Learning Objectives. Sleep and Sleep Disorders NOT called Sleep Apnea. Socioeconomic Consequences. Socioeconomic Consequences

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Sleep and Sleep Disorders NOT called Sleep Apnea Jerrold Kram, MD, FCCP, FAASM Medical Director, California Center for Sleep Disorders Board of Directors, National Sleep Foundation Learning Objectives Describe normal sleep architecture. Discuss the adverse events that sleep disruption and insufficient sleep have on daytime function. Discuss the importance of identifying sleep issues. Reveal the principles of good sleep hygiene. Differentiate sleepiness from fatigue in the tired patient. Socioeconomic Consequences The gravity of the problem: Nearly 40 million Americans suffer from chronic disorders of sleep and wakefulness. Up to 93% of women and 82% of men with moderate to severe obstructive sleep apnea (OSA) and excessive sleepiness (ES) are not clinically diagnosed. Young T, Evans L. Finn L, et al. Estimation of the clinically diagnosed proportion of sleep apnea syndrome in middle aged men & women, Sleep. 1997;20:705-6. Littner M, Kushida CA, Hartse K, et al. Practice parameters for the use of laser-assisted uvulopalatoplasty:an update for 2000. Sleep. 2001;24:603-619. World Health Organization. Obesity and overweight. Fact Sheet 311;2006. http://www.who.int/mediacentre/factsheets/fs311/en/index.html. Accessed March 10, 2009. Socioeconomic Consequences The annual direct cost of sleep-related automobile accidents is $16 billion, with an additional $50 to $100 billion in indirect costs (accidents, litigation, property destruction, hospitalization, death). By 2015 the World Health Organization (WHO) estimates there will be > 700 million obese adults (body mass index [BMI] > 30 kg/m 2 ) worldwide, with expected consequent increase in the prevalence of sleep apnea. Information from Young T, Evans L. Finn L, et al. Estimation of the clinically diagnosed proportion of sleep apnea syndrome in middle aged men & women, Sleep. 1997;20(9):705-6. Littner M, Kushida CA, Hartse K, et al. Practice parameters for the use of laser-assisted uvulopalatoplasty: an update for 2000. Sleeo. 2001;24(5):603-619. World Health Organization. Obesity and overweight. Fact Sheet 311;2006. Available at http://www.who.int/mediacentre/factsheets/fs311/en/index.html.

Socioeconomic Consequences Excessive daytime sleepiness (EDS) impairs: Human performance that can lead to accidents at work, at home, or on the road Academic performance, learning, and judgment Definitions of Sleep One can define sleep as: A reversible behavioral state of perceptual disengagement from, and unresponsiveness to, the environment. A very complex amalgam of physiologic and behavior processes. A process, unlike coma, that is physiologic, recurrent, and reversible. Biologic Clock Activity Circadian and Homeostatic Regulation of Sleep The body s master clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Light-dark signals reach the SCN via a retinohypothalamic track. SCN cells are circadian oscillators, exhibiting a stable, biphasic firing cycle. Circadian Alerting Signal 9 am Awake 3 pm 9 pm 3 am 9 am Asleep Adapted from Kilduff TS, Kushida CA. Circadian regulation of sleep. In: Chokroverty S. Sleep Disorders Medicine: Basic Science, Technical Considerations, and Clinical Aspects. 2nd ed. Woburn, MA: Butterworth-Heinemann; 1999:143.

Circadian Influences on Sleep and Wakefulness Principles of Sleep Hygiene Sleep Drive Wake Keep Circadian Clock on Time Maximize Homeostatic Sleep Drive Reduce Arousals Awake approximately the same time each day Limit napping Limit or eliminate caffeine intake Circadian Alerting Signal 9 am Awake 3 pm 9 pm Asleep 3 am 9 am Sleep Obtain bright light during daytime hours Only go to bed when you re sleepy Shut down your day at least one hour before bedtime Adapted from Kilduff TS, Kushida CA. Circadian regulation of sleep. In: Chokroverty S. Sleep Disorders Medicine: Basic Science, Technical Considerations, and Clinical Aspects. 2nd ed. Woburn, MA: Butterworth-Heinemann; 1999:143. Sleep Hygiene Exercise should be performed at least 2 hours before bedtime. Take hot showers or baths at least 2 hours before bedtime. Place the alarm clock where it cannot be seen. Keep the bedroom dark, quiet, and cool, with no pets. Avoid stressful activities in the evening. Use the bed only for sleep and intimacy. Sleep Review of Systems General Screening Ask the patients the following questions during their yearly well visit or new-patient intake: Do you wake up feeling rested and refreshed? How long does it take you to fall asleep? Do you snore, or has your bed partner complained about you snoring? Do you have any leg discomfort at night?

Taking a Sleep History Uncovering Daytime Sleepiness Attempt to get a history from bed partners, family members, or friends when possible. Patients may be unaware of events occurring during sleep. Many people will deny daytime sleepiness. They fear loss of job, loss of driving license, lazy label Evaluate quality of sleep hygiene. STOP questionnaire Do you Snore loudly (louder than talking or loud enough to be heard through the closed door)? Do you often feel Tired, fatigued or sleepy during daytime? Has anyone Observed you stop breathing during your sleep? Do you have or are you being treated for high blood Pressure? 2+ out of 4 predicts mild apnea 66%, moderate 74% and severe 80% BANG increases sensitivity even more (BMI, Age, Neck size, Gender) When Patients Say They Are Tired EDS vs. fatigue Sleepiness: able to sleep if given a chance Fatigue: tired but does not fall asleep Body is tired but mind is very active Ask the patient: If given a chance to stretch out and sleep right now, what would happen? When is a Sleep Study Useful? Suspected sleep apnea Unexplained daytime somnolence Abnormal movement activity in sleep Unexplained chronic insomnia longer than 2 months when organic cause suspected Quick Tip: Uncovering sleepiness vs. fatigue requires asking the right questions. Patients usually don t volunteer this information!

Background A 30-year-old woman presents to the office for a well-woman visit. Sleep history: Mother of three children: one infant, and two preschoolers Works as a third-grade teacher Nonsmoker, drinks 6 to 10 diet colas a day Exercises at 8 pm with aerobics and weighttraining 3x/week after kids have gone to sleep Routine Sleep Screening The routine sleep screening reveals: She has difficulty falling asleep. Once asleep, she sleeps like a rock. She wakes feeling exhausted most days. No history of snoring (per husband, this is not a problem). Case Scenario Further sleep information: Lies down at 11 pm most nights Doesn t fall asleep until 12:30 am or 1 am States, First I can t seem to quit thinking about the day and things that still need to be finished. Awakens at about 6 am to alarm Physical examination: 5 6, 122 lbs, all else normal What Must Be Addressed Initially for This Patient? 1) Worrying about things to do 2) Day goes up to bedtime 3) Evening exercise 4) Caffeine consumption 5) I m not sure

Take-Home Points Issues for this patient: Psychophysiologic arousal Worrying about things to do Physiologic arousal Caffeine, exercise Keeps day going right up to bedtime Recommendations Encourage patient to decrease caffeine Exercise earlier in the day Begin a quieting bedtime routine Epidemiology of Insomnia Overall prevalence of an insomnia symptom within the last year: ~30% Risk factors: Female gender meta-analysis of 31 studies: relative risk (RR) = 1.41 Medical, psychiatric, and substance abuse issues Social factors (many co-vary) Possible genetic factors Age Information from Johnson EO, Roehrs T, Roth T. Epidemiology of medication as aids in alertness in early adulthood. Sleep. 1999;22(4):485-488. Sleep-Related Arousal As a Trait Markers of hyperarousal: Reduced parasympathetic tone Increased basal metabolism Elevated circulating catecholamines Increased electroencephalogram (EEG) ß activity (cortical activation) Elevated body temperature High activity of hypothalamo-pituitary-adrenal axis Psychophysiologic: Characteristics Contributed to and reinforced by poor sleep hygiene Tension, anxiety, arousal in association with efforts to sleep, or in the usual sleeping environment Negative expectations regarding ability to sleep Clockwatching Ability to fall asleep when not trying to Better sleep away from home

Cognitive-Behavioral Treatment of Insomnia Counseling in sleep hygiene Cognitive therapy and stimulus control therapy Sleep restriction therapy Cognitive Therapy = Patient Education Improve patient s understanding of his/her sleep Establish realistic expectations regarding sleep Review simple relaxation techniques Dissuade patient from believing lack of sleep will be harmful Typical Maladaptive Cognitions I should fall asleep as soon as my head hits the pillow. If I can t sleep, there must be something wrong with me. I must have at least 8 hours of uninterrupted sleep in order to be normal. Behavioral Management of Insomnia Sleep Restriction Therapy Set the alarm for the same time each morning, regardless of the amount of sleep obtained the night before. No daytime naps allowed Keep a sleep diary for at least 7 days and compute the total amount of sleep per night (total sleep time [ TST]) indicated by the diary. Set up a schedule restricting the time spent in bed to equal the TST. As sleep efficiency improves, bedtime is advanced (go to bed earlier) by 15- to 20-minute intervals, maintaining the same wake time. Patient education is a key element of successful therapy.

Sleep Restriction Therapy RLS and Sleep Onset Insomnia Sleep Episode Current Sleep Restriction Ideal Sleep Time 10 pm 12 am 2 am 4 am 6 am 8 am Time of Day 8 hours 5.5 hours 5 hours 5.5 hours 6.5 hours Essential Criteria for RLS A distressing need/urge to move the legs, usually accompanied by an uncomfortable, deep-seated sensation in the legs that is: Brought on by rest Relieved with moving or walking Worse in the night or evening (circadian) Primary vs. Secondary RLS Primary (idiopathic): No precipitating factor Younger age onset Genetic association Autosomal dominant Chromosome 12/14 Secondary: Iron deficiency (~25%) Pregnancy (~25%) Renal failure (up to 60%) Drugs Antidepressants Information from Restless legs syndrome: detection and management in primary care. National Heart, Lung, and Blood Institute Working Group on Restless Legs Syndrome. Am Fam Physician. 2000;62(1):108-114. RLS and Pregnancy RLS is extremely common in pregnancy. Estimates range from 11% to 50%. Severity increases in third trimester. Etiology is uncertain Anemia Abdominal distention Inactivity No increase in fetal risk is documented. Parity increases risk in mothers in a dosedependent way.

Management in RLS: Strategies Consider discontinuing drugs that can worsen RLS: Selective serotonin reuptake inhibitors (SSRIs) (eg, fluoxetine) Tricyclics (eg, amitriptyline) Dopamine antagonists (eg, risperidone) Antihistamines Treat secondary causes: Iron deficiency (ferritin < 50 ng/ml) Renal disease Information from Stiasny K, Oertel W, Trenkwalder C. Clinical symptomatology and treatment of restless legs syndrome and periodic limb movement disorder. Sleep Med Rev. 2002;6(4):253-265; Hening W, Allen R, Earley C, et al. The treatment of restless legs syndrome and periodic limb movement disorder. An American Academy of Sleep Medicine Review. Sleep. 1999;22(7):970-999; Phillips B, Young T, Finn L, et al. Epidemiology of restless legs symptoms in adults. Arch Intern Med. 2000;160(14):2137-2141. Management in RLS: Pharmacologic Management Evidence-based and clinical guidelines identify dopamine agonists as a first-line treatment for RLS. Pramipexole (Mirapex) 0.125 to 1 mg Ropinirole (Requip) 0.25 to 4 mg Start with lowest drug dosage and slowly increase to effective dosage. Dose (30 to 90 minutes) prior to bedtime. If necessary, add an evening dose, then tailor it to relieve patient s symptoms. Anticipate augmentation and rebound. Management in RLS: Drug Options Dopaminergic agents Iron, if ferritin < 50 ng/ml Anticonvulsants Low-potency opiates Benzodiazepines Take-Home Points: RLS RLS is common Prevalence: 3% to 15% of the general population Up to 25% of primary care patients Etiologies of RLS: Most cases are primary and hereditary Secondary etiologies: Iron deficiency, end-stage renal disease (ESRD), peripheral neuropathies Treatment Identify and treat precipitants: Drugs, iron deficiency, sleep deprivation, renal failure Dopamine agonists are first-line pharmacologic agents Pramipexole and ropinirole are FDA-approved for RLS Anticipate augmentation and rebound

Circadian Rhythm Sleep Disorders Jet lag Delayed sleep phase (sleep onset insomnia) Advanced sleep phase (sleep maintenance insomnia) Shift work sleep disorder Irregular sleep-wake rhythm Circadian Rhythm Sleep Disorders Special Populations Shift workers Adolescents Elderly and chronically hospitalized Travelers Physicians and nurses Consider Atypical Antidepressant Approach to Chronic Insomnia Management Education and Sleep Hygiene Cognitive-Behavioral Therapy for Insomnia (CBT-I) Short-Acting Hypnotic (can try as-needed or rescue approach) Sleep Consultation (Comorbid sleep disorder, atypical features, or inadequate response) Combined CBT-I and Hypnotic Conclusions Insomnia is the most common sleep disorder. Prevalence: Up to 30% of US population Pathogenesis may be multifactorial Three principle models: behavioral, cognitive, physiologic Treatment: Cognitive-behavioral therapy works. Similar outcomes to drugs in short-term trials Pharmacologic Benzodiazepine receptor agonists Melatonin receptor agonist (ramelteon)

Case Presentation 65 year old man He is aware of having vivid dreams His wife describes wild actions during his dreams in which he has struck and hurt her, she has moved out of the bedroom His sleep seems otherwise normal with no evidence for sleep apnea REM Behavior Disorder Normal REM sleep associated with inhibition of skeletal muscles to prevent acting out dreams RBD involves failure of the inhibition Now shown to be a precursor to certain degenerative neurologic conditions such as Parkinson s Disease in a significant percent (40%) of these patients Responds well to clonazepine Sleepy Student 17 y/o seen for moderate daytime sleepiness, falling asleep in class or doing homework. Has awakened convinced there was a threatening stranger in his room. Looked drunk and woozy after a funny story at a party What does he have? Narcolepsy Excessive Daytime Sleepiness Cataplexy: brief emotionally triggered episodes of muscle weakness (50%) Sleep paralysis (40-80%) Hypnogogic and hypnopompic hallucinations (40-80%) Fragmented sleep Mild obesity

Other Sleep Stuff Parasomnias Sleep walking Night terrors Bed Wetting Nocturnal eating Hypersomnia Nocturnal Seizures Thank You Jerrold Kram, MD, FCCP, FAASM California Center for Sleep Disorders Sleepsmart.com 510 263 3300