para>Narcolepsy is rare before the age of 5 years. Excessive daytime sleepiness is more often attributable to obstructive sleep apnea (OSA), poor sleep hygiene, and the increased sleep requirements early in life. Recommended amount of sleep decreases with age: newborns 16 to 18 hr/day; preschool-aged children 11 to 12 hr/day; school aged children and teens 10 hr/day; adults 7 to 8 hr/day.
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- Epworth Sleepiness Scale: score ranges from 0 to 24 and >10 is suggestive of a sleep disorder rather than generalized fatigue (1)[A].
- Stanford Sleepiness Scale: patients select one of seven statements that best describe energy level, concentration, and sleepiness. Statements 4 to 7 may indicate excessive sleepiness.
- Nighttime polysomnography (PSG): Monitoring of patients in a sleep laboratory will usually document fragmented sleep with a normal amount of REM sleep but rapid onset REM (within 15 minutes of sleep onset) and decreased sleep efficiency. (2)[A] The PSG is useful to rule out other causes of excessive daytime sleepiness, including sleep apnea syndromes and nocturnal myoclonus.
- Multiple sleep latency test (MSLT): begins ≥90 minutes after nighttime test (2)[A]
- The patient is monitored during 4 to 5, 20 minute naps taken at 2-hour intervals; rapidity of sleep onset and type of sleep pattern are documented. The supportive test includes mean sleep latency (time to fall asleep) of ≤8 minutes and ≥2 sleep-onset REM periods.
- Sensitivity 77%; specificity 97%; positive predictive value 73%
- Maintenance of Wakefulness Test (MWT): used to assess ability to remain awake to determine restrictions (e.g., driving), assess treatment response. Not usually performed during the initial evaluation.
Follow-Up Tests & Special Considerations
- HLA typing for DQB1 in ambiguous cases
- Low CSF hypocretin-1 level: 99% specificity, 87% sensitivity in patients with cataplexy; useful in children when unable to do an MSLT
Diagnostic Procedure/Other
- Narcolepsy type 1 (2)[C]
- Excessive daytime sleepiness daily for ≥3 months
- One of the following:
- Cataplexy with sleep latency ≤8 minutes with ≥2 sleep-onset REM periods within 15 minutes of the onset of sleep (SOREMP)
- Low CSF hypocretin-1 level <110 pg/mL or < ’
; of mean values in normal subjects
- Narcolepsy type 2 (2)[C]
- All above without the cataplexy and low hypocretin-1
- Diagnosis of exclusion
TREATMENT
GENERAL MEASURES
- None of the currently available medications enables people with narcolepsy to consistently maintain a fully normal state of alertness.
- Drug therapy should be supplemented by various behavioral strategies: Avoid shift work, heavy meals, and caffeine later in the day.
- Well-timed 20-minute naps may be helpful.
- Avoid sedating drugs and alcohol.
- Use safety precautions, particularly when driving. People with untreated narcoleptic symptoms are involved in automobile accidents roughly 10 times more frequently than the general population. However, accident rates are at normal levels among patients who have received appropriate medication therapy.
MEDICATION
First Line
- Excessive daytime sleepiness (EDS)
- Modafinil (Provigil) (3)[A]:
- Structurally distinct from amphetamines
- 200 to 400 mg/day divided BID; start with 100 mg/day and increase over 3 to 4 days; maximum of 300 mg/dose, 400 mg/day 3.
- First-line treatment: 60% effective and 20% partially effective
- Half-life of 14 hours, can dose daily
- Fewest adverse effects (headache, GI upset, increased metabolism of oral contraceptives) with less rebound hypersomnia and does not affect BP; tolerance limited
- No decrease in cataplexy
- Armodafinil (Nuvigil):
- Enantiomeric form of modafinil with slightly longer half-life of 15 hours
- 150 to 250 mg every morning
- Cataplexy:
- Sodium oxybate (Xyrem):
- 2.5 to 9 g; may take 3 months for full response
- Preferred treatment for narcolepsy with cataplexy and disturbed nocturnal sleep
- Give ½; dose once in bed and ½; dose 2 to 4 hours later.
- Date rape drug; abuse potential (3)[A]
- Can use with modafinil in severe cases
- May worsen sleep-disordered breathing in patients with OSA
- Expensive with short half-life
- Tricyclic antidepressants
- Protriptyline: 5 to 60 mg/day
- Clomipramine: 10 to 150 mg/day
- High side-effect profile: dry mouth, sedation, urinary retention, impotence
- Serotonin-norepinephrine reuptake inhibitors
- Venlafaxine: 37.5 to 75 mg BID
- Fluoxetine: 20 to 80 mg/day
- Work by suppressing REM sleep
- The patient may develop a tolerance to the anticataplectic drugs and can have rebound cataplexy when a drug is withdrawn.
- Although often used, quality evidence is lacking to demonstrate improvement in cataplexy symptoms from antidepressants (4)[A]
- Auxiliary symptoms (e.g., hypnagogic hallucination, sleep paralysis) require treatment less often than EDS and cataplexy but anticataplectics are useful when symptoms are problematic (4)[C].
Second Line
- EDS
- Amphetamines
- Methylphenidate (Ritalin): initial dose 10 to 60 mg/day divided BID or TID; maximum dose 60 mg/day (3)[B], short-acting, most potent amphetamine available. Can be used in combination with modafinil and armodafinil.
- Dextroamphetamine: initial dose 10 mg/day; can increase by 10 mg weekly to a maximum dose 60 mg/day divided BID or TID (3)[B]
- Contraindicated in patients with HTN
- Adverse reactions: headaches, irritability, hypertension (HTN), psychosis, anorexia, habituation, rebound hypersomnia
- If the patient develops a tolerance to stimulants, switch drugs rather than increase dose; there is little cross-tolerance
- Cataplexy
- Selegiline: selective MAO-B inhibitor
- Anticataplectic effective for excessive daytime sleepiness; 20 to 40 mg/day divided morning and noon (3)[B]
- Doses >20 mg require a low-tyramine diet because the drug begins to lose selectivity.
ISSUES FOR REFERRAL
- Unresponsive to primary medications
- Patient support groups can be very beneficial.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
Frequent BP checks and regular follow-ups (approximately every 6 months) are recommended.
DIET
Selegiline: Doses >20 mg require a low-tyramine diet because the drug begins to lose selectivity.
PATIENT EDUCATION
- Narcolepsy information from the National Institute of Neurological Disorders and Stroke at www.ninds.nih.gov/disorders/narcolepsy/narcolepsy.htm
- Narcolepsy Network, Inc., North Kingstown, RI 02852; www.narcolepsynetwork.org
PROGNOSIS
Narcolepsy is a lifelong disease. Symptoms can worsen with aging. In women, symptoms can improve after menopause.
REFERENCES
11 Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991;14(6):540 " 545.22 American Academy of Sleep Medicine. International Classification of Sleep Disorders: Diagnostic and Coding Manual. 3rd ed. Darien, IL: American Academy of Sleep Medicine; 2014.33 Mohsenin V. Narcolepsy " master of disguise: evidence-based recommendations for management. Postgrad Med. 2009;121(3):99 " 104.44 Vignatelli L, D 'Alessandro R, Candelise L. Antidepressant drugs for narcolepsy. Cochrane Database Syst Rev. 2010;(1):CD003724.
ADDITIONAL READING
- Leschziner G. Narcolepsy: a clinical review. Pract Neurol. 2014;14(5):323 " 331.
- Zaharna M, Dimitriu A, Guilleminault C. Expert opinion on pharmacotherapy of narcolepsy. Expert Opin Pharmacother. 2010;11(10):1633 " 1645.
CODES
ICD10
- G47.419 Narcolepsy without cataplexy
- G47.411 Narcolepsy with cataplexy
- G47.429 Narcolepsy in conditions classified elsewhere w/o cataplexy
- G47.421 Narcolepsy in conditions classified elsewhere with cataplexy
ICD9
- 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
SNOMED
- 60380001 Narcolepsy (disorder)
- 193042000 Cataplexy and narcolepsy (disorder)
- 434241000124107 Secondary narcolepsy (disorder)
- 434251000124109 Secondary narcolepsy without cataplexy (disorder)
- 434261000124106 Secondary narcolepsy with cataplexy (disorder)
CLINICAL PEARLS
- Narcolepsy is a frequently missed disorder, with an average of 15 years of symptoms before a definitive diagnosis is made.
- The classic tetrad of symptoms includes excessive daytime sleepiness, cataplexy, sleep paralysis, and hypnagogic hallucinations but only cataplexy is pathognomonic for the disorder.
- The International Classification of Sleep Disorders has specific diagnostic criteria for narcolepsy.
- Medications are helpful but not curative.