Transcript sleeplecture2014btb2novideo

Sleep Disorders Medicine
Back to Basics
April 9, 2014
Elliott K. Lee
MD, FRCPC, Dip. ABPN, Dip. Amer. Board of Sleep Medicine
Asst. Professor, Dept of Psychiatry, University of Ottawa
Sleep Disorders Service, Royal Ottawa Hospital
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Sleep disorders
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Insomnia
Excessive Daytime Sleepiness
Nocturnal Spells
Insomnia
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Circadian
Psychiatric
“Adjustment”/
Psychophysiologic
Medical/Neurologic
“Adjustment”/Psychophysiologic
(Psychologic factors,
Physiologic factors,
Negative conditioning)
INSOMNIA
Excessive Daytime Sleepiness
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Lack of sleep
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Inadequate quality of sleep
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Narcolepsy; Idiopathic Hypersomnia
Medical/psychiatric disorder
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Sleep Apnea, PLMD
Intrinsic sleepiness
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Insufficient time in bed
Major Depression
Medications, medical – thyroid, anemia etc.
Circadian Rhythm Disturbance
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Shift work, delayed sleep phase, etc.
“Nocturnal Spells”
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NREM parasomnia
Night Terrors, Sleepwalking
REM parasomnia
Nightmares, REM behavior disorder etc
Seizure Disorder
Psychiatric e.g. Panic attack etc.
Purpose of Sleep
Restorative Function
 Energy Conservation
 Immune Function Regulation
 Ontogenetic Hypothesis
 Memory Consolidation
 Protective Mechanism

SLEEP ARCHITECTURE
STAGES OF SLEEP
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NREM & REM
NREM = N1, N2 (light stages)
N3 (SWS – slow wave sleep)
Sleep Cycles
REM increases as the night progresses
Changes across the lifespan
SLEEP HYPNOGRAM
W
N2
1
N1
N3
REM
1
2
3
4
Hours
5
6
7
o
f
S
t
g
.
%
Stg%
Sleep Stage % by Age
REM Sleep
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Rapid Eye Movements
Muscle atonia (paralysis)
Dream recall
90 minute latency
“Paradoxical Sleep” – EEG mimics
wakefulness
Breathing irregular, heart rate
fluctuates
REM sleep onset
Onset of REM
R & K 1968
REM Control Nuclei
SCN
clock
DA
(+)
~
Orexin /
Hypocretin
Histamine
(+)
5HT
(+)
NA
(+)
Monoamines
controlled by
Orexin
Orexin-Hypocretin projections
Sleep waveform schematic
EEG Frequencies
EEG Type
Hz.
Sleep Stg.
Delta
0.5 - 3
SWS
Theta
3-7
REM
Alpha
8 - 12
Wake
Beta
16 - 25
Wake
Spindle
12 - 14
Stg. N2, N3
20 - 50
REM, wake
“Deep”
“Awake”
“Stage II”
Gamma
SLEEP DISORDERS
Sleep Disorders
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Obstructive Sleep Apnea/hypopnea
(OSA)
Restless Legs Syndrome (RLS)
Periodic Limb Movement Disorder
(PLMD)
REM behavior disorder (RBD)
Narcolepsy
SLEEP APNEA
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Two Types: Obstructive & Central
Pauses in breathing > 10 seconds in length
Respiratory Disturbance Index: >5 hr =clinically
significant
ZZZZzzzzzz
OSA Clinical Symptoms
OBSTRUCTIVE SLEEP APNEA
(OSA)
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Causes
▪ Narrow Upper Airway
▪ Elevated BMI
▪ Family Hx
Exacerbated by:
▪ Medications – BDZs, Opioids
▪ Alcohol Consumption
▪ Supine sleep
▪ REM sleep
▪ **Supine + REM sleep
Normal vs. Collapsed Airway
“Kissing” Tonsils
TREATMENTS FOR OSA
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**CPAP – Continuous Positive Airway Pressure
**Weight Loss - ↓ BMI = ↓ RDI
Avoid Alcohol, Sedatives
“Snoreball” Technique / Positional Therapy
Oral Appliance
Provent
Upper Airway Surgery
 Tonsillectomy (pediatrics)
 Uvulopalatopharyngoplasty (UPPP)
 Tracheostomy
Provent
Continuous Positive Airway
Pressure (CPAP)
Uvulopalatopharyngoplasty (UP3)
Motor vehicle accidents
Hypertension
OSA Consequences
Impaired
glucose
control
Irritability, mental illness e.g. depression
Heart attack and stroke
Memory problems
Sleep Deprivation and Children
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Not the same as
adults
May be
“hyperactive”
- fidget
- poor attention
- cranky
Undiagnosed OSA
may be mistaken for
ADHD
Periodic Limb Movements (PLMs)
& Restless Legs Syndrome (RLS)
Periodic Limb Movements (PLMs)
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Repetitive leg (limb) movements DURING
SLEEP
Typically 20-40 seconds apart
Cause awakenings and fragmentation
Patient often unaware. Bedpartner reports
“kicking”
c/o frequent awakenings, light sleep
aka Nocturnal Myoclonus
PLMs 2 MIN
36
Restless Leg Syndrome
“URGE”
U – rge to move legs
R – est – symptoms worsened at rest
G – ets better with movement
E – vening – symptoms worse in evening
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38
RLS/PLMD
Periodic Limb
Movement
Disorder (PLMD)
Restless Leg
Syndrome
(RLS)
20%
80%
RLS – PLMD: neurochemistry

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Likely due to iron deficiency in basal
ganglia (Fe is co-factor in enzymes that
synthesize DA).
May predict onset of “synnucleinopathies” (REM behaviour
disorder, Parkinson’s, Lewy Body
dementia).
Address Exacerbating Factors
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Caffeine
Tobacco
Alcohol
Medications
- dopamine blockers – antipsychotics,
GI motility agents
- antidepressants (SSRI’s)
Check Iron (Ferritin)!
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Intake – food?
Absorption - GI difficulties
Blood loss?
- Anemia – Cough? Poop?
- Menstrual Periods/Pregnancy
- Blood donations
Target ferritin > 50 μg/L
May replace e.g. FeSO4 with vitamin C tid 2
hours before or after meals
Dopaminergic Agents

 Daily or almost daily
Intermittent
(>3x/week)
(<2x/week)
- Pramipexole
- Levodopa
(Mirapex)
(Sinemet)
Ropinirole
eg. Sinemet CR
(Requip)
25/100 1 tab po qhs eg Pramipexole 0.25prn
0.5 mg po qpm
take as abortive
take 2 hours before
therapy when
symptoms are worst
symptoms arise
Silber MH et al. Mayo Clin Proc (2004) 79(7) : 916-22
Side Effects
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Nausea
Nasal stuffiness
Constipation
Leg swelling
Insomnia
Sleepiness
(caution driving)
*Pathological gambling and
compulsive behaviors
Second and Third Line Agents
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Gabapentin (Neurontin) - anticonvulsant
Benzodiazepines (sedative hypnotics)
- Clonazepam (rivotril / klonopin)
- Lorazepam (ativan)
- Diazepam (valium)
Opioids
- Codeine
- Hydrocodone
- Methadone*
(Quinine obsolete)
REM BEHAVIOUR DISORDER
(RBD)
REM Behaviour Disorder (RBD)
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No muscle atonia during REM sleep
Ability to act out complex dream behaviour
Bedpartner often the “victim”
Age of onset: 50 – 60yrs. Males (90%)
Usually opposite of waking personality
Strongly associated with synucleinopathies
- Parkinsonism/Parkinson’s
- Lewy Body Dementia
Treatments for RBD
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Full EEG montage during PSG
CT Scan, MRI – r/o lesions
Securing the environment (mattress on
floor, bed rails, restraints)
Bedpartner sleeps in another room
Rx – Clonazepam
* (Melatonin)
* (Pramipexole)
SLEEPWALKING vs. RBD
Sleepwalking
▪
▪
▪
▪
Stage N3 (NREM)
No dream recall
Children
Not easily awakened
▪
▪
▪
▪
REM Behaviour
Disorder
REM sleep
Dream recall
Adults (elderly)
Easily awakened
NARCOLEPSY
Narcolepsy - DSM-5
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Recurrent periods of irrepressible need
to sleep, ≥ 3x/wk, ≥3 months
Cataplexy*
Hypocretin deficiency (CSF Hcrt1<110pg/mL)
PSG – REM latency ≤ 15 min, or MSLT
with SL ≤ 8 min and ≥ 2 SOREMPs
Narcolepsy “Pentad”
Excessive Daytime Sleepiness
– May fall asleep without warning, unusual situations
Cataplexy (75%)
– Flaccid muscle paralysis; eyes and diaphragm OK; pt. remains
awake but paralyzed.
Hypnagogic / pompic hallucinations (50-60%)
– “Multimodal”. Often highly emotional, sexual, frightening
Sleep Paralysis (50-66%)
– Awakes unable to move anything but eyes. Can’t breathe
voluntarily or talk. HH often occur.
Disturbed nocturnal sleep
Excessive Daytime Sleepiness
(EDS)
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Measure: Multiple Sleep Latency Test (MSLT)
Following an Nocturnal Polysomnogram (PSG)
 Four or five 20 minutes naps at 2 hour intervals
 Example: 9am, 11am, 1pm, 3pm
 Check for: 1) Avg. SOL & 2) REM sleep x2
 Pathological Sleepiness =
fall asleep < 8 mins + 2 or more SOREMPS
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* SOL = sleep onset latency
* SOREMP = Sleep Onset REM period
MSLT interpretation
BOB
Nap 1
5.0 mins
REM
Nap 2
10 mins
No REM
Nap 3
9 mins
No REM
Nap 4
20 mins
No REM
Nap 2
2 mins
No REM
Nap 3
1 min
REM
Nap 4
3 mins
No REM
Nap 2
20 mins
Nap 3
20 mins
Nap 4
20 mins
Bob’s Avg. SOL = 12.8 mins, 1 REM period
JANE
Nap 1
1.5 mins
REM
Jane’s Avg. SOL = 1.9 mins, 2 REM periods
CAROL
Nap 1
20 mins
Carol’s Avg. SOL = 20 mins, no sleep, no REM periods
Nap 5
20 mins
No REM
Markers of Narcolepsy
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Hypocretin/Orexin
90-95% of narcolepsy with cataplexy –
are CSF hypocretin deficient
HLA DQB1*0602 – strongly associated
with hypocretin deficiency (95%)
HLA DQA1*0102
HLA DRB1*1503
Cataplexy
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Sudden onset of full or partial skeletal
muscle weakness or paralysis
Is preceded by heightened emotion
such as laughter, anger or excitement
Lasts seconds to minutes
Results from abnormality of the REM
sleep system
Narcolepsy Treatment
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Rx: Stimulant medication
- Modafinil (Alertec)
- Methylphenidate (Ritalin)
- Dexedrine
Education: EDS is not their fault
Therapeutic napping
REM suppressant medications for cataplexy
- SSRI – e.g. Fluoxetine
- Sodium Oxybate (GHB) - Xyrem
INSOMNIA
INSOMNIA DISORDER (DSM-5)
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Dissatisfaction with quality/quantity of
sleep, ≥1 of following symptoms:
- Problems initiating sleep
- Difficulty maintaining sleep
- Early morning wakenings
Clinically significant distress
≥3 nights/week, ≥3 months
Not due to substance, medical condition,
inadequate sleep time.
Insomnia
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Sleep Deprivation – “Hypoarousal”
- decreased metabolism
- decreased body temperature
- lethargy
- short sleep onset times
Insomnia – “HYPER-arousal” night + day
- increased metabolism
- increased body temperature
- anxiety, agitation
Suggestions
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Elucidate CAUSE/contributing factors
- Stressor?
- Substances – Caffeine? Alcohol?
Nicotine?
- Circadian factors?
- Medical/Sleep – thyroid? RLS? Meds?
- Psychiatric – Depression? Anxiety?
Stress Behavioral factors/Sleep hygiene
Treating insomnia:
Personal Sleep Hygiene
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Maintain a regular wake/sleep schedule.
Refrain from taking naps.
Avoid caffeine after mid-afternoon.
Exercise - but not within 3 hours of bedtime.
Establish a relaxing routine before bedtime.
Use the bedroom for sleep activities.
Avoid clock watching
Set environment (light, noise, temperature)
at comfortable levels.
Insomnia Treatments
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Cognitive Behavioural Therapy
Sleep Restriction Therapy
Relaxation Techniques
Sleep Hygiene
Suggestions
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Stressor/short term relief
- most evidence – non benzodiazepine benzo
receptor agonists – Zopiclone (Imovane)
Trazodone – reasonable –but little evidence
Circadian factors - melatonin
Comorbid psychiatric factors
- Anxiety/Depression
- BDZs – ultra short to medium T1/2
- Mirtazapine
- Atypical antipsychotics – selected cases
BDZ and Non BDZ half lives
Drug
Half life (hours)
Ultra short half life
Zaleplon (Starnoc)
0.9-1.1
Zolpidem (Ambien)
1.4-4.5
Zopiclone (Imovane)
3.5-6.5
Triazolam (Halcion)
2-5
Short to medium half life
Lorazepam (Ativan)
10-20
Temazepam (Restoril)
8-24
Oxazepam (Serax)
6-24
Alprazolam (Xanax)
6-20
Long half life
Clonazepam (Rivotril)
5-30
Diazepam (Valium)
20-80
Chlorodiazepoxide (Librium)
7-30
Chouinard, 2004
Bain, 2006
Fernandez, C et al, 1995
Antipsychotics and sleep
Tmax (h)
Total Sleep
Time
SWS
(Slow wave
Sleep)
Clozapine
3
+++
++
+
Quetiapine
1
+++
0
+++
Ziprasidone
5
+++
+++
+
Olanzapine
5
+++
+++
+
Risperidone
1
+
+++
+
Haloperidol
4-6
+++
++
+++
Krystal, A.D., H.W. Goforth, and T. Roth, Effects of antipsychotic medications
on sleep in schizophrenia. Int Clin Psychopharmacol, 2008. 23(3): p. 150-60.
Sleep
latency
Now for some
questions, if there’s time
x
The most common cause of excessive
daytime sleepiness in the general
population is:
A.
Narcolepsy
B.
Sleep Apnea
C.
Nocturnal myoclonus
D.
Sleep deprivation
E.
Idiopathic hypersomnia
The most common cause of excessive
daytime sleepiness in the general
population is:
A.
Narcolepsy
B.
Sleep Apnea
C.
Nocturnal myoclonus
D.
Sleep deprivation
E.
Idiopathic hypersomnia
Which of the following is necessary for
the rate-limiting step in the
biosynthesis of dopamine?
A.
Magnesium
B.
Copper
C.
Zinc
D.
Iron
E.
None of the above
Which of the following is necessary for
the rate-limiting step in the
biosynthesis of dopamine?
A.
Magnesium
B.
Copper
C.
Zinc
D.
Iron
E.
None of the above
Which of the following drugs is not
indicated for the treatment of Restless
Leg Syndrome (RLS)
A.
Venlafaxine
B.
Propoxyphene
C.
Gabapentin
D.
Ropinirole
E.
Pramipexole
Which of the following drugs is not
indicated for the treatment of Restless
Leg Syndrome (RLS)
A.
Venlafaxine
B.
Propoxyphene
C.
Gabapentin
D.
Ropinirole
E.
Pramipexole
A 72 year old man presents with a 3 year history of
cognitive decline. His wife notes that during the
night he may flail his arms, and lash out at her
during sleep. Upon awakening, he often vaguely
recalls being chased and fighting off “the animals
that were trying to get me”. The most likely
diagnosis is:
A.
Alzheimer’s dementia
B.
Lewy body dementia
C.
Frontotemporal dementia
D.
Malingering
E.
The wife has a dementing illness
A 72 year old man presents with a 3 year history of
cognitive decline. His wife notes that during the
night he may flail his arms, and lash out at her
during sleep. Upon awakening, he often vaguely
recalls being chased and fighting off “the animals
that were trying to get me”. The most likely
diagnosis is:
A.
Alzheimer’s dementia
B.
Lewy body dementia
C.
Frontotemporal dementia
D.
Malingering
E.
The wife has a dementing illness
The wakefulness promoted by caffeine is
mediated by its effect upon which
neurotransmitter:
A.
Histamine
B.
Dopamine
C.
Adenosine
D.
Acetylcholine
E.
Serotonin
The wakefulness promoted by caffeine is
mediated by its effect upon which
neurotransmitter:
A.
Histamine
B.
Dopamine
C.
Adenosine
D.
Acetylcholine
E.
Serotonin
What two laboratory signs on the Multiple Sleep Latency
Test are diagnostic of narcolepsy?
A.
mean sleep latency > 15 minutes and one sleep
onset REM period
B.
mean sleep latency <8 minutes and no sleep onset
REM periods
C.
mean sleep latency >20 minutes and two sleep
onset REM periods
D.
mean sleep latency <8 minutes and two sleep onset
REM periods
E.
mean sleep latency >15 minutes and no sleep onset
REM periods
What two laboratory signs on the Multiple Sleep Latency
Test are diagnostic of narcolepsy?
A.
mean sleep latency > 15 minutes and one sleep
onset REM period
B.
mean sleep latency <8 minutes and no sleep onset
REM periods
C.
mean sleep latency >20 minutes and two sleep
onset REM periods
D.
mean sleep latency <8 minutes and two sleep onset
REM periods
E.
mean sleep latency >15 minutes and no sleep onset
REM periods
Which of the following best describe the narcolepsy
tetrad?
A.
cataplexy, sleep paralysis, nocturnal myoclonus,
sleepiness
B.
epilepsy, sleepiness, hypnagogic hallucinations,
cataplexy
C.
sleepiness, cataplexy, hypnagogic hallucinations,
sleep paralysis
D.
sleep onset REM periods, sleepiness, enuresis,
cataplexy
E.
sleep paralysis, sleepiness, cataplexy, sleep apnea
Which of the following best describe the narcolepsy
tetrad?
A.
cataplexy, sleep paralysis, nocturnal myoclonus,
sleepiness
B.
epilepsy, sleepiness, hypnagogic hallucinations,
cataplexy
C.
sleepiness, cataplexy, hypnagogic hallucinations,
sleep paralysis
D.
sleep onset REM periods, sleepiness, enuresis,
cataplexy
E.
sleep paralysis, sleepiness, cataplexy, sleep apnea
Zzzzzz
QUESTIONS??
Zzzzzz
Special thanks to Chief Technologist Lisa Orr for her enormous assistance in
assembling these slides.