Overview Of Sleep Disorders Sleep Medicine…… 60 years of progress

1. More has been learned about sleep in the last 60 years than in the past 6000 years Mansoor Ahmed. MD, FACCP, FABSM Medical Director, Cleveland Sleep & Research Center Assistant Professor of Medicine Case Western Reserve University Fellow American Academy of Sleep Medicine Overview Of Sleep Disorders Sleep Medicine……60 years of progress

2. History of Sleep Medicine…1953 to PresentFrom Basement To Congress to Wall Street Until 1975, Sleep Medicine was deemed experimental ,1995 Canada followed 4 Mile Stones : 1: REM Sleep 2: PSG 3 : Circadian Biology 4: OSA • 1964: Stanford Narcolepsy Center (C Dement Ad in SF Chronicle for Narcolepsy ..100 responded and 50 were diagnosed to have narcolepsy) • 1964 Association of Professional Sleep Societies (APSS) • 1968: R & K Manual of Sleep Scoring • 1970: Stanford Sleep Center • 1975: 5 Sleep Centers (Montefiore, OH State, Baylor, U-Pittsburg, and U-Cincinnati • 1975-1977: American Sleep Disorders Association, Accreditation • 1978: Certification Exam and Journal of SLEEP • 1990: US Congress Created National Commission on Sleep Disorders • 1991: ICSD-1 , ICSD 2: 2005 • 1996 – At last…The AMA recognized sleep medicine as a specialty European Development: First Sleep Text Book, Human EEG, Sleep Apnea. • 1963: Paris Symposium: ( Prof Fischgold) Sleep Epilepsy, Sleep Walking, Night Terrors. • 1965: Discovery Of Sleep Apnea by Gestualt ,Tassinar and Jung & Khulo

3. Sleep……. A Vital Sign of Human Health: Bi-Directional relationship Diabetes, Weight Gain, Hypothyroid Insomnia and Hypersomnolence PTSD, Anxiety Mood Disorders, ADHD OSA and ….. Hypertension, A Fib MI, Stroke, CHF PTSPD H Opioids & CSA Pain Threshold CFM –Pain & Sleep Alzheimer's Disease, Stroke Parkinson Disease

4. Presentation Summary General Introduction • Normal sleep and why we sleep • Magnitude of Sleep Disorders , Sleep Deprivation and Public Health • Relationship between sleep and other medical specialties: Sleep Disorders : Case Presentation: PTSD • Snoring & Obstructive Sleep Apnea • Circadian Rhythm Sleep Problems: Shift Work, Night Owl • Syndrome,: ADD-ADHD, Jet Lag Insomnia Narcolepsy and other Hypersomnolence Disorders • Restless Leg Syndrome

5. Normal Sleep Put your thoughts to sleep,do not let them cast a shadowover the moon of your heart. Let go of thinking. ……...Rumi Sleep is essential for physical, emotional and mental health

6. Functions of Sleep • We learned more about sleep functions when we don’t sleep • Emotional Integration, Memory Consolidation & REM sleep • Link between REM sleep and PTSD and other psychiatric disorders ……………..From Sigmund Freud to current status Glymphatics • Glial channels carrying CSF expand by 60% during sleep • Clean-up of any unwanted substances/ by products 2X more efficient • Implications in Alzheimer’s disease, stroke and dementia • Shift-workers pre-disposition to neurological disorders

7. Medication and Sleep • Hypnotics and sedatives (benzo and non-benzo • OCD insomnia medications • Stimulants: Caffeine, Ritalin, Modafinil) • Adverse effects of commonly used medicine on sleep & Breathing : • Opioids: Center Sleep Apnea, Respiratory arrest • beta blockers: Melatonin and Insomnia • Alcohol: Most commonly used hypnotic , adverse effect on sleep • Caffeine: The most commonly used stimulant, effect on sleep and alertness.

8. Awake REM 1 2 3 4 1 2 3 4 5 6 7 8 Hours Normal Sleep • Rapid eye movement (REM) sleep • 20% to 25% of total sleep time • Active mind and Motor Paralysis • Intellectual Function • Sexual Functionality • Non–rapid eye movement (NREM) • Stage I Transition to sleep5% of • total sleep • Stage 2 50% of total sleep time • Stages 3 and 4 Slow-wave sleep • 10% to 20% of total sleep time • Growth Hormone • Age and delta sleep Historical Perspective Greeks: Hypnos &Thanatos 1929: Human EEG Alpha Waves (Hansberger) 1953: REM Sleep (Asrenski, Klietman and Dement) 1968: Sleep Stages Scoring Rules ( R&K) 1965: OSA Clinical Studies (Gastaut) 1970: Stanford First Sleep Clinic ( Dement) 1982: CPAP (John Remmer ,Sullivan)

9. Magnitude of the Sleep Disorders Underserved & Under-recognized Discipline 50-60 million American suffer from 80 identified sleep disorders Sleep and Cardio-Vascular Disorders 51% of CHF patients has underlying sleep-breathing disorder OSA is an independent risk factor for hypertension. 30-40% patients with hypertension has OSA Mood Disorders and Sleep, PTSD, ADHD 70% of Patients with mood disorders has sleep pathology Neurological Conditions Sleep disturbance& fatigue are hallmark of MS, Parkinson disease, Alzheimer's Disease, Narcolepsy, Sleep Waking Disorders Sleep Deprivation Challenger Tragedy, >100,000 road accidents annually Circadian Rhythm Shift Work, Delayed Phase Syndrome

10. Sleep Public Health Challenges : Sleep Deprivation, Shift Work, Under Diagnosis of Sleep Disorders :

11. Federal Crash Statistics The National Highway Traffic Safety Administration estimates • 100,000 police-report crashes annually • 1,550 fatalities (4%) • 71,000 injuries • $12.5 billion in monetary losses (Knipling 1995) • Another 1 million crashes are linked to inattention, which increases with fatigue (Wang 1996)

12. Sleep Disorders Case Presentation: A: Snoring & Obstructive Sleep Apnea B: Circadian Rhythm Sleep Problems: Shift Work, Night Owl Syndrome Jet Lag C: Insomnia D: Narcolepsy and other Hypersomnolence Disorders E: Restless Leg Syndrome What we are dealing with here, are two gigantic problems for our society – An epidemic of undiagnosed and untreated sleep disorders; and pervasive sleep deprivation with all its consequences for errors, accidents, disability, damages and death“

13. Sleep and Psychiatry are inherently linked together at every level.. From disease mechanism to clinical Symptoms to outcomes Multiple Psychiatric Pathologies with Multiple Sleep Pathologies 47 Year female, history of depression, anxiety, history noted for childhood trauma, subsequent spousal abuse, alcohol abuse; History of Chronic Fibromyalgia referred by pain specialist for snoring and OSA evaluation : History of Sleep initiation and Sleep Maintenance Insomnia, uncomfortable sensation in legs, night mares, teetth Clenching frequent nocturnal awakening, non-restorative sleep., Wake up tired, severe day-time sleepiness, cataplexy-sleep paralysis Clinical Evaluations: Sleep Wakefulness history, ENT, PTSD scales Investigations: Sleep Diary, PSG-MSLT Sleep Diagnosis: OSA, Restless Legs Syndrome, Chronic Insomnia Bruxism, Narcolepsy: Sleep Disorders………Its Not all about sleep apnea

14. Obstructive Sleep Apnea Choking Choking

15. Stage 2 Sleep with Alpha Intrusions α intrusions

16. Rapid Eye Movement Sleep Increased REM frequency

17. Periodic Limb Movement Syndrome (PLMS) Limb Movements

18. Bruxism (Teeth Clenching) Bruxism Central PLMS

19. Stage 2 Sleep with Alpha Intrusions α intrusions

20. Snoring & OSA……A Trojan Horse of Sleep Medicine

21. Prevalence of Sleep ApneaNo sound epidemiological survey in general population using true random sample and had PSG • Wisconsin: Survey 3513-- 625 Accepted with 25% non snorersparticipants, age 30-60 underwent overnight PSG; • OSAS definition: AHI>5 with hyper somnolence • Ages 50-60 with RDI >15: 4% Women, 9.1% men • Peak Prevalence: 4.7%, Age: 45-64 • Neck Size is more correlated to severity of apnea than BMI • 10% increase//Decrease in weight: 32% increase in AHI, 24% decrease • Age: SHHS: 20% Men, 10% women develop SA in 5 years, • 48% CHF patients have sleep Apnea, • Sleep Apnea incidence is far higher in patients with resistant hypertension, A -Fib, Diabetes T Young, NEJM 1993; 328:1230-5

22. Narrow oropharynx but similar narrowing seen in normal Mechanism different in different patients due to factors related to control of breathingOSA worsens over the time Upper Airway Anatomy Plus Control of Breathing Anatomy: Bony Structure, Soft Tissue, Obesity Control of Breathing : Chemo responsiveness, Negative pressure Upper Airway Muscles: Tongue, Palate, Hyoid Bone Control Of Breathing : Magdy Younes, John Remmer, Jerry Dempsey, SafwanBadr, Neil Cherniack, AtulMalhotra, David White , S Javaheri Sleep Disordered BreathingDisease Mechanism

23. Obstructive Sleep Apnea Choking Choking

24. EKG Airflow Thoracic effort Abd. effort SAO2 Exhale Airway obstructs Airway opens Effort gradually increases Inhale Paradoxing Paradoxing Ends Night Symptoms: Loud Snoring, Choking, Frequent awakening, Restless Sleep Daytime tiredness/Sleepiness, Mood-Memory, Concentration Consequences: Increased BP, Stroke, Diabetes,

25. Sleep-Disordered Breathing…. Disease Mechanism Mechanism of Sleep-Apnea and Sleep Hpoventilation 1) Narrow Upper Airway: Obesity, E.N.T problems, Dysmorphism 2) Control of Breathing: Hormones, Cardiac Dysfunction Apnea Hypopnea Hypoventilation PO2 PCO2 Negative Intra-Thoracic Pressure Arousal, Sympathetic Activation , Systemic-Pulmonary Vasoconst Signs & Symptoms: Sleepiness, Hypertension- LV dysfunction , Corpulmonale

26. STOP-BANGA simple screening tool for Sleep Apnea Snoring • Do you snore loudly (louder than talking or loud enough to be heard through closed doors)? Tired • Do you often feel tired, fatigued, or sleepy during daytime? Observed • Has anyone observed you stop breathing during your sleep? Pressure • Do you have or are you being treated for high blood pressure? BMI • BMI more than 35 kg/m2 Age • Age over 50 yr old? Neck circumference • Neck circumference greater than 40 cm , 15.7 inches? Gender • Gender male? High Risk STOP: Yes to 2 or More STOP BANG: Yes to 3 or more

27. Epworth Sleepiness Scale (ESS) How likely are you to doze off or fall asleep in the following situations, in contrast to feeling just tired? This refers to your way of life in recent times. Even if you have not done some of these things recently, try to work out how they would have affected you. Use the following scale to choose the most appropriate number for each situation 0 = would never dose; 1 = slight chance of dozing2 = moderate chance of dozing; 3 = high chance of dozing SituationChance of Dozing (0-3) Sitting and readingWatching TVSitting, inactive in a public place (eg, a theater or a meeting)As a passenger in a car for an hour without a breakLying down to rest in the afternoon when circumstances permitSitting and talking to someoneSitting quietly after a lunch without alcoholIn a car, while stopped for a few minutes in traffic Mitler and Miller. Behav Med. 1996;21:171.

28. Consequences of OSALongitudinal Findings- Sleep Health Heart Study6441 Patients • Direct Cardiovascular Outcomes between 5 and 8.7 years • Hyperextension, Stroke, CHF . • Increased risk of Hypertension if higher BMI in men • With cardiovascular disease larger increases in AHI • Long Term Outcomes • Positive association between severity of SDB at PSG 1 and subsequent increase in BMI • Men more likely to have an increase in RDI with increase in weight than women • Both men and women had a greater increase in RDI with weight gain than a decrease in RDI with weight loss • Severe SDB showed increased risk of all-cause mortality in the 8.7 years following PSG

29. Evaluation & Diagnosis • Clinical Questions and Epworth • Home Sleep Study • PSG

30. Types of Sleep StudiesHome Sleep Testing ( HST) Type 1 – Attended in-lab polysomnography Type 2 – Comprehensive portable polysomnography – Minimum of 7 channels including EEG, EOG, chin EMG, ECG/HR, airflow, respiratory effort and O2 saturation HST: Type 3 – Modified portable sleep apnea testing – Minimum of 4 channels including ECG/HR, O2 saturation and at least 2 channels of respiratory movement or respiratory movement and airflow Type 4 – Continuous single or dual bioparameters – For example, airflow and/or O2 saturation

31. Emergent OSA Therapy • Weight Loss • CPAP • New PAP Modalities • Correction of enlarged tonsils, Sinuses, UA surgery • Oral Advancement Therapy • Implantable Neuro-stimulator • Provent: PEEP Mechanisms CPAP is the most effective but compliance is the key issue

32. Circadian Sleep Disorders • Wake • During the day, SCN activity promotes arousal • Maintains state of wakefulness • Sleep • At night, SCN arousal is attenuated • Allows normal sleep to occur SCN plays a pivotal role in maintaining wakefulness by generating an “alerting signal” that opposes the homeostatic sleep drive. During the evening, the alerting signal is thought to be attenuated, in part via elevation in melatonin concentration during the night, allowing sleep to occur

33. Sleep Homeostasis and Models of Sleep Regulation Borbély, A., & Achermann, P. (1999). Sleep Homeostasis and Models of Sleep Regulation Journal of Biological Rhythms, 14 (6), 559-570 DOI:

34. Circadian Rhythm Sleep Disorders (CRSD) • “The essential feature of CRSDs is a persistent or recurrent pattern of sleep disturbance due primarily to alterations in the circadian timekeeping system or a misalignment between the endogenous circadian rhythm and exogenous factors that affect the timing or duration of sleep.” – ICSD-2. 6 Distinct CRSDs are recognized in the ICSD-2: • Delayed Sleep Phase Type (DSPD) • Advanced Sleep Phase Type (ASPD) • Irregular Sleep-Wake Phase Type (ISWR) • Free-Running Type (FRD) • Jet Lag Type (JLD) • Shift Work Type (SWD)

35. Treatment- CRSD • Planned napping • Timed light exposure • Administration of melatonin • Enhance Alertness • Hypnotic medications

36. Insomnia • Insomnia is common and can have serious consequences, such as increased risk of depression and hypertension • Acute and chronic insomnia require different management approaches • Chronic insomnia is unlikely to spontaneously remit, and over time will be characterized by cycles of relapse and remission or persistent symptoms • Chronic insomnia is best managed using non-drug strategies and adjunctive use of medications

37. Insomnia A symptom of either difficulty in falling asleep maintaining sleep or just sense of having insufficientsleep, causing an uncomfortable subjective experience, in some ways analogous to chronic pain 30% general population experience insomnia Most of the patients patients with mood disorders has sleep pathology Psychiatric disorders are the single largest cause of chronic insomnia in sleep-clinic population

38. Prevalence of Insomnia* in the General Adult Population Percent Ford1989 Ohayon1998 Ohayon2001 Ancoli-Israel1999 Ishigooka1999 Simon1997 • *Insomnia = sleep disturbance every night for two weeks or more, or similarly stringent criteria. • Ford DE, Kamerow DB. JAMA. 1989;262:1479-1484. • Ohayon MM, et al. Compr Psychiatry. 1998;39:185-197. • Ohayon MM, Roth T. J Psychosom Res. 2001;51:745-755. • Ancoli-Israel S, Roth T. Sleep. 1999;22(suppl 2):S347-S353. • Ishigooka J, et al. Psychiatry Clin Neurosci. 1999;53:515-522. • Simon GE, VonKorff M. Am J Psychiatry. 1997;154:1417-1423.

39. Insomnia in Patients WithChronic Medical Conditions Insomnia* Severe Insomnia† Percentage of Patients With Insomnia Diabetes CHF HipImpairment ObstructiveAirway MI Angina BPH *Sleep disturbance “some” or “a good bit” of the time for four weeks. †Sleep disturbance “most” or “all” of the time for four weeks. MI = myocardial infarction; CHF = congestive heart failure; BPH = benign prostatic hypertrophy. Katz DA, McHorney CA. Arch Intern Med. 1998;158:1099-1107.

40. Insomnia…the most common sleep disorder

41. Insomnia Treatment • Sleep Hygiene • Cognitive Behavior Therapy • Pharmacotherapy

42. Therapeutic Agents • Sedative-hypnotics • Sedating antidepressants • Selective melatonin agonist and Melatonin • Antihistamines • Anxiolytics • Alternative and herbal medications- Valerian Root Extract Hypnotics can be used on long term basis in Primary Insomnia Exercise, CBT, Sleep Hygiene

43. Components of Cognitive Behavior Therapy • Stimulus control (daytime and sleeping environments) • Sleep restriction • Relaxation techniques (progressive relaxation, imagery training, biofeedback, meditation, hypnosis and autogenic training) to reduce physical and mental arousal • Reduce negative perceptions about battle ground of sleep • Write about worries in the evening • Stopping thoughts (repeating word “the” every three sec.) • Sleep hygiene education

44. What to do and not to Do • Recognize that there is a sleep problem & bring it to the attention • What is the nature of Sleep Problem: Insomnia, Sleep Apnea, Restless Legs, Shift Work 3. Determine Circadian Phase Diet/light snack , exercise, hot bath, relaxing techniques, Bed timing and sleep timing, prescription medications What Not to do Clock watching, thinking about next day issues, worrying about sleep, Coffee/Smoking/Alcohol Catching-up over the week-ends

45. Narcolepsy • Idiopathic Hypersomnia • Post-Traumatic Hypersomnia • Mood Disorders • Sleep Apnea • PLMS/Leg Movements • Sleep Walking Mechanistic Approach Sleep-Wake Dysregulation Sleep Disruption Circadian Misalignment Excessive Sleepiness Disorders • Delayed Phase Syndrome • Advanced Phase Syndrome • Shift Work Disorder • Non-24 hour Rhythm

46. Narcolepsy • Characterized by excessive sleepiness + cataplexy and other REM phenomena • Sleep paralysis • Hypnagogic hallucinations • Etiology unknown • Pathology: • Genetic predisposition • Hypocretin/orexin deficiency • Autoimmune disease • Neurochemical abnormalities • Environmental triggers • Head trauma

47. Assessment of Sleepiness Behavioral • Facial expression, posture, yawning, myosis Subjective • Epworth Sleepiness Scale (ESS) • Stanford Sleepiness Scale (SSS) Objective • Multiple Sleep Latency Test (MSLT) • Polysomnography (PSG) • Actigraphy • Maintenance of Wakefulness Test (MWT) Mitler and Miller. Behav Med. 1996;21:171.

48. Sleepiness and REM Sleep Assessed by Multiple Sleep Latency Test (MSLT) Number of REM Periods Recorded in All 5 Naps Sleep Latency 20 5 16 4 Control 13.4 ± 4 12 3 REM periods/5 naps (mean) Minutes 8 2 Narcolepsy 4 1 3.0 ± 2.7 0 0 0 1 2 3 4 5 Narcolepsy Control Naps Control N=17Narcolepsy N=57 Adapted from Mitler et al. Psychiatr Clin North Am. 1987;10:593.

49. Narcolepsy: Traditional Management Approaches Excessive daytime sleepiness • Structured nocturnal sleep • Naps: scheduled and PRN • Stimulants or wake promoting agents Cataplexy • Antidepressants (TCA or SSRI) Sleep fragmentation • Sleep hygiene • Hypnotics (limited utility) General • Personal and family counseling • Support Parkes. Sleep. 1994;17:S93; Mitler M et al. Sleep. 1994;17:352; Daly and Yoss. Narcolepsy. In: Handbook of clinical Neurology. Vol.15.1994;15:836; Bassetti and Aldrich. Neurol Clin. 1996;14:545; Mamelak et al. Sleep. 1986;9:285.

50. Restless Legs Syndrome Key RLS Diagnostic Criteria • Urge to move legs-usually accompanied by uncomfortable sensations • Temporary relief with movement • Onset or worsening of symptoms at rest or inactivity, such as lying or sitting • Worsening of symptoms in the evening or at night Other Diagnostic Considerations • Positive family history of Restless Legs Syndrome • Periodic limb movements during wakefulness or sleep (PLMW or PLMS) • Sleep disturbance