Mind – Body Implications Major Sleep Disorders Mind – Body Implications Charles Atwood, MD, FCCP VA Pittsburgh Healthcare System UPMC Sleep Medicine Center Pittsburgh Mind–Body Center Core D: “the sleep core”

Major Sleep Disorders

Objectives Review major disorders of sleep Provide clinical context for MBC investigators who think about sleep as a mediator of MB processes and interactions Attempt to put the major disorders into the MBC framework

Health Relationships Sleep HEALTH Exercise Nutrition

Lifespan/Development

Attitudes Toward Sleep Sleep ranks among the 3 most important considerations in maintaining good health 62% of US population experiences sleep problems 80% of US adults have NEVER discussed sleep problems with their physician Societal bias equates sleepiness with laziness Adequate nutrition, stress management, and sleep are the 3 most important considerations in the maintenance of good health. An estimated 62% of the US population experiences sleep problems, yet approximately 80% of US adults have never discussed sleep or sleep problems with their physicians. This may largely be due to the stigma that sleepiness equates with laziness. Adapted from National Sleep Foundation. 2000 omnibus sleep in America poll. National Sleep Foundation. 2000 omnibus sleep in America poll. Available at: http://www.sleepfoundation.org/publications/2000poll.htm1. Accessed October 12, 2002.

“All I want is a good night’s sleep…” Sleep in America Poll, 2005 N = 1506

Top 10 Diagnoses by Internists Percentage of visits Source: IM news, 6/1/05

How sleep problems relate to the top 10 diagnoses Sleepiness, fatigue OSA, fatigue Insomnia, poor quality sleep OSA OSA OSA Percentage of visits Source: IM news, 6/1/05

Classification of Sleep Disorders Disorders of Excessive Sleepiness (DOES) Disorders of Initiating and Maintaining Sleep (DIMS) Parasomnias Miscellaneous disorders

Other Classifications Classified by primary site of affliction Neurological Breathing disorders Psychiatric Insomnia Parasomnia Cardiovascular Others

International Classification of Sleep Disorders Version 2 (ICSD-2) Insomnias Sleep-Related Breathing Disorders Hypersomnias Not Due to a Sleep-Related Breathing Disorder Circadian Rhythm Sleep Disorders Parasomnias Sleep-Related Movement Disorders Isolated Symptoms, Apparently Normal Variants and Unresolved Issues Other Sleep Disorders AASM, Chicago

Major Sleep Disorders Insufficient sleep Insomnia Sleep Apnea Shift Work Sleep Disorder Restless Legs Syndrome Narcolepsy

We Get Too Little Sleep 8 hrs recommended = adequate sleep National Sleep Foundation (NSF): 2002 “Sleep in America” Poll (N = 1,010 adults)

Change in average amount of sleep per night over the past century 1910 = 9.0 hrs/night 1975 = 7.5 hrs/night Today = 6.9 hrs/night Bull Psychon Soc 1975 6:47-48 Neurophysiol Clin 1996 26:30-39

ICSD-2: Insomnias Adjustment sleep disorders (acute insomnia) Psychophysiological Insomnia Paradoxical Insomnia (formerly Sleep State Misperception) Idiopathic Insomnia Insomnia due to mental disorder Behavioral Insomnia of Childhood Insomnia due to a medical condition Insomnia due to a a drug or substance Insomnia not due to a substance or known psychological condition (Nonorganic Insomnia, NOS) Physiological (organic) insomnia, unspecified, unspecified; (Organic Insomnia, NOS) AASM, Chicago

Insomnia in the Population Insomnia symptoms -Overall prevalence 30-48% -Often or always: 16-21% -Moderate to extreme: 10-28% Insomnia symptoms + daytime consequences 9-15% Insomnia diagnosis 6% Why DX only 6%? Direct ecomonic costs of insomnia alone in the US are estikmated at close to $14 billion.” Direct economic costs of insomnia in the US are estimated ~ $14 billion Ohayon, Sleep Med Rev, 2002

Insomnia vs. Insufficient Sleep Cannot initiate or maintain sleep “Can’t sleep” May be transient May persist High likelihood of medical/psych sequelae Insufficient sleep Self-limits sleep “chooses not to sleep” Transient Lower likelihood of sequalae

Insomnia: Effects on Health Poor concentration Decreased QOL Contributes to depression and anxiety, other illness Decrements in work quality Increased healthcare utilization PERSONAL SOCIETAL

ICSD-2: Sleep-Related Breathing Disorders Central Sleep Apnea Syndromes Primary Central Sleep Apnea Other Central Sleep Apnea due to a medical condition Central Sleep Apnea due to a drug or substance Other Sleep-Related Breathing Disorder due to a drug or substance Obstructive Sleep Apnea Syndromes Obstructive Sleep Apnea, Adult Obstructive Sleep Apnea, Pediatric Sleep-Related Hypoventilation / Hypoxemic Syndromes Sleep-Related Non-Obstructive Alveolar Hypoventilation, Idiopathic Congenital Central Alveolar Hypoventilation Syndrome Sleep-Related Hypoventilation / Hypoxemia due to a medical condition Other Sleep-Related Breathing Disorder Sleep Apnea / Sleep Related Breathing Disorder, unspecified AASM, Chicago

Sleep Apnea is Common Children (age 2 - 8) Middle aged adults Older adults ( > 65) 2 – 3% 5 -7% >15% AJRCCM 2002 165:1217-39

QUIZ Which upper airway segments or sites are important in OSA pathophysiology? Nasopharynx Velopharynx (tongue base, soft palate) Hypopharynx (lower pharynx)

ANSWER ALL of THEM!!!

Upper Airway Sites Contributing to OSA

Sleep-Sensitive Neuromodulators Phasic Respiratory Input Superior Laryngeal Nerve White, PATS, 2005

Major Variables Contributing to Airway Patency / Collapse Promotion of Airway Collapse Promotion of Airway Patency Negative pressure on inspiration Pharyngeal dilator muscle contraction (genioglossus) Extralumenal positive pressure Fat deposition Small mandible Lung volume (longitudinal traction) White, PATS, 2005

Prevalence of Sleep Apnea 0.3 0.3 0.25 0.25 0.2 0.2 OSA Prevalence 0.15 0.15 0.1 0.1 Plateau 0.05 0.05 35 45 55 65 75 85 Age in years AJRCCM 2002 165:1217–1239

Sleep Apnea is Associated with Significant Co-morbidities Cardiovascular Complications Metabolic Complications Neuro-cognitive Complications

Sleep Disordered Breathing and Cardiovascular Disease Odds Ratio AJRCCM 2001 163:19-25 AHI (Quartiles)

Incident Hypertension within 4 years according to Apnea-Hypopnea Index Adj OR > 15 hr A/H Index Adjusted for baseline hypertension, age, sex, BMI, waist and neck circumference, alcohol and cigarette use. NEJM 2000 342: 1378 - 1384

Sleep Apnea & Sleepiness Apnea / Hypopnea Index AJRCCM 1999 159:502-507

Automobile Accident Rates in OSA Patients * Number per Year n = 581 n = 229 n = 107 n = 246 Sleep 1999 22:790-95

ICSD-2: Hypersomnias not due to a breathing disorder Narcolepsy Narcolepsy with Cataplexy Narcolepsy without Cataplexy Narcolepsy due to a medical condition Narcolepsy, unspecified Other Hypersomnias Recurrent Hypersomnia Idiopathic Hypersomnia with long sleep time Idiopathic Hypersomnia without long sleep time Behaviorally Induced Insufficient Sleep Syndrome Hypersomnia due to a medical condition Hypersomnia due to a drug or substance Hypersomnia not due to a substance or known physiologic condition Physiological (Organic) Hypersomnia, unspecified (Organic Hypersomnia, NOS) AASM, Chicago

Narcolepsy: Epidemiology Prevalence ~1 in 2000 (US) ~150,000+ patients in US Men and women affected equally Age at onset Can present at any age Majority 15-30 years of age 6% prior to 10 years of age Narcolepsy affects approximately 1 in 2000 people in the United States, a prevalence that is greater than that of cystic fibrosis but comparable to that of multiple sclerosis. The prevalence of narcolepsy in men and women is comparable. Although it may occur at any age, narcolepsy usually first appears in patients between 15 to 30 years of age; only 6% of patients under the age of 10 are affected, and the condition is usually present in patients before the age of 55. J Clin Neurophysiol 2001;18:78. Overeem S, Mignot E, van Dijk JG, Lammers GJ. Narcolepsy: clinical features, new pathophysiologic insights, and future perspectives. J Clin Neurophysiol. 2001;18:78-105.

Prevalence of Narcolepsy/Cataplexy (USA) 260 162 Prevalence per 100,000 113 40 Narcolepsy is not a rare disorder. The prevalence of narcolepsy in the United States is only slightly less than that of other well-known and economically significant diseases such as multiple sclerosis, Parkinson's disease, and insulin-dependent diabetes mellitus (IDDM, type 1).1-7 4-6 ALS = amyotrophic lateral sclerosis. National Sleep Foundation. Mittler. An Introduction to Narcolepsy. National Sleep Foundation Slide Kit. 1. Hubin C, Partinen M, Kaprio J, Koskenvuo M, Guilleminault C. Epidemiology of narcolepsy. Sleep. 1994;17:S7-S12. 2. Young T, Palta M, Dempsey J. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993;328:1230-1235. 3. Kurtzke JF. The current neurologic burden of illness and injury in the U.S. Neurology. 1982;32:1207-1214. 4. Kondo K. Epidemiology of motor neuron disease. In: Leigh PN, Swash M, eds. Motor Neuron Disease: Biology and Management. London, UK: Springer-Verlag; 1995:19-33. 5. Merniti-Ippolito F, Spila-Alegiani S, Vanacore N, et al. Estimate of parkinsonism prevalence through drug prescription histories in the province of Rome. Acta Neurologica Scandinavica. 1995;92:49. 6. LaPorte RE, Fishbein HA, Drash AL. The Pittsburgh Insulin-dependent Diabetes Mellitus (IDDM) Registry. Diabetes. 1981;30:279-284. 7. Mittler MM. An Introduction to Narcolepsy. National Sleep Foundation Slide Kit.

…from a narcolepsy patient I saw last year…

Narcolepsy Fundamentally a sleep disorder Drop out of hypocretin neurons in hypothalamic nuclei Results in “loss of boundaries between sleep and wakefulness” “Can’t stay awake during the day; can’t stay asleep during the night”

Narcolepsy Symptoms Sleepiness with more or less discrete attacks Cataplexy (lacking in ~40%) Hypnogogic hallucinations Sleep paralysis Disrupted nocturnal sleep

How often daytime sleepiness was reported to interfere with daily activities? NSF: 2002 “Sleep in America” Poll of adults

ICSD-2: Circadian Rhythm Sleep Disorders Primary Circadian Rhythm Sleep Disorders Circadian Rhythm Sleep Disorder, Delayed Phase type Circadian Rhythm Sleep Disorder, Advanced Phase type Circadian Rhythm Sleep Disorder, Irregular sleep-wake type Circadian Rhythm Sleep Disorder, Free running type Circadian Rhythm Sleep Disorders due to a medical condition Primary (Organic) Circadian Rhythm Sleep Disorder Behaviorally Induced Circadian Rhythm Sleep Disorders Jet lag type Shift work type Delayed phase type Unspecified Other not due to a substance or known physiologic condition Other due to a drug or substance AASM, Chicago

ICSD-2: Parasomnias Disorder of Arousal (From Non-REM Sleep) Confusional arousals Sleepwalking Sleep terrors Parasomnias Usually Associated with REM Sleep REM Sleep Behavior Disorder Recurrent Isolated Sleep Paralysis Nightmare Disorder Other Parasomnias Sleep-Related Dissociative Disorder Sleep-Related Enuresis Sleep-Related Groaning Exploding Head Syndrome Sleep-Related Hallucinations Sleep-Related Eating Disorder Parasomnia, unspecified Parasomnia due to drug or substance Parasomnia due to a medical condition AASM, Chicago

ICSD-2: Sleep-related Movement Disorders Restless Legs Syndrome (included Sleep-Related Growing Pains) Periodic Limb Movement Sleep Disorder Sleep-Related Leg Cramps Sleep-Related Bruxism Sleep-Related Rhythmic Movement Disorder Sleep-Related Movement Disorder, unspecified Sleep-Related Movement Disorder due to a drug or substance Sleep-Related Movement Disorder due to a medical condition AASM, Chicago

What is RLS? Common yet frequently undiagnosed Sensorimotor disorder of extremities Common yet frequently undiagnosed Irresistible urge to move legs Relieved by movement of legs Circadian predilection Earley CJ. New Engl J Med. 2003;348:2103-2109.

Primary RLS Genetic predisposition Tends to be earlier onset and more severe than secondary causes Natural history poorly understood Long delays in seeking attention Few longitudinal studies Allen RP, et al. Sleep Med. 2002;3:S3-S7; Garcia-Borreguero D, et al. Neurology. 2003;61(Suppl 3):S49-55; Desautels A, et al. Am J Hum Genet. 2001;69:1266-1270; Allen RP, et al. Sleep Med. 2003;4:101-119.

Secondary RLS Associated with: Iron deficiency End-stage renal disease Pregnancy Secondary RLS may remit upon resolution of the causative condition (eg, after pregnancy) Akyol A, et al. Clin Neurol Neurosurg. 2003;106:23-27; O’Keeffe ST, et al. Age Ageing. 1994;23:200-203; Winkelman JW, et al. Am J Kidney Dis. 1996;28:372-378; Berger K, et al. Arch Intern Med. 2004;164:196-202; Lee KA, et al. J Womens Health Gend Based Med. 2001;10:335-341.

RLS: Essential Diagnostic Criteria U An urge to move the legs, usually accompanied or caused by uncomfortable and unpleasant sensations in the legs R The urge to move or unpleasant sensations begin or worsen during periods of rest or inactivity, such as lying or sitting G The urge to move or unpleasant sensations are partially or totally relieved by movement, such as walking or getting up, at least as long as the activity continues E The urge to move or unpleasant sensations are worse in the evening or night than during the day or only occur in the evening or night Allen RP, et al. Sleep Med. 2003;4:101-119.

ISCD-2: Isolated symptoms, apparently normal variants and unresolved issues Long Sleeper Short Sleeper Snoring Sleeptalking Sleep Starts, Hypnic Jerks Benign Sleep Myoclonus of Infancy Hypnagogic Foot Tremor and Alternating Leg Muscle Activation during Sleep Propriospinal Myoclonus at Sleep Onset Excessive Fragmentary Myoclonus AASM, Chicago

ISCD-2:Other Sleep Disorders Other Physiologic (Organic) Sleep Disorder Physiological (Organic) Sleep Disorder, unspecified Other sleep Disorder not due to a substance or physiological condition Environmental Sleep Disorder Sleep Disorder not due to a substance or physiologic condition, unspecified Appendix A: Sleep Disorders Associated with conditions Classifiable Elsewhere Appendix B: Other Psychiatric / Behavioral Disorders Frequently Encountered in the Differential Diagnosis of Sleep Disorders AASM, Chicago

Sleep Disorders are... Common Serious Treatable Under-diagnosed Costly

Sleep Disorders are common An estimated 70 million adult Americans have clinically significant sleep problems Insomnia affects about one-third of the adult population at some point and 9 to 10% suffer from chronic insomnia OSA affects 4% of men, 2% of women Over 25% of patients with essential hypertension have OSA

Sleep Disorders are serious Chronic insomniacs impaired daytime functioning, decreased work productivity, quality of life, & physical health Insomnia is a risk factor for depression Sleep disordered breathing (SDB) patients, adults and adolescents with insufficient sleep have an increased incidence of motor vehicle crashes Insufficient sleep and use of sleeping pills may be associated with increased falls, injuries, $$$

Sleep Disorders are treatable Successful treatment modalities exist: pharmacotherapy, behavioral therapy, continuous positive airway pressure (CPAP), dental appliances surgical therapy

Sleep Disorders are under-diagnosed As many as 95% of people with a sleep problem remain unidentified and undiagnosed Few health care providers question patients about sleep Little content in medical schools Essentially everything learned about sleep is in post-graduate courses (a booming academic business)

Sleep Disorders are Costly Possibly 100,000 motor vehicle accidents annually are sleep-related. The annual direct cost estimate of sleep-related problems is $16 billion, with an additional $50-$100 billion in indirect costs: Accidents Litigation Property destruction Hospitalization Death

3 Mile Island Exxon Valdez Oil Spill Challenger Explosion Exxon Valdez – 1989 – cleanup effort was $2billion Challenger – 1986 – declared absence of data on o-ring function at low temperatures and the decision to launch was an error – human factors subcommittee attributed the error to sleep deprivation on behalf of NASA managers Challenger Explosion

Lifespan/Development

How do sleep disorders interact with this model? Increased chronic burdens of disease Primary sleep disorders Secondary effects Decreased coping mechanisms Excess sleepiness Biological pathway interuption Modulator of inflammation?

Sleep disorders medicine and mind-body interactions Sleep medicine is in its adolescence as a field Understanding mind-body interactions with respect to sleep is in its infancy Fundamental processes relating sleep as a mediator of M-B processes is very much needed