TEXTBOOK

READING

SLEEP DISORDER
Charles A Czeisler. John W.Winkleman. Gary
S.Richardson

Pembicara :dr. Ratri Wulandari

Pembimbing : dr Sri Handayani,
SpS

Harrison
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Background
Sleep disturbance is one of the most frequent
complaints a physician could get.

More than one-half adult in USA had at least

intermittent sleep disturbance.

About 50-70 million Americans suffer from

chronic sleep disorder and wakefulness can lead
to serious impairment of daytime functioning.
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background..
Most complains treated with hypnotic
medications without further diagnostic
evaluations.
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Physiology of Sleep and

Wakfulness
Most adult sleep 7-8 hours per day.
Timing, duration and internal structure of
sleep may vary among healthy
individuals.

Infants and elderly have more frequent

interruptions of sleep.

InUSA, adults tend to have one

consolidated sleep episode per day.
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Physiology of Sleep and Weakfulness

Two principles neural system that
control the
expression of sleep :
1. Sleep Homeostat : Potentiate sleep in
proportion to the duration of wakefulness
state within daily cycle.
2. Circadian clock : Modulates sleep rhytmic
and wakefulness tendencies at
appropriate phases of the 24 hour day.
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Physiology of Sleep and Weakfulness

Factors that can affect the neural
systems :
1. Intrinsic anormalities : organ damage,
abnormalities in systems.
2. Extrinsic disturbances : environmental,
drugs, illness-related
States and Stage of 7 8/22/17

Sleep
Defined in basic characterisctic patterns
in
POLYSOMNOGRAPHIC

Electro Electro
Electro
Encephalo Myogram
oculogram
gram

Two state of sleep :

1. Rapid eye movement sleep
2. Non rapid eye movement sleep (N1, N2,
N3)
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Organization of Human
Sleep
After sleep onset, sleep
progresses through

NREM Stages
N1-N3 sleep
within 45-60
minutes

Slow wave sleep (NREM Stage N3 Sleep) predominates the first

third of the night, about 15-25 % of total nocturnal sleep in young
adults.
REM
Stages

Occur in the second hour of sleep, Rapid onset of REM ini adult may
suggest pathology such as endegenous deprression, narcolepsy, circadian
rhythm disorder or drug withdrawal.
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Age has a profound impact on

sleep state organization

Slow wave sleep is most intense and prominent in

childhood, decreasing sharply with puberty and
across the second and third decades of life.

After age 30, the amount of slow wave sleep

continue to declined. The depth of slow wave also
decreased.

In healthy older person, slow wave sleep may be

completely absent.
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Neuroanatomy of sleep

sleep
Generates Medullary reticular formation,
thalamus, basal forebrain

Generates Brainstem reticular formations,

wakefulnes midbrain, subthalamus, thalamus
s and basal forebrain

Experiemental studies in animal

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Capacity of wakefulness and sleep distributed along axial

core of neurons extending from brainstem rostrally to the
basal forebrain.

GABA and galaninergic These neurons project to and

neurons in VLPO inhibit the multiple neural
hypothalamus selectively wakefulnes centers, selective cell
activated coincident with specific lessions of VLPO (which
sleep onset. reduce sleep time)

Another sleep center, Another Specific

median preoptic regions of PONS.
Small lesions in
nucleus of dorsal pons result in Associations with REM
hypothalamus with loss of descending Sleep.
similar activation muscle inhibitions
centre.
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Neurochemistry of Sleep
Raphe nuclei of brainstem and Serotonin as
primary sleep promoting neurotransmitter
Cathecolamines for wakefulness

Multiple
parallel waking systems :histamine,
acetylcholine, dopamine, serotonin and
noradrenalin, orexin are all involve in wake
promotion.
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PHYSIOLOGY OF CIRCADIAN
RHYTHMICITY
The sleep-wake cycle is the most
evident of the many 24-h rhythms in
humans.
Variations can caused by endocrine,
thermoregulatory, cardiac, pulmonary,
renal, gastrointestinal, and
neurobehavioral functions
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PHYSIOLOGY OF CIRCADIAN
RHYTHMICITY
circadian period is shorter in some individuals
who typically rise early compared to those who
typically go to bed late.

Circadian rhtmic is also affected by light-dark

cycle, mediated via the retinohypothalamic
tract, a monosynaptic pathway that links
specialized, photoreceptive retinal ganglion
cells
directly to the SCN.
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BEHAVIORAL CORRELATES OF SLEEP

STATES AND STAGES
Transitional state between wakefulness
and sleep

N1 May respond to faint auditory or visual

signals without awakening
Inhibition of short term memory
incorporation

Awakenings from REM sleep are

REM associated with recall of vivid dream

imagery >80% of the time
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PHYSIOLOGIC CORRELATES OF SLEEP
STATES AND STAGES

Regular respiratory rate

during NREM and tonic
REM, irregular
respiratory rate during
phasic REM

Secretion of :
Decreased blood
growth hormone in
pressure
man.
Prolactine in man and
Complete absence of woman
thermoregulatotion in
LH in puberty woman.
REM sleep.
Inhibitions of TSH

Physiologyca
l changes
while sleep
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SLEEP DISORDERS
Patients mostly come with one of these
symptoms
Acute/chronic inability to initiate
or maintain sleep at night
(insomnia)

Chronic fatigue, sleepiness,

tiredness during the day.

Behavioral manifestation of the

sleep problem.
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Sleep onset insomnia : Difficulty in

falling asleep
Sleep maintenance insomnia :
Frequent or sustained awakenings
Sleep offset insomnia : Early morning
awakenings
Nonrestorative sleep : Persistent
sleepiness/fatigue despite adequate sleep
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Transient Insomnia : insomnia complaint lasting one to

several nights (within a single episode) .Usually as
result of situational stress or a change in sleep
schedule or environment

Short-term insomnia lasts from a few days to 3 weeks.

usually associated with more protracted stress, such as
recovery from surgery or short-term illness.

Chronic insomnia, lasts for months or years and, in contrast

with
short-term insomnia, requires a thorough evaluation of
underlying causes
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An occasional night of poor sleep, typically in the setting

of stress or excitement about external events, is both
common and without lasting consequences.

Persistent insomnia can lead to impaired daytime

function, injury due to accidents, and the development
of major depression.

All
insomnias can be exacerbated and perpetuated by
behaviors that are not conducive to initiating or
maintaining sleep.

Inadequate sleep hygiene is characterized by a behavior

pattern prior to sleep or a bedroom environment that is
not conducive to sleep, or irregularity in the timing or
duration of the nightly sleep episode.
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Primary Insomnia
Many patients with chronic insomnia
have no clear, single identifiable
underlying cause for their sleep
difficulties.
Rather, such patients often have
multiple etiologies for their insomnia,
which may evolve over the years.
Subsyndromal psychiatric disorders ,
negative conditioning to the sleep
environment, amplification of the time
spent awake, physiologic hyperarousal,
poor sleep hygiene may all be present.
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Primary Insomnia
Includes :
Psychophysiologic insomnia :
behavioral disorder in which patients
are preoccupied with a perceived
inability to sleep adequately at night.
Adjustment insomnia (acute
insomnia) : This typically develops
after a change in the sleeping
environment (e.g., in an unfamiliar hotel
or hospital bed) or before or after a
significant life event, such as a change
of occupation.
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Treatment of insomnia is often directed to each of the

Putative contributing factors:
behavior therapies for anxiety and negative
conditioning
Pharmacotherapy
and/or psychotherapy for mood/anxiety disorders
emphasis on maintenance of good sleep hygiene.

If insomnia still persists after treatment of these

contributing
factors, empirical pharmacotherapy is often used on a
nightly or intermittent basis (using variety of sedative,
antihistamines).
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Treatment for primary insomnia

Alcohol
Antihistamine
Benzodiazepine-receptor agonists

Drug Dosage Half-life

Zaleplon 5-20 mg 1-2 hour
Zolpidem 5-10 mg 2-3 hour
Triazolam 0.125 0.25 mg 2-3 hour
Eszopiclone 1-3 mg 5.5-8 hour
Temazepam 15-30 mg 6-12 hour
Lorazepam 0.5 2 mg 6-12 hour
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Benzodiazepine-receptor agonists are the

most effective and well-tolerated class of
medications for insomnia.

Side effects are generally minimal when the

dose and the serum concentration are kept
low.

1 benzodiazepines receptor agonist continues

to be effective for 6 months of nightly use.

Rebound insomnia cqn occur after

discontnuation, can be minimized by short
duration of treatment, intermittent use, or
gradual tappering of the dose.
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COMORBID INSOMNIA
A. Insomnia associated with mental disorder
Approximately 80% of patients with psychiatric
disorders describe sleep complaints, such as in
deprssion, hypomania and mania.
Chronic alcoholics lack slow wave sleep, have
decreased amounts of REM sleep

B. Insomnia associated with neurologic disorder

Neurologic disease through both indirect
nonspecific mechanism (e.g cervical spondylosis or
low
back pain), or impairment of central neural structures
involved in generations and control of sleep.
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Dementia has been associated with sleep

distrubance for a long time. Parkinsons disease,
hemiballismus, Huntingtons disease, Tourrete
disease are also associated with sleep disruptions.

Insomnia associated with other

medical disorders
A number of medical conditions are associated
with disruptions of sleep. The association is
frequently nonspecific, e.g., sleep disruption due
to chronic pain such as rheumatologic disorders,
cardiac ischemia, or even asthma.
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MEDICATION, DRUG, OR
ALCOHOLDEPENDENT
INSOMNIA
Caffeineis most common pharmacologic cause of
insomnia.
Similarly, alcohol and nicotine can
interfere with sleep, despite the fact
that many patients use them to relax
and promote sleep.
Alcohol can increase drowsiness and
shorten sleep latency.
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Amphetamines and cocaine suppress both REM

sleep and total sleep time, which return to normal
with chronic use.
Withdrawal leads to an REM sleep rebound.
Antidepressants, sympathomimetics and
glucocorticoids are common causes of insomnia.
Severe rebound insomnia can result from the acute

withdrawal of hypnotics, especially following the use

of high doses of benzodiazepines with a short half-
life.
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RESTLESS LEGS SYNDROME

(RLS)

Formost patients with RLS, the dysesthesias

and restlessness are much worse in the
evening or night compared to the daytime and
frequently interfere with the ability to fall
asleep. The symptoms appear with inactivity
and are temporarily relieved by movement.
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PERIODIC LIMB MOVEMENT DISORDER

(PLMD)
Periodic limb movements of sleep (PLMS),
consists of stereotyped, 0.5- to 5.0-s extensions
of the great toe and dorsiflexion of the foot,
which recur every 2040 s during NREM sleep, in
episodes lasting from minutes to hours.
It is often unclear whether it is an incidental
finding or the cause of disturbed sleep.
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EVALUATION OF DAYTIME
SLEEPINESS
Daytime impairment maybe difficult to quantify because
patient
may be unaware of the extent of sleep deprivation.
Subjective descriptions from patients may vary.
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Narcolepsy
Narcolepsy is both a disorder of the ability to sustain
wakefulness voluntarily and a disorder of REM sleep
regulation.

Narcolepsy tetrad consist of excessive daytime

somnolence + 3 specific symptomns :
1) sudden weakness or loss of muscle tone without loss of
consciousness, often elicited by emotion (cataplexy)
2) hallucinations at sleep onset (hypnagogic
hallucinations) or upon awakening (hypnopompic
hallucinations)
3) Muscle paralysis upon awakening (sleep paralysis).

Narcolepsy affects about 1 in 4000 people in the United

States and appears to have a genetic basis.
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Narcolepsy

Mean sleep latencies <8 min

Other conditions that cause excessive sleepiness, such as sleep
apnea or chronic sleep deprivation, must be rigorously excluded.
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Treatment for Narcolepsy

Symptomatic, somnolence is treated with wake promoting
therapeutics.
Drug of choice : Modafinil is drug of choice, with dosage 200-
400 mg/day (single dose).
Alternative drug :
Methylpenidhate 10 mg bid to 20 mg qid
Dextroamphetamine 10 mg bid.

Treatment for REM relaed phenomena : antidepressant :

protripthyline 10-40 mg/day. Clomipramine 25-50 mg/dl and
selective serotonine reuptake inhibitors.
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SLEEP APNEA
SYNDROMES
Respiratory dysfunction during sleep is a common
serious cause of excessive daytime somnolence as
well as of disturbed nocturnal sleep.
Around 25 million individuals in the United States
have a reduction or cessation of breathing for 10150
s from 30 to several hundred times every night during
sleep, maybe due to obstructive sleep apnea,
absence of respiratory effort (central sleep apnea), or
a combination of these factors (mixed sleep apnea).
Sleep apnea is particularly prevalent in overweight
men and in the elderly, yet it is estimated to remain
undiagnosed in 8090% of affected individuals.
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PARASOMNIAS
The term parasomnia refers to abnormal
behaviors or experiences that arise from
or occur during sleep.
For example : Brief confusional arousals, sleep
walking, night terrors.
Two main parasomnias occur in REM
sleep: REM sleep behavior disorder
(RBD) and nightmare disorder
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Sleepwalking
(somnambulism)
Patients affected by this disorder carry out
automatic motor activities that range from
simple to complex.
Individuals may walk, urinate inappropriately,
eat, or exit from the house while remaining
only partially aware.
Sleepwalking arises from slow-wave sleep
(NREM stage N3 sleep), usually in the first 2 h
of the night, and is most common in children
and adolescents.
The cause is unknown, though it has a
familial basis in roughly one-third of cases.
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Sleep terrors
Occurs primarily in young children during the
first several hours after sleep onset, in slow-
wave sleep (NREM stage N3 sleep).
The child suddenly screams, exhibiting
autonomic arousal with sweating, tachycardia,
and hyperventilation.
The individual may be difficult to arouse and
rarely recalls the episode on awakening in the
morning.
Parents are usually reassured to learn that this
condition is self-limited and benign and that no
specific therapy is indicated.
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Sleep enuresis
Bedwetting is another parasomnia that occurs during
sleep in the young.
Before age 5 or 6 years, nocturnal enuresis is considered
as a normal feature of development, usually improves
spontaneously by puberty, has a prevalence in late
adolescence of 13%, and is rare in adulthood.
In older patients it should be differentiate between
primary and secondary enuresis.

Treatment of primary enuresis for patients age >5 or 6 years

Consists of bladder training exercises and behavioral
therapy.
Urologic abnormalities are more common in primary
enuresis
Miscellaneous
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parasomnias
Sleep-related movement disorder in that occur
selectively during sleep and are associated with
some degree of sleep disruption.
Examples :
jactatio capitis nocturna (nocturnal headbanging
Rhythmic movement disorder)
Confusional arousals
Sleep-related eating disorder, and
Nocturnal leg cramps.
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REM sleep behavior disorder

(RBD)
RBD is a rare condition that is distinct from other
parasomnias in that it occurs during REM sleep.
It primarily afflicts men of middle age or older.
Approximately one-half of patients with RBD will
develop Parkinsons disease within 20-30 years.

Consistsof : violent behavior during sleep, injury to

patient or bed partner are common, upon
awakening patient reports vivid, often unpleasant
dream imagery.

Seizure activity is absent in EEG. Pathogenesis is

unclear.
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CIRCADIAN RHYTHM SLEEP

DISORDERS
Disorders of sleep timing can be either
organic (i.e., due to an abnormality of
circadian pacemaker[s] or its input from
entraining stimuli) or environmental
(i.e., due to a disruption of exposure to
entraining stimuli from the
environment).
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Jet lag disorder

More than 60 million persons experience
transmeridian air travel annually, which is
often associated with excessive daytime
sleepiness, sleep onset insomnia, and
frequent arousals from sleep, particularly
in the latter half of the night.
Gastrointestinal discomfort is common.
The syndrome is transient, typically
lasting 214 d depending on the number
of time zones crossed, the direction of
travel, and the travelers age and phase-
shifting capacity
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Shift-work disorder
More than 7 million workers in the United States
regularly work at night, either on a permanent or
rotating schedule.
Studies of regular night-shift workers indicate that
the circadian timing system usually fails to adapt
successfully to such inverted schedules.
Sleep disturbance nearly doubles the risk of a fatal
work accident.
Additional problems include higher rates of breast,
colorectal, and prostate cancer and of cardiac,
gastrointestinal, and reproductive disorders n long-
term night-shift workers. Recently, the World Health
Organization has added night-shift work to its list of
probable carcinogens.
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Treatment for shift work

disorder
Caffeine is frequently used to promote wakefulness.
However, it cannot forestall sleep indefinitely, and it

does not shield users from sleep-related

performance lapses. Postural changes, exercise, and
strategic placement of nap opportunities can
sometimes temporarily reduce the risk of fatigue-
related performance lapses.
Properly timed exposure to bright light can facilitate
rapid adaptation to night-shift work.
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Modafinil (200 mg, taken 3060 min

before the start of each night shift) is
the only therapeutic intervention that
has ever been evaluated as treatment
for this specific patient population.
Modafinil is approved by the U.S. Food
and Drug Administration as a treatment
for the excessive sleepiness during night
work in patients with SWD.
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Delayed sleep phase

disorder
(1) reported sleep onset and wake times
intractably later than desired
(2) actual sleep times at nearly the same
clock hours daily
(3) essentially normal all-night

Patients
exhibit an abnormally delayed
endogenous circadian phase.
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Advanced sleep phase

disorder
Advanced sleep phase disorder (ASPD) is the
converse of the delayed sleep phase syndrome.
Most commonly occurs in older people
15% of whom report that they cannot sleep past 5
A.M., with twice that number complaining that
they wake up too early at least several times per
week.
Patients with ASPD experience excessive daytime
sleepiness during the evening hours, when they
have great difficulty remaining awake, even in
social settings.
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Non-24-h sleep-wake
disorder
Occur when the synchronizing input from
environment (e.g light-dark cycle) to the
circadian pacemaker is compromised (e.g
blind person)
or
When the maximal phase-advancing capacity
of the circadian pacemaker is not adequate
to accommodate the difference between the
24-h geophysical day and the intrinsic period
of the pacemaker in the patient.
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Affected patients are not able to

maintain a stable phase relationship
between the output of the pacemaker
and the 24-h day.
Nightly low-dose (0.5 mg) melatonin
administration has been reported to
improve sleep and, in some cases, to
induce synchronization of the circadian
pacemaker.
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MEDICAL IMPLICATIONS OF
CIRCADIAN RHYTHMICITY
Prominent circadian variations have been reported in
the incidence of acute myocardial infarction, sudden
cardiac death, and stroke, the leading causes of death
in the United States.

Platelet aggregability is increased in the early morning

hours, coincident with the peak incidence of these
cardiovascular events.

Misalignment of circadian phase, such as occurs during

nightshift work, induces insulin resistance and higher
glucose levels in response to a standard meal.
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Blood pressure of night workers with

sleep apnea is higher than that of day
workers.

Finally,the physician must be

increasingly aware of the public health
risks associated with the everincreasing
demands made by the duty-rest-
recreation schedules in our round-the-
clock society.
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Terimakasih
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Principles and practice of sleep

medicine
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