Narcolepsy

Diagnosis

Indications for Testing

• EDS with no known etiology occurring almost daily for ≥3 months

Laboratory Testing

• Screening tests
  • CBC – rule out anemia
  • Random blood sugar (glucose) – rule out diabetes mellitus
• Consider testing for drug abuse
• Genetic testing – HLA typing
  • Determines presence of HLA-DQB1*06:02 but not definitively diagnostic
    • 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)
  • Overnight PSG followed by multiple sleep latency tests in the morning is diagnostic if positive
    • Positive test result – sleep latency ≤8 minutes plus the presence of REM sleep in at least 2 naps
• Sleepiness scale (abbreviated)
• Depression scale (abbreviated)
• Symptom-based testing, such as emotion trigger of cataplexy and type of cataplexy

Differential Diagnosis

• Adults
  • Sleep disorders
    • Idiopathic hypersomnia
    • Periodic limb movement disorder
    • Sleep apnea
    • Sleep deprivation state
  • Neurologic diseases
    • Depression
    • Seizures
    • Syncope
      • Head injury
      • Diabetes mellitus
      • Cardiovascular disease (congestive heart failure)
    • Anxiety
    • Transient ischemic attack/stroke
  • Drug/alcohol abuse
  • Other
    • Klein-Levin syndrome
    • Brain tumor
    • Medical condition
      • Chronic obstruction pulmonary disease
      • Chronic renal failure
      • Malignancy
      • Rheumatologic disease
• Children
  • Sleep disorders
    • Sleep-related breathing syndrome
    • Sleep depravation state
    • Idiopathic hypersomnia
    • Sleep apnea
  • Neurologic diseases
    • Schizophrenia
    • Depression
    • Seizures
  • 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 carry 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
    • Knees buckle (typical)
    • Diaphragm and oculomotor muscles are spared
    • No loss of consciousness
    • Duration – 30 seconds to as long as 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

Treatment

• Lifestyle modifications
• Medications include modafinil for EDS, antidepressants and gamma hydroxybutyrate for cataplexy

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