Narcolepsy

Diagnosis

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

Clinical Background

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
    • Only 10-25% 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

Indications for Laboratory Testing

  • 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
Test Name and Number Recommended Use Limitations Follow Up
Narcolepsy (HLA-DQB1*06:02) Genotyping 2005023
Method: Polymerase Chain Reaction/Fluorescence Monitoring
Aids in clinical diagnosis of narcolepsy when other studies are inconclusive

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

Rule out drug abuse as etiology of EDS

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

 
Melatonin 0098816
Method: Quantitative Radioimmunoassay

Identify disruptions of circadian rhythm

   
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Rule out anemia as etiology of excessive daytime sleepiness (EDS)

Glucose, Plasma or Serum 0020024
Method: Quantitative Enzymatic

Rule out metabolic abnormality as etiology of EDS

Drugs of Abuse 9 Panel, Urine - Screen Only 0090453
Method: Qualitative Enzyme Multiplied Immunoassay Technique

Rule out drug abuse as etiology of EDS

Abuse is not confirmed by this test alone; additional panels, reflexed and directed drug confirmation testing in urine and serum/plasma also available

The following opioids are not detected in this test; fentanyl, buprenorphine, meperidine, tramadol, and tapentadol