Dr. Brown is a neurologist and deputy editor for DynaMed (www.dynamicmedical.com), a database of comprehensive updated summaries covering nearly 3,000 clinical topics.

Description
• Sleep disorder
• Defined as recurrent irresistible attacks of daytime sleepiness, often in conjunction with triad of cataplexy, sleep paralysis, and hypnagogic hallucinations

ICD-9 codes
• 347 cataplexy and narcolepsy
— 347.00 narcolepsy, without cataplexy
— 347.01 narcolepsy, with cataplexy
— 347.10 narcolepsy in conditions classified elsewhere, without cataplexy
— 347.11 narcolepsy in conditions classified elsewhere, with cataplexy

Prevalence
• 20-60 cases per 100,000 population
• 80% of patients have first symptoms at ages 15-35 years.
• 2%-50% incidence in first-degree relatives
• Women and men affected equally

Pathogenesis
• Rapid eye movement (REM) disorder
• Usually not attributable to specific underlying condition
• Reduced levels of hypocretin (also known as orexin)

Complications
• Cognitive impairment
— Memory impairment reported subjectively but not clearly confirmed objectively
— Narcoleptic patients have attention deficits in tests requiring long periods of concentration.
— Deficits in executive function may be present.

Symptoms
• Excessive daytime sleepiness
• Involuntary episodes of falling asleep
• Cataplexy—most episodes triggered by strong emotions (surprise, fear, anger)
— Usually last seconds to minutes
— Skeletal muscles affected, from individual body areas to complete paralysis, spares respiratory and eye muscles
— Frequency: one episode per month to 10 per day
• Sleep paralysis (inability to move when falling asleep or awakening, often frightening)
• Hypnagogic hallucinations (vivid, at sleep initiation or awakening, can be confused with partial epilepsy)
• Fragmented nocturnal sleep
— Vivid and frightening dreams
— Increased body movements during sleep

Rule out
• Other causes of excessive daytime somnolence
— Periodic limb movement disorder (including restless legs syndrome)
— Depression
— Circadian rhythm disorders (including delayed sleep phase syndrome)
— Sedating medications
• Dopamine agonist treatment (used for Parkinson disease and restless legs syndrome) or Parkinson disease itself may be associated with sleep attacks.
• Complex partial epilepsy
• Traumatic brain injury
• Malingering (e.g., drug-seeking behavior)

Diagnostic criteria and testing
• Daily excessive daytime sleepiness for at least three months confirmed by nocturnal polysomnography followed by Multiple Sleep Latency Testing (MSLT)
• Sleep studies
— Overnight polysomnography to rule out other conditions and confirm adequate sleep before first MSLT
— MSLT involves four to five nap periods, each two hours apart, with sleep-study monitoring.
— Maintenance of Wakefulness Test (MWT) is recording of time before falling asleep, with patient semirecumbent in darkened room during four 20-minute trials separated by two-hour intervals.
• Epworth Sleepiness Scale (ESS) may be used for diagnosis or monitoring of sleep disorder.
• MWT may not correlate with ESS.
• Cerebrospinal fluid analysis: hypocretin-1 ≤110 pg/mL (or <1/3 of mean normal control values) may be alternative to MSLT for diagnosis of narcolepsy with cataplexy.

Prognosis
• Sleepiness diminishes with age.
• Cataplexy may resolve with or without treatment.

Treatment
• Scheduled sleep periods (daytime napping plus regular bedtimes) may reduce symptom severity.
• Modafinil (Provigil in United States, Alertec in Canada) 200 mg once daily reduces excessive daytime sleepiness.
— FDA-approved for excessive daytime sleepiness in patients with narcolepsy
— 400 mg more effective than 200 mg for some outcomes
• Armodafinil (Nuvigil) 150 or 250 mg daily may improve daytime wakefulness in patients with narcolepsy.
— FDA-approved for excessive daytime sleepiness in patients with narcolepsy
— Possible adverse effects: headache, dizziness, nausea
• Sodium oxybate (Xyrem) 4.5 g twice 2.5-4 hours apart nightly associated with reduced narcolepsy symptoms and reduced number of cataplexy attacks
— FDA-approved for narcolepsy with cataplexy and excessive daytime sleepiness in patients with narcolepsy
— Also known as GHB, the “date rape” drug (Schedule I), but can be prescribed for medical use (Schedule III drug)
• Selegiline (Eldepryl) 20-40 mg/day may reduce symptoms.
— Not recommended in pregnant women
— Concomitant use with triptans and selective serotonin reuptake inhibitors contraindicated
• Stimulants—may be used for hypersomnia but can result in tolerance and abuse
— Might be associated with increase in daytime sleep latency and decreased driving errors (based on study using methamphetamine 40-60 mg)
— Switching from methylphenidate to modafinil generally well tolerated
• Antidepressants—no good evidence to support or refute use for narcolepsy
• Counsel about risks of activities that require consis- tent attention (such as driving—eligibility varies with regional laws).
• Referral to neurologist sleep specialist

For references, see www.dynamicmedical.com.