Sleep & Sleep Disorders

Ting-hsu Chen, MD MPHtchen@bu.edu

Section of Pulmonary & Critical Care Medicine

Overview

• Normal sleep• Sleep deprivation and sleepiness• Specific sleep disorders: diagnosis & treatment

– Obstructive Sleep Apnea (OSA)– Narcolepsy– Restless Legs Syndrome (RLS)– Insomnia

Normal sleep

• Restorative function

• Oxidative repair

• Memory consolidation

• Extreme deprivation leads to death

© American Academy of Sleep Medicine

Interaction of Circadian Rhythms and Sleep

Time

9 PM9 AM 9 AM

SleepWake

Sleep Homeostatic drive (Sleep Load)

Circadian alerting signal

Alertness level

3 PM 3 AM

Sleep deprivation

• Excessive daytime sleepiness is common• Behavioral and physiological consequences

– Psychomotor impairment– Memory deficits– Mood effects– Insulin resistance– Blunted immune response

• Self-assessment may not be reliable• Sleep deprivation is cumulative

Rears T, et al. Daytime sleepiness and alertness. In: Kryger MH et al. (eds). Principles and Practice of Sleep Medicine. 4th Edition. Philadelphia: Elsevier Saunders; 2005: 40. MSLT = Multiple Sleep Latency Test

TIB = time in bed

Daytime sleepiness

Sleepiness in the Clinician

• Survey of 697 emergency medicine residents at Wayne State University (Kowalenko. Acad Emerg Med. 2000;7:451.)– 17% had MVAs– 6.7x more likely to fall asleep driving than prior to

residency

• Anesthesiology residents did not perceive themselves to be asleep almost half of the time they had actually fallen asleep. (Howard. Acad Med. 2002;77:1018-1925.)

Case

• A 55yo man presents to your clinic. His wife complains about his snoring and told him that he stops breathing when he sleeps. He sleeps 9 hours a night and falls asleep immediately, but never feels rested when he wakes up. He tends to doze off during meetings at work. He has fallen asleep driving home from work a couple of times, usually at a stop light.

• Height: 5’8”. Weight 210#. BMI 31.9. Crowded posterior oropharynx (MP III). Enlarged uvula.

“Classic” OSA profile

• Male• Middle-age• Obese• Snoring• Daytime sleepiness• Hypertension

OSA in women

• Similar daytime sleepiness (ESS)• More morning headaches• “Atypical presentations”

– Depression– Hypothyroidism

• Post-menopausal (age > 50)

OSA Diagnosis & Treatment

• Gold standard: polysomnography– Monitor brain activity (EEG), muscle activity (EOG

& EMG), breathing (flow & pressure), snoring and effort, EKG, oxygen saturation

• Treatment: positive airway pressure (gold standard), weight loss, positional therapy, dental devices, surgery

CPAP

• Adjusted during split-night or full-night titration

• Auto-titrating PAP• Bi-level PAP• Adaptive-servo ventilation

– CHF– “Complex” sleep apnea (treatment emergent

central apnea)

Nasal – Full – Pillows – Hybrid

Case

• A 25 year old woman presents to your office. She states she’s always been the “sleepy one” in class as early as junior high school. She has always fallen asleep in lectures in college no matter how much she sleeps. She currently goes to bed at 9pm and sleeps until 6am every day. She wakes up multiple times per night. She never feels like she has a good night’s sleep. She does not snore. She denies depression, other medical problems, substance use. She takes no medications.

• Height: 5’3”. Weight: 115#. BMI: 20.4. Normal thyroid exam. Normal oropharyngeal exam.

Differential diagnosis

• Narcolepsy without cataplexy• Idiopathic hypersomnia• Hypothyroidism• Substance abuse• Depression• Behavioral sleep restriction

Diagnostic criteria for narcolepsy

• (Cataplexy)• Near daily excessive daytime sleepiness for at

least 3 months• Not better explained by other medical,

substance, behavioral conditions• MSLT sleep latency < 8 minutes• 2 SOREMPs despite sufficient sleep

Cataplexy

• Unique to narcolepsy• Sudden bilateral loss of muscle tone provoked

by strong emotion (laughter)– Can vary in muscle groups affected– Can vary in degree of loss of muscle tone

• Associated with loss of CSF hypocretin-1 (orexin-A) – hypothalamic neuropeptide

Additional features of narcolepsy

• Sleep paralysis• Hypnagogic (sleep onset) hallucinations• Nocturnal sleep disruption

• Classic Tetrad = cataplexy + excessive daytime sleepiness + sleep paralysis + hypnagogic hallucinations

Multiple sleep latency test

• Daytime test following a PSG– No OSA (AHI >5) + 6 hours of sleep the night

before

• Series of 5 naps spaced 2 hours apart– 20 minutes to fall asleep -> 15 minutes to sleep– Normal range very broad– Sleep-onset REM Periods (SOREMPs) are

abnormal (2+ can be diagnostic)

Rears T, et al. Daytime sleepiness and alertness. In: Kryger MH et al. (eds). Principles and Practice of Sleep Medicine. 4th Edition. Philadelphia: Elsevier Saunders; 2005: 40. MSLT = Multiple Sleep Latency Test

TIB = time in bed

Daytime sleepiness

Treatment of narcolepsy

• Excessive daytime sleepiness– Stimulants: dextroamphetamine, methylphenidate– Modafinil– Sodium oxybate

• Cataplexy– Sodium oxybate– Antidepressants: TCAs, SSRIs

Case

• A 45 year old woman presents to your office noting difficulties falling asleep which have gotten worse. When she gets into bed she has an irresistible urge to move her legs. This gets better as soon as she gets up and walks around her bedroom. As soon as she gets back into bed the feeling gets worse. She has fewer problems if she lays down in the early afternoon to take a nap.

• She has no periodic limb movements of sleep during a polysomnogram. Her ferritin level and other laboratory testing is normal.

Essential diagnostic criteria

• U: Urge to move legs, triggered or accompanied by unpleasant sensations

• R: Relieved by movement

• G: Gets worse during rest or inactivity

• E: Evening symptoms are worse

Diagnosis

• Made clinically: do not need a PSG– 80-90% of patients with RLS will have PLMs on sleep study– Conversely, most patients with PLMs do not have RLS

• Primary vs. secondary– Low iron stores (ferritin)– Medications (TCAs, SSRIs, neuroleptics, beta-blockers, H2

blockers, anti-convulsants)– Renal failure– Pregnancy– Peripheral neuropathy

Epidemiology

• Affects 10% of US adults

• Age of onset varies widely: commonly ≥40 years

• Women > men

Treatment

• Dopaminergic agents– Carbidopa-levodopa (Sinemet)– Roponirole (Requip)– Pramipexole (Mirapex)

• Iron replacement

• Gabapentin, methadone

Case

• A 65 year old man presents to your office noting persistent difficulties falling asleep and then staying asleep. This has been ongoing for over a month. He feels that sleep is never refreshing. He is retired and has plenty of opportunity to sleep. He is becoming more worried about hie sleep and feels that he is not as sharp during the day, feels fatigued more easily and has been more irritable with his family. An overnight polysomnogram is negative for OSA.

Insomnia syndromeA. Sleep symptoms: At least one of the following present on

most nights: Prolonged sleep latency (> 30 minutes) Sleep maintenance difficulty (> 3 awakenings) Wakefulness after sleep onset (> 30 minutes) Short sleep duration (< 6.5 hours) Poor sleep quality

B. Adequate opportunity for sleepC. Daytime symptomsD. Distress/impairmentE. Duration > 1 month

Symptom vs. co-morbid disorder

• The 1983 NIH consensus suggested that insomnia should be considered as a symptom. Ultimately, the 2005 conference has emphasized that insomnia should be considered as a disorder and that it should be considered as a co-morbid disorder.

The 3 P model of insomnia

• A useful model for insomnia incorporates three factors:– Predisposing – Precipitating– Perpetuating

• The relative influence of these factors in the course of insomnia varies over time

Spielman AJ et al. Psychiatr Clin North Am. 1987;10:541-553.

Treatments

• Cognitive Behavioral Therapy (CBT)– Sleep Hygiene & Restriction

• Pharmacotherapy– Melatonin + Selective MT receptor agonists– Benzodiazepines + BZRAs– Antidepressants (anti-histamine/cholinergic)

• trazodone, doxepin, mirtazapine, amitriptyline

– Herbal• valerian, catnip, kava, chamomile, passion flower

Practical issues

• As the primary care physician your visit counts as the face-to-face evaluation prior to a sleep study– Insurance requirements for sleep study payment

continuously changing– For now at BMC, still mainly in-laboratory PSGs

• Refer your patients!– Logician order: Pulmonary – Sleep Disorders– Order a sleep study using the Lab tab in progress

note (do not use the sleep study test order)