What laboratory tests are used to diagnose myasthenia gravis?

Laboratory Tests for Diagnosing Myasthenia Gravis

Single-fiber electromyography is considered the gold standard for diagnosing myasthenia gravis, with over 90% sensitivity for ocular myasthenia. 1

Primary Diagnostic Tests

Antibody Testing

• Anti-acetylcholine receptor antibodies (AChR-Ab):

  • Includes binding, blocking, and modulating antibodies
  • Positive in approximately 80% of patients with generalized myasthenia gravis
  • Positive in only about 50% of patients with ocular myasthenia gravis 1
  • Highly specific for myasthenia gravis 2

• Anti-muscle-specific kinase antibodies (anti-MuSK-Ab):

  • Present in about one-third of AChR-Ab seronegative patients 1
  • Associated with more severe bulbar symptoms 3
  • Poor response to cholinesterase inhibitors 3

• Anti-lipoprotein-related protein 4 antibodies (anti-LRP4):

  • Associated with both generalized and ocular myasthenia gravis 1
  • More recently identified antibody

Electrophysiological Tests

• Single-fiber electromyography (SFEMG):

  • Gold standard diagnostic test with highest sensitivity
  • Positive in over 90% of patients with ocular myasthenia 1
  • Can detect neuromuscular junction transmission defects

• Repetitive nerve stimulation (RNS):

  • Less sensitive than SFEMG
  • Positive in only one-third of patients with ocular myasthenia 1
  • More useful in generalized myasthenia gravis

Pharmacological Challenge Tests

• Ice pack test:

  • Application over closed eyes for 2 minutes (ptosis) or 5 minutes (strabismus)
  • Positive result: reduction of ptosis by about 2mm or reduction of misalignment
  • Highly specific for myasthenia gravis 1
  • Safe, non-invasive bedside test

• Rest test:

  • Alternative to ice pack test
  • Patient rests eyes, then examiner looks for improvement in ptosis/strabismus 1

• Edrophonium (Tensilon) test:

  • Intravenous administration protocol:
    • Initial dose: 0.2 mL (2 mg) injected over 15-30 seconds
    • If no reaction after 45 seconds, remaining 0.8 mL (8 mg) is injected 4
  • Sensitivity: 95% for generalized myasthenia, 86% for ocular myasthenia 1
  • Must be performed in monitored setting with atropine available
  • Potential adverse effects: muscarinic side effects (excess tearing, salivation, sweating, abdominal cramping, bradycardia, bronchospasm, hypotension, syncope) 4

Special Considerations

• Seronegative myasthenia gravis:

  • Cell-based assays (CBAs) can detect clustered AChR antibodies in 38% of radioimmunoprecipitation assay (RIPA) negative patients 5
  • Patients with antibodies only to clustered AChRs tend to be younger with milder disease 5

• Pediatric testing considerations:

  • Intravenous edrophonium testing dose:
    • Children up to 75 lbs: 0.1 mL (1 mg)
    • Children above 75 lbs: 0.2 mL (2 mg) 4
  • May be titrated up if no response after 45 seconds

Diagnostic Algorithm

1. Initial antibody panel:

   • Anti-AChR antibodies (binding, blocking, modulating)
   • If negative, test for anti-MuSK antibodies
   • If both negative, consider anti-LRP4 antibodies or clustered AChR antibodies

2. If antibody tests are negative or inconclusive:

   • Proceed to electrophysiological testing (SFEMG preferred)
   • Consider pharmacological challenge tests (ice pack test or edrophonium test)

3. If diagnosis remains uncertain:

   • Consider cell-based assays for clustered AChR antibodies
   • Evaluate response to treatment with pyridostigmine

Pitfalls and Caveats

• Antibody-negative myasthenia gravis occurs in about 20% of generalized and 50% of ocular cases 1
• Edrophonium testing should only be performed by experienced practitioners with resuscitation equipment available 1, 4
• Short disease duration may lead to false-negative antibody results; consider retesting patients with strong clinical suspicion 6
• MuSK antibody-positive patients may show hyperactivity to edrophonium testing, including facial fasciculations and throat tightness 3
• Patients with pure ocular myasthenia typically have lower antibody titers 2
• Patients with thymoma tend to have higher antibody titers 2