Disorders of Sleep

Sudhansu Chokroverty, M.D., F.R.C.P., F.A.C.P.
New Jersey Neuroscience Institute at John F. Kennedy Medical Center–Seton Hall University, New York Medical College, University of Medicine and Dentistry New Jersey/Robert Wood Johnson Medical School

Definition/Key Clinical Features
Differential Diagnosis
Best Tests
Best Therapy
Best References

Definition/Key Clinical Features

Insomnia

Difficulty initiating or maintaining sleep, or early awakening with inability to go back to sleep
Associated with a wide variety of medical, psychiatric, and neurologic causes; may be drug- or alcohol-induced

Obstructive Sleep Apnea Syndrome (OSAS)

Cessation of airflow during sleep despite continued respiratory effort

Decrease in breathing ≥ 10 sec, with ≥ 5 episodes per hour of sleep

Common in middle-aged and elderly men; incidence increases in women after menopause

Can lead to hypertension, cardiac arrhythmias, heart failure

Sleep hypopnea (decrease of breathing to < 50% of volume of preceding or following respiratory cycle, associated with arousal or 4% oxygen desaturation) has same clinical significance

Symptoms

Nocturnal
- Loud snoring
Daytime
- Excessive daytime somnolence

Circadian rhythm sleep disorders

Desynchronization between patient's internal circadian rhythm and external time
- Jet lag

Narcolepsy

Sleep attacks (irresistible desire to sleep in inappropriate places and under inappropriate circumstances)
- Attacks last generally a few minutes to 30 min
Cataplexy (transient loss of muscle tone) in most patients occurs after months or years
- Often triggered by emotional outburst
Lifelong disorder; generally less severe with old age

Restless legs syndrome

Urge to move legs, usually accompanied by uncomfortable or unpleasant sensations; arms sometimes affected
Symptoms begin or worsen during rest or inactivity
Partial or total relief of symptoms with movement, at least early in illness
Worse in evening or early part of night
Lifelong; may begin at any age but most severe in middle-aged or elderly persons, with chronic progressive course

Parasomnias

Partial arousal disorders
- Confusional arousals
  - Most common in children < 5 yr of age
Sleepwalking
- Common in children 5–12 yr of age
Sleep terrors
- Peak onset 5–7 yr of age
- Precipitating factors similar to sleepwalking
Rapid eye movement (REM) sleep behavior disorder
- Commonly seen in elderly
- Intermittent loss of REM-related atonia or hypotonia, with abnormal motor activities (often violent)
- Most cases secondary to neurodegenerative disease
Nocturnal frontal lobe epilepsy (nocturnal paroxysmal dystonia)
- Onset any time from infancy to fifth decade of life
- Characterized by ballismic, choreoathetoid, or dystonic movements
- Usually short duration (15 sec to < 2 min)

Differential Diagnosis

Insomnia

Psychiatric disorders
- Anxiety
- Panic attacks
- Depression
- Stress
- Other psychophysiologic factors
- Medical disorders
  - Bronchial asthma
  - Coronary artery disease
  - Peptic ulcer disease
  - Rheumatic disorders
- Neurologic disorders
  - Stroke
  - Neurodegenerative disease
  - Brain tumors
  - Headache syndromes
  - Neuromuscular disorders (e.g., painful peripheral neuropathies)
- Traumatic brain injury
- Pain anywhere in the body
- Sleep–wake schedule disruptions
- Other disorders of circadian sleep rhythms
- Drug or alcohol abuse
REM Sleep Behavior Disorder
- Parkinson disease
- Multiple system atrophy
- Diffuse Lewy body disease
- Olivopontocerebellar atrophy
- Progressive supranuclear palsy
- Corticobasal ganglionic degeneration

Best Tests

History

Sleeping habits
Drug and alcohol consumption
Previous or current psychiatric, medical, or neurologic illness
Family history

Physical Examination

Obesity in 70% of patients with OSAS
Local upper airway anatomic disorders in many cases of OSAS

Diagnostic Studies

MRI or other neuroimaging as indicated, to exclude structural lesions
Laboratory tests to exclude suspected medical disorders

Sleep Laboratory Testing

All-night polysomnography (PSG)
- EEG
- EMG
- Electro-oculography
- Electrocardiography
- Airflow at nose and mouth
- Respiratory effort
- Oxygen saturation
Multiple sleep latency test
Actigraphy

Best Therapy

Insomnia

Transient
- Short-term treatment for a few nights to a few weeks
- Sedative-hypnotics
  - Zaleplon, 5–10 mg h.s.
    - Cost/mo: $96
  - Zolpidem, 5–10 mg h.s.
    - Cost/mo: $100
  - Zolpidem extended release, 6.25–12.5 mg h.s.
    - Cost/mo: $105–$210
  - Eszopiclone, 1–3 mg h.s.
    - Cost/mo: $107
  - Ramelteon, 8 mg h.s.
    - Cost/mo: $102
- Short- or intermediate-acting benzodiazepines
Chronic
- Treatment of underlying disorders
- Sleep hygiene
  - Fixed times for retiring and awakening
  - Avoidance of caffeine, tobacco, alcohol
  - Regular exercise (preferably 4–6 hr before bedtime)
- Stimulus-control therapy
- Sleep restriction
- Relaxation training
- Pharmacotherapy (intermittently combined with above)
  - Eszopiclone, 1–3 mg h.s.
  - Ramelteon, 8 mg h.s.
  - Other sedative-hypnotics or benzodiazepines

OSAS

Avoidance of sedatives, hypnotics, alcohol
Reduction of obesity
Continuous positive airway pressure (CPAP) ventilation in moderate to severe cases
- Optimal pressure determined during overnight PSG
Laser-assisted or radiofrequency uvulopalatopharyngoplasty in some mild to moderate cases
Dental appliance in selected mild to moderate cases

Circadian Rhythm Sleep Disorders

Bright-light therapy
Chronotherapy
Pharmacotherapy (e.g., melatonin, ramelteon, zolpidem)

Narcolepsy

Stimulants for treatment of sleep attacks
- Modafinil, 100–200 mg/day
  - Cost/mo: $255
- Methylphenidate, 10–60 mg/day
- Dextroamphetamine, 5–60 mg/day
- Methamphetamine, 5–50 mg/day
Treatment of cataplexy
- Tricyclic antidepressants
  - Protriptyline, 2.5–20 mg/day
    - Cost/mo: $104
  - Imipramine, 25–200 mg/day
    - Cost/mo: $47
  - Clomipramine, 25–100 mg/day
    - Cost/mo: $34
- Selective serotonin reuptake inhibitors (e.g., fluoxetine, 20–60 mg/day in divided doses; paroxetine, 20–40 mg/day in divided doses)
- Endogenous hypnotics
  - Sodium oxybate (γ-hydroxybutyric acid), 3–9 g in two divided doses nightly

Restless Legs Syndrome

Dopaminergic drugs
- Carbidopa-levodopa, 25/100–100/400 mg in divided doses before bedtime
  - Cost/mo: $81
- Dopamine agonists (best initial agent)
  - Pergolide, 0.05–0.5 mg in divided doses before bedtime
    - Cost/mo: $94
  - Pramipexole, 0.125–1.5 mg before bedtime
    - Cost/mo: $61–$71
  - Ropinirole, 0.25–3.0 mg before bedtime
    - Cost/mo: $68
- Benzodiazepines (e.g., clonazepam, 0.5–2 mg h.s.)
- Opioids
  - Codeine, 30–120 mg/day
  - Propoxyphene, 65–130 mg/day
  - Oxycodone, 10–20 mg/day
  - Hydrocodone, 5–10 mg/day
  - Tramadol, 50–100 mg/day
- Anticonvulsants (e.g., gabapentin, 300–1,200 mg before bedtime, in divided doses)

Nocturnal Frontal Lobe Epilepsy

Carbamazepine, 200–1,000 mg in divided doses
- Cost/mo: $27

REM Sleep Behavior Disorder

Low-dose benzodiazepines (e.g., clonazepam, 0.5–2 mg h.s.)

Best References

Dagan Y: Sleep Med Rev 6:45, 2002 [PMID 12531141]

Earley CJ: N Engl J Med 348:2103, 2003 [PMID 12761367]

Flemons WW: N Engl J Med 347:498, 2003 [PMID 12181405]

Morin CM, et al: Curr Treat Options Neurol 3:9, 2001 [PMID 11123855]

The author has been a member of the speakers' bureau for Sanofi-Aventis and has served as a consultant for Boehringer Ingelheim Corp.

November 2006