What is the diagnostic test for myasthenia gravis?

Diagnostic Tests for Myasthenia Gravis

The primary diagnostic test for myasthenia gravis is the acetylcholine receptor (AChR) antibody blood test, which should be performed first in all suspected cases, followed by additional specialized tests if this is negative. 1

First-Line Diagnostic Testing

1. Serological Testing:

   • Anti-acetylcholine receptor (AChR) antibodies - positive in approximately 80% of patients with generalized myasthenia gravis and 50% of those with ocular myasthenia 1
   • If AChR antibodies are negative, proceed with:
     • Anti-muscle-specific kinase (MuSK) antibodies
     • Anti-lipoprotein-related protein 4 (LRP4) antibodies 1

2. Electrodiagnostic Studies:

   • Single-fiber electromyography (SFEMG) - considered the gold standard with highest sensitivity (>90% of cases) 1, 2
   • Repetitive nerve stimulation (RNS) - positive in approximately 77% of cases 2
   • Neuromuscular junction testing with jitter studies 1

Additional Diagnostic Tests

1. Pharmacological Tests:

   • Ice pack test - highly specific and non-invasive; application of ice over closed eyes for 2 minutes (ptosis) or 5 minutes (strabismus) to observe improvement 1, 3
   • Edrophonium (Tensilon) test - intravenous administration of edrophonium chloride to temporarily improve muscle strength; 95% sensitive for generalized myasthenia and 86% for ocular myasthenia 1, 4
     • Caution: Must be performed in a monitored setting with atropine available due to risk of muscarinic side effects (bradycardia, bronchospasm, hypotension)

2. Supportive Testing:

   • Pulmonary function assessment with negative inspiratory force and vital capacity 1
   • Creatine phosphokinase (CPK), aldolase, ESR, CRP to evaluate for concurrent myositis 1
   • MRI of brain/spine to rule out other neurological conditions 1
   • Cardiac evaluation (ECG, echocardiogram) if respiratory insufficiency or elevated CPK/troponin present 1

Diagnostic Algorithm

1. Start with clinical suspicion based on fatigable muscle weakness (especially ocular, bulbar, or proximal limb muscles)
2. Order AChR antibody test as first-line test
3. If AChR negative:
   • Order anti-MuSK and anti-LRP4 antibodies
   • Proceed with electrodiagnostic studies (SFEMG preferred)
4. If diagnosis still unclear:
   • Perform ice pack test (safer option)
   • Consider edrophonium test if ice pack test inconclusive and no cardiac contraindications

Common Pitfalls and Caveats

• False negatives: Up to 50% of ocular myasthenia patients are seronegative for AChR antibodies
• Delayed diagnosis: SFEMG is the most sensitive test but may not be readily available at all centers
• Misdiagnosis: Conditions that can mimic myasthenia gravis include Lambert-Eaton syndrome, botulism, and Guillain-Barré syndrome 1
• Medication interference: Beta-blockers, magnesium, fluoroquinolones, aminoglycosides, and macrolides can worsen myasthenic symptoms and potentially affect test results 1
• Edrophonium test risks: Avoid in patients with cardiac conditions due to risk of bradycardia and other cardiac effects 4

Special Considerations

• Ocular myasthenia: Lower sensitivity of antibody testing; may require SFEMG for diagnosis
• Thymoma association: Present in approximately 20% of myasthenia gravis patients; chest imaging should be considered 1
• Crisis evaluation: Urgent diagnosis needed; rapid bedside tests (ice pack) may be valuable when laboratory results are pending 3

Remember that while individual tests have varying sensitivities, a combination of clinical assessment and laboratory testing yields the highest diagnostic accuracy for myasthenia gravis.