2. Sleep & Sleep Disorders Ting-hsu Chen, MD MPH tchen@bu.edu Section of Pulmonary & Critical Care Medicine

3. Overview Normal sleep Sleep deprivation and sleepiness Specific sleep disorders: diagnosis & treatment – Obstructive Sleep Apnea (OSA) – Narcolepsy – Restless Legs Syndrome (RLS) – Insomnia

4. Normal sleep Restorative function Oxidative repair Memory consolidation Extreme deprivation leads to death

6. © American Academy of Sleep Medicine Interaction of Circadian Rhythms and Sleep Time 9 PM 9 AM Sleep Wake Sleep Homeostatic drive (Sleep Load) Circadian alerting signal Alertness level 3 PM 3 AM

7. Sleep deprivation Excessive daytime sleepiness is common Behavioral and physiological consequences – Psychomotor impairment – Memory deficits – Mood effects – Insulin resistance – Blunted immune response Self-assessment may not be reliable Sleep deprivation is cumulative

8. Rears T, et al. Daytime sleepiness and alertness. In: Kryger MH et al. (eds). Principles and Practice of Sleep Medicine. 4 th Edition. Philadelphia: Elsevier Saunders; 2005: 40. MSLT = Multiple Sleep Latency Test TIB = time in bed Daytime sleepiness

9. Sleepiness in the Clinician Survey of 697 emergency medicine residents at Wayne State University (Kowalenko. Acad Emerg Med. 2000;7:451.) – 17% had MVAs – 6.7x more likely to fall asleep driving than prior to residency Anesthesiology residents did not perceive themselves to be asleep almost half of the time they had actually fallen asleep. (Howard. Acad Med. 2002;77:1018-1925.)

10. Case A 55yo man presents to your clinic. His wife complains about his snoring and told him that he stops breathing when he sleeps. He sleeps 9 hours a night and falls asleep immediately, but never feels rested when he wakes up. He tends to doze off during meetings at work. He has fallen asleep driving home from work a couple of times, usually at a stop light. Height: 5’8”. Weight 210#. BMI 31.9. Crowded posterior oropharynx (MP III). Enlarged uvula.

11. “Classic” OSA profile Male Middle-age Obese Snoring Daytime sleepiness Hypertension

12. OSA in women Similar daytime sleepiness (ESS) More morning headaches “Atypical presentations” – Depression – Hypothyroidism Post-menopausal (age > 50)

13. OSA Diagnosis & Treatment Gold standard: polysomnography – Monitor brain activity (EEG), muscle activity (EOG & EMG), breathing (flow & pressure), snoring and effort, EKG, oxygen saturation Treatment: positive airway pressure (gold standard), weight loss, positional therapy, dental devices, surgery

14. CPAP Adjusted during split-night or full-night titration Auto-titrating PAP Bi-level PAP Adaptive-servo ventilation – CHF – “Complex” sleep apnea (treatment emergent central apnea)

15. Nasal – Full – Pillows – Hybrid

16. Case A 25 year old woman presents to your office. She states she’s always been the “sleepy one” in class as early as junior high school. She has always fallen asleep in lectures in college no matter how much she sleeps. She currently goes to bed at 9pm and sleeps until 6am every day. She wakes up multiple times per night. She never feels like she has a good night’s sleep. She does not snore. She denies depression, other medical problems, substance use. She takes no medications. Height: 5’3”. Weight: 115#. BMI: 20.4. Normal thyroid exam. Normal oropharyngeal exam.

17. Differential diagnosis Narcolepsy without cataplexy Idiopathic hypersomnia Hypothyroidism Substance abuse Depression Behavioral sleep restriction

18. Diagnostic criteria for narcolepsy (Cataplexy) Near daily excessive daytime sleepiness for at least 3 months Not better explained by other medical, substance, behavioral conditions MSLT sleep latency < 8 minutes 2 SOREMPs despite sufficient sleep

19. Cataplexy Unique to narcolepsy Sudden bilateral loss of muscle tone provoked by strong emotion (laughter) – Can vary in muscle groups affected – Can vary in degree of loss of muscle tone Associated with loss of CSF hypocretin-1 (orexin-A) – hypothalamic neuropeptide

20. Additional features of narcolepsy Sleep paralysis Hypnagogic (sleep onset) hallucinations Nocturnal sleep disruption Classic Tetrad = cataplexy + excessive daytime sleepiness + sleep paralysis + hypnagogic hallucinations

21. Multiple sleep latency test Daytime test following a PSG – No OSA (AHI >5) + 6 hours of sleep the night before Series of 5 naps spaced 2 hours apart – 20 minutes to fall asleep -> 15 minutes to sleep – Normal range very broad – Sleep-onset REM Periods (SOREMPs) are abnormal (2+ can be diagnostic)

22. Rears T, et al. Daytime sleepiness and alertness. In: Kryger MH et al. (eds). Principles and Practice of Sleep Medicine. 4 th Edition. Philadelphia: Elsevier Saunders; 2005: 40. MSLT = Multiple Sleep Latency Test TIB = time in bed Daytime sleepiness

23. Treatment of narcolepsy Excessive daytime sleepiness – Stimulants: dextroamphetamine, methylphenidate – Modafinil – Sodium oxybate Cataplexy – Sodium oxybate – Antidepressants: TCAs, SSRIs

24. Case A 45 year old woman presents to your office noting difficulties falling asleep which have gotten worse. When she gets into bed she has an irresistible urge to move her legs. This gets better as soon as she gets up and walks around her bedroom. As soon as she gets back into bed the feeling gets worse. She has fewer problems if she lays down in the early afternoon to take a nap. She has no periodic limb movements of sleep during a polysomnogram. Her ferritin level and other laboratory testing is normal.

25. Essential diagnostic criteria U: Urge to move legs, triggered or accompanied by unpleasant sensations R: Relieved by movement G: Gets worse during rest or inactivity E: Evening symptoms are worse

26. Diagnosis Made clinically: do not need a PSG – 80-90% of patients with RLS will have PLMs on sleep study – Conversely, most patients with PLMs do not have RLS Primary vs. secondary – Low iron stores (ferritin) – Medications (TCAs, SSRIs, neuroleptics, beta-blockers, H2 blockers, anti-convulsants) – Renal failure – Pregnancy – Peripheral neuropathy

27. Epidemiology Affects 10% of US adults Age of onset varies widely: commonly ≥40 years Women > men

28. Treatment Dopaminergic agents – Carbidopa-levodopa (Sinemet) – Roponirole (Requip) – Pramipexole (Mirapex) Iron replacement Gabapentin, methadone

29. Case A 65 year old man presents to your office noting persistent difficulties falling asleep and then staying asleep. This has been ongoing for over a month. He feels that sleep is never refreshing. He is retired and has plenty of opportunity to sleep. He is becoming more worried about hie sleep and feels that he is not as sharp during the day, feels fatigued more easily and has been more irritable with his family. An overnight polysomnogram is negative for OSA.

30. Insomnia syndrome A.Sleep symptoms: At least one of the following present on most nights:  Prolonged sleep latency (> 30 minutes)  Sleep maintenance difficulty (> 3 awakenings)  Wakefulness after sleep onset (> 30 minutes)  Short sleep duration (< 6.5 hours)  Poor sleep quality B.Adequate opportunity for sleep C.Daytime symptoms D.Distress/impairment E.Duration > 1 month

31. Symptom vs. co-morbid disorder The 1983 NIH consensus suggested that insomnia should be considered as a symptom. Ultimately, the 2005 conference has emphasized that insomnia should be considered as a disorder and that it should be considered as a co-morbid disorder.

32. The 3 P model of insomnia A useful model for insomnia incorporates three factors: – Predisposing – Precipitating – Perpetuating The relative influence of these factors in the course of insomnia varies over time Spielman AJ et al. Psychiatr Clin North Am. 1987;10:541-553.

33. Treatments Cognitive Behavioral Therapy (CBT) – Sleep Hygiene & Restriction Pharmacotherapy – Melatonin + Selective MT receptor agonists – Benzodiazepines + BZRAs – Antidepressants (anti-histamine/cholinergic) trazodone, doxepin, mirtazapine, amitriptyline – Herbal valerian, catnip, kava, chamomile, passion flower

34. Practical issues As the primary care physician your visit counts as the face-to-face evaluation prior to a sleep study – Insurance requirements for sleep study payment continuously changing – For now at BMC, still mainly in-laboratory PSGs Refer your patients! – Logician order: Pulmonary – Sleep Disorders – Order a sleep study using the Lab tab in progress note (do not use the sleep study test order)