SLEEP

NORMAL SLEEP AND

SLEEP DISORDERS • Is a regular, recurrent, easily reversible state that
is characterized by relative quiescence and a
HYACINTH C. MANOOD, MD, FPPA great increase in the threshold response to
external stimuli relative to the waking state.

1 2

PHYSIOLOGICAL STATES OF SLEEP

A. NREM (NON-RAPID EYE MOVEMENT) – 75%; SWS

Stage 1 – (5%); 3 – 7 cps theta waves; hypnic myoclonia
Stage 2 – (45%) – 12 – 14 cps with sleep spindles and K complex
Stage 3 – (12%) – ½ to 2 cps delta waves deep sleep
Stage 4 – ((13%) Enuresis, Somnambulism,
sleep terror
v These stages lasts from 90 – 120 minutes with each stage lasting
from 5 – 15 minutes
v Approximately 90 minutes after onset of sleep, NREM yields to
the first REM episode of the night. – REM latency
v Shortening of REM latency is seen in depressive disorders and
narcolepsy
v Arousal during Stage 3 and 4 (30 min – 1 hour)- disoriented,
disorganized thinking, amnesia

3 4

PHYSIOLOGICAL STATES OF SLEEP

DISTINCTIVE FEATURES OF EACH PHASE:
B. REM –(RAPID EYE MOVEMENT) – 25%
NREM
v Paradoxical sleep - the brain is in excitation mode while the • Pulse rate, respiration, and blood
muscles are immobilized; pressure is ↓
v Low voltage, mixed frequency (theta and slow alpha), sawtooth • Resting membrane potential ↓;
waves few involuntary body
movements;
v Occurs every 90 – 100 minutes during the night;
• Few penile erections
v The first cycle of sleep is completed after the REM phase.
• Blood flow sl. reduced
v The first REM cycle tends to be the shortest (10 minutes);
succeeding REM cycle last 15 – 40 minutes each; • Rare dreams
v The most distinctive feature of REM sleep is DREAMING; • Slow eye movement
• Dreams lucid and purposeful
REM
• Pulse rate, respiration and blood
pressure is ↑
• Brain oxygen use ↑
• ↑ PCO2; no inc. in tidal volume
(ventilatory response depressed)
• Poikilothermia
• Partial or full penile erection
• Near total paralysis of skeletal
muscles
• Dreams typically abstract and surreal
• Rapid eye movement

5 6
 Neurogenesis Energy
/ Development Conservation

The Need to
Sleep?
Sleep 68% Reduction
Adult Rats Deprivation for of New Cells in
Memory
Restoration Consolidation
4 Days Hippocampus

7 8

Memory SLEEP DEPRIVATION

Consolidation • Ego disorganization, hallucinations, delusions

• REM-deprived patients exhibit irritability and lethargy
• “Sleep-deprivation syndrome” – debilitated
appearance, skin lesions, increased food intake, weight
Hippocampus Reactivated loss, increased energy expenditure, decreased body
temperature, death.
activated during Non- • Increased plasma norepinephrine

during tasks REM Sleep • Decrease plasma thyroxine level

9 10

Link between sleep & weight loss SLEEP REQUIREMENTS

• Short sleepers - < 6 hours ; generally efficient, ambitious,

• Sleep deprivation
– can raise cortisol
• Cortisol Ý insulin which promotes fat storage
– Can contribute to insulin resistance
• Linked to obesity, CV disease, type II diabetes
• High fat, high sugar diet can lead to insulin resistance
– ß slow wave sleep (stage III and IV non REM)
• Linked with ß levels of growth hormone
– Has an important role in fat loss and muscle growth
– Individuals who sleep longer (>9 hr) less likely to be obese
than individuals who sleep shorter (<6 hr)
(I.J.Obesity&Metabolic Disorders 24; 1683, 2000.)
socially adept, and content.
• Long sleepers - > 9 hours; tend to be mildly depressed,
anxious, and socially withdrawn; more REM periods with
more rapid eye movements (REM density);
• REM density is considered a measure of the intensity of REM
sleep and related to vividness of dreams.
• Sleep needs increase with physical work, exercise, illness,
pregnancy, general mental stress, and increased mental
activity.
• REM periods increase after strong psychological stimuli, such
as difficult learning situations and stress, and after the use of
chemicals or drugs that decrease brain catecholamines.

11 12
 The Sleep-Wake Cycle and
the Two-Process Model
Control of
• Two-process model explains the sleep-
Sleep wake cycle1
1. Homeostatic Drive2
• Increases with the duration of waking
• Governed by the need for sleep
2. Circadian Rhythms
Homeostasis Circadian • Confines sleep and waking to different phases of
the daily cycle2
– regulates Rhythm –
• Entrained to the light-dark cycle2,3
intensity regulates timing • Sleep-independent1
1. Kild u ff TS, Ku shid a C A . Sle e p D isord e rs M e d ic ine : Ba sic Sc ie nc e , Te c hnic a l C onsid e ra tions, a nd C linic a l
A sp e c ts. 1999; b a se d on Ed g a r D M e t a l. J N e u rosc i. 1993;13:1065-1079.
2. M onk TH , W e lsh D K. Sle e p M e d R e v. 2003;7:455-473. 3. Tu re k JW e t a l. A rc h N e u rol. 2001;58:1781-1787.

13 14

Homeostatic Drive: Circadian Rhythms

The “Sleep Drive” • In humans, modulate daily cycles in2-4
– Core body temperature
• Sleep drive increases the longer one stays – Blood pressure
awake1 – Hormone secretion
• If the sleep drive is not relieved by sleep, – Immune response
sleepiness worsens1 – Sleep-wake cycle
– Cognitive and behavioural functions may • Entrained by light-dark signals transmitted
be impaired2 from the retina to the SCN5
– Light promotes physiologic events leading to
• As the body recovers during sleep, sleep arousal (zeitgeber)
drive is reduced1 – Dark promotes events that attenuate arousal
1. Tu re k FW e t a l. A rc h N e u rol. 2001;58:1781-1787. 2. V a n C a u te r E, Tu re k F. In: C onn PM e t a l, e d s. H a nd b ook of
Physiolog y. Be the sd a , M d : A m e ric a n Physiolog ic ia l Soc ie ty; 2001. 3. M ig not E e t a l. N a t N e u rosc i. 2002;5(su p p l):1071-1075.
1. M onk TH , W e lsh D K. Sle e p M e d R e v. 2003;7:455-473. 2. V a n D ong e n H P e t a l. Sle e p . 2003;26:117-126.
4. D e R ijk R e t a l. J C lin End oc rinol M e ta b . 1997;82:2182-2191. 5. M onk TH , W e lsh D K. Sle e p M e d R e v. 2003;7:455-473.

15 16

Sleep-Wake Cycle Regulation SLEEP REGULATION

• Electrical stimulation of the nucleus tractus solitarius
• Night-time sleep1,2 (NTS) produces Slow wave sleep. (NREM)
– First part of night — sleep because we have • Direct connections between NTS and major areas of the
been awake all day (homeostatic drive high) limbic system exists. (Ant. Thalamus, hypothalamus and
amygdala).
– Second part of night — sleep because • Serotonin appears to modulate sleep thru its effects on other
circadian alertness is low hyponogenic factors in ant. thalamus and suprachiasmatic
• Daytime wakefulness2,3 nucleus.
– Lesions in serotonin-rich raphe nucleus produces insomnia
– First part of day — awake because we slept at – Parachlorophenylalanine (PCPA) , a tryptophan hydroxylase
night (homeostatic drive low) inhibitor, produces insomina by blocking the production of
serotonin
– Second part of day — awake because
circadian alertness is high
1. Pa c e -Sc hott EF, H ob son JA . N a t R e v N e u rosc i. 2002;3:591-605. 2. D ijk J-D , C ze isle r C A . N e u rosc i Le tt. 1994;166:63-68. 3.
R ic ha rd son G , D og hra m ji K. C lin Sym p . 2005;55:3-39.

17 18
 SLEEP REGULATION
• Drugs and manipulation that increase the firing rate of
noradrenergic neurons in the locus ceruleus markedly
reduce REM sleep and increase wakefulness.
• Brain acetylcholine is involved in the production of REM
sleep.
– Injection of cholinergic-muscarinic agonists in the pontine reticular
formation results in shift from wakefulness to REM sleep.
– Sleep changes in Major Depressive Disorder – caused by disturbance
in central cholinergic activity : shortened REM latency, increased
percentage of REM sleep, shift in REM distribution
– Antidepressants reduces REM sleep
– Reserpine increases REM sleep – produces depression
– In dementia of Alzheimer’s type – loss of cholinergic neurons in
basal forebrain produces decreased REM and SWS sleep.
SLEEP REGULATION
• Melatonin enhances sleep.
– Serotonin is the precursor of melatonin.
– Melatonin secretion from the pineal gland is inhibited by bright light.
– The suprachiasmatic nucleus – anatomical site of circadian pacemaker;
regulates the secretion of melatonin
• Dopamine has an alerting effect.
– Dopamine blockers increase sleep time. (Pimozide, Phenothiazines)
• Prostaglandin D2 (supraoptic nucleus) induces both REM and
SWS sleep.
– Prostaglandin inhibition by Indomethacin decrease diurnal sleep
• GABA neurons produce sleep spindles and delta waves.
– Sedative-hypnotics stimulates GABA receptors and promotes sleep.

19 20

SLEEP-WAKE RHYTHM
• External factors:
– light-dark cycle, daily
routines, meal periods
– Phases of menstrual
cycle
– Naps – morning and
noon more REM
– afternoon and
early evening
less REM
SLEEP HYGIENE
EDUCATION
● Fixed sleep and wake-up
times (even on weekends)
●Establish a sleep-
conductive bedroom
setting (no bright
lights or noise, and
comfortable temperature)
● Relax before going to bed
● Avoid caffeine and
nicotine for at least 6
hours before bedtime
● Use alcohol in moderation
and avoid alcohol for at
least 4 hours before
bedtime
● Exercise regularly but
preferably not 2 to 4 hours
before bedtime
● Avoid watching the clock
STIMULUS
CONTROL
● Go to bed when sleepy
● Use bed only for sleep and
intimacy (no watching
television or reading)
● Get out of bed and the
bedroom if unable to fall
asleep in 15 to20 minutes
● Get up at the same time
every morning regardless
of the amount of sleep
obtained the previous night
● Do not nap during the day
SLEEP
RESTRICTION
● Create temporary mild state
of sleep deprivation by
aligning time in bed with
actual sleep time
(“sleep window”)
- 6 hours in bed if someone
sleeps usually 6 hrs
- Never <5 hours in bed
● After sleep window weekly
based on sleep diary from
week before
● If sleep efficiency (total
sleep time/time in bed) is
- >85% increase time in
bed15-20 min
- 80-85%, no change
- <85%, decrease time in
bed 15-20 min

Psychological and Behavioral Therapies for Insomnia Suitable for Primary Care Settings

21 22

Sedative-Hypnotics
Available in the Philippines
PHARMACOTHERAPY
I. Barbiturates
® Antidepressants - Phenobarbital
® Benzodiazepine receptor agonists II. Benzodiazepines
(BzRAs) - Flurazepam (Dalmane)
- Estazolam (Esilgan)
® Non-benzodiazepine receptor - Bromazepam (Lexotan)
agonists - Clonazepam (Rivotril)
- Chlorazepate dipotassium (Tranxene)
® Melatonin receptor agonists - Diazepam (Valium)
- Alprazolam (Xanor)
- Midazolam (Dormicum)
MIMS Neurology and Psychiatry Guide Philippines. 2005/2006 Edition

23 24
 Sedative-Hypnotics
Available in the Philippines

III. Non-Benzodiazepines (Benzodiazepine

receptor agonist)
- Zolpidem (Stilnox, Zionax)

IV. Melatonin Receptor Agonists

- Ramelteon

MIMS Neurology and Psychiatry Guide Philippines. 2005/2006 Edition

25 26

A. DYSOMNIAS

1. PRIMARY INSOMNIA
A. DYSOMNIAS - disorders of quantity or timing of sleep when the chief complaint is nonrestorative
1. Insomnia - is a perceived disturbance in the quantity or quality of sleep or difficulty in initiating or maintaining
sleep, which, depending on the specific condition, may be sleep, and the complaint continues for at least
associated with disturbances in objectively measured sleep a month; independent of any known physical or
mental condition.
2. Hypersomnias - represent conditions that are clinically expressed
as excessive sleepiness. – difficulty falling asleep and by repeated
awakening
B. PARASOMNIAS- are abnormal behaviors during sleep or – generally preoccupied with getting enough
sleep.
the transition between sleep and wakefulness.
• Tx: 1. Deconditioning Tecnique -
2. Relaxation Tecniques and Biofeedback
3. Pharmacotherapy
.

27 28

2. PRIMARY HYPERSOMNIA
- when no other cause can be found for excessive
• …Narcolepsy…
somnolence occurring for at least 1 month.
Treatment : stimulants, non-sedating
antidepressants
3. NARCOLEPSY
- characterized by excessive sleepiness, as well
as auxiliary symptoms that represent the
intrusion of aspects of REM sleep into the
waking state
– episodes of irresistible sleepiness, leading to
perhaps 10 to 20 minutes of sleep, after
which the patient feels refreshed, at least
briefly.
– hypnagogic and hypnopompic
hallucinations, cataplexy, and sleep paralysis
– Occur in .02 to .16% of adults; with familial
incidence
– An abnormality in REM-inhibiting mechanism
– most frequently begins in adolescence or young adulthood,
generally before the age of 30
– Most common symptom is sleep attack;
– nighttime polysomnographic recording reveals a characteristic
sleep-onset REM period
TREATMENT:
1. Regimen of daily naps at a regular time of the day
2. Pharmacotherapy:
Modafanil (Provigil), an a1-adrenergic receptor agonist,
reduce the number of sleep attacks;
TCAC or SSRI – REM sleep-suppressant properties
3. lifestyle adjustment, psychological counseling, drug holidays
to reduce tolerance, and careful monitoring of drug refills,
general health, and cardiac status.

29 30
 4. BREATHING-RELATED SLEEP DISORDER
a. OBSTRUCTIVE SLEEP APNEA SYNDROME -characterized by
periods of functional obstruction of the upper airway during sleep,
resulting in decreases in arterial oxygen saturation and a transient
arousal, after which respiration (at least briefly) resumes normally.
• patients are overweight, and it appears more frequently in
patients with smaller jaws or true micrognathia, acromegaly,
and hypothyroidism.
• characterized by multiple periods of at least 10 seconds in
duration in which nasal and oral airflow ceases completely (an
apnea) or partially (a hypopnea), while the abdominal and chest
expansion leads indicate continuing efforts of the diaphragm
and accessory muscles of respiration to move air through the
obstruction.
• Breakthrough –arousal reflex; brief restless movements

31 32

Continuous Positive Airway

– Central sleep apnea (CSA), which tends to occur in the elderly,
Pressure (CPAP)
results from periodic failure of central nervous system (CNS)
mechanisms that stimulate breathing; a cessation of respiratory
effort is seen in the abdominal and chest expansion leads
– decreased ability to concentrate, decreased libido, memory
complaints, and deficits in neuropsychological testing
– nCPAP is the treatment of choice
– weight loss, nasal surgery, tracheostomy, and uvulopalatoplasty,
eliminate alcohol and sedatives, smoking cessation
– REM is the stage of sleep in which apnea occur most often –
give REM sleep-suppressing medications

95% effective – usually first line treatment for severe disease

Sleep Academic Award 34

33 34

S e p arate b alls slig h tly

b. CENTRAL ALVEOLAR HYPOVENTILATION-impaired
an d p lace o n to se p tu m . ventilation in which the respiratory abnormality appears or greatly
worsens only during sleep and in which no significant apneic
episodes are present. Death may occur during sleep (Ondine’s curse)
TREATMENT : mechanical (nasal) ventilation
5. CIRCADIAN RHYTHM SLEEP DISORDER
a. Delayed Sleep Phase type - sleep and wake times that are intractably
later than desired, actual sleep times at virtually the same daily clock
hour, no reported difficulty in maintaining sleep once begun, and an
inability to advance the sleep phase by enforcing conventional sleep
and wake times.
Chronotherapy, Bright Light Therapy

Often used devices which don’t treat sleep apnea

This one treats the partner ->
Sleep Academic Award 35

35 36

b. Jet lag type – east-to-west trip; usually disappears spontaneously in
3-7 days; no specific treatment required. Melatonin taken orally at
prescribed times is useful for some persons. Maximizing light
exposure during the new daytime and minimizing light during the
new nighttime are also helpful.
c. Shift work type
–typical symptoms of insomnia begin to appear including fatigue,
diminished ability to concentrate or focus, irritability and feelings of
tenseness and depression.
- associated with increased rates of gastrointestinal disorders (eg,
ulcers, functional bowel disorders), hypertension, depression, on-the-
job and automobile accidents, and decreased productivity
37
DYSOMNIAS, NOS:
b. Restless Leg Syndrome ( Ekbom Syndrome)
- uncomfortable, subjective sensation of the limbs, usually the
legs, sometimes described as a creepy crawly feeling or as the
sensation of ants walking on the skin.
- worse at night, and is relieved by walking or moving about
-cause of sleep initiation insomnia
-appears often in pregnancy, iron or vitamin B12 deficiency
anemia, and renal disease.
-first step in treatment is looking for anemia and treating it, if
found.
-L-dopa and carbidopa (Sinemet), bromocriptine (Parlodel), and
pergolide (Permax)
-Ropinirole (Requip) - first drug approved by the FDA for
treatment of moderate to severe RLS.
39
DYSOMNIAS, NOS:
d. Menstrual-Associated Syndrome - intermittent marked
hypersomnia, altered behavioral patterns, and voracious eating at,
or shortly before, the onset of their menses.
e. Sleep Disturbance in Pregnancy - changes in levels of estrogen,
progesterone, cortisol, and melatonin from baseline.
f. Insufficient Sleep - earnest complaint of daytime sleepiness and
associated waking symptoms by a person who persistently fails to
obtain sufficient daily sleep to support alert wakefulness.
g. Sleep Drunkenness - abnormal form of awakening in which the
lack of a clear sensorium in the transition from sleep to full
wakefulness is prolonged and exaggerated.; requires the absence
of sleep deprivation.
41
6. DYSOMNIAS NOT OTHERWISE SPECIFIED
a. Periodic limb movement syndrome - stereotypic, periodic leg
movements (every 20 – 60 secs) during NREM sleep.; no
seizure activity; patient is unaware of the myoclonic events;
extension of the large toe, flexion of the ankle.
– Most prevalent in patients over age 55
– Frequent awakenings; unrefreshing sleep
– Daytime sleepiness is a major symptom.
– Associated with renal disease, Iron and B12 anemia
– Also known as nocturnal myoclonus
– No treatment is universally effective
– BZD, levodopa, quinine, opioids
38
DYSOMNIAS, NOS:
c. Kleine-Levin Syndrome - relatively rare condition consisting of
recurrent periods of prolonged sleep (from which patients may be
aroused) with intervening periods of normal sleep and alert waking.
- withdrawal from social contacts and return to bed at the first
opportunity; apathy, irritability, confusion, voracious eating, loss of
sexual inhibitions, delusions, hallucinations, frank disorientation,
memory impairment, incoherent speech, excitation or depression,
and truculence.
- first attack occurs between the ages of 10 and 21 years
- usually self-limited
40
B. PARASOMNIAS
1. NIGHTMARE DISORDER –
- 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.
-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).
- Nightmares are vivid dreams that become
progressively more anxiety producing, ultimately
resulting in an awakening
-usually occurs after a long REM period late in the
night.
- REM suppressants ( TCAC’s, ), Benzodiazepines
42

2. SLEEP TERROR DISORDER
- arousal in the first third of the night during deep
NREM (stages III and IV) sleep
- patients sit up in bed with a frightened expression,
scream loudly, and sometimes awaken immediately
with a sense of intense terror. Patients may remain
awake in a disoriented state, but more often fall
asleep, and as with sleepwalking, they forget the
episodes.
- frequently develops into a sleepwalking episode
- 1 – 6 per cent in children; more in boys; run in
families;
- when night terrors begin in adolescence and young
adulthood, they turn out to be the first symptom of
temporal lobe epilepsy.
- no dream recall but may occasionally recall a single
frightening image.
- Individual and family therapy; sometimes
Diazepam in small doses.
43
4. PARASOMNIA NOT OTHERWISE SPECIFIED
a. Sleep-related bruxism - teeth grinding; occurs thruout the night , most
prominently in Stage 2 sleep;
- dental bite plate and corrective orthodontic procedures
b. REM sleep behavior disorder - episodes of complex, often violent,
behavior and is thought to represent a patient acting out his or her
dreams
- more common in older men, and often a history exists of a small
stroke or other CNS insult in the last months or year
- can also appear as an early event in the evolution of Parkinson's
disease.
- off-label administration of clonazepam (Klonopin), 0.5 to 2.0 mg a
day. Carbamazepine, 100 mg three times a day, is also effective in
controlling the disorder.
45
47
3. SLEEPWALKING DISORDER
(SOMNAMBULISM)
- sequence of complex behaviors that are initiated in the
first third of the night during deep NREM (stage III and
IV) sleep and frequently, although not always, progress
without full consciousness or later memory of the
episode to leaving bed and walking about.
-occasionally terminates in awakening, with several
minutes of confusion; more frequently, the person
returns to sleep without any recollection of the
sleepwalking event.
-usually begins between ages 4 and 8 and tends to
dissipate in adolescence; peak prevalence is about 12
y/o.; more common in boys.
- Extreme tiredness or previous sleep deprivation
exacerbates attacks
- Benzodiazepine decreases SWS
- Parent education and reassurance
44
PARASOMNIAS, NOS:
c. Sleeptalking (Somniloquy) - talking usually involves a few words
that are difficult to distinguish
- sometimes accompany night terrors and sleepwalking
d. Sleep-related Headbanging (Jactatio Capitis Nocturna)
- rhythmic to-and-fro head rocking (less commonly, total body
rocking) occurring just before or during sleep; occurs in light sleep
- measures to prevent injury
e. Sleep Paralysis - sudden inability to execute voluntary movements,
either just at the onset of sleep or on awakening during the night or
in the morning.
46