What are the diagnostic tests for myasthenia gravis (Muscle Weakness Disorder)?

Diagnostic Tests for Myasthenia Gravis

The diagnostic workup for myasthenia gravis should include anti-acetylcholine receptor antibodies, repetitive nerve stimulation, single-fiber electromyography, and specific clinical tests such as the ice pack test. 1

Primary Diagnostic Tests

Serological Testing

• Anti-acetylcholine receptor (AChR) antibodies: Present in 80-85% of patients with myasthenia gravis 1, 2
• Anti-MuSK antibodies: Found in 5-8% of patients, especially important in AChR-negative cases 2
• Anti-LRP4 antibodies: Present in <1% of patients 2
• Approximately 10% of patients may be seronegative for all known antibodies 2

Electrophysiological Testing

• Repetitive nerve stimulation: Shows decremental response in affected muscles; positive in approximately two-thirds of patients with generalized MG but only one-third with ocular MG 1
• Single-fiber electromyography (SFEMG): Demonstrates increased jitter; considered the gold standard with >90% sensitivity, particularly valuable for ocular MG 1

Clinical Tests

• Ice pack test: Highly specific test where ice is applied to the affected eyelid for 2-5 minutes; improvement in ptosis indicates positive result 1
• Edrophonium (Tensilon) test: 95% sensitive for generalized MG and 86% sensitive for ocular MG; involves IV administration of acetylcholinesterase inhibitor with temporary improvement in muscle strength 1
  • Caution: Carries risks including bradycardia, bronchospasm, and hypotension; emergency equipment should be available 1

Additional Diagnostic Evaluations

Imaging

• Chest imaging (CT or MRI): Essential to evaluate for thymoma, which is present in approximately 10-20% of patients with AChR antibody-positive MG 1, 2

Additional Testing

• Complete rheumatologic and neurologic examination: To assess pattern and severity of muscle weakness 1
• Blood tests for muscle inflammation: To rule out other causes of muscle weakness 1
• Paraneoplastic autoantibody testing: To identify potential associated conditions 1

Diagnostic Algorithm

1. Initial presentation: Patient with fluctuating muscle weakness, typically worse with exertion and improved with rest
2. First-line tests:
   • AChR antibodies (and MuSK if AChR negative)
   • Chest imaging for thymoma evaluation
3. If serology is negative or inconclusive:
   • Perform electrophysiological testing (repetitive nerve stimulation and/or SFEMG)
4. For ocular symptoms:
   • Ice pack test (simple, safe, and specific)
   • SFEMG (highest sensitivity for ocular MG)
5. If diagnosis remains uncertain:
   • Consider Edrophonium test with appropriate safety precautions

Clinical Pearls and Pitfalls

• Pattern recognition: MG typically begins with ocular symptoms (ptosis and/or diplopia) and extends to other muscles in 80% of cases 3

• Variability: Symptoms characteristically fluctuate throughout the day, typically worsening with sustained effort 3, 4

• Respiratory monitoring: Assess for respiratory involvement, as rapid worsening may indicate myasthenic crisis 1, 3

• Medication caution: Several medications can exacerbate MG symptoms and should be avoided during diagnostic workup, including:

  • Aminoglycosides
  • Fluoroquinolones
  • Macrolides
  • Beta-blockers
  • Magnesium (IV)
  • Daptomycin 1

• Diagnostic challenges: 10% of patients may be seronegative, requiring more extensive electrophysiological testing 2

By following this systematic approach to diagnosis, clinicians can accurately identify myasthenia gravis and initiate appropriate treatment to improve patient outcomes.