Narcolepsy

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Topics
  • Videos

Indications for Testing

  • Excessive daytime sleepiness (EDS) with no known etiology occurring almost daily for ≥3 months

Laboratory Testing

  • Screening tests
    • CBC – rule out anemia as etiology of EDS
    • Random blood – rule out metabolic abnormality as etiology of EDS
  • Consider testing for drug abuse
  • Genetic testing – HLA typing
    • To determine presence of HLA-DQB1*06:02
      • Strongly associated with narcolepsy but by itself is not sufficient to cause narcolepsy
      • Highly sensitive in cases with cataplexy
      • More specific and sensitive than HLA-DR2, especially in African Americans
  • Consider melatonin testing – identify disruptions of the circadian rhythm

Other Testing

  • Polysomnography (PSG) – most useful diagnostic test
    • Overnight PSG followed by multiple sleep latency tests in the morning – diagnostic if positive
      • Positive test result – sleep latency ≤8 minutes plus the presence of REM sleep in at least 2 naps
  • Sleepiness and depression scales
  • Symptom-based testing, such as emotional triggering of cataplexy

Differential Diagnosis

  • Adults
  • Children
    • Sleep disorders
      • Sleep-related breathing syndrome
      • Sleep depravation state
      • Idiopathic hypersomnia
      • Sleep apnea
    • Neurologic diseases
    • Drug/alcohol abuse
    • Other
      • Brain tumor

Narcolepsy is a sleep disorder characterized by excessive daytime somnolence, cataplexy, sleep paralysis and hypnagogic hallucinations.

Epidemiology

  • Incidence – 1/2,000
  • Age – first symptoms during teenage years; however, disorder is often not diagnosed for ≥10 years
  • Sex – M>F

Risk Factors

  • Family history of narcolepsy in first-degree relative increases risk by ten- to 40-fold
  • Genetics
    • HLA-DQB1*06:02 haplotype found in many patients
      • Associated with narcolepsy with cataplexy; >99% of patients with narcolepsy-cataplexy have HLA-DQB1*06:02
      • Strongly associated with narcolepsy in the Japanese, African American, Korean, and Hispanic populations

Pathophysiology

  • Abnormality in hypocretin (orexin) neurotransmitter found in the hypothalamus
    • Hypocretins function to stimulate appetite and arousal; increases muscle tone during awake periods
    • Narcoleptics have very low levels of CSF hypocretin-1

Clinical Presentation

  • Tetrad – excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic hallucinations
    • Less than 33% of patients display all four major symptoms
    • EDS – usually the first symptom
    • Cataplexy – sudden episode of muscle weakness; occurs in 60-70% of patients
      • Varies in severity – often triggered by emotion
      • Presence is highly specific for narcolepsy
      • Knees buckle (typical)
      • Diaphragm and oculomotor muscles are spared
      • No loss of consciousness
      • Duration – 30 seconds up to 2 minutes
    • Sleep paralysis – occurs most often while waking up; may also occur while falling asleep
      • Unable to move limbs, speak, or breathe deeply
    • Hypnagogic hallucinations – intense auditory or visual hallucinations at onset of sleep
  • Other sleep disorders often present
    • Sleep apnea
    • Restless limb syndrome
    • Sleepwalking

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Narcolepsy (HLA-DQB1*06:02) Genotyping 2005023
Method: Polymerase Chain Reaction/Fluorescence Monitoring

Limitations

Does not differentiate between heterozygosity and homozygosity of the HLA-DQB1*06:02 allele

Rare diagnostic errors may occur due to primer-site mutations

Alleles other than HLA-DQB1*06:02 will not be identified

Other genetic and nongenetic factors that influence narcolepsy are not evaluated

Drug Screen (Nonforensic), Urine, Qualitative 0090500
Method: Qualitative Immunoassay/Gas Chromatography-Mass Spectrometry/Liquid Chromatography-Tandem Mass Spectrometry

Limitations

Not optimized for most drugs of abuse; instead, refer to drug panel 9, 7, or 5

Melatonin 0098816
Method: Quantitative Radioimmunoassay

Related Tests

General References

Boulos MI, Murray BJ. Current evaluation and management of excessive daytime sleepiness. Can J Neurol Sci. 2010; 37(2): 167-76. PubMed

Cao M. Advances in narcolepsy. Med Clin North Am. 2010; 94(3): 541-55. PubMed

Khan F, Hazin R, Iqbal M. Narcolepsy: clinical decision making for the primary care physician. South Med J. 2009; 102(12): 1246-52. PubMed

Kothare SV, Kaleyias J. Narcolepsy and other hypersomnias in children. Curr Opin Pediatr. 2008; 20(6): 666-75. PubMed

Nevsimalova S. Narcolepsy in childhood. Sleep Med Rev. 2009; 13(2): 169-80. PubMed

Panossian LA, Avidan AY. Review of sleep disorders. Med Clin North Am. 2009; 93(2): 407-25, ix. PubMed

Ramar K, Olson EJ. Management of common sleep disorders. Am Fam Physician. 2013; 88(4): 231-8. PubMed

Woo HIn, Joo EYeon, Hong SBong, Lee KWha, Kang E. Use of PCR with sequence-specific primers for high-resolution human leukocyte antigen typing of patients with narcolepsy. Ann Lab Med. 2012; 32(1): 57-65. PubMed

Medical Reviewers

Last Update: April 2016