning
lark?’
• Particularly helpful in patients with suspected circadian
rhythm sleep disorders (including shift work), behaviorally
induced insufficient sleep, or inadequate sleep hygiene.

188. Objective Measures

189. Nocturnal Polysomnography
• Indications –
1. Sleep-disordered breathing
2. Narcolepsy
3. Idiopathic Hyspersomnia
4. Parasomnias
5. Nocturnal seizures
6. To titrate CPAP or BiPAP as a treatment for
sleep-disordered breathing

190. • Recommended recording montage –
1. Central (C3-A2, C4-A1), frontal (F3-A2, F4-A1), and occipital (O1-A2, O2-
A1) EEGs,
2. Left and right eye electro-oculograms,
3. Mental/submental surface EMG,
4. ECG leads.
• Other recorded parameters - include
1. Thoracic and abdominal effort,
2. Oxygen saturation,
3. Nasal/oral airflow, and
4. Body position.
5. Use of a microphone to record snoring is recommended but not
required.
6. A full, 16-lead EEG and video recording may be performed when
nocturnal seizures are suspected.
7. Leg surface EMG leads are recommended, and additional arm EMG leads
may be applied when the clinical history suggests complex sleep-related
motor behaviors, such as dream enactment.

191. • In most cases the diagnostic NPSG is done on 1 night,
although NPSG on 2 consecutive nights may be
considered in the evaluation of parasomnias.
• Four categories of sleep monitoring devices for use in
the diagnosis of sleep disorders have been described –
Type 1 - Standard, attended, in laboratory
polysomnography;
Type 2 - Comprehensive portable, unattended
polysomnography;
Type 3 - Modified portable sleep apnea testing (often
cardio-respiratory studies that do not record sleep);
and
Type 4 - Continuous single or dual bioparameter
recording (eg, pulse oximetry)

192. • Use of portable monitoring may be indicated
for the -
1. Diagnosis of OSA in patients for whom
attended NPSG is not possible because of
immobility, safety, or critical illness.
2. To monitor the response to non-continuous
positive airway pressure treatments for OSA.

193. Multiple sleep latency test (MSLT)
• Standard for evaluation of excessive daytime sleepiness.
• Recommended Protocol -
1. Five 20-minute nap opportunities held at 2-hour intervals
throughout the day.
2. If sleep is observed, the patient is allowed to sleep for at least 15
minutes.
3. The sleep latency for each nap is measured as the time from the
start of the nap trial to the first epoch of sleep.
4. The mean sleep latency, calculated as the average sleep latency
across all nap trials, is the final result.
5. The presence and number of sleep on set REM periods (SOREMPs)
is also determined, as this information can help to establish a
diagnosis of narcolepsy without cataplexy or to confirm
narcolepsy with cataplexy.

194. • The MSLT should be started 1.5 to 3.0 hours
following completion of a nocturnal
polysomnogram, which should record at least
6 hours of sleep in order for determination of
the mean sleep latency to be valid.
• Drugs that may interfere with sleep latency or
REM latency should be discontinued 2 weeks
before testing, whenever possible.

195. • A mean sleep latency of greater than 10 minutes is often
considered normal, whereas a mean sleep latency of 8 to 10
minutes is considered a physiologic gray zone.
• International Classification of Sleep Disorders: Diagnostic and
Coding Manual (ICSD-2) requires the presence of a mean sleep
latency of less than 8 minutes and two or more SOREMPs as part of
the diagnostic criteria for narcolepsy without cataplexy.
• However, the ICSD-2 also notes that a mean sleep latency of less
than 8 minutes may occur in up to 30% of the general population.
• Therefore, while the MSLT is a helpful and widely used tool, it
remains an imperfect gold standard in the assessment of daytime
sleepiness.
• This necessitates that the evaluation of daytime sleepiness not rest
on the MSLT results alone but assimilate the clinical history,
subjective complaints, diagnostic study results, and other pertinent
medical information.

196. Maintenance of Wakefulness Test
(MWT)
• Objective measure of a patient’s ability to
remain awake, rather than the tendency to fall
asleep, during the day.
• Key difference between the MWT and the
MSLT is that in the former, the patient is asked
to try to stay awake under circumstances
conducive to sleep, rather than to fall asleep.

197. • Recommended protocol -
• Four 40-minute trials that begin at 2-hour
intervals, with the first trial to start 1.5 to 3.0
hours after the patient’s wake-up time.
• A nocturnal polysomnogram on the preceding
night is not required. However, the patient should
obtain a sufficient amount of sleep during the
night before the MWT.
• Each trial is terminated after 40 minutes if no
sleep occurs,or after unequivocal sleep onset
(defined as three continuous epochs of stage N1
sleep or one epoch of any other stage of sleep)
has occurred.

198. • Indications –
1. To assess an individual’s ability to remain
awake when his or her inability to remain
awake constitutes a public or personal safety
issue.
2. To assess treatment response in patients with
known excessive daytime sleepiness

199. Actigraphy
• An actigraph is a watchlike device that is worn on
the wrist for an extended period, usually in the
range of weeks.
• The actigraph records movement and uses an
algorithm to estimate the amounts of sleep and
wake time during the recording period.
• Analysis software uses movement to estimate
when sleep and wakefulness have occurred.
Review of the data can provide objective insight
into the patient’s sleep pattern, including timing
and duration of major sleep disruptions.

200. Indications -
• Evaluation of patients with sleep disorders,
particularly circadian rhythm sleep disorders.
• Measure of treatment response in patients
with insomnia and circadian rhythm sleep
disorders.
• When polysomnography is not available,
actigraphy is indicated to estimate total sleep
time in patients with OSA.

201. Other Assessment Modalities
• CT or MRI – Based on the history
• CBC, Serum chemistry, or measures of thyroid
function if the an underlying medical disorder
is thought to contribute to patient’s sleep
symptoms.
• Serum Ferritin – for RLS

202. Management of Sleep Disorders

203. • Insomnia
• Insufficient Sleep Sydrome
• Obstructive Sleep Apnea
• Narcolepsy
• Hypersomnia
• RLS and PLMD
• Parasomnias
• Circadian Rhythm Sleep Disorders –
1. Delayed Sleep Phase Type
2. Advanced Sleep Phase Type
3. Irregular sleep-wake type
4. Non-24 sleep wake type
5. Shift work type

204. Insomnia
• Non-pharmacologic –
1. Stimulus Control Therapy
2. Relaxation Therapies
3. Sleep Restriction
4. Cognitive therapy
5. Paradoxical Intention
6. Sleep Hygiene Education
7. Cognitive Behavioral Therapy
• Pharmacologic

205. Non-pharmacologic
1. Stimulus Control Therapy
• Method – Patients are instructed to get out of
bed after 15 to 20 mins of sleeplessness while in
bed, go to another room, engage in relaxing
activities, but remain awake and then return to
the bedroom only when sleepy.
• Objective – Re-associate the bedroom and bed
with sleep and break the mental association
between bedroom and wakefulness.

206. Relaxation Therapies
• Progressive Muscle Relaxation
• Biofeedback
• Guided imagery
• Autogenic training
• Abdominal breathing exercises
• Meditation

207. Sleep Restriction Therapy
• Works by producing a state of ‘sleep debt’ – which aids in
consolidating the subsequent sleep.
• Method – Patients are initially instructed to limit the time spent in
bed to the amount of actual time they habitually sleep, as
determined using sleep logs.
• Sleep efficiency for the patient is calculated over a 5-day period.
• When sleep efficiency increases to greater than 90%, patients are
allowed 15-20% of additional time in bed by going to bed earlier.
• If sleep efficiency decreases to below 85%, their time in bed is
curtailed by similar amount.
• Morning rising time – Kept constant
• Napping – disallowed
• Over time sleep becomes more consolidated and productive.

208. Cognitive Therapy
• Strives to identify and dispel thoughts that are tension
producing and have a negative effect on sleep.
• Thoughts –
 Unrealistic expectations – “I must get 8 hrs of sleep every
night”
 Amplification of consequences – “Insomnia is incurable”
 Sleep performance anxiety – “If I do not sleep well tonight,
my performance tomorrow will be seriously jeopardised”
• Once identified – Misperceptions are challenged
consciously and positive perceptions about sleep are
substiuted.

209. Paradoxical Intention
• Attempts to dissolve performance anxiety that
prevents sleep by asking patients to stop
trying to sleep and deliberately attempt to
remain awake,

210. Sleep Hygiene
• Encompasses identifying behaviors and external factors that impair sleep quality and quantity, and
eliminating them.
• Measures –
 Do’s -
1. Increase exposure to bright light during the day
2. Establish a daily activity routine.
3. Exercise regularly in the morning and in afternoon.
4. Set aside a worry time
5. Establish a comfortable sleep environment
6. Do something relaxing before bedtime
7. Try a warm bath
 Don'ts -
1. Alcohol
2. Caffeine, nicotine and other stimulants
3. Exposure to bright light during the night
4. Exercise within 3 hrs of bed time
5. Heavy meals or drinking within 3 hrs of bedtime
6. Using your bed for things other than sleep (or sexual activity)
7. Napping, unless a shift worker
8. Watching the clock
9. Trying to sleep
10. Noise
11. Excessive heat or cold in the room

211. Pharmacotherapy for Insomnia
• Alcohol – one of the most widely “self-prescribed” agents –
enhances sleepiness and decreases sleep latency.
Poor Choice – Nocturnal awakenings and daytime somnolence,
and can further impair sleep related breathing in patients of
OSA.
• Antihistamines - Not recommended wholeheartedly because
of unpredictable effect son sleep and other systemic effects.
• Barbiturates and barbiturate like drugs – Chloral hydrate and
Glutethemide – Used in past – No longer recommended due
to greater potential to cause overseadtion and even death in
overdoses.

212. 1. BZD-GABA receptor agonists –
• BZDs
• Non-BZDs – Zolpidem, Zaleplon, Eszopiclone
2. Melatonin receptor agonists – Agomelatine,
Ramelteon
3. Orexin Receptor Agonists – Suvorexant
4. Histamine receptor antagonists – Hydroxyzine,
Doxepin
5. Sedating antidepressants – Miratzepine, Trazodone
6. Atypical Antipsychotics – Quetiapine, Olanzapine
7. Antiepilepsy Medications – Gabapentin and
Tiagabine.

213. American Academy of Sleep Medicine
Algorithm for Insomnia
1. Short and intermediate acting BZD receptor agonists or
ramelteon.
2. Alternate short and intermediate acting BZD receptor
agonists or ramelteon if the initial agent has been
unsuccessful.
3. Sedating antidepressants, especially when used in
conjunction with treating co-morbid depression/anxiety.
4. Combined BZD receptor agonists or ramelteon and
sedating antidepressant.
5. Other sedating agents; Antiepileptics and atypical
antipsychotics. These medications may only be suitable
for patients with comorbid insomnia who may benefit
from the primary action of these drugs as well as from the
sedating effects.

214. Obstructive Sleep Apnea
1. CPAP – Continuous Positive Airway Pressure
• First-line treatment
• Ambulatory device that introduces room air at a high flow rate into the upper
airway by nasal mask and dissipates apneas by means of a “pneumatic splint”
mechanism.
• The optimum pressure required to eliminate apneas is determined through PSG
with a variable pressure device, after which the patients use CPAP at a constant
pressure at home while asleep.
• Disadvantage – Non-adherence –
a) Upper airway irritation
b) Discomfort at the mask site
c) Feeling of suffocation
• Enhancing adherence –
a) In-line air humidification
b) Mask shapes and sizes tailored to patient’s preference
c) Bilevel positive airway pressure devices that deliver lower pressures during
expiration
d) Demand pressure devices
2. Weight Reduction
3. Oral appliances that prevent mandibular and tongue collapse during sleep

216. 4. Positioning devices – if breathing disturbance is more in
supine position than a device that promotes sleep in non-
supine position can be used – Zzoma Device
5. Uvulopalatopharyngoplasty – uvula is partially removed
along with tonsils and part of the soft palate.
Combing with Genioglossus advancement-hyoid myotomy or
maxillary and mandibular osteotomy increase success
rates.
Second-line management in those who cannot tolerate CPAP.
6. Pharmacotherapy – Modafinil or Armodafinil
7. Upper airway stimulation – FDA approved for Refractory
OSA.

218. Narcolepsy
• Directed at – Daytime somnolence, REM-related aberrations and Psycho-
social consequences.
• Milder cases – excessive sleepiness can be managed with conservative
measures –
1. Spending adequate time in bed
2. Taking 2 or 3 short naps
3. Avoiding alcohol and other sedating agents
• Severe cases – Judiciously timed naps can minimize the dosage of
medications.
Commonly used medications –
For EDS – Modafinil, armodafinil, Methylphenidate, Amphetamine,
Methamphetamine.
For Cataplexy – Protriptyiline, Fluoxetine, Venlafaxine, Clomipramine
For both – Sodium oxybate (the only FDA approved drug for cataplexy)
• Psycho-education is important as drowsiness may be confused with
laziness or lack of motivation.

219. Hypersomnia Disorder
• No drugs specifically FDA approved.
• Same treatment as Narcolepsy except that
there is no role of drugs for cataplexy.

220. RLS and PLMD
• 80% of patients with RLS also have PLMD.
• Both common in middle and older age.
• Can be –
Primary/Idiopathic, or
Secondary – Wide variety of conditions (e.g. Pregnancy), intake of certain
drugs (like caffeine, antidepressants), drug withdrawl states, iron
deficiency, uremia, leukemia, RA.
• Diagnosis – RLS – Doesn’t require PSG and can be made from history
alone.
PLMD – Requires PSG – Periodic leg muscle bursts during quiet wakefulness
and sleep, the latter associated with arousals and wakenings.
• RLS should be distinguished from –
 Nocturnal leg cramps – Pain in deep muscles of lower extremities which
worsen with movt., independent of sleep.
 Akathisia – Motor restlessness that occurs in context with neuroleptics
and antidepressants.

221. • Once diagnosis is established –
 Thorough physical examination
 Chemistry panel
 CBC
 Serum ferritin
• If serum ferritin <50 μg/L – Supplementation with ferrous sulfate and
subsequent follow-up monitoring to avoid iron overload.
• Sleep hygiene
• For the primary disorder – Dopamine agonists – Pramipexole, ropinirole,
rotigotine.
• Gabapentin-enacarbil – also FDA approved for RLS – differs from
gabapentin in that enacarbil moeity is a prodrug that allows for better g. i.
absorption and enhanced bioavailability
• Refractory patients – BZDs or opiates, like codeine – But they are not FDA
approved.
• Levodopa with carbidopa is no longer used – High propensity for
augmentation.

222. Parasomnias
Sleep Walking
C/Fs –
1. Ambulation in sleep
2. Age affected – Prepubertal children
3. Difficulty in arousal during episode
4. Episodes occur in first 1/3rd of night
PSG –
Sleepwalking out of SWS
T/t –
1. Prevention – removal of sharp objects, floor mattress
2. Psychoeducation of parents
3. Psychiatric evaluation of adults
4. BZDs in refractory cases

223. Sleep Terrors
C/Fs –
• Sudden, intense screaming during sleep with
evidence of intense fear
• No dream recall
PSG –
• Sleep terror begin during SWS
Treatment –
• Reassurance in children
• Psychiatric evaluation in adults

224. Nightmare Disorder
C/Fs –
• Sudden awakening with intense fear
• Recall of frightening dream content
• Full alertness on awakening
• Usually occur in latter half of the night
• Frequent nightmares can be indicative of psychiatric conditions.
PSG –
• Abrupt wakening from REM
• Tachycardia and tachypnea during episode
T/t –
• Psychotherapy
• Hypnosis
• Prazosin

225. REM Sleep behavior Disorder
C/Fs –
• Violent or injurious behavior during sleep
• Body movement associated with dreams
• Dream recall present
• Dreams are enacted while they occur
PSG –
• Excessive EMG tone or phasic twitching in REM
T/t –
• Clonazepam
• Melatonin
• Protective measures
• Psycho-education

226. Sleep Bruxism
C/Fs –
• Tooth grinding or clenching during sleep
• Tooth wear
• Jaw discomfort
PSG – bursts of jaw EMG activity during SWS
T/t –
• Dental examination
• Mouth guards
• Relaxation training
• Psycho-education

227. Circadian Rhythm Sleep-Wake
Disorders
Delayed sleep phase type
Diagnosis – Sleep logs and/or actigraphy for at least
7 days
Treatment – Advancing circadian phase –
• Low dose (0.5-3mg) of melatonin, 5 hrs before
habitual bedtime.
• Bright light (at least 500 lux) for 30 min to 2 hrs
on wakening

228. Advanced Sleep Phase Type
Diagnosis –
• Sleep logs and/or actigraphy for at least 7 days
Treatment – Delaying circadian phase –
• Bright light (at least 5000 lux) for 2 hrs in the
evening (e.g. 7-9pm)

229. Shift Work Type
Diagnosis –
• Clinical history – Sleep logs and/or actigraphy may also be
useful.
Treatment – Aligning circadian rhythm to work schedule –
• Sleep hygiene
• Bright light intermittent exposure at work
• Avoid bright light in the early morning
• Low dose melatonin at sleep time
• Excessive sleepiness – Modafinil/armodafinil, scheduled
naps, caffeine, bright light
• Insomnia symptoms – Melatonin, Hypnotics

230. Sleep and Drugs
1. Stimulants – caffeine, nicotine, methylphenidate, amphetamines, cocaine,
modafinil
• All interfere with sleep:
• Increase -
1. WASO
2. # awakenings
3. SOL
4. Stages 1&2
• Decrease -
1. TST
2. stages 3&4
3. stage REM
Note: must consider drug half-life and when take drug relative to bedtime
SOL; sleep onset latency
WASO; wake time after sleep onset
TST; total sleep time

231. 2. Sedative-Hypnotics –
• All facilitate sleep, but may alter sleep architecture/staging:
• Increase
1. TST,
2. stage 2 (esp. sleep spindles)
3. next day sleepiness (“hangover”)
• Decrease
1. WASO
2. # awakenings
3. SOL
4. Marked decrease in stage REM with barbiturates
5. Marked decrease in stages 3&4 with BZDs, slight decrease with
barbs

232. 3. Antidepressants -
May either interfere with or facilitate sleep
• MAOIs:
1. Can completely eliminate stage REM
2. Slight increase in WASO
3. Slight decrease in TST

233. • TCAs:
1. Suppress REM to varying degrees
2. Slight increase in stage 3&4
3. increase TST usually
4. Some are sedating --- decrease WASO, # awakenings, &
SOL
5. Some are activating --- increase WASO, # awakenings, &
SOL
e.g. sedating antidepressants: Amitriptyline, doxepin,
imipramine
e.g. non-sedating (activating) antidepressants:
clomipramine, desipramine, nortriptyline, protriptyline

234. • SSRIs:
1. Suppress REM
2. May markedly delay REM onset
3. May decrease TST
4. May increase SOL
5. Depends on the individual medication -
Fluoxetine: increased insomnia reported in 5 –
19% of patients
6. Fluvoxamine, Paroxetine: sedation reported in
up to 26% of patients

235. • Trazodone -
1. 5 – 45% of patients report “drowsiness”
2. Increased TST, next day EDS, stages 3 & 4
3. Decreased SOL, WASO, slight decrease in REM
• Venlafaxine -
1. 4 – 18% of patients report “insomnia” at usual dose levels
2. 12 – 31% of patients report “somnolence” at higher dose
levels (>150mg)
• Mirtazapine -
1. Up to 52% of patients report “sedation”
• Bupropion -
1. 5 – 19% of patients report “insomnia”
2. No effect on TST or SOL
3. Decreased REM latency, increased % of REM

237. Mood Stabilizers –
• Lithium -
Increased -
1. sedation,
2. TST,
3. may increase stage 3&4
4. Decreased REM
5. Case of induced somnambulism has been reported
• Carbamazepine -
Increased
1. sedation (up to 11% of patients)
2. TST
3. Agitation, restlessness, & insomnia also reported occasionally
• Sodium Valproate -
1. Slight increase in sedation
2. No other significant effects on sleep reported

238. • Opioids -
Acute use:
1. increased WASO,
2. decreased REM & stages 3&4
Chronic use:
1. no change in WASO or stages 3&4,
2. decreased REM

239. • Aspirin:
acute use decreases stages 3&4
• Clonidine:
1. No effect on TST
2. Increases WASO,
3. more fragmented sleep architecture
4. Decreases REM
• Cimetidine:
Increases stages 3&4
• L-Dopa:
1. No effect on TST or stages3/4
2. Increases REM
• Steroids (including Prednisone):
1. Increases SOL, WASO, c/o insomnia
2. Decreases TST
• Tetrahydrocannabinol (marijuana)
1. Acute use: minimal sleep disruption, slight decrease in REM
2. Chronic use: long-term suppression of stages 3&4