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  1. 1. SLEEP DISORDERS 2007<br />Fidaa Shaib, MD, DABSM,CBSM<br />Assistant Professor of Medicine<br />Director, the Center for Sleep and Wake DisordersDivision of Pulmonary, Critical Care, and Sleep MedicineUniversity of Louisville<br />
  2. 2. “Sleep is the intermediate state between wakefulness and death; wakefulness being regarded as the active state of all the animal and intellectual function , and death as that of their total suspension”<br />MacNish. The philosophy of sleep<br />European Philosophy<br />
  3. 3. An active and prescient perception of sleep<br />with the concept of human life being spent in<br />three states: <br />Wakefulness <br />Dreaming sleep<br />Dreamless sleep<br />Hindu Philosophy <br />
  4. 4. “Sleep is a dynamic behavior. Not simply the absence of waking, sleep is a special activity of the brain, controlled by elaborate and precise mechanisms”<br /> Hobson, Sleep.<br />
  5. 5. Non Rapid Eye Movement Sleep (NREM): <br /> a relatively inactive yet actively regulating brain in a movable body <br />Rapid Eye Movement Sleep (REM):<br /> a highly activated brain in a paralyzed body<br />The Duality of Sleep<br />
  6. 6. Non Rapid Eye Movement Sleep (NREM) Stages 1,2,3,4<br />Fragmented mental activity<br />Relative autonomic stability and functional coordination between respiration, pumping action of the heart, and maintenance of arterial blood pressure<br />
  7. 7. Non Rapid Eye Movement Sleep (NREM) Stages 1,2,3,4<br />Stage I (5-10%) : a transition between wake and sleep. It occurs upon falling asleep and during brief arousal periods within sleep.<br /> Stage II (40-50% ): occurs throughout the sleep period<br />Stages III and IV “delta sleep” (40-50%)mostly in the first third of the night.<br />
  8. 8. 20-25%<br />2 Stages: phasic and tonic <br />Cerebral activation with active motor inhibition <br />↠Dreaming and very organized complex brain activity<br />Rapid Eye Movement Sleep (REM)<br />
  9. 9. The 2 Process Model of Sleep:Process C and Process S<br />Circadian pacemaker<br />Sleep debt<br />
  10. 10. Sleepiness and alertnessProcess C: Circadian <br />A mechanism defining the alternation of periods with high and low sleep propensity<br />Absolutely independent from the duration of precedent wake or sleep <br />The Suprachiasmatic nuclei<br />Light and Melatonin<br />
  11. 11. Sleepiness and alertnessProcess S: Sleep homeostasis<br />Describing the sleep-pressure's course during wake-time and its lowering during sleep; <br /> <br />Accumulates during wakefulness and eliminated during slow wave sleep<br />Adenosine / antagonist Caffeine<br />
  12. 12. Max alertness<br />Max sleepiness<br />
  13. 13. Normal sleep<br />Adult: 8-8.4 hours is considered fully restorative<br />Insufficient sleep: most common cause of excessive daytime sleepiness<br />Alternating NREM/REM sleep <br />
  14. 14. Whitehall II Cohort:<br />Decrease in Sleep Duration: affects all cause mortality via increase in cardiovascular deaths<br />Increase in Sleep Duration: affects overall mortality via increase in non-cardiovascular deaths<br />Sleep Duration and Mortality<br />A Prospective Study of Change in Sleep Duration: Associations with Mortality in the Whitehall II Cohortet al. Sleep Dec 2007<br />
  15. 15. First National Health and Nutrition Examination Survey (NAHNES I) <br />8992 subjects, 32-86 yr<br />8-10 period follow up <br />< 5 Hrs : OR = 1.47(1.03-2.09) <br />> 9 hrs : OR = 1.52(1.02-2.18)<br />More likely to have incident Diabetes<br />Sleep Duration and Diabetes<br />
  16. 16. Sleep Disorders<br />Charles Dickens <br />Pickwick Papers 1836<br />Joe, the fat boy<br />Excessively sleepy, loud snorer<br />? Right heart failure<br />(young dropsy)<br />
  17. 17. Dyssomnias: primary disorders of initiating or maintaining sleep or of excessive sleepiness and are characterized by a disturbance in the amount, quality, or timing of sleep <br />Parasominas: disorders that intrude into the sleep process and create disruptive sleep-related events (NREM and REM)<br />Sleep disorders associated with neurologic, mental, or medical disorders<br /> Proposed sleep disorders<br />Sleep Disorders<br />
  18. 18.
  19. 19. Difficulties at sleep onset<br />Problems during sleep that cause disruption or awakening<br />Inability to awaken from sleep at desired time<br />Daytime sleepiness<br />Patient presentation<br />
  20. 20. Evaluation<br />Focused History: BEARS<br />Bed time, sleep time, wake up time<br />Excessive daytime sleepiness<br />Awakenings, restless sleep<br />Regularity<br />Snoring, choking, witnessed apneas, morning headaches<br />Plusabnormal behavior<br />Medical History<br />Behavioral/Psychiatric History<br />Alcohol and Drugs<br />
  21. 21. <ul><li>Sleep Quality Profile (SQP)</li></ul>Berlin Questionnaire:snoring behavior, daytime sleepiness, obesity, and hypertension<br />Screening Tools<br />Prevalence of Symptoms and Risk of Sleep Apnea in the US Population Results From the National Sleep Foundation Sleep in America 2005 Poll<br />Chest - Volume 130, Issue 3 (September 2006)  - <br />
  22. 22. Initial Clinic Evaluation <br />Epworth Sleepiness Scale (ESS)<br /> (>10 suggest and >12 confirms chronic sleepiness )<br />Beck depression inventory (BDI)<br />RLS severity score<br />Evaluation Tools<br />
  23. 23. Nocturnal PolySomnoGram (NPSG) <br /> “ Sleep Study”<br />Multiple Sleep Latency Test (MSLT)<br />Maintenance of Wakefulness Test (MWT)<br />Actigraphy<br />Sleep Diary<br />Evaluation Tools<br />
  24. 24. 51 yo woman with episodic disorientation and memory loss<br />Neurology workup with normal MRI / Angiogram<br />PMH: HTN, migraine headaches, 100 lb weight gain and possible fibromyalgia<br />Meds: acetazolamide, lorazepam, atenolol and paroxetine<br />Case#1<br />
  25. 25. Sleep history reveals EDS, restless sleep, snoring, urinary incontinence, naps are non-refreshing<br />BMI 36.5 <br />Large tongue, Mallampati 3<br />ESS= 16<br />Case#1<br />
  26. 26. Sleep Disordered Breathing ( SDB)<br />Common:<br />Snoring*Excessive daytime sleepiness*Sudden arousals with choking*Non-refreshing sleepFatigueLethargyDepressionMorning dry throatMorning headachesImpotenceEnuresisNocturnal sweating<br />Nocturia<br />Women:<br />Insomnia<br />Palpitation<br />LE edema <br />
  27. 27. Physical exam<br />BMI ( >25 overwieght and > 30 obese)<br />Neck circumference (>16 cm)<br />Anatomy of the oropharynx<br />Alignment of the Jaw<br />Evaluation<br />
  28. 28. Snoring <br />Upper Airway Resistance Syndrome<br /> (UARS)<br />SDB characterized by Obstructive hypopneas<br />Obstructive Sleep Apnea<br />Sleep Disordered Breathing ( SDB)<br />
  29. 29. Upper Airway Resistance Syndrome<br />
  30. 30. SDB characterized by Obstructive hypopneas<br />
  31. 31. Obstructive Sleep Apnea<br />
  32. 32. Obstructive Sleep Apnea<br />Prevalence in the United States estimated to be between 5% and 10%<br />1993 Wisconsin Sleep Cohort: 2% of women and 4% of men (EDS and AHI>5)<br />NSFSleep in America 2005 Poll: <br />9% of women and 24% of men had an AHI of ≥ 5 events per hour, <br />44% of men and 28% of women were habitual snorers.<br />Only 10% of the population has been adequately screened for appropriate diagnosis.<br />Maximum prevalence of OSA occurs between the fifth and seventh decades <br />
  33. 33. Prevalence of chronic illnesses among individuals with high-risk Berlin questionnaire score :<br />Prevalence of Symptoms and Risk of Sleep Apnea in the US Population Results From the National Sleep Foundation Sleep in America 2005 Poll<br />Chest - Volume 130, Issue 3 (September 2006<br />
  34. 34. Consequences<br />
  35. 35. Daytime somnolence resulting in significant impairment of functional capacity and reduced quality of life<br />Decreased cognitive function<br />Increased risk for depression<br />Loss in work productivity<br />Increased risk of automobile crashes<br />OSA: Consequences<br />
  36. 36. Relationship of metabolic syndrome and obstructive sleep apnea.<br />J Clin Sleep Med. 2007 Aug 15;3(5):467<br />
  37. 37. Pathophysiologic pathways in the development of cardiovascular disease in obstructive sleep apnea<br />Pathophysiologic Mechanisms of Cardiovascular Disease in Obstructive Sleep Apnea<br />Sleep Medicine Clinics - Volume 2, Issue 4 (December 2007<br />
  38. 38. SDB: Treatment <br />Positive Airway Pressure<br />Weight loss <br />Behavioral therapies<br />Avoidance of CNS <br /> Depressants<br />Sleep hygiene practices<br />Mandibular repositioning devices<br />Uvulopharyngopalatoplasty (UPPP): 40-50% success rate<br />Tonsillectomy/adenoidectomy<br />Tracheotomy: 100 % cure rate<br />Jaw advancement techniques:97%<br />Alternative Therapy<br />Primary Therapy<br />
  39. 39. Pickwickian Syndrome Obesity Hypoventilation Syndrome<br />BMI>30<br />Awake PCO2>45<br />A. Obstructive sleep apnea-hypopnea syndrome<br />B. Sleep hypoventilation syndrome: <br />1. An increase in PaCO2 >10 mm <br /> Hg from awake supine values<br /> 2. Oxygen desaturation not explained by apneic or hypopneic events<br />C. A combination of obstructive sleep apnea-hypopnea events and sleep hypoventilation<br />
  40. 40. CPAP/ tracheotomy: if associated with SDB<br />BiPAP: if Hypoventilation alone<br />Progesterone: improve ventilation but does not improve apnea frequency or symptoms of sleepiness. <br />Treatment:<br />
  41. 41. 65 yo man with history of insomnia, non-refreshing sleep, and irregular breathing with witnessed apneas per wife<br />PMH: HTN, CHF with EF 30%<br />Meds: Lasix, digoxin, Lisinopril <br />NPSG<br />Case#2<br />
  42. 42.
  43. 43.
  44. 44. Hypercapnic central apnea<br />•Central congenital hypoventilation• Arnold-Chiarri malformation• Muscular dystrophy• Amyotrophic lateral sclerosis• Postpolio syndrome• Kyphoscoliosis<br />Central Sleep Apnea<br />
  45. 45. Nonhypercapnic central apnea<br /> • Central apnea of sleep <br /> onset• Periodic breathing at high <br /> altitude• Congestive heart failure• Acromegaly• Hypothyroidism• Chronic renal failure• Idiopathic CSA<br />Central Sleep Apnea<br />
  46. 46. Central sleep apnea and CHF<br />Javaheri et al :<br /> 51% of male CHF patients had sleep-disordered breathing<br /> 40% had CSA<br /> 11% had obstructive apnea <br />Risk factors for CSA:<br />Male gender<br />Atrialfibrillation<br />Age greater than 60 years<br />Hypocapnia(PCO2<38 mm Hg) during wakefulness <br />
  47. 47. Survival of patients with heart failure, with or without central sleep apnea, after accounting for all confounders<br />Central sleep apnea, right ventricular dysfunction, and low diastolic blood pressure are predictors of mortality in systolic heart failure. J Am Coll Cardiol 2007;49:2028<br />
  48. 48. Nasal continuous positive airway pressure (CPAP):<br />Combined OSA/CSA<br />CSA in supine position <br />CSA in CHF: Canadian Positive Airway Pressure (CANPAP) trial: transplant-free survival curve favored the control group<br />NIPPV: hypercapnic central apnea/hypopnea and nocturnal ventilatory failure <br />CSA Treatment <br />
  49. 49. Pharmacologic:<br />Acetazolamide<br />Theophylline ameliorates Cheyne-Stokes respiration (CSR) in patients who have CHF<br />Supplemental O2: idiopathic CSA and CHF with Cheyne-Stokes respiration <br />Supplemental CO2: effective in eliminating central apnea by virtue of elevating PaCO2 above the apneic threshold <br />CSA Treatment<br />
  50. 50. 35 yo male nurse with excessive daytime sleepiness since age of 15<br />Denies snoring, witnessed apneas<br />reports irresistible sleep attacks, short naps are refreshing<br />Jaw drop and knee buckling when laughing or angry<br />Case#3<br />
  51. 51. NPSG : <br />no sleep disorder/ treated sleep disorder<br />Short latency to REM sleep<br />Fragmented sleep<br />MSLT:<br />5 naps:<br />mean sleep latency is less than 5 or 6 minutes <br />Sleep Onset REM Period (SOREMP) on 2 or more naps<br />Narcolepsy<br />
  52. 52. Morrish et al (Factors associated with a delay in the diagnosis of narcolepsy.<br /> Sleep Med. 2004 Jan;5(1):37-41) <br />Survey of members of the Narcolepsy Association UK:<br />The interval between symptom onset and diagnosis ranged from within 1 to 61 years with a median of 10.5 years<br />Narcolepsy <br />
  53. 53. 0.05% in the United States<br />Narcolepsy pentad: <br />Excessive daytime sleepiness<br />Cataplexy<br />Sleep paralysis<br />Hypnagogic / hypnopompic hallucinations<br />Fragmented sleep<br />Narcolepsy<br />
  54. 54. HLA DQB1∗0602 in >90% of patients with cataplexy<br />Narcolepsy in dogs has been linked to an AR mutation of the gene coding for the hypocretin (orexin) receptor 2 <br />In humans, no detectable hypocretin (orexin) can be found in the cerebrospinal fluid (CSF)of up to 90% of narcoleptics who have cataplexy <br />Narcolepsy<br />
  55. 55. Narcolepsy:<br />Sleep hygiene<br />Scheduled Naps and regular nocturnal sleep times<br />Medications: Amphetamines, modafenil and armodafenil, Sodium oxybate<br />Cataplexy:<br />TCA and Fluoxetin, Sodium oxybate<br />Future Directions<br />Fetal cell transplant <br />Orexin/ Hypocretin agonists<br />Treatment<br />
  56. 56. 36 yo woman CC of difficulty initiating sleep <br />Regular bed time <br />unpleasant crawling sensation in legs, relieved by moving legs or walking<br />Tired during the day, bed partner reports frequent kicking <br />No snoring or witnessed apneas<br />Case#4<br />
  57. 57. PE: unremarkable, normal neurologic exam<br />Laboratory: within normal including iron studies<br />NPSG: prolonged latency to sleep onset, increased leg movement prior to sleep onset<br />Case#4<br />
  58. 58.
  59. 59. PLM’s: “periodic episodes of repetitive and highly stereotyped limb movements that occur during sleep.”<br />Clinically: insomnia and excessive daytime sleepiness <br />no significant association with objective or symptomatic reports of insomnia or daytime sleepiness<br />PLMD: in association with medications, narcolepsy and obstructive sleep apnea <br />Periodic Limb Movement Disorder<br />
  60. 60. PRO : <br />Marker of sleep fragmentation<br />Potential cardiovascular risk factor<br />Predictor of mortality in end-stage renal disease.<br />CON<br />49% of the EEG arousals occurred before the leg movement,31% simul-<br /> taneous ,23%after.<br />NO valid studies documenting that treating isolated PLMs improves either nighttime sleep or daytime functioning in any condition.<br />PLM’s: Do they have any clinical relevance?<br />
  61. 61. RLS: 2% and 6% of the population<br /> (1) an urge to move the limbs <br /> with or without sensations<br /> (2) worsening at rest<br /> (3) improving with activity<br /> (4) worsening in the evening or <br /> night <br />Restless Leg Syndrome<br />
  62. 62. Pathophysiology : <br />central nervous system (CNS) iron homeostatic dysregulation<br />Iron seems to play a role in normal dopaminergic function in the central nervous system, related to dopamine transport and dopamine synthesis<br />Work up: <br />Ferritinlevel < 50 μg/L <br />Elctrolytes, renal function<br />B12, Folate, and cobalamine<br />Restless leg syndrome<br />
  63. 63. Restless leg syndrome<br />Familial: positive family history <br />Primary : if no other explanation <br />Secondary : <br />renal failure<br />iron deficiency<br />Neuropathy/ myelinopathy<br />pregnancy<br />Parkinson's disease (PD)/essential tremor<br />genetic ataxias <br />fibromyalgia /other rheumatologic diseases<br />
  64. 64. Caffeine<br />Antidepressant medications: fluoxetine, paroxetine (Paxil), sertraline (Zoloft), mirtazapine (Remeron), and mianserin<br />Neuroleptics, such as olanzapine (Zyprexa) and risperidone (Risperdal) <br />Others: β-blockers, phenytoin (Dilantin), zonisamide (Zonegran), methosuximide, and lithium<br />??? smoking<br />MedicactionInduced RLS/PLMD<br />
  65. 65. Dopamine agonists: ropinirole, pramipexole, pergolide, <br />bromocriptine, apomorphine, cabergoline<br />Opiates<br />Gabapentin<br />Iron supplement if Ferritin < 50<br />Bupropion (Wellbutrin)<br />Treatment <br />
  66. 66. 35 yo woman<br />Cc: difficulty initiating and maintaining sleep for years<br />Daytime fatigue, no excessive daytimesleepiness<br />Now newly engaged and experiencing worsening of insomnia<br />PMH – anxiety, phobia of flying in recent years<br />Meds – OCP<br />Case # 5<br />
  67. 67. Medical History<br />Alcohol/ caffeine/ medications<br />Bedtime routine <br />Bedroom environment<br />Bedtime / time to sleep onset / continuity of sleep / awakenings <br />Daytime function <br />Insomnia Interview<br />
  68. 68. Model for evolution of Insomnia<br />
  69. 69. Model for evolution of Insomnia<br />
  70. 70. Sleep medications:<br />may provide rapid relief of the symptoms of insomnia<br />many of these medications have side effects <br />Have not been shown to be effective for long-term treatment of insomnia.<br />Insomnia Treatment Pharmacologic therapy<br />
  71. 71. Insomnia Treatment Pharmacologic therapy<br />Hypnotic medications:FDA approved for short term use (Eszopiclone for long term)<br />Antidepressants (amitriptyline and trazodone): have a calming or sedative effect can be used to aid sleep. <br />Antihistamines: may be effective for short-term relief of sleeplessness. <br />Non prescription sleep medications: habit-forming and cause rebound insomnia. Should not be used for more than 7 to 10 days. <br />Rozerem: Melatonin Agonist. <br /><ul><li>Future direction: Orexin/ HypocretinAntagonists</li></li></ul><li>Non-Pharmacologic Insomnia Treatment <br />The most successful long term treatment <br />Relaxation therapy : progressive muscle relaxation, in which different muscle groups are tensed and relaxed, as well as attention-focusing techniques such as meditation, which can help stop sleep-disturbing habits. <br />Cognitive behavioral therapy: recognize certain beliefs a patient holds about self and sleep, to change those beliefs that may contribute to unhealthy patterns, and to introduce positive behaviors that will help create an inviting environment for sleep. <br />Sleep hygiene measures: simple actions that address sleep habits and factors that may keep people from good sleep.<br />Stimulus control therapy: reestablishes the bed as a place for sleeping and sex only-not for sleeplessness. ( can't fall asleep in 15 minutes, get out of bed and do something quiet and relaxing until sleepy again). <br />Sleep restriction therapy: limits the time spent in bed to time spent sleeping. <br />
  72. 72. Sleep Medicine Specialists<br />Behavioral Sleep Medicine Specialists<br />Dental Sleep Medicine Specialist<br />Louisville Sleep<br />
  73. 73.<br />Thank You<br />QUESTIONS?????<br />