Differential Diagnosis and Treatment of Excessive Daytime Sleepiness

1. Differential Diagnosis and Treatment of Excessive Daytime Sleepiness

2. What is EDS? • Excessive daytime sleepiness • The tendency to fall asleep during normal waking hours1 • Contrast with “fatigue” • A desire to rest due to feelings of exhaustion1 • Symptom of underlying disorder 1. Beers MH, et al. Merck Manual of Diagnosis and Therapy; 2006.

3. EDS – a common complaint • Almost ½ of all Americans report a sleep-related problem1 • EDS is the primary complaint of 1 in 8 people seen in sleep clinics2 • More than 1 in 4 patients complain of EDS in the primary care setting3 1. Beers MH, et al. Merck Manual of Diagnosis and Therapy; 2006; 2. Roth T & Roehrs TA; Clin Ther.,1996; 3. Kushida CA, et al. Sleep Breath; 2000.

4. EDS characteristics • Number of daily episodes vary • Occurs during passive activities • TV watching, sitting on a plane • Occurs during more active tasks • Driving, eating, speaking 1. Beers MH, et al. Merck Manual of Diagnosis and Therapy; 2006; 2. Bassetti C & Aldrich MS. Neuro Clin;1996.

5. The Consequences of EDS

6. Consequences to Self •  Productivity1,2 •  Motivation2 •  Interpersonal relationship problems2 •  Depression + anxiety1, 3 •  Insomnia1 •  Quality of life1,2 1. Hasler G, et al. J Clin Psychiatry; 2005; 2. Daniels E, et al. J Sleep Res; 2001; 3. Theorell-Haglow J, et al. Sleep; 2006.

7. Consequences to Health • Sleepiness vs. blood pressure1 •  EDS symptoms = •  Sleep BP •  Daytime systolic/diastolic variability •  Anger, depression, anxiety • More likely to get a diagnosis of hypertension 1. Goldstein IB, et al. Am J Hypertens; 2004.

8. Consequences to Health • Sleepiness vs. CVD in older adults1 •  EDS symptoms = •  CVD mortality • 200% in men; 40% in women •  CVD morbidity • 35% more MI and CHF in men; 66% more in women 1. Newman AB, et al. J Am Geriatr Soc; 2000.

9. Consequences to Society • Crashes when driver falls asleep1 • 100,000 each year in U. S. • 1,500 deaths • Death rate may exceed alcohol-related crashes • ~1/2 of all work-related accidents2 • 1 in 5 public accidents due to falls2 1. Mahowald MW. Postgrad Med; 2000; 2. Leger D. Sleep; 1994.

10. Drivers beware: sleepiness vs. drunkenness • Study compared effects on performance of sleep deprivation and alcohol1 • Drivers who went 17-19 hours without sleep = drivers with 0.05% BAC • Sleepy drivers responded ~50% more slowly/less accuracy than fully awake drivers • Sleepiness can compromise performance needed for road and job safety 1. Williamson AM & Feyer AM. Occup Environ Med; 2000.

11. Patient assessment

12. Is sleep the new vital sign? • Growing evidence shows that sleep is an important ingredient in good health1 • Few MDs address sleep quality in their practices • <10% of patient charts document sleep history2 • Sleep disorders are underdiagnosed, undertreated 1. Wilson JF. Am Coll Physicians; 2005; 2. Namen AM, et al. South Med J; 2001.

13. Pathophysiology of EDS • EDS is not a disorder – but a symptom1 • Causes2: • CNS abnormalities, e. g. narcolepsy • Sleep deficiency, e. g. sleep apnea • Circadian imbalances, e. g. jet lag • Drug side effects, e. g. marijuana 1. Beers MH, et al. Merck Manual of Diagnosis and Therapy; 2006; 2. Roth T & Roehrs TA. Clin Ther; 1996.

14. How does the patient report symptoms? • I’m tired • I feel lazy • I have low energy • I feel drowsy • I feel sleepy

15. Assess for other psychiatric comorbidities • Symptoms of depression? • Mood or memory problems? • Does patient fall asleep suddenly? • Is the patient a “night owl”? • Does the patient drink or take drugs? • How many hours sleep per night, including weekends and weekdays?

16. Epworth SleepinessScale • A quick, in-office test1 • Assesses whether a person will get sleepy in certain situations • Use this scale for each situation: • 0 = would never doze or sleep • 1 = slight chance of dozing or sleeping • 2 = moderate chance of dozing or sleeping • 3 = high chance of dozing or sleeping 1. Johns MW. Sleep; 1991.

17. Epworth SleepinessScale 1. Johns MW. Sleep; 1991.

18. Rule out other medical conditions1 • Stroke • Tumors/cysts • Vascular malformations • Head trauma • CNS infections (sleeping sickness) • Parkinsonism • Alzheimer's, other dementias 1. Black JE, et al. Neurol Clin; 2005.

19. Differential Diagnosis

20. Most frequent causes of EDS • Insufficient sleep syndrome • Obstructive sleep apnea • Substance/medication use • Shift-work sleep disorder • Delayed sleep-phase syndrome • Narcolepsy • Periodic limb movement disorders

21. Insufficient sleepsyndrome • Have patient keep a sleep log1 • Bedtimes • Number/time of awakenings • Arising times • Frequency/duration of naps • Bedtime events (food, alcohol, physical activity) 1. Beers MH, et al. Merck Manual of Diagnosis and Therapy; 2006.

22. Falling asleep vs. staying asleep • Difficulty falling asleep1 • Suggests delayed sleep phase syndrome • Chronic psychophysiologic insomnia • Inadequate sleep hygiene • Restless legs syndrome • Difficulty staying asleep • Suggests advanced sleep phase syndrome • Major depression • Sleep apnea • Limb movement disorder • Aging 1. Beers MH, et al. Merck Manual of Diagnosis and Therapy; 2006.

23. Most frequent causes of EDS • Insufficient sleep syndrome • Obstructive sleep apnea • Substance/medication use • Shift-work sleep disorder • Delayed sleep-phase syndrome • Narcolepsy • Periodic limb movement disorders

24. Obstructive sleep apnea • Absence of breathing during sleep • Obstruction of airways  snoring, decrease in oxygen saturation of hemoglobin, arousal1 • Result is disturbed sleep and EDS • Most common diagnosis of patients with complaint of EDS who seek care at US sleep centers2 • Almost 7 out of 10 patients 1. Victor LD. Am Fam Physician; 1999; 2. Punjabi NM, et al. Sleep; 2000.

25. Obstructive sleepapnea • Associated with: • Not only CVD and obesity, but also: • Metabolic syndrome1 • Untreated OSA  Direct/deleterious effects on CV function and structure3 • Sympathetic activation • Oxidative stress • Inflammation • Endothelial dysfunction 1. Vgontzas AN, et al. Sleep Med Rev; 2005; 2. Shamsuzzaman AS, et al. JAMA; 2003; 3. Narkiewicz K, et al. Curr Cardiol Rep; 2005.

26. Obstructive sleepapnea •  Systolic BP and heart rate1 •  CRP concentrations1 • May contribute to ischemia, CHF, arrhythmia, cerebrovascular disease, stroke •  Atrial fibrillation can predict OSA2 • 49% vs. 32% who do not have OSA • 1 in 15 has moderate to severe OSA3 • 1 in 5 has mild OSA 1. Meier-Ewert HK, et al. J Am Coll Cardiol; 2004; 2. Gami AS, et al. Circulation; 2004; 3. Shamsuzzaman AD, et al. JAMA; 2003.

27. Physical examfor OSA • Check for: 1 • Obesity, especially at midriff & neck • Jaw and tongue abnormalities • Nasal obstruction; enlarged tonsils • Expiratory wheezing • Spinal curvature • Note signs of R ventricular failure • Edema, abdominal distention 1. Beers MH, et al. Merck Manual of Diagnosis and Therapy; 2006.

28. Most frequent causes of EDS • Insufficient sleep syndrome • Obstructive sleep apnea • Substance/medication use • Shift-work sleep disorder • Delayed sleep-phase syndrome • Narcolepsy • Periodic limb movement disorders

29. Substance/medication use • EDS can be a sign of drug-dependent and drug-induced sleep disorders1 • Chronic use of stimulants • Hypnotics, sedatives • Antimetabolite therapy • OCs; thyroid medications • Withdrawal from CNS depressants 1. Beers MH, et al. Merck Manual of Diagnosis and Therapy; 2006.

30. Substance/medication use • Review the patient’s Rx drug use • Check for interactions,high doses • Inquire about OTC medications • Diphenhydramine, anticholinergics • Take alcohol history • Interaction with Rx or OTCs? • Ask about recreational drug use 1. Beers MH, et al. Merck Manual of Diagnosis and Therapy; 2006.

31. Most frequent causes of EDS • Insufficient sleep syndrome • Obstructive sleep apnea • Substance/medication use • Shift-work sleep disorder • Delayed sleep-phase syndrome • Narcolepsy • Periodic limb movement disorders

32. Shift-work disorder • Circadian rhythm sleep disorder1 • Internal/environmental sleep-wake cadence out of synch • Insomnia, EDS, or both1 • ~10% of the night and rotating shift work population2 • 4-fold  in sleepiness-related accidents, absenteeism, depression2 1. Beers MH, et al. Merck Manual of Diagnosis and Therapy; 2006; 2. Drake CL, et al. Sleep; 2004.

33. Shift-work disorder • Resolves as body clock realigns1 • Fixed-shift work is preferable • Full-time night or evening • Rotating shifts should go clockwise • Day  Evening  Night • Helpful: Bright light, masks, white noise • Short t1/2 hypnotics, wake-promoting drugs used judiciously 1. Beers MH, et al. Merck Manual of Diagnosis and Therapy; 2006.

34. Most frequent causes of EDS • Insufficient sleep syndrome • Obstructive sleep apnea • Substance/medication use • Shift-work sleep disorder • Delayed sleep-phase syndrome • Narcolepsy • Periodic limb movement disorders

35. Delayed-sleep phase syndrome • Sleep cycle out of synch with desired wake times1 • Problem: Going to sleep and awakening late (3AM and 10AM) • If earlier wake times are necessary, then EDS can result • Poor performance in work/school • Improved sleep hygiene is key 1. Beers MH, et al. Merck Manual of Diagnosis and Therapy; 2006.

36. Most frequent causes of EDS • Insufficient sleep syndrome • Obstructive sleep apnea • Substance/medication use • Shift-work sleep disorder • Delayed sleep-phase syndrome • Narcolepsy • Periodic limb movement disorders

37. Narcolepsy • Pathologic sleepiness, sudden loss of muscle tone (cataplexy), fragmented sleep, sleep paralysis1 • Affects 1 out of 2,000 people2 • 140,000 Americans2 • Delay of 10 yr from onset to diagnosis is common1 • The cause is unknown 1. Beers MH, et al. Merck Manual of Diagnosis and Therapy; 2006; 2. Ohayon MM, et al. Neurology; 2002.

38. Narcolepsy - Pathophysiology • Cause? –  hypocretin-secreting neurons1,2 • Regulate arousal state in hypothalamus • Marker – REM sleep during ≥2 daytime naps3 • Dysfunctionalswitching to REM sleep  wakefulness during sleep3 • Patients are mentally awake but physically in REM sleep – sleep paralysis syndrome. 1. Thannickal TC, et al. Neuron; 2000; 2. Sutcliffe JG & de Lecea. Nat Rev Neurosci; 2002; 3. Scammell T. Ann Neurol; 2003.

39. Narcolepsy - Pathophysiology • Genetic predisposition1 • Familial clustering • 10- to 40-fold  vs. general population • Hallmark symptom – cataplexy • Bilateral weakness2 • Prevalence ~ 75%2 1. Nishino S, et al. Sleep Med Rev; 2000; 2. Beers MH, et al. Merck Manual of Diagnosis and Therapy; 2006.

40. Narcolepsy – Diagnosis • Diagnostic for narcolepsy1 • History of cataplexy • Nocturnal polysomnography • MSLT • Differential diagnosis1 • Lesions of brain stem, hypothalamus • Encephalitis, metabolic disorders • Urine and blood exams can confirm non-narcoleptic EDS1 1.Beers MH, et al. Merck Manual of Diagnosis and Therapy; 2006.

41. Most frequent causes of EDS • Insufficient sleep syndrome • Obstructive sleep apnea • Substance/medication use • Shift-work sleep disorder • Delayed sleep-phase syndrome • Narcolepsy • Periodic limb movement disorders

42. Periodic limb movement disorders • Abnormal twitching/kicking of legs during sleep1 • Interferes with nocturnal sleep  EDS • ~10% of adults2 • Restless legs syndrome • More common in middle/later years • Creeping/crawling sensations • Abnormalities in dopamine transmission2 1.Beers MH, et al. Merck Manual of Diagnosis and Therapy; 2006; 2. Hornyak M, et al. Sleep Med Rev; 2006.

43. Periodic limb movement disorders • Often occurs in narcolepsy and OSA1 • Seen in pregnancy, renal/hepatic failure, anemia and other disorders • Sleep history/partner’s testimony • Test: Iron, anemia, kidney/liver function • Dopamine agonists can be helpful 1.Beers MH, et al. Merck Manual of Diagnosis and Therapy; 2006; 2. Hornyak M, et al. Sleep Med Rev; 2006.

44. When to refer?

45. Know when to treatand when to refer • Can condition be treated via sleep hygiene? • Insufficient sleep syndrome • Substance/medication use • Delayed sleep-phase syndrome • Shift-work sleep disorder • Counsel on sleep architecture • Do blood work, RFTs/LFTs • Prescribe sedatives prudently

46. Know when to treatand when to refer • Refer when diagnosis appears to be: • Obstructive sleep apnea • Pulmonologist, sleep clinic, surgeon • Narcolepsy • Neurologist, sleep clinic • Periodic limb movement disorders • Internist, endocrinologist, sleep clinic

47. The sleep clinic • Sleep studies evaluate EDS as well as OSA, narcolepsy, periodic limb movement disorders • Polysomnography1 • Data accumulated from patient as s/he sleeps • Quantifies sleep adequacy • Determines what causes EDS 1. AARC-APT. Respir Care; 1995.

48. The sleep clinic - Polysomnography • Measures1: • EEG • Eye movements • Heart rate • O2 saturation • Muscle tone & activity • All-night test 1. AARC-APT. Respir Care; 1995; 2. Beers MH, et al. Merck Manual of Diagnosis and Therapy; 2006.

49. The sleep clinic – MSLT • Multiple Sleep Latency Test • Complimentary test for narcolepsy1 • Assesses speed of sleep onset • REM sleep is monitored • All-day test: 8-10 hours • High ESS scores ~ Low MSLT scores2 1. Beers MH, et al. Merck Manual of Diagnosis and Therapy; 2006; 2. Chervin RD, et al. J Psychosom Res; 1997.

50. Treatment