Richard E. Waldhorn, MD Clinical Professor of Medicine - PowerPoint Presentation

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Richard E. Waldhorn, MDClinical Professor of MedicineDivision of Pulmonary, Critical Care and Sleep MedicineGeorgetown University School of Medicine

Sleep Disorders

The Nightmare-

Henry Fuseli, 1781

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Sleep DisordersWhat 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?

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Sleep - DefinitionSleep 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 RegulatedInvolves different areas in the brain

Purpose is not understood

Essential to life

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Sleep RegulationHomeostatic process: determined by sleep and wakingThe pressure for sleep increases proportionately to the time since last sleepCircadian

process: Approximately 24 hr cycle of sleep and wakefulness periods with high and low sleep propensityindependent of sleep and wakingSuprachiasmatic nucleus- regulated by zeitgebers: sunlight and eating timeUltradian

process: occurring within sleep- the alternation of Non REM and REM sleep

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Sleep StagesTwo 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 bodyFast 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 EEGLowest muscular tone

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Sleep Stages - Adult

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REM Sleep- bilateral synchronous eye movements, muscle atonia

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Normal sleepSleep latencyNormal: 10 minutesStage N1-N2 sleepInitial period: 20-40 minutesStage N3 sleepOnset at 30-40 minutes after lights out

Stage REM sleepOnset at 90 minutes after lights out

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Sleep cycle: normal hypnogram

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Normal SleepN1-N2 sleep—light sleep50-60% of sleep timeSleep onset and in latter part of the nightN3 “deep”—slow wave sleep“restorative” part of the nightEarly in the sleep cycle

20-25% of sleep timeREM “dream” sleepBrain active/muscles paralyzed4 REM periods thru the nightLongest is just prior to awakening20-25% of the night

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Key Polysomnographic TermsSleep latency- lights out until sleep onsetREM latency- sleep onset to the first epoch of REMSleep efficiency- Total sleep time/total recording time

Wake after sleep onset (WASO)Percent REM sleepPercent slow-wave sleep (SWS)Percent stage 1-2 sleep

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What causes sleep ?Activation of neural structures in the brainstemCortex is variably active—most in REM sleepComplex interplayBrain: light and darkHormones: cortisolTemperature

Circadian rhythm

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Circadian Rhythms

Suprachiasmatic Nuclei (SCN)

Light

Output Rhythms

Physiology

Behavior

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Normal Circadian Sleep Rhythm

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Circadian Rhythms

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Sleep Changes with Age

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Breathing during sleepCentral nervous system controlStretch receptorsChemoreceptorsBlood carbon dioxide levelSlightly higher trigger to breathe than when awakeVery sensitiveCan be affected by drugs, chronic diseases

Altitude

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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 dreaming1957- 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.

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Sleep DisordersDOES—disorders of excessive somnolenceQuantity of sleepQuality of sleepDIMS—disorders of initiation and maintenance of sleepSleep onset insomniaSleep maintenance insomnia

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Sleep DisordersCircadian rhythm disordersDelayed sleep phase syndrome “night owl”Advanced sleep phase syndrome “lark”Jet lagNight shift workerParasomnias

Excessive motor activity during sleepSleep walking/talking/eatingSleep terrorsREM behavior disorder

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Question 1What is the most common cause of DOES?1. sleep disordered breathing2. narcolepsy3. inadequate sleep hours4. sleep walking

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DOESInadequate sleep hoursAdult sleep requirement: 7-9 hoursAdequate sleep architecture50-60% light sleep (N1-N2)20-25% deep sleep (N3)20-25% REM sleepGood sleep behaviors

Proper sleep conditions

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Case 162 year old male with history of diabetes, hypertensionChief complaint: “ I am tired all the time”Has been feeling “down “ for the past few weeks every dayHas been having trouble with memory and concentration

Has gained 20 lbs in past 2 yearsSH:20 pack year smoking; drinks beer on weekendsPhysical exam: obese, neck circumference 19 inchesStarted on Paroxetine 20 mg

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Case 1- 3 months laterStill troubled by daytime sleepinessNow reports he fell asleep at red light driving to workWife accompanied him to appointment, reports she has sought refuge on another floor of house due to loud snoring disturbing her sleepWife also reports he is gasping and choking during sleep

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DOESSleep disordered breathing: Obstructive sleep apnea6-12% of the populationMales and femalesObesityAnatomic abnormalitiesIncreases with age

Symptoms snoring, observed apneas, daytime sleepinessAirway disorder

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PATENT vs COLLAPSED AIRWAY

2006 American Academy of Sleep medicine

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Sleep Disordered Breathing

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Central and Obstructive Apnea

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Obstructive Hypopnea

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Consequences of recurrent obstructive sleep apnea/hypopneaExcessive daytime somnolenceSnoringMorning headaches

Sleep maintenance insomniaImpaired cognitive performanceSocial/sexual/psychologic problems

Poor quality of lifeIncreased risk of MVAAdverse cardiovascular outcomes

Systemic hypertension

Pulmonary hypertension

(?DM/metabolic syndrome)

?Stroke

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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)

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Psychologic, cognitive, behavioral sequelae of sleep apneaDaytime sleepiness- different from “fatigue or low energy” as in depressionExcessive sleep

Involuntary napsFighting sleepiness while sedentaryCapacity to nap voluntarilyHyperactivity in childrenImpaired memory, attention, vigilanceDepression extremely common in OSADepressive symptoms reduced with CPAP

Confusional states and psychotic disorders

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Depression and Sleep ApneaWheaton, CDC study; (Sleep, 2012)Survey on sleep disordered breathing and PHQ-9 depression screen 9714 adultsFrequent snorting/stopping breathing, but not snoring, associated with higher prevalence of probable major depression

Possible mechanisms underlying association between depression and OSASleep fragmentation and hypoxemiaNeurobiology 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

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Positive Airway Pressure

2006 American Academy of Sleep Medicine

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Nasal CPAP

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Nasal CPAP/BIPAPBroad acceptance as treatment of choice in moderate to severe OSA with improvement in:Symptoms of sleepiness( Epworth)Objective measures of sleepiness( MSLT)Cognitive function scoresQOL scores

Blood pressure, Pulmonary artery pressureReduction in MVAsWhite et al. Cochrane database 2000,Kaneko et al. NEJM 2003;348:1233-1241

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Dental orthotic or

mandibular repositioning devices

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Surgical Management:Uvulopalatopharyngoplasty (UPPP)

2006 American Academy of Sleep Medicine

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Mandibular advancement surgery

Midface, palate, and mandible advanced anteriorlyIncreases posterior airway spaceFollow up orthodontic procedures, wiring of jaw

For severe disease

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Upper-Airway Stimulation for Obstructive Sleep Apnea

N Engl J Med

Volume 370(2):139-149

January 9, 2014

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“The fat boy for once had not been fast asleep. He was awake—wide awake to what had been going forward.”

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DOES NarcolepsyRelatively rare but under-recognizedOnset in adolescenceFour cardinal symptomsExcessive daytime sleepinessSleep paralysisVivid dreams/hallucinations

CataplexyCNS disorder

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Sleep initiation problemsPrimary sleep disorderMedical problem/ medicationRestless legs syndromePain, “creepy/crawly” sensationPain: arthritis/fibromyalgia, etcMedications: stimulants including caffeine/decongestants

Poor bedroom conditions“Psychophysiologic” insomniaDepression/anxiety

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Sleep maintenance disordersPrimary sleep disorderSleep disordered breathingPeriodic limb movements of sleepMedical problems/medicationsAsthma/GERD/arthritis/urinary frequencyPoor bedroom conditions“

Psychophysiologic insomniaDepression/anxiety

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Co-morbidity between sleep disorders and psychiatric disordersComplex bi-directional relationshipSleep disturbance is a common feature of a wide range of psychiatric disordersDepressionAnxiety DisordersSchizophrenia

Cognitive disordersSubstance abusePsychotropic medications can affect sleep and wakefulnessSleep disorders may be independent risk factors for the development of psychiatric disorders and adverse outcomes

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Treatment emergent side effects of antidepressants (2008- PDR)

AntidepressantInsomnia, %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

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Sleep in DepressionDisturbed sleep is a defining symptom of depressionMore than 90% of patients with major depression have insomniaSleep onset and sleep maintenance insomniaEarly morning awakenings

Fatigue, not usually excessive somnonlence, when awake20 % of patients with insomnia have major depression

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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)

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Sleep disturbance in anxiety disordersGeneralized Anxiety DisorderSleep disorders found in over 50% of patientsSleep onset insomniaPTSDInsomnia

NightmaresAt higher risk of sleep related movement and breathing disordersPanic disorder: sleep onset and sleep maintenance insomnia; Nocturnal panic attacks- can be confused with choking of sleep apnea or night terrors

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Case 222 year old recent college graduate with chief complaint of inability to fall asleep at night and daytime fatigueRecently moved to DC to work on Capitol Hill; first jobTries to get to bed at 11pm, and uses 2 alarms to get up to try to get up at 7:00amCannot fall asleep before 2 am

Sleeps until 10 am on weekends and feels better during the dayStarted on paroxetine for depression and trazodone for sleep by primary care physicianAlso takes Zolpidem 1-2 times per week after several nights of inability to get to sleep

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Sleep diary

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Delayed Sleep Phase SyndromeMost common of circadian rhythm disturbancesOccurs at all ages, but especially adolescentsBiological clock is reset; physiologically impossible to go to sleep earlierSleeping late when able to maintains sleep delayDiagnostic issues: adolescent behavior, depression, complicated by substance abuseTreatment:

chronotherapy, bright light, melatonin

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Advanced sleep phase syndrome“early to bed/early to rise”More common in older peopleUsually not problematic Usually does not require intervention

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Jet lagTime zone changesEast to westWest to east“Natural” solutions bestSynchronizing with day/night in new time zonesAvoidance of alcohol/sedativesNo effective drug remedies

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Shift workersNight shift workAssociated with medical problemsShortened sleep timeRotating shifts worse than consistent nights? Employment of choice for delayed sleep phaseNatural remedies bestControl of light and dark

Alerting medication approved for this indication

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Case 366 year old man with history of snoring and frequent awakenings from sleepAwakenings occur in the latter third of the nightHe wakes up “acting out dreams” according to his wifeDreams relate to someone trying to “hurt his children” and an old burn injuryHe has knocked over bedside table on more than one occasion

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Polysomnogram- Sleep Stage? Diagnosis?

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Parasomnias“things that go bump in the night”Deep sleep parasomniasWalking, talking, screaming, terrors, eatingRocking, repetitive behaviorsUsually do not require medications

Environmental safety measuresREM sleep parasomniasREM behavior disorderOlder malesTreatable with medication

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Parasomnias in AdultsIn 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 sleepwalkingTriggering factors – Sleep deprivation – Alcohol

– Stress/anxiety – Loud noise –

Drugs

(

sedatives

,

neuroleptics, stimulants, antihistamines) – Fever (in children)

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Parasomnias in the Adult Arousal (NREM) disorders • Confusional arousals • Sleepwalking

REM parasomnias • Nightmares • Sleep paralysis • REM behavior disorder

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REM behavior disorderVivid dreams often with a violent themeVigorous behaviors accompanying these dreams which may result in injury to patient or partnerExcessive 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 sleepUsually treated successfully with clonazepamMust rule out Obstructive sleep apnea

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REM Behavior DisorderAcute 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.

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REM Behavior disorderhttp://www.youtube.com/watch?v=rFXYRQ9xPUA

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Differential diagnosis and management of sleep disorders in psychiatric practiceBecause of similarity in clinical manifestations, sleep disorders may be mistaken for primary psychiatric conditionsSleep disorders that are secondary to physical disorders may also be mistakenly viewed as psychiatric in originThree major types of sleep complaints:

DIMS – disorder of initiation or maintenance of sleepDOES- Disorders of Excessive SleepinessParasomnias-episodes of disturbed behavior or experiences related to sleep

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Summary: Sleep disorders at risk of misdiagnosis as primary psychiatric disordersCircadian Rhythm DisordersObstructive Sleep Apnea syndromeNarcolepsyREM Behavior Disorder Other

Parasomnias

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END