1. Obstructive Sleep Apnea and Other Causes of Excessive Daytime Sleepiness

2. Patient Scenario #1
A 45 year old man sought treatment of his snoring, which had been present for many years. His wife slept in another room because the snoring “shook the walls”. The patient reports excessive sleepiness (Epworth sleepiness scale score 18/24. Normal is 10 or less), morning headaches and problems concentrating at work. He admits to drinking more than five cups of coffee daily. There was no history of recent weight gain or alcohol use.

3. The Physical Examination
Height: 5 feet 10 inches
Weight: 190 pounds; Blood Pressure: 150/90
Neck 18 inch circumference
HEENT: long, edematous uvula, dependent palate (low lying)
Chest: clear
Cardiac: normal
Extremities: no edema

4. What is The Next Step?
Sleep Apnea is the most common cause of excessive daytime sleepiness and snoring, but there are many other disorders that must be carefully considered.

5. Evaluating Causes of Excessive Daytime Sleepiness (EDS)
Disorders
Evaluation
All Cases
Sleep Apnea Syndromes
Upper airway resistance syndromes
Narcolepsy
Periodic leg (limb)movements in sleep
Restless leg Syndrome
Circadian Sleep Disorders
Insomnia
Withdrawal from Stimulants
Drug dependence/Abuse
Medication side effects
Idiopathic Hypersomnia
Brain tumors
Parasomnias
History
Self-rating scale of Sleepiness
Sleep-wake diary
Polysomnography
Selected Cases
MSLT
Drug Screen

6. Epworth Sleepiness Scale: Measures average sleep propensity (chance of dozing) over 8 common situations that almost everyone encounters.
Situation
Chance of Dozing
Sitting and reading
Watching T.V.
Sitting inactive in a public place (i.e., theater, meeting)
As a passenger in a car for 1 hour without a break
Lying down to rest in the afternoon when circumstances permit
Sitting talking to someone
Sitting quietly after lunch without alcohol
In a car while stopped for a few minutes in traffic
Total
0-3
0-24 (0-10 normal)
3= High chance of dozing; 2=moderate; 1=slight; 0=never

7. Stanford Sleepiness Scale: Measures subjective feelings of sleepiness
Feeling active and vital; alert, wide awake
Functioning at a high level, but not peak, able to concentrate
Relaxed, awake, not at full alertness, responsive
A little foggy, not at peak, let down
Fogginess, beginning to lose interest in remaining awake, slowed down
Sleepiness, prefer to be lying down, fighting sleep, woozy
Almost in reverie, sleep onset soon, lost struggle to remain awake 1 2 3 4 5 6 7

8. Obstructive Sleep Apnea (O.S.A)
OSA is a common disorder occurring in 4% of men and 2% of women.
During sleep, closure of the upper airway results in cessation or diminished airflow despite continued respiratory effort. The termination of the apneic event is associated with a brief awakening.
These arousals result in sleep fragmentation which reduces the amount of slow wave and REM sleep and causes varying degrees of daytime sleepiness.

9. Risk Factors for Sleep Disordered Breathing
Excess body weight
Large neck circumference
Male gender
Ethnicity
Age
Menopause
Anatomy of airway=soft and hard palate.

10. Indicators for a Polysomnography (PSG)
Suspicion of disorders that disturb sleep like sleep apnea, periodic limb disorder, REM behavior disorder
EDS
Obesity
Insomnia with daytime sleepiness
Nocturnal behavioral disorders

11. Polysomnography
Multiple physiologic parameters are measured and compared with the established norms.
Electrocardiography (EKG)
Electroencephalography (EEG)
Electro-oculography (EOG)
Electromyography (EMG)
Pulse Oximetry
Respiration:
-Effort (chest and abdominal movements)
-Airflow
Snore sensor/microphone
Heat sensors measure airflow by detecting temperature changes in inspired and expired air
*Sleep conditions in the laboratory should be as close to the patients baseline sleep as possible.

12. Human Sleep Architecture
Wake
NREM sleep
Stages 1 and 2 (light sleep)
Stages 3 and 4 (deep sleep)
REM sleep
*Recognition of certain characteristic EEG patterns is essential for staging sleep

13. Electroencephalographic Lead Placement
Central
Occipital
Mastoid
*More electrodes can be added if nocturnal seizure is in the differential

14. Monitoring Eye Movements
Standard : 2 eye channels
Detecting horizontal/vertical eye movements
Determining various stages of sleep

15. Electromyography (EMG)
Diagnosis of Periodic Limb Movements(PLMS)
Chin movement
Diagnosis of certain sleep stages

16. Monitoring Respiration During Sleep
Apnea – cessation of airflow at the nose and mouth for 10 seconds or longer
Central Apnea – an absence of inspiratory effort
Obstructive Apnea – absence of airflow despite persistent respiratory effort
Mixed Apnea – initially no inspiratory effort…then terminates as an obstructive event
Hypopnea – reduction in airflow by 30% from baseline for > 10 seconds with > 4 % drop in oxygen saturation (controversial)
Respiratory Effort Related Arousals(RERAs) – an event not meeting the above criteria, yet produces an arousal from sleep.

17. Important Sleep Parameters on PSG
Sleep stages (percentage)
Sleep efficiency
Apnea Hypopnea index (AHI), Respiratory Disturbance Index (RDI), paradoxical respiration; desaturations and cardiac arrhythmias

18. Sleep Hypnogram

19. Diagnosis of OSA
The Apnea + Hypopnea Index (AHI) a.k.a Respiratory Disturbance Index (RDI) = The Number of Apneas + hypopneas Per Hours of Sleep

20. Treatment of OSA Obesity- Diet and behavior modification
Positional Therapy
-non-supine sleep (pillow, etc.)
-raise the head of the bed
Nasal CPAP, BiPAP, Auto CPAP
Oral appliances
Soft tissue surgery or UPPP (Uvulopalatopharyngoplasty)
Skeletal surgery
Tracheotomy

21. Significance of Sleep Disordered Breathing
Risk factor for stroke
Risk factor for cardiac arrhythmias
Risk factor for CAD and M.I.
Risk factor for pulmonary hypertension and right heart dysfunction
Cause of hypertension

22. Patient Scenario #2
A 40 year old man was referred because his wife complained that he kicked in his sleep and constantly disturbed her. The patient remembered awakening several times each night, but never noticed any discomfort at those times. He admitted that at bedtime he did have an irresistible urge to move his legs and he described a feeling of “pins and needles.” However this delayed his sleep only rarely. His Epworth Sleepiness Scale was 15/24 (sleepy).
PSG shows: Periodic leg movements in sleep (PLMS) – 20% of these events were associated with arousals.

23. Periodic Leg Movement in Sleep (PLMS)
PLMS are repetitive, stereotypic dorsiflexion movements of the toes, ankles, knees and thighs that recur at regular intervals. They occur most commonly in stages 1 and 2 but can occur less commonly in other stages. Patients are rarely aware of the leg movements themselves and complaints are usually from bed partners.

24. Periodic Leg Movement Disorder PLMD
This is a syndrome of leg movements + symptoms (ie. insomnia or excessive daytime sleepiness.
This is a polysomnographic diagnosis; but, it is often incorrectly used interchangeably with Restless Leg Syndrome.
International Classification of Sleep Disorders Criteria for PLMS Severity
Severity
PLM Index/Hour
PLM Arousal Index/Hr
Mild
5 - 24
Not specified
Moderate
Severe
> 50
> 25/ hour

25. Restless Leg Syndrome (RLS)
Characterized by abnormal and uncomfortable sensations in the limbs that compel the person to move to relieve the sensation and these movements are exacerbated by rest. The symptoms occur primarily in the evening or at night.

26. International RLS Study Group Criteria for Diagnosis of RLS
Primary Features
Associated Features
Unpleasant limb sensations: desire to move the limbs usually associated with paresthesias/dysesthesias (abnormal/unpleasant sensations)
Motor restlessness: patient is compelled to move
Symptoms precipitated by rest and relieved by activity: symptoms are worse or exclusively present at rest (i.e., sitting or lying with at least partial and temporary relief by activity
Symptoms worse in the evening or at night
Sleep disturbance and consequences: difficulty initiating or maintaining sleep; less commonly, excessive daytime sleepiness
Involuntary movements during wake or sleep (PLMS)
Normal neurologic exam in primary RLS; in secondary forms, possible evidence of neuropathy
Clinical course: onset any age, usually chronic and progressive, remissions may occur, can be exacerbated by or exclusively during pregnancy
Family history: sometimes present; suggestive of autosomal dominant pattern

27. PSG : Quasi-periodic movements of the legs during wakefulness with a prolonged sleep latency. After sleep, PLMs are noted in 70 –90% of Patients
PLMs
RLS

28. Differential Diagnosis of RLS
Neuropathy
Claudication
Painful toes and moving leg syndrome (lumbrosacral radiculopathy)
Neuroleptic akathesia

29. Causes and associations of PLMs
Any cause of RLS
Withdrawal of anti-convulsant, barbiturates, hypnotics
Associated with narcolepsy, OSA, CPAP titration
Causes of RLS/PLMD
Primary RLS
Secondary RLS
Fe deficiency anemia
ESRD
Pregnancy
Medications
-caffeine
-TCA’s
Cause unknown
? If there’s an abnormality in Fe (iron) transport into the CNS or a defect in the use of Fe as it relates to dopaminergic neurons.
-SSRI’s
-Dopamine blockers

30. Treatment options for RLS/ PLMs
Nonpharmacologic-avoid etoh, caffeine, do light stretching, exercise, warm baths
Dopaminergic agents (ie, Sinemet)
-Treats PLMs and improves sleep quality
Dopamine agonists
Benzodiazepines
Narcotics (usually reserved for severe cases)

31. Patient Scenario #3
A 30 year old woman was evaluated for excessive daytime sleepiness of 5 year duration. There was no history of snoring or observed apnea. The patient recalled having difficulty holding her head up when she laughed or was embarrassed. The patient’s husband reported that sometimes she kicked the covers at night. Rarely, the patient felt she could not move for a while as she was falling asleep at night.

32. 7 of 9 patients with narcolepsy had low orexin levels in their CSF.
Narcolepsy is related to abnormal regulation of REM sleep and inappropriate intrusion of REM sleep physiology into wakefulness.
1998 Hypocretin/orexin (2 peptides) secreted by the hypothalamus and other brain areas.
2 major pathways:
-hypothalamus cortex
-hypothalamus Brain stem
-locus ceruleus- NE secreting neurons important in maintaining wakefulness
7 of 9 patients with narcolepsy had low orexin levels in their CSF.
Other studies have shown an absence of orexin-secreting neurons in the hypothalamus
Antigen DQB1* 0602 is the most sensitive marker for narcolepsy across all ethnic groups

33. Narcolepsy is a Neurological Disorder Characterized by:
Pathognomonic
Prevalence
Symptoms
100%
70%
66%
60%
Excessive daytime sleepiness (EDS); sleep attacks
Cataplexy-loss of muscle tone during periods of high emotion
Hallucinations: Hypnagogic (dreaming at sleep onset)/hypnopompic (dreaming just after awakening)
Sleep paralysis-loss of muscle tone at sleep onset or on awakening
Disrupted nocturnal sleep
Automatisms
Can be followed years later by the other SX’s

34. Narcolepsy
Prevalence of disorder is % in the general population
Adolescence is the common age of onset
Second peak at about 40 years of age
(5% of cases start after age 50)

35. Secondary Narcolepsy Head Trauma Stroke MS Neurodegenerative Disorders
Brain tumors
CNS infections
PSG Findings:
Short REM Latency (low sleep efficiency) Sleep fragmentation; reduced slow wave sleep; +/- PLMs

36. Indications for a Multiple Sleep Latency Test (MSLT)
Unexplained hypersomnolence (sleepiness); sleep apnea and other disorders.
Narcolepsy: to confirm diagnosis and determine the severity before stimulant therapy.
Insomnia with daytime sleepiness.
Circadian rhythm disorders

37. MSLT Scoring and Interpretation Testing
Consists of 4-5 naps at 2 hour intervals conducted in the daytime commencing hours after waking from the PSG.
A mean sleep latency of <5 minutes and 2 or more naps with REM sleep.

38. Treatment of Narcolepsy
Sleep hygiene
Optimizing the amount of sleep
If able, regularly schedule naps during the day (if restorative)
Tx of Daytime Sleepiness
Stimulants are working to increase the availability of NE/DA
Largest doses should be given 1 – 2 hours before the periods of maximum sleepiness
methylphenidate
dextroamphetamine
selegiline
modafinil
Tx of Cataplexy/Hallucinations
TCA’s
Venlafaxine (Effexor)
Tegretol
GHB (Xyrem)

39. Insomnia Patient Scenario #4
A 30 year old Female is referred for complaints of inability to sleep for more than 10 years. The patient reports it usually takes her 2 to 3 hours to fall asleep after going to bed. She also finds herself awakening 3 to 4 times during the night. She reports that it takes at least 30 minutes to fall back asleep after each awakening. Alcohol and over the counter medications sometimes helped. During the day, fatigue, but not definite sleepiness was noted. Her husband denied that she snores, kicks, or jerks during sleep.

40. Insomnia Sleep onset insomnia Sleep maintenance insomnia
Early morning awakening
Non-restorative sleep

41. Common Causes of Insomnia
Primary Insomnia Secondary Insomnia
Psychophysiological
Acute (adjustment sleep disorder)
Chronic
Idiopathic
Sleep state misperception
Sleep disorders (sleep apnea, PLMD, RLS)
Psychiatric disorder(depression, panic attacks)
Inadequate sleep hygiene
Environmental sleep disorder
Drugs (nicotine, ethanol, caffeine)
Medical conditions/medications
Fibromyalgia and chronic pain syndromes
COPD and other respiratory disorders
Medications (beta blockers, theophylline)
Circadian disorders
Delayed sleep phase syndrome
Advance sleep phase syndrome
Shift work or jet lag syndrome

42. Insomnia History Nature and Duration of problem Sleep habits
Time in bed, lights out, sleep onset, wake time
Bedroom environment
Timing and duration of naps
Changes on weekends
Effects of a new sleep environment (vacation)
Medication/beverage history
Symptoms of depression. History of leg jerks, restless leg syndrome, snoring, apnea

43. Diagnosis of the cause of Insomnia based on: Careful History
Review of Patient’s sleep diary
PSG: Typically normal and may not be beneficial unless there’s a suspicion of another underlying sleep disorder Or
Insomnia is severe and doesn’t respond to empiric therapy.

44. Treatments for Insomnia
Optimize sleep hygiene
Behavioral techniques
relaxation therapy
stimulus control therapy
Sleep restriction therapy
Cognitive behavioral treatment
Combined behavioral and pharmacological treatment
Benzodiazepines
BZ receptor agonists (ie ambien, sonata)
Sedating anti-depressants

45. Patient Scenario #4A
-Same as previous patient. She averages 4 hours/night of sleep with EDS
-On weekends able to sleep in and get 7 to 8 hours of sleep and awake feeling refreshed.

46. Sleep Disorders Associated with Alterations in Circadian Rhythm
Delayed sleep phase syndrome
Advance sleep phase syndrome
Time zone change (jet lag) syndrome
Shift work sleep disorder
Irregular sleep wake pattern
Non-24-hour sleep –wake disorder

47. Circadian rhythms are generated by an internal pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus
The main role of the SCN is to synchronize bodily functions with the light – dark cycle.

48. Diagnosis: History Sleep Diary
Treatment:
Chronotherapy (progressive phase delay)
Bright light therapy
Melatonin
Short-acting hypnotics

49. Parasomnias: A motor, verbal, or experiential phenomenon that occurs during sleep and is often undesirable

50. Differential Diagnosis of Unusual Behavior Associated With Sleep
Diagnosis Usual Sleep Stage
Normal Sleep Phenomena
Sleep starts (hypnic jerks) Sleep onset
Nightmares (REM anxiety attacks) REM>>NREM
Parasomnias
Sleep walking (somnabulism) NREM
Sleep terrors NREM
Confusional arousal NREM
Sleep talking (somniloquy) NREM and REM
REM behavior disorder REM
Parasomnia overlap disorder NREM and REM
Bruxism NREM (stage 2)
Enuresis NREM and REM (random)

51. Psychiatric Disorders
Panic attacks NREM (transition stage 2 to stage 3)
Posttraumatic stress syndrome REM and NREM
Seizure Disorders
Nocturnal seizures NREM>Wake>REM
Possible seizure Disorders
Nocturnal paroxysmal dystonia
Episodic nocturnal wandering