Narcolepsy

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

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

Tests generally appear in the order most useful for common clinical situations

Test name: CBC with Platelet Count & Automated Differential

ARUP #: 0040003

Methodology: Automated Cell Count with Flow Cell Differential

Use:

Rule out anemia

Test name: Glucose, Plasma or Serum

ARUP #: 0020024

Methodology: Quantitative Enzymatic

Use:

Rule out diabetes mellitus

Test name: Narcolepsy (HLA-DQB1*06:02) Genotyping

ARUP #: 2005023

Methodology: Polymerase Chain Reaction/Fluorescence Monitoring

Use:

Identify presence of HLA-DQB1*06:02 allele

Limitations:

Presence of HLA-DQB1*06:02 allele is supportive of a clinical diagnosis of narcolepsy but does not by itself establish a diagnosis

Other alleles are not identified

Test name: Drugs of Abuse 9 Panel, Urine - Screen Only

ARUP #: 0090453

Methodology: Qualitative Enzyme Multiplied Immunoassay Technique

Use:

Rule out drug abuse as etiology of EDS

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

Test name: Drug Screen (Nonforensic), Urine, Qualitative

ARUP #: 0090500

Methodology: Qualitative Immunoassay/Gas Chromatography-Mass Spectrometry

Use:

Rule out drug abuse as etiology of EDS

Limitations:

Abuse is not confirmed by this test alone; serum/plasma testing also available

Test name: Melatonin

ARUP #: 0098816

Methodology: Quantitative Radioimmunoassay

Use:

Identify disruptions of circadian rhythm