Circadian Rhythm Sleep Disorders 04-'10 (1)

7/31/2019 Circadian Rhythm Sleep Disorders 04-'10 (1)

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Circadian Rhythm Sleep

Disorders

Herbert Yue, MD

Stanford Sleep Medicine Center


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Introduction

Two modular processes that govern sleep andwakefulness

Referred to as two process model of sleepwake regulation Homeostatic drive for sleep

Intrinsic circadian rhythm

For each hour of wakefulness, homeostatic drivefor sleep increases Typically after 14-16 hours, sufficient homeostatic

sleep drive is obtain


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Introduction

Circadian rhythm important regulator ofwakefulness

Allows synchronization of physiologic processto desired sleep wake cycle

Exerts active promotion of wakefulness


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Introduction


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Circadian Rhythm Biology

Circadian rhythms generated from superchiasmaticnucleus (SCN) of hypothalamus

Signals from SCN modulate daily rhythms in sleep and

alertness Core body temperature

Secretion of cortisol and melatonin

Intrinsic rhythm of clock slightly longer than 24 hours Synchronization occurs to 24hr schedule using external cues

Zeitgeibers: Temporal timing signals, light exposure


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Photoreceptors in retina important signalcollectors

Receptors discovered in cells of retina Important for entrainment

Contain photopigment melanopsin

Most sensitive to blue wavelength of light


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Circadian Phase Markers

Active investigation into markers ofcircadian phase in humans

?Clinical utility of markers Two currently utilized markers

Core body temperature

Dim light melatonin measurement (DLMO)


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Core Body temperature

Drop in tempassociated with

stability in sleep Three dips in temp 8:00pm-12:00am

3:00-5:00am

1:00-4:00pm


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Melatonin Secretion

Increase in levelsaround 8:00pm

Levels peak atapproximately3:00am and beginto decrease

Lowest levels justbefore awakening


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Circadian Phase Markers

Measurement of markers difficult Core body temperature altered by activity, food

intake, and sleep

Melatonin secretion very sensitive to lightexposure, needs to be obtained under dim lightconditions Dim light melatonin onset (DLMO)


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Circadian Rhythm

Disruptions in the circadian rhythmphysiology consequently can cause a

number of circadian rhythm sleepdisorders

Disorders can be secondary to externalinference with sleep wake mechanism

Remainder of disorders are related toinherent disruption of the circadian rhythm


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Classification

Six distinct circadian rhythm disordersrecognized by the International

Classification of Sleep Disorders (ICSD-2) Essential feature: Persistent/recurrent

pattern of sleep disturbance

Alterations in circadian timekeeping system Misalignment between internal circadian

timing and exogenous influences


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Classification

Diagnostic criteria require impairment Social, occupational, etc

Phase tolerance may exist; i.e. sleep not disrupted bysleep alignment

Diagnosis also must not be better explained byother sleep disorder

Unconventional sleep cycle CRSD Persistent insomnia no matter timing of sleep

Congruence of sleep timing and circadian rhythm


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Classification

Six distinct CRSDs Delayed sleep phase disorder

Advanced sleep phase disorder Jet lag type

Shift work type

Irregular sleep wake cycle disorder

Free running type

ICSD also recognizes CRSD NOS Secondary to medical condition, etc


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Prevalence

Exact prevalence not known, althoughhigh numbers if shift workers/travelers

considered One formal study using diagnostic criteriawith epidemiologic sample; looked at SWD 30% of night workers and 26% of rotating

workers met minimal criteria for SWD Little data for other CRSDs


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Common Themes

All dxs require 2 week actigraphy/sleepdiary

Goal is to create congruence Treatment Light in AM = backward shift and vice versa

Melatonin works in opposite manner fromlight

Light, exercise in periods of activity


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Shift Work Disorder (SWD)

Minimal criteria for diagnosis Work in shift work position, either night-shift

or rotating shift for the past 2 weeks Impairment in daytime functioning, typically

insomnia or excessive daytime sleepiness,present for > 1 month


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Rotating shift workers show increasedrates of impairment

>30% of rotating shift workers with reportedsleep latencies of greater than 30 minutescompared to 10% of night and day shiftworkers

Increased rates of absenteeism, accidents atwork and poor job satisfaction


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Risk factors for SWD Increasing age; peak in sleep disturbances at

age 52 with decreases after age 62 Female gender; women with less sleep on

average then men and increase complaints

Intrinsic tolerance of individuals


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Non-pharmacologictreatment

Sleep hygiene

Scheduled naps

Assessment of workschedule

Exercise Light exposure


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Pharmacologic treatmentsinclude modafinil/stimulants

Only modafinil or armodafinilcurrently FDA approved as tx

for SWD Improvements in self reported

sleepiness, objective sleeplatencies, and accident rates

Other stimulants, such asamphetamines not indicated Rebound insomnia


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Delayed Sleep Phase Disorder(DSPD)

Characterized as bedtimes that are 3-6 hours later thanconventional times Typically problems sleeping before 2:00am and waking up earlier

than 10:00am

Subjective sleepiness worst in the mornings, with highest

levels of alertness during the late evening


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Difficulty with sleep onset at desired time, butsleep once initiated is normal

Most common CRSD referral, althoughpopulation data lacking Population estimates of prevalence of 0.17%

Prevalence increases to >15% amongst adolescents

Positive family history


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Bright light therapygenerally given inthe early morning for

1-2 hours Induces phase shift

backwards

Typically takesupwards of 2 weeksto see effects Compliance often

limited


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Melatonin Secretion


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Melatonin may also begiven, typically 5-7hours before the DLMO

DLMO typically occurs 2-3

hours before sleep onsetin healthy individuals

Effects of melatonin maynot be long lived

Some studies showreversion to DSPD aftermedication stopped


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Advanced Sleep Phase Disorder(ASPD)

Habitual and undesired sleep/wake up times severalhours earlier than desired Sleep onset 6:00-9:00pm and wake up times 2:00-5:00am

Symptoms of early morning awakenings, sleep

maintenance problems, or excessive daytime sleepiness


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Associated with increasing age Non age associated cases rare

Prevalence approx 1% of middle aged adults Genetic markers identified, ?autosomal dominant

transmission

-Missense mutation in Period 2 gene


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Treatment typically lightexposure in earlyevening

Usually in the hours of7:00-9:00pm

Delays DLMO

Compliance limited in thefew studies performed

No current role forhypnotics or stimulants


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Melatonin Secretion


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Jet Lag Disorder (JLD)

Defined as disruption in sleep after travel across2-3 time zones

Typically benign and self limited, although can

be distressing to patients productivity Circadian rhythm resetsApprox 90 minutes later for westward flights 60 minutes earlier for eastward flights

Treatment typically involves: Light administration Melatonin administration


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Treatment with light or melatonin usuallyinvolves corresponding exposure

Light exposure: Maximize exposure in the morning for westwardflights, exposure in evening for eastward flight

Melatonin admin

Most studies evaluated 5mg dose at bedtime, typicallyfor eastward travel


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Melatonin Secretion


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Hypnotics 3-4 day course of Ambien associated with improved

sleep quality

Short acting hypnotic such as Sonata may be helpfulfor an overnight flight

Armodafanil Recent data showing improved subjective alertness

and reduced jet lag sx Current pending application as FDA approved

treatment for JLD


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Free Running Disorder (FRD)

Characterized as gradual drift of major sleep period by1-2 hours daily

If scheduled sleep/wake times attempted, pts report

insomnia and excessive daytime sleepiness Sx occur when non-entrained circadian rhythm out of phase withconventional sleep/wake times

Majority of cases in the blind Lack of photic entrainment

Estimated 50% have free running disorder, 70% with chronicsleep disturbances

Cases described for non-blind, usually after head trauma


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Treatment in sighted individuals Scheduled sleep and wake cycles

Timed bright light Melatonin admin

Treatment in blind individuals

Regular work/sleep schedule non photic cue Melatonin admin (1 hr before bedtime)


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Irregular Sleep Wake Disorder(ISWD)

Characterized as absence of clear circadianrhythm

Although total amount of sleep normal, sleep

periods scattered throughout the day Napping prevalent, with sleep episodes > 3 per day Rare condition

Likely secondary to primary disturbance of circadianrhythm

Lack of external time cues, such as light and activity Seen most commonly in dementia, developmentally

disabled children, and with severe brain trauma


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Treatment primarily restoring externaltime cues

Scheduled social and physical activities Timed bright light

Some role for hypnotics to improve sleep


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Conclusion

CRSD occur secondary to incongruence ofsleep time and circadian rhythm orintrinsic disruption in circadian rhythm

Light and melatonin are useful adjuncts intx

Zeitgebers are critically important Growing literature demonstrating genetic

basis for these conditions


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Circadian Rhythm Sleep Disorders 04-'10 (1)