1 sleep disorders medicine back to basics april 10, 2015 elliott k. lee md, frcpc, dip. abpn, dip....
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Sleep Disorders MedicineBack to BasicsApril 10, 2015
Elliott K. LeeMD, FRCPC, Dip. ABPN, Dip. Amer. Board of Sleep MedicineAsst. Professor, Dept of Psychiatry, University of Ottawa
Sleep Disorders Service, Royal Ottawa Hospital
Sleep disorders
Insomnia Excessive Daytime Sleepiness Nocturnal Spells
Insomnia
“Adjustment”/Psychophysiologic
(Psychologic factors,Physiologic factors,
Negative conditioning)
INSOMNIA
Circadian Psychiatric “Adjustment”/
Psychophysiologic
Medical/Neurologic
Excessive Daytime Sleepiness
Lack of sleep Insufficient time in bed
Inadequate quality of sleep Sleep Apnea, PLMD
Intrinsic sleepiness Narcolepsy; Idiopathic Hypersomnia
Medical/psychiatric disorder Major Depression Medications, medical – thyroid, anemia etc.
Circadian Rhythm Disturbance Shift work, delayed sleep phase, etc.
“Nocturnal Spells”
NREM parasomniaNight Terrors, Sleepwalking
REM parasomniaNightmares, 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 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
REM
N3
N2
N1
W
1
Hours
1 2 3 4 5 6 7
Table of Stg. %
Stg%
Sleep Stage % by Age
12
REM Sleep Rapid Eye Movements Muscle atonia (paralysis) Dream recall 90 minute latency “Paradoxical Sleep” – EEG mimics
wakefulness Breathing irregular, heart rate
fluctuates
Onset of REMR & K 1968
REM sleep onset
REM Control Nuclei
Orexin-Hypocretin projections
OREXIN(“Flip Flop switch)
REM Off
(REM On)
Wake On(sleep fragmentation)
Sleep On/(Wake off)(Sleep attacks)
(Sleep paralysis, cataplexy, hypnagogic hallucinations)
Orexin
• Novel sleeping agent approved by FDA in US (Aug 2014)Belsomra (suvorexant)
• Orexin antagonist- for treatment of insomnia
Sleep waveform schematic
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
Gamma 20 - 50 REM, wake
EEG Frequencies
“Deep”
“Awake”
“Stage II”
SLEEP DISORDERS
Sleep Disorders
Obstructive Sleep Apnea/hypopnea (OSA)
Restless Legs Syndrome (RLS)Periodic Limb Movement Disorder (PLMD)
REM behavior disorder (RBD) Narcolepsy
SLEEP APNEA Two Types: Obstructive & Central Pauses in breathing > 10 seconds in length Respiratory Disturbance Index: >5 hr
=clinically significant
ZZZZzzzzzzZZZZzzzzzz
OSA Clinical Symptoms
OBSTRUCTIVE SLEEP APNEA (OSA)
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
**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
OSA Consequences
Memory problemsIrritability, mental illness e.g. depression
Motor vehicle accidents
Hypertension
Heart attack and stroke
Impaired
glucose control
Sleep Deprivation and Children
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)
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
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Restless Legs Syndrome – DSM-5
“URGE” Unpleasant sensationU – rge to move legsR – est – symptoms worsened at
restG – ets better with movementE – vening – symptoms worse in
evening≥ 3x/week, ≥ 3monthsSignificant distressNot due to medical condition, substance
RLS/PLMD
Periodic Limb Movement Disorder (PLMD)
Restless Leg
Syndrome (RLS)
80%20%
RLS – PLMD: neurochemistry
Likely due to iron deficiency in basal ganglia (Fe is co-factor in enzymes that synthesize DA).
Address Exacerbating Factors
IRON DEFICIENCY Caffeine Tobacco Alcohol Medications
- dopamine blockers – antipsychotics, GI motility agents- antidepressants (SSRI’s)
Dopaminergic Agents Intermittent
(<2x/week)- Levodopa (Sinemet)eg. Sinemet CR 25/100 1 tab po qhs prntake as abortive therapy when symptoms arise
Daily or almost daily (>3x/week)- Pramipexole (Mirapex)- Ropinirole
(Requip)eg Pramipexole 0.25-0.5 mg po qpmtake 2 hours before symptoms are worst
Silber MH et al. Mayo Clin ProcSilber MH et al. Mayo Clin Proc (2004) 79(7) :
916-22
Side Effects Nausea Nasal stuffiness Constipation Leg swelling Insomnia Sleepiness/sleep attacks
(caution driving) *Pathological gambling and
compulsive behaviors
Second and Third Line Agents 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)
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 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
SleepwalkingSleepwalking
▪ ▪ Stage N3 (NREM)Stage N3 (NREM)
▪ ▪ No dream recallNo dream recall
▪ ▪ ChildrenChildren
▪ ▪ Not easily Not easily awakenedawakened
REM Behaviour REM Behaviour DisorderDisorder
▪ ▪ REM sleepREM sleep
▪ ▪ Dream recallDream recall
▪ ▪ Adults (elderly)Adults (elderly)
▪ ▪ Easily awakenedEasily awakened
NARCOLEPSY
Narcolepsy - DSM-5 Recurrent periods of irrepressible
need to sleep, ≥ 3x/wk, ≥3 months Cataplexy* Hypocretin deficiency (CSF Hcrt-
1<110pg/mL) PSG – REM latency ≤ 15 min, or
MSLT with SL ≤ 8 min and ≥ 2 SOREMPs
Narcolepsy “Pentad”Narcolepsy “Pentad”
EExcessive Daytime Sleepinessxcessive Daytime Sleepiness– May fall asleep without warning, unusual situationsMay fall asleep without warning, unusual situations
Cataplexy (75%)Cataplexy (75%)– Flaccid muscle paralysis; eyes and diaphragm OK; pt. remains Flaccid muscle paralysis; eyes and diaphragm OK; pt. remains
awake but paralyzed.awake but paralyzed.
Hypnagogic / pompic hallucinations (50-60%)Hypnagogic / pompic hallucinations (50-60%)– ““Multimodal”. Often highly emotional, sexual, frighteningMultimodal”. Often highly emotional, sexual, frightening
Sleep Paralysis (50-66%)Sleep Paralysis (50-66%)
– – Awakes unable to move anything but eyes. Can’t Awakes unable to move anything but eyes. Can’t breathe breathe voluntarily or talk. HH often occur. voluntarily or talk. HH often occur.
Disturbed nocturnal sleepDisturbed nocturnal sleep
Excessive Daytime Excessive Daytime Sleepiness (EDS)Sleepiness (EDS)
Measure: Measure: Multiple Sleep Latency TestMultiple Sleep Latency Test (MSLT)(MSLT) Following an Nocturnal Polysomnogram Following an Nocturnal Polysomnogram
(PSG)(PSG) Four or five 20 minutes naps at 2 hour Four or five 20 minutes naps at 2 hour
intervalsintervals Example: 9am, 11am, 1pm, 3pmExample: 9am, 11am, 1pm, 3pm Check for: 1) Avg. SOL & 2) REM sleep x2Check for: 1) Avg. SOL & 2) REM sleep x2 Pathological Sleepiness = Pathological Sleepiness =
fall asleep < 8 mins + 2 or more SOREMPSfall asleep < 8 mins + 2 or more SOREMPS
* SOL = sleep onset latency* SOREMP = Sleep Onset REM period
MSLT interpretation
BOBNap 1 Nap 2 Nap 3 Nap 4 Nap 55.0 mins 10 mins 9 mins 20 mins 20
minsREM No REM No REM No REM No
REMBob’s Avg. SOL = 12.8 mins, 1 REM period
JANENap 1 Nap 2 Nap 3 Nap 41.5 mins 2 mins 1 min 3 minsREM No REM REM No REMJane’s Avg. SOL = 1.9 mins, 2 REM periods
CAROLNap 1 Nap 2 Nap 3 Nap 420 mins 20 mins 20 mins 20 minsCarol’s Avg. SOL = 20 mins, no sleep, no REM periods
Markers of Narcolepsy 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 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 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)
Dissatisfaction with quality/quantity of Dissatisfaction with quality/quantity of sleep, ≥1 of following symptoms:sleep, ≥1 of following symptoms:- Problems initiating sleep- Problems initiating sleep- Difficulty maintaining sleep- Difficulty maintaining sleep- Early morning wakenings- Early morning wakenings
Clinically significant distressClinically significant distress ≥≥3 nights/week, ≥3 months3 nights/week, ≥3 months Not due to substance, medical Not due to substance, medical
condition, inadequate sleep time.condition, inadequate sleep time.
Insomnia 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
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
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
Cognitive Behavioural Therapy Sleep Restriction Therapy Relaxation Techniques Sleep Hygiene
Suggestions
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 livesDrug Half life (hours)
Ultra short half life
Zaleplon (Starnoc) 0.9-1.1
Zolpidem (Sublinox) 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, 2004Bain, 2006Fernandez, C et al, 1995
Antipsychotics and sleepTmax (h)
Total Sleep Time
SWS(Slow wave Sleep)
Sleep latency
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.
Zzzzzz QUESTIONS?? Zzzzzz
Special thanks to Chief Technologist Lisa Orr for her enormous assistance in assembling these slides, and for my twins Isaac and Jacob
for letting me sleep.
Now for some questions, if there’s
time
x
The most common cause of excessive daytime sleepiness in the general population is:
A. NarcolepsyB. Sleep ApneaC. Nocturnal myoclonusD. Sleep deprivationE. Idiopathic hypersomnia
The most common cause of excessive daytime sleepiness in the general population is:
A. NarcolepsyB. Sleep ApneaC. Nocturnal myoclonusD. Sleep deprivationE. Idiopathic hypersomnia
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 dementiaB. Lewy body dementiaC. Frontotemporal dementiaD. MalingeringE. 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 dementiaB. Lewy body dementiaC. Frontotemporal dementiaD. MalingeringE. The wife has a dementing illness
The wakefulness promoted by caffeine is mediated by its effect upon which neurotransmitter:
A. HistamineB. DopamineC. AdenosineD. AcetylcholineE. Serotonin
The wakefulness promoted by caffeine is mediated by its effect upon which neurotransmitter:
A. HistamineB. DopamineC. AdenosineD. AcetylcholineE. 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
Continuous Positive Airway Pressure (CPAP)
Uvulopalatopharyngoplasty (UP3)
Oral Appliances (Mandibular Repositioning Devices (MRDs)
Silencer-
Johns Dental Labs
Klearway-
Great Lakes Orthodontics