Why am I so tired? Carol Ash, D.O., D ABSM, FCCP. ACOI 2008 Marco Island

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1 Why am I so tired? Carol Ash, D.O., D ABSM, FCCP ACOI 2008 Marco Island

2 Sleepiness Is a normal physiologic phenomenon Physical manifestations Sensation to close eyes (ptosis) and recline, yawning, decreased attention span, loss of neck extensor tone, pupillary constriction Depends on interplay between two factors time in the circadian cycle process C length of time since last sleep period process S modified by prior sleep debt

3 Physiology of Sleep and Wake Behavioral Definition A reversible state characterized by a decreased responsiveness to the environment and motor activity, and, when deprived there is a tremendous need for recovery. Neurophysiologic Definition Defined by EEG characteristics N 1 3 REM See measurable changes in neurochemistry and functional neuroanatomy.

4 Wake Promoting It s Complex Ascending reticular activating center Thalamus gateway to activation of the cortex Other regions Hypocretin, acetylcholine, histamine, catecholamines, serotonin, dopamine Suprachiasmatic nucleus (SCN) in the hypothalamus

5 Sleep Promoting Hypothalamus Ventral lateral preoptic (VPLO) area Thalamus Neurotransmitters GABA, adenosine, melatonin

6 Circadian Rhythm Process C Near 24 hour SCN Involved in regulating timing of sleep and wake Promotes wakefulness Maintains other physiologic rhythms such as Cortisol Temperature Melatonin For optimal function internal rhythms must be synchronized to each other and the external light dark cycle and social rhythms.

7 SNC Endogenous rhythm is not 24 hours Light predominant synchronizing agent Regulates secretion and synthesis of melatonin Receptors for Melatonin (MT1 and MT2)

8 Melatonin Dark Hormone Suppressed by light Melatonin promotes sleep by inhibiting firing rate of the SCN through MT1 MT2 agonism is important for phase shifting Melatonin may play a role in dropping core body temperature

9 Homeostasis Process S Throughout the day build up drive for sleep You are not in control of sleep, sleep ignites when homeostatic pressure to sleep is high enough. Drive to sleep related to total amount and consecutive wakefulness. Sleep habits and sleep disorders limit the amount of sleep you get.

10 Process C Works in opposition to the homeostatic drive At it s weakest 3 5 pm, and 3 5 am Sends out stronger and stronger drive to wake as the day progresses. As long as you are keeping a regular schedule, the rise in sleep promoting melatonin will quiet the pacemaker 1 2 hours prior to habitual bedtime Decreased rate of firing of the SCN means the VPLO is unopposed to promote sleep

11 Excessive Daytime Sleepiness EDS Excessive sleepiness is not well defined Frequency, Duration, Naps Subjective Epworth Sleepiness Scale Objective MSLT, MWT No test that can appropriately evaluate Other terms: tired, fatigue

12 Fatigue vs. Sleepiness Terms are often used interchangeably, especially in transportation industry Sleepiness is a drive for sleep (neural state). Fatigue is a drive for rest (neuromuscular state). Sleepy persons often deny their sleepiness or attribute sleepiness to some other cause.

13 Maggie s Law No longer an accident if there is a death it is a felony. Establishes that driving a vehicle or vessel when knowingly fatigued shall constitute recklessness. It shall be considered criminal and vehicular homicide when it results in a death.

14 Investigation EDS Sleepiness scales Epworth Sleepiness Scale Highest score 24, Normal Polysomnogram To diagnose OSA, CSA, PLMD, & required prior to MSLT MSLT 4 5 nap opportunity, two hour intervals SOL less than 5 min severe EDS Narcolepsy see SOREMs MWT Measures effectiveness of therapy Assesses alertness in real life situations

15 Causes of Sleepiness Defined in several ways subjective, objective Insufficient sleep. Most impact - previous night sleep. Debt is cumulative. Poor quality sleep Sleep disorders i.e. OSA, RLS Drugs Neurologic conditions Mental or physical exhaustion relieved with rest Thyroid disease, anemia, liver disease, testosterone-more fatigue Pregnancy

16 Sleep Disorders OSA, RLS, Circadian Rhythm Narcolepsy Chronic Hypersomnia Klein Levin Syndrome Neuromuscular disorders Parkinson s Disease Post stroke hypersomnia TBI

17 Circadian Rhythm Sleep Disorders CRSD Delayed Sleep Phase Syndrome More prevalent adolescents 7% Advanced sleep Phase Syndrome Seen middle age 1 % Shift Work Jet Lag

18 CRSD treatment Chronotherapy Appropriately timed bright light therapy Melatonin for DSPS What about stimulants, Provigil? Corporate wellness programs for jet lag and shift workers fatigue counter measures Strategic napping Caffeine Melatonin, hypnotic use, adjusting sleep wake schedules

19 Narcolepsy Cataplexy, Hypnagogic or hypnopompic hallucinations Sleep paralysis Sleep logs for 2 weeks, PSG and MSLT CSF hypocretin 1 HLA testing

20 Narcolepsy Treatment Amphetamine like CNS Stimulants Modafinil Provigil BZD or Gama hydroxybutyrate/xyrem Consolidates sleep TCA or Xyrem Cataplexy

21 Interactive Question #1 Which of the following is commonly increased with sleep restriction? 1. leptin 2. ghrelin 3. early morning cortisol 4. appetite for protein rich foods Answer 2 Included to highlight that there are metabolic and endocrinologic abnormalities associated with sleep debt

22 Interactive Question #2 A medical student who stays up for 30 hours will have: 1. a build up of homeostatic process S 2. a circadian rhythm process that is dependent on the length of the wake period 3. no effect on either process C or S 4. microsleeps Answer 1

23 Interactive Question #3 All of the following are correctly defined except: 1. Phase shift means the displacement forward or backward in time of the circadian rhythm as a result of sedative hypnotics 2. Entrainment means behavior is timed by the circadian clock and adjusts their periods each cycle so that the organisms internal day is synchronized to the environmental day. 3. Zeitgeiber means environmental time cues such as light and alarm clocks. 4. PRC is a plot that shows the magnitude of the shift in the circadian phase for a given time of presented light. Answer 1.

24 Interactive Question #4 Which of the following is usually associated with severe excessive sleepiness and excessive sleep needs? 1. Chronic sleep debt 2. Narcolepsy 3. Sleep disordered breathing 4. REM sleep behavior disorder 5. Restless leg syndrome Answer 2

25 Interactive Question #5 Which of the following would not be indicated in a teenager who had difficulty getting up in the morning and delayed onset : 1. Improved sleep hygiene 2. Smoking cessation 3. Bright light therapy at night 4. Reassure him that although this is not a normal pattern it is not uncommon and psychiatric intervention is not necessary in most cases 5. Melatonin to phase advance

26 Conclusion There are multiple causes of Excessive Daytime Sleepiness (EDS) Understanding the basics of sleep physiology will make it easier to get at the root cause and resolve the EDS. EDS can have serious health consequences and the underlying causes have been linked to many common diseases and even premature death. All healthcare providers should become familiar with the causes of EDS and work to identify and treat them. More sleep specialists are needed. Consider pursuing board certification.

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