Narcolepsy

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Basics

Description

  • Narcolepsy is a chronic incurable neurologic sleep disorder mainly characterized by excessive daytime sleepiness (EDS) and may be associated with cataplexy (sudden loss of muscle control), hypnagogic hallucinations (vivid perceptual experiences while falling asleep), or sleep paralysis (temporary inability to move or speak that happens during transition from sleeping to awake state).
  • Mainly two types identified by American Academy of Sleep Medicine:
    • Type 1 (60–70%) (formerly narcolepsy with cataplexy) and type 2 (formerly narcolepsy without cataplexy) (1)
  • Usually diagnosed late—5 to 15 years after the onset of symptoms (2)
  • No cure, symptomatic management

Epidemiology

Incidence
  • Affects 0.03 to 0.16% general population with incidence 1/2,000 worldwide (3)
  • Bimodal distribution, age of onset peak at 15 years and again at 35 years of age
  • Predominant sex: male > female (1.6:1)
  • 5% familial cases (1)

Prevalence
  • Narcolepsy type 1 (with cataplexy): 25 to 50/100,000 people
  • Narcolepsy type 2 (without cataplexy): 20 to 34/100,000 people (1)
  • Highest in Japan, lowest in Israel

Etiology and Pathophysiology

  • Primarily caused by degeneration of hypothalamic neurons that produce orexin (hypocretin). Postmortem studies show 85% loss of these neurons in type 1 and about 33% loss in type 2 (1).
  • Orexin is crucial to promote wakefulness, it stimulates the RAS (reticular activating system) and inhibits REM.
  • Neurodegeneration may be caused by autoimmune process, probably stimulated by infections (such as influenza or Streptococcus) or environmental factors (occurs commonly in late spring) (2).
  • Alterations in the L-PGDS (lipocalin-type prostaglandin D synthase) level also seem to be involved in causing EDS in narcolepsy (1).
  • Rarely by insult to hypothalamus due to sarcoidosis, stroke, tumor, or paraneoplastic disorder (2)
  • International Classification of Sleep Disorders 3rd edition (ICSD-3) classification:
    • Narcolepsy
    • Narcolepsy type 1 (with hypocretin deficiency)
    • Narcolepsy type 2 (without hypocretin deficiency)
    • Narcolepsy due to medical conditions

Genetics
  • Usually sporadic but increased incidence in families with positive history: 1–2% in first-degree relative of index case (10 to 40 times the general population) (2)
  • Twin concordance is 25–31% (suggests environmental contribution).
  • 98% of patients with narcolepsy type 1 have human leukocyte antigen (HLA) DQB1*0602; 40–50% of patients with narcolepsy type 2 express this antigen. HLA DQB1*0602 is present in 12–30% of the general population (2).
  • Heterozygous subjects have 7- to 25-fold increased risk, whereas homozygous have 2- to 4-fold increased risk (1).
  • Presence of DQB1*0602 gene increased risk of narcolepsy by a factor of 200 (2).
  • Autosomal recessive inheritance pattern
  • Affects 12% of Asians, 25% of whites, and 38% of African Americans are gene carriers

Risk Factors

  • Age (peaks at 15 and 35 years)
  • Obesity
  • Head trauma
  • CNS infectious disease
  • Anesthesia
  • Psychological stress
  • Positive family history
  • Recent influenza A, streptococcal infection, or H1N1 vaccine

Commonly Associated Conditions

Obstructive sleep apnea (OSA) (up to 25%), obesity, anxiety

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