1. Clinical Sleep Disorders Meena Khan MD Assistant Professor, Department of Neurology and Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine Meena.Khan@osumc.edu

2. Learning Objectives  Understand the diagnostic procedures used in sleep medicine and their appropriate use  Understand the following sleep disorders  Insomnia  Obstructive sleep apnea  Narcolepsy  Parasomnias  Restless leg syndrome

3. Diagnostic Procedures  Overnight Polysomnograpy (PSG)  Study done at night while patient is sleeping  Purpose is to diagnose obstructive sleep apnea and periodic limb movements of sleep  Multiple mean sleep latency test (MSLT)  Daytime study  Purpose is to objectively evaluate a person’s tendency to fall asleep during the day

4. Diagnostic Procedures  Overnight Polysomnograpy (PSG)  There are 2 types of polysomnography that can be conducted  Full PSG done in the sleep lab  Portable study that can be done at home

5. Diagnostic Procedures  Full Polysomnography (PSG)  Done in the sleep lab Sleep staging Respiratory flow and effort Pulse oximetry Leg movements

6. Diagnostic Procedures  Portable PSG  Can be done at home Respiratory flow and effort Pulse oximetry

7. Diagnostic Procedures  Multiple sleep latency test  5 nap opportunity to fall asleep and see if one achieves REM sleep  Each nap Lights turned off and pt asked to try to fall asleep The patient is given 20 min to see if they can fall asleep and if they do- 15 more min to see if they achieve REM sleep REM within 15 minutes of falling asleep- sleep onset REM period (SOREM) Record the sleep latency (time to fall asleep) and the presence of REM sleep.

9. Common sleep disorders  Disorders of hypersomnia  Obstructive Sleep apnea  Narcolepsy  Disorders leading to inability to sleep  Insomnia  Restless leg syndrome  Abnormal behavior associated with sleep  Parasomnias

10. Disorders of Hypersomnia  Obstructive sleep apnea (OSA)  Narcolepsy

11. Obstructive Sleep Apnea (OSA)  Intermittent collapse of the upper airway during sleep  Mechanism of collapse is reduced upper airway size and altered control of upper airway muscles

12. Obstructive Sleep Apnea (OSA)  What happens as result of closure of the upper airway??  Arousals from sleep - unrefreshing sleep and daytime sleepiness  Drops in oxyhemoglobin saturation- cardiovascular morbidity and mortality Hypertension Myocardial infarction Stroke Death

13. Symptoms  Nighttime symptoms  Snoring- loud and habitual  Gasping/choking during sleep  Witnessed apneas  Awakenings during sleep  Restless sleep  Daytime symptoms  Unrefreshing sleep  Fatigue/Sleepiness  Impaired concentration/memory

14. Risk Factors for OSA  Obesity (BMI>=30)  Male gender (2-3:1)  Menopausal women (M:F- 1:1)  Age>=65 yrs  Neck size  Male neck size >=17in.  Female >=16 in.  Family history -inc by 2-4 fold  Race Africa Am and Asians

15. Factors that contribute to increased OSA severity  Weight gain (10% inc in body weight associated with 32% increase in AHI)  Alcohol- prolong apnea and worsen associated hypoxemia  Sedatives (benzodiazepines, anesthetics, narcotics)  Current smoking (assoc w/higher prevalence of snoring and OSA) Proc Am Thorac Soc 2008; Vol 5; 136-143

16. Obstructive Sleep Apnea  Two types of airway closures that occur in obstructive sleep apnea  Apnea  Complete closure of the airway resulting in absence of airflow  Hypopnea  Partial closure of the airway leading to decrease in airflow associated with a drop in oxyhemoglobin saturation

17. Apnea Absence of air flow for >=10 seconds

18. Hypopnea Decrease in airflow of >=10 seconds with oxygen desaturation of >= 4%

19. Obstructive Sleep Apnea  Presence and severity of obstructive sleep apnea is measured by the number of apneas and hypopneas per hour of sleep.  This measurement is called the apnea- hypopnea Index (AHI) Normal AHI <5 Mild OSA-AHI of >=5 to <15 Moderate is AHI of 15>= to <30 Severe is AHI>=30

20. Treatment of OSA  Behavioral modification  Weight loss  Positional therapy  Interventional treatment  Continuous positive airway pressure (CPAP)- Gold standard of therapy  Oral appliance  Surgery

23. Narcolepsy  Clinical Features  A syndrome of excessive daytime somnolence and abnormalities of REM sleep.  Tetrad of symptoms Excessive daytime sleepiness- first symptom Cataplexy Hypnogogic/hypnopompic hallucinations Sleep paralysis  Disturbed nocturnal sleep Abnormalities of REM sleep

24. Narcolepsy  The prevalence is 0.05%  The prevalence is increased at 1-2% for family members of those with narcolepsy  Onset of symptoms is typically the second decade usually between ages 10 – 25 years.

25. Narcolepsy  Etiology  Dysfunction of hypothalamic hypocretin systems.  Hypocretin 1 is in the lateral hypothalamus and has role in sleep-wake regulation.  This is deficient in narcoleptics with cataplexy and thought to be the etiology of the syndrome.  There is also an association with gene- DQB1*0602.

26. Narcolepsy  Standard for diagnosis is an in lab full PSG/MSLT  PSG- 360 minutes of total sleep time without presence of OSA  MSLT- Mean sleep latency (MSL) of =2 naps with SOREM.

27. Narcolepsy  Supplementary testing  Gene test for DQB1-0602: This gene is positive in 95% of those with narcolepsy with cataplexy but also is present in 18-35% of the general population  Cerebrospinal fluid (CSF) hypocretin levels: 94% of narcolepsy with cataplexy will have CSF hypocretin level <110 pg/ml. All those with a low hypocretin level will be positive for the DQB1- 0602 gene.

28. Narcolepsy- Treatment  Behavioral management  Adequate nocturnal sleep  Scheduled naps  Good sleep hygiene  Support groups National Sleep Foundation Narcolepsy Network

29. Narcolepsy- Treatment  Pharmacologic management  Excessive daytime sleepiness Stimulants  Modafinil /Armodafinil  Amphetamine salts Sodium oxybate (xyrem)  Cataplexy Sodium oxybate REM suppressing medication  Venlafaxine

31. Disorders that lead to inability to sleep  Insomnia  Restless leg syndrome

32. Definition of insomnia  Repeated difficulty with sleep initiation, duration, consolidation, or quality that occurs despite adequate time and opportunity for sleep and results in daytime impairment.  Impairments  Fatigue, depressed mood, irritable, cognitive impairment  Physical symptoms- HA, GI upset  Marked distress and/or significant impairment in social or occupational functioning.

33. Insomnia  Common sleep disturbance  Survey in 2005  75% have had a sleep problem  50% had one symptom of insomnia over the previous year  1/3 reported nightly symptoms National sleep foundation 2005 sleep in America poll  Underreported and under treated  5% of pts with insomnia seek medical treatment  26% mention it to physicians during visits for other complaints

34. Insomnia  Chronic insomnia  Correlated with increased morbidity:  Higher disability levels  Increase calling off work  Frequent use of medical resources- doctor visit/testing/medication  Chronic health problems  Increased use of drugs  Decreased quality of life 34

35. Risk Factors for insomnia  Female- risk 1.3 times higher than men  Older age (age >65- 1.5X more likely to experience insomnia)  Divorced/ separated/widowed  Low economic/education  Poor health  Mood D/O  Chronic medical problems  Substance abuse- recovery period

36. Features of chronic insomnia  Life and thoughts revolve around sleep and the effect of lack of sleep  Sleep anticipatory anxiety about not being able to sleep  Clock watch  Calculate time left for sleep  Strong and at times unrealistic thoughts about sleep requirements and daytime consequences due to lack of sleep

37. Insomnia Dysfunctional thoughts Anxiety about sleep Neg thoughts about sleep/and daytime symptoms AND Maladaptive Behavior Too much time in bed Irregular sleep schedule Naps or resting during the day Watch TV/ read etc Caffeine and alcohol use Trigger event Predisposition 1.Hyperarousal 2.Tend to ruminate 3. Blunted sleep homeostasis Insomnia

38. Treatment Pharmacologic Recommended for short term use although no medical contraindication for long term use Cognitive Behavioral Therapy Cognitive therapy Aimed at maladaptive thoughts about sleep Behavioral therapy Aimed at maladaptive behaviors Sleep hygiene Relaxation Therapy Stimulus Control Sleep restriction

39. Sleep Hygiene  Educate about lifestyle and bedroom environment factors that can promote good sleep  The bedroom should be dark, quiet, and comfortable  Avoid watching TV, reading, using the computer or doing other activities other than sleep in the bedroom.  No caffeine at least four hours before bed  Avoid tobacco at night  Avoid alcohol at least 4 hours before bed  Exercise late afternoon, early evening

40. Relaxation Therapy  Goal- reduce sleep related tension  Somatic, mental relaxation and biofeedback  Regularly practice therapies during the day and implement them while in bed

41. Stimulus Control  Aimed at idea that those with insomnia have developed an association of their bedroom with poor sleep  Goal is to re-associate bedroom with rapid sleep  Eliminate the stimuli that interfere with sleep in the bedroom -bed for sleep only- Avoid reading, TV, eating, talking on the phone  Go to bed only if sleepy  Get out of bed if no sleep after 20 min  Same rise time every AM  Avoid naps

42. Sleep restriction  Insomniacs tend to increase time in bed to allow for more sleep but this results in decreased sleep efficiency (ex: in bed for 8-9 hours but only sleep 5-6 hours)  Goal  Restrict person’s time in bed so there is a better match of sleep time to time in bed Example- someone states they sleep only 6 hours. Have them pick a wake time- must get up at that time every morning Bedtime is 6 hours before that Should only be in bed for those times Ex- wake time is 6 AM, bedtime would be 12 am. Never restrict less than 5 hours

43. Restless Leg Syndrome (RLS)  4 cardinal criteria  Abnormal sensation leading to urge to move legs  Movement of legs improves sensation  Occurs at rest  Occurs mostly at night

44. Restless Leg Syndrome (RLS)  Etiology: Most cases are idiopathic but can be hereditary. There are also secondary causes of RLS which include:  iron deficiency anemia  pregnancy  end stage renal disease  medications  peripheral neuropathy  Diabetes  Rheumatoid arthritis

45. Restless Leg Syndrome (RLS)  Diagnosis- made by history not sleep study  Evaluation and treatment  Check serum ferritin (should be >=50) – if less than 50 than give patient iron supplementation  Standard medical therapy- dopamine agonists

46. Periodic Limb Movements of Sleep  Leg movements that occur during sleep  Commonly seen in patients with RLS  Diagnosis made by sleep study  Evaluation and Treatment is same as RLS

48. Abnormal movements during sleep  Parasomnias  Definition  Undesirable and typically abnormal motor or subjective phenomena that occur during the transition of wake/sleep or during arousals from sleep

49. Parasomnias  NREM Parasomnias  Confusional arousals  Sleep walking  Night terrors  REM Parasomnias  REM behavior disorder

50. NREM Parasomnias  NREM (Disorders of Arousal)  Occur during slow wave sleep (SWS)  First third of sleep when SWS more prominent  Occurs in 20% children- most resolve once child reaches adulthood but 25% persist into adulthood  Occurs in 4% adults

51. NREM Parasomnias  Confusional arousals  Arousals out of NREM sleep- associated with confusion and disorientation  Simple or complex movements in bed without walking or night terror behavior  Amnestic of event  Not violent but may become agitated if forcibly awakened

52. NREM Parasomnias  Sleep walking  Ambulation with impaired consciousness- behavior is inappropriate Ex: Cook, eat, drink, play instruments, drive a car  Memory impairment for the event but the person may remember fragments  Difficult to arouse person during an event

53. NREM Parasomnias  Night terrors  Sudden arousal from sleep with scream or cry  Afraid, anxious, panicked, fearful, disoriented  Inconsolable!!!!!!  Motor activity- intense and disorganized  Autonomic activity Tachycardia, tachypnea, sweating, flush skin, mydriasis  Amnestic to event- increased agitation if try to arouse

54. REM sleep behavior disorder (RBD)  Person has loss of normal muscle atonia that occurs during REM sleep  Clinical symptoms  Dream enactment behavior-moving in response to content of their dreams  Dream content may be more violent leading to violent actions  Typically patient is alert if awoken during the event and can recall the dream vividly

55. RBD  More common in age>50  Males > females (9:1)  Often associated with the development of neurological disorders- most commonly- Parkinson’s disease

57. Conclusions  A good history is key to the diagnosis of most if not all sleep disorders  Sleep studies of various types have a specific role to diagnose certain sleep disorders but are not beneficial to diagnose all sleep disorders or to be done without a specific goal in mind.

58. Thank you for completing this module Questions? Contact me at: Meena.Khan@osumc.edu

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