Download Sleep - Definition

Sleep Disorders
The Nightmare- Henry Fuseli, 1781
Richard E. Waldhorn, MD
Clinical Professor of Medicine
Division of Pulmonary, Critical Care
and Sleep Medicine
Georgetown University School of Medicine
Sleep Disorders
 What is sleep and how is it structured?
 What are the normal rhythms of sleep and
wakefulness?
 How does sleep change as we age?
 What are the presenting symptoms of the
most common sleep disorders?
Sleep - Definition
 Sleep is a physiologic, recurrent, reversible behavioral
state of perceptual disengagement from and
unresponsiveness to the environment.
 Influenced by a homeostatic and a circadian drive
 Sleep is not the absence of wakefulness:
•
•
•
•
•
Active
Highly Regulated
Involves different areas in the brain
Purpose is not understood
Essential to life
Sleep Regulation
 Homeostatic process: determined by sleep and waking
 The pressure for sleep increases proportionately to the
time since last sleep
 Circadian process: Approximately 24 hr cycle of sleep
and wakefulness
 periods with high and low sleep propensity
 independent of sleep and waking
 Suprachiasmatic nucleus- regulated by zeitgebers:
sunlight and eating time
 Ultradian process: occurring within sleep- the
alternation of Non REM and REM sleep
Sleep Stages
 Two separate sleep states have been defined on the basis of
a constellation of physiological parameters:
 Non-rapid eye movement (NREM) sleep:
 A relatively inactive (yet actively regulating) brain in a movable body


Fast wave sleep (Stages 1 & 2)
Slow wave sleep (Stages 3 & 4; delta)
 Rapid eye movement (REM) sleep:
 A highly activated brain in a paralyzed body



Rapid eye movements
Low amplitude, mixed frequency EEG
Lowest muscular tone
Sleep Stages - Adult
REM Sleep- bilateral synchronous eye
movements, muscle atonia
Normal sleep
 Sleep latency
 Normal: 10 minutes
 Stage N1-N2 sleep
 Initial period: 20-40 minutes
 Stage N3 sleep
 Onset at 30-40 minutes after lights out
 Stage REM sleep
 Onset at 90 minutes after lights out
Sleep cycle: normal hypnogram
Normal Sleep
 N1-N2 sleep—light sleep
 50-60% of sleep time
 Sleep onset and in latter part of the night
 N3 “deep”—slow wave sleep
 “restorative” part of the night
 Early in the sleep cycle
 20-25% of sleep time
 REM “dream” sleep
 Brain active/muscles paralyzed
 4 REM periods thru the night
 Longest is just prior to awakening
 20-25% of the night
Key Polysomnographic Terms
 Sleep latency- lights out until sleep onset
 REM latency- sleep onset to the first epoch of REM
 Sleep efficiency- Total sleep time/total recording time
 Wake after sleep onset (WASO)
 Percent REM sleep
 Percent slow-wave sleep (SWS)
 Percent stage 1-2 sleep
What causes sleep ?
 Activation of neural structures in the brainstem
 Cortex is variably active—most in REM sleep
 Complex interplay
 Brain: light and dark
 Hormones: cortisol
 Temperature
 Circadian rhythm
Circadian Rhythms
Light
Suprachiasmatic Nuclei (SCN)
Output Rhythms
Physiology
Behavior
Normal Circadian Sleep Rhythm
Circadian Rhythms
Sleep Changes with Age
Breathing during sleep
 Central nervous system control
 Stretch receptors
 Chemoreceptors
 Blood carbon dioxide level
 Slightly higher trigger to breathe than when awake
 Very sensitive
 Can be affected by drugs, chronic diseases
 Altitude
Sleep and Psychiatry- Historical note
 1900-Freud: The Interpretation of Dreams
 1953 -Kleitman and Aserinsky at the University of Chicago




describe the rapid eye movement (REM) stage of sleep and
propose a correlation with dreaming
1957- Dement and Kleitman describe the repeating stages
of the human sleep cycle.
1968-Rechtschaffen and Kales publish a scoring manual
that allows for the universal, objective comparison of human
sleep stage data.
1980- Sullivan, Rapoport, Sanders: nasal CPAP for OSA
2000-Mignot and colleagues at Stanford discover that
human narcolepsy also is associated with hypocretin
deficiency.
Sleep Disorders
 DOES—disorders of excessive somnolence
 Quantity of sleep
 Quality of sleep
 DIMS—disorders of initiation and maintenance of
sleep
 Sleep onset insomnia
 Sleep maintenance insomnia
Sleep Disorders
 Circadian rhythm disorders
 Delayed sleep phase syndrome “night owl”
 Advanced sleep phase syndrome “lark”
 Jet lag
 Night shift worker
 Parasomnias
 Excessive motor activity during sleep
 Sleep walking/talking/eating
 Sleep terrors
 REM behavior disorder
Question 1
 What is the most common cause of DOES?
 1. sleep disordered breathing
 2. narcolepsy
 3. inadequate sleep hours
 4. sleep walking
DOES
 Inadequate sleep hours
 Adult sleep requirement: 7-9 hours
 Adequate sleep architecture



50-60% light sleep (N1-N2)
20-25% deep sleep (N3)
20-25% REM sleep
 Good sleep behaviors
 Proper sleep conditions
Case 1
 62 year old male with history of diabetes, hypertension
 Chief complaint: “ I am tired all the time”
 Has been feeling “down “ for the past few weeks every





day
Has been having trouble with memory and concentration
Has gained 20 lbs in past 2 years
SH:20 pack year smoking; drinks beer on weekends
Physical exam: obese, neck circumference 19 inches
Started on Paroxetine 20 mg
Case 1- 3 months later
 Still troubled by daytime sleepiness
 Now reports he fell asleep at red light driving to work
 Wife accompanied him to appointment, reports she
has sought refuge on another floor of house due to
loud snoring disturbing her sleep
 Wife also reports he is gasping and choking during
sleep
DOES
 Sleep disordered breathing:
 Obstructive sleep apnea
 6-12% of the population
 Males and females
 Obesity
 Anatomic abnormalities
 Increases with age
 Symptoms
snoring, observed apneas, daytime sleepiness
 Airway disorder
PATENT vs COLLAPSED AIRWAY
2006 American Academy of Sleep medicine
Sleep Disordered Breathing
Central and Obstructive Apnea
Obstructive Hypopnea
Consequences of recurrent obstructive
sleep apnea/hypopnea









Excessive daytime somnolence
Snoring
Morning headaches
Sleep maintenance insomnia
Impaired cognitive performance
Social/sexual/psychologic problems
Poor quality of life
Increased risk of MVA
Adverse cardiovascular outcomes




Systemic hypertension
Pulmonary hypertension
(?DM/metabolic syndrome)
?Stroke
Burwell et al: Extreme Obesity associated with alveolar hypoventilation: A
pickwickian syndrome. Am J Med 1956;21: 811- 818
•An obese patient came to the emergency room of the Peter Bent Brigham Hospital
•CC: Fell asleep at Poker with a full house and a large pot
•PE: Obese, hypersomnolence, hypoventilation, cor pulmonale
This reminded Burwell of Joe, the fat boy
From the Dickens novel, “The posthumous papers of the
Pickwick Club.”
The term was initially coined by Osler (1918)
Psychologic, cognitive, behavioral
sequelae of sleep apnea
 Daytime sleepiness- different from “fatigue or low energy”
as in depression
 Excessive sleep
 Involuntary naps
 Fighting sleepiness while sedentary
 Capacity to nap voluntarily





Hyperactivity in children
Impaired memory, attention, vigilance
Depression extremely common in OSA
Depressive symptoms reduced with CPAP
Confusional states and psychotic disorders
Depression and Sleep Apnea
 Wheaton, CDC study; (Sleep, 2012)
 Survey on sleep disordered breathing and
PHQ-9 depression screen 9714 adults
 Frequent snorting/stopping breathing, but not snoring,
associated with higher prevalence of probable major
depression
 Possible mechanisms underlying association between
depression and OSA
 Sleep fragmentation and hypoxemia
 Neurobiology of depression and upper airway control:
serotonin mediated, SSRIs in treatment of OSA?
 Shared risk factors- Depression in patients with obesity,
hypertension, diabetes should raise suspicion of coexisting
OSA
Positive Airway Pressure
2006 American Academy of Sleep Medicine
Nasal CPAP
Nasal CPAP/BIPAP
 Broad acceptance as treatment of choice in moderate
to severe OSA with improvement in:
 Symptoms of sleepiness( Epworth)
 Objective measures of sleepiness( MSLT)
 Cognitive function scores
 QOL scores
 Blood pressure, Pulmonary artery pressure
 Reduction in MVAs

White et al. Cochrane database 2000,Kaneko et al. NEJM
2003;348:1233-1241
Dental orthotic or mandibular
repositioning devices
Surgical Management:
Uvulopalatopharyngoplasty (UPPP)
2006 American Academy of Sleep Medicine
Mandibular advancement surgery
 Midface, palate,
and mandible
advanced
anteriorly
 Increases posterior
airway space
 Follow up
orthodontic
procedures, wiring
of jaw
 For severe disease
Upper-Airway Stimulation for Obstructive Sleep
N Engl J Med
Apnea
Volume 370(2):139-149
January 9, 2014
“The fat boy for once
had not been fast
asleep. He was
awake—wide awake to
what had been going
forward.”
DOES
 Narcolepsy
 Relatively rare but under-recognized
 Onset in adolescence
 Four cardinal symptoms




Excessive daytime sleepiness
Sleep paralysis
Vivid dreams/hallucinations
Cataplexy
 CNS disorder
Sleep initiation problems
 Primary sleep disorder
 Medical problem/ medication
 Restless legs syndrome

Pain, “creepy/crawly” sensation
 Pain: arthritis/fibromyalgia, etc
 Medications: stimulants including
caffeine/decongestants
 Poor bedroom conditions
 “Psychophysiologic” insomnia
 Depression/anxiety
Sleep maintenance disorders
 Primary sleep disorder
 Sleep disordered breathing
 Periodic limb movements of sleep
 Medical problems/medications
 Asthma/GERD/arthritis/urinary frequency
 Poor bedroom conditions
 “Psychophysiologic insomnia
 Depression/anxiety
Co-morbidity between sleep disorders
and psychiatric disorders
 Complex bi-directional relationship
 Sleep disturbance is a common feature of a wide range of
psychiatric disorders
 Depression
 Anxiety Disorders
 Schizophrenia
 Cognitive disorders
 Substance abuse
 Psychotropic medications can affect sleep and wakefulness
 Sleep disorders may be independent risk factors for the
development of psychiatric disorders and adverse outcomes
Treatment emergent side effects of
antidepressants (2008- PDR)
Antidepressant
Insomnia, %
Anxiety, %
Somnolence,%
Trazodone
6
6
41
Mirtazapine
6
….
54
Fluoxetine
16-33
12-14
13-17
Sertraline
16-28
6
13-15
Paroxetine
13
5
23
Venlafzine
18
6-13
23
Bupropion
11-16
5-6
2-3
Nefazodone >300mg
11
…
25
Nefazodone <300mg
9
…
16
Sleep in Depression
 Disturbed sleep is a defining symptom of depression
 More than 90% of patients with major depression
have insomnia
 Sleep onset and sleep maintenance insomnia
 Early morning awakenings
 Fatigue, not usually excessive somnonlence, when
awake
 20 % of patients with insomnia have major
depression
Sleep Disturbance in Depression:
more than a symptom?
 Insomnia seems to predict greater risk of development
of depression( Chang: Am J Epidemiol 1997, Salo: Sleep Med 2012)
 Chronic insomnia may contribute to the persistence of
depression (Pigeon: Sleep, Vol 31, No 4 2008)
 Addition of hypnotic agent to antidepressant leads to
greater improvement of sleep and faster, more
complete antidepressant response (Fava: Biol Psyhciatry 2006)
 CBT of insomnia alone improved symptoms of
depression in patients with mild depression ( Taylor,
Behavior Therapy 2007)
Sleep disturbance in anxiety disorders
 Generalized Anxiety Disorder
 Sleep disorders found in over 50% of patients
 Sleep onset insomnia
 PTSD
 Insomnia
 Nightmares
 At higher risk of sleep related movement and breathing
disorders
 Panic disorder:
 sleep onset and sleep maintenance insomnia;
 Nocturnal panic attacks- can be confused with choking of sleep
apnea or night terrors
Case 2
 22 year old recent college graduate with chief complaint of






inability to fall asleep at night and daytime fatigue
Recently moved to DC to work on Capitol Hill; first job
Tries to get to bed at 11pm, and uses 2 alarms to get up to
try to get up at 7:00am
Cannot fall asleep before 2 am
Sleeps until 10 am on weekends and feels better during the
day
Started on paroxetine for depression and trazodone for
sleep by primary care physician
Also takes Zolpidem 1-2 times per week after several nights
of inability to get to sleep
Sleep diary
Delayed Sleep Phase Syndrome
 Most common of circadian rhythm disturbances
 Occurs at all ages, but especially adolescents
 Biological clock is reset; physiologically impossible to
go to sleep earlier
 Sleeping late when able to maintains sleep delay
 Diagnostic issues: adolescent behavior, depression,
complicated by substance abuse
 Treatment: chronotherapy, bright light, melatonin
Advanced sleep phase syndrome
 “early to bed/early to rise”
 More common in older people
 Usually not problematic
 Usually does not require intervention
Jet lag
 Time zone changes
 East to west
 West to east
 “Natural” solutions best
 Synchronizing with day/night in new time zones
 Avoidance of alcohol/sedatives
 No effective drug remedies
Shift workers
 Night shift work
 Associated with medical problems
 Shortened sleep time
 Rotating shifts worse than consistent nights
 ? Employment of choice for delayed sleep phase
 Natural remedies best

Control of light and dark
 Alerting medication approved for this indication
Case 3
 66 year old man with history of snoring and frequent




awakenings from sleep
Awakenings occur in the latter third of the night
He wakes up “acting out dreams” according to his wife
Dreams relate to someone trying to “hurt his children”
and an old burn injury
He has knocked over bedside table on more than one
occasion
Polysomnogram- Sleep Stage?
Diagnosis?
Parasomnias
 “things that go bump in the night”
 Deep sleep parasomnias




Walking, talking, screaming, terrors, eating
Rocking, repetitive behaviors
Usually do not require medications
Environmental safety measures
 REM sleep parasomnias



REM behavior disorder
Older males
Treatable with medication
Parasomnias in Adults
 In the past, believed to be associated with significant
psychopathology; usually not present in
persistent adult parasomnias
 Violence or aggressive behavior can occur
with arousal disorders such as confusional
arousals and sleepwalking
 Triggering factors
– Sleep deprivation
– Alcohol
– Stress/anxiety
– Loud noise
– Drugs (sedatives, neuroleptics, stimulants,
antihistamines)
– Fever (in children)
Parasomnias in the Adult
Arousal (NREM) disorders
• Confusional arousals
• Sleepwalking
REM parasomnias
• Nightmares
• Sleep paralysis
• REM behavior disorder
REM behavior disorder
 Vivid dreams often with a violent theme
 Vigorous behaviors accompanying these
dreams which may result in injury to patient or partner
 Excessive chin or extremity EMG tone during
REM sleep on PSG (REM without atonia)
 Excessive limb or body jerking, complex
movements, vigorous or violent movements
during REM sleep
 Usually treated successfully with clonazepam
 Must rule out Obstructive sleep apnea
REM Behavior Disorder
 Acute form:
– Withdrawal from drugs or alcohol
– Adverse reaction to antidepressant drugs,
especially SSRIs
 Chronic form:
– Males, > 60
– Lengthy prodrome of subtle abnormalities of sleep
– Associated with alpha-synucleinopathies with
dementia, including Parkinson’s disease, dementia
with Lewy bodies and multi-system atrophy, about 10
years after the diagnosis of RBD.
REM Behavior disorder
 http://www.youtube.com/watch?v=
rFXYRQ9xPUA
Differential diagnosis and management of
sleep disorders in psychiatric practice
 Because of similarity in clinical manifestations, sleep
disorders may be mistaken for primary psychiatric
conditions
 Sleep disorders that are secondary to physical disorders
may also be mistakenly viewed as psychiatric in origin
 Three major types of sleep complaints:
 DIMS – disorder of initiation or maintenance of sleep
 DOES- Disorders of Excessive Sleepiness
 Parasomnias-episodes of disturbed behavior or
experiences related to sleep
Summary: Sleep disorders at risk of misdiagnosis
as primary psychiatric disorders
 Circadian Rhythm Disorders
 Obstructive Sleep Apnea syndrome
 Narcolepsy
 REM Behavior Disorder
 Other Parasomnias