Sleep, sleep disorders
Mária Tünde Magyar MD, PhD
About the sleep…
Each of us will spend about 27 years of his or
her lifetime sleeping…..
…..And 1/3 part of the population has sleep
disorder
„Why we sleep remains one of
nature’s greatest mysteries”
(MG Frank, The function of sleep, 2006)
Somatic theories of sleep function
Neural metabolic theories: detoxification and
regeneration
Cognitive theories of sleep function: learning
and brain development
Normal human sleep
Sleep cycle – occurs about every 90 minutes,
approximately 4-6 cycles occur per major sleep episode
Microarousal
1. NREM (70-80%)
• I-IV stage
• slow wave sleep
• heart rate, BP, breathing ↓
• body temperature, muscle tone ↓
2. REM (20-25%)
• rapid eye movement, paradox, fast wave sleep
• heart rate, BP, breathing ↑, metabolic rate ↑
• dreaming, erection
• muscleatonia, BUT: myoclonus!
Sleep and aging
Sleeping time:
• newborns: 16 hours
• adolescence: 8 hours
• in 50 –s : 6 hours
Newborns: 50% REM stage
After 3 years: 20% REM stage
Slow wave sleep (III-IV stage) declines after
adolescence
Sleep disorders
Sleep diagnostics
Sleep 2007:8:402-28
Polysomnography
• multiparametric monitoring during 1 sleep period
(1 night)
• EEG
• Electrooculogram staging of the sleep
• EMG
• ECG
• Respiratory effort
• SpO2
• Body position
• Snoring
More than 80 sleep disorders are known
(International Classification of Sleep Disorders, 2nd Edition
American Academy of Sleep Medicine, 2005)
I. Insomnias (33%)
II. Sleep related breathing disorders (1,4-40%)
III. Hypersomnias (0,3-16,3%)
IV. Cirkadian rhythm sleep disorders
V. Parasomnia
VI. Sleep related movement disorders
VII. Isolated symptoms, normal variants
VIII. Other sleep disorders
Insomnias
• Difficulty in initiating sleep or in staying asleep or
waking up earlier
• Nonrefreshing, nonrestorative sleep
Daytime symptoms
• Fatigue, concentration or memory impairment
• Mood disturbances, motivation, initiative reduction
• Daytime sleepiness
• Tension headache
Insomnias
• Prevalence: 33%
• Accompanied with daytime consequences:
10%
• Last less than 1 month: 4% (transient
insomnia)
• Last more than 1 year: 85% (persistent
insomnia)
• Male:female = 1:1.4
• Increase with age: above 65 years: 50%
Insomnias
1. Primary (idiopathic)
2. Secondary
1. Inadequate sleep hygiene (10%)
2. Paradoxical insomnia (10%)
3. Insomnia due to mental disorder (30-40%)
4. Psychophysiological insomnia (15%)
5. Insomnia due to drug or substance
6. Insomnia due to medical conditions
7. Sunday night insomnia
AFF 2007;76:517-26
Nonpharmacologic Therapy:
Behavioral Treatments
Sleep Hygiene
Stimulus Control
Sleep Restrictions
Relaxation Training
Cognitive Therapy
GOOD SLEEP
GOOD SLEEP
Circadian Rhythm Entrainment
Pharmacotherapy: Indications
Acute Stress Shift Work / Jet Lag
Chronic Insomnia Predictable Stress
Pharmacologic Treatment:
Approach
• Select appropriate medication
• Evaluate carefully for apnea, respiratory
impairment, organic mental disorders, substance
abuse history
• Use lowest effective dose
• Use at bedtime (or later, if indicated)
• Duration of therapy
– Use as needed for 2 to 4 weeks
– Reduce dose as tolerated
– Intermittent use suggested
• Combine with behavioral strategies
Pharmacotherapy
• GABAA receptor agonists
– Benzodiazepines
– Z-hypnotics
• Melatonin, melatonin receptor agonist
(ramelteon)
• Antidepressants
• Antihistamines
• Others
Pharmacotherapy:
Benzodiazepine Receptor Agonists
• Actions • Side effects
• Hypnotic • Sedation
• Anxiolytic • Anterograde amnesia
• Myorelaxant • Ataxia, falls
• Anticonvulsant • Respiratory depression
• Tolerance, dependence, abuse
Pharmacologic treatment
Benzodiazepines
1. midazolam, triazolam ~ rebound
insomnia
2. cinolazepam, quazepam
3. brotizolam, temazepam
4. nitrazepam ~ drowsiness
Pharmacologic treatment
Selective GABAA agonists: nonbenzodiazepines
– no rebound insomnia
– zolpidem, zopiclon, zaleplon (Z-hypnotics)
Phys&Beh:2007:90:285-293
Sleep related breathing disorders
(International Classification of Sleep Disorders, 2nd Edition
American Academy of Sleep Medicine, 2005)
1.
2.
3. Sleep related hypoventilation/hypoxemia
Apnea-hypopnea index (AHI)
- Numbers of apneas and hypopneas/ 1 sleeping
hour
Severity of sleep related breathing
disorders:
- Normal: AHI30/h
Sleep, 1999:22:667-89.
Central sleep apnea
• Unknown etiology
• Possible reason:
abnormality of ventilating
control
• Normo- és hypocapnic:
idiopathic CA and
Cheyne-Stokes breathing
• Hypercapnic: alveolar
hypoventilation
OSAHS: symptoms
Daily Nightly
• Excessive daytime • snoring
sleepiness • apneas
• Unrefreshing sleep • choking, gasping
• Memory disturbances • arousals
• Morning headache • sweating
• Depression • dry mouth
• Decreased libido • palpitation
• Stomach ache • nycturia
Excessive daytime sleepiness
In USA, drowsiness is the reason
in 30% of the traffic accidents
Objective:
PSG, MSLT test
sleep latency: >10 min: norm.
12 point: excessive sleepiness
(Johns 1991)
Treatment of benign snoring
• Weight loss, alcohol withdrawal
• Position training
• Nasal, pharyngeal surgery (UPPP)
• Oral appliances
Witnessed apneas/gasping
• 75%: bedpartner
Sleep 1993:16:118-22.
• lasts 20-30 s Sleep Medicine 2007:8:402-428
OSAHS: diagnostic criteria
(1. or 2.) and 3.
AASM, Sleep, 1999:22:667-89.
Risk factors of OSAHS
• Obesitas
• Age
• Male gender
• Pozitive family history of OSAHS
• Alcohol consumption before bedtime
• Race
• Smoking
• Sedatives
• Craniofacial anomalies
• Hypothyroidism, acromegaly
Spectra of sleep related breathing
disorders
Obesitas-hypoventilation Pickwick/syndroma
• 1837: Dickens
• Obesitas: BMI>35 kg/mm2
• paCO2>45 Hgmm
• Cor pulmonale
• Erythrocytosis
• Daytime sleepiness
• Morning headache
• High mortality
Am J Med 2005:118:948-56.
CPAP: evidence based therapy
AHI
The Cochrane Library, 2006, Issue 4
CPAP: evidence based therapy
The Cochrane Library, 2006, Issue 4
CPAP: evidence based therapy
Hypersomnias
Narcolepsy (0,02-0,18%)
• Genetics (HLA DQB1 0602, HLA-DR2)
• Hypocretin-1 (orexin) levels in cerebral spinal
fluid are low
• Begins: 15-25 years
• Excessive Daytime Sleepiness
• Cataplexy
• Sleep Paralysis
• Hypnagogic Hallucinations
• Treatment: modafinil, methylphenidate, tricyclic
antidepressant
Excessive Daytime Sleepiness
(EDS)
• EDS is required for a diagnosis of narcolepsy,
and is usually the most disabling symptom
• EDS is typically episodic in narcolepsy, resulting
in frequent napping during the day
• There is often a “refractory period” after naps
with normal levels of alertness before sleepiness
returns
• Sleepiness is more likely to occur in boring
situations and after a meal
Sleep Paralysis
• Inability to move or speak in the transition
between sleep and wakefulness
• Usually lasts several minutes
• May be frightening and may be associated with
a feeling of inability to breathe
• Occurs in 40% to 80% of narcoleptics
• Occasional episodes may occur in normals
Hypnagogic Hallucinations
• Vivid perceptual experiences at sleep onset
• Include visual, tactile, kinetic and auditory
phenomena
• Usually accompanied by fear or dread
• Occur in 40% to 80% of narcoleptic patients
• May occur in normals
Cataplexy
• Sudden loss of muscle tone
• Provoked by strong emotions that are usually
positive (laughter, pride, elation, surprise)
• Can be generalized or local (buckling knees,
sagging chin)
• Blurred vision may occur
• Respiratory muscles never affected
• Lasts a few seconds to several minutes
Cirkadian rhythm sleep disorders
• Primary
– Delayed sleep phase type
– Advanced sleep phase type
– Irregular sleep phase type
• Secondary
– Jet lag type
– Shift work type
• Treatment
– Sleep hygiena
– Cronotherapy
– Light therapy
– Melatonin, ramelteon, zolpidem
Sleep related movement disorders
• Restless legs syndroma (primary or
secondary)
– Therapy: dopamin agonists
• Periodic limb movement disorder
• Sleep related leg cramps
• Sleep related rhythmic movement disorder